World Drug Delivery Summit - SciTechnol

Drug Delivery 2015Page 76

342nd OMICS International Conference

August 17-19, 2015 Houston, USAWorld Drug Delivery Summit

Posters

Volume 3, Issue 3J Pharm Drug Deliv Res

ISSN: 2325-9604 JPDDR, an open access journal

Page 77

Drug Delivery 2015August 17-19, 2015


Preparation and application of a novel intact solid lipid nano-vesiclesZhijun Yang and Aiping LuHong Kong Baptist University, Hong Kong

We have successfully achieved the preparation of intact solid lipid nano-vesicles that carry active pharmaceutical ingredients (API) and upon rehydration form liposomes with controlled drug release capability. To demonstrate this, solid lipid nano-

vesicles were prepared by lyophilizing the mixture of liposomes combined with or without ligands such as DSS or CA9, entrapped water-soluble API such as albuterol or siRNA or insulin, mixed with cryo-protectant lactose and a plasticizer glycerol and water. Liposome structure, entrapped API and controlled release capability were retained after lyophilization and rehydration, and the in vivo delivery effectives were confirmed. Since solid lipid nano-vesicles are more adaptable than liposomes or other nanoparticles to a wide variety of APIs and dosage forms, our novel invention allows a much wider usage of liposome technology in numerous pharmaceutical, chemical and biological situations.

BiographyZhijun Yang graduated at Shenyang Pharmaceutical University in 1986, after that he became a tutor and then lecturer in China Pharmaceutical University. During the period, he learned basic theories of Traditional Chinese Medicine at Nanjing University of Traditional Chinese Medicine, and conducted research in Gifu Pharmaceutical University in Japan as a visiting scholar. In 1993, he studied in Chiba University in Japan as a doctoral candidate, and obtained the PhD. in Pharmaceutical Science in 1997. Subsequently, Yang assumed the duty of a researcher in TaiYo Pharmaceutical Industry Ltd in Japan. In 2000, he carried out his postdoctoral research in University of British Columbia, Canada.

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Zhijun Yang et al., J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Use of PEG-cholane as solubility enhancer – Novel colloidal formulation for Amphotericin B deliveryClaudia Luengo AlonsoUniversity of Padova, Italy

PEG5kDa-cholane polymeric micelles were prepared for Amphotericin B delivery. The new formulation was characterized by DLS, RX, DSC, FTIR, circular dichroism, ITC and chromatography. The micelles were found to be stable after long term incubation and

promptly re-dispersed after freeze-drying. In vitro efficacy studies showed that the formulation was [email protected]

Claudia Luengo Alonso, J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Synthesis of natural macroporous sporopolline exine capsules extracted from Phoenix dactylifera L. and their application in oral colon-specific delivery of IbuprofenHamad A Al-Lohedan1, Saad M Alshehri1, Anis Ahmad Chaudhrary2, Tansir Ahamad1, Zuheir A Issa1 and Sami A A Al-Hussain1

1King Saud University, Saudi Arabia2Al-Imam Muhammad Ibn Saud Islamic University, Saudi Arabia

In this work, we have extracted Sporopollenin Macroporous Capsules (SMC) from date palm (Phoenix dactylifera L.) spores which were further coated by natural polymer composites (chitosan with gluteraldehyde). The polymer coated capsules were used in the

in vitro controlled delivery of ibuprofen. Characterization of the materials were performed by SEM, XRD and nitrogen adsorption-desorption isothermes together with spectral and thermal analyses. Effect of various factors such as pH, temperature and inital concentration was seen on the ibuprofen releasing. The loading of ibuprofen increased by decreasing its concentration and followed the Langmuir adsorption isotherm. pH 6.0 was found to be the most favorable pH for the loading of ibuprofen at which 97.2% (50 mg/ml) drug was loaded to the capsules. The release of ibuprofen was faster when the pH was changed from 1.4 to 7.4. Cytotoxicity results of SMC and its capsules were also tested against human intestinal Caco-2 cell line using MTT assay which has shown that all the materials in the study were biocompatible.

BiographyHamad A Al-Lohedan has more than 36 years of extremely active and productive career in the field of surfactant and polymer chemistry. After finishing his MSc in Organic Chemistry in 1979 from University of California, USA, he joined research and obtained PhD from the same University in 1981. He worked in the field of physical organic chemistry involving the role of surfactant on the rate of organic reactions. His current research interests include drug delivery formulations using biocompatible substances, drug-protein interactions, nanomaterials synthesis, corrosion inhibition by surfactants. He has authored more than 120 research publications.

