List of Abstracts for 2015 Granulation Workshop Updated on .../file/2015... · 2 Glatt...

List of Abstracts for 2015 Granulation Workshop Updated on: 2015-06-10 at 15:58 GMT

Number Abstract Title Names of Author (s) Authors' details Presentation Type

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1. QUANTIFYING TABLET PUNCH ADHESION RISK USING A COMPACTION SIMULATOR

Monwara Hoque1, Elaine Harrop Stone1, Darren Wilkes2 & Vicki

Wilkes2

1 Merlin Powder Characterisation Ltd, UK

2 Phoenix Calibration and Services Ltd, UK

POSTER

2. DISCRETE ELEMENT MODELLING OF PARTICLE COLLLISIONS IN GRANULAR FLOWS WITH

SPECIAL REFERENCE TO SPHERONIfSATION

A. Alharbi, H. Elmsahli and I.C. Sinka University of Leicester, UK ORAL

3. CONTINUOUS PHARMACEUTICAL MELT GRANULATION: RHEOLOGY AS A PREDICTIVE

TOOL TO DETERMINE FORMULATION PROCESSABILITY

Tinne Monteyne1, Chris Vervaet2, Jean-Paul Remon2 & Thomas De

Beer1

1 Ghent University, Belgium


ORAL

4. A NEW CONTACT LIQUID DISPERSION MODEL FOR DISCRETE PARTICLE SIMULATION

Kimiaki Washino, Koki Miyazaki, Takuya Tsuji & Toshitsugu Tanaka

Osaka University, Japan ORAL

5. MONITORING CALCIUM CARBONATE PRECIPITATION AND AGGLOMERATION: A

COMPARISON OF INLINE AND OFFLINE TECHNIQUES

W.N. Al Nasser1, K. Pitt2, M. J. Hounslow2 & A. D. Salman2

1 Saudi Aramco Company, Saudi Arabia

2 University of Sheffield, UK

POSTER

6. FORMULATION DEVELOPMENT, CHARACTERIZATION AND EVALUATION OF

LIQUISOLID TABLET CONTAINING ORLISTAT

Sanjana Gaikwad, Madhukar Tajne & Naresh Gaikwad

RTM Nagpur University, India POSTER

7. INFLUENCE OF THE PELLETIZING PROCESS

PARAMETERS ON THE MECHANICAL PROPERTIES OF THE RECEIVED ALUMINA OXIDE PELLETS

Z. Radeva, P. Müller & J.Tomas Otto von Guericke University, Germany POSTER

8. MEASUREMENT & QUANTIFICATION OF CAKING

IN POWDERS

Tim Freeman, Jamie Clayton, Katrina

Brockbank & Doug Millington Smith

Freeman Technology, UK. POSTER

9. EFFECT OF NANOPARTICLES TO CONTROL CALCIUM CARBONATE SCALING USING INLINE

TECHNIQUE

W. AL Nasser1, U. Shah2, K. Nikiforou2, P. Petrou2 & J. Heng2

1 Saudi Aramco Company, Saudi Arabia

2 Imperial College London, UK

ORAL

10. MICROMERITIC, GRANULATING AND DISSOLUTION PROPERTIES OF RICE STARCH IN

METRONIDAZOLE BASED FORMULATIONS

O.N.C Umeh, K.C Ezeagwu & S.I Ofoefule

University of Nigeria, Nigeria POSTER

11. DEVELOPING AND UNDERSTANDING THE DESIGN

SPACE FOR CONTINUOUS & BATCH PHARMACEUTICAL WET GRANULATION

Tim Freeman, Jamie Clayton, Doug

Millington Smith

Freeman Technology, UK ORAL

12. EXPERIMENTAL ANALYSIS OF THE MICROSTRUCTURE OF SINGLE PARTICLES

Franziska Sondej, Andreas Bück & Evangelos Tsotsas

Otto-von-Guericke University, Germany ORAL

13. SPECIFIC ENERGY CONSUMPTION AND QUALITY OF WOOD PELLETS PRODUCED USING HIGH

MOISTURE LODGEPOLE PINE

Jaya Shankar Tumuluru & Craig. C. Conner

Idaho National Laboratory, Idaho ORAL

14. PREDICTING LOCAL SHEAR IN POWDER FLOW USING DEM: EFFECT OF SIMULAITON

PARAMETERS

Nathan J. Davis1, Rachel M. Smith2 & James D. Litster1

1 Purdue University, USA


ORAL

15. INFLUENCE OF PROCESS PARAMETERS AND MECHANICAL PROPERTIES OF PHARMACEUTICAL

Andreja Mirtic & Gavin Reynolds AstraZeneca, UK POSTER


MATERIALS ON MILLING OF ROLLER COMPACTED

RIBBONS

16. IMPACT OF MILLING PROCESS CONDITIONS ON

THE GRANULE'S PROPERTIES: EFFECT OF MILLING SPEED AND ROTATION

Lucia Perez-Gandarillas1, Ana Perez-

Gago2, Alon Mazor1, Peter Kleinebudde2, Abderrahim Michrafy1

& Olivier Lecoq1

1 Université de Toulouse, France

2 Heinrich-Heine-University, Germany

ORAL

17. CAKING OF COMPLEX SUCROSE MIXTURES Sophie Samain, Mohammed Benali, Mikel Leturia, Elisabeth Van Hecke,

Isabelle Pezron & Khashayar Saleh

Equipe d’Accueil "Transformations Intégrées de la Matière Renouvelable" (EA 4297), France POSTER

18. APPLICABILITY OF THE RYSHKEWITCH-DUCKWORTH EQUATION ON DIRECT AND DRY

GRANULE COMPRESSION

Johanna Mosig & Peter Kleinebudde Heinrich-Heine-University, Germany POSTER

19. EFFECT OF FOOD/MICROORGANISM (F/M) RATIO

ON GRANULAR SLUDGE CHARACTERISTICS IN SBR

SYSTEM

Muhammad Sajjad1,2 & Kwang S.

Kim1,2

1 Korea University of Science and Technology, Republic of Korea

2 Korea Institute of Civil Engineering and Building Technology, Republic of Korea

POSTER

20. USE OF CONTINUOUS TWIN SCREW WET GRANULATION TECHNIQUE TO DEVELOP HIGH

DRUG LOADING TABLET FORMULATION AND

ROBUST PROCESS FOR CHALLENGING ACTIVE PHARMACEUTICAL INGREDIENTS

Claire Tridon, Indra Yadav & Terry Ernest

GlaxoSmithKline R&D, UK ORAL

21. POPULATION BALANCE MODELING OF TWIN SCREW WET GRANULATION THROUGH

MECHANISTIC UNDERSTANDING

Ridade Sayin1,2, Dana Barrasso3, Juan G Osorio1,2, Rohit

Ramachandran3, James D Litster1,2,4



3 The State University of New Jersey, USA


ORAL

22. FABRICATING OF HIERARCHICALLY ASSEMBLED CERAMIC-POLYMER COMPOSITES USING A

SPOUTED BED SPRAY GRANULATION PROCESS

Eduard Eichner1, Stefan Heinrich1, Michael F. H. Wolff1, Gerold A.

Schneider2 & Sergiy Antonyuk3

1 Institute of Solids Process Engineering and Particle Technology, Hamburg University of Technology, Denickestrasse 15, 21073 Hamburg, D

2 Institute of Advanced Ceramics, Hamburg University of Technology, Denickestrasse 15, 21073 Hamburg, D

3 Chair of Particle Process Engineering, Department of Mechanical and Process Engineering, University of Kaiserslautern, Gottlieb-Daimler-Strasse, 67663 Kaiserslautern, D

POSTER

23. PREPARATION AND CHARACTERIZATION OF ADSORBENTS BY GRANULATION AND EXTRUSION

Edith Goldnik, Yanira Lopéz, Ranja Plätzer, Björn Lamprecht, Christian

Eichler, Tharsha Thiripuvanam & Thomas Turek

Institute of Chemical and Electrochemical Process Engineering, Clausthal University of Technology, Leibnizstrasse 17, Clausthal-Zellerfeld, Germany

POSTER

24. MULTI-SCALE MODELLING OF FLUID BED GRANULATION PROCESSES THROUGH A COUPLED

PBM-DEM-CFD FRAMEWORK TO FACILITATE QBD

IN PHARMACEUTICAL DRUG PRODUCT MANUFACTURING

Ashutosh Tamrakar1, Dana Barrasso1, Celia N. Cruz2 & Rohit

Ramachandran1

1 Department of Chemical and Biochemical Engineering, Rutgers, the State University of New Jersey, Piscataway, NJ, USA

2 Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA

ORAL

25. MODELLING FRAMEWORK FOR THE DYNAMIC FLOWSHEET SIMULATION OF SOLIDS PROCESSES

Vasyl Skorych, Eduard Eichner, Maksym Dosta, Ernst-Ulrich Hartge &

Stefan Heinrich

Hamburg University of Technology (TUHH), Institute of Solids Process Engineering and Particle Technology, Denickestrasse 15, 21073 Hamburg, Germany

POSTER

26. PILOT SCALE OPTIMIZATION OF ROLLER

COMPACTION PROCESS USING NEAR-IR CHEMICAL IMAGING

Milad Khorasani1, José M. Amigo2,

Poul Bertelsen3, Changquan C. Sun4 & Jukka Rantanen1

1 Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen,

Universitetsparken 2, 2100, Copenhagen, Denmark

2 Department of Food Science, Faculty of Science, University of Copenhagen, Denmark

3 Takeda Pharmaceutical GmbH, Robert Bosch Strasse 8, Germany

ORAL


4 Department of Pharmaceutics, College of Pharmacy, University of Minnesota, USA

27. MECHANISTIC TIME SCALES IN ADHESIVE PARTICLE MIXING

Duy Nguyen1, Anders Rasmuson1, Ingela Niklasson Björn2 & Kyrre

Thalberg2

1 Department of Chemical Engineering, Chalmers University of Technology, Sweden

2 Astra Zeneca Pharmaceutical Development R&D Mölndal, Sweden

POSTER

28. INFLUENCE OF NOZZLE CONFIGURATION ON PROCESS STABILITY OF CONTINUOUS FLUIDIZED BED LAYERING WITH EXTERNAL CLASSIFICATION

A. Bück1, K. Meyer1, S. Palis2, C. Neugebauer3, A. Kienle2,3, S. Heinrich4 & E. Tsotsas1

1 Chair of Thermal Process Engineering, Otto von Guericke University Magdeburg, Germany

2 Chair of Automation and Modelling, Otto von Guericke University Magdeburg, Germany

3 Max Planck Institute for Dynamics of Complex Technical Systems, Germany

4 Solids Process Engineering, Hamburg University of Technology, Germany

POSTER

29. OBLIQUE IMPACT OF PARTICLES ON WET

SURFACES

Britta Crüger1, Stefan Heinrich1,

Sergiy Antonyuk2, Niels G. Deen3 &

Johannes A.M. Kuipers3

1 Institute of Solids Process Engineering and Particle Technology, Hamburg University of Technology,

Hamburg, D

2 Chair of Particle Process Engineering, Department of Mechanical and Process Engineering,

University of Kaiserslautern, Kaiserslautern, D

3 Multiphase Reactors Group, Department of Chemical Engineering and Chemistry, Eindhoven

University of Technology, NL

ORAL

30. INFLUENCE OF THE SOLID BOND MODEL ON AN

IRREGULAR SHAPED AGGLOMERATE BEHAVIOUR IN DEM SIMULATIONS

Sergii Kozhar1, Maksym Dosta1,

Vitalij Salikov1, Sergiy Antonyuk2 & Stefan Heinrich1


Hamburg, Germany

2 Chair of Particle Process Engineering, University of Kaiserslautern, Kaiserslautern, Germany

POSTER

31. CHARACTERISATION OF THE WORK OF ADHESION OF FOOD GRADE COATING MATERIALS ON A

MALTODEXTRIN MODEL SURFACE

Adrian Kape, Bärbel Ruick & Stephan Drusch

Technical University of Berlin, Department of Food Technology and Food Material Science, Berlin ORAL

32. PREDICTING THE SURFACE COMPOSITION OF A

SPRAY DRIED PARTICLE BY MODELLING

COMPONENT REORGANIZATION IN A DRYING

DROP

Anna Porowska1, Maksym Dosta1

Alessandro Gianfrancesco2, Lennart

Fries3 Stefan Palzer4 & Stefan

Heinrich1

1 Hamburg University of Technology, Germany

2 Nestlé Product Technology Center Konolfingen, Switzerland

3 Nestlé Research Center Lausanne, Switzerland

4 Nestlé Beverages Business Unit, Switzerland

POSTER

33. A MECHANISTIC UNDERSTANDING OF GRANULE

BREAKAGE IN CONTINUOUS TWIN SCEW GRANULATION

Juan G. Osorio1, Ridade Sayin1 &

James D. Litster1,2

1 Department of Chemical Engineering, Purdue University, USA

2 Department of Industrial and Physical Pharmacy, Purdue University, USA

POSTER

34. COMPARATIVE STUDY OF MATRIX TABLETS -

EFFECT OF THE GRANULATION METHOD

Andreas Sauer1, Miyuki Fukusawa2 & Taka Hoshino2

1 Shin-Etsu Pharma & Food Materials Distribution GmbH, Germany

2 Shin-Etsu Chemical Co., Ltd. Cellulose Technical Support Center, YBP Technical center, Japan

POSTER

35. GAINING PROCESS KNOWLEDGE BY USING

MECHANISTIC MODELS FOR FLUIDIZED BED DRYING IN A CONTINUOUS MANUFACTURING

ENVIRONMENT

Séverine T.F.C. Mortier1, Krist V.

Gernaey2, Thomas De Beer2 & Ingmar Nopens3

1 BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of

Bioscience Engineering, Ghent University, Belgium

2 Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium

3 CAPEC-PROCESS, Department of Chemical and Biochemical Engineering, Technical University of Denmark, Denmark

POSTER

36. VISCOSITY INFLUENCE ON THE ATOMIZATION BEHAVIOUR IN A ROTARY DISC SPRAY DRYER

Lucas Bernardo Monteiro, Igor Paiva Sansão, Kauana Martins Iglesias, Aldo

Ramos Santos & Deovaldo de Moraes

Júnior

Santa Cecília University, Brazil

ORAL

37. IMPLEMENTATION OF ROLLER COMPACTION INTO A CONTINUOUS MANUFACTURING ENVIRONMENT

Kirk A. Overhoff, Varsha Dhamankar & Catherine Metzler

Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, USA POSTER


38. DEVELOPMENT AND CHARACTERIZATION OF

TERNARY SOLID DISPERSION GRANULES: PREDICTION OF GLASS TRANSITIONS

Ahmad B. Albadarin1,2, John A.

Collins1, Mark Davis1, David Egan1, Chirangano Mangwandi2, Mark

Southern & Gavin Walker1,2

1 Department of Chemical and Environmental Sciences, Synthesis and Solid State Pharmaceutical

Cluster and Pharmaceutical Technology Manufacturing Centre, University of Limerick, Ireland

2 School of Chemistry & Chemical Eng., Queens University Belfast, UK.

POSTER

39. ANALYSIS OF MESO-SCALE EFFECTS IN HIGH

SHEAR GRANULATION THROUGH A CFD-PBM COUPLED COMPARTMENT MODEL

Per J. Abrahamsson1, Patric Kvist1,

Xi Yu2, Gavin Reynolds3, Ingela Björn Niklasson4 & Anders

Rasmuson1

1 Department of Chemical and Biological Engineering, Chalmers University of Technology, Sweden

2 European Bioenergy Research Institute, Aston University, UK

3 Pharmaceutical and Analytical Research and Development, AstraZeneca, Macclesfield, UK

4 Astra Zeneca Pharmaceutical Development R&D Mölndal, Sweden

POSTER

40. INLINE PARTICLE SIZE MEASUREMENT IN ROLL COMPACTION/DRY GRANULATION

Haress A. Mangal & Peter Kleinebudde

Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Germany POSTER

41. SOLID CRYSTAL SUSPENSIONS - AN ADVANCED

FORMULATION STRATEGY FOR POORLY WATER SOLUBLE DRUGS

Elena Reitz1, Chris Vervaet2, Stefanie

Weidtkamp-Peters3 & Markus Thommes1

1 Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Germany

2 Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium

3 Center for Advanced Imaging, Heinrich-Heine-University, Duesseldorf, Germany

ORAL

42. EVALUATION OF THE ABILITY OF POWDERED

MILK TO PRODUCE MINI-TABLETS DELIVERY OF PARACETAMOL IN PEDIATRICS

Joana T. Pinto1, Mariya Brachkova1,

Ana I. Fernandes1 & João F. Pinto2

1 CiiEM, Instituto Superior de Ciências da Saúde Egas Moniz, Portugal

2 iMed – Research Institute for Medicines and Pharmaceutical Sciences, Faculdade de Farmácia, Univ.

de Lisboa, Av. Prof. Gama Pinto, Portugal

ORAL

43. A THEORETICAL STUDY OF THE HYDRODYNAMIC

BEHAVIOUR OF FLUIDIZED BEDS OPERATED UNDER REDUCED PRESSURE

Sayali Zarekar1, Franziska Sondej1,

Andreas Bück1, Evangelos Tsotsas1 & Michael Jacob2

1 Thermal Process Engineering, Otto-von-Guericke University, Germany

2 Glatt Ingenieurtechnik GmbH, Germany

POSTER

44. JAMMING AND THE ONSET OF GRANULATION IN A MODEL PARTICLE SYSTEM

Daniel J. M. Hodgson & Wilson C. K. Poon

School of Physics and Astronomy, James Clerk Maxwell Building, The University of Edinburgh, UK ORAL

45. FUZZY COMPREHENSIVE EVALUATION OF POWDERS IN ULTRAFINE GRINDING

Zhenfu Luo1, Zaisheng Zhu2, Yuemin Zhao1 & Yunfei Qin1

1 School of Chemical Engineering and Technology, China University of Mining & Technology, China

2 Huainan Mining Industry Group Coal Preparation Branch, Anhui, China

ORAL

46. AMORPHOUS SOLID DISPERSIONS OF BCS CLASS II

DRUGS: A RATIONAL APPROACH TO SOLVENT

AND POLYMER SELECTION

Mark T. Davis1,3, David P. Egan2,3,

Manuel Kuhs1,3, Ahmad B.

Albadarin1,3, Ciara S. Griffin1,3, John

A. Collins2,3 & Gavin M. Walker1,2,3

1 Solid State Pharmaceutical Centre, SSPC, University of Limerick, Limerick, Ireland

2 Pharmaceutical Manufacturing Technology Centre, PMTC, University of Limerick, Limerick, Ireland

3 Materials and Surface Science Institute, MSSI, University of Limerick, Limerick, Ireland

ORAL

47. SORPTION KINETIC STUDIES OF HYDROXYPROPYL

METHYL CELLULOSE SAMPLES

Graham E. O Mahony1,2, Mary E.

Crowley1,2, Rakesh C. Dontireddy1 & Abina M. Crean1,2

1 School of Pharmacy, University College Cork, Ireland

2 Synthesis and Solid State Pharmaceutical Centre

ORAL

48. COMPRESSION ANALYSIS FOR ASSESSMENT OF PELLET PLASTICITY

Ann-Sofie Persson, Josefina Nordström, Göran Frenning & Göran

Alderborn

Department of Pharmacy, Uppsala University, Sweden ORAL

49. CFD-PBE SIMULATION TO PREDICT PARTICLE

GROWTH IN A FLUIDIZED BED MELT GRANULATION BATCH PROCESS

Philipp Lau & Matthias Kind Karlsruhe Institute of Technology, Department of Thermal Process Engineering, Germany ORAL

50. MONO-MODAL PARTICLE SIZE DISTRIBUTIONS IN

TWIN-SCREW GRANULATION - DO NOT FORGET

THE FEEDING SYSTEMS

Robin Meier1, Markus Thommes1,

Markus Krumme2, Norbert

Rasenack2, Klaus-Peter Moll2 & Peter Kleinebudde1

1 Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Germany

2 Novartis AG, Basel, Switzerland

ORAL

51. STRUCTURE AND PROPERTIES OF ACTIVE ENZYME MICROCAPSULES FORMED BY SPRAY DRYING

WITH 3-FLUID NOZZLE

Martin Jakubec, Monika Majerská, Vojtěch Klimša, Ondřej Kašpar &

František Štěpánek

Laboratory of Chemical Robotics, Institute of Chemical Technology Prague, Czech Republic ORAL

52. CONTINUUM MODELING OF DENSE AND DILUTE

PARTICLE FLOWS IN HIGH SHEAR GRANULATION

Mohammad Khalilitehrani, Eva María

Gómez Fino, Per J. Abrahamsson &

Department of Chemical Engineering, Chalmers University of Technology, Sweden POSTER


Anders Rasmuson

53. FEM STUDY OF DIFFERENT ROLL COMPACTOR SEALING SYSTEM DESIGN

Alon Mazor, Lucia Perez-Gandarillas, Abderrahim Michrafy & Alain deRyck

Universitè de Toulouse, Mines Albi, CNRS, Centre RAPSODEE, Campus Jarlad, France POSTER

54. ON THE ROLE OF POROSITY FOR THE COMPRESSIBILITY AND TABLET TENSILE

STRENGTH OF GRANULES PREPARED BY DRY AND WET GRANUALTION

Josefina Nordström & Göran Alderborn

Department of Pharmacy, Uppsala University, Sweden POSTER

55. EFFECTS OF WATER QUANTITY ON TABLETS PROPERTIES MADE BY HIGH SHEAR

GRANULATION WITH L-HPC

Andreas Sauer1, Miyuki Fukasawa2 & Naosuke Maruyama3

1 SE-PFMD, Germany

2 Shin Etsu Chemical Co., Ltd, Cellulose Technical Support Center, Yokohama, Japan

3 Shin Etsu Chemicals Co., Specialty Research Center, Niigata, Japan

POSTER

56. NEW INSIGHTS IN SCALE UP OF SPHERONIZATION PROCESS

Dennis Thaete, Elena Reitz & Markus Thommes

Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Germany, POSTER

57. MICROSCOPIC MEASUREMENT OF LAYER

THICKNESS OF COATED PELLETS

Mario Scharmer1, Stefanie Bartsch1,

Jürgen Kodura1, Dimitri Wiegel2,

Bertram Wolf2 & Ingo Schellenberg1

1 Center of Life Sciences, Institute of Bioanalytical Sciences Anhalt University of Applied Science,

Germany

2 Department of Applied Biosciences and Process Engineering, Anhalt University of Applied Sciences,

Germany

ORAL

58. FLUID-BED MELT GRANULATION: GROWTH REGIME PREDICTION

M. Villa, I. Cotabarren, D. Bertín, J. Piña & V. Bucalá

Department of Chemical Engineering, PLAPIQUI, Universidad Nacional del Sur, CONICET, Argentina.

POSTER

59. ROLL COMPACTION AS AN ALTERNATIVE TO SPRAY-DRYING FOR THE PROCESSING OF Α-

LACTOSE MONOHYDRATE IN DIRECT COMPRESSION APPLICATIONS

Deeb Abu-Fara1, Iyad Rashid2, khouloud Alkhamis3, Mohammed

Shubair4, Mahmoud Al-Omari2, Adnan Badwan2

1 Chemical Engineering Department, University of Jordan, Jordan

2 The Jordanian Pharmaceutical Manufacturing Company, Jordan

3 Faculty of Pharmacy, Jordan University of Science and Technology, Jordan

4 Department of Pharmaceutics and Pharmaceutical Technology, Petra University, Amman, Jordan

ORAL

60. COMPUTATIONAL FLUID DYNAMIC SIMULATION OF A PERFORATED ROTATING BUCKET: AN

INDUSTRIAL CASE STUDY

Samuel Verdier1, Erwan Jarry1, Peter Olley2 & Nejat Rahmanian2

1 CESI Saint-Nazaire (Engineering School), France

2 School of Engineering and Informatics, University of Bradford, Bradford, UK

POSTER

61. ESTIMATION OF DESIGN SPACE FOR AN

EXTRUSION-SPHERONIZATION PROCESS USING RESPONSE SURFACE METHODOLOGY AND

ARTIFICIAL NEURAL NETWORK MODELING

Tamás Sovány1, Zsófia Tislér1,

Katalin Kristó1, András Kelemen2,

& Géza Regdon jr. 1

1 Department of Pharmaceutical Technology, University of Szeged, Hungary

2 Department of Computer Sciences, University of Szeged, Hungary

ORAL

62. EXPERIMENTAL INVESTIGATIONS TOWARDS

UNDERSTANDING IMPORTANT PARAMETERS IN WET DRUM GRANULATION OF BIOMASS

Klein E. Ileleji1, Rose P. Ambrose2,

Yi Li1 & Perry H. Doane3


2 Kansas State University, USA

3 ADM Research, USA

ORAL

63. PRODUCTION OF SELF-EMULSIFYING GRANULES

BY HIGH SHEAR GRANULATION PROCESS

Erica Franceschinis1, Andrea C.

Santomaso2, Laura Benda1, Beatrice Perissutti3, Dario Voinovich3 &

Nicola Realdon1

1 University of Padua, Italy

2 University of Padova, Italy

3 University of Trieste, Italy

ORAL

64. CHARACTERIZATION OF INDOMETHACIN

MICROPARTICLES FOR INHALATORY ADMINISTRATION

Nazareth E. Ceschan, Loreana C.

Gallo, Verónica Bucalá & María V. Ramírez-Rigo

Universidad Nacional del Sur (UNS), Argentina POSTER

65. INFLUENCE OF SPRAY DRYING PARAMETERS ON INTERNAL STRUCTURE AND MECHANICAL

PROPERTIES OF GRANULES

Susanna Eckhard & Manfred Fries Fraunhofer Institute for Ceramic Technologies and Systems IKTS, Germany ORAL

66. THE COMPRESSION BEHAVIOR OF BINARY AND

TERNARY EXCIPIENT BLENDS OF DIFFERENT MECHANICAL PROPERTIES

Faysal Al-akayleh1, Iyad Rashid2,

Mahmoud Al-Omari2, Mohammed shubair1, Adnan Badwan2

1 Petra University, Jordan


POSTER


67. HIGH SHEAR GRANULATION PROCESS USING

CRYSTALLINE SUGARS

Erica Franceschinis1, Chiara Pialorsi1,

Andrea C. Santomaso2, Federico Zorzi3, Gabriella Salviulo3 & Nicola

Realdon1

1 University of Padua, Italy



ORAL

68. FLUIDIZED-BED MELT GRANULATION:

POPULATION BALANCE MODELLING TO IDENTIFY THE AGGREGATION KERNEL

M. Villa, D. Bertín, I. Cotabarren, J.

Piña & V. Bucalá

Universidad Nacional del Sur, CONICET, Argentina POSTER

69. THE IMPORTANCE OF MIXING VESSEL CONFIGURATIONS ON THE DISPERSION OF FOOD

POWDERS IN WATER

W. Robert Mitchell1, 2, Laurent Forny3, Tim O. Althaus4, Gerhard

Niederreiter2, Stefan Palzer1, 5,

Michael J. Hounslow1 & Agba D. Salman5


2 Nestlé Product Technology Center, Switzerland

3 Nestlé Research & Development, Singapore

4 Nestlé Product Technology Center, UK

5 Nestlé Corporate Headquarters, Switzerland

POSTER

70. ANALYSIS OF A TWIN-SCREW GRANULATION

PROCESS USING A COMBINED EXPERIMENTAL AND COMPUTATIONAL APPROACH

Ashish Kumar1,2, Jurgen

Vercruysse3, Krist V. Gernaey 4, Thomas De Beer 2,* & Ingmar

Nopens1



3 Ghent University, Ghent, Belgium

4 Technical University of Denmark, Denmark

POSTER

71. FINITE VOLUME APPROXIMATIONS OF POPULATION BALANCE EQUATIONS

Jitraj Saha1, Jitendra Kumar1, Andreas Bück2 & Evangelos Tsotsas2

1 Indian Institute of Technology, India

2 Otto-von-Guericke University, Germany

ORAL

72. EFFECT OF POLYMERS ON THE STABILITY OF

ANHYDROUS OLANZAPINE DURING PROCESSING

Maria Paisana1, Martin Wahl 2 & João

F. Pinto3

1 Universidade de Lisboa, Portugal

2 Universität Tübingen, Germany

POSTER

73. KINETICS OF IMBIBITION OF A COLLOIDAL AGGREGATE

Alban Debacker1,2, Stanislav Makarchuk1, Didier Lootens2 &

Pascal Hébraud1

1 IPCMS/CNRS, France

2 SIKA, Switzerland

ORAL

74. DEVELOPMENT OF REGIME MAP FOR STEADY-

STATE HIGH SHEAR WET TWIN-SCREW GRANULATION

Ashish Kumar1,2, Jens Dhondt2,

Jurgen Vercruysse3, Fien De Leersnyder2, Valérie Vanhoorne3,

Krist V. Gernaey 4, Thomas De Beer

2,* & Ingmar Nopens1

1 BIOMATH, Ghent University, Belgium


3 Ghent University, Ghent, Belgium

4 Technical University of Denmark, Denmark

ORAL

75. COMPARISON OF EXCIPIENT ONLY & DRUG

FORMULATIONS FOR TWIN-SCREW CONTINUOUS GRANULATOR

Ian P. Gabbott, Adam Khan & Gavin

K. Reynolds

Pharmaceutical Development, AstraZeneca, Macclesfield, UK POSTER

76. THE APPLICATION OF TERAHERTZ PULSED IMAGING IN CHARACTERISING DENSITY

DISTRIBUTION OF ROLL-COMPACTED RIBBONS

Chuan-Yu Wu1, Jianyi Zhang1, Chunlei Pei1, Serena Schiano1 &

David Heaps2

1 Department of Chemical and Process Engineering, University of Surrey, UK

2 Advantest Inc., Princeton, USA

ORAL

77. DE-MIXING CHARACTERISTICS OF FINE COAL IN

AN AIR DENSE MEDIUM FLUIDIZED BED

Pengfei Zhao1, Yuemin Zhao2,

Zhenfu Luo2 & Ran Zhu1

1 China University of Mining and Technology, China

2 China University of Mining and Technology, China

POSTER

78. THE COMBINED EFFECT OF WET GRANULATION PROCESS PARAMETERS AND GRANULE MOISTURE

CONTENT ON TABLET QUALITY ATTRIBUTES

Farhan Al Husban & Ian P. Gabbott AstraZeneca, UK ORAL

79. INFLUENCE OF LIQUID FORMULATION AND IMPACT CONDITIONS ON THE WETTING OF

HYDROPHOBIC SURFACES BY AQUEOUS

POLYMERIC SOLUTIONS

Amal Khoufech, Mohammed Benali, Jérémie Castello & Khashayar Saleh

Laboratoire de Transformations Intégrées de la Matière Renouvelable, France ORAL


80. A ROBUSTNESS STUDY OF AN EXTENDED-

RELEASE TABLET FORMULATION USING A SAMPLE KIT OF HYPROMELLOSE FOR QBD

CONCEPT

Shilpa Mistry1, Takafumi Hoshino2 &

Hiroyasu Kokubo2


2 Shin-Etsu Chemical Co., Ltd., Japan

POSTER

81. EVALUATION OF A NEW CO-PROCESSED

EXCIPIENT FOR ORALLY-DISINTEGRATING TABLETS

S. Mistry1, Y. Hirama2, S. Obara2 &

N. Maruyama2


2 Shin-Etsu Chemical Co., Ltd., Japan

POSTER

82. THE INTERDEPENDENCY OF MATERIAL, PROCESS AND EQUIPMENT PARAMETERS FOR EXTRUSION-

SPHERONISATION FORMULATIONS

John A. Collins1, Ahmad B. Albadarin2, Mark T. Davis2, David

Egan3, Ciara S. Griffin2 & Gavin M.

Walker1,2,4

1 University of Limerick, Ireland



4 Queens University Belfast, UK

POSTER

83. THE EFFECTS OF COMPRESSION SPEED, PUNCH SHAPE AND WALL FRICTION ON

THERMOMECHANICAL BEHAVIOUR OF POWDERS

DURING COMPRESSION

Alexander Krok1,2, Marian Peciar2 & Chuan-Yu Wu1

1 University of Surrey, UK

2 Slovak University of Technology, Slovakia

POSTER

84. EFFECTS OF POLYMER TYPE, PARTICLE SIZE AND

ADDITIVE ON THE MICROMERITIC AND DISSOLUTION PROPERTIES OF THEOPHYLLINE

GRANULES AND TABLETS

E.I Akpabio1, O.N.C. Umeh2, M.O.

Emeje3 & S.I. Ofoefule2

1 University of Uyo, Nigeria

2 University of Nigeria, Nsukka

3 National Institute for Pharmaceutical Research and Development, Nigeria

ORAL

85. MICRO-STRUCTURE OF MALTODEXTRIN

AGGLOMERATES PRODUCED IN FLUIDIZED BED

Reihaneh Pashminehazar, Abdolreza

Kharaghani & Evangelos Tsotsas

Otto von Guericke University Magdeburg, Germany ORAL

86. INVESTIGATING THE EXTRUSION-SPHERONISATION OF PHARMACEUTICAL PASTES

Matthew P. Bryan, Sarah L. Rough & D. Ian Wilson

New Museums Site, UK ORAL

87. REDUCTION OF ENERGY CONSUMPTION IN

FLUIDIZED BED GRANULATION PROCESSES

Lisa Mielke1, Torsten Hoffmann1,

Mirko Peglow2, Markus Henneberg3,

Andreas Bück1 & Evangelos Tsotsas1

1 Otto-von-Guericke University, Germany

2 IPT Pergande GmbH, Germany

3 Anhaltinische Verfahrens- und Anlagentechnik GmbH, Germany

POSTER

88. DROP IMPACT BEHAVIOUR ON ALTERNATELY HYDROPHOBIC AND HYDROPHILIC LAYERED

BEAD PACKS

Shaun Atherton1, Christopher A. E. Hamlett1, Neil J. Shirtcliffe2, Glen

McHale3, Sujung Ahn4, Stefan H.

Doerr4, Robert Bryant4 & Michael I. Newton1

1 Nottingham Trent University, UK

2 Department of Technology and Bionics, Germany

3 Northumbria University, UK

4 Swansea University, UK

ORAL

89. STOCHASTIC MODELING OF LAYERING GROWTH PROCESSES IN FLUIDIZED BEDS

Christian Rieck, Andreas Bück & Evangelos Tsotsas

Otto-von-Guericke-University, Germany POSTER

90. IMPACT OF SCREW CONFIGURATION ON THE PARTICLE SIZE DISTRIBUTION OF GRANULES

PRODUCED BY TWIN SCREW GRANULATION

J. Vercruysse1, A. Burggraeve2, M. Fonteyne3, P. Cappuyns4, U. Delaet5,

I. Van Assche5, T. De Beer3, J.P.

Remon1 & C. Vervaet1


2 Janssen Pharmaceutica, Beerse




POSTER

91. CFD SIMULATION OF PARTICLE RESIDENCE TIME DISTRIBUTION IN MULTISTAGE FLUIDIZED BEDS

Kaicheng Chen1, Lisa Mielke1, Andreas Bück1, Michael Jacob2 &

Evangelos Tsotsas1

1 Otto-von-Guericke-University, Germany


POSTER

92. POPULATION BALANCE MODELING OF SPRAY GRANULATION

IN HORIZONTAL FLUIDIZED BEDS

Katja Meyer, Reihaneh Pashminehazar, Andreas Bück &

Evangelos Tsotsas

Otto-von-Guericke University, Germany POSTER


93. EXPERIMENTAL INVESTIGATION OF PROCESS

STABILITY OF CONTINUOUS SPRAY FLUIDIZED BED LAYERING PROCESSES

Martin Schmidt, Christian Rieck,

Andreas Bück & Evangelos Tsotsas

Otto-von-Guericke University, Germany POSTER

94. ELIMINATING BI-MODAL PSD’S IN A CONTINUOUS TWIN SCREW WET GRANULATION PROCESS

Jim Holman1 & Tessa Van Hoek2 1 GEA Pharma Systems Ltd, UK

2 GEA Pharma System nv, Belgium

POSTER

95. MANUFACTURING AND MECHANICAL TESTING OF

BRIQUETTES FROM INERTINITE-RICH HIGH ASH COAL FINES USING VARIOUS BINDERS

Nthabiseng T. Modiri1, John R.

Bunt1, 2, Hein W.J.P. Neomagus1 & Frans B. Waanders1

1 North-West University, South Africa

2 Sasol Technology (PTY) Ltd., South Africa

POSTER

96. EFFECT OF HIGH-SHEAR WET GRANULATION PROCESS SCALE-UP ON THE DISSOLUTION

KINETICS OF HIGH-ACTIVE PHARMACEUTICAL GRANULES

David Smrčka1, Jiří Dohnal2 & František Štěpánek1

1 Institute of Chemical Technology Prague, Czech Repblic

2 Zentiva, k.s., Czech Republic

ORAL

97. DISCRETE ANALYSIS OF PARTICLE COLLISION

BEHAVIOR IN FLUIDIZED BEDS

Thomas Hagemeier, Zhaochen Jiang,

Andreas Bück & Evangelos Tsotsas

University of Magdeburg, Germany ORAL

98. MESOSCALE MODEL AND EXPERIMENTAL ANALYSIS OF COLLOIDS AGGREGATION FOR

COATING AND BINDER FORMULATION

Jarray Ahmed, Gerbaud Vincent & Hémati Mehrdji

Université de Toulouse, France ORAL

99. EXPERIMENTAL AND CFD SIMULATION FOR A LAB-SCALE FLUDIZED BED GRANULATION

PROCESS WITH WURSTER TUBE

Haigang Wang1, Guzhi Qiu1, Jiamin Ye1 & Wuqiang Yang2

1 Chinese Academy of Sciences, UK

2 University of Manchester, UK

ORAL

100. DEVELOPMENT OF A CONTROLLED RELEASE FORMULATION BY CONTINUOUS TWIN SCREW

GRANULATION

Valérie Vanhoorne1, Jurgen Vercruysse1, Fien De Leersnyder2,

Thomas De Beer2 Jean-Paul Remon1 & Chris Vervaet1

1 Laboratory of Pharmaceutical Technology, Ghent University, Belgium

2 Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium

POSTER

101. ASYMMETRIC DISTRIBUTION IN TWIN SCREW

GRANULATION

Tim Chan Seem1, Neil A. Rowson1,

Ian Gabbot2, Marcel de Matas2, Gavin

K. Reynolds2 & Andy Ingram1

1 School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, UK

2 Pharmaceutical Development, AstraZeneca, Macclesfield, UK

ORAL

102. ROLL COMPACTION OF SPRAY-DRIED MANNITOL

USING DIFFERENT COMPACTION DESIGNS AND PROCESS PARAMETERS

Kitti Csordas & Peter Kleinebudde Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Dusseldorf, Germany POSTER

103. PRACTICAL APPLICATION OF UNIFIED COMPACTION CURVE TO ROLLER COMPACTION

FORMULATION DESIGN AND EQUIPMENT TRANSFER

Gavin K. Reynolds, Ron J. Roberts, S. Claxton, Andreja Mirtic & Jeff Parry

Pharmaceutical Development, AstraZeneca, Macclesfield, UK POSTER

104. CONTROL STRATEGIES FOR ALTERNATIVE CONFIGURATIONS IN CONTINUOUS INDUSTRIAL

GRANULATION PROCESSES

Ivana M. Cotabarren, Diego E. Bertín, Verónica Bucalá & Juliana Piña

Department of Chemical Engineering, PLAPIQUI, Universidad Nacional del Sur, CONICET, Argentina

ORAL

105. IMPROVED MICROENCAPSULATION PROCESS FOR

PROBIOTICS BY BOTTOM SPRAY FLUIDIZED BED GRANULATION AND WURSTER COATING WITH

MALTODEXTRIN AND SHELLAC

Ádám Gy. Nagy1,2, Christopher

Beermann2 & Günter J. Esper2

1 Erdősor Street 4. X./60. H-1046, Budapest, Hungary

2 Faculty of Food Technology, University of Applied Sciences of Fulda, Germany

ORAL

106. UNDERSTANDING CONTENT NON-HOMOGENEITY IN HIGH SHEAR WET GRANULATION: EFFECTS OF POWDER SEGREGATION, PREFERENTIAL WETTING

AND SOLUBILITY

Sarang S. Oka 1, Heather N. Emady1, Ondřej Kašpar2, Viola Tokárová2, František Štěpánek2, Rohit

Ramachandran1 & Fernando J.

Muzzio1

1 Department of Chemical & Biochemical Engineering, Rutgers, The State University of New Jersey, USA

2 Department of Chemical Engineering, Institute of Chemical Technology Prague, Czech Republic

POSTER


107. EVALUATION OF THE TABLET SURFACE FLOW

VELOCITIES WITHIN PAN COATERS WITH IMPLICATION TO PROCESS UNDERSTANDING

Rok Dreu1, Gregor Toschkoff2,

Adrian Funke3, Andreas Altmeyer4, Klaus Knop5, Johannes Khinast2 &

Peter Kleinebudde5

1 Department of Pharmaceutical Technology, University of Ljubljana, Slovenia

2 Research Center Pharmaceutical Engineering GmbH, Austria

3 Global Chemical and Pharmaceutical Development, Bayer Pharma AG, Germany

4 L.B. Bohle Maschinen Verfahren GmbH, Germany

5 Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Germany

ORAL

108. MEASUREMENT OF PARTICLE CONCENTRATION IN A WURSTER COATER DRAFT TUBE USING LIGHT

ATTENUATION

Rok Šibanc1, Iztok Žun2 & Rok Dreu1

1 Faculty of Pharmacy, University of Ljubljana, Slovenia

2 Faculty of Mechanical Engineering, University of Ljubljana, Slovenia

ORAL

109. INFLUENCE OF MODIFIED WURSTER DRAFT TUBE

ON COATING UNIFORMITY OF PELLETS

Matevž Luštrik & Rok Dreu Department of Pharmaceutical Technology, Faculty of pharmacy, University of Ljubljana, Slovenia POSTER

110. EFFECTS OF TYPE OF BATCH GRANULATOR ON FORMATION OF SEEDED GRANULES

Mbako Jonas & Nejat Rahmanian School of Engineering and Informatics, University of Bradford, Bradford, UK ORAL

111. INFLUENCE OF EXCIPIENT MATERIAL PROPERTIES ON A DRY GRANULATION PROCESS

Mary E. Crowley1,2, Graham E. O Mahony1,2 Micheal A.P. McAuliffe3,

Rakesh C. Dontireddy1 & Abina M.

Crean1,2



3 Centre for Advanced Photonics and Process Analysis, Applied Physics and Instrumentation

Department, Cork Institute of Technology, Cork

POSTER

112. THE DEVELOPMENT OF AN NIR INTERFACING

DEVICE FOR THE IN-LINE MONITORING OF A CONTINUOUS TWIN-SCREW GRANULATION

PROCESS

Fien De Leersnyder1, Elisabeth

Peeters2, Chris Vervaet2, Jean Paul Remon2 & Thomas De Beer1

1 Laboratory of Pharmaceutical Process Analytical Technology, Belgium

2 Laboratory of Pharmaceutical Technology, Belgium

POSTER

113. EVALUATION OF OPERATING MODE AND SEED

PARTICLE SIZE ON TOP SPRAY FLUIDIZED BED ENCAPSULATION OF HERBAL EXTRACT BY

PRESSURE FLUCTUATION ANALYSIS

Lucimara Benelli & Wanderley P.

Oliveira

Laboratory of R&D on Pharmaceutical Process, LAPROFAR, University of São Paulo, Faculty of

Pharmaceutical Sciences of Ribeirão Preto, Brazil

ORAL

114. COMPARTMENTAL APPROACH TO WET

GRANULATION MODELS WITHIN A

FLOWSHEETING FRAMEWORK

Daniel A. Pohlman1, David Slade3,

Sean Bermingham3, Mark Bollinger4,

Poul Bach4, & James D. Litster1,2

1 Department of Chemical Engineering, Purdue University, USA

2 Department of Industrial and Physical Pharmacy, Purdue University, USA

3 Process Systems Enterprise Limited, United Kingdom

4 Novozymes A/S, Denmark

POSTER

115. THE INFLUENCE OF MANUFACTURING METHOD ON PHYSICAL PROPERTIES AND DRUG RELEASE

FROM PUSH PULL OSMOTIC PUMP (PPOP) PRODUCTS

Gus LaBella1, Manish Ghimire2, Manish Rane1 & Piyush Patel1

Colorcon, Inc., USA

Colorcon Ltd., Flagship House Victory Way Dartford Kent DA2 6Q, UK

POSTER

116. EFFECT OF VARYING PROCESS PARAMETERS ON GRANULE SIZE DISTRIBUTION OF ROLL

COMPACTED MCC, MANNITOL AND THEIR

MIXTURES

Ana Pérez Gago & Peter Kleinebudde Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Germany POSTER

117. COMPRESSIVE STRENGTH OF PHARMACEUTICAL

PELLETS SPRAY COATED IN A WURSTER

FLUIDIZED BED

Alexander Russell1, Rok Šibanc2,

Peter Müller1, Rok Dreu2 & Jürgen

Tomas1

1 Chair for Mechanical Process Engineering, Otto von Guericke University of Magdeburg, Germany

2 Chair for Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Slovenia

POSTER

118. IMPROVING THE FUNCTIONAL PERFORMANCE OF EXCIPIENTS: EMPLOYING THE KNOWLEDGE OF

INTERACTIVE MIXING

Sharad Mangal, Felix Meiser, David AV. Morton & Ian Larson

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, Australia ORAL

119. ADVANCED CHARACTERISATION AND MODELLING TO PREDICT IRON ORES

Rafael J. Contreras1, Frédéric Van Loo1, Maxime Evrard2, Marek

1 Centre for Research in Metallurgy, Avenue du bois St. Jean/21 Liège, Belgium


POSTER


GRANULATION BEHAVIOUR Schöngut3, Eric Pirard2 & František

Štěpánek3

3 Department Génie Minéral, Matériaux et Environnement, University of Liège, Belgium

120. DEVELOPMENT OF DRY GRANULATES: FROM CA.

25 GRAMS PER FORMULATION TOWARDS LARGE SCALE ROLLER COMPACTION (WITH A GERTEIS

MACRO OR MINI-PACTOR)

Barbara Fretter 1, Katharina Freischlad

1 & Robert F. Lammens 2

1 Solids Development Consult GmbH, Germany

2 Gerteis Maschinen + Processengineering AG, Switzerland

ORAL

121. GRANULATION OF BIOWASTE INTO GREEN FERTILIZER: OPTIMISATION OF THE ENERGY

CONSUMPTION OF A GRANULATION PLANT USING ASPEN PLUS

Emma Stuart, Yoann F. Glocheux, Matheus R. Mendes de Araújo, Ahmad

B. Albadarin & Chirangano Mangwandi

Queen's University Belfast, School of Chemistry and Chemical Engineering, UK

POSTER

122. INVESTIGATION OF NUCLEATION IN TWIN SCREW GRANULATOR USING COMPACT POWDER BEDS

Qing Ai, Ranjit M. Dhenge, Michael J. Hounslow & Agba D. Salman

Department of Chemical and Biological Engineering, University of Sheffield, UK POSTER

123. SPOUTING IN A PRISMATIC BED: A NUMERICAL

AND EXPERIMENTAL EVALUATION

Vitalij Salikov1, Stefan Heinrich1,

Sergiy Antonyuk2, Vinayak S.

Sutkar3, Niels G. Deen3 & J.A.M. Kuipers3


Germany

2 Particle Process Engineering, Department of Mechanical and Process Engineering, University of

Kaiserslautern, Germany

3 Multiphase Reactors Group, Department of Chemical Engineering and Chemistry, NL

ORAL

124. TWIN SCREW GRANULATION: EFFECT OF FILL LEVEL

Sushma V. Lute, Ranjit M. Dhenge, Michael J. Hounslow & Agba D.

Salman


125. MAGNETIC PARTICLE TRACKING: ANALYSIS OF THE PARTICLE MOTION IN ROTOR BASED

GRANULATION EQUIPMENT

Johannes Neuwirth & Stefan Heinrich Institute of Solids Process Engineering and Particle Technology, Hamburg University of Technology, Germany

POSTER

126. DESIGN OF GRANULAR ADSORBENT MATERIAL FOR ASERNIC REMOVAL FROM CONTAMINATED

WASTEWATER

Chirangano Mangwandi1, Siti Nur Ain Suhaimi, Jiang Tao Liu,Yoann F.

Glocheux1 & Ahmad B. Albadarin1,2

1 Queen's University Belfast, UK


ORAL

127. INVESTIGATION OF THE GRANULAR DISPERSION BEHAVIOUR IN A FLUID BED ROTOR PROCESSOR

Johannes Neuwirth & Stefan Heinrich Institute of Solids Process Engineering and Particle Technology, Hamburg University of Technology, Germany

POSTER

128. UNDERSTANDING THE INFLUENCE OF GRANULE MICROSTRUCTURE ON GRANULE COMPRESSION

BREAKAGE

Steven A. Dale1, Maksym Dosta2, Sergiy Antonyuk3, Carl Wassgren1,

Stefan Heinrich2 & James D. Litster1


2 Hamburg University of Technology, Germany

3 University of Kaiserslautern, Germany

POSTER

129. REAL-TIME PARTICLE IMAGING OF PHARMACEUTICAL TABLET DISINTEGRATION

Arthi D. Rajkumar1, Gavin K. Reynolds2, David Wilson2, Michael J.

Hounslow1 & Agba D. Salman1

1 Department of Chemical and Biological Engineering, University of Sheffield, UK

2 AstraZeneca, Charter Way, UK

POSTER

130. AN EXPERIMENTAL STUDY OF DROPLET-PARTICLE COLLISIONS

Sandip K. Pawar1, Filip Henrikson1, Giulia Finotello1, Johan T. Padding1,

Niels G. Deen1, Alfred Jongsma2,

Fredrik Innings2 & J.A.M. Kuipers1

1 Multiphase Reactors Group, Department of Chemical Engineering and Chemistry,

Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, NL

2 Tetra Pak CPS, Heerenveen, NL

ORAL

131. KINETICS OF IMMERSION NUCLEATION DRIVEN

BY SURFACE TENSION

Kate Pitt1, Rachel Smith1, Michael J

Houslow1, James D. Litster2

1 University of Sheffield, Sheffield, UK


POSTER

132. MOVEMENT OF SECONDARY IMMISCIBLE LIQUID WITHIN A SUSPENSION USING X-RAY CT

Syed F. Islam1, Steve Whitehouse2, Ramana V. Sundara2, Tim O.

Althaus2, Stefan Palzer3, Michael J. Hounslow1 & Agba D. Salman1


2 Nestlé PTC York, York, UK

3 Nestlé Headquarters, Vevey, Switzerland

ORAL


133. TWIN SCREW WET GRANULATION: EFFECT OF

TYPES OF POWDERS

Ranjit M. Dhenge1, Sushma V. Lute1,

Chalak S. Omar1, Mohammed F. Saleh1, James J. Cartwright2, Michael

J. Hounslow1 & Agba D. Salman1


2 GSK, Third Avenue, Harlow, Essex, CM19 5AW, UK

POSTER

134. ENGINEERING PLASTICITY MODEL OF ROLL COMPACTION

J. W. Andrews1, M.J Adams1, C-Y Wu2 & G. Reynolds3

1 School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, UK

2 Department of Chemical and Process Engineering, University of Surrey, Guildford, UK

3 Pharmaceutical Development, AstraZeneca, Macclesfield, Cheshire, UK

ORAL

135. MAKING INDIVIDUAL PARTICLE INTERACTIONS IN PRESSURE AGGLOMERATION OF AMORPHOUS

FOOD POWDERS ACCESSIBLE

Christine I. Haider1 , Tim Althaus2, Gerhard Niederreiter3, Stefan Palzer4,

Michael J. Hounslow1, Agba D. Salman1



3 Nestlé PTC Orbe, Switzerland


POSTER

136. FLUIDIZED BED COATING CONTROL BY IN-LINE PARTICLE SIZE MEASUREMENT

Dimitri Wiegel1, Guenther Eckardt2, Michael Jacob3, Mario Scharmer4,

Ingo Schellenberg4 & Bertram Wolf1

1 Department of Applied Biosciences and Process Engineering, Anhalt University of Applied Sciences, Germany

2 Parsum GmbH, Germany


4 Institute of Bioanalytical Sciences, Anhalt , University of Applied Sciences, Germany

POSTER

137. A PROPOSAL FOR A DRUG PRODUCT MANUFACTURING CLASSIFICATION SYSTEM

(MCS) FOR ORAL SOLID DOSAGE FORMS

Michael Leane1, Kendal Pitt2 & Gavin Reynolds3

1 Bristol-Myers Squibb, Moreton, UK

2 GlaxoSmithKline, Ware, UK

3 AstraZeneca, Macclesfield, UK

POSTER

138. UNDERSTANDING AND PREVENTING AGGLOMERATION IN FILTER DRYING PROCESS

Hong Lee Lim1, Karen P. Hapgood1 & Brian Haig2

1 Monash Advanced Particle Engineering Laboratory, Department of Chemical Engineering, Australia

2 GlaxoSmithKline, Australia

ORAL

139. CREATING TUNEABLE AGGLOMERATES VIA 3D

PRINTING

Ruihuan Ge1, Mojtaba Ghadiri2 &

Karen Hapgood1

1 Monash Advanced Particle Engineering Laboratory, Department of Chemical Engineering, Australia

2 Institute of Particle Science and Engineering, University of Leeds, UK

POSTER

140. USE OF FOAM IN TOP-SPRAY FLUIDIZED BED GRNULATION: EFFECT OF VARIABLES ON

GRANULES QUALITY ATTRIBUTES

Vinita Kale, Kalyan Wagh & Abhay Ittadwar

Department of Pharmaceutics, Gurunanak College of Pharmacy, Nagpur, India ORAL

141. EFFECT OF COLLOIDAL SILICA DIOXIDE ON RHEOLOGICAL PROPERTIES OF COMMON

PHARMACEUTICAL EXCIPIENTS

Diana Majerová1, Lukáš Kulaviak2, Marek Růžička2 & František

Štepanek3

1 Department of Organic Technology, Institute of Chemical Technology, Prague, Czech Republic

2 Institute of Chemical Process Fundamentals of the ASCR, Prague, Czech Republic

3 Department of Chemical Engineering, Institute of Chemical Technology, Prague, Czech Republic

POSTER

142. EFFECT OF VARYING VOLUME OF A SECONDARY IMMISCIBLE LIQUID ON THE MOVEMENT WITHIN

A SUSPENSION

Syed F. Islam1, Steve Whitehouse2, Ramana V. Sundara2, Tim O.

Althaus2, Stefan Palzer3, Michael J.





POSTER

143. UNDERSTANDING PHARMACEUTICAL POWDER

BLENDING - IRON OXIDE TRACER BEHAVIOUR

AND DIFFERENT EXCIPIENT POWDERS

Kahlil Desai1, Karen Hapgood1,

David Barling2, Peter Stewart2, David

Morton2

1 Monash Advanced Particle Engineering Lab, Department of Chemical Engineering, Monash

University, Australia

2 Monash Institute of Pharmaceutical Science, Monash University, Australia

POSTER

144. NOVEL ELECTROSTATIC IONIZER FOR CHARGED

POLYPROPYLENE GRANULES

Kwangseok Choi 1, Tomofumi

Mogami 2, Teruo Suzuki 2 & Mizuki Yamaguma 1

1 Japan National Institute of Occupation Safety and Health, Tokyo, Japan

2 Kasuga Denki, 2-4 Shinkawasaki, Saiwai, Kanagawa, Japan

POSTER

145. DEVELOPMENT AND CHARACTERISATION OF SLAKED LIME GRANULES FOR CHEMISORPTION IN

DESULPHURATION REACTORS

Erik Nordenswan1, Annica Lindfors1, Nenne Nordström1 & Abhay Bulsari2

1 Nordkalk Oy Ab, Pargas, Finland

2 Abhay Bulsari, Ab Nonlinear Solutions Oy, Turku, Finland

ORAL


146. INNOVATIVE GRANULATED MATERIALS FROM

INDUSTRIAL AND ORGANIC WASTES AS SORBENTS FOR WASTEWATER TREATMENT

Evgenia Iakovleva1, 2, Mika

Sillanpää1, Philipp Maydannik1, Stephen Allen2, Ahmad B.

Albadarin2,3 & Chirangano

Mangwandi2

1 Chemtech, Laboratory of Green Chemistry, Lappeenranta University of Technology, Finland

2 Innovative Molecular Materials (IMM) Group, School of Chemistry and Chemical Engineering,

Queen's University Belfast, UK

3 University of Limerick, Department of Chemical and Environmental Science, Ireland

POSTER

147. AGGLOMERATION OF FINE COAL USING A HIGH VISCOSITY WATER-IN-OIL EMULSION

Kim van Netten, Roberto Moreno-Atanasio & Kevin P. Galvin

Centre for Advanced Particle Processing and Transport, Newcastle Institute for Energy and Resources, University of Newcastle, Callaghan, Australia

ORAL

148. EFFECTS OF BINDER ADDITION POLITICS ON THE WET AGGLOMERATION PROCESS

Silvia Nalesso1, Erica Franceschinis2, Nicola Realdon2 & Andrea C.

Santomaso1

1 APTLab-Advanced Particle Technology Laboratory Department of Industrial Engineering University of Padova, Italy

2 PharmaTeG-Pharmaceutical Technology Group- Department of Pharmaceutical and Pharmacological Science, University of Padua, Italy

POSTER

149. VOLCANIC ASH AGGREGATION IN THE LAB – CAN WE MIMIC NATURAL PROCESSES?

Sebastian B. Mueller1, Ulrich Kueppers1, Michael Jacob2, Paul

Ayris1, Donald B. Dingwell1, Melanie Guttzeit2, Ulrich Walter2

1 Ludwig-Maximilians-Universität München (LMU), Department of Earth and Environmental Sciences, Theresienstrasse 41, 80333 München, Germany

2 Glatt Ingenieurtechnik GmbH, Weimar, Germany

POSTER

150. WET GRANULATION IN A MINI TWIN SCREW EXTRUDER: EFFECT OF PROCESS AND

FORMULATION VARIABLES ON RESIDENCE TIME DISTRIBUTION AND GRANULE CHARACTERISTICS

Manuel Kuhs1, Ahmad B. Albadarin1,2, David Egan1, Shaikh

Rahamatullah1, Mark Southern1, Denise Croker1, Gavin Walker1

1Chemial & Environmental Sciences, University of Limerick, Plassey, Co. Limerick, Ireland

2School of Chemical Engineering, Queen’s University Belfast, Belfast, United Kingdom

POSTER

151. MODELLING OF PARTICLE-AIR INTERACTIONS DURING FLOW INTO CLOSED CAVITIES

H. Elmsahli, A. Alharbi, R. Baserinia and I.C. Sinka

Department of Engineering, University of Leicester, UK POSTER

152. FORMULATION AND EVALUATION OF METHACRYLIC AND POLY (ACRYLIC) ACID

MATRIX TABLETS OF MEBENDAZOLE FOR COLON TARGETED DELIVERY

J.E Okorie, F.N Uba, O.N.C Umeh & S.I Ofoefule

Drug Delivery and Nanotechnology Research Unit (RUNDD)

Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nigeria

POSTER

153. APPLICATION OF THE EYECON, AN IN-LINE NON

PRODUCT CONTACT PROCESS ANALYTICAL

TECHNOLOGY TO PERFORM PARTICLE

CHARACTERISATION DURING FLUIDISED BED PROCESSES

Paul Cruise1, Emmet Hogan1, Ian

Jones1, Stephen Banahan1, Claudio

Cortazzo2, Joachim Fröhlich2, Lilia

Sprich2, Raoul Pila2

1 Innopharmalabs 405 Q House, Furze Road, Sandyford Industrial Estate, Dublin 18, Ireland

2 Glatt GmbH, Process Technology, Binzen, Germany

POSTER

154. USE OF MULTIEYE, AN IN-LINE NIR BASED PAT SOLUTION FOR REAL-TIME, NON-PRODUCT

CONTENT MONITORING OF MOISTURE CONTENTS IN A FLUIDISED BED GRANULATION/DRYING

PROCESS

Paul Cruise1, Luke Kiernan1, David Byrne1 Ian Jones1, Denisio Togashi2


2 Dublin Institute of Technology (DIT), Cathal Brugha Street, Dublin 1

POSTER

155. EVALUATION OF THE GRANULATION PROCESS USING FLOW AND PARTICLE SIZE ANALYSIS

PARAMETERS

Eduardo J. Barbosa, Natalia V. Souza, Leandro Giorgetti, Marcelo D. Duque,

Michele G. Issa & Humberto G. Ferraz

Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 580, Cidade Universitária, São Paulo, Brazil

POSTER

156. HIGH SHEAR GRANULATION PROCESSING

PARAMETERS ON THE MECHANICAL PROPERTIES

OF DIATOMITE BASED POROUS GRANULATES (FOR

THE MACRO SCALE I: PROCESSING FOR GRANULATION)

Yujing Liu, Dagobert Scharf, Thomas

Graule & Frank Clemens

EMPA, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for High

Performance Ceramics, Duebendorf, Switzerland

POSTER

157. A PRACTICAL APPROACH FOR THE SCALE UP OF ROLLER COMPACTION PROCESS

Weixian Shi & Omar Sprockel Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive ORAL

158. RESPONSIVE POLYMER COATED PARTICLES FOR CONSUMER PRODUCTS

Lisa E. Scullion, Paul. H Findlay & David A. Pears

Revolymer (U.K.) Limited, 1 Newtech Square, Zone 2, Deeside Industrial Park, Flintshire, UK POSTER


159. ASSESSMENT OF WETTING AND DISPERSING

MEASUREMENTS OF DAIRY POWDERS AND THE AGGLOMERATES

Junfu Ji1, 2, John Fitzpatrick2, Kevin

Cronin2, Abina Crean3 & Song Miao1

1 Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland

2 School of Engineering, University College Cork, College Road, Cork, Ireland

3 School of Pharmacy, University College Cork, College Road, Cork, Ireland

POSTER

160. THE SPECIFICATIONS FOR THE SUSTAINABLE-DESIGN OF THERMO-HYDRO-MECHANICAL

PROCESSES OR THE ELABORATION OF

AGGLOMERATED PRODUCTS

Bettina Bellocq, Agnès Duri, Bernard Cuq & Thierry Ruiz

UMR IATE 1208 CIRAD/INRA/Montpellier SupAgro/Université Montpellier – 2 Place Pierre Viala,

Montpellier cedex 5, France

POSTER

161. DETERMINATION OF COMPARTMENT RESIDENCE

TIMES WITHIN BATCH GRANULATORS USING COLORIMETRIC ANALYSIS

Andrew D. McGuire, Sebastian

Mosbach, Kok Foong Lee & Markus Kraft

Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK POSTER

162. DEVELOPMENT OF EXTENDED RELEASE coated PELLETS FOR HYPERTENSION AND ANGINA

TREATMENT

Luciane F. G. Souza1 , Marcello Nitz1 & Osvaldir P. Taranto2

1 School of Chemical Engineering, Mauá Institute of Technology (IMT), São Caetano do Sul, SP, BR

2 School of Chemical Engineering, University of Campinas (UNICAMP), Campinas, SP, BR

ORAL

163. STUDY ON TWO-WAY COUPLING OF GAS-SOLID TWO-PHASE FLOW OF CYLINDRICAL PARTICLES

Cai Jie1,2, Zhong Wen Qi1 & Yuan Zhu Lin2

1 Thermal-Energy Institute, Southeast University, 78 Bancang street, Nanjing, P. R. C.

2 School of Energy and Mechanical Engineering, Nanjing Normal University, 2 Sipailou, Nanjing, P. R. C.

ORAL

164. MODEL PREDICTIVE CONTROL OF CONTINUOUS MECHANOCHEMICAL SYNTHYSIS BASED ON SELF-

SUSTAINING REACTIONS

Ahmad B. Albadarin1,2, Ciara Griffin, Mark Davis, David Egan1, and Gavin

Walker1,2

1 Chemial & Environmental Sciences, University of Limerick, Plassey, Co. Limerick, Ireland

2 School of Chemical Engineering, Queen’s University Belfast, University Road, Belfast, United Kingdom

POSTER

165. MECHANOCHEMICAL SYNTHYSIS OF HYDROXYAPATITE EMPLOYING HIGH AND LOW

SHEAR MILLING PROCESSES

Ahmad B. Albadarin1,2, Ciara Griffin, Mark David, David Egan1, and

Gavin Walker1,2


2 School of Chemical Engineering, Queen’s University Belfast, University Road, Belfast, United Kingdom

POSTER

166. LIQUISOLID TECHNOLOGY APPLIED TO PELLETS

Bianca R. Pezzini1, 2, André O. Beringhs3, Humberto G. Ferraz1,

Marcos A. Segatto Silva3, Hellen K.

Stulzer3 & Diva Sonaglio3

1 Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

2 Department of Pharmacy, University of Joinville Region, Joinville, Brazil

3 Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, Brazil

POSTER

167. COUPLED GAS FLOW AND POWDER DEFORMATION UNDER ROLLER COMPACTION

Abderrahim Michrafy, Lucia Prerez Gandarillas, Alon Mazor

Université de Toulouse, Mines Albi, CNRS, Rapsodee, Campus Jarlard, Albi cedex 09, France POSTER

168. PROTECTIVE EFFECT OF SUGARS ON THE VIABILITY OF LACTOBACILLUS RHAMNOSUS GG

AFTER SPRAY-DRYING

Géraldine AM. Broeckx & Filip Kiekens

Department of Pharmaceutical Technology and Biopharmacy, University of Antwerp, Wilrijk, Belgium POSTER

169. INVESTIGATION OF THE AXIAL PARTICLE

TRANSPORT IN A CONTINUOUSLY OPERATED HOROZONTAL FLUIDIZED BED

Eugen Diez & Stefan Heinrich Institute of Solids Process Engineering and Particle Technology, Hamburg University of Technology,

Denickestraße 15, 21073 Hamburg, Germany POSTER

170. THE EFFECT OF PROCESSING ROUTE ON MATERIAL SURFACE PROPERTIES

Majid Naderi1, Nektaria Servi1, Anett Kondor1, Manaswini

Acharya1, Jurgen Dienstmaier1 and

Dan J. Burnett2

1 Surface Measurement Systems, Alperton, Middlesex, HA0 4PE, UK

2 Surface Measurement Systems, Allentown, PA 18103, USA

POSTER

171. STUDY OF THE INFLUENCE OF THE DIAMETER OF

A CONICAL HOPPER ORIFICE ON THE PARAMETERS OF THE FLOW EQUATION FOR SIZE

FRACTIONS OF SORBITOL GRANULES

Hana Hurychová, Malek Azar,

Zdeňka Šklubalová & Jan Stoniš

Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy,

Hradec Králové, Czech Republic POSTER

172. IMPACT OF SURFACE PROPERTIES ON WETTING

BEHAVIOR OF THIN FILMS AND POWDERS

Alessandro Gianfrancesco &

Constantijn Sanders

Nestec Ltd., Nestlé Product Technology Centre, Konolfingen, Switzerland ORAL


173. MODELING GRANULATION BEHAVIOR IN AN

AGITATED FILTER DRYER

Ashutosh Tamrakar1, Alfeno

Gunadi2, Patrick M. Piccione2 & Rohit Ramachandran1

1 Department of Chemical and Biochemical Engineering, Rutgers, the State University of New Jersey,

USA

2 Process Studies Group, Technology & Engineering, Syngenta Ltd., United Kingdom

POSTER

174. ROLLER COMPACTOR: THE EFFECT OF NANO-INDNTATION HARDNESS OF PRIMARY PARTICLE

Riyadh B. Al Asady, Michael J. Hounslow & Agba D. Salman


175. TWIN SCREW WET GRANULATION: EFFECT OF VARIABLES ON CAKING

M. F. Saleh1, R. M. Dhenge1, J. J. Cartwright2, M. J. Hounslow1, A. D.

Salman1

1 University of Sheffield, UK; 2 GSK, UK

ORAL

176. ROLLER COMPACTOR: MECHANICAL PROPERTY OF PRE-COMPACTED BODY

R. B. Al Asady, R. M. Dhenge, M. J. Hounslow & A. D. Salman

University of Sheffield, UK POSTER

177. ROLLER COMPACTION: EFFECT OF RELATIVE HUMIDITY

C. S. Omar1, R. M. Dhenge1, S. Palzer2, M. J. Hounslow1 & A. D.

Salman1


2 Nestlé SA Headquarters, Switzerland. POSTER

178. ROLLER COMPACTOR: POWDER STICKINESS Osama Mahmah, Michael J.

Hounslow & Agba D. Salman

Department of Chemical and Biological Engineering, University of Sheffield, Newcastle Street,

Sheffield, S1 3JD, UK POSTER

179. ‘RIGHT-FIRST TIME’ PRODUCTION OF GRANULES’

PROPERTIES MODELLING AND OPTIMIZATION APPROACHES

Wafa’ Alalaween1, Mahdi Mahfouf1

& Agba Salman2

1 Department of Automatic Control and Systems Engineering, University of Sheffield, S1 3JD, UK

2 Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, S1 3JD, UK POSTER

180. TWIN SCREW GRANULATION: UNDERSTANDING THE GRANULATION MECHANISM OF MIXING

HYDROPHOBIC AND HYDROPHILIC POWDERS

Aquinoscise L. Mundozah1, James J. Cartwright2, Claire C. Tridon2,

Michael J. Hounslow1 & Agba D. Salman1

1 Department of Chemical and Biological Engineering, University of Sheffield, Mapping Street Sheffield, UK, S1 3JD 2 GSK, Third Avenue, New Frontiers Science Park, Harlow, Essex, UK, CM19

5AW

POSTER

181. ROLLER COMPACTION: EFFECT OF MORPHOLOGY AND AMORPHOUS CONTENT OF LACTOSE ON

PRODUCT QUALITY

Chalak S. Omar1, Ranjit M. Dhenge1, James D. Osborne2, Tim

Althaus2, Stefan Palzer3, Michael J. Hounslow1 & Agba D. Salman1

1 Department of Chemical and Biological Engineering, University of Sheffield, Mappin Street, Sheffield S1 3JD, UK

2 Nestle´ Product Technology Centre York, Haxby Road, York YO9 11XY, UK

3 Nestlé SA Headquarters, Avenue Nestlé 55, CH-1800 Vevey, Switzerland

POSTER

182. TWIN SCREW WET GRANULATION: BINDER DELIVERY

Mohammed F. Saleh1, Ranjit M. Dhenge1, James J. Cartwright2,

Michael J. Hounslow1 & Agba D.

Salman1

1 Department of Chemical and Biological Engineering, University of Sheffield, Mappin Street,

Sheffield, S1 3JD, UK 2 GSK, Third Avenue, Harlow, Essex, UK, CM19 5AW

POSTER

183. TWIN SCREW GRANULATION: A STEP TOWARDS GRANULE DESINGING

Sushma V. Lute, Ranjit M. Dhenge, Michael J. Hounslow & Agba D.

Salman


Sheffield, S1 3JD, UK POSTER

184. GRANULE AND TABLET PROPERTIES IN A HIGH SHEAR MIXER AND A FLUIDIZED BED

GRANULATOR

Zhiyu Wang, Michael J. Hounslow & Agba D. Salman

Department of Chemical and Biological Engineering, University of Sheffield, Newcastle Street, Sheffield, S1 3JD, UK

POSTER

185. GRANULAR FLOW IN HIGH SHEAR MIXER Ali Al Hassn1, Kimiaki Washino2, Ei L. Chan2, Michael J. Hounslow1 &

Agba D. Salman1

1 Department of Chemical and Biological Engineering, University of Sheffield, Newcastle Street,

Sheffield, S1 3JD, UK

2 Mechanical Engineering Department, Osaka University, Suita, Osaka, 565-0871, Japan

POSTER

1. QUANTIFYING TABLET PUNCH ADHESION RISK USING A

COMPACTION SIMULATOR

Monwara Hoque1, Elaine Harrop Stone1, Darren Wilkes2 & Vicki Wilkes2

1 Merlin Powder Characterisation Ltd, Unit 1A, Pavilion Way, Jubilee Drive, Loughborough,

Leicestershire, LE11 5GW, UK

2 Phoenix Calibration and Services Ltd, Unit 8, The Wallows Industrial Estate, Fens Pool Avenue,

Brierley Hill, DY5 1QA, UK

E-mail: [email protected]

Sticking and picking is a common tableting problem, occurring when particles of the tablet

formulation adhere to the punch face and disrupt the integrity of the tablet surface. The

sticking tendency of a new formulation has traditionally been difficult to predict during

development due to short production runs and limited press data.

The aim was to develop a simple method to quantify sticking risk using a minimal amount

of material, which could be used early in development. A Phoenix hydraulic Compaction

Simulator and a novel instrumented adhesion punch were used to characterise the sticking

behaviour of 5 formulations, some of which were known to adhere to tablet punches during

compression. The upper punch was replaced with an instrumented adhesion punch. The

punch has a removable 10 mm diameter tip which is fixed to a transducer held in the punch

body and records a signal when adhesion occurs, relative to the strength of the adhesion

between tip and compact.

Picking index vs compact tensile strength for the five formulations

Compacts were made at two different punch displacements. Compact diameter, thickness

and crushing strengths were measured to calculate the compact tensile strength. The adhesion

force was used to calculate the adhesion strength of the compact to the upper punch face. If

attraction to the punch faces is low or compact bonding is strong, then the Picking Index is

high and the risk of picking is low. If the ratio between compact tensile strength and adhesion

strength is low, weaker areas of the tablet may detach and adhere to the punch face causing

visible disruption to the tablet surface. For example, Picking Index:

The Picking Index gives the possibility of screening for picking risk and setting limits for

new formulations.

2. DISCRETE ELEMENT MODELLING OF PARTICLE

COLLISIONS IN GRANULAR FLOWS WITH SPECIAL

REFERENCE TO SPHERONISATION

A. Alharbi, H. Elmsahli and I.C. Sinka

Department of Engineering, University of Leicester, UK


Spheroids (or pellets) are used in pharmaceutical industry to create controlled release drug

delivery systems which are manufactured by a process called extrusion-spheronisation. The

process includes mixing of powders and liquids to create a wet mass, extrusion of the material

through a die or mesh to create spaghetti-like extrudates, and spheronisation. The spheroniser

is a cylindrical vessel with a rotating base which breaks the extrudates into small rods which

are transformed into spheroids as a result of a large number of impacts.

Modelling the evolution of the shape of a particle is straightforward in principle: a body

deforms a small amount following each impact it experiences. This can be achieved explicitly

using the finite element method [1] or an alternative method [2] which includes three main

ingredients: 1) a geometric transformation which determines a sphere with a radius equivalent

to the radius of curvature of the initial spheroid at the location of the impact; 2) a contact law,

which determines the plastic deformation of the equivalent sphere after impact and 3) a

rounding law that uses the plastic deformation to update the semi-axes of the new spheroid.

In this paper we develop a discrete element based method to obtain information regarding

impact velocity and location on a particle which is required for modelling spheronisation. The

method can readily be implemented into popular open source or commercial DEM codes and

be applied to any other particulate flow situation where detailed contact information is

required.

[1] I.C. Sinka, A first order numerical study of the spheronisation process, Powder Technology, 206

(2010) 195–200.

[2] I.C. Sinka, A model for the deformation of an ellipsoid subject to a large number of successive

impacts with special reference to spheronisation, Powder Technology, (2014) In Press, Accepted

Manuscript, Available online 11 July.

3. CONTINUOUS PHARMACEUTICAL MELT GRANULATION:

RHEOLOGY AS A PREDICTIVE TOOL TO DETERMINE

FORMULATION PROCESSABILITY

Tinne Monteyne1, Chris Vervaet2, Jean-Paul Remon2 & Thomas De Beer1

1 Laboratory of Pharmaceutical Process Analytical Technology, Ghent University,

Ottergemstesteenweg 460, Ghent, Belgium

2 Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, Ghent,

Belgium


Within the scope of increased pharmaceutical process efficiency, there is a growing

interest in continuous manufacturing. Twin-screw hot melt granulation (HMG) is a valuable,

still unexplored alternative to granulate temperature and moisture sensitive drugs. The

understanding of the material behavior during processing is necessary to reduce the amount of

preliminary experiments and to optimize the process and product quality attributes.

The aim of this study was to evaluate rheology combined with microscopy and FTIR-

spectroscopy as predictive tools for the elucidation of the melt agglomeration mechanism, and

to examine how rheological information can be used to optimize the process.

Soluplus® was used as a binder to agglomerate two model drugs: anhydrous caffein and

metoprolol tartrate (MPT), which are respectively soluble and insoluble in the molten binder.

The Soluplus®/drug ratio was varied from 5/95 to 70/30 (w/w %). Continuous HMG was

performed using a co-rotating twin screw granulator. Rheological measurements were

executed in parallel using three rheometers: 1. the Haake Mars III, 2. the Haake Mars III

Rheoscope (microscope), and 3. The Haake Mars III Rheonaut (FTIR).

The rheological parameter tan(δ) was used as index for mixture deformability, which is a

determining factor for the granulation mechanism. Rheoscope measurements revealed that the

samples Soluplus®/caffein with a binder concentration ≥ 25% (w/w) showed phase separation

at temperatures (T) above 120°C. Furthermore, these mixtures were not suitable for HMG

since big lumps were formed. In contrast, the samples Soluplus®/MPT did not show any

motion during the rheoscope temperature ramp as they behaved as one phase due to

binder/drug hydrogen-interactions which could be identified after rheonaut analysis. These

interactions caused an increased deformability as these samples showed a tan(δ) which was 2

times higher compared to the ones containing caffein. Granulation experiments confirmed that

max. 12,5% of Soluplus® can be used with MPT, which is half of the amount of binder when

caffeine is used. Furthermore, granulation experiments pointed out that the T resulting in the

maximum tan(δ) value correlated with the T leading to the maximum mean granule size.

Additionally, after heating till 120°C, a varying cooling curve was observed compared to a

max. heating T of 100°C, which reveals material reorganization between 100°C and 120°C.

This could help to understand the particle flow behavior during heating and hence helps to

elucidate the melt granulation mechanism.

The combination of rheological parameters, FTIR spectra and microscopic images is useful

to reach in-depth understanding of the material behavior during HMG and a promising

predictive tool to optimize binder concentration and process T. Furthermore, it provides an

insight on granule particle size in function of T, making it possible to optimize the yield

fraction.

4. A NEW CONTACT LIQUID DISPERSION MODEL FOR

DISCRETE PARTICLE SIMULATION

Kimiaki Washino, Koki Miyazaki, Takuya Tsuji & Toshitsugu Tanaka

Mechanical Engineering Department, Osaka University, Suita, Osaka, 565-0871, Japan


In wet granulation, liquid dispersion among powder plays an important role since poor

liquid dispersion can significantly degrade the quality of the final products. The liquid

dispersion during wet granulation can largely fall into two categories: (a) convective

dispersion and (b) contact dispersion. In convective dispersion, liquid is transferred with the

movement of wet powder mass, whilst in contact dispersion, liquid is redistributed from one

particle to another by particle-particle contact. Generally speaking, convective dispersion is

dominant at the early stage of the wetting process, and contact dispersion becomes more

prominent with time. However, it is particularly difficult to observe the contact dispersion by

experiment.

Recently, a few contact dispersion models [1,2] were proposed in literature and

implemented in the framework of the Discrete Element Method (DEM). However, one big

assumption in these models is that the particle surface is uniformly coated with a thin liquid

layer. In other words, the liquid redistributed by the contact instantaneously spreads over the

entire particle surface. This assumption may only be valid for extremely hydrophilic particle

surface with low viscous liquid (for instance, clean glass surface with distilled water).

However, in many industrial applications, the particle surface can be less hydrophilic and/or

liquid can be highly viscous. Hence, the currently existing models can overestimate the liquid

dispersion.

In order to properly capture the contact dispersion, it is of paramount importance to take

into account the partial wetting of the particle surface. In the new model proposed in this

work, the particle surface is uniformly divided into a number of sub-surfaces and liquid is

locally stored in these sub-surfaces. During the collision event, the liquid is redistributed

between the sub-surfaces of the adjacent particles. The proposed model showed a potential to

provide more accurate results compared to the currently available dispersion models, and it

requires much smaller computational effort compared to the DEM – CFD coupling model [3].

[1] D. Shi and J.J. McCarthy, Numerical Simulation of Liquid Transfer between Particles, Powder

Technology, 184 (2008), 64-75.

[2] B. Mohan, C. Kloss, J. Khinasta, S. Radl., Regimes of Liquid Transport through Sheared Beds of

Inertial Smooth Particles, Powder Technology, 264 (2014), 377-395.

[3 K. Washino, H.S. Tan, M.J. Hounslow, A.D. Salman, A New Capillary Force Model Implemented

in Micro-scale CFD-DEM Coupling for Wet Granulation, Chemical Engineering Science, 93 (2013),

197-205.

5. MONITORING CALCIUM CARBONATE PRECIPITATION AND

AGGLOMERATION: A COMPARISON OF INLINE AND

OFFLINE TECHNIQUES

W.N. Al Nasser1, K. Pitt2, M. J. Hounslow2 & A. D. Salman2

1 Saudi Aramco Company, Dhahran 31311, Saudi Arabia.




Calcium carbonate (CaCO3) scale is one of the most common types of inorganic deposits

occurring in industrial water systems, oil and gas production as well as processing operations

such as boilers, cooling towers and surface facilities. It may form at different locations due to

changes in the water composition or physical conditions such as pressure and temperature.

Calcium carbonate agglomeration occurs when Ca++ and CO3- - ions in water react to form an

insoluble solid. In order to prevent potential scaling problems, it is important to understand

the mechanism of calcium carbonate deposition. The impacts of CaCO3 scale range from

reduced process efficiency and increased maintenance cost due to unscheduled system

shutdowns.

This paper reports an extended study on the understanding of calcium carbonate crystal

formation, agglomeration and deposition, and a comparison between inline and offline

techniques to determine the precipitation of calcium carbonate is presented. The inline

technique is based on focused beam reflectance measurement, Mettler Toledo (FBRM). The

effect of calcium ion concentrations on the scale rate is determined. The inline results were

validated using an offline scale measurement technique using turbidity measurements.

The present techniques not only determine the precipitation and scaling mechanisms under

different conditions, but can also be used to evaluate calcium carbonate agglomeration and

scaling in the presence of inhibitors or when employing other scale prevention methods.

6. FORMULATION DEVELOPMENT, CHARACTERIZATION AND

EVALUATION OF LIQUISOLID TABLET CONTAINING

ORLISTAT

Sanjana Gaikwad, Madhukar Tajne & Naresh Gaikwad

University Department of Pharmaceutical Sciences, RTM Nagpur University, Nagpur (M.S.) India


The aim of present study was to improve the solubility of Orlistat, a practically insoluble

antiobesity drug by using Liquisolid technique. Orlistat is class II molecule according to BCS

(Biopharmaceutical Classification System), having low solubility and low permeability. The

rate and extent of absorption of class II compounds is highly dependent on the performance of

the formulated product. These drugs can be successfully formulated for oral administration,

but care needs to be taken with formulation design to ensure consistent bioavailability.

Solubility of Orlistat was evaluated in various nonaqueous carriers. Different Liquisolid

tablets were prepared using a mathematical model to calculate the required quantities of

powder and liquid ingredients to produce acceptably flowable and compressible admixture.

Avicel PH 102, Aerosil 200 and Sodium starch glycolate were employed as carrier, coating

material and disintegrant respectively. The drug release rates of Liquisolid tablets were

distinctly higher as compared to directly compressed tablets, which show significant benefit

of Liquisolid tablets in increasing wetting properties and surface area of drug available for

dissolution. The optimized formulation showed the higher drug release during ex-vivo and in-

vivo study against conventional and marketed tablet preparation. From this study it concludes

that the Liquisolid technique is a promising alternative and best suitable method for

enhancing solubility of Orlistat.

Apparatus for the Ex -vivo study using Rat Ileum

Ileum with formulation

Dissolution medium

Stirring bead

mailto:[email protected]

7. INFLUENCE OF THE PELLETIZING PROCESS PARAMETERS

ON THE MECHANICAL PROPERTIES OF THE RECEIVED

ALUMINA OXIDE PELLETS

Z. Radeva, P. Müller & J.Tomas

Institute of Process Engineering, Mechanical Process Engineering, Otto von Guericke University,

Magdeburg, Germany


Pelletizing is a common procedure for optimizing the mechanical properties of different

powder materials. The improvement of the flow behaviour, the dosage and the decrease of the

bulk density are only few of possibilities that this size enlargement concede.

Industrial produced alumina oxide (γ-Al2O3) granules are used as primary particles for the

pelletizing process, carried out in a laboratory rotating pan pelletizer. Solution of viscoelastic

polymer - hydroxypropyl methylcellulose (HPMC) is used as binder. The rotational velocity

of the pelletizer pan was varied in order to find the speed, which provides the highest amount

of pellets. Experiments with six different process durations were accomplished. By changing

the time duration in the process chamber it was found that there is an optimum processing

time for the investigated material. When the duration is too short, the primary particles and

the added binder do not have enough time to mix each other in requisite rate and to form

pellets. During the pelletizing the γ-Al2O3 granules are exposed on impact of centrifugal and

friction forces, which could break or destroy them. When the particles are wetted by the

binder this impact is reduced. However in progress of the process the binder is consolidated

between the particles and could not protect the granules and the pellets from the friction and

the centrifugal forces. This is way the longer processing time causes a reduction in the pellets

amount. The influence of the process duration on the received pellet’s properties like density

and porosity, size distribution mechanical strength, and stiffness were also tested and

analysed. The solid bonds between the single particles were observed and analysed using

SEM. The conclusions from the experimental work help us to understand the basics of

agglomeration process and tend to develop and facilitate the operating with particle

collectives in science and industry.

a) b)

a) 3D structure analyse of the pellet surface b) Light microscope image of a single pellet

8. MEASUREMENT & QUANTIFICATION OF CAKING IN

POWDERS

Tim Freeman, Jamie Clayton, Katrina Brockbank & Doug Millington Smith

Freeman Technology, 1 Miller Court, Severn Drive, Tewkesbury, GL20 8DN, UK


In most powder processing systems materials are often stored for extended periods and

some will gain strength due to local humidity induced particle/particle interaction resulting in

unwanted/uncontrolled agglomeration. This is generally referred to as ‘caking’ and can

significantly limit the ability of a powder to pass uninterrupted through the process and can

detrimentally impact product quality. Thus, accurately quantifying unacceptable

characteristics and how quickly a powder develops such properties is vital to the process

designers and operators. This poster presents a way of evaluating the extent and strength of

powder caking using powder rheometry.

Four powders were chosen to evaluate the effect of environmental moisture and time on

caking. Samples were placed into a cylindrical vessel and initially conditioned, using a

powder rheometer, by passing a specially shaped blade through the powder in a prescribed

manner. Excess material was removed to generate a 25ml test sample which was then stored

in a controlled humidity environment for pre-determined time periods. The humidity levels

were created by the saturated solution method at equilibrium moisture levels of 53% and

75%RH. The caked samples were then tested using the same specially shaped blade (but

moving in a different, more aggressive path) and measuring the resistance to its motion from

the caked sample.

Analysis of the energy data, with respect to position of the blade, provides strong evidence

of localized caking within some of the samples at both relative humidities which is initiated at

the powder/air interface (crusting). It is also possible to easily evaluate both the strength and

the depth of such a crust and thus mechanistic and kinetic information relating to the water

migration processes can be established.

These results show that caking is a complex phenomenon and that powder rheometry

provides a process relevant way of measuring powder properties that indicate the progression

of caking as a function of time and relative humidity.

Homogeneous caking (top graph - Sorbitol @ 75% RH) and non-homogeneous caking

(bottom graph - Skimmed Milk Powder @ 53%RH) between 0 and 6 days exposure

9. EFFECT OF NANOPARTICLES TO CONTROL CALCIUM

CARBONATE SCALING USING INLINE TECHNIQUE

W. AL Nasser1, U. Shah2, K. Nikiforou2, P. Petrou2 & J. Heng2

1 Saudi Aramco, Research and Development Centre, Dhahran 31311, P.O. Box 961,

2 Department of Chemical Engineering, Imperial College London, London SW7 2AZ


Scale minerals in oil and gas industry are a major concern to reservoir and operation

engineering. The main types of oilfield scales found are carbonate and sulfate scales.

Calcium carbonate (CaCO3) is a major component of fouling in heat transfer surfaces across

different sectors of industry, resulting in additional capital, maintenance and operating costs.

Various techniques, including the use of chemical inhibitors, have been used to prevent the

formation of scale, the uses of chemical is one of the effective methods. In the last decade,

there have been considerable advances in the development of chemicals, effective in small

concentrations for the control of scale deposits. The only challenge to be solved, being the

choice of the most suitable inhibitor, the amount of concentration, the design of the system for

application and injection into the industrial applications and facility of the communities. In

addition, the difficulty in choosing an inhibitor for a particular application is due to the

fundamentals of inhibition mechanisms.

The purpose of this study was to investigate the possibilities of utilising nanoparticles as

sacrificial surface for enhancement and control of nucleation crystallisation of CaCO3, as a

method for fouling mitigation by studying the turbidity profile of the solution, using a light

reflection technique. Silica nanoparticles of different size and surface functional groups were

added to the solution. The results showed a reduction in the induction period, consequently

indicating improved control over crystallisation. Modified silica nanotemplates with –NH2

functional group exhibited the highest reduction in induction time. It might be due to the

attraction of the charged surface with the aqueous ions. This conclusion is very important to

be studied further in detail to understand the mechanisms of reactions between the

nanoparticles and scaling ions.

10. MICROMERITIC, GRANULATING AND DISSOLUTION

PROPERTIES OF RICE STARCH IN METRONIDAZOLE BASED

FORMULATIONS

O.N.C Umeh, K.C Ezeagwu & S.I Ofoefule

Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka

410001, Nigeria

Starches play a vital role in solid dosage forms where they can be used as granulating,

bulking and as disintegrating agents. Industrially, maize / corn and potato starches are widely

employed as granulating, disintegrating and bulking agents in oral tablet formulations. In this

study, we investigated the compactibility and cohesiveness of starch extracted from a local

rice (Oryza sativa L) farm. The starch was employed as a granulating agent at concentration

levels of 5.0, 7.5 and 10.0 %w/w in the formulation of metronidazole granules and tablets

prepared by the wet granulation technique. The micromeritic properties of the granules

evaluated as a function of the starch concentration include: Particle/granule density, bulk and

tapped densities, flow rate and angle of repose, Carr’s compressibility index and Hausner’s

quotient. The effect of the concentration of the starch on the mechanical properties (hardness

and friability) and on the dissolution properties (disintegration and dissolution) of the

metronidazole tablets was also assessed. Commercial maize starch at the same concentration

served as a standard for comparison. There was an increase from the bulk densities to the

tapped densities of the granules as a result of densification. Granules containing rice starch

had significantly higher bulk and tapped densities than those containing maize starch at a

concentration of 7.5% w/w. A similar effect was observed in the Hausner’s quotient, Carr’s

compressibility index and granule porosity. The flow rates of the granules generally decreased

with an increase in the starch concentrations with maximum flow rate obtained at starch

concentration of 5.0% w/w. At all the three concentrations of the starch, granules containing

rice starch had higher flow rates than those containing maize starch. Similarly, tablets

containing rice starch also had higher crushing strength than those containing maize starch. In

both starches, maximum crushing strength occurred at concentration of 7.5% w/w. All the

tablet batches exhibited friability of less than 1% and are considered non friable. Release of

metronidazole from the tablet formulations increased with increase in rice starch

concentration, while release from tablets containing maize starch decreased with increase in

the starch concentrations.

11. DEVELOPING AND UNDERSTANDING THE DESIGN SPACE

FOR CONTINUOUS & BATCH PHARMACEUTICAL WET

GRANULATION

Tim Freeman, Jamie Clayton & Doug Millington Smith

Freeman Technology, 1 Miller Court, Severn Drive, Tewkesbury, GL20 8DN, UK


The adoption of a Quality by Design approach to wet granulation, a key unit operation in

pharmaceutical manufacturing, requires manufacturers to fully understand the relationships

between processing variables, including powder properties, and Critical Quality Attributes of

the manufactured product – the Design Space. This paper shows how powder rheometry can

link processing parameters and CQA’s, in both continuous and batch manufacturing

processes, through a series of laboratory and pilot scale experiments.

The results show that granulate properties are predictable from a knowledge of the

processing parameters such as solid-to-water ratio, binder temperature, mixing time and

impeller/screw speed. Thus manufacturing granules with specific properties can be

undertaken. Subsequent analysis of the tableting results shows that granule properties are also

linked to tablet CQAs and thus a direct link between granulate production and tablet

properties can be defined.

These results further show that defining a wet granulation process by the quality of the

granules allows the operator to develop a fully functional Design Space for each

manufacturing step based on flow properties. The graph below exemplifies the relationships

between the properties of granules manufactured in a continuous processing regime and a

Critical Quality Attribute of the tablets.

Tablet Hardness vs Basic Flowability Energy of Wet, Dried, Milled &

Lubricated Granules from a Continuous Granulation Process

12. EXPERIMENTAL ANALYSIS OF THE MICROSTRUCTURE OF

SINGLE PARTICLES

Franziska Sondej, Andreas Bück & Evangelos Tsotsas

NaWiTec, Thermal Process Engineering, Otto-von-Guericke University Magdeburg, Germany


In food, chemical and pharmaceutical industries, processes such as layering or

agglomeration play a significant role. In order to create specific product and layer properties,

e.g. in fluidized bed coating, an analysis of the micro-processes, which lead to layer formation

during the drying on the single particle, is required. A detailed investigation of the surface and

the interior of coating layer is possible using Confocal Laser Scanning Microscopes (CLSM).

The CLSM offers several advantages in comparison to conventional microscopes and

tomographic methods, e.g. a representation of the sample surface and layer structure in detail

in a short time, using small amounts of dyes and fluorescent materials.

In the framework of this study, the investigation of coated particles with the addition of

fluorescent dyes will be compared with existing data from literature; [1,2]. Primarily porous

gamma-alumina particles, which are coated with sodium benzoate under various process

conditions in a top-spray fluidized bed, are analyzed. Evaluations of expected coating

thicknesses are compared with theoretical thicknesses and geometrical equations, which

correlate measured chord lengths to coating thicknesses. Furthermore the coating layer

uniformity and the local porosity inside the shell will be evaluated in detail by analysis of

single sections of the measured particles.

[1] M. Dadkhah, M. Peglow and E. Tsotsas, Characterization of the internal morphology of

agglomerates produced in a spray fluidized bed by X-ray tomography, Powder Technology, 228

(2012) 349-358.

[2] F. Sondej, A. Bück, K. Koslowsky, P. Bachmann, M. Jacob, E. Tsotsas, Investigation of coating

layer morphology by micro-computed X-ray tomography, Powder Technology (in review).

13. SPECIFIC ENERGY CONSUMPTION AND QUALITY OF

WOOD PELLETS PRODUCED USING HIGH MOISTURE

LODGEPOLE PINE

Jaya Shankar Tumuluru & Craig. C. Conner

750 University Blvd, Biofuels and Renewable Energy Technology, Idaho National Laboratory, Idaho

Falls, Idaho-83415

Wood pellets are commonly used in energy application. Yancey et al. [1] indicated that in

a commercial wood pellet production process rotary dryer takes of about 70% of energy

whereas pellet mill takes about 7% of the total energy. Tumuluru [2] in his studies made corn

stover pellets at high feedstock moisture content of >28% (w.b.). His results indicated that the

process heat developed in the die and further cooling helps to reduce the feedstock moisture

content by 5-8% and makes partially dried pellets. He has suggested that the partially dried

pellets can be dried further to safe storage moistures using low cost and energy efficient

dryers like grain or belt dryer. Techno-economic analysis on conventional and high moisture

pelleting indicated that high moisture pelleting offer significant energy saving (>50%), mainly

due to switching to a grain dryer from rotary dryer [3]. Current study is to evaluate the

technical feasibility of pelleting high moisture ground lodgepole pine samples using a flat die

pellet mill. A Box-Behnken experimental design was used to test the effect of feedstock

moisture (33-39%, w.b.), die speed (40-60Hz) and preheating temperature (30-90°C) on the

pellet quality attributes (pellet moisture content, unit, bulk, tapped density, and durability) and

specific energy consumption. The power data for each pelletization run was recorded to

calculate the specific energy consumption. Pellet moisture content was recorded immediately

after pelleting and cooling. As the pellets produced had high moisture contents in the range of

20-30% (w.b.), they were further dried to <9% (w.b.) at 70°C for 3 hours in a mechanical

oven to increase the storage stability. These pellets were further evaluated for physical

properties. Experimental data was used to develop response surface models (RSM) and plots.

Surface plots drawn indicated higher unit, bulk and tapped density (1050, 520, 560 kg/m3)

were observed at feedstock moisture content of 33-34% (w.b.), die speed of 60Hz and

preheating temperature of 30-60°C. Increasing the feedstock moisture content to 39% (w.b)

reduced significantly the unit, bulk and tapped density to <912, 396 and 452 kg/m3. The

highest durability values of >95% were obtained at 33-35% (w.b.) at lower preheating

temperatures of 30-40°C and higher die speed of 60Hz. Higher preheating temperature of

90°C, higher die speed of 60Hz and feedstock moisture of 33% (w.b.) resulted in lowering the

specific energy consumption to <116 kWhr/ton. The RSM models developed are further

optimized to find the process variables which can maximize density and durability and

minimize pellet moisture content and specific energy consumption.

[1] N.A. Yancey, J.S Tumuluru, C.T Wright, Grinding and Densification Studies on Raw and

Formulated Woody and Herbaceous Biomass Feedstocks, Journal of Biobased Materials and

Bioenergy, 7(5) (2013) 549-558.

[2] J. S. Tumuluru, Effect of process variables on the density and durability of pellets made form high

moisture corn stover, Biosystems Engineering, 199 (2014) 44-57.

[3] J. S. Tumuluru, K. G. Cafferty, K. L. Kenney, Techno-economic analysis of conventional, high

moisture pelletization and briquetting process, ASABE Proceedings, Paper number 141911360, 2014

Montreal, Quebec Canada July 13 – July 16, 2014.

14. PREDICTING LOCAL SHEAR IN POWDER FLOW USING

DEM: EFFECT OF SIMULAITON PARAMETERS

Nathan J. Davis1, Rachel M. Smith2 & James D. Litster1

1 Purdue University, School of Chemical Engineering, Forney Hall of Chemical Engineering, 480

Stadium Drive, West Lafayette, IN 47907-2100




Discrete Element Method (DEM) models have become an important tool for modelling

granular flow. This DEM information is important for determining the parameters of the rate

process kernels in the population balance models. Unfortunately current computational

limitations limit the size and number of particles that can be feasibly modelled. While the

most advanced DEM models can accommodated 1*109 particles, real systems in granulation

contain more than 1*1012 particles. The large particle simulations can be useful for studying

bulk granule flow, but are not reliable for particle scale information [1].

In this study a "unit cell" DEM simulation is used to determine how the bulk properties of

granule flow translate to particle level forces. As seen in figure 1, a single large particle is

placed in a bed of smaller particles and a shear field is induced. The resulting forces and shear

on the large particle are then characterized to determine how the bulk properties of the shear

field are affecting the local shear of the particle. Sensitivity studies are also discussed

including coefficient of restitution, Young's modulus, and particle size ratio. Shear rates

between 0.01 and 10 s-1 are evaluated. Using this method a better understating of the

limitations of DEM models is achieved. Additionally, the translation of granulator scale DEM

to more realistic systems is bridged using the unit cell approach.

[1] B. Freireich, J.D. Litster, C. Wassgren, Using the discrete element method to predict collision-

scale behaviour: A sensitivity analysis, Chemical Engineering Science, 64 15 (2009) 3407-3416.

Unit Cell DEM simulation depicting induced shear field and single large particle.

15. INFLUENCE OF PROCESS PARAMETERS AND MECHANICAL

PROPERTIES OF PHARMACEUTICAL MATERIALS ON

MILLING OF ROLLER COMPACTED RIBBONS

Andreja Mirtic & Gavin Reynolds

Pharmaceutical Development, AstraZeneca, Macclesfield SK10 2NA, UK


Milling in roller compaction consists of the breakage of a dry compacted 'ribbon' into a

granulated product consisting of particles with a desired size distribution. In general,

understanding the milling parameters relating to size reduction is extremely important in

achieving a desired particle size distribution, allowing for better product uniformity, tablet

strength and optimizing formulation dissolution properties. Despite extensive literature on

particle size reduction, mechanistic insight into milling processes still remains poorly

understood. The aim of this study was to determine the influence of process parameters and

material properties of roll compacted ribbons on the the underlying breakage mechanisms and

subsequent granule size.

Population balance modelling (PBM) can be used to fit experimental data in a particle size

reduction process [1]. One particular aspect of PBM is that the breakage behaviour of each

particle of a given size class can be described by a selection function, giving the rate

dependence, and a breakage function, giving the fragment distribution. Parameter estimation

of these functions can give insight to the underlying breakage mechanisms and can also be

related to milling process parameters and material properties. The size of the milled granules

is controlled by the mill screen size and the milling speed as well as by the ribbon porosity,

hardness and fracture toughness [2]. Methodologies have been developed to measure tensile

and shear fracture properties as a function of ribbon porosity. The process characteristics and

material properties of the ribbons have been correlated with the milling kinetics to build a

mechanistic understanding of the milling process and to predict the subsequent granule size

distribution.

[1] G.K. Reynolds, Modelling of pharmaceutical granule size reduction in a conical screen mill,

Chemical Engineering Journal, 164 (2010) 383 – 392.

[2] R.C. Rowe, R.J. Roberts, The mechanical properties of powders, Advances in Pharmaceutical

Sciences, 7 (1995) 1 – 66.

Acknowledgements: This work was supported by the IPROCOM Marie Curie initial training

network, funded through the People Programme (Marie Curie Actions) of the European

Union’s Seventh Framework Programme FP7/2007-2013/ under REA grant agreement No.

316555.

http://www.sciencedirect.com/science/journal/13858947

http://www.sciencedirect.com/science/bookseries/00653136

http://www.sciencedirect.com/science/bookseries/00653136

16. IMPACT OF MILLING PROCESS CONDITIONS ON THE

GRANULE'S PROPERTIES: EFFECT OF MILLING SPEED AND

ROTATION

Lucia Perez-Gandarillas1, Ana Perez-Gago2, Alon Mazor1, Peter Kleinebudde2,

Abderrahim Michrafy1 & Olivier Lecoq1

1 Université de Toulouse, Mines Albi, CNRS, Centre RAPOSDEE, Albi, France

2 Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Duesseldorf, Germany


Powders are often granulated in order to improve their manufacturing properties such as

flowability. For this goal, dry granulation by roll compaction has been widely used in the

pharmaceutical industry. After roll compaction, the produced ribbons are milled and granules

of different sizes are obtained together with a percentage of fines. The generation of fines

should be avoided especially when active ingredients are involved. On the other hand, large

sized granules improve the flow but the tablet tensile strength is reduced. Therefore, in order

to optimise the roll compaction process, it is required to find a controlled particle size

distribution, which keeps the balance between loss of reworkability and good flow. A direct

way of controlling the particle size distribution is through the control of the milling

parameters.

Some authors have reported research work on the effect of the milling on granules

properties for wet granulation but less attention has been given for dry granulation [1]. The

aim of this study is to analyse the influence of the milling system and the applied conditions

(speed and angle of rotation) on the microstructural properties of roll compacted granules.

Two common excipients with different mechanical behaviour were used: microcrystalline

cellulose (Avicel® PH-101, FMC Biopolymer) and mannitol (Pearlitol® 200SD, Roquette)

and a binary mixture of both with a proportion of 50% of each component. The production of

ribbons was performed using a roll compactor (MiniPactor, Gerteis) equipped with knurled

rolls. Resulting ribbons were milled using two different milling systems (star rotor and pocket

mould-grooved granulator). The ribbons were milled at speeds of 30 and 120 rpm and the

angles of rotation were varied from 360° clockwise to 150° clockwise/counter-clockwise.

In order to better understand the effect of the milling conditions on the granule’s

properties, measurements of particle size distribution, shape and surface area (BET and

inverse chromatography) are done for all the batches. This information together with the

characterization of work hardening of die compaction of granules allow us to determine the

optimal conditions for these systems and to design granules with a good quality for tableting.

[1] A.K. Samanta, K.Y. Ng, P.W.S. Heng, Cone milling of compacted flakes: process parameter

selection by adopting the minimal fines approach. International Journal of Pharmaceutics, 422 (2012)

17–23.

Acknowledgemet: This work was supported by the IPROCOM Marie Curie initial training


Union's Seventh Framework Programme FP7/2007-2013/ under REA grant agreement No.

316555.


17. CAKING OF COMPLEX SUCROSE MIXTURES

Sophie Samain, Mohammed Benali, Mikel Leturia, Elisabeth Van Hecke,

Isabelle Pezron & Khashayar Saleh

UTC/ESCOM, Equipe d’Accueil "Transformations Intégrées de la Matière Renouvelable" (EA 4297),

Rond-Point Guy Deniélou, 60200 Compiègne, France


Maintaining powder flowability and preventing powder caking are of utmost importance

for pharmaceutical, chemical and food industries. Regarding crystalline sucrose, moisture is

often identified as the cause of caking. The presence of water induces the formation of liquid

bridges; at lower humidity, these bridges undergo efflorescence, leading to solid bridges

which strongly link the particles with each other. Efflorescence is a key phenomenon for the

characterization of sucrose caking. Moreover, sucrose in foods is usually mixed with other

components like NaCl and/or other sugars (glucose, fructose, polymers…) which may

strongly affect sucrose crystallization. The presence of fructose, glucose and corn syrup

induces a delay in crystallization [1], and the sucrose:NaCl mixture is likely to stay in an

amorphous state depending on the proportions [2].

The aim of this work is to better understand the mechanism of sucrose crystallization, in

pure state or in mixtures. Experiments on a Dynamic Vapour Sorption (DVS) equipment

allow studying the drying conditions and their influence on the final state of the product

(amorphous and/or crystalline) and on the Efflorescence Relative Humidity of the crystals; the

glass transition temperature of amorphous components is determined by Differential Scanning

Calorimetry (DSC). These experiments will be related to the characterization of the cake

strength to see the impact of caking at a macroscopic level.

[1] A.K. Laos, B.E. Kirs, C.A. Kikkas, D.T. Paalme, Crystallization of the supersaturated sucrose

solutions in the presence of fructose, glucose and corn syrup, Proceedings of European Congress of

Chemical Engineering, Copenhagen, (2007).

[2] M. Dupas-Langlet, M. Benali, I. Pezron, K. Saleh, L. Metlas-Komunjer, The impact of

deliquescence lowering on the caking of powder mixtures, Powder Technology (n.d.).

doi:10.1016/j.powtec.2014.05.011.

ESEM micrographs - drying of NaCl and sucrose particles in contact with each other


18. APPLICABILITY OF THE RYSHKEWITCH-DUCKWORTH

EQUATION ON DIRECT AND DRY GRANULE COMPRESSION

Johanna Mosig & Peter Kleinebudde

Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Duesseldorf, Germany


Ryshkewitch and Duckworth found 1953 a linear relationship between the logarithm of the

tensile strength (σ) and the porosity (ε) of ceramic compacts [1,2]. Since then, the equation

(lnσ = lnσ0-k*ε) was also applied in pharmaceutics to describe the tableting behaviour of

different materials. The aim of the study was to check the applicability of the Ryshkewitch-

Duckworth equation to describe the compaction behaviour of dry granules and the

corresponding raw materials. Two types of microcrystalline cellulose (MCC), powder

cellulose, lactose and magnesium carbonate were roll compacted with five different specific

compaction forces between 2 and 12 kN/cm. Ribbons were dry granulated and sieved into

three defined particle fractions. The granule fractions were tableted with compression

pressures between 60 and 418 MPa by internal and external lubrication and the tablets

characterized according to their weight, height, diameter and crushing force. Porosity and

tensile strength were calculated.

The Ryshkewitch-Duckworth equation could be applied successfully for the compression

of the starting and granule materials (Figure 1a, R2 > 0.98). In contrast to literature [3], direct

and granule compression form no uniform curve, as it was observed for direct compression of

one material with different tableting speeds. Therefore, the solid fraction or porosity cannot be

used as sole factor for the scale-up of tableting processes. For tablets made from dry granules,

the total porosity can be divided into the intra- and extragranular porosity. The absolute slope

(k) of the Ryshkewitch-Duckworth plot increase with an increasing specific compaction force

of the granules and with this, a stronger dependency between the tablet porosity and the

strength is observable (Figure 1b). This can be explained by the primarily reduction of the

intergranular porosity with increasing compaction force. Intragranular porosity will be less

affected during compression for granules from higher specific compaction forces. Resulting

from this, porosity decrease in such tablets will mainly be caused by the reduction of

intergranular porosity, affecting sharply the strength. As the increasing slope correlates with a

decreasing strength of the dry granule tablets, it can be used as a measure of the influence of

porosity changes on the reduced compactibility of dry granules.

Figure 1. (a) logarithm of the tensile strength vs. porosity of MCC granules (315-630 µm) and

the direct compression with internal lubrication (mean ± sd), (b) slope of the Ryshkewitch-

Duckworth plot vs. specific compaction force of the granule compressions of MCC

[1] E. Ryshkewitch, Compression strength of porous sintered alumina and zirconia, Journal of the

American Ceramic Society, 36 (1953) 65-68.

[2] W. Duckworth, Discussion of Ryshkewitch paper by Winston Duckworth, Journal of the American

Ceramic Society, 36 (1953) 68.

[3] C.K Tye, C. Sun, G.E. Amidon, Evaluation of the effects of tableting speed on the relationships

between compaction pressure, tablet tensile strength, and tablet solid fraction, Journal of

Pharmaceutical Sciences, 94 (2005) 465-472.

19. EFFECT OF FOOD/MICROORGANISM (F/M) RATIO ON

GRANULAR SLUDGE CHARACTERISTICS IN SBR SYSTEM

Muhammad Sajjad1,2 & Kwang S. Kim1,2

1 Korea University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon, 305-350,

Republic of Korea

2 Environmental Engineering Research Division, Korea Institute of Civil Engineering and Building

Technology, 283 Goyangdae-ro, Ilsanseo-gu, Goyang-Si, Gyeonggi-Do, 411-712, Republic of Korea


In the current studies, two reactors (R-1 and R-2) were operated for 45 days to highlight

the effects of food/microorganism (F/M) ratio on the granular sludge characteristics in the

sequencing batch reactor (SBR) system. R-1 and R-2 were run on 3 and 6 cycles/day basis by

maintaining an F/M ratio of 0.15 and 0.30 kg COD/kg MLSSˑd, respectively, using glucose.

Mixed liquor suspended solids (MLSS) concentration was 3000 mg/L in both the reactors and

extra MLSS discharged from the reactors to ensure a constant F/M ratio throughout the

investigative period. The workable volume of each SBR was 3.0 L and effluent was

discharged from the center of the reactors. All the unit operations like feeding, aeration,

settling and effluent drainage were automatically controlled through the installation of timers

with them. MLSS, SVI30, NH4-N and PO4-P and COD were measured by using the standard

methods [1]. Extracellular polymeric substances (EPS) were extracted and measured by

following the methods mentioned in [2].

The SVI30 values were found to be 65 and 42 ml/g in R-1 and R-2 (Figure 1A),

respectively, at the close of experiment which were very lower than the seed sludge (SVI30 =

230 ml/g). The particle size of majority of R-2 granules was higher than R-1 and found

around 700 µm, while that of R-1 was less than 500 µm. The SVI30 and particle size

distribution results showed that the high F/M ratio in R-2 accelerated the granulation process

in that reactor, while the process was much slower in R-1, which was run about half of the

F/M ratio of R-2. It was witnessed by the difference in EPS contents of two SBRs. The total

EPS contents measured in terms of proteins and polysaccharides were high in R-2 than R-1

(Figure 1B). EPS are the organic polymers which attracted the negatively charged

microorganism in the wastewater, and eventually helped in the increase of granulation rate by

increasing the sludge particle size.

Figure 1. Variation in (A) SVI30 and (B) EPS contents in R-1 and R-2 in SBR system.

0

25

50

75

100

125

150

175

200

225

250

0 5 10 15 20 25 30 35 40 45 50

SV

I 30

(ml/

g)

Time (d)

R-1 R-2

0

20

40

60

80

100

120

140

0 5 10 15 20 25 30 35 40 45 50

EP

S c

on

ten

ts (

mg

/g V

SS

)

Time (d)

R-1 R-2(A) (B)


[1] APHA, Standard methods for the examination of water and wastewater, Washington DC. USA,

American Public Health Association (1998).

[2] B. FrØlund, R. Palmgren, P.H. Nielsen, K. Keiding, Extraction of extracellular polymers from

activated sludge using a cation exchange resin, Water Research, 30 (1996) 1749–1758.

20. USE OF CONTINUOUS TWIN SCREW WET GRANULATION

TECHNIQUE TO DEVELOP HIGH DRUG LOADING TABLET

FORMULATION AND ROBUST PROCESS FOR CHALLENGING

ACTIVE PHARMACEUTICAL INGREDIENTS

Claire Tridon, Indra Yadav & Terry Ernest

GlaxoSmithKline R&D, 3rd Avenue, Harlow, Essex, UK, CM19 5AW

E-mail: [email protected], [email protected]

Cohesive and low bulk density Active Pharmaceutical Ingredients (API) present a number

of technical challenges for formulation and process development via traditional granulation

techniques, especially when high drug loading is required. Batch high shear wet granulation

of high loading low bulk density APIs often results in a ‘bed drop’ within the granulator as

densification takes place during granulation. This restricts maximum batch size and results in

variability in mixing and poor control over the granulation process giving potentially more

variable, less robust drug products. This paper compares the development of two challenging

drug substances through both the batch and continuous Twin Screw Granulation (TSG)

processes [1]. This paper also illustrates advantages of the TSG process over the batch process

[2]. Two challenging small particle size low bulk density APIs were successfully formulated

into tablets at commercial scale using TSG (Figure 1). More robust products (granules and

tablets) were produced by TSG compared to batch high shear granulation with improved

compressibility, disintegration and dissolution.