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Hamad A Al-Lohedan et al., J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Preparation and pharmaceutical evaluation of acetaminophen nano-fiber tablets: Application of solvent-based electrospinning method for tablettingMami Hamori, Rina Amano, Yoko Fuse, Ayuko Ikemoto, Kei Ishizumi, Kanako Ishino, Megumi Goto, Asako Nishimura, Kazumasa Naruhashi and Nobuhito ShibataDoshisha Women’s College of Liberal Arts, Japan

In this study, we described an application of the solvent-based electrospinning (ES) method, which is mainly employed in the textile industry, to the field of pharmaceutics. Using a modified ES instrument, nano-fiber sheet including acetaminophen (AAP, a model

drug) was prepared. Where, Methacrylic Acid Copolymer S (MAC) was used as a base polymer to produce nano-fiber, and then three types of tablets were prepared and evaluated pharmaceutically. By attaching a conductor-rod made from stainless steel to the central part of nano-fiber-collection plate of the ES apparatus, MAC nano-fiber sheet with or without AAP could be produced effectively. In vitro release profiles of AAP from a tablet prepared by MAC nano-fiber with AAP (NFT), a tablet prepared by absorbing AAP to drug-free MAC nano-fiber (NFTfree) and a tablet prepared by semi-absorbing AAP to MAC nano-fiber (NFTsemi) showed controlled release aspects of AAP as compared to a conventional physical mixture. Moreover, these tablets showed pH and compressed force-dependent release profiles of AAP. In vivo pharmacokinetic study in rats after intra-duodenal administration of these tablets including MAC nano-fiber clearly demonstrated that application of nano-fibrotic technique based on the ES method is a useful one to expand drug delivery system. Moreover, tableting of MAC nano-fibers can be performed using a tableting machine without lubricants, and addition of Tween 20 into the nano-fiber enabled regulation of the release profile of AAP. Thus, the ES method reported here is a useful technique for the controlled-release of drugs and has wide-ranging potential for pharmaceutical applications.

BiographyMami Hamori is, currently, a PhD student in Japan at Doshisha Women’s College of Liberal Arts (Department of Biopharmaceutics). Her research interests focus on the drug delivery systems using nano-fibers.

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Mami Hamori et al., J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Effect of Acetazolamide on cytokines in rats exposed to high altitude hypoxia environmentRong Wang, Chang Wang, Hua Xie, Wenbin Li, Hui Lu and Zhengping JiaLanzhou General Hospital, China

Introduction: It was known the relationship between environment and immunity as a result of the interaction between neuroendocrine and immune systems. Environmental conditions (hypoxia, temperature, physical exercise) represent some of the stimuli that may influence the functional behavior of immunocompetent cells [1]. Many parameters include the evaluation of cytokine expression and lymphocyte subsets in relationship to hormone production and strenuous exertion have been considered [2]. Both acute and chronic hypoxia is known to influence cytokine levels [3]. More and more articles [4,5] reported that hypoxia cause systemic inflammatory response, which was the major factor causing high altitude multiple organ dysfunction syndromes. In this paper, we designed to rapidly exposure to the high-atitude areas, studied the influence of acute exposure to high altitude on the body and screened for the major cytokines that might be involved in the development of high altitude disease.

Conclusion: In summary, the results indicate that the exposure to high altitude and the consequent hypoxia are able to alter a number of cellular and functional immunologic parameters. Further studies in other subjects are needed to evaluate the physiologic significance of these changes, particularly in terms of chemokine and cytokine expression.

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Rong Wang et al., J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Curcumin loaded nanoparticles of a grafted copolymer for the treatment of inflammatory bowel diseaseNeelam SutharManipal University, India

Novel pH-sensitive hydrolyzed polyacrylamide-grafted-xanthan gum (PAAm-g-XG) nanoparticles (NPs) loaded with curcumin were prepared for the colonic delivery in the treatment of inflammatory bowel disease (IBD). PAAm-g-XG copolymer was

synthesized by free radical polymerization mechanism by grafting PAAm on the backbone of XG with the aid of ammonium persulfate. Independent factors including drug and polymer content, concentration and volume of AlCl3 solution, volume of organic and aqueous phases, and sonication parameters were varied to optimize curcumin loaded NPs. The optimized nanoparticles (CN20) freeze dried with 10% w/v mannitol were spherical in shape (as assessed by scanning electron microscopy and transmission electron microscopy) with an average size of 425 nm. In-vitro drug release studies demonstrated that, these NPs displayed good resistance to drug release in acidic media. In pH 1.2, 4.6 and 6.8 buffer solutions, a total of <30% cumulative amount of drug was released over 6 h; whereas, 82.88% release was observed in pH 7.4 phosphate buffer within 6 h, which confirms ionization and electrostatic repulsion of COO- functional groups of NPs leading to a path for drug and pH dependent solubility of the grafted polymer. In addition to pH-sensitivity, microflora activated property as indicated by >90% release of curcumin within 2 h in pH 7.4 containing 1% w/v rat caecum content, makes this polymer suitable for colon targeting. Curcumin NPs found to attenuate colitis in acetic acid induced IBD rats with alleviation of myeloperoxidase and nitrate levels, and normalization of body weight, colon length and colon weight. High Tmax of NPs compared to plain curcumin established occurrence of curcumin absorption after reaching colon and increased Cmax (~3 fold) and AUC (~2.5 fold) concluded enhanced absorption and effectiveness.