[1] H. Leuenberger, New trends in the production of pharmaceutical granules: batch versus continuous

processing, European Journal of Pharmaceutics and Biopharmaceutics, 52(3) (2001) 289–96.

[2] U. Shah, Use of a modified twin-screw extruder to develop a high strength tablet dosage form,

Pharmaceutical Technology, 29 (2005) 52–66.

Figure 1. Tablet attributes. TSG versus Batch

0.0

1.0

2.0

3.0

4.0

5.0

6.0

0 50 100 150 200 250 300 350

Tens

ile S

tres

s (M

Pa)

Compaction Stress (MPa)

Tablet Compression ProfileBatch versus TSG using same Drug Substance

Continuous TSG Tablet batch (Fette 1200i, 9.0 mm round NC tooling)

Batch High Shear Wet Granulation Tablet batch (Compaction Simulator, 10.5 mm round NC tooling)

TSG

300 mg core weight,

disintegration time = 3

min (at 2.0 MPa tensile

strength)

BATCH

500 mg core weight,

disintegration time = 7

min (at 2.0 MPa tensile

strength)


21. POPULATION BALANCE MODELING OF TWIN SCREW WET

GRANULATION THROUGH MECHANISTIC UNDERSTANDING

Ridade Sayin1,2, Dana Barrasso3, Juan G Osorio1,2, Rohit Ramachandran3, James

D Litster1,2,4 1 Center for Particulate Processes and Products, Purdue University, West Lafayette, Indiana, USA

2 School of Chemical Engineering, Purdue University, West Lafayette, Indiana, USA 3 Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey,

Piscataway, USA 4 Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, USA


There is an increasing interest in twin screw granulation (TSG) in the pharmaceutical

industry due to its design flexibility, wide range of throughputs and short residence times. In

the pharmaceutical industry, innovators are encouraged by the regulatory agencies to develop

advanced understanding of underlying physical phenomenon and build quality into their

products. In previous studies, experiments were performed on a Thermo-Fisher 16 mm

granulator to elucidate the granule growth mechanisms for different configurations with

kneading elements (KEs) [1] and distributive mixing elements (DMEs) [2]. Measured granule

properties were granule size distribution (GSD), shape, porosity, and liquid distribution (LD).

To model these phenomena, Barrasso et al. developed a multi-dimensional multi-component

model of a TSG process to predict granule attributes, which demonstrated similar trends to

those observed experimentally [3]. This study aims to combine the two approaches and

presents a population balance model of a TSG process using the framework developed by

Barrasso et al. and experimental data and mechanistic understanding studied at Purdue

University. The population balance model presented utilizes the regime-separated nature of

TSG. Based on this mechanistic approach, the TSG is modeled as a series of compartments,

where each element type represents one compartment in which the mechanisms are clearly

established. In the liquid addition zone, drop controlled granules are formed, and are partially

broken up in the screw. Each downstream element involves breakage (only of larger lumps

and granules), fine layering, and, at high liquid to solid ratio, possibly additional coalescence.

The element characterization data allows the fitting of the breakage rate constants and other

rate parameters on an element by element basis. The combined model for the whole screw

length can then be used to track the evolution of granule properties from any combination of

elements. The model is validated against experiment for a variety of screw configurations.

Schematic of mechanistic approach proposed for population balance modelling of twin screw

wet granulation.


[1] D. Barrasso, S. Walia, R. Ramachandran, Multidimensional population balance modeling of

continuous granulation processes: a parametric study, Powder Technology, 241 (2013) 85-97.

[2] A. S. El Hagrasy, J. D. Litster, Granulation rate processes in the kneading elements of a twin screw

granulator, AIChE Journal, 59.11 (2013) 4100-4115.

[3] R. Sayin, A. S. El Hagrasy, J. D. Litster, Distributive mixing elements: Towards improved granule

attributes from a twin screw granulation process, Chemical Engineering Science (2014) DOI:

10.1016/j.ces.2014.06.040.

22. FABRICATING OF HIERARCHICALLY ASSEMBLED

CERAMIC-POLYMER COMPOSITES USING A SPOUTED BED

SPRAY GRANULATION PROCESS

Eduard Eichner1, Stefan Heinrich1, Michael F. H. Wolff1, Gerold A. Schneider2

& Sergiy Antonyuk3

1 Institute of Solids Process Engineering and Particle Technology, Hamburg University of

Technology, Denickestrasse 15, 21073 Hamburg, D

2 Institute of Advanced Ceramics, Hamburg University of Technology, Denickestrasse 15, 21073

Hamburg, D


University of Kaiserslautern, Gottlieb-Daimler-Strasse, 67663 Kaiserslautern, D


The properties of the spray granulation in spouted beds offers many advantages in terms of

the process design for the fabrication of novel ceramic-polymer-composites. Particles in the

µm-range can be structured with this technique, and optimal properties for further processing

to materials can be obtained. For this, prestructured particles can be used, which then lead to a

hierarchical assembly, which is similar to natural materials, such as nacre and teeth.

Naturally occuring load-bearing materials are always ceramic-polymer composites with

several hierarchical levels, which are optimized for the specific surroundings and

requirements. Even though the structure of biological materials and its interconnection with

their outstanding mechanical properites has been studied in detail in recent years, it has so far

not been possible to mimick this structural design. We present a process route for the

fabrication of hierarchical materials which involves the spouted bed spray granulation process

of prestructured particles. With this approach a genuine hierarchically structured ceramic-

polymer composite material with brick-and-mortar-structure was fabricated. Agglomerates

which were prestructured were used as bed particles for the spouted bed spray granulation.

The granules were then compressed to form a solid material with brick-and-mortar structure.

The experimental approach as well as experimental results (4-point bending, nanoindentation)

and simulative results of the manufactured samples are shown and discussed.

Light micoscopic (left) and scanning electron microscopic images of the manufactured

hierarchical material

23. PREPARATION AND CHARACTERIZATION OF ADSORBENTS

BY GRANULATION AND EXTRUSION

Edith Goldnik, Yanira Lopéz, Ranja Plätzer, Björn Lamprecht, Christian Eichler,

Tharsha Thiripuvanam & Thomas Turek

Institute of Chemical and Electrochemical Process Engineering, Clausthal University of Technology,

Leibnizstrasse 17, Clausthal-Zellerfeld, Germany


In many environments undesirable gas compounds occur causing unpleasant odours and

respiratory irritations. The removal of such undesired gases from ambient air is usually

realized by absorption with a suitable solvent. As an alternative way it is possible to perform a

dry separation trough a packed bed of pellets. These pellets are developed and analyzed in this

work.

The adsorbents consist of support material, additives and active components. The support

provides a high surface and porosity to obtain a good distribution of the active component.

Additives can increase the mechanical strength, produce pores and enhance the capacity. For

extrusion the addition of a plasticizer is required.

The adsorbents are prepared by different forming processes including extrusion in a single-

screw extruder and granulation on a pelletizing plate. The main challenge in preparation is to

improve the mechanical stability without reducing the porosity of the material. The addition

of most binders results in a blocking of pores. A high input of mechanical energy during the

shaping leads to strong and dense pellets, but also to a low porosity. In extrusion the amount

of plasticizer and the extrusion rate seem to be the most important parameters. In Granulation

the spraying position, the amount of moisture added during spraying and the rotational speed

are key parameters.

Efficient adsorbents are characterized by a high capacity for the challenge gas, small

pressure drop and sufficient properties concerning stability and abrasion. These properties

depend on the chemical composition and on the shaping process. First experiments show that

particularly the porosity and the distribution of active component play an important role in

obtaining a high capacity and efficiency in the removal of undesired gases. It was found that

granulates show advantageous adsorption properties due to a high porosity. Extrudates,

however, have a higher mechanical stability but a low capacity in breakthrough experiments.

Preparation of adsorbents by extrusion and granulation.

24. MULTI-SCALE MODELLING OF FLUID BED GRANULATION

PROCESSES THROUGH A COUPLED PBM-DEM-CFD

FRAMEWORK TO FACILITATE QBD IN PHARMACEUTICAL

DRUG PRODUCT MANUFACTURING

Ashutosh Tamrakar1, Dana Barrasso1, Celia N. Cruz2 & Rohit Ramachandran1


Piscataway, NJ, 08854, USA

2 Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD,

20993, USA


Aligned with the FDA and pharmaceutical industry's efforts to implement the Quality by

Design (QbD) paradigm and incorporate design-based principles to both new and existing

manufacturing processes, this work aims to move towards a predictive model-based analysis

to establish a process design space linking critical process parameters (CPPs) and formulation

properties to critical quality attributes (CQAs). A fluid bed granulation (FBG) process is used

to demonstrate a comprehensive process model development by efficiently coupling multi-

scale simulation techniques for effective process design, development and scale-up.

A novel framework is presented that couples population balance modelling (PBM),

discrete element methods (DEM) and computational fluid dynamics (CFD), and incorporates

CPPs (e.g. liquid spray rate, airflow rate, and vessel temperature) and formulation properties

of both liquid and particles (e.g. liquid viscosity and liquid-particle contact angle). The

framework relies on the PBM to simulate the changes in the particle size distribution (PSD)

due to rate processes including aggregation, breakage, liquid addition and consolidation, and

on DEM-CFD simulations to provide dynamic mechanistic information such as flux data,

collision frequencies and drag forces needed to evaluate the rate kernels involved. The

heterogeneity of liquid distribution and particle collisions as the system is fluidized and

sprayed with binder is captured and embedded into PBM calculations via associated rate

kernels which are functions of PSD and liquid content changes (see Figure 1).

Figure1. Snapshots of liquid content (a, b) and particle diameter (c, d) at time = 1s and 2s

respectively.

25. MODELLING FRAMEWORK FOR THE DYNAMIC

FLOWSHEET SIMULATION OF SOLIDS PROCESSES

Vasyl Skorych, Eduard Eichner, Maksym Dosta, Ernst-Ulrich Hartge & Stefan

Heinrich

Hamburg University of Technology (TUHH), Institute of Solids Process Engineering and Particle

Technology, Denickestrasse 15, 21073 Hamburg, Germany


Many production processes in solids processing technology consist of several apparatuses

and process steps connected with energy and material flows. For the dynamic simulation of

such processes the development of a novel flowsheet simulation system has been started

within the German DFG priority program SPP-1679, which contains 31 projects from

different German universities (www.dynsim-fp.de). In this contribution the architecture of the

new modelling framework and its application for the investigation of transient behaviour of

continuous fluidized-bed granulation processes are presented.

The system is based on the sequential-modular approach, where each model is calculated

separately. This makes it possible to use multiple specialized solvers for the calculation of a

flowsheet simultaneously. This leads to a high flexibility in the development of models. For

the dynamic simulation a modified Waveform Relaxation method is used, in which the total

simulation time is divided into smaller intervals, and models are solved separately using some

initial guess for the solution.

Due to the fact that the solids are described by distributed parameters, special techniques

such as transformation matrices are used for their handling. These matrices allow preserving

interdependency between distributed parameters during the simulation.

Distinctive features of the new system are: dynamic calculation of complex process

structures considering solid, liquid and vapour phases and their mixtures; advanced handling

of multidimensional dependent distributed properties; providing standardized interfaces for

implementation of new models.

General architecture of the dynamic flowsheet simulation system

http://www.spe.tu-harburg.de/de/institut/mitarbeiter/details.html?tx_wecstaffdirectory_pi1%5Bcurstaff%5D=8&cHash=bde0eba9bc6164d00c0a3c4ba5bd8521

26. PILOT SCALE OPTIMIZATION OF ROLLER COMPACTION

PROCESS USING NEAR-IR CHEMICAL IMAGING

Milad Khorasani1, José M. Amigo2, Poul Bertelsen3, Changquan C. Sun4 &

Jukka Rantanen1

1 Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen,

Universitetsparken 2, 2100, Copenhagen, Denmark

2 Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 30, 1957,

Frederiksberg C, Denmark

3 Takeda Pharmaceutical GmbH, Robert Bosch Strasse 8, D-75224, Singen, Germany

4 Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Harvard St. SE, 308,

MN 55455, Minneapolis, USA


Dry granulation using roller compaction is an important unit operation for the

pharmaceutical industry. In contrast to many wet granulation techniques, dry granulation is a

continuous process and it is a suitable process for moisture and heat-sensitive compounds.

This results in various economic advantages. During dry granulation, the powder is

compacted between two rolls to form compacts (ribbons). These ribbons are subsequently

milled into granules and the porosity of the ribbons influences the granule properties and final

product quality.

In this work, model ribbons with varying porosity were prepared at different roll pressures

and roll speeds. The ribbons were further milled to granules and these granules were

compacted into tablets. Using Near-Infrared Chemical Imaging (NIR-CI) and chemometric

method, we visualized the porosity distribution in the ribbons. In order to investigate the

relation between ribbon porosity and granule particle size distribution (GPSD), the 10, 50 and

90% fractions of the ribbon porosity distributions and GPSDs, were correlated by linear

regression. Promising correlation coefficient for the 50% and 90% fractions were achieved.

Ribbons with higher strengths resulted in granules with larger size. The corresponding tablets

from these granules had lower tensile strength. Using NIR-CI it was also possible to visualize

the chemical variation, e.g. composition distribution. Our study confirms the potential of NIR-

CI for process monitoring and control of continuously operating roller compaction line.

Porosity distribution of roller compacted ribbons


27. MECHANISTIC TIME SCALES IN ADHESIVE PARTICLE

MIXING

Duy Nguyen1, Anders Rasmuson1, Ingela Niklasson Björn2 & Kyrre Thalberg2

1 Department of Chemical Engineering, Chalmers University of Technology, SE-412 96, Gothenburg,

Sweden 2 Astra Zeneca Pharmaceutical Development R&D Mölndal, SE-431 83, Mölndal, Sweden


This study investigates the mechanisms governing mixing of adhesive mixtures, i.e.

random mixing, de-agglomeration and adhesion, and their relative importance to achieve

mixing homogeneity. To this end, blending of micronized particles (fines) with carrier

particles was carried out using a high shear mixer. Dry particle sizing using laser diffraction

was employed to assess blend homogeneity and to evaluate the relative strength of the

agglomerates present in the fines. Particle sizing using a non-destructive imaging technique

was used to monitor changes in particle size during blending. It was shown that the de-

agglomeration of the fine-particle agglomerates is the slowest mechanism and hence the rate-

limiting step as regards achieving a homogeneous adhesive mixture. Consequently, a longer

mixing time is needed for blending of larger agglomerates. Being fast, simple and

reproducible, the laser diffraction technique was shown to be an efficient method for

measurement of fine particle content and homogeneity of a mixture, while the non-destructive

image analysis was able to give relevant information on the rate of de-agglomeration of the

fine-particle agglomerates as well as on the size of the resulting carrier-fine particle

assemblies.

Figure 1. Schematic representation of adhesive mixing mechanisms

28. INFLUENCE OF NOZZLE CONFIGURATION ON PROCESS

STABILITY OF CONTINUOUS FLUIDIZED BED LAYERING

WITH EXTERNAL CLASSIFICATION

A. Bück1, K. Meyer1, S. Palis2, C. Neugebauer3, A. Kienle2,3,

S. Heinrich4 & E. Tsotsas1

1 Chair of Thermal Process Engineering, Otto von Guericke University Magdeburg, Universitätsplatz

2, 39106 Magdeburg, Germany

2 Chair of Automation and Modelling, Otto von Guericke University Magdeburg, Universitätsplatz 2,

39106 Magdeburg, Germany

3 Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstraße 1,


4 Solids Process Engineering, Hamburg University of Technology, Denickestr. 15,

21073 Hamburg, Germany


Fluidised bed layering is an important process in many industries, for example foods, and

fertilisers. The aim often is the production of a solid, free-flowing powder from solutions or

suspensions by spraying and subsequent evaporation of the solvent, thus changing the

properties of the particles in the powder, for example size, moisture content, or temperature.

The process is often run continuously with external classification where particles are removed

from the bed and are classified by screening and milling. The portion that does not comply

with required specifications is milled and re-fed to the apparatus. In general, each particle has

its own values for the characteristic properties, i.e. the particles possess a property

distribution.

Macroscopically, the temporal evolution of the particle property distribution can be

described in the population balance framework. For modelling this process, the granulation

chamber is divided into two compartments: the spraying zone, where the particles are covered

with the solution, and the drying zone where the liquid evaporates. Due to fluidisation, the

particles are able to flow from the spraying to the drying zone and vice versa. Depending on

the process parameters, e.g. spray zone size, residence time in the two zones, and milling

diameter, the process can either be open-loop stable or open-loop unstable. The unstable

process is characterised by usually undesired self-sustained oscillations in the particle size

distribution and in product mass flow.

In this work, a bifurcation stability analysis of the process with respect to the spray zone

size which depends on the nozzle characteristics, e.g. nozzle pressure and spray angle, as well

as the amount of sprayed solution and bed height, is presented. The size of the spray zone α is

correlated to the nozzle operating parameters, allowing the derivation of stability charts and

operating regimes.


Stability chart for spray zone size α and size of milled and re-fed particles Lmill for different

mean residence times in the drying zone.

29. OBLIQUE IMPACT OF PARTICLES ON WET SURFACES

Britta Crüger1, Stefan Heinrich1, Sergiy Antonyuk2, Niels G. Deen3 & Johannes

A.M. Kuipers3




University of Kaiserslautern, Gottlieb-Daimler-Strasse, 67663 Kaiserslautern, D

3 Multiphase Reactors Group, Department of Chemical Engineering and Chemistry, Eindhoven

University of Technology, P.O. Box 513

5600 MB Eindhoven, NL


Granulation processes are characterized by intense particle-particle and particle-wall

contacts. Furthermore, these collisions often happen in the presence of liquid layers due to

liquid injection. Therefore the knowledge of micromechanics during such wet collisions is

fundamental for the exact description of a granulation process.

In this work the collision behaviour of dry particles obliquely impacting a target plate

covered by liquid layers is investigated by means of restitution coefficients. The coefficient of

restitution characterizes the energy dissipation during an impact and is defined as the ratio of

the velocities after and before impact. It is an important parameter for DEM simulations and

depends strongly on the collision parameters (such as collision velocity and angle), particle

behaviour (i.e. elastic or plastic) as well as on the properties of the injected liquid (viscosity,

layer thickness). To investigate the influence of these parameters on the wet collision

behaviour particle-wall impacts were recorded by two synchronized high-speed cameras

allowing a three-dimensional analysis (figure).

In dependence of the collision angle the normal component of the coefficient of restitution

has a maximum and the tangential component a minimum at approximately 20 °. The impact

velocity, liquid viscosity and liquid layer thickness also feature a strong influence on the

coefficient of restitution, but no effect on the overall dependence of the coefficient of

restitution on the impact angle.

Schematic representation of the experimental setup and example of the particle movement and

liquid bridge formation during the collision of a dry glass particle with a glass target plate

covered with a water film of 300 µm thickness (recorded by camera 1)

30. INFLUENCE OF THE SOLID BOND MODEL ON AN

IRREGULAR SHAPED AGGLOMERATE BEHAVIOUR IN DEM

SIMULATIONS

Sergii Kozhar1, Maksym Dosta1, Vitalij Salikov1, Sergiy Antonyuk2 & Stefan

Heinrich1


Technology, Hamburg, Germany

2 Chair of Particle Process Engineering, University of Kaiserslautern, Kaiserslautern, Germany


In order to simulate numerically the particle behaviour within particle collectives, the

discrete element method (DEM) is often employed. The contact interactions and dynamic

behaviour of particles on the microscale are mainly characterised by contact models used in

DEM simulations. An imprecise implementation of the particle shapes and material properties

affect the accuracy of simulations with a bulk. Often in DEM simulations bulk is represented

by ideal spherical particles. Contrary to this, the particles used in industries have usually

irregular shapes. Such shape simplification is undesirable since a complex shaped body

behaves differently from a spherical one.

To consider the real shape of particles, the bonded-particle model has been used in this

contribution. Particles have been represented as agglomerates consisting of non-overlapping

primary spherical particles connected with solid binder bonds. The process of the structure

creation and DEM calculation of the agglomerates under static and dynamic loading were

performed by means of the in-house developed component-based simulation system MUSEN

[1].

To describe elastic-plastic behaviour of material the different contact models and the

models for the description of the solid bonds have been tested and their influence on contact

interactions has been analysed.

[1] M. Dosta, S. Antonyuk, S. Heinrich, Multiscale simulation of agglomerate breakage in fluidized

beds, Industrial & Engineering Chemistry Research, 52 (2013) 11275-11281.

31. CHARACTERISATION OF THE WORK OF ADHESION OF

FOOD GRADE COATING MATERIALS ON A MALTODEXTRIN

MODEL SURFACE

Adrian Kape, Bärbel Ruick & Stephan Drusch

Technical University of Berlin, Department of Food Technology and Food Material Science,

Königin-Luise-Str. 22, 14195 Berlin


For the application of a proper functional coating the interactions of the particle and the

coating solution needs to be taken in concern. With respect to material science, relevant

parameters in this particle-liquid-interaction (PLI) are wettability and adhesion. Aim of the

present study was to validate the applicability of two different methods for the determination

of the work of adhesion with respect to food-related applications.

To fulfil the aim of estimating the adhesion of food grade coating solutions on food grade

primary particle, there are two different models. The first one is the Owens-Wendt-Rabel &

Kaelble-model (OWRK), where in the first place, the free surface energy (SE) with its polar

and disperse parts of the particles material needs to be examined. After characterising the

surface tension (SFT) with polar and disperse parts of the coating solution, the work of

adhesion (WA) can be calculated. The second model is the Young-Dupré- model (Y-D), where

only the directly measured contact angle and the SFT of the coating solutions are required.

Experiments show, that the WA as derived from the two different models may vary to a

significant degree. When using the OWRK method, the determination of the SE is based on

linear regression, for which at least two different reference liquids are required. For two

points in a linear regression did not lead to a realistic SE, the contact angle of at least three

reference liquids covering a wide range of polar and disperse fraction in surface tension

should be measured. When a reference liquid with high polar fraction in SFT is missing, an

underestimation of the SE occurred. Lack of a reference liquid with high disperse fraction led

to an underestimation of the polar fraction of the SE of food grade model surfaces. For

determination of the SE of maltodextrin-based food grade model surfaces, as used in this

study, a combination of water, diiodomethane and at least a third reference liquid e.g.

ethylene glycol or formamide proved to be suitable. When it comes to the estimation of the

wetting properties of coating solutions on maltodextrin model surfaces, by calculating a

theoretical contact angle, the OWRK model shows 0° for two of the samples, examined in this

study (MC and Nutrateric). In contrast to the calculated contact angle, the direct measurement

of the contact angle of both coating solutions showed higher values of the contact angle.

Compared to the OWRK-model, the Y-D-model showed lower values of WA for two of the

examined coating solutions (carboxymethylcellulose and hydroxymethylpropylcellulose) and

higher WA for the other two examined coating solutions (methylcellulose and Nutrateric®). It

is hypothesized that the difference results from physical interactions of the reference liquids

and the coating solution on the maltodextrin model surface, e.g. porosity affects the contact

angle.

Using the OWRK model is convenient, when the wetting and adhesion properties of

coating solutions on model surfaces are characterised, because once the SE is estimated, only

the SFT of the coating solutions needs to be determined. The two models lead to different

values of WA and therefore to differences in the evaluation of the coating properties.


32. PREDICTING THE SURFACE COMPOSITION OF A SPRAY

DRIED PARTICLE BY MODELLING COMPONENT

REORGANIZATION IN A DRYING DROP

Anna Porowska1, Maksym Dosta1 Alessandro Gianfrancesco2, Lennart Fries3

Stefan Palzer4 & Stefan Heinrich1

1 Hamburg University of Technology, Denickestr. 15, 21073 Hamburg, Germany

2 Nestlé Product Technology Center Konolfingen, Nestlestrasse 3, 3510 Konolfingen, Switzerland

3 Nestlé Research Center Lausanne, PO Box 44, 1000 Lausanne 26, Switzerland

4 Nestlé Beverages Business Unit, Av. Nestlé 55, 1800 Vevey, Switzerland


Properties of powder, such as flowability, reconstitution behaviour or particle adhesion

depend on the surface properties, which are related to the surface composition. In spray

drying of a multicomponent system, redistribution of the feed components along a droplet

radius can take place. This redistribution can be driven by the difference in the diffusivity of

the components, component solubility, density, surface activity and hydrophobicity of

components. The final composition on the surface of a dried particle is a resultant of these

forces.

Modelling of the drying of a single drop in a hot air stream including two and three

components in the feed was applied to predict the radial distribution of the components in the

particle. In the model the mass transfer is described as diffusion. It is assumed that an

amorphous solid is formed, thus no kinetics of the solid formation was introduced. The

influence of the initial solid content, drying air temperature and component ratio on the time

for skin formation and the solid content gradient along the droplet radius during drying were

studied. The results obtained from the simulations are compared with the properties of

powders obtained by spray drying.

Figure 1. Left: Schematic presentation of the ternary model of a single drop drying with two

solutes (A1 and A2) having different diffusion coefficients (rc - radius of the liquid core, rL -

radius of the drop, R0 - initial drops radius, Di - diffusion coefficient, mvap - vapour mass

stream). Right: Influence of the initial total solid content and solutes ratio on the final

concentration profile in a dried particle

33. A MECHANISTIC UNDERSTANDING OF GRANULE

BREAKAGE IN CONTINUOUS TWIN SCEW GRANULATION

Juan G. Osorio1, Ridade Sayin1 & James D. Litster1,2

1 Department of Chemical Engineering, Purdue University, West Lafayette, IN, 47906, USA

2 Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, 47906,

USA


Continuous pharmaceutical manufacturing has gained popularity and deeper understanding

in recent years. Within this scope, a novel continuous wet granulation technique - twin screw

granulation (TSG) - has been characterized. TSG has shown the capability of producing

granules with a range of properties depending on the parameters used (e.g. screw

configuration) used [1, 2]. From these studies, it was concluded that the TSG design yields

"well-defined regions for the different granulation rate processes" to occur [1]. Although this

is true, a mechanistic and physical understanding of how these rate processes occur is lacking.

Due to the poor initial liquid distribution, breakage is an essential mechanism to give

reasonable granule size and liquid distributions. This work focuses in understanding the

breakage mechanisms in TSG using different techniques. These techniques include the use of

model materials with known particle size (e.g. play dough and polystyrene beads) to

determine the breakage critical particle size and the daughter particle distribution, the use of

visualization experiments using high speed imaging to determine where breakage is

happening, and the use of discrete element method (DEM) modelling to determine the applied

stresses in the TSG and their impact on breakage. The effect of screw element design, screw

speed and screw diameter will be presented. The implementation of these results into

mechanistically based breakage kernels for population balances and the implications for

optimizing screw deign will be discussed.

[1] A. Al Hagrasy, J.D. Litster, Granulation rate proccesses in the kneading elements of a twin screw

granulator, AIChE Journal, 59 (2013) 4100-4115.

[2] R. Sayin, A. El-Hagrassy and J.D. Litster, Distributive mixing elements: Towards impoved granule

attributes from a twin screw granulation process, Chemical Engineering Science, Accepted, 2014.

Conveying and kneading elements (top) with sample DEM images (bottom) of a continuous

twin screw granulator

34. COMPARATIVE STUDY OF MATRIX TABLETS -

EFFECT OF THE GRANULATION METHOD

Andreas Sauer1, Miyuki Fukusawa2 & Taka Hoshino2

1 Shin-Etsu Pharma & Food Materials Distribution GmbH, Rheingaustraße 190-196, H391, 65203

Wiesbaden, Germany

2 Shin-Etsu Chemical Co., Ltd. Cellulose Technical Support Center, YBP Technical center, 134,

Godo-cho, Hodogaya-ku, Yokohama, 240-0005, Japan


Sustained release matrix tablets are widely used in the pharmaceutical industry to provide a

therapeutically effective drug level in the body over several hours. By administration of

sustained release tablets, the number of doses can be reduced to the benefit of the patient.

Highly viscous cellulose derivatives are binders for hydrophilic sustained release matrix

tablets [1]. To produce tablets with uniform weight and drug content, mixtures with good

flowability and homogenous distribution of the drug are required. Flowability and the

homogeneity of drug distribution can be increased by granulation of the drug and the

excipients [2,3].

We present different granulation techniques for the production of theophylline sustained

release matrix tablets with 10%, and 20% Shin-Etsu METOLOSE® SR (Hypromellose 2208,

HPMC). The effect of wet (fluid bed and high shear mixer granulation) and dry granulation

(roller compaction) on the tablet's dissolution profile is evaluated and compared with direct

compression of the ingredients.

Matrix tablet production by using granulated powder or direct compression

[1] H. Patel, D. R. Panchal, U. Patel, T. Brahmbhatt, M. Suthar, Matrix Type Drug Delivery System:

A Review, JPSBR, 1 (3) (2011), 143-151.

[2] Y. Qiu, Y. Chen, G. G. Z. Zhang, L. Liu, W. R. Porter, Developing Solid Oral Dosage Forms

(2009), Elsevier, 469-517.

[3] N. Shinde, N. Aloorkar, Ajit K., Bhaskar B., S. Sulake, P. Kumbhar, Recent Advances in

Granulation Techniques, Asian Journal of Pharmaceutical Sciences, 4 (1) (2014), 38-47.

http://www.asianjps.com/

35. GAINING PROCESS KNOWLEDGE BY USING MECHANISTIC

MODELS FOR FLUIDIZED BED DRYING IN A CONTINUOUS

MANUFACTURING ENVIRONMENT

Séverine T.F.C. Mortier1, Krist V. Gernaey2, Thomas De Beer2 & Ingmar

Nopens3

1 BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of

Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium

2 Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical

Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000

Ghent, Belgium

3 CAPEC-PROCESS, Department of Chemical and Biochemical Engineering, Technical University of

Denmark, Building 229, 2800 Kgs. Lyngby, Denmark


Nowadays, the pharmaceutical industry is taking the step towards continuous

manufacturing. Traditionally, batch processes are used where product quality evaluation

mainly relies on off-line, time-consuming and, hence, less efficient laboratory testing. The

continuous approach has some advantages as the processing efficiency can be improved by

relying on in-line measurements and real-time adjustment of sensitive process variables.

However, an approved Design Space is required by the Food & Drug Administration (FDA)

before the process can be applied. The development of the Design Space requires process

knowledge, which can be obtained through validated mechanistic models. The ConsiGmaTM

(ColletteTM, GEA Pharma Systems, Wommelgem, Belgium) is a fully continuous from-

powder-to-tablet manufacturing line intended for tablet production. It consists of a high shear

twin-screw wet granulation unit, followed by a six-segmented fluid bed drier in which the wet

granules are dried. The focus of this study is the mechanistic modelling of this drying system.

The mechanistic modelling has been performed in a step-wise approach. The drying

behaviour on single particle level has been modelled and validated using experimental data. A

Global Sensitivity Analysis (GSA) identified the gas temperature as the main influential

factor. Subsequently, a model reduction strategy was developed to enable the implementation

of the single particle model into a Population Balance Model (PBM), allowing the modelling

of the drying behaviour of a population of granules. The PBM-model, analysed using a GSA

and a scenario analysis, revealed that the gas temperature and the filling time are the key

parameters impacting the moisture content distribution of the dried granules. The width and

the mean of this distribution should be controlled to enable appropriate further downstream

processing of the granules. A Computational Fluid Dynamics (CFD) model was used to study

the flow pattern of the wet granules inside the six-segmented fluid bed dryer, which is an

interesting tool to detect dead zones and to propose suggestions for improvements in the

design of the drying unit. In a next phase the CFD-model can be coupled with the PBM-

model. However, the validation of the coupled CFD-PBM-model is a challenging task.

In conclusion, modelling was performed to gain more detailed process knowledge on the

drying process. This knowledge can now be used to develop control strategies and defining

the Design Space for the ConsiGmaTM.

36. VISCOSITY INFLUENCE ON THE ATOMIZATION

BEHAVIOUR IN A ROTARY DISC SPRAY DRYER

Lucas Bernardo Monteiro, Igor Paiva Sansão, Kauana Martins Iglesias, Aldo

Ramos Santos & Deovaldo de Moraes Júnior

Santa Cecília University, Rua Oswaldo Cruz, 277, Boqueirão, Santos, São Paulo, Brazil.

Drying consists of a heat and mass transfer where the moisture moves itself from a

saturated solid to an insaturaded gas. During this process, the solid temperature is the same

from the fluid's wet bulb. In permanent flow, with liquid covering the surface from the solid,

the drying rate is constant. When the first dry region is formed on the surface, the drying rate

falls, and the solid aproximates it's temperature to the fluid's dry bulb. Inside the solid

material, at the evaporation surface, it's temperature remains at the fluid's wet bulb. One of the

equipments used to do this procedure is the spray dryer, which consists of an atomization

system, where micro droplets from the solution are formed inside a hollow chamber. After the

contact of the droplets with the dry and hot gas, a quick evaporation of the water present in

the atomization cloud occurs, allowing to obtain a dried and granulated material. One of the

biggest problems from this equipment is the lack of data to do a precise design for this kind of

equipment. The present work has as objective study the infuence from the liquid viscosity on

the atomization range and distribution of the post atomized material in a rotary disc spray

dryer.

The experiments were realized on the spray dryer unit, located on the Unit Operation

Laboratory, on Santa Cecília University, Santos, São Paulo, Brazil; 81 collectors with

adsorbent material, an 30,10 mm diameter atomizer disc with 16 round orifices with 3,5 mm

of diameter each. The solutions used were water and green banana biomass with average

viscosity of 4350 cP. The green banana is a functional aliment without gluten, rich in fiber,

minerals, vitamins and resistant starch which acts as a natural impurities collector from the

human intestine. The results allowed to observe that with the viscosity increase, the

atomization range also has increased and the product distribution were more homogeny if

compared with water.

37. IMPLEMENTATION OF ROLLER COMPACTION INTO A

CONTINUOUS MANUFACTURING ENVIRONMENT

Kirk A. Overhoff, Varsha Dhamankar & Catherine Metzler

Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210


Pharmaceutical product development and manufacturing has traditionally followed a

batch-wise process primarily due to simplified lot tracking capabilities to ensure rigorous

product quality and safety standards are met. Developing a continuous process for

manufacturing pharmaceutical products may offer benefits over traditional batch-wise

processes through reduction in development cycle times and scale up activities while offering

equivalent product quality and safety as batch manufacturing through implementation of

science-based approaches (e.g. Quality by Design) [1].

The objective of this study was to provide greater fundamental and operational

understanding of roller compaction in a variable process state (i.e. a continuous state) when

subjected to potential upstream perturbations and process changes contributing to non-steady

operation and through programed variable line rate conditions. Two separate experiments

were performed using a commercial roller compactor and placebo blend. In the first, the

effect of a sudden roll speed change on ribbon thickness and product quality was evaluated as

a function of equipment process feedback controls. Gap correction to roll speed changes

corresponded to traditional P/I/D control understanding making it possible to predict impact

of perturbation to product key quality. In the second experiment, a resolution V half-factorial

experimental design was executed to evaluate key parameters affecting line rate in and out of

the roller compactor. Roll speed, gap, and pressure affected granule throughput as well as

accumulation of ribbons in the mill. Higher ribbon throughput settings led to backlog of

ribbons in the mill and compaction region, thus having an impact on an ability to operate at

steady-state.

[1] M. Warman, Continuous processing in secondary production, in: D.J. am Ende (Ed.) Chemical

Engineering in the Pharmaceutical Industry: R&D to Manufacturing, Wiley, Hoboken, 2010, 837-851.

38. DEVELOPMENT AND CHARACTERIZATION OF TERNARY

SOLID DISPERSION GRANULES: PREDICTION OF GLASS

TRANSITIONS

Ahmad B. Albadarin1,2, John A. Collins1, Mark Davis1, David Egan1, Chirangano

Mangwandi2, Mark Southern & Gavin Walker1,2

1 Department of Chemical and Environmental Sciences, Synthesis and Solid State Pharmaceutical

Cluster and Pharmaceutical Technology Manufacturing Centre, University of Limerick, Ireland

2 School of Chemistry & Chemical Eng., Queens University Belfast, N. Ireland, BT9 5AG, UK.


Amorphous drugs are classically formulated as solid dispersions for which the addition of

excipients is utilized to improve the properties of the formulation i.e. apparent solubility of

poorly soluble APIs and dissolution rate [1]. It has been demonstrated that ternary solid

dispersion compositions can be more efficient than binary compositions in terms of their

excellent physical stability and ability to inhabit the recrystallization of API's in bio-relevant

media [2].

The resulting ternary solid dispersions are essentially more complex than formulations

containing the crystalline API, and the advanced characterization of such systems is presently

an increasingly active area of research. Determining the glass transition(s) of solid dispersions

provides useful information regarding the physical properties of these systems. This

information includes: the miscibility of the drug with the excipient, the physical state of the

drug and excipient, possible interactions through hydrogen bonding and proper storage

conditions post production to ensure the maintained physical stability of the solid dispersion.

When evaluating Tg of a dispersion system, it is very important to compare experimental

values with values predicted for perfectly mixed systems so as to gain an understanding of the

physical state of the system.

In this study, various drug-polymer combinations containing fine particle HPMCAS and

Kollidon 30 and Felodipine as the model drug were prepared by extrusion-spheronization.

The ternary solid dispersion composition comprising: 10%‒40% wt. Felodipine; 30%‒90%

wt. of a water-soluble polymer, Kollidon 30; and 30%‒90% HPMCAS (Hypromellose

Acetate-Succinate, a water-insoluble polymer). After a general screening of the variables

which highly affected the results, an optimal (custom) design was employed to study the

effect of formulation combinations on the properties of the granules to produce and develop a

model to estimate the glass transition of ternary mixtures as a function of composition.

Detailed characterization using powder X-ray diffractometry, differential scanning

calorimetry, scanning electron microscopy and infrared spectroscopic measurements for

specific polymer-polymer and drug-polymer interactions were performed.

[1] D.D. Sun, P.I. Lee, Crosslinked hydrogels—a promising class of insoluble solid molecular

dispersion carriers for enhancing the delivery of poorly soluble drugs, Acta Pharmaceutica Sinica B 4

(2014) 26-36.

[2] H.M. Yan, Z.H. Zhang, Y.R. Jiang, D.M. Ding, E. Sun, X.B. Jia, An attempt to stabilize

tanshinone IIA solid dispersion by the use of ternary systems with nano-CaCO 3 and poloxamer 188,

Pharmacognosy Magazine 10 (2014) 311-317.

39. ANALYSIS OF MESO-SCALE EFFECTS IN HIGH SHEAR

GRANULATION THROUGH A CFD-PBM COUPLED

COMPARTMENT MODEL

Per J. Abrahamsson1, Patric Kvist1, Xi Yu2, Gavin Reynolds3, Ingela Björn

Niklasson4 & Anders Rasmuson1

1 Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412

96, Göteborg, Sweden

2 European Bioenergy Research Institute, Aston University, Aston Triangle, Birmingham, B4 7ET,

UK

3 Pharmaceutical and Analytical Research and Development, AstraZeneca, Macclesfield, SK10 2NA

UK

4 Astra Zeneca Pharmaceutical Development R&D Mölndal, SE-431 83, Mölndal, Sweden

In high shear granulation it has been pointed out that there is a need for meso-scale

resolution and coupling between flow field information and the evolution of particle

properties. A tool that could solve flow properties in vessels of all types and sizes and relate it

to the evolution of particle properties would be of great value for scale up and process control.

In this article we develop a modelling framework that discretizes the high shear

granulation process based on process relevant parameters both in time and space. It is built up

by a coupled flow field and population balance solver and is used to resolve and analyse the

effects of meso-scales on the evolution of particle properties. The flow solver is based on a

continuum approach allowing for large scale units to be modelled. The population balance

contains aggregation, layering and breakage and is solved with a Monte Carlo algorithm. The

solvers are iteratively connected, and the flow field is determined with constant particle

properties and used to determine compartment sizes and properties in the Monte Carlo solver.

An analysis is made to determine the frequency of updating the flow information as the

particle properties change. A Diosna high shear mixer is modelled with calcium carbonate

powder as the granulation material. The results show that for the EKE aggregation kernel the

spatial compartmentalization has no visible effect but the temporal discretization is of

importance. In the case of breakage or regime based collision kernels with thresh hold values

between different regimes, the spatial compartments become of significant importance and

different regimes can be found in different regions of the vessel.

40. INLINE PARTICLE SIZE MEASUREMENT IN ROLL

COMPACTION/DRY GRANULATION

Haress A. Mangal & Peter Kleinebudde

Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstraße 1,

40225 Duesseldorf, Germany


Continuous manufacturing is attracting more interest in pharmaceutical industry, recently.

Therefore, roll compaction/dry granulation, as a continuous process, is shifting into focus as

granulation technique. To profit from the advantages that continuous manufacturing offers, it

is necessary that processes are well understood, monitored and controlled. For that reason

process analytical technology tools are needed to monitor critical quality attributes throughout

the process.

This study focusses on inline particle size monitoring during roll compaction/dry

granulation using a fibre-optical spatial filtering probe (Parsum IPP70-S, Parsum GmbH,

Chemnitz, Germany). The particle size was chosen as quality attribute, since it greatly

influences the granule properties. Therefore it should be controlled over process time. As

illustrated in Figure 1 the probe was installed centred in a tube below the granulator. At this

position granules have to pass the measuring zone after granulation. Compressed air was used

to clean the measurement zone, periodically.

Co-processed Mannitol-Povidone (Mannitol TAG, Wei Ming Pharmaceutical, Taiwan)

was used as model substance. Roll speed and granulator settings were kept constant. The gap

was maintained constant by use of an automatic gap control, which adjusts feeding and

tamper auger speeds. The specific compaction force was changed approximately every 20

minutes between 2 kN/cm and 8 kN/cm. The star granulator was set to 50 rpm and a sieve

with a mesh width of 1.5 mm was employed. The probe settings were also modified, e.g. the

size of the ring buffer, from which the particle size distribution is calculated as a moving

average.

The x50-values changed from 540 µm at 2 kN/cm to approximately 890 µm by increasing

the specific compaction force to 4 kN/cm (Fig. 2). Even more, x50-value of 1044 µm was

obtained by increasing specific compaction force to 8 kN/cm. A broad particle size

distribution during roll compaction/dry granulation typically was generated, the particle size

data of the probe varied using a buffer size of 50.000, even when the same conditions were

used. Larger buffer sizes minimized these variations, even so it lead to a delay in observing

changes. This study showed that it is basically possible to monitor the particle size during roll

compaction/dry granulation using fibre-optical spatial filtering technique.

Figure 1. Installed Parsum IPP70-S

Figure 2. x50 values calculated of different buffer sizes dependent on specific compaction

force

41. SOLID CRYSTAL SUSPENSIONS - AN ADVANCED

FORMULATION STRATEGY FOR POORLY WATER SOLUBLE

DRUGS

Elena Reitz1, Chris Vervaet2, Stefanie Weidtkamp-Peters3 & Markus Thommes1

1 Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, University Street 1,

40225 Duesseldorf, Germany

2 Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium

3 Center for Advanced Imaging, Heinrich-Heine-University, Duesseldorf, Germany


Solid crystal suspensions (SCS) are physically stable solid dispersions and capable to

enhance the bioavailability of poorly soluble drugs. The aim of this study was to optimize the

formulation in order to simplify the manufacturing while maximizing the bioavailability. The

preparation of the SCS was done using a lab scale extruder (Mikro 27, Leistritz). The product

was characterized by in vitro dissolution, confocal laser scanning microscopy (CLSM) and

bioavailability testing in beagle dogs.

The combination of a low and a high melting sugar alcohol (Xylitol and Mannitol) was

favourable for manufacturing when running the extrusion process at temperatures between the

melting points of both components. In this way the viscosity of the melt could be adjusted

improving the processability especially with respect to the down-stream-processing. The

addition of small quantities of sodium lauryl sulphate increased the dissolution rate from the

product, which was attributed by a higher dispersity determined by CLSM.

The in vivo study in beagle dogs was done in comparison to two commercially available

griseofulvin products. Therefore tablets containing the solid crystal suspension formulations

were administrated to dogs and the plasma profiles were measured. The solid crystal

suspension formulation had a 1.32 times higher bioavailability as a formulation containing

micronized griseofulvin (Griseo-CT). However, the bioavailability was 1.54 times less

compared to a nanonized drug formulation (Gis-PEG).

In conclusion, a new formulation for solid crystal suspensions was developed. A

combination of two sugar alcohols was advantageous with respect to an increase of the

viscosity of the melt during processing. The addition of wetting agent increased the dispersity

of the drug particles in the carrier.

CLSM images from SCS formulations standard (left) and with sodium lauryl sufate (right)

(Red = Carrier, Green = Griesofulvin)

42. EVALUATION OF THE ABILITY OF POWDERED MILK TO

PRODUCE MINI-TABLETS DELIVERY OF PARACETAMOL IN

PEDIATRICS

Joana T. Pinto1, Mariya Brachkova1, Ana I. Fernandes1 & João F. Pinto2

1 CiiEM, Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica,

2829- 511 Caparica, Portugal

2 iMed – Research Institute for Medicines and Pharmaceutical Sciences, Faculdade de Farmácia,

Univ. de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal


This work aims to evaluate the usefulness of powdered milk as an excipient for direct

compression into mini-tablets specifically designed for the pediatric population.

A 23 full factorial design was carried out to identify the effect of selected variables and

their interactions (paracetamol to milk ratio, fraction of disintegrant and compression force),

on selected responses (weight variation, thickness, tensile strength and dissolution time) of the

mini-tablets manufactured. Tablets were manufactured according to a matrix design resulting

in eight combinations of four different tableting formulations compacted at two distinct

forces. Each tablet batch was evaluated for thickness (n=6), uniformity of weight (n=20),

diametric crushing strength and tensile strength (σ) (n=6) and dissolution testing (n=12), were

carried out according to Eur. Pharm. A stepwise multiple linear regression was used to

identify and quantify the relationships between each response and the variables studied and

their interactions. Results were analyzed by ANOVA in order to identify the significant

variables and variable interactions responsible for the effects observed; the criterion

considered to accept or reject a variable was based on its significance, reflected by the F-value

(p< 0.05).

The increase on milk fraction in the formulation improved the compressibility of

paracetamol with a decrease on weight variation. Thinner and harder compacts with slower

paracetamol releases were obtained. These observations were not surprising if powdered milk

composition is taken into consideration: milk proteins, lactose (widely used as diluent) and

lipids (often used as binders and taste masking agents), which individually or in combination

contribute to easier the production of tablets. A marked decrease on the dissolution time was

observed as sodium croscarmellose was added to the milk rich formulations. These findings

are in good agreement with the expected use of sodium croscarmellose. The increase of the

compaction force was reflected by the production of thinner compacts with slightly higher

tensile strengths but random effect on the dissolution median time. At high pressures it is

often observed the level off crushing strength and an increase of the importance of particle

deformation in disintegration time. The former may explain why no significant effect was

detected when analyzing tensile strength and dissolution profile.

The experimental design and statistical analysis enabled the identification of the most

significant variables and their interactions affecting the properties of the mini-tablets,

particularly the milk/paracetamol ratio which proved to be critical for the proprieties of the

final product.


43. A THEORETICAL STUDY OF THE HYDRODYNAMIC

BEHAVIOUR OF FLUIDIZED BEDS OPERATED UNDER

REDUCED PRESSURE

Sayali Zarekar1, Franziska Sondej1, Andreas Bück1, Evangelos Tsotsas1 &

Michael Jacob2

1 Thermal Process Engineering, Otto-von-Guericke University, Universitätsplatz 2, 39106

Magdeburg, Germany

2 Glatt Ingenieurtechnik GmbH, Nordstrasse 12, 99427, Weimar, Germany


Fluidized bed granulation is widely used in the formulation of bioactive materials such as

foodstuff, dairy products, and drugs. Such materials are often temperature sensitive, and it is

important to minimize their deactivation during the course of the drying process. While the

deactivation can be lowered by reducing the drying temperature, it can also lead to a low

process throughput due to the reduced drying capacity of the gas medium. Other low

temperature methods such as freeze-drying can be used, but they are costly and time

consuming for bulk production as compared to high temperature drying processes. An

alternate approach is to operate the fluidized bed at moderate vacuum conditions which can

result in considerable reduction in the product temperature. This also allows the gas to be used

as a heat carrier and equipment cost can be lowered.

Fluidized beds operating under reduced pressure have not been extensively investigated.

Some authors have reported correlations for the minimum fluidization velocity of fluidized

beds under vacuum [1,2]. They argue that as the pressure is decreased, the slip flow of gas in

the fluidized bed becomes the major factor influencing the hydrodynamic behaviour. The

decrease in pressure however, also influences the gas properties such as density. There is no

clear distinction between the influences due to change in gas properties and those due to the

slip flow. This distinction is essential, because if the slip flow term is the only major factor

governing the flow regime then the modelling of the fluidized bed process would have to be

changed completely with respect to elutriation, expansion, and heat and mass transfer. In this

contribution, the individual effects of gas properties and slip flow on the hydrodynamic

behaviour of vacuum fluidized beds have been quantified. This has been achieved by

expanding the classical minimum fluidization velocity correlation, applied for atmospheric

conditions [3], to include the slip flow term. The results obtained describe the critical

Knudsen number which indicates when the slip term begins to dictate the flow behaviour. The

derived correlation has been compared with the correlations reported in literature as well as

validated with experimental data.

[1] M.F. Llop, F. Madrid, J. Arnaldos, J. Casal, Fluidization at vacuum conditions. A generalized

equation for the prediction of minimum velocity, Chemical Engineering Science, 51 (1996) 5149-

5157.

[2] Y. Tatemoto, S. Yano, Y. Mawatari, K. Noda, N. Komatsu. Drying characteristics of porous

material immersed in a bed of glass beads fluidized by superheated steam under reduced pressure,

Chemical Engineering Science, 62 (2007) 471-480.

[3] D. Kunii, O. Levenspiel, Fluidization Engineering, 2nd ed., Butterworth-Heinemann, Boston,

1991.


44. JAMMING AND THE ONSET OF GRANULATION IN A MODEL

PARTICLE SYSTEM

Daniel J. M. Hodgson & Wilson C. K. Poon

School of Physics and Astronomy, James Clerk Maxwell Building, The University of Edinburgh,

Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK

Experiments using a model system consisting of glass microspheres and a mixture of water

and glycerol show that the onset of granulation is intimately connected to a recently

established understanding of shear thickening in suspension rheology [1,2]. The system

exhibits a stress induced transition from a suspension to granules above a critical solid volume

fraction (φm). Using rheological data we find two divergent viscosity branches (see Figure 1)

that correspond to frictional and frictionless flow. Above a critical stress (σ*) particles

overcome a repulsive barrier and are pushed into frictional contact. Below φm the sample

remains a flowing suspension at all applied stresses. Above φm the frictionless branch has no

flowing state to jump to and the system jams. The system fractures and granulates as further

stress is applied and the liquid surface tension is no longer sufficient to withstand the outward

pressure. Above particle random close packing (φrcp) there is no longer sufficient liquid to

form a suspension leading to fracture at all applied stresses. This work provides experimental

evidence supporting the understanding of the onset of granulation in the context of jamming

in shear thickening suspensions. It allows the lower volume fraction limits of granulation to

be predicted from simply measuring φm and φrcp for a given solid composition.

[1] M. Wyart, M. E. Cates, Discontinuous shear thickening without inertia in dense non-Brownian

suspensions, Physical Review Letters 112 (2014), 098302

[2] R. Mari, R. Seto, J. F. Morris, M. M. Denn, Shear thickening, frictionless and frictional rheologies,

arXiv 1403.6793

Figure 1. Schematic showing viscosity as a function of solid volume fraction, φ. Two

diverging branches are observed at φm and φrcp corresponding to frictional and frictionless

contacts respectively

45. FUZZY COMPREHENSIVE EVALUATION OF POWDERS IN

ULTRAFINE GRINDING

Zhenfu Luo1, Zaisheng Zhu2, Yuemin Zhao1 & Yunfei Qin1

1 School of Chemical Engineering and Technology, China University of Mining & Technology,

Jiangsu, Xuzhou, 221116

2 Huainan Mining Industry Group Coal Preparation Branch, Anhui, Huainan, 232000


Fuzzy mathematical theory based on the analytic hierarchy process was innovatively used

for fuzzy comprehensive evaluation of ultrafine powders in ultrafine grinding. The weight set

was confirmed by analytic hierarchy process and the evaluation set was calculated using

relevant fuzzy mathematical knowledge. Afterwards, fuzzy comprehensive evaluating value

was elicited, which provided the comprehensive index for the evaluation of product quality.

During ultrafine grinding potassium shale mineral powders by ball mill for 3h, the mass of

product of -10μm was 1.313Kg, the fractal dimension of particle size distribution was 2.348,

d97=14.27μm. Weight set of the indexes W= (0.69, 0.149, 0.161)T and fuzzy evaluating set P=

(0.737, 0.106, 0.847), the fuzzy comprehensive evaluating value was 0.661.


46. AMORPHOUS SOLID DISPERSIONS OF BCS CLASS II DRUGS:

A RATIONAL APPROACH TO SOLVENT AND POLYMER

SELECTION

Mark T. Davis1,3, David P. Egan2,3, Manuel Kuhs1,3, Ahmad B. Albadarin1,3,

Ciara S. Griffin1,3, John A. Collins2,3 & Gavin M. Walker1,2,3

1 Solid State Pharmaceutical Centre, SSPC, University of Limerick, Limerick, Ireland

2 Pharmaceutical Manufacturing Technology Centre, PMTC, University of Limerick, Limerick,

Ireland

3 Materials and Surface Science Institute, MSSI, University of Limerick, Limerick, Ireland


A method has been developed to rationally select (i) polymer and (ii) solvent system when

generating amorphous solid dispersions (ASD) from poorly soluble drugs. The technique was

rapid, straightforward and could be used in pre-formulation to reduce the risk of drug product

crystallisation on storage. Felodipine, fenofibrate, indomethacin and acetaminophen were the

model active pharmaceutical ingredients (API) employed. The polymers used were

Poly(vinylpyrrolidone) grades PVP10, K25 and K30, Soluplus, Kollidon VA 64, Kollidon

SR, HPMC, HPMC-AS and HPMC-P. The ASD were analysed over a 4 week period by

XRD, PLM and ssNMR. The ease of forming a stable ASD by drug was Felodipine >

Indomethacin > Acetaminophen >> Fenofibrate. The ease of forming a stable ASD by

polymer was Soluplus = PVP = Kollidon VA 64 > Kollidon SR = HPMC-P > HPMC-AS.

Acetone, methanol, acetonitrile, ethanol and water were used as solvents. It was found that

alcoholic solvents were more likely to produce a stable ASD. The importance of hydrogen

bonding was discussed.

47. SORPTION KINETIC STUDIES OF HYDROXYPROPYL

METHYL CELLULOSE SAMPLES

Graham E. O Mahony1,2, Mary E. Crowley1,2, Rakesh C. Dontireddy1 & Abina

M. Crean1,2 1 School of Pharmacy, University College Cork, Ireland.

2 Synthesis and Solid State Pharmaceutical Centre.


Hydroxypropyl methyl cellulose (HPMC) is a semisynthetic hydrophilic polymer derived

from cellulose, used predominantly as a controlled release agent in oral drug delivery systems.

A key property of HPMC is its high swellability, which has a significant effect on the release

kinetics of the incorporated API [1]. When a HPMC matrix comes into contact with water, the

polymer absorbs the water and undergoes swelling or hydration to form a viscous gel layer.

This rapid formation of a gel layer on hydration is an essential step in achieving controlled

drug release from HPMC matrices.

This study examines the sorption kinetics (sorption profiles obtained via Dynamic Vapour

Sorption (DVS)) of different HPMC grades. The kinetic curves were analysed using the

parallel exponential kinetics (PEK) model which describes sorption kinetics using two

exponential terms which represent fast and slow processes, with their own characteristic times

and moisture contents. It has been suggested that the fast kinetic process is related to sorption

at available sites of “external” surfaces while the slow kinetic process has been related to

sorption onto the “inner” surfaces [2]. The slow process has been described as the rate

limiting step associated with the polymer chains swelling [3]. The characteristic rate constants

(K1 and K2) and corresponding times (T1 and T2) for the fast and slow processes have been

calculated, using the PEK model, for each of the samples analysed.

Figure 1. Sorption kinetic curve for Benecel E15, showing the slow (green) and fast (red)

kinetic processes as determined by the PEK model (50-60% RH)

[1] S. Kiil, K. Dam-Johansen, Controlled drug delivery from swellable hydroxypropyl methylcellulose

matrices: model based analysis of observed radial front movements, Journal of Control Release, 1

(2003), 1-21.

[2] S. Okubayashi, U.J Griesser, T. Bechtold, Moisture sorption/desorption behavior of various

manmade cellulosic fibers, Journal of Applied Polymer Science 4 (2005), 1621-1625.

2.5

3

3.5

4

4.5

0 20 40 60 80 100

Exp Data

FAST

SLOW

% Moisture content

Time (min)

Benecel E15

[3] C.A.S. Hill, A. Norton, G. Newman, The water vapour sorption behaviour of natural fibers, Journal

of Applied Polymer Science, 3 (2009), 1524-1537.

48. COMPRESSION ANALYSIS FOR ASSESSMENT OF PELLET

PLASTICITY

Ann-Sofie Persson, Josefina Nordström, Göran Frenning & Göran Alderborn

Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23 Uppsala, Sweden


Although sometimes criticized, e.g. [1], the Heckel relationship is commonly used for

deriving an indication of the plasticity of particles from powder compression data. An aspect

often overseen when using the expression is however the calculation of the effective powder

bed porosity for agglomerates. We have earlier shown that the tensile strength of tablets was

related to the diameter of the inter-granular voids and not to the average diameter of all pores

(including voids and intra-granular pores). It was concluded that void size reflects the plastic

deformation of agglomerates during compression. A consequence is that the voidage rather

than the global porosity of the column of agglomerates in the die reflects the relevant reactant

pore system if an indication of agglomerate plasticity should be derived. In this work, Heckel

profiles were derived using two types of spherical agglomerates of microcrystalline cellulose

(pellets) of high (HP) and low (LP) porosity. The porosity of the pellets and tablets have

previously been thoroughly characterized by mercury porosimetry and the pores divided into

intra-granular pores and inter-granular voids [2]. Thus, these tablets represent a model system

with differently distributed air within the tablets. Heckel parameters were calculated from

global porosity and from voidage data and compared with single pellet deformation properties

as well as compression parameters derived by the Adams and Kawakita equations.

The pellets were compressed in a materials testing instrument (Zwick Z100, Zwick/Roell

GmbH & Co. KG, Ulm, Germany) with a stationary lower punch. Single pellet compressions

were made with a Texture analyser (TA.HDi Texture Analyser, Stable Micro Systems, UK).

The single pellet plasticity was calculated from the linear force-displacement profiles.

Two approaches to derive the global Heckel profiles were used; in-die and out-of-die. The

difference in plasticity for the HP and LP pellets was differentiated to a small extent from the

in-die profiles, whereas no differentiation was evident from the out-of-die profiles (Table 1).

Thereby, the Heckel relationship was considered as non-applicable for describing pellet

plasticity. However, a clear differentiation was found using the inter-granular voidage Heckel

parameter. A differentiation was also found from the Kawakita 𝑏−1 and Adams parameters

(Table 1).

[1] J.M. Sonnergaard, A critical evaluation of the Heckel equation, International Journal of

Pharmaceutics, 193 (1999) 63-71.

[2] J. Nordström, A.-S. Persson, L. Lazorova, G. Frenning, G. Alderborn, The degree of compression

of spherical granular solids controls the evolution of microstructure and bond probability during

compaction, International Journal of Pharmaceutics, 442 (2013) 3-12.

49. CFD-PBE SIMULATION TO PREDICT PARTICLE GROWTH IN

A FLUIDIZED BED MELT GRANULATION BATCH PROCESS

Philipp Lau & Matthias Kind

Karlsruhe Institute of Technology, Department of Thermal Process Engineering, Kaiserstraße 12,

76131 Karlsruhe, Germany


The process of fluidized bed spray granulation unites the steps of solid formation and

product formulation in one apparatus and is used for the continuous industrial production of

granules. Thereby, a hot suspension or melt is atomized with nozzles and sprayed into the

fluidized bed which contains granulate particles. The droplets deposit on the particles near the

spray zone and form a film which solidifies to a crystalline layer in the cold fluidization air.

Step-by-step, an onion-like product is formed. Besides drop deposition, abrasion due to

particle-particle collisions is another important mechanism which influences the particle

growth. The tailored product size distribution can be obtained by a downstream screening-

crushing process. Granules larger than the product size desired are crushed in a mill and

recycled to the granulator together with the too small particles.

The aim of our work is to minimize this recirculation. For this, it is necessary to know

growth and attrition rates of the granules. Due to the large number of nozzles in a chamber

and the large dimension of such a device, a granulator cannot be described completely using a

numerical simulation. Hence, a 2D rotationally-symmetric model with one nozzle is

developed to extract internal process variables which are not available in experimental

research, e.g. particle size-dependent growth rates. With this data it is possible to solve the

population balance equation and to predict the development of the particle size distribution

during the process.

Considering fluid dynamics, granulation mechanisms and energy equations (implemented

with user-defined functions) a six-fluid model is solved. The interactions between particles

and air can be described with the model of Gidaspow [1]. The particle-particle momentum

exchanges are modelled with the equations of Syamlal and O’Brien [2]. Extracting particle

size-dependent growth rates from CFD, the population balance can finally be solved to predict

the particles size distribution of the product. The numerical results are validated with

experimental data of a melt granulation in batch mode.

In this research, a 2D-multiphase model with one nozzle is developed to generate space

and time averaged growth and attrition rates of the granules which are needed to predict the

particle size distribution of the product. With this information it is possible to optimize

process parameters and minimize recirculation. This investigation is still in progress, so that

first approaches and results are provided here.

[1] D. Gidaspow, Multiphase Flow and Fluidization: Continuum and Kinetic Theory Description,

Academic Press, New York, 1994

[2] M. Syamlal, The Particle-Particle Drag Term in a Multiparticle Model of Fluidization, National

Technical Information Service, Springfield, VA, DOE/MC/21353-2373, 1987

50. MONO-MODAL PARTICLE SIZE DISTRIBUTIONS IN TWIN-

SCREW GRANULATION - DO NOT FORGET THE FEEDING

SYSTEMS

Robin Meier1, Markus Thommes1, Markus Krumme2, Norbert Rasenack2, Klaus-

Peter Moll2 & Peter Kleinebudde1

1 Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University,

Universitätsstraße 1, 40225 Düsseldorf, Germany, [email protected]

2 Novartis AG, 4002 Basel, Switzerland

Mono-modal particle size distributions (PSD) in a twin-screw granulation process are

desirable to enable process robustness of downstream operations like tableting or capsule

filling. Approaches as varying the viscosity of the binder liquid [1] or applying different types

of screw elements [2] in some cases led to mono-modal PSD - this study examines feeding

systems in detail as uniform feeding is assumed to be a main factor in achieving mono-

modality.

Due to poor flowability and differences in the bulk density, powder feeders show huge

deviations from the set value, which is permanently adjusted by inbuilt controllers during the

process. However, depending on the controller settings powder feeders display gliding

averages over longer time periods and sham not existing accuracy.

At first the feeder performance (KT 20, Coperion K-Tron) was examined offline by

feeding powder (placebo and high drug load mixtures) on an analytical balance and evaluating

the performance by an innovative method, developed by Meier, Mühlenfeld and Thommes

[3]. Afterwards different controller settings that were assumed as good, acceptable and poor,

were applied to a twin screw granulation process, using three different screw setups. A micro

annular gear pump (HNP-Mikrosysteme) was used as liquid feeder, which pumps the liquid

by pressures up to several bars into the barrel, resulting in a pulsation free flow.

By using distributive feeding elements after the second kneading zone, all controller

settings resulted in mono modal and narrow PSD. One kneading zone without distributive

feeding elements, combined with the poor settings resulted in a distinctive bimodal PSD,

whereas, the good settings again resulted in mono modal distributions. Even by a pure

conveying screw homogeneous granules could be produced, if maintaining good controller

settings. These results underline the importance of evaluating feeding systems with respect to

accuracy and uniformity by applying rational methods.

[1] R. M. Dhenge, K. Washino, J. J. Cartwright, M. J. Hounslow, A. D. Salman, Twin screw

granulation using conveying screws: Effects of viscosity of granulation liquids and flow of powders,

Powder Technology, 238, (2013) 77-90

[2] R. Sayin, A. S. El Hagrasy, J. D. Litster, Distributive mixing elements: Towards improved granule

attributes from a twin screw granulation process, Chem. Eng. Sci. (2014),

doi: 10.1016/j.ces.2014.06.040

[3] R. Meier, C. Mühlenfeld, M. Thommes, Evaluation of continuous powder feeding, Poster, 9th

world meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Lisbon, (2014)

51. STRUCTURE AND PROPERTIES OF ACTIVE ENZYME

MICROCAPSULES FORMED BY SPRAY DRYING WITH 3-

FLUID NOZZLE

Martin Jakubec, Monika Majerská, Vojtěch Klimša, Ondřej Kašpar & František

Štěpánek

Laboratory of Chemical Robotics, Institute of Chemical Technology Prague, Technická 5, 166 28,

Czech Republic


This contribution deals with polymeric particles prepared by spray drying in combination

with a novel 3-fluid nozzle, which were used for in situ production of unstable active

substances directly in the targeted area. The 3-fluid nozzle offers the possibility of in situ

cross-linking within individual droplets, because both phases are fed into the nozzle

separately and come in contact only for a short time during atomization. This allows to

produce stable particles in a wide cross-linking ratio [1]. In the present work, a laboratory

spray dryer Buchi mini B290 and a 3-fluid nozzle were used to prepare two kinds of

microparticles: chitosan microparticles cross-linked by TPP anions with immobilized enzyme

laccase [2], and alginate microparticles cross-linked by Ca2+ that can contain a substrate. The

chitosan particles had a mean diameter of 5 μm and a TPP/chitosan cross-linking ratio of

0.094 for optimum swelling/stability behaviour (Figure 1a). Based on electrostatic

interactions, these particles were used for controlled agglomeration with alginate particles

with immobilized substrate to form structured particle-reactors that allowed in situ production

of an unstable oxygen radical (Figure 1b). The functionality of such aggregates was

demonstrated in vitro by investigating the viability of cancer cells in the presence of these free

radical producing particles.

a) b)

Figure 1. a) SEM image of spray-dried chitosan-TPP microparticles with immobilised

laccase. b) Scheme of agglomerated microcapsules for in situ production of oxygen radical.

[1] O. Kašpar, M. Jakubec, F. Štěpánek, Characterization of spray dried chitosan–TPP microparticles

formed by two- and three-fluid nozzles, Powder Technol., 240 (2013) 31-40.

[2] O. Kašpar, V. Tokárová, G.S. Nyanhongo, G. Gübitz, F. Štěpánek, Effect of cross-linking method

on the activity of spray-dried chitosan microparticles with immobilized laccase, Food Bioprod. Proces,

91 (2013) 525-533.

52. CONTINUUM MODELING OF DENSE AND DILUTE PARTICLE

FLOWS IN HIGH SHEAR GRANULATION

Mohammad Khalilitehrani, Eva María Gómez Fino, Per J. Abrahamsson &

Anders Rasmuson

Department of Chemical Engineering, Chalmers University of Technology, SE-412 96, Göteborg,

Sweden


High shear granulation (HSG) is a common process in pharmaceutical industry. In a typical

HSG equipment there is a coexistence of relatively dilute (solid volume fractions ranging

from 0.3 to 0.5) and dense regions (ranging from a volume fraction of 0.5 to the maximum

packing of the material). A better understanding of the flow conditions of powders and

granulates in large scale HSG equipment is crucial for constructing predictive models. The

staggering amount of particles in the process makes the use of continuum flow models highly

attractive. The traditional models like KTGF with added friction provide an unrealistic stress

field and typically high error. Consequently, a more precise formulation of transport

coefficients is demanded.

This article compares and evaluates different approaches for continuum modelling in HSG

systems covering the full range of solid volume fraction. The study is focused on, and

compared with experimental data for, a MiPro granulator. The dilute regions are modelled

with the standard KTGF model. The dense regions are either modelled using a framework

developed by Jop et al. [1], treating the dense flows with pseudo-plastic rheology; or using

modifications to the transport coefficients describing the solid phase stresses proposed by

Bocquet et al. [2]. The intermediate range of volume fraction which shows a transitional

behavior from dilute to dense is specifically discussed.

Results show significant improvement compared to similar studies in the past. A very good

agreement between simulation and experiments is achieved. It should be noted that the

proposed modelling frameworks are formulated for the full range of volume fractions and

could be applied to various particulate flows. To sum up, this research provides a better

understanding of the multi-regime granular flows, in particular the transitional behavior at

intermediate range of volume fractions.

[1] P. Jop, Y. Forterre, O. Pouliquen, A constitutive law for dense granular flows, Nature, 441 (2006)

727–30, doi:10.1038/nature04801.

[2] L. Bocquet, W. Losert, D. Schalk, T. Lubensky, J. Gollub, Granular shear flow dynamics and

forces: Experiment and continuum theory, Physical Review E, 65 (2001) 011307,

doi:10.1103/PhysRevE.65.011307.

53. FEM STUDY OF DIFFERENT ROLL COMPACTOR SEALING

SYSTEM DESIGN

Alon Mazor, Lucia Perez-Gandarillas, Abderrahim Michrafy & Alain deRyck

Universitè de Toulouse, Mines Albi, CNRS, Centre RAPSODEE, Campus Jarlad,

F-81013 Albi cedex 9, France


Roll compaction is a continuous process for densifing powder by passing between two

counter-rotating rollers, which applies mechanical pressure on the powder. The friction

between the feed material and roller surface pushes the powder to a narrow gap, where the

powder is subjected to high stresses leading to the formation of compacted ribbons.

Understanding the roll compaction process is essential in optimizing manufacturing

efficiency and product quality. The ribbons produced in the roll compaction process are then

milled to produce granules. Different size distribution and strength of the ribbon, i.e., the

density distribution, have a direct affect on the milled granules properties. This gives the

motivation for a better understanding and predicting the density distribution of the ribbons, in

order to improve the roller compaction process effectiveness and quality of granules.

Different studies showed that, due to the friction between the powder and the side sealing

plates, a higher density is obtained in the middle of the ribbon’s width compared to the edges.

Most roll compactors have a stationary side seal plates while some compactors integrate the

side seals together with the roll, i.e., rim-roll. Integrating the seals with the roll has an effect

of the stress distribution, thus affecting the density distribution of the ribbon.

In this paper, 3D finite element method (FEM) modelling is used to predict the ribbon

density distribution in roll compaction of microcrystalline cellulose using different sealing

systems. The analysis is conducted assuming the powder as a single-phase porous media. The

Drucker-Prager cap model with density dependency is calibrated and used to represent the

powder behaviour [1]. Depending on the seal system design, FEM results show the

compacted material flow between rolls and the roll pressure distribution, which affects the

resulting density distribution in the ribbon. As expected, different density distribution across

the ribbon’s width can distinguish between the two cases of side plates and rim-roll. The

results are compared with experimental work for validation the predictive quality of the FEM

modelling.

Roll compaction FEM model with rim-roll (seals integrated with rolls)

[1] V. Bonnefoy, P. Doremus, Guidelines for modeling cold compaction behaviour of various

powders, Powder Metallurgy 47 (2004) 285–290 (N°3).

Acknowledgements: This work was supported by the IPROCOM Marie Curie initial training network, funded through the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013/ under REA grants agreement No. 316555.

54. ON THE ROLE OF POROSITY FOR THE COMPRESSIBILITY

AND TABLET TENSILE STRENGTH OF GRANULES

PREPARED BY DRY AND WET GRANUALTION

Josefina Nordström & Göran Alderborn

Department of Pharmacy, Uppsala University Box 580, SE-751 23 Uppsala, Sweden


Granulation of powders is usually required to increase the manufacturability of the

particles when producing solid dosage forms. Granules are often created by adding a liquid

binder into the powder bed. Dry granulation techniques have however emerged as interesting

approaches partly because of the applicability in a continuous manufacturing process.

The aim of this study was to investigate the role of porosity on the compression behaviour

and tablet tensile strength for granules prepared by dry granulation (DG) with varying

structure in terms of porosity. Microcrystalline cellulose (MCC) was used as a typical

pharmaceutical excipient and a comparison was made with the effect of granule porosity on

the compression behaviour and tablet tensile strength of wet processed granules (WG) of the

same composition.

Both wet and dry granulated powders showed lower compactibility than the ungranulated

starting MCC powder up to a critical point of granule porosity. At this point, the granulated

powders showed similar compactibility as the MCC powder. It was concluded that high

porosity granules nearly collapsed completely into primary particles during compression and

the micro-structure and tensile strength of the formed tablets resembled that of tablets formed

from the original ungranulated powder. However, with reduced porosity the compactibility of

the granules decreased (Fig. b) as well as the maximal degree of compression (Fig. a). It is

proposed that for both DG and WG granules, their compressibility over the main part of the

porosity range was controlled by granule deformation. In this range, the DG granules showed

higher compactibility than the WG granules.

Maximal straining of the powder bed (Cmax) (a) and tablet tensile strength (b) as a function

of granule porosity for granules prepared from wet and dry granulation (MCC_WG and

MCC_DG respectively).

a) b)

55. EFFECTS OF WATER QUANTITY ON TABLETS PROPERTIES

MADE BY HIGH SHEAR GRANULATION WITH L-HPC

Andreas Sauer1, Miyuki Fukasawa2 & Naosuke Maruyama3

1 SE-PFMD, Rheingaustrasse 190-196, 65203 Wiesbaden, Germany

2 Shin Etsu Chemical Co., Ltd, Cellulose Technical Support Center, Yokohama, Japan

3 Shin Etsu Chemicals Co., Specialty Research Center, Niigata, Japan


L-HPC is a low substituted hydroxypropylcellulose developed by Shin-Etsu that can be

used as disintegrant and binder in solid dosage forms formulations. L-HPC is a non-ionic

excipient. Thus it is less reactive to active ingredients compared with ionic excipients [1].

The wet granulation is commonly used for improving the flow and compactibility of

tableting masses. During the process, the water capability of the excipients is important in

order to control the robustness of the formulation.

L-HPC, compared to standard formulation with MCC and super disintegrant, gives a buffer

effect stabilizing the wet massing process for a wide range of water content [1]. All over the 9

different L-HPC grades, LH-21 and NBD 020 are recommended for high shear granulation

process. In this study, we will in a first step evaluate the effect of the added water quantity to

the granules and tablet properties at high shear granulation process with formulations based

on L-HPC and NBD. In a second step compare both formulation with regard to tablet

hardness and disintegration. The model drug used is Ethenzamide (hydrophobic API) with

high dosage amount. Following parameters were checked related to water amount:

-Appropriate water quantity

-Average particle D50

-Bulk density (loose and taped), Carr Index

-Tablet hardness and disintegration

[1] Shin-Etsu brochure L-HPC, 2011.9/400

56. NEW INSIGHTS IN SCALE UP OF SPHERONIZATION

PROCESS

Dennis Thaete, Elena Reitz & Markus Thommes

Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University,

Universitaetsstraße 1, 40225 Duesseldorf, Germany,


Spheronization is widely used to produce spherical agglomerates with high density and

narrow size distribution (Figure 1). The aim of this study was to investigate the pellet

formation kinetics considering two different scales of 120 mm and 300 mm friction plate.

A powder mixture of 20 % microcrystalline cellulose and 80 % α-lactose monohydrate was

extruded (Leistritz Mikro 27 GL-28D, Germany) using an adequate amount of deionized

water. Spheronization was executed either in a Caleva Model 120 (Caleva, United Kingdom)

or in a Schlueter RM300 (Schlueter, Germany) using cross-hatched friction plates. The filling

degree was fitted to the diameter of the plates. The particle shape (aspect ratio) and size

(equivalent diameter) were determined via image analysis (CamsizerXT, Retsch, Germany),

where at least 300 particles were characterized.

The scale up in spheronization is commonly done according to Newton et al. [1]. Thereby

the peripheral speed is kept constant when using different friction plate diameters. According

to this, different loads and rotation speeds were tested and the particle shape and size were

measured with respect to time.

The equivalent diameter and the aspect ratio decreased in a similar manner in both

spheronizers (Figure 2). However the larger spheronizer (Schlueter RM300) led to lower

values of size and shape after the same time. This is related to a different flow regime: due to

the lower amount of particles in the Caleva less weight force to the particles on the friction

plate occured. That leads to less interaction of these particles with the friction plate and

accordingly to a slower pellet formation. This study showed that the peripheral speed is not

the only parameter to keep in mind regarding the scale up of a spheronization process.

[1] J.M. Newton, S.R. Chapman, R.C. Rowe, The assessment of the scale-up performance of the

extrusion/spheronisation process, International Journal of Pharmaceutics, 120 (1995) 95-99.

Figure 1. Changes in pellet size and shape during spheronization

Figure 2. Median equivalent diameter and median aspect ratio calculated for mean load and

mean rotation speed

57. MICROSCOPIC MEASUREMENT OF LAYER THICKNESS OF

COATED PELLETS

Mario Scharmer1, Stefanie Bartsch1, Jürgen Kodura1, Dimitri Wiegel2,

Bertram Wolf2 & Ingo Schellenberg1

1 Center of Life Sciences, Institute of Bioanalytical Sciences Anhalt University of Applied Science,

Strenzfelder Allee 28, 06406 Bernburg, Germany

2 Department of Applied Biosciences and Process Engineering, Anhalt University of Applied

Sciences, Strenzfelder Allee 28, 06406 Bernburg, Germany


There are various methods for measuring the particle size of pellets, e.g. sieve analysis,

light scattering and diffraction methods and calculation based on the true density of the

components. But there is a lack of direct measurement of the thickness of coating layers. For

the implementation of a microscopical method pellets of microcrystalline cellulose were

coated in a laboratory fluidized bed coater GPCG 1.1 (Glatt Ingenieurtechnik GmbH,

Weimar, Germany) by using a model drug substance and a polymer. The coated pellets were

embedded in light- curing resin and sanded with the grinding machine Smart Lam 2.0

(Heraeus Kulzer GmbH, Wehrheim, Germany) to a thin section. The radii of the cores and the

coated pellets were measured with a transmitted- light microscope AxioPlan Imaging 2 (Carl

Zeiss Microscopy GmbH, Jena, Germany) with three different tools (circle- point, circle-

radius and straightedge tool) and evaluated using the software bundle AxioVision. The

difference between the radius of the core and the radius of the coated pellet is the coating

layer thickness.

Pellet size of more than 1000 µm was too large for the microscopic image section.

Therefore the panorama function of the software was used. To improve low depth focus an

extended depth focus based on a z- stack was calculated for each sample. These data and the

microscopic data ware compared statisticallys All measuring tools show a linear correlation

with the calculated layer thickness. The circle- point- measuring tool is easy to handle, in

good correlation to the calculated coating thickness and also independent of subjective

influence of the operator. The described microscopic method is a useful tool for the

calibration of inline measurement systems like NIR (Near-infrared) or HIS (Hyper Spectral

Imaging).

Microphotograph of coated pellets, polarization microscope with panorama function, lens

10x/0.3

58. FLUIDIZED BED MELT GRANULATION: GROWTH REGIME

PREDICTION

M. Villa, I. Cotabarren, D. Bertín, J. Piña & V. Bucalá

Department of Chemical Engineering, PLAPIQUI, Universidad Nacional del Sur, CONICET.

Camino La Carrindanga Km. 7, (8000), Bahía Blanca, Argentina.


Among the processes that handle particulate systems, granulation is a widely used unit

operation that allows producing granules with well-defined particle size distributions and

shapes for many industries (e.g., pharmaceutical, agrochemical, detergent, food, etc).

Granulation processes are usually classified according to the binder nature as wet, dry or melt.

Nowadays, melt granulation has gained interest for many applications since it is an attractive

strategy over wet granulation for materials incompatible with water.

Depending on granules requirements, either agglomeration or coating may be preferred.

Even though the amount of articles related to wet granulation processes is vast (e.g., Smith

and Nienow [1], Pont et al. [2] and Hemati et al. [3], among others, studied the influence of

process variables and seeds/binders physicochemical properties on the particles growth

kinetics when aqueous solutions were sprayed in beds of solids fluidized by hot air), the

theories developed for wet granulation are not fully appropriate in describing fluidized bed

melt granulation (FBMG). Consequently, many authors have been focused on revealing the

influence of some of the most important experimental variables on the product quality. To

name a few, Abberger et al. [4], Seo et al. [5], Boerefijn and Hounslow [6] and Tan et al. [7]

studied the effects of binder spray rate and droplet size, seeds size, bed temperature,

atomization air pressure and fluidization air velocity on the performance of FBMG. Mainly,

the studies comprised in situ or top spray-on melt granulation based on model systems

(polyethylene glycol or Poloxamer as binder and glass ballotini or lactose as seeds). In

addition, all these processes involved seeds of very small size, similar to or even smaller than

the sprayed binder droplets. Therefore, the particles preferentially grew by agglomeration,

being insignificant the growth by pure coating. Even though the conclusions of these studies

provide valuable insights into the melt granulation field, they cannot be applied

straightforward to the production of relative big granules via coating. Regarding the

production of this type of granules by FBMG, Cotabarren et al. [8] and Veliz et al. [9], [10]

explored the effect of the operating variables on the process performance and particle

properties for urea granulation, identifying the operating regions that led to pure coating or

combined growth by agglomeration and coating. Based on experimental data, (which are

representative of relatively big seeds particles with respect to droplets size, high binder/seeds

mass ratios, bottom spray configuration, and binder and seeds of the same chemical nature), in

this work the transition of growth regimes was studied. A parameter adapted from the

Akkermans theory [11] allowed to predict the growth mechanisms satisfactorily. This

parameter involves the most relevant process variables: binder flowrate, fluidization air

velocity, bed temperature, atomization air flowrate and seeds sizes.

[1] P.G. Smith, A.W. Nienow, Particle Growth Mechanisms in Fluidised Bed Granulation - I,

Chemical Engineering Science, 38 (1983) 1223–1231.

[2] V. Pont, K. Saleh, D. Steinmetz, M. Hemati, Influence of the physicochemical properties on the

growth of solid particles by granulation in fluidized bed, Powder Technology, 120 (2001) 97–104.


[3] M. Hemati, R. Cherif, K. Saleh, V. Pont, Fluidized bed coating and granulation: influence of

process-related variables and physicochemical properties on the growth kinetics, Powder Technology,

130 (2003) 18–34.

[4] T. Abberger, A. Seo, T. Schaefer, The effect of droplet size and powder particle size on the

mechanisms of nucleation and growth in fluid bed melt agglomeration., International Journal of

Pharmaceutics, 249 (2002) 185–197.

[5] A. Seo, P. Holm, T. Schæfer, Effects of droplet size and type of binder on the agglomerate growth

mechanisms by melt agglomeration in a fluidised bed., European Journal of Pharmaceutical Sciences,

16 (2002) 95–105.

[6] R. Boerefijn, M.J. Hounslow, Studies of fluid bed granulation in an industrial R&D context,


[7] H.S. Tan, A.D. Salman, M.J. Hounslow, Kinetics of fluidised bed melt granulation I: The effect of

process variables, Chemical Engineering Science, 61 (2006) 1585–1601.

[8] I.M. Cotabarren, D. Bertín, S. Veliz, L. Mirazú, J. Piña, V. Bucalá, Production of Granular Urea as

Nitrogenous Fertilizer, in: C.M. Muñoz, A.M. Fernández (Eds.), Urea: Synthesis, Properties and Uses,

NOVA Publishers, (2012) 1–63.

[9] S. Veliz, L. Mirazú, J. Piña, M. Pedernera, V. Bucalá, Efecto del Caudal de Aire de Fluidización

sobre la Calidad de Urea Granulada Obtenida en un Granulador de Lecho Fluidizado Escala Piloto, in:

VI Congreso Argentino de Ingeniería Química, Mar del Plata, Argentina, (2010).

[10] S.V. Moraga, M.P. Villa, D.E. Bertín, I.M. Cotabarren, J. Piña, M. Pedernera, et al., Fluidized-

bed melt granulation: The effect of operating variables on process performance and granules

properties, Chemical Engineering Science, Submitted (2014).

[11] J. H. Akkermans, M. F. Edwards, A. T. Groot, C. P. Montanus, R. W. Pomeren and K. A.

Yuregir, Production of detergent granulates, (1998) WO 1998058048 A1.

59. ROLL COMPACTION AS AN ALTERNATIVE TO SPRAY-

DRYING FOR THE PROCESSING OF Α-LACTOSE

MONOHYDRATE IN DIRECT COMPRESSION APPLICATIONS

Deeb Abu-Fara1, Iyad Rashid2, khouloud Alkhamis3, Mohammed Shubair4,

Mahmoud Al-Omari2, Adnan Badwan2

1 Chemical Engineering Department, University of Jordan, Jordan


3 Faculty of Pharmacy, Jordan University of Science and Technology, Jordan

4 Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy and Medical

Sciences, Petra University, Amman, Jordan

Processing of α-lactose monohydrate into a directly compressible excipient has been dealt

with a diverging approach in the current work from conventional techniques. Although labor,

cost, and time intensive, spray-drying has long been the only industrial effective way of α-

lactose monohydrate processing. This work exploits, for the first time, the application of roll

compaction technique as an alternative to spray drying. After crystallographic characterization

of the granules, roll compaction was found to convert lactose into a different crystallographic

nature rendering the granules a plastically deforming character suitable for use in direct

compression pharmaceutical applications. The resulted powder and tabletting properties were

superior in powder flow and compactibility respectively. Heckel analysis and force

displacement curves emphasized the plastically deforming nature of the granules. Therefore, it

can be right to suggest that roll compaction would represent a good replacement methodology

to spray-drying.

60. COMPUTATIONAL FLUID DYNAMIC SIMULATION OF A

PERFORATED ROTATING BUCKET: AN INDUSTRIAL CASE

STUDY

Samuel Verdier1, Erwan Jarry1, Peter Olley2 & Nejat Rahmanian2

1 CESI Saint-Nazaire (Engineering School), 1 Bd de l’université 44600, Saint-Nazaire, France

2 School of Engineering and Informatics, University of Bradford, Bradford, West Yorkshire,

BD7 1DP, UK


The prilling process is a finishing process to produce almost uniform size of prills where a

massive quantity of products is required. The application of this process is mainly in fertiliser

industry for production of urea and ammonium nitrate. This process takes place in a prilling

tower with height and diameter of 30-70 m and 10-20 m, respectively, depending on the

capacity of the plant. The molten urea is sprayed inside the prilling tower by a perforated

bucket located at the top of the tower. The large quantities of perforated holes along the

bucket wall allow the molten solution to exit from the bucket with a high velocity and form a

jet of solution. The jets break to droplets of almost uniform size while scattering inside the

tower. By the gravity effect, these droplets fall down freely though the tower against a

counter-current cooling air causing them to solidify into prills as they eventually reach the

bottom of the prilling tower. During prilling, the quality of the final urea product can be

affected by several operational parameters. The most important ones are the temperature,

pressure and moisture inside the tower in addition to the velocity field caused by the bucket’s

rotation. [1]

In our previous work [1], we modelled a perforated rotating bucket with a single orifice in

a lab scale using CFD. The main objective of this work is to simulate an industrial bucket

used in urea plant with capacity of 1500 MTPD. It is aimed to investigate the influences of

several design parameters of the bucket on the productivity of the prilling process.

[1] A. Muhammad, N. Rahmanian, R. Pendyala, Analysis of fluid flow of urea in a perforated rotating

bucket: single orifice case, Journal of Applied Sciences, 14 (2014) 1252-1258.

61. ESTIMATION OF DESIGN SPACE FOR AN EXTRUSION-

SPHERONIZATION PROCESS USING RESPONSE SURFACE

METHODOLOGY AND ARTIFICIAL NEURAL NETWORK

MODELING

Tamás Sovány1, Zsófia Tislér1, Katalin Kristó1, András Kelemen2,

& Géza Regdon jr. 1

1 Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, H-6720, Szeged,

Hungary

2 Department of Computer Sciences, University of Szeged, Boldogasszony sgt 6., H-6725, Szeged,

Hungary


Determination of a reliable Design Space (DS) for the production process is the key issue

of the Quality by Design concept which has increasing importance in the pharmaceutical

industry. Nevertheless, the reduction the development time and cost necessitates the

decreasing of the applied experiment number.

In present study the effect of the applied design of experiments (DOE) layout was studied

on the reliability of the estimation of DS. Since the statistical methods which are generally

used for this purposes uses first or second polynomial functions for the estimation of the

response surface it often provides only a rough approximation of the real relations. In order to

compare the effectiveness of the numerical analysis with higher level nonlinear simulations

the data from the various experimental layouts was used for the teaching of artificial neural

networks (ANNs). It was found that the ANN models are much more useful to estimation of

the slight changes in the tendencies within a wide range of experimental settings and are

capable to estimate the prospective values of the product critical quality attributes. In addition

the effectiveness of a genetic algorithm in the optimization of the network layout in

comparison with a DOE based manual screening was also examined.

General layout of the optimal ANN

62. EXPERIMENTAL INVESTIGATIONS TOWARDS

UNDERSTANDING IMPORTANT PARAMETERS IN WET DRUM

GRANULATION OF BIOMASS

Klein E. Ileleji1, Rose P. Ambrose2, Yi Li1 & Perry H. Doane3

1 Agricultural & Biological Engineering Department, Purdue University, 225 South University Street,

West Lafayette, Indiana 47907, USA

2 Grain Science and Industry, Kansas State University, 312 Shellenberger Hall, Manhattan, KS 66505

3 ADM Research, 1001 N. Brush College, Decatur, IL 62521


Biofeestocks such as corn coproducts or biomass such as corn stover are typically

densified in a dry process using pellet mills to enhance transportability and use as livestock

feed. Our work presents data of an experimental study using a non-traditional means,

granulation with a lab-scale rotary drum agglomerator to determine key parameters that affect

granule properties produced from corn stover and two liquid coproducts from corn

bioprocessing, corn steep liquor (CSL) and corn molasses (CM) that are condensed fermented

corn extractives from wet-milling ethanol plant. Our goals were to maximize liquid

coproducts in granules while producing given uniformly sized granules for ruminant feed

application. Our investigation presents a first attempt to produce granular products from very

difficult to handle biomass particulate materials and will attempt to take the study from the art

to developing the fundamentals of granulating biomass particulates. We anticipate that

developing the science of granulating biofeedstocks such as biomass will open opportunities

for using granulation as a means of producing products of enhance value and end-use

performance from biomass.

Granules of corn stover and corn steep liquor blend.

63. PRODUCTION OF SELF-EMULSIFYING GRANULES BY HIGH

SHEAR GRANULATION PROCESS

Erica Franceschinis1, Andrea C. Santomaso2, Laura Benda1, Beatrice Perissutti3,

Dario Voinovich3 & Nicola Realdon1

1 PharmaTeG –Pharmaceutical Technology Group- Dept. of Pharmaceutical and Pharmacological

Science, University of Padua, via Marzolo 5, 35131 Padova, Italy

2 APTLab - Advanced Particle Technology Laboratory, Dept. of Industrial Engineering, University of

Padova, via Marzolo 9, 35131 Padova, Italy

3 Dept. of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste,

Italy


The absorption of class II molecules can be greatly improved by formulating them in self-

emulsifying drug delivery systems (SEDDS) [1] that are mixtures of drug, oils, surfactants

and/or co-solvents which form fine oil-in-water emulsions upon dilution [2]. The drawbacks

of liquid SEEDS can be avoided producing solid-SEDDS by high shear granulation (HSWG)

using a microemulsion as granulating liquid [3]. The purpose of this study was to compare the

effects of impeller speed and massing time on the granule properties when water or an oil-in-

water microemulsion were used as granulating liquids. The experiments were planned using

an factorial design consisting of 12 experiments. In order to evaluate also their effect on the

drug release, simvastatin (SV) was selected as model drug and included in the granulating

liquid. The microemulsion formulation was selected on the basis of SV solubility study and

taking into account the viscosity and the modal droplet size. The results showed that the

particle size distributions of the granules obtained with microemulsion were broader then that

with water. The morphological analysis have showed that while an increase in massing time

produced an increase in roundness (ΦR), the impeller speed did not affected the shape.

Moreover the microemulsion-based granules resulted in larger value of ΦR. In conclusion,

data showed that the granulation process are greatly influenced by the type of binder. In

particular, when water is used as binder the final characteristics of the granules are influenced

by all the experimental variables studied, instead when microemulsion is used as granulating

liquid the system was relatively insensitive to impeller speed and could only be moderately

modified through the massing time..

[1] R.G. Strickley, Currently Marked Oral Lipid-based dosage forms: drug products and excipients. In:

Oral lipid-based formulations enhancing the bioavailability of poorly water-soluble drugs, Ed. Hauss

D.J. (2007).

[2] R.N. Gursoy, S. Benita, Self-emulsifying drug delivery systems (SEDDS) for improved oral

delivery of lipophilic drugs, Biomedicine &. Pharmacotherapy 58 (2004) 173 - 182.

[3] E. Franceschinis, C. Bortoletto, B. Perissutti, M. Dal Zotto, D. Voinovich, N. Realdon, Self-

emulsifying pellets in a lab-scale high shear mixer: Formulation and production design, Powder

Technology 207 (2011) 113-118.

64. CHARACTERIZATION OF INDOMETHACIN

MICROPARTICLES FOR INHALATORY ADMINISTRATION

Nazareth E. Ceschan, Loreana C. Gallo, Verónica Bucalá & María V. Ramírez-

Rigo

Planta Piloto de Ingeniería Química (PLAPIQUI), CONICET- Universidad Nacional del Sur (UNS),

Camino La Carrindanga Km 7 (8000) Bahía Blanca, Argentina


Indomethacin (IN) is a non-steroidal antiinflammatory drug, which is an interesting

candidate for being administered by an alternative route due to its gastrolesive and oral

bioavailability problems[1]. An inhalatory drug delivery system containing IN could be useful

for both local and systemic treatments of rheumatoid arthritis and its pulmonary

complications. Microparticles based on an IN and polylysine (PL, a biocompatible cationic

polymer) were obtained by spray drying (SD) with adequate yields for a lab scale

equipment[2]. The aim of this work is to characterize the particulate product in order to

determine its applicability for pulmonary drug targeting.

The SD operating conditions were selected based on a previous work[3]: air inlet

temperature (co-current flow): 140 °C, drying air flow rate: 35 m3/h, liquid feed flow rate: 6

mL/min and atomization air flow rate: 601 L/h. Several formulations, varying the relative

composition IN/polymer and the total solid content of the feed solutions, were tested. Product

properties (crystallinity, density, morphology and particle size distribution by laser diffraction

(LD) and using a next generation impactor) and the IN- PL ionic interaction (assessed by FT-

infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD) and thermal analysis) were

studied.

The ionic interaction between the IN and PL was proved by FT-IR. The powder was

amorphous and this state was found to be stable for nine months of storage.The SD particles

were rounded, smooth and exhibited some holes. Particular attention was focused on the

particle size distribution to evaluate the feasibility of employing the powder for pulmonary

deposition. The aerodynamic diameter distribution obtained with the next generation impactor

showed that the powders presented a high respirable fraction, being then adequate for the

inhalatory administration of IN. By comparing this data with the information obtained by LD

technique, it was found that LD can be used to preliminary evaluate the aerodynamic

diameters and then to assess the particles deposition pattern.

[1] M. El-Badry, G. Fetih, M. Fathy, Improvement of solubility and dissolution rate of indomethacin

by solid dispersions in Gelucire 50/13 and PEG4000, Saudi Pharmaceutical Journal : SPJ : the Official

Publication of the Saudi Pharmaceutical Society, 17 (2009) 217–25.

[2] N.E. Ceschan, V. Bucalá, M.V. Ramirez Rigo, Influence of the feed composition on the production

of polylysine-indomethacin microparticles by spray-drying, TYBF82. III Reunión Internacional de

Ciencias Farmacéuticas, Sept. 18-19th 2014, Córdoba, Argentine.

[3] N.E. Ceschan, V. Bucalá, M.V. Ramírez-Rigo, New alginic acid-atenolol microparticles for

inhalatory drug targeting., Materials Science & Engineering. C, Materials for Biological Applications,

41 (2014) 255–66.

65. INFLUENCE OF SPRAY DRYING PARAMETERS ON

INTERNAL STRUCTURE AND MECHANICAL PROPERTIES OF

GRANULES

Susanna Eckhard & Manfred Fries

Fraunhofer Institute for Ceramic Technologies and Systems IKTS, Winterbergstr. 28, 01277 Dresden,

Germany


Spray dried granules have to show defined properties depending on their future

applications: If they will be used as catalyst carriers, high fracture strengths and low fracture

deformation values are desired. For other applications like die pressing, lower fracture

strengths and higher granule ductility are expected. Therewith the mechanical properties of

spray dried granules are decisive granule characteristics.

Fracture strength and fracture deformation of spray dried granules can be tailored by the

use of defined additives within the suspension previous to spray drying or by the modification

of the internal granule structures. As the used additive type and combination are often fixed

because of economic or patents reasons, a desired change of mechanical granule properties

can only be achieved by the modification of the internal granule structure. The internal

structure can be changed by variation of suspension properties like solid content, particle size

or particle surface charge. Furthermore a variation of resulting internal structures can be

achieved via modification of the spray drying conditions.

Within this study the effect of the variation of spray drying parameters like inlet

temperature, nozzle gas mass flow, dryer scale as well as operation mode of the dryer (co-

current vs. fountain spray system) on the resulting internal structures is investigated. For

identical aqueous alumina suspensions clear effects of these changed drying parameters on the

internal structure were found and visualized using SEM images of internal cross sections. To

validate the detectable differences a structure quantification was done using image analysis.

The determined structure changes were associated with measured differences of

mechanical properties. A clear impact of changed spray drying parameters on resulting

internal structures and therewith mechanical properties was found.

Effect of changed nozzle gas mass flow on resulting internal structures and mechanical

properties of spray dried granules.

Low nozzle gas mass flow High shell thickness Low micro porosity

(denser packed particles)

High nozzle gas mass flow Lower shell thickness Higher micro porosity

(looser packed particles)

0

5

10

15

20

0 20 40 60

Fo

rce F

[m

N]

Deformation D [%]

High nozzle gas mass flow

Low nozzle gas mass flow

Break

Break

66. THE COMPRESSION BEHAVIOR OF BINARY AND TERNARY

EXCIPIENT BLENDS OF DIFFERENT MECHANICAL

PROPERTIES

Faysal Al-akayleh1, Iyad Rashid2, Mahmoud Al-Omari2, Mohammed shubair1,

Adnan Badwan2

1 Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy and Medical

Sciences, Petra University, Amman, Jordan

2 The Jordanian Pharmaceutical Manufacturing Company, Naor 11710, Jordan

The complexity of processing of pharmaceutical blends of different mechanical properties

has been elucidated by investigating the compression behavior of binary and ternary excipient

mixtures and their resulted tablet properties. In this regard, much of the attention has been

given to test the extent of powders’ plasticity, elasticity and brittleness as the main mechanical

properties of powders. The attribution of each of the aforementioned components has been

analyzed in single, binary, and ternary excipient mixtures. Micocrystalline cellulose (MCC),

starch, and magnesium (Mg) silicate were the three excipients subjected to compression

analysis. Force displacement curves and Heckel/Kawakita analysis were used as the

methodological approaches. Results indicate that binary mixtures containing MCC powder

represent plastic flow and have a ductile characteristic; thus, producing a strong and coherent

compact. On the other hand, binary mixtures containing starch and Mg silicate show that

starch powder’s intrinsic properties are slightly ductile. However, upon unloading, the force-

displacement curves show a large amount of stored elastic strain, or high elastic recovery,

hence more energy is dissipated, and consequently it is difficult for the binary mixtures to be

formed into a strong and coherent compact. Amongst all types of binary mixtures, MCC-

starch binary mixtures provide the most highly plastically deforming with superiority in

compacts’ strength; MCC-Mg silicate mixtures provide the lowest in elastic recovery with

moderately high compacts tensile strength values, and starch-Mg silicate compacts provide

superiority in disintegration. Finally, ternary mixtures of MCC, starch and Mg silicate

perform better than the binary mixtures of MCC/Starch, MCC/Mg silicate, and Starch/Mg

silicate with respect to compression and tabletting properties.

67. HIGH SHEAR GRANULATION PROCESS USING

CRYSTALLINE SUGARS

Erica Franceschinis1, Chiara Pialorsi1, Andrea C. Santomaso2, Federico Zorzi3,

Gabriella Salviulo3 & Nicola Realdon1

1 PharmaTeG –Pharmaceutical Technology Group- Dept. of Pharmaceutical and Pharmacological

Science, University of Padua, via Marzolo 5, 35131 Padova, Italy

2 APTLab - Advanced Particle Technology Laboratory, Dept. of Industrial Engineering, University of

Padova, via Marzolo 9, 35131 Padova, Italy

3 Dept. of Geosciences, University of Padova, via, 35131 Padova, Italy


Sugars can be used in granulation process with different purposes; in particular, they can

act as diluents, binders but also as taste masking agents, sweeteners and agents for drug

controlled release (e.g. sugar beads). Sugars are soluble and sticky excipients [1,2] and their

manipulation in high shear granulators may be very difficult because they can adhere to the

mixer walls or lead to an uncontrolled granule growth. The purpose of this research was to

evaluate the different behavior in high shear wet granulation of four selected sugars: mannitol,

sorbitol, xylitol and sucrose in the size range of 60-300 µm. In order to investigate the

mechanism of their agglomeration the four sugars were initially characterized by flowability

(shear cell tests) and viscosity measurements and their solid state was studied by X-ray

diffraction. Also the hygroscopicity was evaluated by conditioning powders at different

relative humidity (RH 65 and 80%). Results highlighted that the humidity uptake did not

produce any change in the solid state of the sugars but caused a reduction in flowability that

was stronger in the case of sorbitol and xylitol. Powder flowability showed good correlation

to hygroscopicity but it was not related to the final powder thickening of dissolved sugars. In

order to predict the optimal amount of water required for the high shear granulation, mixtures

composed of 25% (w/w) of microcrystalline cellulose and 75% (w/w) of sugar were analyzed

with a mixer torque rheometer [3]. Granulation experiments demonstrated not only the

feasibility of the process with the selected sugars but also the possibility to predict the amount

of water necessary to the process through the mixer torque rheometer. Data also showed the

effect of higher thickening power on the reduction of the water required for the granulation.

[1] B. Adhikari, T. Howes, B.R. Bhandari, V. Truong Stickiness in food: a review of mechanisms and

test methods, International Journal of food properties, 4 (2001) 1-33.

[2] P. Boonyai, B. Bhandari, T. Howes, Stickiness measurement techniques for food powders: a

review Powder Technology 145 (2004) 34-46.

[3] A. Faure, End-point control and scale-up in pharmaceutical mixer-granulators, PhD Thesis

University of Bradford (1998).


68. FLUIDIZED-BED MELT GRANULATION: POPULATION

BALANCE MODELLING TO IDENTIFY THE AGGREGATION

KERNEL

M. Villa, D. Bertín, I. Cotabarren, J. Piña & V. Bucalá

Department of Chemical Engineering, PLAPIQUI, Universidad Nacional del Sur, CONICET

Camino La Carrindanga Km. 7, (8000), Bahía Blanca, Argentina


Within the operations that handle solids, granulation is considered as one of the most

important processes. It allows producing granules with well-defined particle size distributions

and shapes for many industries such as the pharmaceutical, agrochemical, detergent, food, etc.

[1,2]. Granulation processes are usually classified according to the binder nature as: wet, dry

or melt. Nowadays, research in melt granulation has gained interest for many applications.

Particularly for materials incompatible with water; the melt granulation avoids the use of

solvents and the disadvantages associated with their recovery and final disposal, and

minimizes the energy cost related to solvent evaporation [3,4]. Among the melt granulation

technologies, the fluidized-bed melt granulation is widely used. The final granules size

distributions strongly depend on the operating conditions, the seeds size and binder properties.

Modelling would allow improving the performance of the granulation process. However, the

equation (population balance) that describes the particle size transformation as the granulation

proceeds is quite complex involving kinetic parameters to describe the growth and breakage

mechanisms and nucleation or elutriation phenomena.

Cotabarren et al. [2] and Veliz et al. [5,6] explored the effect of the operating variables on

the process performance and particle properties for urea melt granulation carried out in a

batch fluidized bed, identifying the operating growth regions that led to pure coating or

combined growth by agglomeration and coating. Based on experimental data, (which are

representative of relatively big seeds particles with respect to droplets size, high binder/seeds

mass ratios, bottom spray configuration, and binder and seeds of the same chemical nature), in

this work the kinetic parameters related to pure coating and combined mechanisms of coating

and aggregation are established. As suggested by several authors [7-9], the aggregation kernel

can be represented by two factors: one depending exclusively on the particle size (φ) and the

other on the process operating conditions (β0). Two different formulations are proposed: 1) φ

is considered independent of particle size (i.e., φ = 1) and 2) φ is represented by the EKE

model [10]. For both cases, the kinetic parameter β0 is adjusted for each experiment. Finally,

a fitted mathematical expression for β0 as a function of the binder flowrate, fluidization air

velocity, bed temperature, atomization air flowrate and initial particle sizes, which allows

predicting the experimental particles size distribution, is presented.

[1] D. Bertín, I.M. Cotabarren, J. Piña, V. Bucalá, Granule size distribution for a multi-chamber

fluidized-bed melt granulator: Modeling and validation using process measurement data, Chemical

Engineering Science. 104 (2013) 319-329.

[2] I.M. Cotabarren, D. Bertín, S. Veliz, L. Mirazú, J. Piña, V. Bucalá, Production of Granular Urea as

Nitrogenous Fertilizer, in: C.M. Muñoz, A.M. Fernández (Eds.), Urea: Synthesis, Properties and Uses,

NOVA Publishers, (2012) 1–63.


http://yadda.icm.edu.pl/yadda/element/bwmeta1.element.elsevier-2d4f28f1-35b5-35c4-9f3d-685348c25d92

http://yadda.icm.edu.pl/yadda/element/bwmeta1.element.elsevier-2d4f28f1-35b5-35c4-9f3d-685348c25d92


mechanisms of nucleation and growth in fluid bed melt agglomeration., International Journal of

Pharmaceutics. 249 (2002) 185–197.


mechanisms of nucleation and growth in fluid bed melt agglomeration, International Journal of

Pharmaceutics. 249 (2002) 185–197.

[5] S. Veliz, L. Mirazú, J. Piña, M. Pedernera, V. Bucalá, Efecto del Caudal de Aire de Fluidización

sobre la Calidad de Urea Granulada Obtenida en un Granulador de Lecho Fluidizado Escala Piloto, in:

VI Congreso Argentino de Ingeniería Química, Mar del Plata, Argentina,( 2010).

[6] S. Veliz, M.P. Villa, D.E. Bertín, I.M. Cotabarren, J. Piña, M. Pedernera, et al., Fluidized-bed melt

granulation: The effect of operating variables on process performance and granules properties,

Chemical Engineering Science, Submitted (2014).

[7] M. Catak, K. Cronin, D. Medina-Tellez, Markov Chain Modeling of Fluidized Bed Granulation

Incorporating Simultaneous Aggregation and Breakage, Ind. Eng. Chem. Res. 50 (2011) 10811-10823.

[8] M.J.V. Goldschmidt, Hydrodynamic Modelling of Fluidised Bed Spray Granulation, PhD Thesis,

Twente University, Enschede, The Netherlands, (2001).

[9] K.V.S. Sastry, Similarity Size Distribution of Agglomerates During Their Growth by Coalescence

in Granulation or Green Pelletization, Int. J. Miner. Process., 2 (1975) 187-203.

[10] M.J. Hounslow, The Population Balance as a Toll for Understanding Particle Rate Processes,

KONA, (1998) 179-193.

69. THE IMPORTANCE OF MIXING VESSEL CONFIGURATIONS

ON THE DISPERSION OF FOOD POWDERS IN WATER

W. Robert Mitchell1, 2, Laurent Forny3, Tim O. Althaus4, Gerhard Niederreiter2,

Stefan Palzer1, 5, Michael J. Hounslow1 & Agba D. Salman1

1 University of Sheffield, Department of Chemical and Biological Engineering, S1 3JD Sheffield, UK

2 Nestlé Product Technology Center, CH-1350 Orbe, Switzerland

3 Nestlé Research & Development, 618802 Singapore

4 Nestlé Product Technology Center, PO Box 204, YO91 1XY York, UK

5 Nestlé Corporate Headquarters, CH-1800 Vevey, Switzerland


The dispersion of powders in a stirred vessel is a common unit operation in the food

industry. However due to the complex properties of food materials, difficulties related to

reconstitution of these powders often arise; e.g. powders might float at the surface or form

lumps that are difficult to disperse [1]. As mixing operations can be energetically costly, a

better understanding of the influence of agitation conditions on dispersion behavior may help

optimize process conditions. However in much of the relevant scientific literature, mixing

configurations are left either unspecified or too vague. For example the impeller type, the

impeller off-bottom clearance, impeller diameter-to-tank diameter/height ratio, number and/or

size of baffles, and feeding conditions (e.g. height/position of feeding and mass flow rate of

addition) may be unspecified, making it difficult to understand how mixing affects dispersion.

Moreover, in many cases the measurement technique itself has important consequences on

the flow behavior or particle dispersion. For instance, in some studies, aliquots of sample are

taken from the mixing rig at regular intervals for or samples are continuously taken from the

mixing vessel using and hose/pump system for analysis. This is troubling as the sampling of

the liquid can introduce additional stresses on the particles. In addition to the above-

mentioned ex situ measurement techniques, there also exist in situ measurement techniques,

such as the use of a turbidity/conductivity probe or ultrasonic device, which are often

positioned in the medium by introduction via the liquid free surface. However such an

approach will baffle the liquid flow, introducing unintended complications to the flow.

In the current study, particle population and size distribution measurements are taken using

a Focused Beam Reflectance Measurement (FBRM) probe, placed into the medium from the

side, such that it does not baffle the liquid flow. A video camera is also placed to record the

liquid surface. The custom-built vessel used adheres to the standard dimensions defined by

Rushton et al. [2] and contains removable baffles to compare baffled and unbaffled conditions

at equivalent power draw. Feeding is controlled using a vibratory feeder from a fixed

height/position. In the current talk, we discuss the importance of the mixing vessel

configurations: impeller type (Lightnin A100 vs. R100), baffling, feed rate, as well as scale-

up considerations, using a geometrically similar tank, both at equal power draw and tip speed.

[1] W.R. Mitchell, L. Forny, T.O. Althaus, G. Niederreiter, S. Palzer, M.J. Hounslow, A.D. Salman,

Mapping the rate-limiting regimes of food powder reconstitution in a standard mixing vessel, Powder

Technology, (2014).

[2] J. Rushton, E. Costich, H. Everett, Power characteristics of mixing impellers, Chemical

Engineering Progress, 46 (1950) 395-476.

70. ANALYSIS OF A TWIN-SCREW GRANULATION PROCESS

USING A COMBINED EXPERIMENTAL AND

COMPUTATIONAL APPROACH

Ashish Kumar1,2, Jurgen Vercruysse3, Krist V. Gernaey 4, Thomas De Beer 2,* &

Ingmar Nopens1

1 BIOMATH, Dept. of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience

Engineering, Ghent University, Belgium

2 Laboratory of Pharmaceutical Process Analytical Technology, Dept. of Pharmaceutical Analysis,

Faculty of Pharmaceutical Sciences, Ghent University, Belgium

3 Laboratory of Pharmaceutical Technology, Dept. of Pharmaceutics, Faculty of Pharmaceutical

Sciences, Ghent University, Ghent, Belgium


Denmark, Denmark

E-mail: [email protected], *Shared last authorship

Continuous processing in steady state, smaller equipment footprint and less tedious scale-

up is a potential alternative for the currently applied batch wise methods in secondary

pharmaceutical manufacturing. Consequently, twin-screw granulation has recently emerged as

a popular continuous wet granulation technique. This granulation method depends on several

process variables. However, available studies have primarily focused on the effect of these

variables on granule properties at the outlet of the twin-screw granulator due to the opacity of

the multiphase system. Thus, little is in fact known about how these variables affect the

evolution and kinetics of granule formation and the resulting granule structure. This work is

the combination of theoretical development and experimental validation of a population

balance modelling framework for twin-screw granulation. For the first time, a Population

Balance Model (PBM) has been developed to model twin-screw granulation which accounts

for the granulator design and the process parameters such as number and location of kneading

discs, along with the effect of the number of axial compartments. The rate processes which

are considered dominant in a twin-screw, i.e. aggregation and breakage, were included. The

work demonstrated that a good agreement between experimental and simulated results can be

achieved for the evolution of particle size distributions in a twin-screw granulator. The

modelling framework presented in this paper forms the basis of the kinetic analysis of

granulation experiments that may lead to the development of a modelling tool and

combination with micro-level models such as Discrete Element Models (DEM) in a hybrid

framework. Such a framework can be used both to simulate and predict twin-screw

granulation.

Agreement between experimental and simulated granule size distribution results in a twin-

screw granulator

71. FINITE VOLUME APPROXIMATIONS OF BREAKAGE

POPULATION BALANCE EQUATION

Jitraj Saha1, Jitendra Kumar1, Andreas Bück2 & Evangelos Tsotsas2

1 Department of Mathematics, Indian Institute of Technology Kharagpur, Kharagpur-721302, India

2 Chair of Thermal Process Engineering, Institute for Process Engineering, Otto-von-Guericke

University, Magdeburg-39106, Germany


Breakage is one of the most important particulate processes in which particles break into

smaller fragments. Since the particles are undergoing certain physical changes due to the

breakage process, it is of high interest to predict and track these changes over process time.

Macroscopically, breakage population balance equations (PBEs) can be used in order to

estimate the particle number density and also various integral quantities (moments) of the

particles undergoing breakage process, e.g. mean particle size and volume or surface area.