BiographyNeelam Suthar completed her Masters in Pharmaceutics from Manipal University. She has published 1 paper on drug delivery in a reputed journal. She is currently working as a Pharmacist in Kenya.

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Neelam Suthar, J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Automation of biologics formulation stability testing: Achieving equivalent results with less manual effortRussell BurgeFreeslate Inc., USA

Biologic drugs can be inherently prone to degradation and instability, which can make designing safe, stable and effective formulations challenging. To develop a stable and effective formulation, scientists perform multiple screening, robustness and

stability studies throughout drug development to build a strong knowledge base. However, personnel are often limited in the number of formulations they can screen in any given study due to the rigors of current manual workflows, short timelines and often limited resources. Automation of formulation screening, forced degradation studies and preparation of analytical samples can increase efficiency and throughput, but must provide comparable results to current processes and analytical methods. Therefore, a set of automated processes were developed by a team of scientists to provide equivalent results to traditional manual processes. Automated systems and their procedures were used to evaluate multiple formulations of two drug products, and then results were compared to those from manual processes generated at the biopharmaceutical company, which developed the drug products. Multiple formulations of both protein drug products were investigated. Each formulation was first stressed by stirring, heat or agitation, and then analyzed by fully automated visual inspection, and semi-automated UV/Vis, DLS and SE-UPLC. Software running the integrated automation system also managed data, so that reporting results was easily performed. For both drug products, formulation robustness rank-orders resulting from automated procedures were comparable to those from manual methods. We also describe productivity gains achieved by incorporating automation into formulation development.

BiographyRussell Burge earned a PhD in molecular biology and biochemistry from The Scripps Research Institute in La Jolla, California. He worked on characterization of aptamers as part of Post-doctoral training at the University of Colorado, Boulder. He worked as a Formulation and Analytical Development Scientist at KBI Biopharma, where he contributed to numerous biopharmaceutical development projects. He is an Applications Scientist at Freeslate where he designs and performs demonstrations of automated systems used for research and development of pharmaceuticals. His additional contributions to Freeslate range from market research to the development of new technologies and products.

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Russell Burge, J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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SV40 T/t-common polypeptide enhances the sensitivity of HER2-overexpressing human cancer cells to anticancer drugs Cisplatin and DoxorubicinWon-Bo Wang and Shu-Ping Hsueh National Taiwan University, Taiwan

HER2-overexpressing cancer cells are resistant to cisplatin (CDDP) and doxorubicin (DXR). Previously, we reported that SV40 T/t-common polypeptide can specifically induce apoptosis in many HER2-overexpressing cancer cells but not in non-HER2-

overexpressing cancer cells. Here, we report that SV40 T/t-common polypeptide could specifically sensitize HER2-overexpressing cancer cells to CDDP and DXR and specifically enhance CDDP or DXR-induced apoptosis in these cells. This activity of T/t-common may be attributed to its ability to down-regulate Bcl-2 and Bcl-XL and to modulate ERK and JNK activities in CDDP or DXR-treated HER2-overexpressing cancer cells. T/t-common could enhance the antitumor activity of DXR on HER2-overexpressing ovarian tumor in NOD/SCID mice, suggesting that combination therapy using T/t-common and chemotherapeutic agents may provide a new approach for treating HER2-overexpressing cancers.

BiographyWon-Bo Wang completed his PhD at Purdue University and was a Postdoctoral Fellow at Dana-Farber Cancer Institute. He, now, is a Professor in College of Medicine, National Taiwan University.

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Won-Bo Wang et al., J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Study on the component analysis and establishes reference standards for the pharmacopoeial raw materialsSe Jin Lee and Hoon Sik ChoKorea Conformity Laboratories, Korea

Conditions to be equipped this drug is to ensure safety and efficacy. Safety and efficacy with respect to the materials developed as a means for securing to secure the development of a method through the preclinical studies and clinical trials, and then a method

of securing to ensure the quality of the commercial product.The former is a secure time already developed the inherent property of the material, the latter manages to establish whether a suitable gauge by means of commercially available products for quality assurance standards to maintain the quality of a certain level.