In this work, a comparative study of two newly developed numerical methods

approximating the pure multiple breakage PBEs based on the finite volume scheme has

conducted. For a numerical scheme it is a very essential criterion to keep the total mass of the

system constant, i.e. to avoid a loss in total mass in calculation of the distribution of the

fragments. When approximating the pure multiple breakage PBEs by quadrature rules, it is

found that the total mass of particles before and after the breakage does not remain constant.

So, suitable adjustments are made in the discrete formulation such that it obeys the mass

conserving law.

This idea has led to the development of a new mass conserving finite volume

approximation of the pure multiple breakage PBEs. In some applications, besides conserving

the total mass of the system, the estimation of the zeroth moment is of great importance. To

ensure the mass conserving numerical scheme to predict the zeroth moment as good as the

exact result some suitable adjustments are made in the numerical scheme which lead to the

development of another finite volume approximation of the pure multiple breakage PBEs.

Several test problems are considered in order to assess the accuracy of the two different

schemes.


72. EFFECT OF POLYMERS ON THE STABILITY OF ANHYDROUS

OLANZAPINE DURING PROCESSING

Maria Paisana1, Martin Wahl2, João F. Pinto1

1 iMed – Research Institute for Medicines and Pharmaceutical Sciences, Faculdade de Farmácia,

Universidade de Lisboa, Av. Prof. Gama Pinto, P-1649-003, Lisboa, Portugal

2 Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, D-72076

Tübingen, Germany


APIs are frequently exposed to water in several pharmaceutical processes

(e.g.crystallization, wet granulation) which may induce the production of hydrates. Also,

during certain manufacturing steps (drying, tabletting) the hydrates could dehydrate and

metastable anhydrous or amorphous forms could be obtained. These modifications are likely

to affect the bioavailability of the drug, requiring a particular control over these processes.

The aim of the study was to investigate whether polymeric excipients, such as, polyethylene

glycol, polyvinylpyrrolidone and hydroxypropyl cellulose can influence the hydrate formation

of olanzapine during the manufacture of pellets by extrusion-spheronization. In addition, the

impact of olanzapine hydration on the final mechanical properties of the pellets was also

evaluated.

Extrudates, with the same fractions of olanzapine (15%w/w), excipients, (MCC, 75%w/w

and PEG-6000/PVP-K25/HPC-LF, 10%w/w) and water (75%, based on the dry powder mass)

were manufactured. 50% of the formed mass (#1.1) was extruded immediately whereas the

remaining (#1.2) was left to rest in a hermetic container for 6 hours, prior to extrusion. Pellets

were manufactured from the extrudates in a spheroniser (500 rpm) for 5 minutes. Wet pellets

were dried in a fluid bed drier at 45C (Aeromatic). XRPD and FTIR analyses were

considered to detect and characterize different solid phases of olanzapine in all pellets’

manufacturing steps. Polarized light microscopy and SEM analyses were used to evaluate

changes on the crystal shape and size of olanzapine crystals in the different phases of the

process.

The pellets #1.1 and #1.2 manufactured with PEG-6000 presented significant differences

on loss on drying, strength, density and porosity proprieties. Also changes on the olanzapine

crystal shape were detected by microscopy. One explanation to all these modifications is

related to the hydration of olanzapine into a mixture of 2 different hydrates during the resting

time of the wet mass (dihydrate B and higher hydrate). The drying of the pellets #1.2 for

30/60/120 minutes at 45oC was not enough to remove one of the hydrated forms of olanzapine

(dihydrate B) due to its high stability. Although the resting time of the mass has contributed to

a narrow size distribution of the pellets due to a better distribution of water, the hydrate

conversion of olanzapine during the resting time, together with the physical/mechanical

alterations on the final product (pellets), influenced negatively the dissolution rate of

olanzapine. PVP-K25 and HPC-LF were capable to avoid hydration of the drug and no

significant differences were detected in both mechanical and dissolution proprieties of the

pellets #1.1 and #1.2. This study revealed that both PVP-k25 and HPC-LF were capable of

inhibiting the hydration of olanzapine in the wet extrusion process, therefore preventing

changes that are likely to affect the performance of the drug in the final solid dosage forms.

73. KINETICS OF IMBIBITION OF A COLLOIDAL AGGREGATE

Alban Debacker1,2, Stanislav Makarchuk1, Didier Lootens2 & Pascal Hébraud1

1 IPCMS/CNRS 23 rue du Loess 67034 Strasbourg France

2 SIKA, Tüffenwies 16, CH-8048, Zürich, Switzerland


The imbibition kinetics of a millimeter-sized aggregate of 300 nm diameter colloidal

particles by a wetting pure solvent is studied [1]. Three successive regimes are observed.

First, the imbibition proceeds by compressing the air inside the aggregate. Next, the solvent

stops when the pressure of the compressed air is equal to the excess of capillary pressure at

the meniscus of the wetting solvent in the porous aggregate. The interface is pinned and the

aggregate slowly degases up to the point where the pressure of the entrapped air stops

decreasing and is controlled by the capillary pressure. Finally, the imbibition starts again at a

constant excess of pressure, smaller than the capillary pressure but larger than the one of the

atmosphere. This last stage leads to the complete infiltration of the aggregate.

Image of an aggregate of colloidal silica particles during the imbibition. The outer shell is

wetted by the solvent whereas the inner core is dry.

[1] A. Debacker, S. Makarchuk, D. Lootens and P. Hébraud, Imbibition kinetics of spherical colloidal

aggregates, Physical Review Letters, 113 (2014) 028301.

74. DEVELOPMENT OF REGIME MAP FOR STEADY-STATE

HIGH SHEAR WET TWIN-SCREW GRANULATION

Ashish Kumar1,2, Jens Dhondt2, Jurgen Vercruysse3, Fien De Leersnyder2, Valérie

Vanhoorne3, Krist V. Gernaey 4, Thomas De Beer 2,* & Ingmar Nopens1

1 BIOMATH, Dept. of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience

Engineering, Ghent University, Belgium

2 Laboratory of Pharmaceutical Process Analytical Technology, Dept. of Pharmaceutical Analysis,

Faculty of Pharmaceutical Sciences, Ghent University, Belgium

3 Laboratory of Pharmaceutical Technology, Dept. of Pharmaceutics, Faculty of Pharmaceutical

Sciences, Ghent University, Ghent, Belgium


Denmark, Denmark

E-mail: [email protected], *Shared last authorship

Twin-screw granulation is an emerging continuous granulation technique in the

pharmaceutical industry. The flexibility in process settings such as the applied binder addition

method, screw configuration, screw speed and material throughput allows the manipulation of

size and shape properties of the granules. However, due to the fact that it is a rather new

granulation technique, twin-screw granulation is not as well understood as batch-wise high

shear wet granulation. Most of the twin-screw granulation studies are limited to a certain

design and scale of the twin-screw granulator. In this study, in order to consolidate the

understanding about the granulation process and to comprehend the applicability and limits of

the process variables in a scale independent manner, the regime theory was applied. Scale

dependence of parameters limits the ability of the study towards multiple-scale application. In

this study, α-Lactose monohydrate was granulated with Polyvinylpyrrolidone (2.5%, w/w) as

binder in the granulation liquid, with 1×6 and 2×6 kneading discs at 60° stagger angle in the

screw configuration. The specific mechanical energy, which involves the combination of

screw speed, material throughput and torque required for the rotation of the screws at the used

process conditions, was correlated with the applied liquid-to-solid ratio. The study suggested

that, although increasing liquid-to-solid ratio strongly drives the granule size distribution

towards a large mean granule size, increasing the energy input to the system can be

effectively used to lower the mean granule size and also narrow down the size distribution.

Further experiments are desired in the near future such as evaluating other screw

configurations, the effect of the stagger angle and other formulations with significantly

different raw material properties.

Change in the granule size distribution for different screw configuration when liquid-to solid

ratio and specific mechanical input are changed.

75. COMPARISON OF EXCIPIENT ONLY & DRUG

FORMULATIONS FOR TWIN-SCREW CONTINUOUS

GRANULATOR

Ian P. Gabbott, Adam Khan & Gavin K. Reynolds

Pharmaceutical Development, AstraZeneca, Charter Way, Macclesfield, SK10 2NA


The primary objective of granulation in the pharmaceutical industry is to agglomerate

formulation particles to improve granule physical and flow properties so that subsequent

tablet manufacturing phases can be achieved with better results. Over the past few years

twin-screw granulation has generated increasing industrial interest as an alternative to current

batch granulation methods. Nguyen et al. [1] have shown that wet granulation process

significantly affect tablet properties such as compressibility & strength.

Several studies were carried out using a twin-screw continuous granulator (TSG) in order

to further understand the effects of changing screw speed, screw configuration and feed rate

of powders and water on granule properties such as density and particle size distribution and

compressibility. A unified compaction curve was used to investigate the impact of TSG on

tablet tensile strength.

Furthermore, at present very limited publications which analyse the residual moisture

content and its effect on granule and tablet properties in a continuous granulation process

have been found. This report analyses the influence of TSG process parameters in

combination with the moisture content after drying on granule and tablet properties and

presents a comparison of such properties between excipient only and drug formulations.

[1] T.H. Nguyen, D.A.V. Morton, K.P. Hapgood, Application of the unified compaction curve to link

wet granulation and tablet compaction behaviour, Powder Technology 240 (2013) 103-115.

76. THE APPLICATION OF TERAHERTZ PULSED IMAGING IN

CHARACTERISING DENSITY DISTRIBUTION OF ROLL-

COMPACTED RIBBONS

Chuan-Yu Wu1, Jianyi Zhang1, Chunlei Pei1, Serena Schiano1 & David Heaps2

1 Department of Chemical and Process Engineering, University of Surrey, Guildford, GU27XH, UK

2 Advantest Inc., Princeton, New Jersey, USA


Roll compaction is a commonly used dry granulation process in pharmaceutical, fine

chemical and agrochemical industries for materials sensitive to heat or moisture. The ribbon

density distribution plays an important role in controlling properties of granules (e.g. granule

size distribution, porosity and strength). Accurate characterisation of ribbon density

distribution is critical in process control and quality assurance. The terahertz imaging system

has a great application potential in achieving this as the terahertz radiation has the ability to

penetrate most of the pharmaceutical excipients and the refractive index reflects variations in

density and chemical compositions. The aim of this study is to explore whether terahertz

pulse imaging is a feasible technique for quantifying ribbon density distribution.

A series of ribbons were made of MCC Avicel PH102 using a roll compactor at various

process conditions and the ribbon density variation was investigated using terahertz imaging

and sectioning methods. The density variations obtained from both methods were compared

to explore the reliability and accuracy of the terahertz imaging system. An average refractive

index is calculated from the refractive index values in the frequency range between 0.5 and

1.5 THz (Figure1). It is shown that the refractive index gradually decreases from the middle

of the ribbon towards to the edges. Variations of density distribution across the width of

ribbon are also obtained using both the sectioning method and the terahertz imaging system

(Figure 2). It is found that the terahertz imaging results are an excellent agreement with that

obtained using the section method, demonstrating that terahertz imaging is a feasible and

rapid tool to characterize ribbon density distributions.

Figure 1. A typical contour plot of refractive index distribution

Figure 2. Bulk density distribution along the width of the ribbons

Acknowledgement: This work was partially supported by the IPROCOM Marie Curie initial

training network, funded through the People Programme (Marie Curie Actions) of the

European Union's Seventh Framework Programme FP7/2007-2013/ under REA grant

agreement No. 316555.

77. DE-MIXING CHARACTERISTICS OF FINE COAL IN AN AIR

DENSE MEDIUM FLUIDIZED BED

Pengfei Zhao1, Yuemin Zhao2, Zhenfu Luo2 & Ran Zhu1

1 School of Electric Power Engineering, China University of Mining and Technology, Xuzhou

221116, China

2 School of Chemical Engineering and Technology, China University of Mining and Technology,

Xuzhou 221116, China


Air dense medium fluidized bed (ADMFB) offers a better alternative approach for dry coal

beneficiation. The de-mixing (segregation) characteristics can determine the quality of the

final products significantly.

In this study, the segregation characteristics of fine coal (-3+1 mm) in ADMFB was

compared with those of ordinary fluidized bed. Specifically, the pressure drop, the behaviours

of density-segregation and size-segregation as a function of bed height, the ash separation

degree, the bed snapshots, and the bubble size was determined by varying the superficial gas

velocity. Both density-segregation and size-segregation emerged at a low superficial gas

velocity in ADMFB. However, an increasee of the superficial gas velocity, both segregations

gradually transformed to mixing state. There existed an optimum air velocity to maximize

segregation when the fluidization velocities were between the minimum fluidization velocities

of the flotsam (clean coal) and jetsam (gangue). The comparative ash segregation degree and

pressure drop characteristics confirmed that the bubble-drive flotsam-jetsam mechanism was

responsible for the transition. Furthermore, application dense medium to a fluidized bed could

obtain a higher segregation degree due to reducing the bubble sizes.


78. THE COMBINED EFFECT OF WET GRANULATION PROCESS

PARAMETERS AND GRANULE MOISTURE CONTENT ON

TABLET QUALITY ATTRIBUTES

Ian P. Gabbott, Farhan Alhusban & Gavin K. Reynolds



A pharmaceutical compound was used to study the effect of batch wet granulation process

parameters in combination with the residual moisture content remaining after drying on

granule and tablet quality attributes. The effect of three batch wet granulation process

parameters was evaluated using a multivariate experimental design, with a novel constrained

design space. Batches were characterised for moisture content, granule density, crushing

strength, porosity, disintegration time and dissolution.

Mechanisms of the effect of the process parameters on the granule and tablet quality

attributes are proposed. Water quantity added during granulation showed a significant effect

on granule density and tablet dissolution rate. Mixing time showed a significant effect on

tablet crushing strength, and mixing speed showed a significant effect on the distribution of

tablet crushing strengths obtained. The residual moisture content remaining after granule

drying showed a significant effect on tablet crushing strength. The effect of moisture on

tablet tensile strength has been reported before [1], but not in combination with granulation

parameters and granule properties, and the impact on tablet dissolution was not assessed.

Correlations between the energy input during granulation, the density of granules produced,

and the quality attributes of the final tablets were also identified. Understanding the impact of

the granulation and drying process parameters on granule and tablet properties provides a

basis for process optimisation and scaling.

[1] J.B. Wade, G.P. Martin, D.F. Long; A methodological approach for determining the effect of

moisture content on the compaction properties of powders: Granular hydroxyapatite; Powder

Technology, 246 (2013) 511-519.

79. INFLUENCE OF LIQUID FORMULATION AND IMPACT

CONDITIONS ON THE WETTING OF HYDROPHOBIC

SURFACES BY AQUEOUS POLYMERIC SOLUTIONS

Amal Khoufech, Mohammed Benali, Jérémie Castello & Khashayar Saleh

Laboratoire de Transformations Intégrées de la Matière Renouvelable, EA4279, UTC/Escom,

Compiègne, France


Controlling drop deposition is of great importance for a wide variety of practical

applications such as spray coating, pesticide deposition on plant leaves, inkjet printing, spray

painting, etc. The efficiency of drop deposition from sprays is limited by two phenomena:

splashing and bouncing. These phenomena can lead to an important decrease of the coating

efficiency especially in powder coating processes [1, 2]. However, these limiting factors can

be inhibited by adding small amounts of a flexible polymer into the wetting solution. For

example, in our previous study about the droplet impact on a hydrophobic surface [3], we

showed that droplet rebound and splashing phenomena could be completely suppressed by

adding a certain quantity of a commonly used polymeric binder (CarboxyMethylCellulose

sodium salt) into water. The objective of the present work is to study the droplet impact on a

hydrophobic surface for polymeric binder solutions with different natures and rheological

behaviours in order to investigate the influence of polymer flexibility and molecular weight

on the droplet behaviour. These solutions exhibit higher elasticity and much lower shear

viscosity than Na-CMC aqueous solutions. Impacts of single droplets on horizontal

hydrophobic surfaces were visualized using a high speed camera. The droplet’s size, velocity

and the time evolution of droplet base diameter and thickness were determined by image

analysis. The use of different polymer solutions with varying concentrations showed the role

of viscosity in splashing and rebound inhibition. In addition, increasing the solution

concentration lead to a decrease in the maximum extent of spreading, recoil velocity, as well

as the maximum height of rebound. The effect of droplet inertia was also investigated through

the variation of droplet size and impact velocity. The impact velocity was found to promote

both spreading and receding of droplets. In the case of low viscosity solutions, increasing

droplet inertia lead to droplet rebound or disintegration. Finally, a regime diagram with

different zones (deposition, rebound and splashing) was established based on the collected

data.

[1] S.R.L. Werner, J.R. Jones, A.H.J. Paterson, R.H. Archer, D.L. Pearce, Droplet impact and

spreading: Droplet formulation effects, Chemical Engineering Science, 62 (2007) 2336- 2345.

[2] C.K. Link, E.U. Schlünder, Fluidized bed spray granulation: Investigation of the coating process

on a single sphere, Chemical Engineering and Processing, 36 (1997) 443-457.

[3] A. Khoufech, M. Benali, K. Saleh, Influence of liquid formulation and impact conditions on the

coating of hydrophobic surfaces, Powder technology, Available online 1 July 2014, ISSN 0032-5910,

http://dx.doi.org/10.1016/j.powtec.2014.06.048.

80. A ROBUSTNESS STUDY OF AN EXTENDED-RELEASE

TABLET FORMULATION USING A SAMPLE KIT OF

HYPROMELLOSE FOR QBD CONCEPT

Shilpa Mistry1, Takafumi Hoshino2 & Hiroyasu Kokubo2


Wiesbaden, Germany




When hydrophilic matrix tablets are prepared using Hypromellose (HPMC), the solubility

behavior of HPMC is one of the critical attributes for drug dissolution. Additionally the

solubility behavior is affected by the viscosity, hydroxypropoxy (HPO) content and particles

size of HPMC. In accordance with ICH guideline, implementation of “Quality by Design”

(QbD) principles to formulation development is strongly recommended. It leads to an

understanding of how the properties and performance of the dosage forms are influenced by

the formulation, including the quality attributes of HPMC. In this study, the effects of HPMC

properties on robustness of in vitro drug release were investigated using QbD principles.

Dipyridamole (Solubility in water: 0.0037 g/L) was used as a model API. All ingredients

in the formulation were blended manually and compressed into tablets (11.3 mm-d, flat) by a

single punch tablet tester (Sankyo Pio-Tech, Japan). The dissolution test was conducted

according to USP paddle method. Paddle rotation: 50 rpm. Test fluid: Water (900 mL).

Detection: UV. Testing time: 16 hrs.

Effect of Viscosity: Difference in dissolution profiles between viscosity grades was

observed. However, within the same viscosity grade, the difference was insignificant. Effect

of HPO Content: For the lowest viscosity grade (90SH-100SR), the release rate was

depended on the HPO level. In case of higher viscosity grades, it was not significant. Effect

of Particle Size: Difference was not significant (within 10%) by variation in particle size.

The formulation in this study was indicated to be robust regarding variability of the key

excipient. The sample kit used in this study was found to be useful for Quality-by-Design

projects.

81. EVALUATION OF A NEW CO-PROCESSED EXCIPIENT FOR

ORALLY-DISINTEGRATING TABLETS

S. Mistry1, Y. Hirama2, S. Obara2 & N. Maruyama2


Wiesbaden, Germany




To evaluate compressibility, disintegration, and stability of a newly developed co-

processed compound for orally disintegrating tablets.

The co-processed compound was prepared using D-Mannitol, Low-substituted

Hydroxypropyl Cellulose (L-HPC), and Polyvinyl alcohol by a spray granulation process.

Two grades (QD-50 and QD-100), having different particle size, were prepared by changing

processing condition. Performance of placebo tablets was tested as follows. Compressibility

of the compound was evaluated by direct compression using a rotary tableting machine and a

hardness tester. Disintegration test was carried out according to USP. Variation of tablet

weight, hardness, and disintegration time were also evaluated from periodical sampling from

the same tableting equipment operated for 60 minutes. Stability test was carried out at 40°C

75%RH for sample in open bottle.

The median particle size of QD-50 and QD-100 was 57 μm and 86 μm, respectively. Both

grades showed a good flowability with the angle of repose less than 40° (QD-50: 38°, QD-

100: 37°). It achieved hardness of around 50 - 190 N at the compression force ranging 5-12.5

kN. QD-100 gave slightly higher hardness compared to QD-50 (152 N vs 125 N at the

compression force of 10 kN). Disintegration time was less than 60 seconds for both grades,

with the tablet hardness up to 150 N. QD-50 showed faster disintegration than QD-100 (35

sec vs 50 sec at hardness of 150N). The relative standard deviation of tablet weight, hardness,

and disintegration time of tablets during 1-hour compression time was less than 6%. In the

stability study at 40°C 75% RH for 6 months, the thickness of tablet was not significantly

changed. During this period, change in tablet hardness was 58 N to 65 N for QD-50, and 63 N

to 75 N for QD-100. Change in disintegration was 11 sec to12 sec for QD-50, and 13 sec to

20 sec for QD-100.

The study showed that the present co-processed compound has an excellent capability as

the main excipient for orally disintegration tablets from direct compression.

82. THE INTERDEPENDENCY OF MATERIAL, PROCESS AND

EQUIPMENT PARAMETERS FOR EXTRUSION-

SPHERONISATION FORMULATIONS

John A. Collins1, Ahmad B. Albadarin2, Mark T. Davis2, David Egan3, Ciara S.

Griffin2 & Gavin M. Walker1,2,4

1 Pharmaceutical Manufacturing Technology Centre, PMTC, University of Limerick, Ireland

2 Synthesis and Solid State Pharmaceutical Cluster, SSPC, University of Limerick, Ireland

3 Enterprise Research Centre, ERC, University of Limerick, Ireland

4 School of Chemistry and Chemical Engineering, Queens University Belfast, Belfast BT9 5AG,

Northern Ireland, UK


The current work explores the complex interdependency between process, equipment and

materials, manufacturability and drug product function. There are many important processing

operations that can impact or be impacted by the particulate or extended properties of the API

powder and excipients. Extrusion-spheronization is a process used in the pharmaceutical

sector to produce uniformly sized pellets for encapsulation. It is used for making dense

granules for controlled-release oral solid dosage pellets with very low quantities of excipients.

Such pellets typically exhibit slow release of the API [1], with the rate controlled by

shape/size, porosity, quantity and nature of the binder and the excipients used to assist

processing. Microcrystalline cellulose (MCC) is the most widely used excipient [2] since

wetted MCC powder masses provide mixtures with appropriate rheological properties for

successful extrusion-spheronization. Typically if other excipients are used the rheological

properties are more dependent on the precise amount of binder added, making it more difficult

to process the materials and control final size and shape of the pellets. The reluctance of

MCC-based pellets to disintegrate even in the presence of disintegrating agents deters its use

in pellets when faster release of drugs with poor solubility in aqueous media is desired.

The results report an iterative approach to increasing formulation complexity to determine

the key factors that affect the extrusion-spheronization process and drug release from pellets.

Increasing levels of complexity are explored in terms of formulation components and

processing parameters. A model API, MCC and several other candidate excipients are chosen.

Some process and equipment parameters explored include: (i) mixing (speed, binder volume),

(ii) extrusion: (type - screw and screen), speed, die size/depth), (iii) spheronization: (speed

and time). An initial assessment of the rheology of the product is reported from Mixer Torque

Rheometer measurements by varying the formulation (excipients, API level, water content),

or physically (mixing time & speed). The effects of these parameters will be examined by

morphological characterisation of the uncoated pellets, e.g., SEM (friability, shape and size),

Raman imaging (component distribution), particle size (EyeconTM) and % porosity from

envelope-/true density analysis. Disintegration testing is used as an initial assessment of end

product performance.

[1] F.J. Otero-Espinar, A. Luzardo-Alvarez, J. Blanco-Mendez, Non-MCC materials as extrusion-

spheronisation aids in pellets production, J. Drug Del. Sci. Technol. 20(4) (2010) 303- 318.

[2] A. Dukic-Ott, M. Thommes, J.P. Remon, P. Kleinebudde, C. Vervaet, Production of pellets via

extrusion-spheronisation without the incorporation of microcrystalline cellulose: a critical review, Eur.

J. Pharm. Biopharm. 71 (2009) 38-46.


http://en.wikipedia.org/wiki/Rheology

http://www.youtube.com/watch?v=EcyvKQBYcZQ

http://www.youtube.com/watch?v=EcyvKQBYcZQ

83. THE EFFECTS OF COMPRESSION SPEED, PUNCH SHAPE

AND WALL FRICTION ON THERMOMECHANICAL

BEHAVIOUR OF POWDERS DURING COMPRESSION

Alexander Krok1,2, Marian Peciar2 & Chuan-Yu Wu1

1 Department of Chemical and Process Engineering, University of Surrey, Guildford, GU27XH, UK

2 Department of Chemical and Hydraulic Machines and Equipment, Slovak University of Technology,

Bratislava, 812 31, Slovakia


During powder compaction, the powder is compressed under high pressure, the internal

structure and deformation mechanism change significantly. In addition, heat can be generated

by the friction between particle/particle and particle/walls and irreversible deformation of

particles, which can cause significant temperature rise and degradation of heat sensitive

materials. Therefore, the objective of this study is to perform a systematic study on

thermomechanical behaviour of powders during compaction.

Finite element methods are used to numerically analyse the thermomechanical behaviour

of powders during die compaction with various punch shapes at different compression speeds.

In particular, the temperature evolutions during producing flat-face (FF), shallow convex (SC)

and standard convex (STC) tablets are analysed. Mechanical properties of the powder are

determined from experimental calibration of the Drucker-Prager Cap (DPC) model and

thermal properties published in the literature are used. A coupled thermo-mechanical finite

element analysis is performed using the commercial package ABAQUS/Standard. To model

the transformation of irreversible compaction work to heat, a user defined subroutine

HETVAL is implemented. Friction between the die and the powder is also considered

according to Coulomb's law of friction. From the numerical analysis, temperature

distributions in the FF, SC and STC tablets are obtained. In addition, how the density and the

temperature evolve with time during the compaction process is determined. It is found that the

punch shape, the compression speed and the wall friction have significant impacts on the

thermomechanical behaviour of powders. The temperature of the compressed powder increase

as the compression speed, the friction coefficient or the surface curvature increases.

Temperature and relative density distributions throughout tablet during compression

Acknowledgement: This work was supported by the Marie Curie Intra-European Fellowships

with acronym ThermoPC, funded through the People Programme (Marie Curie Actions) of

the European Union's Seventh FP7 under REA grant agreement No. 622874.


84. EFFECTS OF POLYMER TYPE, PARTICLE SIZE AND

ADDITIVE ON THE MICROMERITIC AND DISSOLUTION

PROPERTIES OF THEOPHYLLINE GRANULES AND TABLETS

E.I Akpabio1, O.N.C. Umeh2, M.O. Emeje3 & S.I. Ofoefule2

1 Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of

Uyo, Nigeria

2 Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka

3 National Institute for Pharmaceutical Research and Development, Abuja, Nigeria

Particle size affects some properties of granulations such as flow behavior and flow

properties, densification and interaction between particles and as they flow from the hopper to

the die cavity of a tablet press. Particle size also affects weight uniformity and content

uniformity of the final tablet or capsule dosage forms. This later effect, impacts on the

ultimate bioavailability of the final dosage form. The presence of hydrophobic polymer as

additive in a matrix tablet could alter the dissolution properties of the tablets. We investigated

the effects of some polymers – semi-synthetic polymers (hydroxypropylmethylcellulose,

HPMC and ethylcellulose, EC), synthetic polymers (carbopol 940), inorganic polymers

(sodium alginate) and natural occurring polymer (guar gum) on the in vitro granule and tablet

properties of theophylline prepared by the wet granulation technique. The effects of three

particle size fractions on the mechanical properties of the tablets and on the dissolution of

theophylline from matrix tablets were also investigated. The effect of cellulose acetate

phthalate (CAP), a hydrophobic polymer on the flow indices and on the dissolution properties

of theophylline hydrate granules and tablets were also assessed as well. CAP was used at

concentration levels of 0.0 to 0.2%w/w. The addition of 0.05 to 0.2%w/w CAP, led to a 50%

reduction in hopper flow rates of theophylline granules containing HPMC, 40% in that

containing Guar gum, 60% in that containing ethylcellulose, 50% in that containing Carbopol

940 and about 25% in that containing Sodium alginate. Other flow indices such as Hausner’s

quotient, Compressibility index and angle of repose were affected to varying degrees as the

concentration of CAP was increased from 0.0 to 0.2%w/w. The hardness of the tablets

decreased as the particle size increased from 0.25 to 1.0mm. Change in particle size had no

significant effect on the abrasive resistance of the tablets. There was retardation in

theophylline release from tablets containing either sodium alginate or ethylcellulose in the

presence of CAP. In tablets containing either HPMC or Guar gum or Carbopol 940, the

presence of CAP had no significant effect on theophylline release. A similar effect was

observed with the different particle size fractions except in tablets containing Guar gum which

showed reduced drug release with particle size of 0.25 mm. Generally, change in the

concentrations of CAP did not produce any significant effect on theophylline release, while

for the particle sizes, it was only in tablets containing Guar gum that significant release

occurred at particle size 0.25 mm. Results of the study showed that sustained release of

theophylline could be achieved using HPMC, Guar gum, sodium alginate, ethylcellulose and

Carbopol 940. The presence of CAP resulted in the modification of theophylline release from

sodium alginate and ethylcellulose but had no significant effect on its release from HPMC,

Guar gum, ethylcellulose and Carbopol 940. Particle sizes in the range of 0.25 to 1.0 did not

produce significant effect on theophylline release except from tablets containing sodium

alginate.

85. MICRO-STRUCTURE OF MALTODEXTRIN AGGLOMERATES

PRODUCED IN FLUIDIZED BED

Reihaneh Pashminehazar, Abdolreza Kharaghani & Evangelos Tsotsas

Thermal Process Engineering, Otto von Guericke University Magdeburg, Universitätsplatz 2,

Magdeburg, 39106, Germany


Though spray fluidized bed agglomeration is a widespread process in the food,

pharmaceutical and chemical industry, the structure of the respective agglomerates had hardly

been investigated until recently. The first systematic results were published by Dadkhah et al.

(2012). However, only hard primary particles (glass, ceramic) have been used in this work.

In the present study, experimental investigations are conducted on maltodextrin

agglomerates as amorphous polar (water soluble) powder with a low glass transition

temperature. The agglomerates are produced in top spray fluidized beds under varying

operating conditions by spraying pure water without additional binder. The physical

properties of the agglomerates are evaluated in terms of agglomerate size, particle size

distribution and sphericity.

Moreover, by X-ray µ-computed tomography (µ-CT) a morphological evaluation of the

three dimensional micro-structure of soft agglomerates made of maltodextrin particles is

conducted, in order to find the relation between process parameters of the fluidized bed and

the properties of real products. By performing different sequences of image processing

operations on volume images of the agglomerates and developing additional codes, the

following morphological descriptors are investigated: porosity, shape factor, fractal dimension

and primary particle separation (see picture). Based on the results, maltodextrin agglomerates

have a very irregular shape with high porosity. Changes in the production process parameters

affect the morphological properties and size of the agglomerates.

a: 3D view of agglomerate, b: Separated primary particles of agglomerate, c: Redrawing by

Matlab

a b c

86. INVESTIGATING THE EXTRUSION-SPHERONISATION OF

PHARMACEUTICAL PASTES

Matthew P. Bryan, Sarah L. Rough & D. Ian Wilson

Department of Chemical Engineering and Biotechnology, New Museums Site, Pembroke Street,

Cambridge, CB2 3RA, UK

Extrusion-spheronisation of stiff pastes is widely used in the pharmaceutical industry to

manufacture dense, highly spherical pellets for subsequent tablet pressing and/or capsule

filling. Powders are mixed with a liquid binder to generate a paste which can be readily

extruded into long cylinders, usually of diameter 1-2 mm. These are then fed into a

spheroniser, which consists of a rotating friction plate; here, the extrudates are broken down

into smaller lengths and rounded to form near-spherical pellets.

The mechanisms behind the spheronisation stage are not completely understood and

empirical testing is commonly used to identify suitable paste formulations and processing

parameters in order to scale up laboratory results to pilot plant and production scale. The

extrusion and spheronisation steps are linked by the rheology of the paste, which is complex,

particularly when excipients such as microcrystalline cellulose (MCC) readily absorb water to

form a soft solid matrix.

In this study, we investigated the effects of the paste mixing technique and spheronisation

conditions upon the pellet size and shape characteristics. A series of 45 wt% MCC water-

based pastes were prepared in two types of mixer at different shear strain rates. The mixers

were (i) a planetary mixer, where shear rate was controlled by adjusting the mixer speed, and

(ii) a screw extruder, where the shear rate could be manipulated by adjusting the auger speed

and the auger-die plate clearance. The rheology of each of the pastes was quantified by the

Benbow-Bridgwater characterisation method for ram extrusion. The rheological parameters

showed a systematic dependency on mixer shear strain rate. This result can explain some of

the differences in extrusion-spheronisation observed between lab-scale testing and pilot-scale

work featuring single and twin-screw extruders.

87. REDUCTION OF ENERGY CONSUMPTION IN FLUIDIZED

BED GRANULATION PROCESSES

Lisa Mielke1, Torsten Hoffmann1, Mirko Peglow2, Markus Henneberg3, Andreas

Bück1 & Evangelos Tsotsas1

1 Thermal Process Engineering/NaWiTec, Otto-von-Guericke University Magdeburg,

Universitätsplatz 2, Magdeburg, D-39106, Germany

2 IPT Pergande GmbH, Wilfried-Pergande-Platz 1, Weißandt-Gölzau, D-06369, Germany

3 AVA – Anhaltinische Verfahrens- und Anlagentechnik GmbH, Mittagsstraße 16P, Magdeburg, D-

39124, Germany


Nowadays demands for product quality and energy efficiency are increasing due to

ongoing industrial development and rising costs of resources. In case of fluidized bed spray

granulation processing the profitability mainly depends on the total energy input required for

fluidization, evaporation of the sprayed liquid and drying, with balance of product quality and

process efficiency. Therefore investigations of the process require detailed consideration of

fluidized bed granulation as a particle growth and drying process on one hand and on the

other hand an overall investigation of total energetic and economic performance of the

process.

Next to heat recovery measures one path of energy reduction is further process

intensification. This paper is focused on temporal separation of process steps like growth and

liquid evaporation as one way of intensification of batch processing. In order to optimize both

sub-processes, granulation and particle drying, are operated alternating by switching the

spraying rate and other process parameters.

For determining of the internal usage of energy a dynamic model containing coupled

population, energy and mass balances has been developed to describe the fluidized bed.

Furthermore all additional parts of the plant, e.g. fans and heat exchangers, are included.

In order to obtain the required data, experimental and model based investigations for

different parameter configurations are performed. The analysis of results is carried out in

comparison to a benchmark case, for batch operation this comparison is based either on equal

process time or product quality. The evaluation delivers product and process specific

characteristic numbers as well as energy and mass flow charts. The results show significant

advantages in temporal separation in batch processes with respect to energy consumption

while conserving product quality.

88. DROP IMPACT BEHAVIOUR ON ALTERNATELY

HYDROPHOBIC AND HYDROPHILIC LAYERED BEAD PACKS

Shaun Atherton1, Christopher A. E. Hamlett1, Neil J. Shirtcliffe2, Glen McHale3,

Sujung Ahn4, Stefan H. Doerr4, Robert Bryant4 & Michael I. Newton1

1 School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11

8NS, UK

2 Department of Technology and Bionics, Hochschule Rhein-Waal, Landwehr 4, 47533 Kleve,

Germany

3 Faculty of Engineering and Environment, Northumbria University, Pandon Building, Camden Street,

Newcastle upon Tyne NE1 8ST, UK

4 College of Science, Swansea University, Singleton Park, Swansea SA2 8PP, UK


A high level of water repellency in soils has an impact on soil hydrology, plant growth and

soil erosion. Studies have been performed previously on man-made bead packs; consisting of

close packed layers of μm sized glass beads, to mimic the behaviour of rain water on water

repellent soils. In this study measurements were performed on multi-layered bead packs, with

different combinations of hydrophobic and hydrophilic layers. High speed video recording

was used to record the impacts of water droplets onto the bead packs, recording the impact

event, spreading and the subsequent rebound behaviour of the droplet. Using the video

recordings observations were made of the liquid marble effect on the droplet and how it

differs depending on the hydrophobicity/hydrophilicity of the initial contact with the bead

pack. By varying the impact speed a relationship between impact speed and the degree to

which the droplet forms a liquid marble was observed, with higher impact speeds leading to a

greater degree of liquid marbling. Measurements were also made to find the transition speeds

between the three rebound conditions; rebound, pinning and fragmentation.

Video frames showing 1.17ms-1 water drop impact on hydrophobic bead pack. Droplet forms

liquid marble.

89. STOCHASTIC MODELING OF LAYERING GROWTH

PROCESSES IN FLUIDIZED BEDS

Christian Rieck, Andreas Bück & Evangelos Tsotsas

NaWiTec, Thermal Process Engineering, Otto-von-Guericke-University, Universitätsplatz 2, 39106

Magdeburg, Germany


Layering growth processes in fluidized beds are applied in many industries, e.g. the

pharmaceutical and food industry, to produce free-flowing and dust free particles. In fluidized

bed layering, a liquid containing solid material is sprayed onto particles. The liquid part

evaporates and the remaining solid builds a layer around the core particle. This layer can be

used to protect an active ingredient (odor or taste masking) or it can contain the active

substance itself.

In this contribution it is presented, how a stochastic modeling approach based on a Monte

Carlo method can be used to model a layering growth process by describing micro-scale

processes. In case of layering growth in a fluidized bed, the considered micro-processes are

droplet deposition on a particle, droplet drying and solidification. In the simulation, droplets

are deposited randomly on the particles. After the drying time of a deposited droplet has

passed, it is considered to be dry. Then, its remaining solid volume is added to the particle

volume. Those micro-processes are executed sequentially in the simulation until a given

process time is reached. The presented method allows multiple droplet deposition (a wet

droplet can be deposited on a solidified droplet) and accounts for the increase of the particle

surface area due to growth in the droplet deposition algorithm. First results show a good

agreement of the particle size distribution obtained from the model with experimental data.

Additionally, other properties, e.g. the layer thickness distribution and coating coverage can

be predicted with this model.

Comparison of normalized number density functions obtained by experiments and the

presented Monte Carlo method.

0 0.2 0.4 0.6 0.8 1.0 1.2 1.40

1

2

3

4

5

6

7

diameter (mm)

no

rmal

ized

nu

mb

er d

ensi

ty f

un

ctio

n (

1/m

m)

q

0(t=0) (Exp.)

q0(t=t

end) (Exp.)

q0(t=0) (MC)

q0(t=t

end) (MC)

90. IMPACT OF SCREW CONFIGURATION ON THE PARTICLE

SIZE DISTRIBUTION OF GRANULES PRODUCED BY TWIN

SCREW GRANULATION

J. Vercruysse1, A. Burggraeve2, M. Fonteyne3, P. Cappuyns4, U. Delaet5, I. Van

Assche5, T. De Beer3, J.P. Remon1 & C. Vervaet1

1 Department of Pharmaceutics, Laboratory of Pharmaceutical Technology, Ghent University,

Ottergemsesteenweg 460, 9000 Ghent, Belgium

2 Department of Analytical Development, Johnson&Johnson Pharmaceutical Research and

Development, Janssen Pharmaceutica, Turnhoutseweg 30, 2340 Beerse

3 Department of Pharmaceutical Analysis, Laboratory of Pharmaceutical Process Analytical

Technology, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium

4 Global Technical Services, Janssen Supply Chain, Janssen Pharmaceutica, Turnhoutseweg 30, 2340

Beerse

5 Department of Pharmaceutical Development, Johnson&Johnson Pharmaceutical Research and

Development, Janssen Pharmaceutica, Turnhoutseweg 30, 2340 Beerse


Twin screw granulation (TSG) has been reported by different research groups as an

attractive technology for continuous wet granulation. However, in contrast to fluidized bed

granulation, granules produced via this technique typically have a wide and multimodal

particle size distribution (PSD), resulting in suboptimal flow properties. The aim of the

current study was to evaluate the impact of granulator screw configuration on the PSD of

granules produced by TSG.

Experiments were performed using a 25-mm co-rotating twin screw granulator, being part

of the ConsiGmaTM-25 system (a fully continuous from-powder-to-tablet manufacturing line

from GEA Pharma Systems). Besides the screw elements conventionally used for TSG

(conveying and kneading elements), alternative designs of screw elements (tooth-mixing-

elements (TME), screw mixing elements (SME) and cutters) were investigated using an α-

lactose monohydrate formulation granulated with distilled water.

Granulation with only conveying elements resulted in wide and multimodal PSD. Using

kneading elements, the width of the PSD could be partially narrowed and the liquid

distribution was more homogeneous. However, still a significant fraction of oversized

agglomerates was obtained. Implementing additional kneading elements or cutters in the final

section of the screw configuration was not beneficial. Furthermore, granulation with only

TME or SME had limited impact on the width of the PSD. Promising results were obtained by

combining kneading elements with SME, as for these configurations the PSD was narrower

and shifted to the size fractions suitable for tableting.


91. CFD SIMULATION OF PARTICLE RESIDENCE TIME

DISTRIBUTION IN MULTISTAGE FLUIDIZED BEDS

Kaicheng Chen1, Lisa Mielke1, Andreas Bück1, Michael Jacob2 & Evangelos

Tsotsas1

1 Thermal Process Engineering, Otto-von-Guericke-University, Magdeburg

Universitätsplatz 2, Magdeburg, D-39106, Germany

2 Glatt Ingenieurtechnik GmbH, Nordstrasse 12, Weimar, D-99427, Germany


Multistage fluidized beds are widely used in all fields of solid processing, e.g. chemical,

pharmaceutical and food industry. The particle residence time distribution has a great

influence on the product quality, e.g. in drying or coating process. For materials which are

sensitive to the process duration, a spread in residence time is highly undesirable; for instance,

over-drying will lead to a scorched product. Therefore, the residence time correlates directly

with the product quality. In the multistage horizontal fluidized bed, the particle residence time

can be better controlled by specifying the internal structure, e.g. number or position of baffles.

Therefore, this work focuses on the internal structure of multistage fluidized beds.

The fluid dynamic characteristics in the fluidized bed are very essential for the apparatus

design and operation. CFD simulation can improve the understanding of the current design of

fluidized bed systems and provide information and guidance for the design of new improved

multistage fluidized bed.

In this work, Euler-Euler (two-fluid) method was used to study the hydrodynamics of gas-

solid flow in an existing pilot scale horizontal fluidized bed (Glatt Ingenieurtechnik GmbH).

The particle residence time distribution was investigated by using two-dimensional simulation

because of the influence of the fluidized bed's width is not as significant as the length and the

height in such a rectangular, narrow horizontal fluidized bed. The validity of the CFD

simulation was established by comparison with plant-scale experimental data. The influence

of the internal structure (e.g. the internal baffles, outlet weir height, underflow & overflow) on

the particle residence time distribution of this horizontal fluidized bed was then investigated.

Example of solid distribution in a continuous fluidized bed

(three internal baffles, steady-state)

50 100 150 200 250 300

50

100

150

200

250

300

92. POPULATION BALANCE MODELING OF SPRAY

GRANULATION

IN HORIZONTAL FLUIDIZED BEDS

Katja Meyer, Reihaneh Pashminehazar, Andreas Bück & Evangelos Tsotsas

Chair of Thermal Process Engineering, Otto-von-Guericke University, Universitätsplatz 2,



Particulate processes are of huge importance in many industrial applications and consist in

most cases of multiple apparatuses or functional sections, which are interconnected by

streams of mass, energy or information. One important measure to characterize the product

quality is the particle size distribution (PSD).

This work considers particle formulation by spray granulation in horizontal fluidized beds.

In order to achieve an optimal operating behaviour and to handle disturbances, the dynamics

of the process have to be known. Currently, only very few process models for describing

particle formation process are available in general, mostly in drum granulation and in

crystallization. In this work, a generic multi-compartment, multi-zone population balance

model (PBM) for spray layering granulation in a horizontal fluidized bed was developed.

In fluidized bed spray granulation process particles grow by spraying a solution or

suspension onto them. A horizontal fluidized bed is a sequence of several process chambers

separated by weirs. In each chamber the granulation occurs in different functional zones, i.e.

the spraying zone and drying zone. The interconnection between the zones, chambers and

particle flows is shown in the Figure 1 (left). The multi-zone model considers particle

properties as well as the geometric coordinates. Further features of the presented model

include the arbitrary position of particle recycle, the possibility to include different operating

condition in each chamber as well as diverse transport mechanisms through the apparatus. In

order to quantify the transport and dispersion, particle movement and separation during

traversing of overflow weirs was investigated by particle tracking velocimetry (PTV).

Figure 1. Interconnection of solid streams in a multi-chamber horizontal fluidized bed (left),

analysis of particles traversing an overflow weir by Particle Tracking (right).

y d

irec

tio

n [

pix

el]

93. EXPERIMENTAL INVESTIGATION OF PROCESS STABILITY

OF CONTINUOUS SPRAY FLUIDIZED BED LAYERING

PROCESSES

Martin Schmidt, Christian Rieck, Andreas Bück & Evangelos Tsotsas

NaWiTec, Thermal Process Engineering, Otto-von-Guericke University, Universitätsplatz 2, 39106

Magdeburg, Germany


Spray fluidized bed layering is used to produce free flowing and dust free granules from

solid-containing liquids. In spray fluidized bed layering processes, the liquid is sprayed onto

seed particles, and solidifies as a shell on the particles. Thus, onion shaped granules are

obtained.

In chemical and pharmaceutical industries spray fluidized bed layering is used to produce,

e.g., fertilizer, detergents or coatings for active pharmaceutical ingredients. To generate high

product throughputs, the layering process needs to be conducted in continuous mode. For

constant product output and constant product quality, chosen process parameters need to

ensure a stable process. The product discharge and seed particle input have a huge influence

on the process stability. Particles big enough are discharged from the fluidized bed. Therefore

the product particles can be separated internally, while being discharged through a classifying

tube, or externally, through sieves. Seed particles can be provided internally, e.g. via

overspray from the spray droplets or crushing of oversized particles by a mill, and also by an

external feed of new seed particles. Previous work [1] describes the process behavior for

internal separation and internal seed particle production. This work describes experimentally

the process stability for external separation combined with internal seed particle production.

Simulations regarding process stability are presented elsewhere [2]. For the different

experiments, initial, drying, and fluidizing conditions remain constant and only the power of

the mill, crushing oversized particles, is varied. Different mill power generates different

process behavior due to its influence on the seed particle provision. Thus, e.g., oscillating and

stable particle size distributions of the particles in the fluidized bed are observed throughout

the process.

Temporal evolution of the PSD for a layering process with external product separation and

internal seed particle production

[1] M. Schmidt, A. Bück, E. Tsotsas, Experimental investigation of spray fluidized bed layering with

internal separation, Chemical Engineering Science (under review).

[2] S. Heinrich, M. Peglow, M. Ihlow, M. Henneberg, L. Mörl, Analysis of the start-up process in

continuous fluidized bed spray granulation by population balance modeling, Chemical Engineering

Science, 57 (2002) 4369-4390

94. ELIMINATING BI-MODAL PSD’S IN A CONTINUOUS TWIN

SCREW WET GRANULATION PROCESS

Jim Holman1 & Tessa Van Hoek2

1 Process Development Group, GEA Pharma Systems Ltd, School Lane, Eastleigh, Hampshire, SO53

4DG, UK

2 Process Development Centre, GEA Pharma System nv, Keerbaan 70, Wommelgem, 2160, Belgium


Many products manufactured using continuous Twin Screw Granulation (TSG) exhibit a

"bi-modal" size distribution where the primary granules manufacture undergo subsequent

secondary agglomeration to form large clusters. This leads to the need to mill the oversized

particles prior to compression, which can cause issues for fragile formulations or products

with a functional binder (i.e. taste masking).

Using the ConsiGma Continuous Tableting line this study uses a different TSG barrel

configuration to eliminate the bi-modal distribution and generate a uni-modal size distribution

suitable for further processing without the need for a dry milling stage. Using different

designs of the screw elements enable a tighter control of the size distribution exiting the

granulator resulting in a product suitable for compression.

Figure 2. Example Size Distribution comparison of granules made with the standard

configuration and the new proposed configuration.

95. MANUFACTURING AND MECHANICAL TESTING OF

BRIQUETTES FROM INERTINITE-RICH HIGH ASH COAL

FINES USING VARIOUS BINDERS

Nthabiseng T. Modiri1, John R. Bunt1, 2, Hein W.J.P. Neomagus1 & Frans B.

Waanders1

1 School of Chemical and Minerals Engineering, North-West University, Potchefstroom Campus,

Private Bag X6001, Potchefstroom 2520, South Africa

2 Sasol Technology (PTY) Ltd., Box 1, Sasolburg, 1947, South Africa


South Africa produced an average of 36 million tonnes of coal fines in 2012 alone, and in

2003 it was estimated that fine discard coal had already consumed 4000 hectares of land,

which poses enormous economic and environmental implications. One technique for utilizing

fine coal is through agglomeration for use in technologies that require lump coal.

Agglomeration of vitrinite-rich coal, having been studied extensively, is well understood with

a high success rate in binderless briquetting; producing mechanically strong and waterproof

briquettes. Binderless briquetting of inertinite-rich, high ash coal has been unsuccessful,

producing briquettes that are not water resistant or as mechanically strong as the vitrinite-rich

briquettes. Fine coal briquetting, while making use of a suitable binder, enhances

agglomeration and therefore reduces the briquetting pressing temperatures and pressures,

paving the way for producing affordable and durable products to be utilized in industrial

applications.

Inertinite rich, high ash coal was used during this study and the binders investigated were

clays (attapulgite and bentonite), bio char, cow dung, lignosulphonate, kraft lignosulphonate,

paraffin, wax as well as 2 South African coal tar pitches. The method of investigation entailed

pre-screening the binders using the Lloyd LRX Plus press, adding 0 to 10 % of each binder

and conducting compression strength tests, drop tests as well as water submersion tests where

cured and uncured briquettes were compared to each other. It was found that the uncured

briquettes (with binders) and the binderless briquette yielded similar compressive strengths,

averaging c.a. 1 MPa. The briquettes were cured at 100 ˚C for 3 hours, and the binders which

yielded the best mechanical strength were the lignosulphonate and resin with compressive

strengths of 15.5 and 11.7 MPa respectively at a 7.5 wt % binder concentration. The

binderless, cured briquette only had an average compressive strength of 5 MPa. Cured and

uncured, the briquettes (with and without binder addition) all retained their shape and size

during drop tests and none of the briquettes proved to be water resistant; hence paraffin was

introduced as a waterproofing agent after pressing and curing. After coating the briquettes

with paraffin, they were submerged in water for 2 hours and weighed. It was found that the

more water resistant and mechanically strong briquettes were manufactured from using either

lignosulphonate or resin as binders, with subsequent coating with paraffin after curing to

enhance water resistance.

96. EFFECT OF HIGH-SHEAR WET GRANULATION PROCESS

SCALE-UP ON THE DISSOLUTION KINETICS OF HIGH-

ACTIVE PHARMACEUTICAL GRANULES

David Smrčka1, Jiří Dohnal2 & František Štěpánek1

1 Institute of Chemical Technology Prague, Department of Chemical Engineering, Technicka 3, 166

28 Prague 6, Czech Repblic

2 Zentiva, k.s., U Kabelovny 130, Prague 10, Czech Republic


The scale-up of a granulation unit is considered rather difficult due to many contributing

and often competing factors. For geometrically similar equipment, simple scale-up rules could

be attempted. Due to geometrical similarity of equipment along the size scale, typically some

quantity or dimensionless group is maintained constant (Froude number, Swept Volume or

Tip Speed). Since the granulation process is described as a multi-scale operation, macroscopic

properties (e.g. bulk density or particle size distribution) must be considered with same care

as microscopic (e.g. porosity). In pharmaceutical industry both macro and micro scale

properties are important for the following processing and meeting the final product

requirements, e.g. dissolution. In spite of their wide and varied use in the chemical process

industries, there is little published literature on the scale-up of batch granulators, especially

with a view of the conservation (or not) of microscale properties.

The aim of this work is to study the scale-up of wet pharmaceutical granulation in high

shear mixer using a formulation where the major part consists of the active component. For

these purposes geometrically similar high shear mixer apparatus equipped by granulation

vessels with volume of 0.5, 2, 4, 25 and 50 l were available. Employing low volume vessels

(0.5, 2, 4 l), a study mapping the parametric space was carried out. In the first approach the

Froude number calculated from earlier pilot experiment in a 50 l vessel was used for setting

agitation rate in low volume vessels and in addition by changing the Froude number,

parametric sensitivity was obtained. Since binder distribution within the granulation batch

could be strongly time-dependent but also some desired steady state could be observed on

granulation time scale, a kinetic study was made for investigating the evolution of granule

attributes and to reveal the prevailing sub-processes (e.g. coalescence, consolidation,

attrition). The macroscopic properties of granulates were described by means of particle size

distribution and bulk density. Froude number has been shown as a useful scale-up parameter.

Success of scale-up was assessed by using standard f-factors (similarity and difference

factors) comparing dissolution profiles between two curves. Despite granulates produced from

different size of equipment provided different bulk densities, particle size distributions and

dissolution profiles were kept similar. Since microscopic properties of particles play a

significant role during dissolution an effort to find relationship between granule structure and

dissolution properties was made and the conservation of granule structure during scale-up was

investigated. For observing 3-D structure and describing granules via evaluated porosity,

computer tomography methods were used.

a) b)

Results for scale-up with maintaining constant Froude number: a) particle size distributions;

b) dissolution profiles

97. DISCRETE ANALYSIS OF PARTICLE COLLISION BEHAVIOR

IN FLUIDIZED BEDS

Thomas Hagemeier, Zhaochen Jiang, Andreas Bück & Evangelos Tsotsas

Thermal Process Engineering, NaWiTec, University of Magdeburg, Universitaetsplatz 2, 39106

Magdeburg, Germany


Fluidized bed spray granulation is a key technique to produce granules with desired

properties, for instance to improve flowability, solubility, storage behavior or the release of

pharmaceutical ingredients. Besides the particle-fluid interaction which affects particle

mixing and drying, particle-particle collisions are decisive for the product quality. However,

the number of particle collisions is an unknown quantity for real-scale apparatuses and only

hard to estimate on laboratory scale [1]. Often, collision models are used to obtain a rough

estimate of the number of particle collisions [2].

This paper describes an approach to study inter-particle collisions based on experimental

investigations using particle tracking velocimetry in a pseudo-2D fluidized bed. The

experiments provide discrete data for particle-particle collisions for different fluidization

conditions. The local collision frequencies show strong dependency on the solid volume

fraction that can be correlated with an existing model [2]. However, major deviation was

observed for solid volume fractions εp < 0.15, as shown in the figure below. Therefore, model

adaptations are required which will be presented in the final contribution for the granulation

workshop.

Additional contact properties, for instance relative particle velocity and impact forces are

available and yield additional information for the granulation process.

Discrete estimate of particle collision frequency as function of solid volume fraction in

comparison with Gidaspow [2] model (red line)

[1] C. You, H. Zhao, Y. Cai, H. Qi, X. Xu, Experimental investigation of interparticle collision rate in

particulate flow, International Journal of Multiphase Flow, 30 (2004) 1121-1138.

[2] D. Gidaspow, Multiphase flow and fluidization, (1994) Academic Press.

0 0.1 0.2 0.3 0.4 0.50

200

400

600

800

Solid volume fraction

Part

icle

colli

sio

n fre

quency [1/s

]

Time-average Collision Frequency

Gidaspow fit

Sub-region9

Sub-region16

Sub-region25

98. MESOSCALE MODEL AND EXPERIMENTAL ANALYSIS OF

COLLOIDS AGGREGATION FOR COATING AND BINDER

FORMULATION

Jarray Ahmed, Gerbaud Vincent & Hémati Mehrdji

Université de Toulouse, INP, ENSIACET, LGC (Laboratoire de Génie Chimique),

4 allée Emile Monso, F-31432 Toulouse Cedex 04, France


In coating and agglomeration processes, the properties of the final product, such as

solubility, size distribution, permeability, and mechanical resistance depend on the process

parameters and the binder solution properties. These properties include the type of solvent

used, the binder composition and the affinity between its constituents. This latter controls also

the stability of the colloidal formulations.

In this study, we investigate the ability of dissipative particle dynamics (DPD) to elucidate

the behaviour of aqueous colloidal formulations that includes film forming polymer

(Hydroxypropyl-methylcellulose, HPMC), a hydrophobic filler (Stearic acid, SA) and a

plasticizer (Polyethylene glycol, PEG). DPD is a coarse-grained molecular dynamics

simulation method where the fluid is described as a set of soft beads interacting according to

the Flory-Huggins model. The DPD simulation results are compared to experimental results

obtained by Cryogenic-SEM and laser diffraction particle size analyzer.

It is shown from the DPD simulation results that the aggregating structure of HPMC-SA

mixture in water is different under different amounts of SA. The aggregate morphologies are

characterized via the structure factor and the polymer end-to-end distance. We also observe

that the HPMC polymer is able to form a gel network that covers SA particles and thus

produces stable colloids. PEG has a good affinity with both HPMC and SA, and diffuses

between HPMC layer and SA microsphere aggregate in water. The structures obtained using

DPD simulations are similar to the experimental observations obtained by Cryogenic-SEM

(see Figure).

a) DPD simulation of HPMC (blue)-SA (grey) mixture in water. b) Cryogenic-SEM image of

sublimated HPMC-SA mixture. HPMC cover SA particles and prevent their aggregation

99. EXPERIMENTAL AND CFD SIMULATION FOR A LAB-SCALE

FLUDIZED BED GRANULATION PROCESS WITH WURSTER

TUBE

Haigang Wang1, Guzhi Qiu1, Jiamin Ye1 & Wuqiang Yang2

1 Institute of Engineering Thermophysics, Chinese Academy of Sciences, PO Box 2706, Beijing,

100190

2 University of Manchester, PO Box 88, Sackville Street, Manchester, M13 9PJ, UK


A lab-scale fluidized bed with Wurster tube was designed and applied to investigate the

particle drying, granulation and coating process based on experimental and CFD simulation.

A combined electrical capacitance tomography (ECT) sensor was used to measure the particle

concentration both inside and outside of the Wurster tube. The CFD simulation is based on

CPFD and two-phases Euler-Euler multiphase fluid model. Key process parameters, including

concentration, pressure, moisture and geometrical parameters of Wurster tube are investigated

and analysis. The optimum operating ranges of the Wurster fluidization process for different

particles are given. CFD simulation results are given and compared with the measurement

results by ECT.

Figure 1. CPFD simulation for the fluidized bed process with Wurster tube

100. DEVELOPMENT OF A CONTROLLED RELEASE

FORMULATION BY CONTINUOUS TWIN SCREW

GRANULATION

Valérie Vanhoorne1, Jurgen Vercruysse1, Fien De Leersnyder2, Thomas De Beer2

Jean-Paul Remon1 & Chris Vervaet1

1 Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, 9000 Ghent,

Belgium

2 Laboratory of Pharmaceutical Process Analytical Technology, Ghent University,

Ottergemsesteenweg 460, 9000 Ghent, Belgium


Continuous twin screw granulation (TSG) has already been validated as an attractive wet

granulation method for the production of immediate release tablets. However, up-to-now, this

innovative technology has not yet been evaluated for the manufacturing of controlled release

formulations.

Metoprolol tartrate (MPT), a highly water soluble drug, was used as model drug in a

concentration of 20% and different types of hydroxypropylmethylcellulose (HPMC) were

used as hydrophilic matrix former (concentration: 10-40%). Lactose and mixtures of

lactose/native maize starch (ratio 70/30, 50/50) were used as fillers. Water or aqueous binder

solutions were used as granulation liquid. The influence of moisture content, filling degree of

the barrel, granulation temperature and screw design on granule and tablet quality were

assessed. Torque during wet granulation, particle size distribution, granule shape and friability

of oven-dried and fluid-bed dried granules and dissolution behaviour of the tablets were

evaluated.

Increasing the HPMC percentage and the number of kneading disks resulted in high torque

values (up to 7 Nm). Using screw configurations adopted from hot melt extrusion, bimodal

particle size distributions were obtained. However, a screw configuration with mixing

elements after the kneading disks reduced and stabilized the torque readings. This

combination also resulted in less oversized and more spherical granules with a monomodal

particle size distribution. Compared to oven drying, fluid bed drying created more fines,

especially when low viscosity HPMC grades were used. When incorporating higher viscosity

grades the fraction of fines did not increase during dynamic drying which was attributed to the

stronger bridges formed during the granulation process.

Increasing the HPMC content in the granules from 10 to 20% reduced the MPT release

rate, no further delay was detected at an HPMC percentage of 40%. The molecular weight and

substitution degree of HPMC did not significantly affect the dissolution behavior. Complete

release of MPT was achieved over 16h, showing that TSG is a promising method for the

production of controlled release formulations with HPMC using aqueous solutions as

granulation liquid.

101. ASYMMETRIC DISTRIBUTION IN TWIN SCREW

GRANULATION

Tim Chan Seem1, Neil A. Rowson1, Ian Gabbot2, Marcel de Matas2,

Gavin K. Reynolds2 & Andy Ingram1

1 School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT,

UK

2 Pharmaceutical Development, AstraZeneca, Charter Way, Macclesfield SK10 2NA, UK


Twin Screw Granulation (TSG) is a method of continuous wet granulation rapidly

developing interest in the pharmaceutical industry. As a replacement for traditional batch

granulation methods the amenability to Process Analytical Technology (PAT) makes the

potential of TSG clear. Currently process understanding is limited and there is a need to

develop models of granulation mechanisms.

The size distributions of granules produced by TSG are characteristically broad and

bimodal, only becoming sharply mono-modal at high L/S ratios. Liquid is non-uniformly

distributed among granules and is concentrated toward the top end of the population size

range. Through measurement of the liquid content of granules, it has been observed that the

variance in liquid distribution can be reduced by increasing the local material fill level at the

point of liquid addition. It is believed that a higher fill level allows for more homogenous

wetting of the powder bed. Additionally maintaining a high material fill level in the

conveying zone results in low shear mixing and further improves liquid distribution.

It has been observed that the distribution of material in conveying zones is asymmetric at

low fill, with the bulk of material being conveyed by a single screw. Material flows in “plugs”

corresponding to the screw channels and with minimal transverse distribution. Flow

asymmetry at low fill is a result of the granulator geometry and results in a size selective

segregation of granules. An evaluation of the transverse distribution as a function of material

feed rate (and hence fill level) has been undertaken. Figure 1 shows the poor distribution of

material at low feed rates, only approaching near-homogeneity at close to 100% conveying

capacity. Confirmation of this uneven material distribution has been attempted through the

reprocessing of PEPT (Positron Emission Particle Tracking) data and results add confirmation

of the measured uneven distribution.

Distribution of material at 100rpm

Feed rate (kg/h)

0 1 2 3 4 5 6

Ma

ss fra

ctio

n

0.0

0.2

0.4

0.6

0.8

1.0

Right Screw

Left Screw

Figure 1. Transverse distribution of material discharged from conveying screws at 100rpm

102. ROLL COMPACTION OF SPRAY-DRIED MANNITOL

USING DIFFERENT COMPACTION DESIGNS AND PROCESS

PARAMETERS

Kitti Csordas & Peter Kleinebudde

Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Dusseldorf,

Universitatsstrasse 1. 40225, Dusseldorf, Germany


Roll compaction/ dry granulation is a continuous process, which is widely used in the

pharmaceutical, chemical and mineral industry. The process has several advantages: it

improves poor powder flow properties, increases the bulk density and compressibility,

reduces the loss of material during production and ensures the uniformity of the formulation.

Roll compaction does not require a liquid binder and, thus, the drying stage can be avoided,

resulting in a time and cost-effective process. Furthermore, roll compaction is attractive for

moisture and or heat-sensitive materials [1].

Pure spray-dried mannitol (Pearlitol 200 SD) was compacted using a Gerteis Minipactor®

250/25 (Gerteis Maschinen + Prozessengineering AG, Jona, Switzerland) as a brittle filler

excipient. Due to its larger surface area, the spray-dried form is more suitable for roller

compaction, than the unprocessed material [2]. Beside the importance of selecting an

appropriate material, system design can influence the product quality. The impact of four

different system designs were examined on the ribbon and granule properties: side-sealing

system and rim-rolls were used to avoid the bypass of the material, using a pair of smooth

rolls or a pair of knurled rolls. Specific compaction forces were 2 kN/cm, 4 kN/cm, 6 kN/cm,

8 kN/cm and 10 kN/cm. The gap width was set at 1.5 mm and 3 mm and the roll speed to 2

rpm and 4 rpm. The ribbons were milled with a fixed granulation method using a star

granulator. The granule size distribution was determined by digital image analysis using

CamSizer® XT-Jet module.

The highest amount of fines (<90 µm) were produced using 2 kN/cm specific compaction

force, 3 mm gap width, 2 rpm and 4 rpm roll speeds, respectively. Setting 8 kN/cm, 1.5 mm, 2

rpm and 4 rpm or 10 kN/cm, 1.5 mm and 2 rpm and 4 rpm resulted the maximum amount of

coarse fraction (>710 µm) and the maximum value of Q90%. In the rim-roll sealing system

the amount of fines was lower when using the smooth roll surface.

[1] P. Kleinebudde, Roll compaction/dry granulation: pharmaceutical applications, European Journal

of Pharmaceutics and Biopharmaceutics, 58 (2004) 317-326.

[2] M. Wagner, M. Pein, J. Breitkreutz, Roll compaction of mannitol: Compactability study of

crystalline and spray-dried grades, International Journal of Pharmaceutics, 453 (2013) 416-422




316555.


103. PRACTICAL APPLICATION OF UNIFIED COMPACTION

CURVE TO ROLLER COMPACTION FORMULATION DESIGN

AND EQUIPMENT TRANSFER

Gavin K. Reynolds, Ron J. Roberts, S. Claxton, Andreja Mirtic & Jeff Parry



Farber et al. [1] describe the "loss of compactibility" that is observed when a formulation is

roller compacted and milled, before compression. The resultant tablets typically do not

develop as much strength as tablets made by direct compression of the ungranulated blend.

The unified compaction curve model [1] allows this loss in tablet tensile strength after roller

compaction to be taken into account whilst still maintaining usage of the same tabletability

(tensile strength vs. compaction pressure) relationship for a given material. This analysis can

be further modified in order to provide a description of the material compactibility (tensile

strength vs. porosity) as a function of ribbon porosity [2].

A new methodology for prediction of powder mixture compactibility is presented.

Combining this with the loss of compactibility model provides a practically useful tool for

tablet formulation design for direct compression and roller compaction processes. A further

application of this approach is explored in the context of transfer of processes between roller

compaction equipment. Models are available for relating material properties, equipment

dimensions and process parameters to ribbon porosity to facilitate process transfer between

roller compaction equipment, for example [3]. However, although in practise the ribbon

porosity may be matched, differences in feeding, sealing and milling systems can result in

variation in the subsequent powder used for tabletting. Consideration of variation in the level

of uncompacted formulation incorporated in the granule in addition to extragranular

excipients can be predicted by the model in order to assess the resultant impact on tablet

robustness.

[1] L. Farber, K.P. Hapgood, J.N.Michaels, X-Y. Fu, R. Meyer, M-A. Johnson, F. Li, Unified

compaction curve model for tensile strength of tablets made by roller compaction and direct

compression, International Journal of Pharmaceutics, 346 (2008) 17-24.

[2] E. Gavi, G.K. Reynolds, System model of a tablet manufacturing process, Computers and

Chemical Engineering, 71 (2014) 130-140.

[3] G.K. Reynolds, R. Ingale, R. Roberts, S. Kothari, B. Gururajan, Practical application of roller

compaction process modeling, Computers and Chemical Engineering, 34 (2010) 1049-1057.




316555.

104. CONTROL STRATEGIES FOR ALTERNATIVE

CONFIGURATIONS IN CONTINUOUS INDUSTRIAL

GRANULATION PROCESSES

Ivana M. Cotabarren, Diego E. Bertín, Verónica Bucalá & Juliana Piña

Department of Chemical Engineering, PLAPIQUI, Universidad Nacional del Sur, CONICET,

Camino La Carrindanga Km. 7, (8000), Bahía Blanca, Argentina


Within solids processes, granulation is one of the most important operations. In the

fertilizers industry, it particularly provides products with high resistance to breakage and low

tendency to caking and lump formation [1]. The operation of granulation circuits, which

include not only particle size enlargement in the central granulator but also particle size

classification in screens and particle size reduction in mills or crushers, is generally not

simple. In fact, industrial circuits are usually operated by trial and error, being difficult to run

the plants at steady state without frequent undesired shut-downs [2,3].

Even though particulate process are involved in approximately three quarters of all

industrially processed goods, it is noteworthy that the field of automatic control has mainly

been committed to processes handling only liquid or gases [4]. This is basically due to the

many difficulties encountered in implementing control strategies in plants that handle solids

(i.e., process multivariable nature, lack of adequate instrumentation to measure solid

properties, insufficient degrees of freedom or manipulated variables, etc. [4]).

In view of the above-mentioned difficulties, this work is focused on the development of

closed-loop feedback control strategies for a complete dynamic simulator corresponding to a

urea granulation circuit (based on fluidized-bed granulation) that considers the flowsheet

configuration presented in a previous contribution [5]. This new configuration includes the

bypass of fines coming out of the crusher (flowrate and size fraction of seeds fed back to the

granulator), the granulator discharge, the fluidization air temperature and flowrate, and the

gap between the crusher rolls as potential manipulated variables. In order to maintain the

operation within the desired limits, it is necessary to control the granulator top vacuum

pressure, the fluidized bed levels and temperatures, and the product particle size distribution

mean size and span. Through sensitivity analysis and/or the Relative Gain Array criterion, the

optimal pairing between manipulated and controlled variables was first determined.

Subsequently, the proposed controllers were tuned following an optimization-based method

(integral of time absolute error, ITAE). For all the controlled variables, the implemented

strategy successfully allows both: rejecting disturbances and reaching new set points.

[1] N. Balliu, I.T. Cameron, Performance assessment and model validation for an industrial

granulation circuit, Powder Technology, 179 (2007) 12–24.

[2] N. Balliu, An object oriented approach to the modelling and dynamics of granulation circuits,

(2005).

[3] F.Y. Wang, I.T. Cameron, A multi-form modelling approach to the dynamics and control of drum

granulation processes, Powder Technology, 179 (2007) 2–11.

[4] M. Dueñas Diez, B. Erikydstie, M. Fjeld, B. Lie, Inventory control of particulate processes,

Computers & Chemical Engineering, 32 (2008) 46–67.

[5] I. Cotabarren, D. Bertín, V. Bucalá, J. Piña, A validated flowsheeting tool for the study of an

industrial granulation process, Industrial & Engineering Chemistry Research. 52 (2013) 15198–15210.

105. IMPROVED MICROENCAPSULATION PROCESS FOR

PROBIOTICS BY BOTTOM SPRAY FLUIDIZED BED

GRANULATION AND WURSTER COATING WITH

MALTODEXTRIN AND SHELLAC

Ádám Gy. Nagy1,2, Christopher Beermann2 & Günter J. Esper2

1 Erdősor Street 4. X./60. H-1046, Budapest, Hungary

2 Faculty of Food Technology, University of Applied Sciences of Fulda, Marquardstraße 35, 36039

Fulda, Germany


Probiotic microorganisms have been widely applied for dairy products with various health

benefits. Food production processes and storage conditions strongly influence the survival of

probiotic microorganisms and accordingly their effectiveness. The aim of this study was to

establish an effective drying and coating process for probiotics with a specific bottom spray

fluidized bed granulation process with maltodextrin combined with a dietary shellac wurster

coating process.

Lactobacillus reuteri DSM 20016 was cultured in shaking flask batch slurry fermentation

with 20w/v% aqueous sweet whey powder solution supplemented with 5w/v% yeast extract.

This culture was directly sprayed with maltodextrin powder within a fluid bed bottom spray

process with an air flow rate of 15-25 N*m3*h-1 and an inlet air temperature of 40°C, slurry

spray rate of 3 ml*min-1. The granules were wurster coated with a 25w% aqueous shellac

solution supplemented with 5w% plasticizer (Kollidon-30) for 30 minutes with an air flow

rate of 40-50 N*m3*h-1, inlet air temperature of 40°C, shellac spray rate of 2 ml*min-1,

atomizing pressure of 1.6 bar. Particle size distribution after granulation and coating was

measured by standard laser diffraction method. Product humidity after microencapsulation

was measured by standard infrared moisture balance. The bacterial survival rate during the

process and storage period as well as after incubation in gastric and intestinal conditions

within an artificial gastrointestinal in vitro test was evaluated by pour plate counting.

Median diameter after granulation varied between 144.33 ± 1.79 µm and 481.42 ± 7.04

µm. After coating, these parameters were increased by 22.78 ± 3.26 µm. Product humidity

after granulation varied between 4.28 ± 0.19 w% and 6.49 ± 0.16 w%. Survival rates after

granulation varied between 25.99 ± 8.34 % and 77.46 ± 10.23 %. After coating, the survival

rates were not significantly decreased. After granulation the viable cell concentrations of the

granules compared to the viable cell concentrations of the sprayed slurry (100%) varied

between 16.42 ± 6.55 % and 75.37 ± 9.42 %. After coating, these results were not

significantly decreased. After 4 hours of incubation in artificial gastrointestinal conditions the

viable cell concentrations compared to the start of the test (100%) varied between 81.45 ±

16.93 % and 229.9 ± 21.8 %. After coating, the viable cell concentration was increased by

46.32 ± 23.65 % compared to non-coated cell-vesicles. After one month of storage at 4°C the

samples maintained their viable cell concentrations and after two month of storage the viable

cell concentrations were 53 ± 14.71 % of the concentrations at the start of the test.

In conclusion, fluidized bed bottom spray granulation with maltodextrin combined with a

shellac wurster coating protects probiotics during production and storage period as well as in

gastrointestinal conditions and therefore improves the effectiveness of probiotic nutrition.

106. UNDERSTANDING CONTENT NON-HOMOGENEITY IN

HIGH SHEAR WET GRANULATION: EFFECTS OF POWDER

SEGREGATION, PREFERENTIAL WETTING AND SOLUBILITY

Sarang S. Oka 1, Heather N. Emady1, Ondřej Kašpar2, Viola Tokárová2, František

Štěpánek2, Rohit Ramachandran1 & Fernando J. Muzzio1

1 Department of Chemical & Biochemical Engineering, Rutgers, The State University of New Jersey,

Piscataway, New Jersey



One of the key needs in wet granulation is to improve confidence in content uniformity.

This is presumably achieved by wet massing the powder ingredients in a high shear or a fluid

bed environment. Unfortunately, granulation may not always be successful. Ingredients often

exhibit a preferential tendency to accumulate in either fine or coarse granule fractions [1].

Subsequent granule size segregation can then cause significant fluctuations in drug content.

This study investigates the combined effects of powder segregation, and a difference in

wettability and solubility of ingredients with respect to the binder fluid, on content uniformity

of the product granules in a high shear wet granulation process. A two component API-

excipient system comprising of micronized acetaminophen (APAP) and microcrystalline

cellulose PH-101 (MCC) has been examined at 3% and 7% (w/w) active loads in a 3.9 L high

shear bladed mixer using water as a binder. The powder bed was continually sampled along

the duration of the process to develop content-distribution contours.

It is hypothesized that the APAP, being significantly smaller in particle size, sifts to the

bottom of the powder bed by finding spaces between the larger MCC particles in the high

shear environment. A drop of binder that falls on the bed will thus disproportionately be

surrounded by MCC particles, giving them a superior chance of being wetted and

consequently nucleated. Additionally, the wettabilities of MCC and APAP with respect to

water (binder fluid) have been experimentally measured. It was found that the contact angle of

MCC (36.0 ± 5.6°) is substantially lower than APAP (89.0 ± 0.03°), making the former

significantly more wettable. It can be envisaged that a wet nuclei or a granule will

preferentially adhere to MCC over APAP particles, thereby causing biased growth. In

addition, it is known that APAP is fairly soluble in water, while MCC is completely insoluble.

If a fraction of the APAP in the powder mixture dissolves in the binder during the process,

then it could remain trapped in the binder and get incorporated in the granule. However, some

of the dissolved APAP will recrystallize during the drying process on the crust of the granule

as the evaporating binder leaches out its dissolved contents. Subsequent powder handling may

lead to shedding of this dust, thereby making the fines super-potent. This possibility is

investigated by performing experiments using an aqueous binder that is saturated to varying

degrees with APAP. A trend in the content uniformity metric of the granules as a function of

the degree of saturation would be indicative of the underlying mechanism.

Thus, three distinct causative agents of content non-uniformity are combined in a single

investigation to examine the role played by each agent. The qualitative understanding and

quantitative analysis of factors that contribute to the occurrence of granule content non-

uniformity is a prerequisite to the design of inherently robust granulation processes.

[1] H. Egermann, W. Reiss, Effect of particle size of drug and diluent on drug distribution in granule

size fractions, Acta Pharmaceutica Suecica, 34 (1988) 5S.

107. EVALUATION OF THE TABLET SURFACE FLOW

VELOCITIES WITHIN PAN COATERS WITH IMPLICATION TO

PROCESS UNDERSTANDING

Rok Dreu1, Gregor Toschkoff2, Adrian Funke3, Andreas Altmeyer4, Klaus Knop5,

Johannes Khinast2 & Peter Kleinebudde5

1 Department of Pharmaceutical Technology, University of Ljubljana, Aškerčeva cesta, Ljubljana,

1000, Slovenia

2 Research Center Pharmaceutical Engineering GmbH, Inffeldgasse, Graz, A-8010, Austria

3 Global Chemical and Pharmaceutical Development, Bayer Pharma AG, Müllerstraße, Berlin, 13353,

Germany

4 L.B. Bohle Maschinen Verfahren GmbH, Industriestraße, Ennigerloh, 59320, Germany

5 Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstraße,

Düsseldorf, 40225, Germany


The process of tablet pan coating is by its nature a high particle to particle obscuration

coating process and can be a demanding unit operation when a low coating mass variation is

to be achieved. Satisfactory results in terms of coating variation should be maintained from

the development level up to production scale [1]. In order to achieve this goal in a controlled

manner one should understand the dynamics and limitations of the pan coating process.

In this study we have established a methodology for estimation of tablet translational

surface velocities within a fully operational pan coater and assessed dependence of tablet

translational velocities on tablet drum filling degree, pan speed, presence of baffles and

selected tablet properties. Biconvex two-layer tablets were used before, during and after the

process of active coating. Obtained results can be used as a part in the mosaic of process

understanding or can be regarded as a validation set of data for simulations of the tablet pan

coating process. Experiments were conducted on a lab-scale and pilot-scale side-vented pan

coaters. In order to determine tablet surface flow velocities a high-speed tablet surface flow

video was recorded via borescope inserted in the coating drum and then analysed by cross-

correlation algorithm. Dynamic distances of borescope to tablet bed were measured by

ultrasonic distance sensor. Representative tablet bed avalanching angles were determined by

analysing the tablet bed surface contour movement video. Average surface velocities of

tablets in pixels/s were transformed to velocity units by applying object distance dependent

scale and corrected for misalignment between bed avalanching and optical axis angle.

Obtained tablet velocity data were arranged in a linear fashion as a function of coating drum

radius and frequency [1]. Slopes k’, obtained by linear regression, were used for velocity data

set comparison. Velocity data obtained during active coating were close to those of dry tablets

after coating. Interestingly, filling degree had little influence on the k’ value, when coating

drum with baffles was used, while omission of baffles facilitated dependence of k’ on the

filling degree. Tablets with lower angle of repose exhibited velocity profiles with lower k’

values than tablet samples with higher inter-tablet friction. This particular behaviour can be

explained by values of tablet bed avalanching angles.

[1] R. Mueller, P. Kleinebudde, Prediction of tablet velocity in pan coaters for scale-up, Powder

Technology, 173 (2007) 51-58.

108. MEASUREMENT OF PARTICLE CONCENTRATION IN A

WURSTER COATER DRAFT TUBE USING LIGHT

ATTENUATION

Rok Šibanc1, Iztok Žun2 & Rok Dreu1

1 Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia

2 Faculty of Mechanical Engineering, University of Ljubljana, Aškerčeva 6, 1000 Ljubljana


Particle concentration in a coating zone of fluid bed coater is important to ensure

appropriate coating uniformity and process yield. A transmissive optical setup at the top of

the Wurster draft tube was used in a lab scale coater. Measured transmittances were converted

to volume fraction distributions using results of Monte Carlo calculations. The effect of gap

between the draft tube and distribution plate, fluidizing air flow rate, particle size and load

was studied. The ranges of measured transmittances were from 0.002 to 0.285 and the range

of volume fraction was from 1.36 % to 5.44 %. Comparisons of volume fraction results with

results of stop method, CFD simulations and coating experiments were also performed. In

order to study the dynamics of the system as a function of different process parameters

frequency analysis of transmittance signals was performed. Four distinct frequency responses

were identified.

Optical system in Wurster chamber, the view from the side and a sample transmittance signal

109. INFLUENCE OF MODIFIED WURSTER DRAFT TUBE ON

COATING UNIFORMITY OF PELLETS

Matevž Luštrik & Rok Dreu

Department of Pharmaceutical Technology, Faculty of pharmacy, University of Ljubljana, Aškerčeva

cesta 7, Ljubljana, 1000, Slovenia


The objective of the fluid-bed coating process is, apart from the high process yield and low

degree of agglomeration, to prepare particles with a well-controlled thickness and even

coating layer. The coating thickness and its uniformity are correlated with the motion and

volume fraction of particles inside the draft tube. Use of novel construction modification of

the Wurster draft tube, enabling the introduction of air through the perforated inner wall, has

been studied with regard to the particle coating uniformity.

Pellets of a narrow size fraction were coated by the polymer dispersion, containing the dye.

In the first set of coating experiments, the conventional and swirl generator equipped process

chambers [1] were equipped with a modified draft tube and in the second, reference set of

experiments, the conventional draft tube was used. Spectrophotometric evaluation of the dye

distribution was carried out for sets of pellet samples in order to evaluate per-particle coating

thickness uniformity. The results clearly indicated the influence of the airflow through the

draft tube perforations on the coating deposition uniformity. Lower coating variability was

noticed in every experiment conducted in a conventional Wurster chamber, equipped with a

modified draft tube when compared to the reference experiment; regardless of the air flow

rate and gap size. Additional improvement in coating uniformity with regard to reference

experiments was achieved also in case of swirl generator equipped coater but not at all

process settings.

[1] R. Dreu, M. Luštrik, M. Perpar, I. Žun, S. Srčič, Fluid-bed coater modifications and study of their

influence on the coating process of pellets, Drug development and industrial pharmacy, 38 (2012) 501-

511.

Modified Wurster draft tube, comprised of (A) an inner wall with perforations (1) and (B) a

housing with connections for the compressed air (2).

110. EFFECTS OF TYPE OF BATCH GRANULATOR ON

FORMATION OF SEEDED GRANULES

Mbako Jonas & Nejat Rahmanian

School of Engineering and Informatics, University of Bradford, Bradford, BD7 1DP, UK


Seeded granulation was introduced as a form of granulation in which all produced granules

in desired size range have a large particle at their core surrounded by finer particles [1].

Production of seeded granules has previously been reported using several scales of Cyclomix

batch granulator manufactured by Hosokawa Micron B.V. where calcium carbonate (Durcal)

and aqueous polyethylene glycol (PEG) used as the feed materials. This paper presents an

experimental investigation on the possibility of production of seeded granules using different

high shear granulators as compared to the previous work [1] .

The experiments were carried out using Roto Junior high shear mixer (manufactured by

Romaco, Italy) and 5 L Cyclomix. The formulation and process conditions were kept identical

for both granulators to compare effect of shearing conditions in different equipment. The

granules produced were dried and sieved into various sizes. Characterisation of granules was

later carried out to analyse the structure and strength. Investigations in this research seeks to

understand the mechanism leading to formation of seeded granules. Further experimental

work and characterisation is still being carried out.

[1] N. Rahmanian, M. Ghadiri, X. Jia, Seeded Granulation, Journal of Powder Technology, 206 (2011)

53-62.


111. INFLUENCE OF EXCIPIENT MATERIAL PROPERTIES

ON A DRY GRANULATION PROCESS

Mary E. Crowley1,2, Graham E. O Mahony1,2 Micheal A.P. McAuliffe3, Rakesh

C. Dontireddy1 & Abina M. Crean1,2



3 Centre for Advanced Photonics and Process Analysis, Applied Physics and Instrumentation

Department, Cork Institute of Technology, Cork


Microcrystalline cellulose (MCC) is a commonly used binder and diluent in wet and dry

granulation. In a quality by design (QbD) environment, knowledge and understanding of raw

material critical quality attributes (CQAs) is essential. In this study MCC PH 102 was stored

under different relative humidity conditions, 11% at room temperature, 43% at room

temperature and 75% at 40°C. These storage conditions resulted in MCC moisture contents of

4.12, 4.86 and 6.96% w/w respectively. In this study, how the moisture content influences

MCC performance for two different compression processes, roller compaction and tableting

was studied.

MCC tablets were produced on an AIM™ instrumented Piccola™ rotary tablet press. The

compression profiles for MCC stored under different % RH were constructed (Figure 1(a)).

The MCC was also dry granulated on a Fitzpartick CCS220 roller compactor and the resulting

ribbon and granule properties were analysed. During dry granulation a MultiEye® Near IR

probe was used to monitor the MCC moisture content at-line. Results show that the moisture

content of MCC influences ribbon, granule and tablet properties. During direct compression

tabletting, the high moisture content MCC reached maximum compaction at lower

compression forces compared to lower moisture content MCC (Figure 1(a)). These results

agree with those previously reported by Sun [1]. Conversely the roller compaction study

showed that higher moisture content resulted in increased compaction giving denser ribbons

(Figure 1(b)). These results confirm that while there is an optimal MCC moisture content

range for compaction, the range is dependent on the type of compression process.

Figure 1. The effect of MCC moisture content after storage under different % RH conditions

on the compression profile of MCC for two different compression processes, (a) tableting

(direct compression) and (b) dry granulation (roller compaction)

B A


[1] C.C. Sun, Mechanism of moisture induced variations in true density and compaction properties of

microcrystalline cellulose. Int. J. Pharm., 346(1-2) (2008) 93-101.

112. THE DEVELOPMENT OF AN NIR INTERFACING DEVICE

FOR THE IN-LINE MONITORING OF A CONTINUOUS TWIN-

SCREW GRANULATION PROCESS

Fien De Leersnyder1, Elisabeth Peeters2, Chris Vervaet2, Jean Paul Remon2 &

Thomas De Beer1

1 Laboratory of Pharmaceutical Process Analytical Technology, Ottergemsesteenweg 460, 9000

Ghent, Belgium

2 Laboratory of Pharmaceutical Technology, Ottergemsesteenweg 460, 9000 Ghent, Belgium


There is the intention within the pharmaceutical industry to move from traditional batch

processing to continuous manufacturing. The ConsiGma25 line (GEA Pharma Systems,

Belgium) enables the continuous production of tablets, based on twin-screw wet granulation.

An increasing demand from the regulatory authorities towards the pharmaceutical industries

to gain a comprehensive understanding of their production processes together with an

accurate estimation of their robustness and reliability is associated with this increased interest

for continuous production. This study focuses on the development of a robust Near Infrared

(NIR) interfacing device for the twin-screw granulation process, to measure the moisture

distribution, the blend uniformity, the drug product solid state and the size distribution of the

wet granules using NIR spectroscopy. The spectrometer used in this study was the SentroPAT

system (Sentronic GmbH, Dresden, Germany). The NIR interfacing device (Figure 1, A) was

made out of a chute, in which an NIR probe is implemented from the bottom. In this way, the

wet granules are moving directly over the NIR probe. In preliminary tests, it was noticed that

the flow of the granules never fully covered the surface of the NIR probe resulting in noisy

spectra. Therefore it was decided to attach a paddle wheel on the slide which enables a more

continuous, denser granule flow and a continuous renewal of the material on the probe surface

(Figure 1, B). When using this device, it was observed that when the paddle wheel was

rotating in a counterclockwise manner, the densest granule flow is observed at the left side of

the paddle wheel. Therefore, the probe hole position was changed from the top of the paddle

wheel to the left side of the paddle wheel (Figure 1, C). Finally, it was also aimed to eliminate

the disturbance of the paddle wheel fingers on the NIR signal. One of the six paddle wheel

fingers was replaced by a finger made out of sintered PTFE. Sintered PTFE is exactly the

material applied as a reference for the used NIR spectrometer. Hence this finger is expected

to give a zero signal when passing over the NIR probe surface. The other five fingers were

made two millimetre shorter so that their distance to the probe surface became larger, in order

to avoid the disturbance of the NIR signal (due to large enough probe to sample distance).

Preliminary tests showed that C is the best device to continue the tests, the signal of the PTFE

finger on the NIR signal is much smaller compared to the signal of the other five fingers.

Figure 1. Three steps in the development of the NIR interfacing tool


113. EVALUATION OF OPERATING MODE AND SEED

PARTICLE SIZE ON TOP SPRAY FLUIDIZED BED

ENCAPSULATION OF HERBAL EXTRACT BY PRESSURE

FLUCTUATION ANALYSIS

Lucimara Benelli & Wanderley P. Oliveira

Laboratory of R&D on Pharmaceutical Process, LAPROFAR, University of São Paulo, Faculty of

Pharmaceutical Sciences of Ribeirão Preto, Ribeirão Preto, SP, Brazil


Herbal extract encapsulation technique is an efficient process to protect bioactive

compounds from degradation and also produce a particulate system for controlled drug

release. Top spray fluidized bed coating of seed particles with an encapsulating matrix

containing herbal extract can produce granules with good pharmacotechnical properties for

tableting in order to obtain a phytopharmaceutical product for oral administration.

Fluid bed coating is a complex process where the growing of the particles can occur by

layering or agglomeration according to operational conditions, seed particles and coating

composition properties. When agglomeration mechanism predominates over layering, large

agglomerates can be formed causing alterations on system dynamics and flow regime, leading

to system collapse. Time series analysis of in-bed pressure fluctuation signals is a method

used to characterize alterations on fluid dynamic system of fluidized bed due to the formation

of large agglomerates.

In this study, the standard deviation of pressure fluctuation was used to evaluate two

operational modes, intermittent and continuous, using two different seed particles size on top

spray fluidized bed encapsulation of herbal extract. Model plant species used to obtain the

herbal extract was Rosmarinus officinalis L. (Labiatae), known as rosemary. Encapsulating

blend with herbal extract was composed by Poloxamer 40, stearic acid, maltodextrin D10 and

Arabic gum. Microcrystalline cellulose pellets - Celphere® CP-507, 500 to 710 µm mean

diameter and Celphere® CP-305, 300 to 500 µm, were used as seed particles. Process

performance was evaluated by coating efficiency and percentage of agglomeration. Products

were characterized through mean size, polydispersity, shape factor and flow properties as a

function of time process.

The results obtained in the intermittent and continuous assays with seed particles of

different sizes showed that the increase in the percentage of agglomeration to a certain size

causes an increase in the standard deviation of the amplitude of the pressure fluctuation in the

system until the moment when the system instability begins. When the percentage of

agglomeration reaches a value able to destabilize the system, tending to cause its collapse, the

standard deviation of pressure fluctuation decreases, which is most evident in the continuous

operational mode. The intermittent operational mode presented higher percentage of layering

than agglomeration growth mechanism than the continuous one. The process with seed

particles with smaller size showed system instability faster than larger particles due to the

higher percentage of agglomeration. Variations occurring in the amplitude of pressure

fluctuation in the system evidenced that time series analysis can be a useful tool for process

control and determination of appropriate operational variables for microencapsulation of

herbal extracts in fluidized bed, yielding products with desired characteristics.


114. COMPARTMENTAL APPROACH TO WET

GRANULATION MODELS WITHIN A FLOWSHEETING

FRAMEWORK

Daniel A. Pohlman1, David Slade3, Sean Bermingham3, Mark Bollinger4, Poul

Bach4, & James D. Litster1,2

1 Department of Chemical Engineering, Purdue University, 480 Stadium Mall Drive, West Lafayette,

IN 47906, USA

2 Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47906,

USA

3 Process Systems Enterprise Limited, 5th Floor East, 26-28 Hammersmith Grove,

London, W6 7HA, United Kingdom

4 Novozymes A/S, Krogshoejvej 36, 2880 Bagsvaerd, Denmark


Wet granulation is a particulate design process that distributes a liquid binder across a

flowing mixture of solid material. The range of desired granule product properties across

many industries has led to a wide variety of wet granulation equipment geometries, process

conditions, and formulation properties. Because the granular product depends on all of these

factors, the analysis of these systems can easily become formulation and device specific.

More flexible tools are therefore desired to improve the understanding of granulation

phenomena.

In this work the flowsheeting software gPROMS ModelBuilder is used as a tool to develop

a multi-dimensional population balance model for wet granulation. This modelling framework

uses a compartmental approach to segregate rate processes into well-mixed zones that

represent general features of many granulators. The configuration used in the case study for

this work is shown in Figure 1. A spray zone represents the region of a granulator where

liquid first comes into contact with both primary particles and existing granules. Within the

spray zone we chose to model non-uniform liquid distribution according to the characteristic

parameters, dimensionless spray flux and droplet size distribution. The nucleation of this

spray is also captured with a physically derived model for solid layering onto the wet nucleus.

A circulation zone represents the bulk volume of the granulator. This zone contains variety of

rate processes and for high-shear granulation, consolidation, coalescence, and breakage are

included. Finally, a breakage zone is used to represent a high rotation speed knife, or chopper

where a higher breakage rate is expected. These compartments are linked according to a

simple network of well-mixed unit with constant flow back and forth. Value for the residence

times in each zone are estimated based on heretical understanding of mixing and flow within

the wet granulation system.

A case study evaluating the flexibility and usefulness of the multi-scale approach is also

discussed. The scale-up analysis of a 5L, 10L, 20L, and 50L horizontal axis mixer with

variation of impeller speed across each size is used to analyse the compartment model. The

particular changes in spray parameters and chopper dimension across experimental systems

can be taken into account with this heuristic compartmental approach, while other formulation

effects on rate processes is held constant. This compartmental approach is shown to be an

extremely useful tool for predicting changes to granulation based on changes in process

conditions and scale up.


Figure 3. The heuristic approach to compartmental modelling of wet granulation systems. The

zones are described for the horizontal mixer case study

1. Spray Zone

2. Circulation

Zone

3. Breakage

Zone

Q32 Q23

Q21 Q12

1: Spray Zone

3: Breakage Zone

2: Circulation Zone

115. THE INFLUENCE OF MANUFACTURING METHOD ON

PHYSICAL PROPERTIES AND DRUG RELEASE FROM PUSH

PULL OSMOTIC PUMP (PPOP) PRODUCTS

Gus LaBella1, Manish Ghimire2, Manish Rane1 & Piyush Patel1

1 Colorcon, Inc., 275 Ruth Road, Harleysville, PA 19438 USA

2 Colorcon Ltd., Flagship House Victory Way Dartford Kent DA2 6Q, UK


The objectives of this study were to evaluate manufacturing methods to prepare PPOP

tablets via Direct Compression (DC), Fluid Bed (FB), High Shear (HS) and Roller

Compaction (RC) granulation methods. From these processes, understand the difficulties of

processing POLYOX™ water soluble resin, in different equipment, to understand the impact

on granule and tablet physical and chemical properties and to understand the impact on drug

release.

Each process produced very different granule characteristics ranging in particle size from

120 - 377 microns, bulk density from 0.321 - 0.526 g/cc and FloDex flow orifice diameter of

4 - 6 mm. In general, drug layers were smaller in particle size than their counterpart push

layers processed by the same technique. This may be due to the sodium chloride in this layer

or the higher viscosity of the POLYOX™ polymer. The roller compaction process produced

the larges granule sizes. This is due to the high compactibility of POLYOX™ in the

formulations. Typical roll pressures used for standard immediate release roller compacted

products, resulted in ribbons of extremely high hardness. Milling these produced very large

granules. The push layers also showed higher density as compared to the drug layers. This is

primarily due to the dense sodium chloride in this layer.

Assay by sieve cut showed interesting results. In each case, both drug and salt assays were

low in the coarse sieve cuts and high in the fine sieve cuts. Variation was lowest with the fluid

bed granulation process. Segregation of the drug is of major concern for PPOP products as

many are low dose products.

Roller compaction produced the lowest quality (hardness) product out of the four

techniques. Tablet weight variation was lowest with the DC batch producing an RSD of

1.38% while RC produced the highest RSD of 2.34%. This is most likely attributed to the

large particle size of the granules produced by this method. Content uniformity followed the

same trend as weight variation, DC = RSD 1.0%, RC = RSD 2.7%.

The products were coated with Opadry® CA. A formula with an 80:20 ratio of cellulose

acetate to polyethylene glycol was applied to the tablets to achieve a 10% weight gain.

Dissolution of these tablets yielded similar release profiles. F2 values were calculated using

the HS batch as the reference. All residual solvents (alcohol and acetone) were below 20 ppm.

Regardless of wide variation in granule and tablet properties, drug release remained fairly

consistent yielding passing f2 values. Operations such as high shear granulation, roller

compaction and milling can be challenging for PPOP formulations. Care must be taken to

optimize these processes to ensure manufacture of acceptable product. Segregation of API and

salt from the formulations is a concern on the tablet press. Semi-permeable film coating

weight gain and CA: PEG ratio can be used to modulate drug release.

116. EFFECT OF VARYING PROCESS PARAMETERS ON

GRANULE SIZE DISTRIBUTION OF ROLL COMPACTED MCC,

MANNITOL AND THEIR MIXTURES

Ana Pérez Gago & Peter Kleinebudde

Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Düsseldorf, Germany


Roll compaction/ dry granulation is a continuous process, in which many parameters and

process conditions can be changed in order to obtain different properties of the final and

intermediate products. The properties of the material being compacted have also a clear

impact in the roll compaction process. Microcrystalline cellulose (MCC) and mannitol are two

excipients widely used in the pharmaceutical industry with different mechanical properties.

MCC suffers a plastic deformation while mannitol is a typical brittle material. The objective

and interest of this study is to investigate the effect of varying the main process parameters

and material properties on the granule size distribution.

Mixtures of MCC (Avicel PH 101, FMC) and mannitol (Pearlitol SD 200, Roquette)

containing 0, 15, 30, 50, 70, 85, and 100% of MCC were roll compacted in a Gerteis

Polygran® following a design of experiments (DOE) consisting in a multilevel full factorial

design with gap width, roll speed and specific compaction force as factors, which is

performed for each material and mixtures. Ribbons were milled under standard conditions in a

Frewitt sieving machine and the granules produced were analysed in a dynamic image

analysis (Camsizer XT, Retsch) obtaining the volumetric granule size distribution.

Cumulative distribution (Q3) curves were calculated in order to establish comparison

between the different materials. The amount of fines (< 180µm) changed depending on the

DOE conditions from 24% to 57% for MCC and from 15% to 39% for mannitol. If the tenth,

fiftieth and ninetieth percentiles (X10, X50 and X90) are taken into consideration, it is

possible to observe how these values evolve from pure MCC to pure mannitol. However, this

behaviour does not vary proportionally to the percentage, but follows a parabolic tendency.

Cumulative granule size distribution for pure MCC (left) and pure Mannitol (right)




316555.

117. COMPRESSIVE STRENGTH OF PHARMACEUTICAL

PELLETS SPRAY COATED IN A WURSTER FLUIDIZED BED

Alexander Russell1, Rok Šibanc2, Peter Müller1, Rok Dreu2 & Jürgen Tomas1

1 Chair for Mechanical Process Engineering, Otto von Guericke University of Magdeburg,

Universitätsplatz 2, 39106 Magdeburg, Germany

2 Chair for Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana,

Aškerčeva cesta 7, 1000 Ljubljana, Slovenia


For the production of high quality pharmaceutical products by direct tableting, pellets i.e.

fine agglomerates (typically 100 < d < 1000 µm) are required to possess good flowability,

compressibility and compactability. However, due to the distributed micro-macro mechanical

strength of a certain pellet population, the resulting tableted product quality suffers from

structural imperfections. In recent times, fluidized bed spray coating of pellets prior to

tableting or capsuling is being increasingly favoured to ensure better protection, controlled

release and stability of the drug. Concurrent to such therapeutic and medical advantages,

fluidized bed spray coating alters the mechanical properties of pellets’ surface. Thus, to

design handling processes with no undesirable deformation and tableting processes with

maximum desirable deformation, precise knowledge of the micro-macro mechanical strength

distribution of pellets is necessary.

In this communication, we present the influences of model polymer coatings on the

compressive micro-yield and compressive macro-breakage probability of individual model

pharmaceutical pellets, spray coated using a Wurster fluidized bed (see Figure 1). We also

describe the swelling and weakening of pellets when loaded with moisture, reflecting pellet

behaviour in the spray zone. We further present novel insights such as the energetic

coefficient of restitution for simulating pellet behaviour during mechanical processes where

low strain rates dominate, the micro-macro porosity of coatings by scanning electron

microscopy, the strengthening of wetted pellets by thermal drying and the influences of pre-

loading on the strength of pellets.

Figure 1. (a) Influence of 20 µm thick hydroxypropyl methylcellulose (HPMC) and Eudragit

coatings on the micro-yield strength and (b) influence of moisture content on the apparent

macro-breakage strength of microcrystalline cellulose pellets

118. IMPROVING THE FUNCTIONAL PERFORMANCE OF

EXCIPIENTS: EMPLOYING THE KNOWLEDGE OF

INTERACTIVE MIXING

Sharad Mangal, Felix Meiser, David AV. Morton & Ian Larson

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, 381 Royal

Parade, Parkville, VIC 3052, Australia


Previously, we have shown that a small surface lubricated binder exhibits excellent binder

and glidant activity at low proportions to API. Such excipient could be potentially effective

for direct compression of high-dose APIs. In this study, we aimed to investigate the impact of

surface lubricant concentration on its binder and glidant activity. Polyvinylpyrrolidone (PVP)

was spray dried with varying concentrations of L-leucine to create interactive excipients with

varying surface lubricant concentrations. The physico-chemical and bulk properties such as

particle size, surface composition, surface energy and bulk cohesion of spray dried excipients

were measured and compared to spray dried PVP (PVP-SD). The mixing behaviour of these

excipients and their effect on flow and binder activity of paracetamol was assessed. The mean

particles sizes of all spray dried formulations were 2-3 µm. Surface characterization indicated

that L-leucine achieved higher surface concentration compared to the PVP. Additionally, the

surface concentration of L-leucine increased with higher feed concentration indicating that L-

leucine feed concentration influences the surface composition of these interactive excipients.

The surface energy of the lubricated binder decreased with increasing L-leucine surface

concentration. In addition, the bulk powder cohesion reduced with higher surface L-leucine

concentration, implying a relationship with L-leucine surface concentration. The excipients

were blended with paracetamol. Spray dried PVP-based particles adhered to the paracetamol

particles and PVP co-sprayed with L-leucine de-agglomerated more efficiently and blended

more homogeneously with paracetamol compared to PVP-SD. Blend flow increased with

higher surface L-leucine concentrations indicating that surface lubricant concentration

influences the glidant activity of interactive excipients. It was noted that the binder activity of

PVP reduced significantly due to surface L-leucine coating. However, varying surface

concentration of L-leucine had negligible effect on the binder activity of PVP indicating that

manipulating surface lubricant concentration does not affect the binder activity of PVP. Thus,

the glidant activity of interactive binders can be improved by increasing surface lubricant

concentration without compromising their binder activity.


119. ADVANCED CHARACTERISATION AND MODELLING TO

PREDICT IRON ORES GRANULATION BEHAVIOUR

Rafael J. Contreras1, Frédéric Van Loo1, Maxime Evrard2, Marek Schöngut3, Eric

Pirard2 & František Štěpánek3

1 Centre for Research in Metallurgy, Avenue du bois St. Jean/21 Liège, Belgium

Email: [email protected]

2 Department of Chemical Engineering, Institute of Chemical Technology Prague, Czech Republic,

Email: [email protected] , [email protected]

3 Department Génie Minéral, Matériaux et Environnement, University of Liège, Belgium


Since the 50’s, the main iron ore deposits are the Banded Iron Formation and are exploited

in the Precambrian shield of Brazil, Mauritania, Australia, China, etc. To be reduced and

transformed into steel, iron ores have to be sent to the blast furnace where the temperature

reaches 1600°C. However, the finest particles (< 6.3 mm) tend to decrease the permeability in

the blast furnace, which reduces its effectiveness. Hence, these particles have to be sintered.

The first step of this technique is the granulation. It consists in forming micropellets (small

iron ore balls) from a mixture of iron ores, coke, flux (limestone, olivine…) and water. This

mixture then is heated and gives a semi-molten mass that solidifies into porous pieces of

sinter having sufficiently good size and strength characteristics to be fed into the blast

furnace. A good understanding of the link between these properties and the granulation

efficiency therefore serves the overall process optimization. Iron ores show a downward trend

of their quality (finer particles, broader size distribution, lower grades and higher fluctuation

of properties). To ensure its competitiveness and sustainability, the European steel industry

must use such ores together with recycled materials at the sinter plant, while improving sinter

quality and productivity at lowest possible environmental impact and energy consumption.

Pre-processing of iron ores and especially granulation before sintering might level off the

downward evolution in sinter quality. Laboratory-scale granulation tests have been done on

six iron ores (one magnetite ore, one goethite ore and four hematite ores) which have been

characterized. For each ore, the contact angle, the amount of liquid absorbed into the pores

and of interparticular liquid required to promote granulation have been measured to fully

characterize the wettability and the interactions with liquid binder. The measured granulation

kinetics has been linked to the initial properties.

A methodology combining theoretical and experimental techniques for analysing the

growth of granules in a drum granulator was developed. The methodology combines the

Stokes number analysis for calculation of successful collisions and well-controlled

experimental study of the wet granulation for modelling the granule formation. The final

structure of the granules (porosity and distribution of primary particles) has been precisely

characterised to assess the granulation performances. The application of an innovative

measurement technique coupling X-ray microtomography with an image processing gives

access to the whole 3D structure of the granules (nuclei/fines, porosity and different textures

such as layering, cracks...). Finally, the mechanical properties – namely the resistance to

attrition and breakage during impact – of the granules have been determined using a high-

speed video camera for slow motion analysis.





120. DEVELOPMENT OF DRY GRANULATES: FROM CA. 25

GRAMS PER FORMULATION TOWARDS LARGE SCALE

ROLLER COMPACTION (WITH A GERTEIS MACRO OR MINI-

PACTOR)

Barbara Fretter 1, Katharina Freischlad 1 & Robert F. Lammens 2

1 Solids Development Consult GmbH, Am Turm 38, 53721 Siegburg, Germany

2 Gerteis Maschinen + Processengineering AG, Stampfstrasse 85, 8645 Jona, Switzerland


During the early stage of formulation development, often only a few grams of API are

available. Therefore, it is desirable to save as much API as possible, which e.g. also holds for

very expensive API material. When using a small roller compactor, a meaningful series of

experiments at least requires about 0.3 to 0.5 kg of formulation. In order to reduce this amount

of material whilst collecting all information required for developing a dry granulate

formulation, a development strategy based on tablets has been established.

This strategy is based on the analogy of densifying a powder at a roller compactor and at a

tablet press, and so, a single stroke tablet press is used for mimicking the process of making

ribbons. The comparability of granulates based on dry granulates obtained by tableting and by

roller compactions has been verified for all critical process steps, namely compaction and

milling. Since most dry granulates are processed to tablets, the recompactability of the

formulation is one of the important parameters. So, for testing their properties, the granulates

are densified to tablets under conditions resembling production closely.

Replacing for development purposes a roller compactor by a single stroke tablet press and

being able to evaluate tableting data independent of tooling format, it is possible to

characterize the dry granulation properties of a formulation with ca. 25 grams of material.

After having identified a proper small scale formulation, the number of trials to be

performed with a roller compactor is rather small. If possible, the manufacturing space should

be determined and roller types specified. Different roller compactor settings (namely gap and

specific compaction force) must be evaluated concerning their influence on the (re-)

compactability and standard deviation of tablet weight of the formulation when being

compressed to tablets at production conditions. For these experiments, ca. 30 to 50 kg of

powder are required, when using a MacroPactor 100, but for a MiniPactor only 7 to 12 kg

need to be available. Scale up towards larger batches is not a problem, since at least for

Gerteis roller compactors, all scale up knowledge is known in detail.

So, when using the procedure of developing a dry granulate based on tablets, it is possible

to save an enormous amount of API or to enlarge the number of formulations, which can be

investigated, considerably. This allows in the early stage of development a reasonable and

reliable decision regarding the granulation method, and the composition and processability of

the formulation, whilst avoiding that formulation development becomes the limiting factor in

time to market.

121. GRANULATION OF BIOWASTE INTO GREEN

FERTILIZER: OPTIMISATION OF THE ENERGY

CONSUMPTION OF A GRANULATION PLANT USING ASPEN

PLUS

Emma Stuart, Yoann F. Glocheux, Matheus R. Mendes de Araújo, Ahmad B.

Albadarin & Chirangano Mangwandi

Queen's University Belfast, School of Chemistry and Chemical Engineering, David Keir Building

Belfast BT9 5AG


One of the challenges of the anaerobic digestion sector is the treatment of the remaining

digestate after the process. The high nutrient content of such stream makes it a good candidate

for being re-used as a green fertilizer. The granulation of biowaste has attracted lots of

attention and is regarded as a good technology to produce low cost fertilizer or soil

conditioners [1].

In the present work the solid fraction of a farm based digestate was co-granulated with

limestone used as a filler and lignosulphonate used as a binder under different dosing rate.

The granules were produced using a high shear granulator and were dried using a horizontal

tray drier. The granules thus produced showed very good physical characteristics in terms of

particle size distribution and strength analysis.

Based on the experimental results obtained, a granulation plant producing up to 1 T/day of

green fertilizer was simulated using ASPEN PLUS. This study presents the optimisation of

the energy consumption of the plant as a function of the types of granules produced.

Figure 4. Process design of a green fertilizer granulation plant under ASPEN PLUS

[1] C. Mangwandi, A.B. Albadarin, L. JiangTao, S. Allen, G.M. Walker, Development of a value-

added soil conditioner from high shear co-granulation of organic waste and limestone powder, Powder

Technology. 252 (2014) 33–41. doi:10.1016/j.powtec.2013.10.039.

http://www.sciencedirect.com/science/article/pii/S0032591014005646


122. INVESTIGATION OF NUCLEATION IN TWIN SCREW

GRANULATOR USING COMPACT POWDER BEDS

Qing Ai, Ranjit M. Dhenge, Michael J. Hounslow & Agba D. Salman

Department of Chemical and Biological Engineering, University of Sheffield,

S1 3JD, Sheffield, UK


Nucleation is a crucial step for granulation in which liquid and powder mix to form

primary granules. The nuclei properties are considered to have a direct influence on the final

granule properties [1]. Nucleation can also be mimicked by way of using a droplet of binder

placed on a loose powder bed to form a nucleus. Although the work concerning droplet and

powder has been done quite extensively (i.e., nucleation regime map), the research in this area

is limited as it has not been applied truly into the granulation process, and a link between

droplet and granule has not been well-established.

In this research, single droplet nucleation using lactose (soluble), calcium phosphates

(insoluble) and microcrystalline cellulose (insoluble, swells upon water addition) were carried

out. A series of plastic deformation measurements were carried out on the compacted powder

beds to investigate the relationship between the compaction forces used to make the powder

bed and the nucleus strength. Furthermore, Hydroxypropyl cellulose (HPC) was added to

reveal what role the binder is playing in nucleation process. Results indicated that the

properties of powder significantly influence the properties of nuclei including (size, stress and

etc.) which could enhance the understanding about how the solid binder and excipient

powders behave during nucleation process.

[1] K. P. Hapgood, J. D. Lister and J. Smith, Nucleation regime map for liquid bound granules, AIChE

Journal, 49 (2003) 350-361.

123. SPOUTING IN A PRISMATIC BED: A NUMERICAL AND

EXPERIMENTAL EVALUATION

Vitalij Salikov1, Stefan Heinrich1, Sergiy Antonyuk2, Vinayak S. Sutkar3,

Niels G. Deen3 & J.A.M. Kuipers3



2 Particle Process Engineering, Department of Mechanical and Process Engineering, University of

Kaiserslautern, Gottlieb-Daimler-Strasse, 67663 Kaiserslautern, D

3 Multiphase Reactors Group, Department of Chemical Engineering and Chemistry,

Den Dolech 2, 5600 MB Eindhoven, NL


A spouted bed is a widely used and very effective gas-solid contactor. In this study a

prismatic spouted bed was investigated experimentally and modeled by using a Discrete

Particle Model (Discrete Element Method coupled with Computational Fluid Dynamics). The

main focus was set on the transformations of the spouting state at increasing gas velocity and

the impact of the geometrical conditions on this behaviour. The bed hydrodynamics were

characterized by means of high speed video recordings and additional by Fast Fourier

Transformation (FFT) and evaluation of chaotic properties of the pressure drop signal.

Different operational regimes were identified and correlated by means of the pressure

behaviour. The simulations performed for selected regimes and modifications of the apparatus

geometry showed a good agreement with experiment in both, particle and gas dynamics. The

spouted bed was characterized regarding the particle micromechanics within the entire

apparatus and for bed regions with very different hydrodynamics, such as the spout, fountain

and annulus. Additionally, the stability of the fluidization could be improved with an

optimized apparatus geometry with inserted draft plates close to the gas inlets. The better

performance of this design has been experimentally investigated at different gas inlet

velocities (Figure).

Spouting behaviour at increasing gas flow rate. (a) Flow instability at high gas velocity shown

snapshots from simulations and experiment; (b) Flow behaviour in the optimized geometry

obtained by an experiment.

(a) (b)

Draft plates

124. TWIN SCREW GRANULATION: EFFECT OF FILL LEVEL

Sushma V. Lute, Ranjit M. Dhenge, Michael J. Hounslow & Agba D. Salman




Twin screw granulation (TSG) has recently become popular as a wet granulation

technique of choice in the pharmaceutical sector for its advantages such as continuous powder

processing with high productivity, energy efficiency and cost reduction [1]. In TSG, the effect

of process and formulation variables on granule properties have been studied previously [1,2].