In this regard, there are three raw material components(pregabalin, p-aminophenol, L-cystein) for use as a reference standard with respect to the raw materials and the method for evaluation of the impurity components of the raw meal to determine the material through optical analysis. In addition, a review of whether to perform Mass Balance method (volatile impurities, inorganic impurities, purity analysis reflects the organic impurity content measurements) the amount of the check for the results of the Republic of Korea Pharmacopeia, USP and EP standards of quality cross after three or more organizations the reliability is verified by performing a high-quality verification methods (statistical analysis) to verify the quality.

Therefore, in this study were confirmed by the quality assurance with respect to the ingredients and contents in the raw materials of the three, is ensuring the safety and efficacy in pharmaceutical companies plan to be used with confidence. Import through which the standard is expected to be able to replace.

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Se Jin Lee et al., J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003




e-Posters



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Poly(3,4-ethylenedioxypyrrole) – biocompatible matrix for local drug delivery systemsKatarzyna Krukiewicz, Barbara Gniazdowska and Jerzy K ZakSilesian University of Technology, Poland

Introduction: In the past few years local drug delivery systems became very popular methods of treatment, making this process easier and more effective. Since conducting polymers are extensively studied in the field of biosensors, artificial scaffolds and neural probes, they are supposed to be promising materials for controlled drug delivery systems. Two most popular conducting polymers exhibiting biocompatibility are polypyrrole (PPy) and poly(3,4-ethylenedioxytiophene) (PEDOT). Recent literature reports indicate poly(3,4-ethylenedioxypyrrole) (PEDOP) as an ideal candidate as material for biomedical engineering, mainly because of its biocompatibility. PEDOP combines the most desirable properties of PPy and PEDOT: it has lower polymerization potential than PEDOT and, simultaneously, is more stable than PPy. In this study, we present one of the first efforts to utilize PEDOP for the immobilization of drugs. Two model drugs have been chosen – quercetin (Que) and ciprofloxacin (Cipro). Quercetin is one of flavonoid drug with wide spectrum of activities. Ciprofloxacin mainly treats bacterial infections caused by Gram-positive and Gram-negative bacteria.

Methods: Drug immobilization was performed via two methods – one step immobilization and three steps immobilization. In one step method, EDOP was electropolymerised in the presence of quercetin or ciprofloxacin. In three step method, drugs were immobilized as the result of the ion-exchange process on PEDOP matrix. Drug release process was performed by immersing polymer matrix in electrolyte solution (passive mode) or by the application of constant potential -0,7 V (active mode). The efficiency of controlled release of drugs was studied with UV-Vis spectroscopy. The morphology of PEDOP matrices was investigated by SEM.

Conclusions: Both methods of drug immobilization, one step and three steps, have been successfully applied to obtain drug-modified polymer matrices. Depending on the immobilization technique and model drug, there have been major differences in the dominant release modes. For PEDOP/Cipro films the dominant release modes is active release, while the passive release is dominant for PEDOP/Que films. SEM images show large variety of surface morphologies attainable by the proper choice of synthesis conditions.

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Katarzyna Krukiewicz et al., J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Modelling of in-vivo tissue electroporation and subsequent cellular drug uptakeBradley BoydUniversity of Canterbury, New Zealand

The primary motivation of this study is to develop a macroscopic model of mass transport in electroporated biological tissue in order to determine the cellular drug uptake. The model captures the influences of both irreversible electroporation as well as

the transient resealing of the cell membrane associated with reversible electroporation. The model attempts to fit the microscopic behaviour of the cell membrane to the macroscopic transport characteristics through an empirically based representation of the bulk tissue electrical conductivity. Two case studies are conducted to illustrate the applicability of this model by comparing transport associated with two electrode arrangements: side-by-side arrangement and the clamp arrangement. The results show increased drug transmission to viable cells is possible using the clamp arrangement due to the more uniform electric field produced.

BiographyBradley is in the first year of his PhD at Canterbury University in Christchurch, New Zealand. His project involves numerical modelling of biological processes relating to transdermal drug delivery. He is supervised by Dr Sid Becker of the Mechanical Engineering Department. Bradley was awarded an honours degree from Canterbury University at the end of 2014.