However, the impact of varying Fill Level (FL) on granule properties has received limited

attention [3]. It can be very important factor to consider when increasing the throughput of the

TSG while maintaining the desired quality of the granules. Therefore, this research was

focussed on investigating the influence of varying the FL on the size and shape of the

granules.

[1] R. M. Dhenge, R. S. Fyles, J. J. Cartwright , D. G. Doughty, M. J. Hounslow, A. D. Salman, Twin

screw wet granulation: Granule properties, Powder Technology, 164 (2010) 322–329.

[2] R. M. Dhenge, K. Washino, J. J. Cartwright, M. J. Hounslow, A. D. Salman, Twin screw

granulation using conveying screws: Effects of viscosity of granulation liquids and flow of powders,

Powder Technology, 238 (2013) 77-90.

[3] R. M. Dhenge, J. J. Cartwright, M. J. Hounslow, A. D. Salman, Twin screw wet granulation:

Effects of properties of granulation liquid, Powder Technology, 229(0) (2012) 126-136.

125. MAGNETIC PARTICLE TRACKING: ANALYSIS OF THE

PARTICLE MOTION IN ROTOR BASED GRANULATION

EQUIPMENT

Johannes Neuwirth & Stefan Heinrich

Institute of Solids Process Engineering and Particle Technology,

Hamburg University of Technology, Hamburg, Germany


Measuring the particle motion in granulation systems has been an area of increasing

interest in recent years. A detailed knowledge of the particle dynamics (translational and

rotational) is essential for a better understanding of the macro mechanisms during the

granulation or blending processes. To visualize and quantify the granular flow continuously, a

novel non-intrusive 3D measurement technique, the Magnetic Particle Tracking (MPT) has

been further developed [1]. The technique is based on the continuous tracking of a single

magnetically marked particle. Due to the precisely defined magnetic dipole axis of the tracer,

the MPT allows a detailed and simultaneously analysis of the translational as well as

rotational movement of tracer particles in a dense granular flow and different zones of the

apparatus.

In this contribution, the Magnetic Particle Tracking is used to evaluate the complex granular

flow and macroscopic particle dynamics in the dense gas-solid system of a lab-scaled fluid

bed rotor processor experimentally. The time-averaged velocity profiles and distributions as

well as residence times in several zones, e.g. spray and shear zones, are determined. The focus

in this work is the detailed analysis of the particle rotation behaviour at different process

conditions, e.g. fluidization velocity, rotor speed and filling degree by using the MPT

technique. Furthermore, to study the particle dynamics under wet conditions the experiments

also are performed by spraying a Polyethylenglycol solution (PEG-400) into the particle bed.

The results indicate that the bed porosity has a significant effect on the particle rotation.

Furthermore, the rotational movement of the particles is mainly influenced by the viscous

force of the liquid. Generally, a narrower angular velocity distribution is detected. The

information obtained by MPT can be used to optimize the design of a wide range of industrial

process systems.

Figure 1. Granular flow in a rotor granulator (left), time averaged particle flow field measured

with Magnetic Particle Tracking (right)

up,t

up,r

up,z

Process

airAir gap

Bulk

Rotor disc

up,r up,t up,z Spatial particle velocity, m/s

x [mm]

X

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-75

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0 0.5-1 -0.5

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rm.

len

gth

y/Y

[-]

dry

conditions

1

A A

A - A

[1] J. Neuwirth, S. Antonyuk, S. Heinrich, M. Jacob: CFD–DEM study and direct measurement of the

granular flow in a rotor granulator, Chemical Engineering Science 86, 2013, 151-163.

126. DESIGN OF GRANULAR ADSORBENT MATERIAL FOR

ASERNIC REMOVAL FROM CONTAMINATED WASTEWATER

Chirangano Mangwandi1, Siti Nur Ain Suhaimi, Jiang Tao Liu,Yoann F.

Glocheux1 & Ahmad B. Albadarin1,2

1 Queen's University Belfast, School of Chemistry and Chemical Engineering

David Keir Building, Belfast BT9 5AG 2 University of Limerick, Synthesis & Solid State Pharmaceuticals Center (SSPC),

Department of Chemical and Environmental Science, Ireland


The objective of this research was to design a granular product from iron oxide for use as

an adsorbent for heavy metals from contaminated wastewater. The first task of the project was

identification of a water insoluble polymer for use as a binder in the granulation process.

Polyvinyl acetate was chosen as suitable polymer as it is water insoluble. Initial trial

experiments on selection of suitable solvent of the polymer were carried using three solvents

namely, methanol acetone and toluene. Based on the initial tests on strength and product yield

acetone was selected as the solvent for polyvinyl acetate binder. Design of experiment was

then used to investigate the influence of granulation process variables (impeller speed; binder

concentration and liquid to solid ratio), on the properties of the granular adsorbents. The

response variables in the study were granules mean size, stability in water and granule

strength. The results obtained that combination of high impeller speed and high binder

concentration favour formation of strong granules which were very stable in water.

Effect of process variables on the stability coefficient of the adsorbent granules.

Design-Expert® SoftwareFactor Coding: ActualSC (-)

Design points above predicted valueDesign points below predicted value0.992

0.750

X1 = A: Conc.X2 = B: speed

Actual FactorC: l/s = 0.25

103.00

112.50 122.00

131.50

141.00 150.50

160.00

10.00

12.00

14.00

16.00

18.00

20.00

0.750

0.800

0.850

0.900

0.950

1.000

1.050

SC

(-)

A: Conc. (g/L)B: speed (rpm)

http://www.sciencedirect.com/science/article/pii/S0032591014005646


127. INVESTIGATION OF THE GRANULAR DISPERSION

BEHAVIOUR IN A FLUID BED ROTOR PROCESSOR

Johannes Neuwirth & Stefan Heinrich

Institute of Solids Process Engineering and Particle Technology,

Hamburg University of Technology, Hamburg, Germany


In pharmaceutical, food and chemical industries the application of the fluid-bed rotor

processor (FBRP) for the production of dense granules with a high strength and sphericity is

widely distributed. For a better understanding of the granulation process a detailed knowledge

of particle motion is essential. In general, rotor-based granulation equipment are characterized

by a high mixing performance, which is an important quality parameter.

In this work the complex granular flow and the mixing patterns in a fluidized bed rotor

processor are investigated. The Discrete Element Method (DEM) coupled with the

computational fluid dynamics (CFD) is used to characterize the influences of the process

parameters: rotorspeed and fluidization gas velocity on the particle dynamics and thus the

mixing efficiency. A viscous and capillary force model was implemented to describe the

interactions between surface-wetted particles. The mixing is quantified by using anisotropic

dispersion coefficients based on the numerical approach.

In this contribution the flow of mono-dispersed, spherical particle blends are investigated.

Finally, the mixing efficiencies are characterized by homogeneity analysis based on the CFD-

DEM simulations. Furthermore, the granular flow and mixing pattern based on the CFD/DEM

model were validated by a novel particle tracking system, the Magnetic Particle Tracking.

The mixing quality within the rotor processor was found to be strongly depending on the

fluidization air velocity.

Figure 1. Time dependent mixing degree for a mono-disperse granular system under wet and

dry conditions

128. UNDERSTANDING THE INFLUENCE OF GRANULE

MICROSTRUCTURE ON GRANULE COMPRESSION

BREAKAGE

Steven A. Dale1, Maksym Dosta2, Sergiy Antonyuk3, Carl Wassgren1,

Stefan Heinrich2 & James D. Litster1

1 Purdue University, West Lafayette, IN 47907, USA

2 Hamburg University of Technology, Denickestr. 15, 21073 Hamburg, Germany

3 University of Kaiserslautern, Gottlieb-Daimler-Str. 44, 67663 Kaiserslautern, Germany


The goal of the current work was to use a well characterized system to understand how the

distribution of components within granules, i.e., the granule's microstructure, relates to the

force vs. displacement curve and the fragment size distribution created during compression

breakage. Granules made of glass ballotini and PVP using different formation techniques

were characterized using X-ray computer tomography (XRCT) to obtain the glass ballotini,

PVP, and air distributions within the granules (Figure 1a). The granules were then broken

using uni-axial compression breakage experiments and the fragments were collected to

measure their size. Although there is considerable scatter in the results, more homogeneous

particle fractions within the granules generally corresponded to a larger maximum breakage

force and a larger fragment specific surface area.

To better understand the particle level interactions that led to these differences, discrete

element method (DEM) simulations have been performed using the simulation framework

MUSEN (Figure 1b). MUSEN is an in-house, component-based framework, where several

components have been developed to investigate the breakage behaviour and strength of

agglomerates. The DEM-modeled granules were generated as a set of primary particles

connected with solid bonds. The XRCT measurements were used to reproduce the

agglomerate size, shape, and internal microstructure of experimental granules. In this way,

simulated force vs. displacement curves and fragment surface areas were obtained using

realistic granule microstructures. The simulated and experimental results were compared in

order to verify input material parameters and validate the simulation code. Implications for

designing granule microstructure to give specific product attributes are discussed.

Figure 1. Granule microstructures a) experimentally measured using XRCT and b) digitally

re-created for DEM simulation.

a) b)

129. REAL-TIME PARTICLE IMAGING OF

PHARMACEUTICAL TABLET DISINTEGRATION

Arthi D. Rajkumar1, Gavin K. Reynolds2, David Wilson2, Michael J. Hounslow1

& Agba D. Salman1



2 AstraZeneca, Charter Way, Macclesfield, Cheshire East, SK10 2NA, UK


Utilisation of tableted material is a highly desirable concept in industries such as food and

drink, and their usage is already quite well-established in the pharmaceutical industry. This is

due to the controllable and convenient methods in which tablets can be synthesised and

distributed to the customer. Pharmaceutical tablets conventionally contain an active

ingredient, i.e. a drug substance, which is the biologically active substance that the tablet is

administering. However the majority of the tablet consists of inactive excipients, such as the

filler, binder and disintegrant, which influence how the tablet behaves inside the human body.

Once the tablet is ingested it will come into contact with liquid such as water and stomach

fluids in which the tablet will dissolute. Tablet dissolution is aided by disintegration which is

the process of the tablet breaking into smaller fragments. While the tablet disintegration

phenomenon influences the tablet activity, it is poorly understood.

Tablet disintegration is a fundamental parameter that is tested in vitro before a product is

released to the market, to determine approximately how the tablet in question will behave in

vivo. Variations in tablet properties cause variation in disintegration behaviour. While the

standardised disintegration analysis results can be used to differentiate the in vitro behaviour

between various tablets, no information as to why this happens is gained as the tests are used

only to determine whether or not the tablet is suitable for its purpose. An improved

understanding into tablet disintegration could help to provide a more knowledge-based

approach to the research and development of tablet formulations.

The aim of the present research is to gain a better understanding of tablet disintegration

using a particle imaging approach. A purpose-built flow cell was employed capable of on-line

observation of tablet disintegration, which can give information attaining to the changing

tablet dimensions and the particles released with time. This additional information will

improve the understanding of how different materials and process parameters affect tablet

disintegration. The disintegration behaviour of different tablets was observed to ultimately

develop a predictive model that could be applied to future formulations.

Images obtained from the flow cell after being processed, showing the tablet and particles

released at a = 1 sec, b = 1092 sec and c = 1944 sec after dissolution

130. AN EXPERIMENTAL STUDY OF DROPLET-PARTICLE

COLLISIONS

Sandip K. Pawar1, Filip Henrikson1, Giulia Finotello1, Johan T. Padding1, Niels

G. Deen1, Alfred Jongsma2, Fredrik Innings2 & J.A.M. Kuipers1

1 Multiphase Reactors Group, Dept. Chemical Engineering and Chemistry, Eindhoven, NL

2 Tetra Pak CPS, Heerenveen, NL


When spray drying a liquid slurry such as milk, collisions between droplets, partially dried

particles and completely dry particles are important because coalescence, agglomeration and

breakup events influence the size and morphology of the produced powder. When modelling

such a spray drying process, it is therefore important to be able to predict the outcomes of

individual binary collisions. Both binary dry particle collisions and binary droplet collisions

have individually been thoroughly researched over the years due to their widespread

occurrence. The importance of understanding binary particle-droplet collisions has been

emphasized more recently, but available studies are limited. To produce and record particle-

droplet collisions, an experimental setup that enables synchronized release of both a particle

and a droplet was used. One single hanging droplet was released from above onto a particle

that initially was held in place by vacuum suction. A high speed camera was synchronised

with the setup, and recorded the collisions. Image files were then analysed in Matlab to find

velocities and sizes of the particle and droplet before and after impact. The contrast of particle

and droplet against the illuminated background was a key factor in succeeding with this.

Different collision outcomes were identified as either agglomeration (merging), where the

whole droplet would stick to the surface of the particle, or a stretching separation (breaking),

where the droplet collides with the particle in an oblique position and stretches out until a part

of the droplet detaches from the liquid sticking to the particle. The formation of satellite

droplets, i.e. droplets with a radius significantly smaller than the leaving droplet was also

detected. The relation of these collision outcomes to impact conditions such as Weber number

and impact parameter was reviewed and put into regime maps.

131. KINETICS OF IMMERSION NUCLEATION DRIVEN BY

SURFACE TENSION

Kate Pitt1, Rachel Smith1, Michael J Houslow1, James D. Litster2

1 University of Sheffield, Sheffield, UK

2 Purdue University, West Lafayette, IN 47907, USA


Nuecleation is the first stage in any granulation process. Where the liquid drop size is large

compared the primary particle size, immersion or penetration nucleation will occur. In

immersion nucleation, particles surround a drop are drawn into the drop by surface tension or

other mechanisms. Similarly, nuclei may be formed by penetration of a drop into a static or

moving powder bed surface driven by capillary pressure. We know that the nucleation

process is critical to good liquid distribution and ultimately the whole granulation process.

However, most models of wet granulation neglect the kinetics of this nucleation process

completely. Hounslow, Oullion and Reynolds (2009) proposed a kinetic model for immersion

nucleation driven by surface tension suitable for inclusion in a population balance framework.

However, there is no experimental data available with which to validate this modelling

approach.

In this paper, the kinetics of the penetration of single drops into static powder beds are

carefully measured. Drops of model liquids (aqueous HPMC solution and silicone oil) are

placed on static powder beds of zeolite and lactose. Nuclei granules are carefully excavated

at different times and the change in granule mass with time is measured. In all cases, after an

initial adjustment period, the granule mass increases with the square root of time to a

maximum granule size at a time 𝑡𝑚𝑎𝑥 as predicted by Hounslow’s model (Figure 1). The

corresponding critical packing fraction is a function of powder type only. The measured

effect of primary particle size, liquid viscosity and surface tension on nucleation kinetics are

also well predicted by the model. However, the kinetics of the process are one to two orders

of magnitude slower than the immersion nucleation model predicts. This implies that there is

significant secondary migration of liquid within the bed after the drop had fully penetrated the

powder. This secondary nucleation stage may make an important contribution to liquid

distribution and granule growth kinetics in granulators.

Figure 1. Normalized nucleation kinetics for all systems studied. Granule mass increases with

𝑡1/2 until 𝑡𝑚𝑎𝑥


132. MOVEMENT OF SECONDARY IMMISCIBLE LIQUID

WITHIN A SUSPENSION USING X-RAY CT

Syed F. Islam1, Steve Whitehouse2, Ramana V. Sundara2, Tim O. Althaus2,

Stefan Palzer3, Michael J. Hounslow1 & Agba D. Salman1

1 Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, S1 3JD, UK

2 Nestlé Product Technology Centre, Haxby Road, York, YO31 8TA, UK



Many food products are composed of suspensions containing hydrophilic particles within a

continuous hydrophobic phase. An example of this type of product is peanut butter spread.

Extensive work has been reported on the effects of rheological properties of suspensions with

the addition of small quantities of a secondary immiscible liquid [1]. However, how the

secondary liquid propagates initially and then redistributes over long timescales during static

storage requires further research to be fully understood.

The movement of the secondary liquid after addition was tracked using a non-invasive and

non-destructive technique of X-ray CT in a qualitative manner. These scans were then further

processed quantitatively to look at the change in dimensions of the secondary liquid as it

moves throughout the suspension.

[1] E. Koos and N. Willenbacher, Capillary Forces in Suspension Rheology, Science, 331(6019)

(2011) 897-900.

133. TWIN SCREW WET GRANULATION: EFFECT OF TYPES

OF POWDERS

Ranjit M. Dhenge1, Sushma V. Lute1, Chalak S. Omar1, Mohammed F. Saleh1,

James J. Cartwright2, Michael J. Hounslow1 & Agba D. Salman1



2 GSK, Third Avenue, Harlow, Essex, CM19 5AW, UK


Continuous twin screw wet granulation has recently become a method of choice for the

granulation of powders in the pharmaceutical industry. It provides several advantages; high

throughput, reduced time and cost and thereby increased profitability, over the conventional

batch granulation techniques such as high shear granulation and fluidised bed granulation. So,

by all means the primary aim is to produce the desired quality granules with efficiency. But

producing desired quality granules requires thorough understanding of the mechanism of the

granule production within the granulator. The research published so far highlighted the effects

of process and formulation parameters on the granules properties. However, how different

types of powders used in the pharmaceutical industry perform during the twin screw

granulation has received limited attention. The present research is focused on understanding

the granulation mechanism of range of powders.

134. ENGINEERING PLASTICITY MODEL OF ROLL

COMPACTION

James Andrews1, Michael J. Adams1, Chuan-Yu Wu2,

Gavin Reynolds3 & Ron Roberts3

1 School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.

2 Department of Chemical and Process Engineering, University of Surrey, Guildford GU2 7XH, UK

3 Pharmaceutical Development, AstraZeneca, Macclesfield, Cheshire, SK10 2NA, UK.


The well-established theory developed by Johanson provides a useful theoretical

framework for analysing roll compaction and it predicts the nip angle and pressure profile in

the nip region. However, it is limited in several important respects:

it assumes that the maximum pressure occurs at the minimum gap, but there is

mounting experimental and numerical evidence that generally this is not the case;

the velocity field is assumed to be uniform across any plane between locations of

equal angles and thus the stress field is assumed to be uniaxial whereas in practice

there is a maximum in the flow rate in the centre of the compaction zone and this

must involve shear components of the stress field;

the model does not account for the reduction in the pressure with increasing roll

speed;

the pressure is under-predicted by a factor of about two.

The above limitations have been overcome by developing and implementing a novel

analytical model based on theories employed in the field of engineering plasticity for

applications to metal forming. A particular advantage of the model is that more realistic stress

(frictional) rather than kinematic (slip) boundary conditions and also inhomogeneous rather

than uniform feed pressures may be used as inputs. All parameters introduced can be

determined experimentally using conventional equipment for powders. The robustness of this

model has been validated using experimental data for microcrystalline cellulose (MCC) and

dicalcium phosphate dehydrate (DCPD) obtained with an instrumented roll compactor. A

considerably more accurate prediction of the pressure distribution was obtained compared

with that from Johanson’s theory in terms of both the pressures (with an error less than 10%)

and the angular location of the maximum pressure. It also correctly predicted the trends in

experimental data obtained as a function of roll speed.


135. MAKING INDIVIDUAL PARTICLE INTERACTIONS IN

PRESSURE AGGLOMERATION OF AMORPHOUS FOOD

POWDERS ACCESSIBLE

Christine I. Haider1 , Tim Althaus2, Gerhard Niederreiter3, Stefan Palzer4,

Michael J. Hounslow1, Agba D. Salman1



2 Nestlé PTC York, Haxby Road, York, YO31 8FZ, UK

3 Nestlé PTC Orbe, Route de Chavornay 3, 1350 Orbe, Switzerland

4 Nestlé Headquarters, Avenue Nestlé, 1800 Vevey, Switzerland


Many dehydrated products in the food industry can be found in powder form and often

exhibit an amorphous structure. To improve the handling of these products, they are often

agglomerated by applying external pressure to force the individual powder particles into

contact and make them adhere to each other or even sinter together.

Numerous studies have been conducted to assess this agglomeration behaviour of

hygrosensitive amorphous bulk powders under pressure and the resulting agglomeration

result. In this way, valuable findings on multi-particle level could be generated for industrial

applications. However, it remains widely unknown what exactly happens in individual

particle contacts and which contact mechanisms act to create a stable compact with a defined

internal structure and porosity. Consequently, this study is focussed on two important

knowledge building blocks to assess interparticle bonding strength and deformation/flow

behaviour of the particle material: the experimental exploration of particle contact

mechanisms as well as their theoretical description using profound knowledge in material

science of amorphous substances. Based on the obtained information, useful data for

modelling approaches was generated as well as a qualitative and quantitative guide for the

adjustment of process parameters to trigger desired contact mechanisms and influence their

kinetics within a particle assembly under external pressure.

For the experimental studies, an amorphous model material (maltodextrin DE 21) with

high relevance as a food ingredient was chosen as a basis to produce spherical particles in a

size range of 1-1000 µm following a specially developed emulsion technique. Pairs of the

obtained smooth spheres were exposed to strain-controlled contact tests in a novel

Micromanipulation Particle Tester (MPT) device as well as to stress-controlled interaction

studies using an Atomic Force Microscope (AFM). Both devices made it possible to control

and adjust the most relevant process conditions force/distance, contact holding time, velocity

on the particle approach/retract path as well as temperature and humidity to account for the

changing rheological character of hygrosensitive maltodextrin as a function of the

environmental conditions. In the MPT studies, particles larger than 500 µm were tested,

which made video imaging of the contact zone and deformation kinetics possible.

Furthermore, force relaxation tests on particles could be conducted with this device to assess

the changing mechanical behaviour of maltodextrin in its glass transition. For the AFM tests,

smaller particles in the low micrometre range were employed for high precision force

spectroscopy. Finally and in dependence of the environmental conditions, theoretical models

could be identified, which describe the experimental findings for changing test parameter sets

very well. These were then used for the set-up of contact zone and cohesion regime charts,


which - when applied to pressure agglomeration of bulk powders - can give guidance for a

beneficial choice of process conditions to control compact porosity and stability.

136. FLUIDIZED BED COATING CONTROL BY IN-LINE

PARTICLE SIZE MEASUREMENT

Dimitri Wiegel1, Guenther Eckardt2, Michael Jacob3, Mario Scharmer4, Ingo

Schellenberg4 & Bertram Wolf1

1 Department of Applied Biosciences and Process Engineering, Anhalt University of Applied

Sciences, Strenzfelder Allee 28, 06406 Bernburg, Germany

2 Parsum GmbH, Reichenhainer Straße 34-36, 09126 Chemnitz, Germany

3 Glatt Ingenieurtechnik GmbH, Nordstraße 12, 99427 Weimar, Germany

4 Institute of Bioanalytical Sciences, Anhalt University of Applied Sciences, Strenzfelder Allee 28,

06406 Bernburg, Germany


In-line particle size measurement during fluidized bed coating opens the advantage of

continuous process control compared to time consuming probe sampling and separate particle

size analysis. A Spatial Filter Velocimetry probe (Parsum GmbH, Chemnitz, Germany) was

installed directly into the process chamber of the laboratory fluidized bed apparatus GPCG

1.1 (Glatt Ingenieurtechnik GmbH, Weimar, Germany) between Wurster partition and inner

chamber wall. Large initial pellets of microcrystalline cellulose were coated with a model

drug substance and in a consecutive step with different amounts of a protective polymer.

The coating process with the model substance as well as the polymer was stable and

reproducible. The coated pellets were received as homogeneous product, agglomeration was

never detected. The integrity of the polymer film was investigated by in vitro-release. Increase

of the polymer film thickness led to prolonged lag-time. Determination of the thickness of the

coating layers was performed by microscopic investigation of thin pellet sections.

During the whole coating process the in-line particle size measurement with the SFV probe

was possible and gave the expected particle size increase with increasing coating amount.

Coincidence error was avoided by definition of a suitable particle size fraction. Apprehended

overload of the measuring volume of the probe was never detected. The particle size

distribution showed insignificant fine particle amounts deriving from abrasion and perhaps by

a low tendency of spray drying in the fluidized bed coating process. For control, the particle

size distribution was measured by an off-line optical method (Camsizer®, Retsch GmbH,

Haan, Germany). The mean particle size values were in good agreement with those of the

SFV probe using the chord length as measuring parameter in both cases. The in-line particle

size measurement is a useful Process Analytical Technology tool in the fluidized bed coating

process.

Particle size measuring probe (Parsum GmbH) installed into the fluidized bed coater

137. A PROPOSAL FOR A DRUG PRODUCT MANUFACTURING

CLASSIFICATION SYSTEM (MCS) FOR ORAL SOLID DOSAGE

FORMS

Michael Leane1, Kendal Pitt2 & Gavin Reynolds3

1 Bristol-Myers Squibb, Reeds Lane, Moreton, CH46 1QW, UK

2 GlaxoSmithKline, Priory St., Ware, SG12 0DJ, UK

3 AstraZeneca, Silk Road Business Park, Charter Way, Macclesfield, SK10 2NA, UK


The Manufacturing Classification System (MCS), proposed here is intended as a tool for

scientists to rank the feasibility of different processing routes for the manufacture of oral solid

dosage forms, based on selected properties of the Active Pharmaceutical Ingredient (API) and

the needs of the formulation, [1]. The MCS will have many applications in pharmaceutical

development, in particular, it will provide a common understanding of risk by defining what

the “right particles” are (i.e. the physical properties of the particles that have been identified

for each process route), enable the selection of the best process, and aid subsequent transfer to

manufacturing. The ultimate aim is one of prediction of product developability and

processability based upon previous experience. The four classes proposed are:

Class 1: Direct Compression

Class 2: Dry Granulation

Class 3: Wet Granulation

Class 4: Other Technologies.

This proposal is intended to stimulate contribution from a broad range of stakeholders

across the pharmaceutical sciences to develop the MCS concept further and apply it to

practice. In particular, feedback is sought on what API properties are important when

selecting or modifying materials to enable an efficient and robust pharmaceutical

manufacturing process. The proposal aims to provide a frame of reference for level of risk vs.

process type. Two concepts in particular have been expanded upon: the first is to define API

developability. The second consideration is drug loading: as this increases, API properties

have an increased influence on the formulation properties and processability. The team is

proposing the use of percolation (impact) levels, which may vary across different attributes

and parameters, to quantify this risk.

[1] Michael Leane, Kendal Pitt, Gavin Reynold. A Proposal for a Drug Product Manufacturing

Classification System (MCS) for Oral Solid Dosage Forms, Powder Development and Technology

(2014). ( doi/abs/10.3109/10837450.2014.954728)

http://informahealthcare.com/doi/abs/10.3109/10837450.2014.954728

138. UNDERSTANDING AND PREVENTING

AGGLOMERATION IN FILTER DRYING PROCESS

Hong Lee Lim1, Karen P. Hapgood1 & Brian Haig2

1 Monash Advanced Particle Engineering Laboratory, Department of Chemical Engineering, Monash

University, Wellington Road, Clayton, Victoria, 3800, Australia,

2 GlaxoSmithKline, Princes Highway, Port Fairy, Victoria, 3280, Australia


Agitated Filter Dryers (AFD) are one of the most commonly used equipment items during

the manufacture of active pharmaceutical ingredients (API) which incorporates both the

filtration and drying processes in a single unit operation. However, it is also well known for

its susceptibility to agglomeration or “balling” issues which can cause downstream processing

problems. Previous work to minimize the extent of agglomeration has not yet understood the

fundamental mechanisms. Furthermore, powders may exhibit unique “personalities” where a

general or universal solution to minimize the formation of lumps does not exist. This study

aims to understand the possible mechanisms that may lead to the agglomeration phenomena

during an agitated filter drying process. Through comprehensive understanding of the

underlying agglomeration mechanisms, the extent of undesired agglomeration for a particular

powder system may be controlled using suitable mitigation method.

The drying behavior of free-flowing sodium bicarbonate, cohesive calcium carbonate as

well as an API intermediate with high balling tendency will be investigated using a lab-scale

AFD. Using Design of Experiment (DoE) as a tool, the influence of some of the key process

parameters (such as agitation speed, drying temperature, dryer fill volume and filtration

period) on the formation of lumps were studied. Other possible root causes of agglomeration

such as condensate drips on powder bed, initial drying moisture content and crystal properties

were investigated as well. Various characterization techniques were also carried out to

determine the compressibility, surface morphology and other important particle properties in

order to strengthen the understanding on the agglomeration behaviour while also identifying

other possible major contributors to this phenomenon.

Preliminary results have shown that by controlling the process operation, the formation of

lumps may be controlled even though the complete elimination of agglomerates is not

achieved. On the other hand, the dripping of condensate due to saturated environment was

found to contribute to the formation of lumps. The reduction of initial drying moisture content

beyond the critical moisture level through extended blowdown period was able to minimize

the agglomeration but only to a limited extent.

139. CREATING TUNEABLE AGGLOMERATES VIA 3D

PRINTING

Ruihuan Ge1, Mojtaba Ghadiri2 & Karen Hapgood1

1 Monash Advanced Particle Engineering Laboratory, Department of Chemical Engineering, Monash

University, Clayton, Victoria 3800, Australia

2 Institute of Particle Science and Engineering, University of Leeds, UK


To improve the process design and end-product quality, it is essential to investigate the

breakage behavior of agglomerates. Discrete Element Method (DEM) modelling is commonly

used but is limited by the lack of identical, controlled agglomerates to test and validate simple

models, let alone replicate the complex structure of real industrial agglomerates.

This paper presents a novel 3D printing production method of test agglomerates with

defined properties. Agglomerate models with different sizes and structures were designed

using Solidworks 2014 software and printed by an Object500 Connex 3D printer. During the

printing process, different digital materials were used to print the particles and the inter-

particle bridges, allowing infinite combinations of bond strength, particle strength and

agglomerate structure to be tested. Several different model agglomerates were printed at

varying scales, using rigid polymer to print the spherical particles and ductile polymer to

produce the inter-particle bridges. The surface roughness and printing accuracy of printed

agglomerate models were assessed by atomic force microscopy (AFM) and scanning electron

microscopy (SEM). Preliminary compression tests were performed to compare the breakage

behavior of printed agglomerates with different bond strength and at different scales. This 3D

printing technique will allow more rigorous testing of agglomerate breakage models.

Complex ball-like agglomerate model (Left: designed agglomerate, Right: 3D printed

agglomerate)

140. USE OF FOAM IN TOP-SPRAY FLUIDIZED BED

GRNULATION: EFFECT OF VARIABLES ON GRANULES

QUALITY ATTRIBUTES

Vinita Kale, Kalyan Wagh & Abhay Ittadwar

Department of Pharmaceutics, Gurunanak College of Pharmacy, Nari, Nagpur, Maharashtra, India

E-mail: [email protected]; [email protected]

Fluidized bed granulation is common unit operation for forming granules used in various

application areas like pharmaceuticals, agrochemicals, food and dairy industry. The high dose

API under study has poor granulating and tableting properties and hence poses difficulty to

achieve balance between friability, granule size and disintegration. To address the above

challenges a new granulation process was employed whereby liquid binder was added as

aqueous foam, of food grade saponin, and top-sprayed on to fluidized bed of powder. The

experiments were carried out to examine the effects of various process parameters on the

granules produced using Plackett Burman and Box-Behnken design of experiments. Influence

of amount of foam binder, volume of binder solution and binder solution flow rate were

initially studied to establish operational values for these parameters. This was followed by

investigation on the effect of inlet airflow rate, inlet air temperature, atomization pressure and

drying time on granule properties. It was found that the amount of binder solution had

positive correlation with granule size and % lumps but negative correlation with size

distribution and Hausner ratio of granules. Best batch of product was received with inlet air

temperature between 55-650C, atomization pressure 0.65- 0.9 psi and drying time between 5-

7 min. The whole granulation process was stable and reproducible and the data can be used to

predict parameter values for processing at manufacturing scale.

141. EFFECT OF COLLOIDAL SILICA DIOXIDE ON

RHEOLOGICAL PROPERTIES OF COMMON

PHARMACEUTICAL EXCIPIENTS

Diana Majerová1, Lukáš Kulaviak2, Marek Růžička2 & František Štepanek3

1 Department of Organic Technology, Institute of Chemical Technology, Technická 5, Prague,

160 00, Czech Republic

2 Institute of Chemical Process Fundamentals of the ASCR, Rozvojová 2/135, Prague,

165 02, Czech Republic

3 Department of Chemical Engineering, Institute of Chemical Technology, Technická 3,

Prague, 160 00, Czech Republic


Pharmaceutical tablets are manufactured through a series of batch steps finishing with

compression into a form using a tablet press. The knowledge of flow (bulk, dynamic, shear)

properties of raw excipients and their mixtures is essential to predict behaviour during

blending, compression, handling or leaving in storage. Lubricants are added to the powder

mixture prior to the tableting step to ensure that the tablet is ejected properly from the press.

The addition of lubricants also affects tablet properties and can affect the behaviour of the

powder mixture.

In this work, rheological properties of four common excipients (pregelatinized maize

starch, microcrystalline cellulose, crosscarmellose sodium and magnesium stearate) were

studied by FT4 Powder Rheometer, which was used for measuring compressibility index by

vented piston and flow properties of powder by rotational shear cell. After the initial set of

measurements, two excipients (pregelatinized maize starch and microcrystalline cellulose)

were chosen and mixed, in varying amounts, with anhydrous colloidal silicon dioxide (Aerosil

200) used as lubricant. The bulk (conditioned and compressed densities, compressibility

index), dynamic (basic flow energy) and shear (friction coefficient, flow factor) properties

were determined to find an optimum ratio of the lubricant. Simultaneously, the particle size

data were obtained using a low-angle laser light scattering (LALLS) system and the scanning

electron microscopy was performed in order to examine the relationship between the

rheological properties and inner structure of the materials and their binary mixtures. The

optimum of flowability was found for the mixtures, but also it has also been seen that

additional phenomena are behind the flowability of binary mixtures (blends).


142. EFFECT OF VARYING VOLUME OF A SECONDARY

IMMISCIBLE LIQUID ON THE MOVEMENT WITHIN A

SUSPENSION

Syed F. Islam1, Steve Whitehouse2, Ramana V. Sundara2, Tim O. Althaus2,

Stefan Palzer3, Michael J. Hounslow1 & Agba D. Salman1


2 Nestlé Product Technology Centre, Haxby Road, York, YO31 8TA, UK



Numerous food products are composed of suspensions containing hydrophilic particles

within a continuous hydrophobic phase. An example of this type of product is peanut butter

spread. A key attribute of these types of suspension is the highly hygroscopic nature of the

solid phase within the system. The rheological properties and physical appearance of

suspensions can change substantially with the addition of small quantities of a secondary

immiscible liquid. This has been attributed to the formation of liquid bridges between the

solid particles and secondary liquid.

Model suspensions were prepared of hydrophilic particles within a continuous hydrophobic

phase. Different volumes of secondary immiscible liquid were added, and the movement of

this with time was monitored. Also, how the droplet spreads with time was also quantified

with time.

143. UNDERSTANDING PHARMACEUTICAL POWDER

BLENDING - IRON OXIDE TRACER BEHAVIOUR AND

DIFFERENT EXCIPIENT POWDERS

Kahlil Desai1, Karen Hapgood1, David Barling2, Peter Stewart2, David Morton2

1 Monash Advanced Particle Engineering Lab, Department of Chemical Engineering, Monash

University, Clayton , VIC, Australia

2 Monash Institute of Pharmaceutical Science, Monash University, Royal Parade, Parkville, VIC,

Australia


Blending of one or more powders is critical for many pharmaceutical powders, including

formulations used for Dry Powder Inhalers. Recent work [1] demonstrated that the colour

change of an iron oxide tracer powder can be used to observe the mixing process and is linked

to the quality of the mixing .The study used a 99wt% high purity Ferroxide® iron oxide in a

range of lactose powders, and showed two key mixing stages linked to the total mixing energy

applied and to the level of dispersion and deagglomeration of the tracer powder.

This study extends the previous work by investigating whether the technique also can be

used to examine the mixing behaviour of several common excipient powders (mannitol,

MCC, methyl cellulose). In addition, four different iron oxides grades were used to explore

the behaviour of different colour oxides while blending a bulk lactose powder. For each

experiment, 1 wt% of the tracer powder was added to 2-3kg of the bulk excipient and blended

in a 5L Key high shear mixer and samples were taken as a function of mixing time and their

colour readings in the CIELch spectrum were recorded. The results showed that different

excipient powders show a similar overall behaviour pattern although the absolute colour

values varied for each excipient as expected. Only the red iron oxides showed the ability to

change hue as mixing time/intensity increased - the yellow and black oxides showed very

little or no change in hue. The two grades of red iron oxide had different CIELch spectrum

values because of their overall colour but also due to their morphology and size. The results

show that the use of coloured tracer powder to track the progression of powder blending can

be applied to a wide range of powders, and that more than one grade of red iron oxide

displays the required change in hue. Further work is underway to understand the

fundamentals of the hue change and determine whether there is a direct link between the

blending colour endpoint and the final product performance.

[1] D. Barling, D.A.V. Morton, K. Hapgood, Pharmaceutical dry powder blending and scale-up:

Maintaining equivalent mixing conditions using a coloured tracer powder, Powder Technology,

(2014).

144. NOVEL ELECTROSTATIC IONIZER FOR CHARGED

POLYPROPYLENE GRANULES

Kwangseok Choi1, Tomofumi Mogami 2, Teruo Suzuki 2 & Mizuki Yamaguma 1

1 Japan National Institute of Occupation Safety and Health, 1-4-6 Umezono Kiyose, Tokyo, Japan

2 Kasuga Denki, 2-4 Shinkawasaki, Saiwai, Kawasaki, Kanagawa, Japan


The polymer granules have been commonly used in powder handling processes. As the

charged polymer granules fills the large storage silo, the charge amount inside the silo

accumulates. This charging phenomenon often leads to incendiary electrostatic discharges in

the silo.

In this work, in order to prevent and mitigate electrostatic charges on polypropylene

granules (300 kg, 2 to 3 mm) during silo loading, the novel electrostatic ionizer has

developed. The novel ionizer consists of one pair of corona needle electrodes situated within a

grounded nozzle shield, an electrode supports, a DC high-voltage power source, a punched

plate, and a slender tube 8 mm in diameter for air supply, an air compressor, a fully automatic

air dryer. To one of the corona needle electrodes, DC + 7 kV was applied with a DC high

power source. To the other, DC - 7 kV was applied. The performance evaluation of the novel

ionizer was conducted in a full-size pneumatic powder transport facility. The Four arranged

novel ionizers in a circular line along the outside wall of the connecting pipe (stainless steel;

diameter, 0.1 m; length, 0.25 m) were attached to the end of the loading pipe. As the

experimental result, it is noteworthy that specific charge, q/m of the falling polypropylene

granules before using the four arranged novel ionizers was -9.0 C/kg. The q/m for the four

arranged ionizers was -1.5 C/kg. Namely, the specific charge of polypropylene was clearly

decreased by approximately eighty-five percent with the novel ionizer. This is expected to be

very useful and reliable to prevent and mitigate problems originating from electrostatic

charges on polymer granules.

Novel electrostatic ionizer used in this study

145. DEVELOPMENT AND CHARACTERISATION OF SLAKED

LIME GRANULES FOR CHEMISORPTION IN

DESULPHURATION REACTORS

Erik Nordenswan1, Annica Lindfors1, Nenne Nordström1 & Abhay Bulsari2

1 Nordkalk Oy Ab, Skräbbölevägen 18, 21600 Pargas, Finland

2 Abhay Bulsari, Ab Nonlinear Solutions Oy, Turku, Finland

E-mail: annica@[email protected]

Recently imposed limitations of sulphur emission of vessels increases the interest in

development of efficient solutions for sulphur removal from flue gases. Chemisorption

reactors (dry scrubbers) with slaked lime granules have the advance that they do not produce

liquid waste which is expensive to treat on the vessels. Slaked lime granules remain solid and

the spent granules can be unloaded at ports and used for other purposes. Besides, the reaction

can be carried out in compact reactors.

Performance of such granules is a multidimensional issue. However, it becomes necessary

to find methods to characterise the granules for comparing granules of different suppliers,

different sizes, different porosities, different prices, etc. so that the performance and

eeconomy in full scale applications can be guaranteed.

In case of chemisorption of sulphur dioxide by slaked lime granules, it is highly desirable

that they have a large chemisorption capacity, and that the rate of chemisorption is fast

enough. Chemisorption capacity at infinite time is one important theoretical measure, but for

industrial purposes, more realistic measures are needed. Similarly, the initial chemisorption

rate is not a sufficient measure of how fast the uptake of sulphur dioxide is.

In this work, experiments were carried out with a variety of granules of different sizes with

different incoming sulphur dioxide concentrations at different temperatures with a pilot scale

reactor, and a few practical performance measures of chemisorption capacity and rate were

calculated from the experimental results. Nonlinear models were then developed for

predicting those measures.

The tests also relate the granulation process variables with the performance characteristics

of slaked lime granules from experimental data.

146. INNOVATIVE GRANULATED MATERIALS FROM

INDUSTRIAL AND ORGANIC WASTES AS SORBENTS FOR

WASTEWATER TREATMENT

Evgenia Iakovleva1, 2, Mika Sillanpää1, Philipp Maydannik1, Stephen Allen2,

Ahmad B. Albadarin2,3 & Chirangano Mangwandi2

1 Chemtech, Laboratory of Green Chemistry, Lappeenranta University of Technology, Sammonkatu

12, 50130, Mikkeli, Finland

2 Innovative Molecular Materials (IMM) Group, School of Chemistry and Chemical Engineering,

Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast, BT9 5AG, UK

3 University of Limerick, Department of Chemical and Environmental Science, Ireland


Innovative granulated materials from coffee waste, limestone and sulphate tailings were

produced and used for waste water treatment. Experiments proved efficiency of sorbents from

coffee and limestone in neutralisation acid mine drainage (AMD) (from 1.5 to 6 pH) and

removal of metal ions (Fe, Cu, Zn and Ni), while adsorbents from sulphate tailings were

efficient for cyanides removal.

In this work, novel sorbents with different composition and various bunches were

compared. For industrial application of these granules, low wettability and high strength are

extremely important. Various binders such as poly vinyl acetate (PVA), and ethyl acetate

(EA), as well as various combinations of materials have been used to improve these

parameters. It was found that EA increases the granule strength and facilitates preparation of

granules with larger size in comparison with the PVA. The sorption capacity of granules was

examined by removal of acidic (methylene blue (MB)) and alkaline (Orange II (OII)) dyes

from single and multi-solutions. The maximum efficiency removal for MB and OII was 95%

and 40%, respectively.

147. AGGLOMERATION OF FINE COAL USING A HIGH

VISCOSITY WATER-IN-OIL EMULSION

Kim van Netten, Roberto Moreno-Atanasio & Kevin P. Galvin

Centre for Advanced Particle Processing and Transport, Newcastle Institute for Energy and Resources,

University of Newcastle, Callaghan, NSW 2308, Australia


Selective agglomeration can be applied to an aqueous suspension of coal and mineral

particles as a means of retrieving the valuable coal. Using a pure oil binder, such as diesel, the

fine coal can be formed into a high quality, granular product and separated from the unwanted

mineral matter. However, the use of the pure oil also comes at a relatively high cost and this

cost prohibits commercial implementation of this highly effective process. In this work a new,

economic binder was introduced. This binder consisted of a high internal phase water-in-oil

emulsion which was nominally 95 vol% water and 5 vol% organic. This type of binder was

selected as it possessed the hydrophobic surface functionality of oil while the space filling

functionality of the binder was primarily satisfied by the dispersed water droplets within the

emulsion. In this way, the amount and cost of the oil required in the process was reduced.

More specifically, the application of this emulsion binder in the fine coal agglomeration

process led to a 10-fold reduction in the organic liquid dosage required to achieve

agglomeration as compared to tests in which pure oil was used. It was also observed that the

agglomeration time required when using the emulsion binder was one order of magnitude less

than required when using a pure oil binder. Only 3 s was required for complete agglomeration

of the fine particles when using the emulsion binder therefore, indicating the action of a

different agglomeration mechanism with respect to the case of pure oil. This variation in the

agglomeration mechanism was considered to result from the five orders of magnitude

difference in the viscosity of the two binders. That is, it seems that the extremely high, > 100

Pa s, viscosity of the emulsion binder has caused an increase in the collection efficiency and a

modified solid/binder interaction. Overall, the application of this new binder has resulted in a

rapid and reduced cost coal agglomeration process and has, therefore, improved the viability

of beneficiating fine coal.


148. EFFECTS OF BINDER ADDITION POLITICS ON THE WET

AGGLOMERATION PROCESS

Silvia Nalesso1, Erica Franceschinis2, Nicola Realdon2 & Andrea C. Santomaso1

1 APTLab-Advanced Particle Technology Laboratory Department of Industrial Engineering

University of Padova, via Marzolo 9, 35131 Padova, Italy

2 PharmaTeG-Pharmaceutical Technology Group- Department of Pharmaceutical and

Pharmacological Science, University of Padua, via Marzolo 5, 35131 Padova, Italy


Wet agglomeration is achieved by adding a liquid in an agitated powder mixture. The

liquid is often pure water or a dispersion of a solid binder (typically a polymer) in water to

enhance the agglomeration between particles. The process is carried out in a granulator, which

is designed to obtain a good contact between solid and liquid.

Monitoring the agglomeration process and study the kinetics of the process are necessary

to understand the basic mechanisms of agglomeration. A way to perform this tasks is the

direct observation of the granules growth with a sensor that takes digital images of the powder

bed during all the process. Images can then be processed by digital image analysis to obtain

information about granules size. In particular texture analysis (TA) can be an interesting tool

since image texture contains the information on the granules size. In particular from the

histograms of grey levels intensities of the images it is possible to get information on the

contrast which is related to the average size of the granules.

In this work texture analysis was used in order to study the granulation kinetics of a

system constituted by cellulose microcrystalline (MCC) and xanthan gum (XG). In particular

XG has been added in two different ways: as liquid (pre-dispersed in the water) or as solid

(pre-mixed in the MCC). Granulation experiments were performed in an orbital mixer.

The experiments have shown that, to obtain granules with the same size, a much larger

amount of XG (up to 10 time) was required when pre-mixed in solid form. From kinetics

analysis it appeared that the growth was also faster in this case even if with an initial delay,

probably due to the hydration time of the polymer. Solid binder hydration indeed is a missing

step in the case of pre-dispersion in water. Because of the larger amount of solid binder when

pre-mixed in MCC, the final granules were also mechanically more stable and a good

agreement between texture analysis and sieve analysis was always found independently of the

liquid binder addition rates. Instead in the case of XG pre-dispersed in water the agreement

between TA and sieving was found only for high binder addition rates, suggesting that with

low XG amount the binder addition rate can impact on the strength of the final granules as can

be deduced by the final PSDs which resulted modified by the sieving operation.

149. VOLCANIC ASH AGGREGATION IN THE LAB – CAN WE

MIMIC NATURAL PROCESSES?

Sebastian B. Mueller1, Ulrich Kueppers1, Michael Jacob2, Paul Ayris1, Donald B.

Dingwell1, Melanie Guttzeit2, Ulrich Walter2

1 Ludwig-Maximilians-Universität München (LMU), Department of Earth and Environmental

Sciences, Theresienstrasse 41, 80333 München, Germany

2 Glatt Ingenieurtechnik GmbH, Nordstrasse 12, 99427 Weimar, Germany

Explosive volcanic eruptions release large amounts of particles into the atmosphere.

Volcanic ash, by definition pyroclasts smaller than 2 mm, can be distributed around the globe

by prevailing winds. Ash poses hazards to aviation industry by melting in jet turbines, to

human health by entering respiration systems and to society by damaging infrastructure.

Under certain circumstances, ash particles can cluster together and build ash aggregates.

Aggregates range in size from few mm to few cm and may exhibit complex internal

stratigraphy. During growth, weight, density and aerodynamic properties change, leading to a

significantly different settling behaviour compared to individual ash particles. Although ash

aggregation has been frequently observed in the geologic record, the physical and chemical

mechanisms generating the aggregates remain poorly understood. Based on chemical and

physical data of natural ash aggregates, we have designed experiments using the ProCell Lab

System® of Glatt Ingenieurtechnik GmbH, Germany. In this device, a continuous fluidized

bed can be applied on solid particles and simulate gas-particle flow conditions as they would

be expected in volcanic plumes or pyroclastic density currents. We use both analogue material

(Na-glass beads) and natural volcanic ash (from the Eifel volcano field, Germany) for our

experiments. As a binder, we apply salts typically observed on volcanic ash and in natural ash

aggregates, such as NaCl, MgSO4, CaSO4 or KCl. During the aggregation experiments, we

further control parameters such as grainsize, specific surface area and concentration of the

starting material, degree of turbulence, temperature and moisture in the process chamber and

the composition of the liquid phase to influence form, size, stability and production rate of

aggregates. We were able to experimentally produce round, unstructured ash pellets up to

5mm in diameter. A detailed textural description highlights the strongly different properties of

single ash grains and ash aggregates. These experiments aim at experimentally constraining

the boundary conditions required for the generation of strong ash aggregates. A better

mechanistic understanding will serve for more adequate ash mass distribution modelling.

150. WET GRANULATION IN A MINI TWIN SCREW

EXTRUDER: EFFECT OF PROCESS AND FORMULATION

VARIABLES ON RESIDENCE TIME DISTRIBUTION AND

GRANULE CHARACTERISTICS

Manuel Kuhs1, Ahmad B. Albadarin1,2, David Egan1, Shaikh Rahamatullah1,

Mark Southern1, Denise Croker1, Gavin Walker1

1Chemial & Environmental Sciences, University of Limerick, Plassey, Co. Limerick, Ireland 2School of Chemical Engineering, Queen’s University Belfast, University Road, Belfast BT7 1NN,

United Kingdom


Wet granulation using a twin screw extruder is a promising continuous processing

technique for granulation of pharmaceutical formulations. Although granulating with more

consistency than a traditional high shear batch mixer, [1] the understanding of the granulation

mechanisms in twin screw granulation is still not complete. A particular concern of the

pharmaceutical industry is the high shear rates imposed on formulations during twin screw

granulation.[2] The effect of these high shear rates on the formulation depends, in part, on the

residence time.

Here we analyse the dependence of the residence time in a mini twin screw granulator on

process parameters (screw speed, powder feed rate, liquid-to-solid ratio, viscosity of

granulating liquid), screw configuration (kneading and/or distributive mixing elements) and

formulation (powder size distribution), and also measure the granule size and shape

distributions (GSSD) corresponding to the different residence times. The formulation, a

mixture of microcrystalline cellulose (different batches from different manufacturers) and

polyvinylpyrrolidone, was granulated in a 9 mm twin screw extruder (Extruder Technologies,

NJ, USA) with a length-to-diameter ratio of 39. Water was used as the granulating liquid, and

its viscosity varied by addition of a lubricant. The resultant GSSD was monitored in-line

using an EyeconTM 3D imaging particle sizer and offline analyses. A high resolution Raman

microscope was used to measure the formulation homogeneity of the granules. The residence

time distribution was measured by adding a small dose of dye into the powder feeding port

during steady state operation, followed by the sampling cup method described elsewhere.[3]

Parameter values were chosen using a factorial design, and the results rationalised to further

elucidate the granulation mechanisms in the different screw regions/screw elements and these

effects on the residence time.

In the future it is envisaged that the same experiments will be performed for multiple

pharmaceutical formulations to evaluate the effect of shear on APIs. Such work is possible

due to the small size of the twin screw granulator employed; a formulation can be granulated

and fully characterised using a few grams of powder.

[1] E.I. Keleb, A. Vermeire, C. Vervaet, J.P. Remon, Extrusion granulation and high shear granulation

of different grades of lactose and highly dosed drugs: A comparative study, Drug Development and

Industrial Pharmacy. 30 (2004) 679–691.

[2] M.R. Thompson, Twin screw granulation - review of current progress, Drug Development and

Industrial Pharmacy. (2014) 1–9. doi:10.3109/03639045.2014.983931.

[3] A.S. El Hagrasy, J.R. Hennenkamp, M.D. Burke, J.J. Cartwright, J.D. Litster, Twin screw wet

granulation: Influence of formulation parameters on granule properties and growth behavior, Powder

Technology. 238 (2013) 108–115.

151. MODELLING OF PARTICLE-AIR INTERACTIONS

DURING FLOW INTO CLOSED CAVITIES

H. Elmsahli, A. Alharbi, R. Baserinia and I.C. Sinka

Department of Engineering, University of Leicester, UK


The flow behaviour of powders into dies is important for pharmaceutical tablet

manufacturing because after a die is filled the quantity and structure of the material “locked”

in place define weight and content uniformity. Die fill, however, presents a particular feature:

as the powder is deposited into a closed cavity, the ambient pressure is increased as more and

more powder is introduced and this opposes flow. The interplay between the granular skeleton

and air creates a dynamic process with unique features which have significant practical

implications.

We present a coupled discrete element (DEM) - computational fluid dynamics (CFD)

model which takes into account 1) the drag force as the particle travels through air and 2) the

influence of particles on air flow. The model prediction is compared with experimental

studies. Unique to this study is the experimental measurement of air pressure evolution in the

die during filling and comparison with the model.

152. FORMULATION AND EVALUATION OF METHACRYLIC

AND POLY (ACRYLIC) ACID MATRIX TABLETS OF

MEBENDAZOLE FOR COLON TARGETED DELIVERY

J.E Okorie, F.N Uba, O.N.C Umeh & S.I Ofoefule

Drug Delivery and Nanotechnology Research Unit (RUNDD)

Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka

410001, Nigeria


A colon targeted mebendazole matrix tablets for once daily administration were formulated

with four polymers. Two methacrylic acid polymers (Eudragit L-100 and Eudragit S®) and

two poly acrylic acid polymers (carbopol 940 and carbopol 941) were used in formulation of

the mebendazole granules and tablets. The Eudragits were used at concentration levels of

10%, 15% and 20% while the carbopols® were used at concentration levels of 5%, 10% and

15%. The granules and tablets were prepared by the wet granulation method and were

evaluated in vitro for flow behavior (for the granules) and for weight uniformity, hardness,

friability, drug content and drug profile studies for the tablets. Erosion rate studies and

medium diffusion rate studies were carried out on the mebendazole tablets in acidified

methanol, pH 6.8 and 7.4. The effects of a super disintegrant, primogel and cellulose acetate

phthalate (CAP) on the release of mebendazole from the matrices were also investigated. The

overall effect of the polymers on the bulk and tapped densities showed that these values for

these parameters were higher for mebendazole granules containing the Eudragits than the

batches containing carbopols. The flow indices based on angle of on repose indicated slight

improvement in the flow of the granules occasioned by the presence of the polymers. Other

indices of flow – Hausner’s quotient and compressibility index indicated good flow for all the

granule batches. The results showed that tablets containing Eudragit® eroded faster in the two

media than tablets containing carbopols®. The Eudragits were found to have higher release

rates than the Carbopols. Carbopol 941 had better release parameters than carbopol 940. It

was also observed that the release of drug from the tablets were relatively higher at pH 7.4

than at pH 6.8 for all the formulations. Primogel increased the rate of release of mebendazole

from all the tablets while CAP exerted retardating effect on the rate of release of the drug

from formulations containing Carbopols. When the release parameters were fitted into

different kinetic models, it was evident that drug release from the tablets followed mixed

order kinetics, while the mechanism of drug released from majority of the formulations was

by fickian diffusion. The release of mebendazole at pH values of 1.2, 6.8 and 7.4 (mimicking

the condition of mouth to colon transit), showed that 66.64% to 73.38% of the drug will

probably be released at the colon. The two formulations containing the Eudragits sustained

the release of mebendazole for up to 14 and 17 h respectively while all the formulations

containing the carbopols sustained the release for up to 24 h. This indicate that though all the

formulations could be utilized as a colon targeted mebendazole formulation for the treatment

of helminthiasis, only the tablets containing Carbopols can be used to formulate a once daily

dosage formulation of mebendazole.


Eyecon in-line integration with a fluid bed

granulator

Captured image of particles during a fliud bed

coating process.

153. APPLICATION OF THE EYECON, AN IN-LINE NON

PRODUCT CONTACT PROCESS ANALYTICAL TECHNOLOGY

TO PERFORM PARTICLE CHARACTERISATION DURING

FLUIDISED BED PROCESSES

Paul Cruise1, Emmet Hogan1, Ian Jones1, Stephen Banahan1, Claudio Cortazzo2,

Joachim Fröhlich2, Lilia Sprich2, Raoul Pila2


2 Glatt GmbH, Process Technology, Binzen, Germany

Fluidised bed processes which include granulation, drying and coating improve particle

properties such as compressibility, flowability and dissolution profiles. The agglomeration of

primary powder particles during fluidised bed granulation produces large aggregate granules.

These granulates have improved bulk properties including flowability and compressibility and

also act to reduce the occurrence of segregation of material during manufacturing processes.

Fluidised bed drying reduces the moisture content of the agglomerates prior to further process

steps. Fluidised bed coating is used to improve the dissolution profile, increase the stability of

a drug and to mask unpleasant tastes. The ability to control fluidised bed processes is

therefore crucial to producing consistent quality product, optimising efficiency, preventing

rejection and reducing production cycle time.

An investigation was conducted to determine the ability of the Eyecon, a process analytical

technology (PAT), to monitor granule growth and reduction during fluid bed granulation and

drying processes. An Eyecon was integrated onto a fluid bed granulator for in-line real-time

image capture, analysis of particles and determination of particle size distribution.

The Study showed that Eyecon could be used to successfully monitor particle size

distribution during the process and successfully distinguish process end points in real time

including particle growth, agglomeration and drying phases.

This study highlights the opportunity to use Eyecon as a PAT solution to optimise fluidised

bed processes for a given formulation as a means of controlling a process.

Moisture monitoring from Multieye NIR response data. Multieye, multi-channel NIR spectrometer

154. USE OF MULTIEYE, AN IN-LINE NIR BASED PAT

SOLUTION FOR REAL-TIME, NON-PRODUCT CONTENT

MONITORING OF MOISTURE CONTENTS IN A FLUIDISED

BED GRANULATION/DRYING PROCESS

Paul Cruise1, Luke Kiernan1, David Byrne1 Ian Jones1, Denisio Togashi2


2 Dublin Institute of Technology (DIT), Cathal Brugha Street, Dublin 1

The development of Process analytical technology (PAT) instruments provides

opportunities to control processes through the measurement of Critical Process Parameters

(CPP) which affect Critical Quality Attributes (CQA). This will improve the pharmaceutical

industries ability to produce products with consistent quality while reducing waste and costs

while also facilitating migration towards continuous manufacturing.

Near infrared spectroscopy (NIRS) is one such technology used as a PAT alternative to lab

based, solvent intensive wet testing and high performance liquid chromatography (HPLC).

NIRS can be utilised to determine moisture content, blend uniformity and density at line and

in-line for a number of processes including fluidised bed granulation and drying, twin screw

continuous granulation and drying and roller compaction. NIRS allows for high speed

analysis of specific spectral points of interest to monitor critical process parameters for

control of a process.

A trial was undertaken to assess the ability of Multieye to track moisture changes in both a

fluid bed granulation batch process and a continuous twin screw wet granulation and drying

process. Multieye is a multiprobe NIRS solution from Innopharma Labs which can record and

present NIR spectra from up to four channels concurrently thereby improving representative

sampling. For a process such as fluid bed granulation and drying this will allow for blend

uniformity and moisture content to be monitored at numerous locations within the fluid bed

granulator.

Using multivariate analysis a model was constructed based on process specific data. By

applying this model, Multieye successfully monitored moisture content over time for fluidised

bed granulation and drying and twin screw continuous granulation processes.

This study successfully demonstrated the use of Multieye NIRs multiprobe as a PAT

solution for real time non product content monitoring of moisture content for fluidised bed

granulation and drying and also twin screw continuous granulation.

155. EVALUATION OF THE GRANULATION PROCESS USING

FLOW AND PARTICLE SIZE ANALYSIS PARAMETERS

Eduardo J. Barbosa, Natalia V. Souza, Leandro Giorgetti, Marcelo D. Duque,

Michele G. Issa & Humberto G. Ferraz

Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof.

Lineu Prestes, 580, Cidade Universitária, São Paulo, Brazil


Evaluation of rheological behavior, as well as the characterization of the particle size of

material obtained through granulation processes, may significantly contribute in the scaling-

up of a formulation, and in ascertaining the Design Space, when the product is the result of

Quality by Design. The purpose of this study was to compare granules produced by

conventional humid granulation methods with those produced in a fluidized bed, using an FT4

Powder Rheometer (Freeman Technology) and a 1090 (Cilas) laser diffractometer in dry

mode. The formulations were obtained according to fractional factorial planning (23-1), using

the diluent (microcrystalline cellulose or lactose), the granulation process (conventional or in

a fluidized bed) and percentage of the flocculant agent PVP (5 % or 10 %). The outcomes

were evaluated in two stages, firstly using the flow rate index (FRI) and the average diameter

of the granules for analysis of the experimental design; subsequently, in addition to the latter,

the values '10s, '50s, '90s, stability indexes (SI) and compressibility indexes (CI) were

included in the multivariate analysis of the main components (PA). In the analysis of the

experimental design, for the FRI parameter, the diluent was the variable that proved to have

the greatest influence over the outcomes; however, all the values obtained are very close to

1.0, which is indicative of material with an adequate flow. With regards to average diameter,

the diluent variables and process proved to have significant influence, considering that the

formulations that contained cellulose resulted in larger granules. With regards to the process,

although the granules derived from conventional granulation present a reduced size, it is very

probable that these suffer breakage due to the elevated air flow employed in the drying stage.

For the creation of two new latent orthogonal variables, with 94.2 % retention of original

information, the multivariate analysis enabled a comparison of the formulations to be

established after all the parameters had been analyzed, proving that, regardless of the process,

diluent or quantity of flocculant used, the resulting granules are similar, but with properties

that are different from the starting material (cellulose and lactose) and, most importantly, with

improved flow.

156. HIGH SHEAR GRANULATION PROCESSING

PARAMETERS ON THE MECHANICAL PROPERTIES OF

DIATOMITE BASED POROUS GRANULATES (FOR THE

MACRO SCALE I: PROCESSING FOR GRANULATION)

Yujing Liu, Dagobert Scharf, Thomas Graule & Frank Clemens

EMPA, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for High

Performance Ceramics, Uebenlandstrasse 129, 8600 Duebendorf, Switzerland


Diatomite is categorized as a type of natural porous material, with wide pore size

distribution and large surface area, providing it for applications in the fields of catalysts

supports, separation filters, bio-device scaffolds and other related areas. However, for

diatomite application as catalyst supporting materials using in fluidized bed reactors (e.g.,

chemical looping combustion process, methanation industry, et.al), another requirement on its

mechanical stability is also of great necessity, in addition to the sound needs on its porous

network. In this work, the enhancement of mechanical properties of diatomite based porous

granulates was carried out through adjusting the processing parameters during high shear

granulation process[1].

Via tuning the granulation parameters, such as pan rotation speed, rotation modes between the

pan and the impeller, as well as the factor of granulation time, the size distribution and the

mechanical stability of formed granulates were adjusted. Specifically, the pan rotation speed

can assist the change of granulate growth mechanism and thus affect their mechanical attrition

resistant ability; the rotation mode between impeller and pan has an influence on the powder

distribution inside of the pan and the modification of granulate growth rate can be observed; a

certain prolongation of granulation time has no influence on granulates mechanical stability

but only increases the granulate size. This work provides interesting insights into the

understanding of granulation mechanism.

Illustration image: Granulates fabrication route variation and resulted granulate surface

morphology differences

[1] Y. Liu, D. Scharf, T. Graule, F. J. Clemens, Powder Technology, 263 (2014) 159-167.


157. A PRACTICAL APPROACH FOR THE SCALE UP OF

ROLLER COMPACTION PROCESS

Weixian Shi & Omar Sprockel

Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive

New Brunswick, NJ 08903 USA

Roller compaction as a unit operation has been studied extensively. Based on the Johanson

model, which describes the principle of ribbon formation, various methods with the emphasis

of matching normal stress betweens scales have been derived and unitized for scale up.

However, since measuring the material properties required in the models is challenging,

design of experiment (DoE) at the commercial scale is still conducted to identify proper

conditions for operating roller compaction. Additionally, there are much fewer investigations

on scale up of milling, the step following ribbon formation. While milling can be a

mechanically separate unit operation, some roller compactors have combined ribbon

formation and milling mechanism, making it a continuous operation. In this study, we focus

on the scale up of such roller compactor. We investigated an alternative approach for the scale

up of ribbon formulation, which required only one batch at the commercial scale to set the

operational conditions. Moreover, we identified that the milling operation at pilot scale and

commercial scale had different impact on the granules.

The scale up of ribbon formation was based on a probability method. It was sufficient in

describing the mechanism of ribbon formation at both scales. In this method, a statistical

relationship between roller compaction parameters and ribbon attributes (thickness and

density) was first defined with DoE using a pilot Alexanderwerk WP120 roller compactor.

While milling parameters was included in the design, it has no effect on any of granule

properties within the study range. The statistical relationship was then adapted to a

commercial Alexanderwerk WP200 roller compactor with one experimental run on the

Alexanderwerk WP200. The experimental run served as a calibration of the statistical model

parameters. The proposed transfer method was then confirmed by conducting a mapping

study on the Alexanderwerk WP200 using a factorial DoE, which showed a match between

the predictions and the verification experiments.

When scale up the milling, we selected to maximize the throughput on the commercial

scale, which dictated that matching the linear speed of milling blades between the two scales

was impossible as the milling chamber would be jammed at the commercial scale using the

same linear speed as that at the pilot scale. Thus a milling study at the commercial scale was

conducted. Contrarily to the pilot scale, the milling study showed significant impact on the

particle size distribution despite its ineffectiveness of downstream processes. More

interestingly, there was an optimal milling speed at which particle size was minimized or

milling, as a size reduction method, had least effectiveness.

The current study demonstrates the applicability of the ribbon formation transfer method

using the statistical model from the pilot scale calibrated with one experiment point at the

commercial scale. It also suggested that milling operation have different impacts at different

scales.

Polymer

coating

protects

the active

from

attack by

media

component

Coating

dissolves in

end use

application

to release

the active

into solution

158. RESPONSIVE POLYMER COATED PARTICLES FOR

CONSUMER PRODUCTS

Lisa E. Scullion, Paul. H Findlay & David A. Pears

Revolymer (U.K.) Limited, 1 Newtech Square, Zone 2, Deeside Industrial Park, Flintshire, CH5 2NT

UK


There are many challenges associated with stabilisation of active benefit agents in

detergent, personal care and other household and professional product formulations.

Revolymer’s encapsulation and particle processing technologies aims to enable new types of

formulation with improved consumer benefits whilst having long shelf life and fast release of

actives in use. Such technology will for example enable superior performance at low

temperatures and with short wash cycles.

The market for liquid formulations of laundry detergents and other non-laundry cleaners

continues to grow more rapidly at the expense of the conventional powder market, fuelled by

retailer and end user preferences. However, current liquid laundry formulations do not

contain bleaching agents, which are important constituents of most modern powder

formulations and play a key role in cleaning and hygiene. This is because it has not, to date,

been possible to stabilise such actives in a liquid formulation. Revolymer’s household

technology team have developed polymeric barrier materials which are able to stabilise the

cleaning actives in liquid formulations so their shelf lives are significantly extended. These

polymeric coating materials are ‘stimuli-responsive’ in that the actives are protected whilst

they remain in the liquid product formulation. When the product is used during the cleaning

process, the responsive polymer coatings are sensitive to changes in environment such as pH,

dilution or ionic strength and quickly disperse to release the active into the cleaning cycle.

High performance cleaning actives can also be stabilised in powder and tablet forms for

laundry and autodishwash formulations using a combination of granulation or spheronisation

in combination with the responsive barrier coating to give robust, free-flowing uniform

particles that protect the active from incompatible formulation ingredients.

159. ASSESSMENT OF WETTING AND DISPERSING

MEASUREMENTS OF DAIRY POWDERS AND THE

AGGLOMERATES

Junfu Ji1, 2, John Fitzpatrick2, Kevin Cronin2, Abina Crean3 & Song Miao1

1 Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland 2 School of Engineering, University College Cork, College Road, Cork, Ireland

3 School of Pharmacy, University College Cork, College Road, Cork, Ireland


Rehydration is an important powder property and is regarded as a critical issue by the dairy

industry. As most dairy powders either exhibit poor wettability with the material floating on

the surface of solution, or disperse very slowly accompanied by lump formation, traditional

powder rehydration measurements are relatively empirical with poor reproducibility. Thus,

more reliable techniques tailored for dairy powders should be developed based on varied

rehydration behaviours and applications. In this paper, a critical assessment to identify the

measurement characteristics of dairy powder rehydration is presented. Milk protein powders,

and their agglomerates, which were produced from fluidised bed granulation, were used as

model systems in this study. Wettability measurements based on four different wetting

procedures (Immersion, Capillary rise, Condensation and Spreading) and dispersability

measurements (Dispersed solids in supernatant, Size of dispersing particles, Light

transmission and Conductivity of suspension) are compared and analysed respectively. The

results show that the method based on immersional wetting procedure is only appropriate for

skimmed milk powder while the method for capillary rise wetting is more useful for the

agglomerated powders with porous structures. Contact angle in spreading wetting approach is

found more straightforward to show the hydrophobicity or hydrophilicity of dairy powders.

At the same time, if compared with traditional dispersibility measurements, light transmission

of suspension is suitable to reflect optical properties of slow dispersion process of casein-

dominant powders. Light scattering methods can also be used to measure the dynamic size

change of particles and thus monitor the dispersion process. Furthermore, the conductivity of

suspensions is considered as a useful indicator to quantify the dispersibility indirectly by the

release of minerals during rehydration. In summary, it is necessary to understand the

specialities and applications of dairy powders before choosing the appropriate rehydration

methods.


160. THE SPECIFICATIONS FOR THE SUSTAINABLE-DESIGN

OF THERMO-HYDRO-MECHANICAL PROCESSES OR THE

ELABORATION OF AGGLOMERATED PRODUCTS

Bettina Bellocq, Agnès Duri, Bernard Cuq & Thierry Ruiz

UMR IATE 1208 CIRAD/INRA/Montpellier SupAgro/Université Montpellier – 2 Place Pierre Viala,

34060 Montpellier cedex 5, France.


Although scientific works have been conducted over the 15 last years, theory of

agglomeration are still missing to understand the uses of reactive powders during the

processing of durum wheat into agglomerated couscous grains. Due to the multiplicity of

mechanisms, the end product properties cannot be predicted. More over the current industrial

process is particularly poorly eco-efficient and energy consuming. The objective of the

present work is to generate relevant data for the specifications for the sustainable-design of

thermo-hydro-mechanical processes for the elaboration of couscous grains. Our approach is

based on coupling experimental and modeling works to investigate the contributions at

complementary scales: at the products and process scale. Knowledge integration is based on

the elaboration of functional diagrams using a Dimensional approach (DA). The

representation by dimensionless numbers for water/solid particle meeting, particle sticking

and grain mobility, associated with the governing ratios which characterize the mechanisms of

mass and energy transfers, allows to propose specific diagrams to describe the couscous

process. Dimensional analysis (DA) is considered as a way to allow the decomposition of the

whole couscous process. Dimensional Analysis is first conducted to investigate the rotating

durum process under different trimming parameters and process conditions. The target

parameters have been chosen from the physicochemical properties of the final agglomerated

powder.

161. DETERMINATION OF COMPARTMENT RESIDENCE

TIMES WITHIN BATCH GRANULATORS USING

COLORIMETRIC ANALYSIS

Andrew D. McGuire, Sebastian Mosbach, Kok Foong Lee & Markus Kraft

Department of Chemical Engineering and Biotechnology, University of Cambridge, New Museums

Site, Pembroke Street, Cambridge, CB2 3RA, UK


Granulation equipment rarely consists of a singular well-mixed volume with constant

processing conditions. As a result, such systems are now typically modelled as a series of

compartments, with each compartment exhibiting its own processing conditions (binder

addition rate, shear rate, residence time etc.). The rate at which particles are to be transferred

between compartments is a key input parameter in the compartmental simulation of wet

granulation processes; however, it is generally unknown.

In this work, wet mixing experiments using coloured granules are coupled with

colorimetric image analysis methods to evaluate the concentrations of various particle colours

across the bed surface and their evolution in time. This method is particularly advantageous

due to its inherent simplicity, speed and low cost relative to competing technologies. The data

derived using this method is used to estimate the rate at which particles are transferred

between compartments. These rates (and the notion of particle colour) are incorporated into

an existing compartmental population balance model for the simulation of high shear batch

granulation processes. The colorimetric method is compared with previous PEPT results

within the literature which were obtained using the same mixing equipment.

Particle concentration tracking within a compartment with model fit.

162. DEVELOPMENT OF EXTENDED RELEASE COATED

PELLETS FOR HYPERTENSION AND ANGINA TREATMENT

Luciane F. G. Souza1 , Marcello Nitz2 & Osvaldir P. Taranto3

1,2 School of Engineering, Mauá Institute of Technology (IMT), São Caetano do Sul, SP, BR

3 School of Chemical Engineering, University of Campinas (UNICAMP), Campinas, SP, BR


Among the various pharmaceutical forms for oral use, pellets have attracted increasing

interest due to several advantages, such as the suitability to film coating. Nifedipine is a

poorly soluble active principle widely used in the hypertension and angina treatment. Many

studies have been performed in order to improve the solubility of slightly soluble drugs with

the use of a disintegrating agent. In this study, nifedipine extended release pellets were

produced by extrusion-spheronization, and then received a coating layer with commercially

available aqueous polymer, Opadry®II, in a fluid bed coater with a Wurster insert. The

coating layer aimed to avoid degradation by exposure to light without affecting the release

profile. The 25% w/w nifedipine pellets were formulated with microcrystalline cellulose,

lactose, sodium croscarmellose (desintegrating agent), PVP-K30 and PEG4000. A

comparison study of the dissolution profiles of coated and uncoated pellets using 0.50%

sodium lauryl sulfate in simulated gastric fluid (pH 1.2) was performed. The results showed

an extended release profile for the coated and uncoated pellets in accordance with the US

Pharmacopeia standards. The drug content and the release profiles were not significantly

affected by storage at 40 ºC and 75% relative humidity in both coated and uncoated pellets.

However, when exposed to fluorescent light, the coated pellets lost only 5% of the drug

content, while the uncoated pellets lost more than 35%.

Uncoated pellets (150 x)

Coated pellets (150 x)

Dissolution profile of uncoated pellets Dissolution profile of coated pellets

163. STUDY ON TWO-WAY COUPLING OF GAS-SOLID TWO-

PHASE FLOW OF CYLINDRICAL PARTICLES

Cai Jie1,2, Zhong Wen Qi1 & Yuan Zhu Lin2 1 Thermal-Energy Institute, Southeast University, 78 Bancang street, Nanjing 210096, P. R. C.

2 School of Energy and Mechanical Engineering, Nanjing Normal University, 2 Sipailou, Nanjing

210042, P. R. C.

In this study, a three-dimensional model of slender particle gas-solid two-phase flows

based on rigid dynamics, κ - ε model was established. In this model, the two-way coupling

correlation between slender particle and flow field was established based on the correction

between Lagrangian time scales and κ - ε model, the force and motion model of slender

particle was established according to Euler dynamics, and the coupling correlation between

two slender particles was taken into account by using the rigid collision dynamics and

modified Nanbu collision probability theory. To validate the model, a fluidized experiments

of slender particles in a cold-state fluidized bed was carried out. The gas-solid two-phase

fluidization characteristics of slender particles are obtained. It is found that slender particles

arriving at the exit of the riser the earliest come from the near-wall regions, the horizontal

transfer of so many slender particles from the radial centre regions to the near-wall regions is

evident. Meanwhile, there is no distinct relationship between the number concentration and

inlet wind velocity.

Fluidization of cylindrical particles in a riser at different time step

164. MODEL PREDICTIVE CONTROL OF CONTINUOUS

MECHANOCHEMICAL SYNTHYSIS BASED ON SELF-

SUSTAINING REACTIONS

Ahmad B. Albadarin1,2, Ciara Griffin, Mark Davis, David Egan1 &

Gavin Walker1,2


2 School of Chemical Engineering, Queen’s University Belfast, University Road, Belfast BT7 1NN,

United Kingdom


The aim of continuous material processing is to intrinsically inter link each unit operation

in order to eliminate the requirement for corrective processing steps, via the development of

hybrid technologies. The possible approach for developing the predictive control model can

involve the mapping of the continuous granulation process, which will provide a basis for

advanced processing and mechanochemical synthesis. In this study we analyse the data from

a number of published works on mechanochemical synthesis, with the aim of establishing

critical material attributes and key process parameters in order to formulate an empirical

model to predict ignition time of self-sustaining reactions, which has been used previously as

a tool to study mechanochemical activation [1]. Ultimately, we aim to use these batch data

and empirical models as a basis for the design of continuous mechanochemical processes.

A self-sustaining reaction can be induced after a certain activation time if a sufficiently

exothermic powder mixture undergoes mechanical shear, typically in a ball mill, under the

term Mechanically induced Self-sustaining Reactions (MSR's). Previous researchers have

indicated that SMR's depend mainly on their adiabatic temperature [1], which is often

simplified to the ratio of the reaction enthalpy to the room temperature heat capacity of the

products (ΔH/Cp), but also to engineering process parameters such as the configuration of the

mill and the kinetic energy imparted on the reactant powders.

In this work we analysed of a number of previously reported data sets on MSR's and

related them to the adiabatic temperature and process parameters. Previous researchers

proposed a ΔH/Cp rule-of-thumb to determine when a self-sustaining reaction might occur,

where an MSR can propagate without the use of an external energy when ΔH/Cp is >2000K

[2]. Indeed, on analysis of the MSR data compiled in a recent review [3], we found that there

is no correlation between adiabatic temperature and ignition time above the 2000K threshold.

Moreover, the adiabatic temperature and the arithmetic mean of the melting points of the

materials, indicate an almost normal distribution with respect to ignition time. Significantly,

we determined a stronger correlation between engineering process parameters and the system

kinetic energy to ignition time, above the 2000K threshold.

[1] L. Takacs, Self-sustaining reactions as a tool to study mechanochemical activation, Faraday

Discuss., 2014, 170, 251

[2] Z.A. Munir, U. Anselmi-Tamburini, Mater. Sci. Eng. R 3 (1989) 277–283

[3] R. Ebrahimi-Kahrizsangi, Ignition time of nanopowders during milling: A novel simulation,

Powder Technology 272 (2015) 224–234

165. MECHANOCHEMICAL SYNTHYSIS OF

HYDROXYAPATITE EMPLOYING HIGH AND LOW SHEAR

MILLING PROCESSES

Ahmad B. Albadarin1,2, Ciara Griffin, Mark David, David Egan1, and

Gavin Walker1,2


2 School of Chemical Engineering, Queen’s University Belfast, University Road, Belfast BT7 1NN,

United Kingdom


The invention and application of cleaner, more sustainable ways of performing chemical

synthesis in the pharmaceutical, biomedical and fine chemical sectors is a priority goal

internationally for the foreseeable future. Mechano-chemistry, in which solid reactants are

vigorously ground together with minimal or even no solvent, is now attracting attention as an

alternative to traditional solvent-intensive approaches.

Here we analyse the mechano-synthesis of hydroxyapatite from calcium hydroxide and di-

ammonium phosphate, which follows the reaction below [1]:

Reaction 1: 10Ca(OH)2 + 6(NH4)2HPO4 → Ca10(PO4)6(OH)2 + 12NH3 + 18H2O

The mixed reactants with a molar ratio of 1.67 Ca/P were milled by using tungsten carbide

vials and balls in a rotary ball mill. The powder to ball mass ratio was varied from 1/4 - 1/6 -

1/8. Three rotation speeds were employed 50 rpm, 100 rpm and 200 rpm for a period of up to

24 hours. A further set of experiments were undertaken in an industrial high energy planetary

ring-and-puck mill for a period of up to 1 hour. The process parameters normally considered

within a ball milling process are: (i) revolution speed or rotational speed at a constant speed

ratio; (ii) milling time (equivalent to reaction time); (iii) filling ratio of milling balls or the

number of milling balls at constant chamber size; (iv) filling ratio of grinding material or ball

to powder ratio [2].

Results from the high and low shear experimental processes were compared for both

reaction kinetics and reaction yield, with respect to formation of hydroxyapatite as measured

by PXRD and Raman spectroscopy. The experimental data indicated that hydroxyapatite was

successfully formed in both experimental procedures, with the reaction giving almost 100%

yield within the planetary mill. Correlation of the experimental data to the average kinetic

energy imparted on the reactant powders and to the reaction time was undertaken. It was

determined that the kinetic energy of the system played a critical role in determining both the

rate and extent of the reaction. This correlates with previous research on organic

mechanochemical synthesis of Suzuki–Miyaura reactions using ball mill processes [3].

[1] S. Adzila, et al., Mechanochemical synthesis of nanohydroxyapatite bioceramics, Indian Journal of

Chemistry, Vol 52A, December 2013, pp 1570

[2] C.F. Burmeister and A, Kwade, Process engineering with planetary ball mills, Chem. Soc. Rev.,

2013, 42, 7660

[3] F. Schneider, A. Stolle, B. Ondruschka and H. Hopf, Org. Process Res. Dev., 2009, 13, 44–48.

166. LIQUISOLID TECHNOLOGY APPLIED TO PELLETS

Bianca R. Pezzini1, 2, André O. Beringhs3, Humberto G. Ferraz1, Marcos A.

Segatto Silva3, Hellen K. Stulzer3 & Diva Sonaglio3

1 Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

2 Department of Pharmacy, University of Joinville Region, Joinville, Brazil

3 Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, Brazil

E-mail [email protected]

Liquisolid technology is a poorly explored but promising technique to improve the

dissolution rate of low solubility drugs. These systems can be obtained by dissolving or

dispersing the drug in a non-volatile solvent and mixing it with solid excipients (carrier and

coating material). The mixture can be converted in a final dosage form by compression into

tablets or filling into capsules. The purpose of this study was to evaluate the feasibility of

liquisolid pellets (LSP) as an innovative drug delivery system combining the advantageous

properties of multiple-unit dosage forms and the liquisolid formulations. In this way, four

LSP formulations (F1, F2, F3 and F4) were obtained by extrusion-spheronization and fluid

bed drying, using felodipine as a model drug. Copovidone (Kollidon® VA 64) in water (1%)

was employed as the granulating liquid and microcrystalline cellulose PH 102 as the carrier

material. The effects of the concentration of crospovidone (Kollidon® CL-SF) as a coating

and disintegrant material (4% or 8%) and the type of non-volatile solvent, polyethylene glycol

400 (PEG 400) or macrogolglycerol ricinoleate (Cremophor® EL), on the drug dissolution

profile were assessed. Two conventional pellets formulations (CF1 and CF2) were also

obtained without the addition of any non-volatile solvent. The dissolution profiles were

determined using the paddle method, 100 rpm, 900 mL of 0.1 N HCl pH 1.2 containing

sodium lauryl sulphate 1% at 37 °C. The dissolved drug was quantified by absorption

spectrophotometry at 364 nm. All LSP formulations had increased drug dissolution profiles

compared to its correspondent conventional formulations (Figure 1), and the percentage of

drug released in 60 min (Q60min) followed the decreasing order: F2>F4>F1>F3 (ANOVA,

p<0.05). Cremophor® EL was considered more effective in improving the drug dissolution

rate compared to PEG 400. The presence and the amount of crospovidone in the formulations

also showed remarkable positive effects on the drug dissolution. The liquisolid pellets

developed have excellent flow properties and can be easily converted into a final dosage form

by encapsulation. In addition, this study showed that liquisolid systems might be successfully

incorporated into multiparticulate systems such as pellets. The literature didn’t describe so far

the development of liquisolid pellets and the use of crospovidone as a coating material in

liquisolid formulations. Therefore, this study consists in an innovation and expansion of the

current liquisolid technology.

Figure 1. Dissolution profiles obtained for felodipine liquisolid (F1, F2, F3 and F4) and

conventional (CF1 and CF2) pellets

167. COUPLED GAS FLOW AND POWDER DEFORMATION

UNDER ROLLER COMPACTION

Abderrahim Michrafy, Lucia Prerez Gandarillas & Alon Mazor

Université de Toulouse, Mines Albi, CNRS, Rapsodee, Campus Jarlard, F-81013 Albi cedex 09


Dry granulation of powder is a continuous process used in the pharmaceutical industry to

produce free flowing granules. Ribbons are firstly formed using a roll press and then milled to

produce granules. In the operation of roller compaction, the entrapped air in the powder

influences the production conditions and the ribbon’s quality particularly for fine powders.

For this, most of the roller presses are equipped with pumping systems offering different

designs. The effect of air in powder processing is often emphasized in the literature, but few

experimental and modeling works have been addressed [1, 2]. Practically, the achievement of

the optimum process performance in the pharmaceutical industry is based on trial-and-errors

techniques, but this approach results in an increase of operating cost and time, especially with

high-value materials. Modeling approach can be used as an alternative method to gain a better

understanding of the interaction “solid-air” and “process parameters” by providing necessary

information for proper equipment and operating conditions.

The goal of this work is to investigate this problem by 2-D finite element modeling using

coupled gas flow and solid deformation in porous media. In this approach, the deformation of

solid material is described by Drucker-Prager Cap model and the gas flow is governed by a

pressure-dependent effective permeability based on Darcy’s law where the permeability is

expressed as a function of the porosity using Carman–Kozeny relationship. In this modeling,

the gas is assumed ideal and isotherm and the effect of gas pressure on solid stress is

neglected between rolls. Numerical simulations were conducted using input data of bentonite

powder. Solid and gas properties distributions were computed. The predicted gas pressure

showed a sudden increase just after the nip angle wherein the pumping of air is often

recommended. Results of the gas velocity (Figure 1) showed a relative delay to solid speed

with high values in the vicinity of the roller. This result is in agreement with the low

permeability of the solid in the contact zone with the roll where the air is better brought by the

movement of the solid.

Figure 1. Gas speed (arrow) and Dimensionless Pressure Gradient at the entry of rolls ÑPg / rsg

in [0.6 – 36], where g is the gravity, ÑPg the gas pressure gradient and rs the solid density

[1] J.R. Johanson, B.D. Cox, Fluid entrainment effects in roll press compaction, Powder Handl.

Process. 1 (1989) n°2.

[2] V. Esnault, A. Michrafy, D. Heitzmann, M. Michrafy, D. Oulahna, Processing fine powders by roll

press, Powder Technology 270 (2015) 484–489


168. PROTECTIVE EFFECT OF SUGARS ON THE VIABILITY

OF LACTOBACILLUS RHAMNOSUS GG AFTER SPRAY-

DRYING

Géraldine AM. Broeckx & Filip Kiekens

Department of Pharmaceutical Technology and Biopharmacy, University of Antwerp,

Universiteitsplein 1, B-2610 Wilrijk, Belgium


Increasing research on the health benefits of probiotics, not only for the gut microbiota, is

showing the growing interest of the pharmaceutical industry in probiotics! Many diseases are

characterized by an increase in pathogenic bacteria and a decrease in beneficial bacteria, the

so-called probiotics. If the manufacturing processes to obtain viable probiotics are better

understood, better, more precise results can be obtained and more clarity can be given

concerning the health benefits of probiotic bacteria. One of the key challenges of processing

probiotics is their viability, associated with the shelf life of the finished product, since the

probiotics are expected to have only limited effects when dead. During manufacturing and

storage, probiotics are prone to a number of environmental factors such as heat, moisture, air,

high pressure, light, chemical stability, etc. that tend to hamper the final quality of the

ingredients. There is a consensus that preservation of products, particularly enzymes and

bacteria, in their dry form enhances long term storage stability and activity.

In this project the effect of saccharide protectants is evaluated on the viability of

Lactobacillus rhamnosus GG (LGG). The saccharides tested are lactose, trehalose, mannitol

and dextran. They are added at two different time intervals to the probiotic cells: 1) addition

to the growth medium or 2) addition to the bacterial suspension prior to spray-drying. From

the sugars added to the growth medium of LGG mannitol gave the best viability results. When

the saccharides were added to the bacterial suspension just before spray-drying samples

spray-dried with trehalose showed the highest viability. The higher the amount of saccharide

added to the bacterial suspension the higher the survival rate. The cumulative effect of the

addition of mannitol to the growth medium and the addition of trehalose to the bacterial

suspension gave no better viability than the addition of solely trehalose to the bacterial

suspension. The influence of storage temperature was evaluated on a sample as such, without

addition of any sugars and a sample with addition of 2 parts trehalose. Results show that

storage of the samples at room temperature have a viability of less than 107 CFU/100 mg

spray-dried powder. The sample as such showed a one log reduction after storage at 4°C, the

sample with 2 parts trehalose added showed no viability loss after 1 year. It can be concluded

that the addition of saccharides enhances the viability not only after spray-drying, but also

after storage of 1 year.

The viability of probiotic bacteria after spray-drying can also be enhanced by pretreatment

procedures that lead to increased resistance of the bacteria to the spray-drying process. The

influence of a stress procedure prior to spray-drying will be examined. The hypothesis states

that bacteria which are exposed to sublethal stress can form resistance factors that can render

the bacteria more resistant to the spray-drying process and thus higher viability results can be

obtained.

169. INVESTIGATION OF THE AXIAL PARTICLE TRANSPORT

IN A CONTINUOUSLY OPERATED HOROZONTAL FLUIDIZED

BED

Eugen Diez & Stefan Heinrich

Institute of Solids Process Engineering and Particle Technology, Hamburg University of Technology,

Denickestraße 15, 21073 Hamburg, Germany


For continuous treatment of powders progressively horizontal fluidized beds are used.

These horizontally structured apparatuses are characterized by a rectangular cross section. An

advantage of a horizontal fluidized bed is the flexible partitioning of the process chamber into

several stages due to weirs to apply different processes like granulation, drying or cooling in a

single apparatus. The compartmentation provides a targeted impact on the transport behaviour

and the residence time of the particles which are feed into the process chamber.

In this work the particle transport behaviour across the stage boundaries is investigated

utilizing different weir configurations (over, under and lateral flow). Particularly particle

classification and segregation effects are taken into account to examine the influence of

different weir assembly on the residence time of particles in the process chamber. Based on

the fluidized bed spray granulation process courser particles are fed into a bed (starting

material) of smaller particles analyse the transport and residence time behaviour of the coarse

fraction.

Set-up of horizontal fluidized bed apparatus

Acknowledgement: The financial support of DFG (Deutsche Forschungsgemeinschaft) within

the priority program SPP 1679 "Dynamic simulation of interconnected solids processes

DYNSIM-FP" is gratefully acknowledged.

170. THE EFFECT OF PROCESSING ROUTE ON MATERIAL

SURFACE PROPERTIES

Majid Naderi1, Nektaria Servi1, Anett Kondor1, Manaswini Acharya1, Jurgen

Dienstmaier1 & Dan J. Burnett2

1 Surface Measurement Systems, Alperton, Middlesex, HA0 4PE, UK

2 Surface Measurement Systems, Allentown, PA 18103, USA


Crystalline active pharmaceutical ingredients can become amorphous either intentionally

(i.e. spray-drying, freeze-drying, extrusion, etcetera) or unintentionally during different

manufacturing processes (e.g. blending and micronization). Although all above routes may

produce amorphous regions, the physical properties and ultimate behaviour of these materials

may vary dramatically.

Finite concentration Inverse Gas Chromatography (IGC) experiments allow for the

determination of surface energy distributions which more accurately describe the anisotropic

surface energy for real materials. In this study, the surface energy heterogeneity and surface

acid-base properties of Indomethacin were measured to investigate the effect of processing

route on material surface properties.

Dispersive surface energy profiles show similar shapes for crystalline and quench cooled

Indomethacin (Figure 1).

Figure 1. Dispersive surface energy distributions

There is no evidence of any bulk amorphisation in milled Indomethacin. High dispersive

surface energy values could be due to formation of defect sites, kinks, steps etc. or exposure

of higher energy crystal facets during the milling process.

25.0

30.0

35.0

40.0

45.0

50.0

0.00 0.02 0.04 0.06 0.08 0.10

Dis

pe

rsiv

e S

urf

ace

En

erg

y [m

J/m

2]

Fractional Surface Coverage [n/nm]

Crystalline

Milled

Quench Cooled

171. STUDY OF THE INFLUENCE OF THE DIAMETER OF A

CONICAL HOPPER ORIFICE ON THE PARAMETERS OF THE

FLOW EQUATION FOR SIZE FRACTIONS OF SORBITOL

GRANULES

Hana Hurychová, Malek Azar, Zdeňka Šklubalová & Jan Stoniš

Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy,

Hradec Králové, Czech Republic


Flowability of pharmaceutical particulate materials is important in processing of dosage

forms. To avoid any discharge problems, determination how material flows is necessary. The

influence of the diameter of a hopper orifice on mass flow rate of powder is generally

described using power law equation.

This work studies the dependence of the mass flow rate Q (g/s) of the size fractions of

granules in the range of 0.346-0.669 mm on the diameter of the aperture D (cm) of a conical,

stainless steel hopper in the range of 0.6 -1.5 cm. The granules were prepared from free-

flowable pharmaceutical powder excipient, sorbitol (Merisorb®200), by wet granulation

method. The results were modelled with a general power equation and with the Jones-Pilpel

power equation [1]. Using the actual parameters of the detected power equation, the precision

of the flow rate prediction was compared for both equations using an average relative

deviation between the experimentally obtained value of mass flow rate and the reverse

estimated one.

The proposed power equation in which the intercept represents the estimate of the particle

flow rate through orifice of unit diameter allows the estimation of the mass flow rate with the

same precision as the traditional power flow equation. The clear meaning of the parameters

makes the proposed equation beneficial for possible use in pharmaceutical technology.

[1] T. M. Jones, N. Pilpel, The flow properties of granular magnesia. J. Pharm. Pharmacol., 18 (1966)

429-442.

172. IMPACT OF SURFACE PROPERTIES ON WETTING

BEHAVIOR OF THIN FILMS AND POWDERS

Alessandro Gianfrancesco & Constantijn Sanders

Nestec Ltd., Nestlé Product Technology Centre, Nestlé Strasse 3, 3510 Konolfingen, Switzerland


Good wetting behaviour is a key property to achieve dissolution or dispersion of food

powders. This is a function of composition and agglomeration degree of the particles, but also

of the state of the surface. Depending on the processing and storage conditions, the

composition of the powder surface can be different from the bulk. Other physical properties

such as water activity and water content might also differ. In this work we use the contact

angle method to measure the wetting behaviour of spin-coated thin films with different

composition, which are representative of possible composition at the surface of a powder. We

put into evidence how overrepresentation of proteins at the surface could lead to a worse

wetting compared to substrates where low molecular weight carbohydrates such lactose are

present. We then discuss how processing conditions in particular during spray drying can be

adjusted to generate different surface compositions leading to different wetting behaviour.


173. MODELING GRANULATION BEHAVIOR IN AN

AGITATED FILTER DRYER

Ashutosh Tamrakar1, Alfeno Gunadi2, Patrick M. Piccione2 & Rohit

Ramachandran1


Piscataway, NJ, 08854, USA

2 Process Studies Group, Technology & Engineering, Syngenta Ltd., Bracknell, Berkshire, United

Kingdom


During the agitated drying phase in an AFD operation, the mechanical agitation of the wet

cake, implemented to enhance heat and mass transport, has been commonly observed to result

in formation of undesired agglomerates that require further processing. Only relatively few

experimental studies of the effects of operating parameters (temperature, agitation rate),

design parameters (vessel/impeller geometry) and material properties (particle size, particle

size distribution, thermal properties of solvent and solid) on the drying and granulation

kinetics have been described in the literature. In absence of robust predictive models, the go-

to solution in order to avoid the granulation behavior of APIs during drying has been use

minimal amount of agitation which is not only suboptimal but also significantly increases the

drying times.

The simulation of granulation behavior in AFD is particularly challenging because the

filter-drying processes are mechanistically governed by simultaneous heat, mass and

momentum transfer equations. In addition, the behavior of agglomeration growth and drying

pathway varies significant with the physical properties of the residual solvents in the cake as

well as the operating conditions of the agitated dryer. A comprehensive modeling approach to

simulate both drying and granulation behavior in AFDs through implementation of a coupled

Discrete Element Modeling (DEM) - Population Balance Modeling (PBM) simulation is

proposed. Additionally, experimental analysis of the drying behavior at various conditions are

also studied to provide preliminary validation and to get insight into the competition between

attrition and agglomeration phenomena.

Figure 1. a) Experimental setup for agitated drying experiments b) Identical simulation setup

for conducting DEM calculations

a) b)

174. ROLLER COMPACTOR: THE EFFECT OF NANO-

INDNTATION HARDNESS OF PRIMARY PARTICLE

Riyadh B. Al Asady, Michael J. Hounslow & Agba D. Salman

Department of Chemical and Biological Engineering, University of Sheffield, Mappin Street,

Sheffield,

S1 3JD, UK


Roller compaction is a continuous dry granulation process in which primary powder is

compressed at high pressure by two counter rotating rollers to produce a ribbon. The

compressibility of the material plays an important role in the bonding mechanism between the

powder particles and, therefore, influences the properties of the ribbon. Choosing the right

formula of the primary powders is a key point to get desired ribbon and granules properties.

However this is still not fully understood.

Measurement of nano-indentation hardness requires a few particles of the powder. This

means the hardness of the material can be estimated even when the material is not available in

large quantities or it is expensive. This is the case with new pharmaceutical products. So

finding a correlation between single particle hardness and ribbon properties is useful.

In this study, the nano indentation hardness of a single primary particle was measured for

different materials. This was linked to the properties of the ribbons produced by roller

compaction using different hydraulic pressures in the range of 30-230 bar. It was found that

the nano-indentation hardness of the powder particles is important in controlling and

predicting ribbon properties.

175. TWIN SCREW WET GRANULATION: EFFECT OF

VARIABLES ON CAKING

Mohammed F. Saleh1, Ranjit M. Dhenge1, James J. Cartwright2, Michael J.

Hounslow1, Agba D. Salman1



2 GSK, Third Avenue, Harlow, Essex, UK,CM19 5AW


The purpose of this work was to monitor the rate and mass of the built up/caking of α-

lactose monohydrate (Pharmatose 200M) and microcrystalline cellulose (Avicel PH 101);

while varying the process and formulation variables in Twin Screw Granulator (TSG) (i.e.

granulation liquid viscosity & screw configuration). The granule size distribution was also

determined for both materials. The experiments were conducted using an acrylic transparent

barrel. However, for validation; α-lactose monohydrate (Pharmatose 200M) was used, where

the steel barrel was used. The results of the two extreme granulation liquid viscosities

(0%w/w of HP & 15%w/w HPMC) at different screw configuration, obtained using

transparent barrel were compared to the results generated while using the stainless steel

barrel.

In the case of conveying elements, Lactose showed a continuous increase with time for all

viscosities, whereas MCC showed insignificant change with time (except for the water where

it increased). Furthermore, as the granulation liquid viscosity increased (i.e. 15%w/w) the

development of caking emerged from the centre of the transparent barrel, where the use of

less viscous liquid caused caking to emerge from the centre as well as the side of the

transparent barrel. However, introducing the kneading elements caused caking to have the

same pattern on the barrel regardless of the viscosity (or material), where it mainly started

from the sides of the transparent. Additionally, using Lactose gave a similar trend for the

kneading elements as that when conveying elements only were used. However, using the

kneading elements gave a higher mass and rate of caking in comparison with their

corresponding, where conveying elements were used. Conversely, kneading elements showed

inconsistent trend for caking of MCC in comparison with their corresponding findings, where

conveying elements were used. Using granulation liquid of water, MCC showed to be

unaffected by the kneading elements. Furthermore, as the viscosity varied up to 7.5%w/w of

HPMC, it showed a slight decrease from the water, in spite of giving a higher mass of caking

than their corresponding, when conveying elements were used. Further increase of HPMC (up

to 15%w/w) gave a higher mass and rate of caking comparing to 0%w/w (i.e. distilled water).

The size distribution also showed a difference as the granulation liquid viscosity and the

screw configuration was varied. The results, for Lactose, obtained from the stainless steel

barrel compared well with their corresponding conditions from the transparent barrel, as the

same trends of caking and size distribution, were observed for both screw configurations.

176. ROLLER COMPACTOR: MECHANICAL PROPERTY OF

PRE-COMPACTED BODY

Riyadh B. Al-Asady, Ranjit M. Dhenge, Michael J. Hounslow & Agba D.

Salman

Department of Chemical and Biological Engineering, University of Sheffield, Mappin Street,



In roller compactor, the material compaction behaviour is mainly a function of two

parameters, the nip angle and the maximum pressure applied. The nip angle is indication of

the size of the powder compaction zone. Johanson [1] presented the first model to predict the

behaviour of the powder undergoing roller compaction. The model determines the nip angle

and the maximum pressure applied on the powder as a function of roller dimension, roll gap,

powder properties and roll separating force. In this study a new method has been introduced

to determine the nip angle by investigating the mechanical properties of the real pre-

compacted body using microcrystalline cellulose (Avicel PH-101) as a primary powder. The

results showed that the suggested method can be used to determine the nip angle as a function

of different process conditions including roller speed which is not included in Johanson`s

theory.

[1] J.R. Johanson, A rolling theory for granular solid, Journal of applied mechanics, 32 (1965)

842-848.

177. ROLLER COMPACTION: EFFECT OF RELATIVE

HUMIDITY

Chalak S. Omar1, Ranjit M. Dhenge1, Stefan Palzer2, Michael J. Hounslow1 &

Agba D. Salman1


Sheffield S1 3JD, UK

2 Nestlé SA Headquarters, Avenue Nestlé 55, CH-1800 Vevey, Switzerland.


Roller compaction is a dry granulation technique used in many industries especially the

food, chemical and pharmaceutical industries. Within these industries lactose is one of the

most important materials used. The relative humidity of the environment affects the powder

moisture content. The aim of this study is to investigate the effect of the relative humidity of

different types of lactose on roller compaction behaviour and on the product properties.

Three types of lactose were used in this study; anhydrous lactose SuperTab21AN, spray

dried lactose SuperTab11SD and α-lactose monohydrate 200M. The powders were stored in

the climatic chamber at different relative humidity ranging from 10 % to 80 % RH. These

powders have different amorphous content due to the difference in the manufacturing

processes. It was found that the roller compaction behaviour was different for powders

conditioned at different relative humidities. The amount of fines in the product, a

disadvantage in the roller compactor, decreased with increasing the relative humidity of the

powder and increased again with further increase in the relative humidity. This was due to the

difference in ribbon width at different relative. The width of the ribbon increased and then

decreased with increasing the relative humidity. The tensile strength of the produced ribbon

(for both 200M and SD) increased with increasing the powder relative humidity and then

decreased with further increase in the humidity. The tensile strength of ribbon produced from

the 21AN was increasing with increasing the RH.


178. ROLLER COMPACTOR: POWDER STICKINESS

Osama Mahmah, Michael J. Hounslow & Agba D. Salman




Roller compaction is a dry agglomeration process which uses high pressure to bond

powder particles together to form a ribbon. Unlike the batch wet granulation processes this

continuous technique offers a higher productivity without the need of any liquid or drying

stage. Stickiness on roll surface, loss of workability, the amount of fine are the major

limitations of this technique.

In order to enhance the efficiency of the process and extend the range of materials that

could be processed by this technique, this work exploit the ejection and compaction behaviour

of a range of materials of different mechanical properties in order to further understand the

sticking phenomena during roller compaction.

Normailized ejection force required to take off the tablet of the die

0

50

100

150

200

250

0 2 4 6 8 10 12

No

rmal

ize

d T

ake

off

Fo

rce

(N

/mm

)

compaction Force (KN)

MCC

KCL

Lactose

179. ‘RIGHT-FIRST TIME’ PRODUCTION OF GRANULES’

PROPERTIES MODELLING AND OPTIMIZATION

APPROACHS

Wafa’ Alalaween1, Mahdi Mahfouf1 & Agba Salman2

1 Department of Automatic Control and Systems Engineering, University of Sheffield, S1 3JD, UK



Among the units of production of drugs in the pharmaceutical industry, one could identify

‘granulation’ as an important step since, as a single operation, it can determine the fate of the

product downstream. Hence, accurate output prediction of such a process will ensure

downstream product ‘optimal’ quality. Particularly, modelling and simulation of granulation

process that received great deal of attention has hitherto focused on analytical and numerical

based techniques in the form of empirical based models and experimentation [1, 2]. Such

methodologies, which are unsuitable for real-time (on-line) applications, also, are known to

require a considerable computing power and a significant amount of process information

before they can perform reliably. Moreover, if the process itself is partially understood and

the associated physical equations are not known or are too complex as the case in granulation,

then these methodologies on their own will simply fail. In this research, we will show how to

develop a ‘generic’ framework utilizing intelligent systems for defining and locating optimal

process operating windows for the granulation process in the pharmaceutical industry to

achieve ‘right-first time’ production. The ultimate goal of the study being to optimise this

process systematically from two viewpoints: (i) Product quality; (ii) Process control and

repeatability.

[1] W. J. Wildeboer, J. D. Litster, I. T. Cameron, Modelling nucleation in wet granulation, Chemical

Engineering Science, 60 (2005) 3751–3761.

[2] J. M. Poon, C. D. Immanuel, F. J. Doyle III, J. D. Litster, A three-dimensional population balance

model of granulation with a mechanistic representation of the nucleation and aggregation phenomena,



180. TWIN SCREW GRANULATION: UNDERSTANDING THE

GRANULATION MECHANISM OF MIXING HYDROPHOBIC

AND HYDROPHILIC POWDERS

Aquinoscise L. Mundozah1, James J. Cartwright2, Claire C. Tridon2, Michael J.


1 Department of Chemical and Biological Engineering, University of Sheffield, Mapping Street

Sheffield, UK, S1 3JD

2 GSK, Third Avenue, New Frontiers Science Park, Harlow, Essex, UK, CM19 5AW

E-mail address: [email protected]

Twin screw granulation based on extrusion technology, has been considered as a much better

alternative to the current batch mode granulation. The main advantages of this process is that it

can be run continuously for longer periods. However, the complex attributes of the machinery

configuration in relation to the granulation of poorly wetting formulations is not well understood.

The aim of this study was to obtain an understanding of the twin screw granulation mechanisms

using increasing amount of hydrophobic powder in the formulation composition, comparing the

results with those for hydrophilic powders with regards to wetting-nucleation, coalescence-

consolidation and breakage-attrition. Granulation experiments were carried out with screws

consisting only of conveying elements and using water as the granulation liquid. The physical

properties (granule size distribution, shape, surface morphology and strength) and segregation

tendency of hydrophobic content across the granule size distribution were then compared.

Transitions in the granulation behavior were observed with increase in formulation

hydrophobicity. The hydrophobicity results in a decrease in the average granule size and a large

amount of fines (un-granulated material) due to poor liquid distribution and decrease in liquid

bridge strength between the particles. From results obtained, granulation mechanisms are

proposed to describe the resultant granule properties.

181. ROLLER COMPACTION: EFFECT OF MORPHOLOGY

AND AMORPHOUS CONTENT OF LACTOSE ON PRODUCT

QUALITY

Chalak S. Omar1, Ranjit M. Dhenge1, James D. Osborne2, Tim Althaus2, Stefan

Palzer3, Michael J. Hounslow1 & Agba D. Salman1


Sheffield S1 3JD, UK

2 Nestle´ Product Technology Centre York, Haxby Road, York YO9 11XY, UK



Roller compaction is a dry granulation technique used in many industries especially the

food, chemical and pharmaceutical industries. Within these industries lactose is one of the

most important materials used. The presence of amorphous lactose in predominantly

crystalline lactose influences powder compaction properties. The aim of this study is to

investigate the effect of morphology and amorphous content of lactose powder on the

properties of the ribbons and granules produced through the roller compactor.

Three types of lactose were used, with different morphologies and varying amorphous

content: anhydrous lactose (0.2% amorphous), spray dried lactose (10.3% amorphous) and α-

lactose monohydrate (2.7% amorphous). These types of lactose have different morphologies

and amorphous content due to the different manufacturing processes. Anhydrous lactose

produced from the crystallization of lactose solution using roller drying and spray died lactose

produced using the spray drier. These two types of lactose are considered to be granular types

of lactose as the particle consists of small crystals aggregated in one structure. The α-lactose

monohydrate was made by the slow crystallization of lactose solution which results is a single

crystal only, therefore, it can be considered as non-granular type of lactose. It was found that

the granular type of lactose showed better binding properties than the non-granular type of

lactose. The best binding capacity was shown by the spray dried lactose, which contains the

highest amount of amorphous lactose. It produced ribbons with the highest tensile strength

and lowest amount of fines in the product. It is known that amorphous powder deforms visco-

elastically during compression, which results in an increase in contact area between the

particles and decrease the distance between them [1]. This will lead to an increase in the Van

der Waals forces between particles and results in stronger ribbon. SEM images showed that

ribbons produced from lactose with the highest amorphous content exhibited a more flat and

smooth surface, in comparison to the other two types of lactose. This is an indication of

greater plastic deformation during compression, which resulted in an increase in the bonding

area and thus improves product quality. This type of lactose also produced stronger ribbons

and larger granules after milling.

[1] S. Palzer, Influence of material properties on the agglomeration of water-soluble amorphous

particles, Powder Technology, 189 (2009) 318-326.


182. TWIN SCREW WET GRANULATION: BINDER DELIVERY

Mohammed F. Saleh1, Ranjit M. Dhenge1, James J. Cartwright2, Michael J.




2 GSK, Third Avenue, Harlow, Essex, UK, CM19 5AW


The effects of three ways of binder delivery into the twin screw granulator (TSG) on the

residence time, torque, properties of granules (size, shape, strength) and binder distribution

were studied. The binder distribution was visualised through the transparent barrel using high

speed imaging as well as quantified using offline technique. Furthermore, the effect of binder

delivery and the change of screw configuration (conveying elements only and conveying

elements with kneading elements) on the surface velocity of granules across the screw

channel were investigated using Particle Image Velocimetry (PIV). The binder was delivered

in three ways; all solid binder incorporated with powder mixture, 50% of solid binder mixed

with powder mixture and 50% mixed with water, all the solid binder dissolved in water.

Incorporation of all solid binder with powder mixture resulted in the relatively longer

residence time and higher torque, narrower granule size distribution, more spherical granules,

weaker big-sized granules, stronger small-sized granules and better binder distribution

compared to that in other two ways. The surface velocity of granules showed variation from

one screw to another as a result of uneven liquid distribution as well as shown a reduction

while introducing the kneading elements into the screw configuration.


183. TWIN SCREW GRANULATION: A STEP TOWARDS

GRANULE DESINGING

Sushma V. Lute, Ranjit M. Dhenge, Michael J. Hounslow & Agba D. Salman




The objective of this study was to develop the knowledge space for preferential granulation

or designing of the granules to achieve the desired attributes of the granules. The change in

the granule attributes (size, shape, surface and structure) along the length of the granulator

was studied in order to understand the mechanism of granulation at varying liquid to solid

ratio (L/S) and screw speeds. The mechanistic understanding was developed which allowed to

control and design the granules with smaller median size, monomodal and narrower size

distribution with improved sphericity and denser structure.

184. GRANULE AND TABLET PROPERTIES IN A HIGH SHEAR

MIXER AND A FLUIDIZED BED GRANULATOR

Zhiyu Wang, Michael J. Hounslow & Agba D. Salman

Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, S1 3JD, UK


For the same liquid to solid ratio, the influence of process variables such as impeller speed

of the high shear mixer (HSM), air velocity of the fluidized bed granulator (FBG) and

granulation time for both processes were investigated. Granules were produced by granulating

calcium carbonate as the primary powder and PEG 1000 as the binder. Experiments were

performed to assess the effects of these variables on median granule size, granule size

distribution, bulk granule strength and granule porosity at different conditions. The properties

of the tablets made from granules such as tablet strength, disintegration time and surface

structure were analysed.

It was found that the median granule size increased with granulation time in both HSM and

FBG, and then decreased if the experiment was continued beyond a critical point. In HSM, it

was observed for a low impeller speed resulted in formation of granules with a wider size

distribution, which can be attributed to poor binder distribution. In FBG, increasing air

velocity improved the distribution of binder and helped break up oversized granules, resulting

in a narrow size distribution. It was also noticed that at the same liquid to solid ratio, the

granules produced by HSM were generally stronger and more spherical in shape in

comparison to those produced by FBG. As the tablet porosity plays an important role in tablet

disintegration time, consequently, the disintegration time of HSM tablets was quicker than the

FBG, since the tablet porosity was higher. These findings help build the knowledge space for

HSM and FBG melt granulation.

185. GRANULAR FLOW IN HIGH SHEAR MIXER

Ali Al Hassn1, Kimiaki Washino2, Ei L. Chan2, Michael J. Hounslow1 & Agba D.

Salman1



2 Mechanical Engineering Department, Osaka University, Suita, Osaka, 565-0871, Japan


High shear granulator is one of the principal equipment used in many pharmaceutical,

detergent and food industries. It usually produces high quality of granular properties, namely

high strength. However, the final granule properties are immensely sensitive to the particle

flow pattern within the moving bed due to its effect on the growth and breakage rates of the

granules. There are significant numbers of researches devoted to tackle this topic.

In this study, experimental and numerical approaches have been carried out to study the

particle flow pattern in a high shear mixer. Eirich mixer (Maschinenfabrick Gustav Eirich

GmbH & Co KG, type: EL1) which is an intensive mixer because both the impeller and

mixing pan can rotate together is used in this work. The movement of Calcium Carbonate

(CaCO3) and Polyethylene Glycol (PEG) granules within the mixer is examined. The flow

pattern of the granules is studied using Discrete Element Method (DEM) and compared with

the Particle Image Velocimetry (PIV). PIVlab is used to analyse the images taken by a high

speed camera. Experiments and the numerical modelling have been carried out for different

speeds and directions of impeller and mixing pan. The flow pattern was not symmetric in

radial direction neither around the impeller nor the centre of the pan. This is mostly due to the

eccentricity of the impeller from the centre of the pan. The velocity vectors obtained by both

methods were similar in the most areas of the mixer.

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