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Bradley Boyd, J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Motivations for a custom experimental apparatus for ultrasound enhanced transdermal drug delivery experimentationJeremy RobertsonUniversity of Canterbury, New Zealand

This poster outlines the motivations and initial design specifications relating to a custom experimental apparatus for sonoporation and sonophoresis experimentation. These experiments usually involve inserting a cylindrical transducer into a glass Franz

diffusion cell. The motivations for a custom apparatus are: the hypothesis that the pressure amplitude that is applied to the current system by the transducer is not equal to the pressure amplitude at a point on the skin surface due to acoustic reflections in the system (this is supported by preliminary qualitative results from a numerical model under development); the ultrasound induced heating within Franz diffusion cells that often requires researchers to change experimental fluids mid experiment; and the high standard deviations in published results. Some proposed design specifications are: to maximize the uniformity of the ultrasound field; to allow for the control of temperature in all mediums present; to allow for experimental input parameter values at the skin surface to be measured or accurately estimated; and to minimize standard deviation between repetitions (maximize repeatability). Numerical modelling and 3D printing are both expected to be vital to the development of this apparatus. This proposed apparatus is intended to improve the validity and repeatability of in vitro sonoporation and sonophoresis experiments.

BiographyJeremy is in the first year of his PhD at Canterbury University in Christchurch, New Zealand. His project is in the field of active enhancement methods in transdermal drug delivery. He is supervised by Dr Sid Becker of the Mechanical Engineering Department. Jeremy was awarded a first class honours degree from Canterbury University at the end of 2014.

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Jeremy Robertson, J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Physical stability and absorption increase of encapsulated vitamins with liposomal carrier to formulate therapeutic cream for Psoriasis disease treatmentAzadeh Izadyari1, Masood Sahraie1, Saharnaz Rakizadeh2 and Fariba Sadat Alambin1Islamic Azad University, Iran2Pars Azmaye Teb, Iran 3College of Science, Iran4University of Tehran, Iran

One of the negative aspects of vitamins is their low absorption through skin. Also, the combination of water or lipo-soluble vitamins and their biological properties protection such as anti-oxidant are difficult for formulating in therapeutic products.

Encapsulation of these macromolecules, by liposomal carrier is an important method to preserve their native properties. The aim of this research is producing multi-layer liposomes for encapsulation of vitamins D3, E, A, C and B5 and increasing physical stability of vitamins in therapeutic cream for psoriasis disease treatment. In the current study, liposomes containing vitamins were prepared with thin-film hydration-sonication method. According to FTIR and DSC results, no interaction was observed between encapsulated vitamins and liposome constituents. The particle size and its distribution and encapsulation efficiency were respectively calculated about 250 nm, 0.70–0.85 and more than 92%. Also, liposomes morphology analysis by scanning electron microscopy (SEM) showed spherical form for multi-layer vesicles. Then liposomal carriers were formulated in anti-psoriasis cream to compare its absorption rate and effectiveness with/without encapsulated vitamins. For treated group with liposomal cream, the results showed an increase in its absorption rate through skin (less than 4 minutes) and rapid improvement of lesions (in comparison with cream without vitamin vesicles). So, it can be said the liposomes containing bioactive materials and macromolecules have therapeutic potential applications, improvement of drugs shelf life and its stability in cosmetic products. In this field, physical stability of vitamins in various industry (such as medicine and dermatology) are most important effect of encapsulation method and liposomes as cover, play the great protection role against vitamins degradation.

BiographyAzadeh Izadyari has completed her master in Chemical Engineering. Currently, she is a doctoral student in Chemical Engineering, University of Ayatollah Amoli Branch. Her thesis is in field of drug delivery and has published many papers in reputed journals. Now, she is working in Pars Azmae Teb(Cerita) as scientific head of southern Iran and Researcher in R&D. Saharnaz Rakizadeh has completed her master in plant biology-Systematics & ecology graduated from University of Tehran, Iran. Now, she is working in research company Pars AzmaeTeb as Science department manager. She has many scientific articles in international authentic scientific journals. Masood Sahraie has completed his PhD in dental science and graduated from University of Shahid Beheshti, Tehran, Iran. Now he is the CEO in Pars Azmaye Teb (Cerita), producing many skin & hair care. Fariba sadat Alambin is Master of science student of Nanobiotechnology in University of Tehran, Iran. She has many papers in international authentic scientific journals. Now, she is working in Pars Azmay Teb (Cerita) as scientific expert.

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Azadeh Izadyari et al., J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003



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Novel Inhalable Drug Delivery System for Tuberculosis TreatmentVishnu Vardhan Reddy Beeram1, Venkata Nadh R2 and Krupanidhi S1

1Vignan’s University, India2GITAM University, India

Novel targeted drug delivery systems have gained attention for the treatment of various chronic diseases with the limitations associated with conventional drug delivery treatment. Among various routes of drug delivery systems, the pulmonary route

gained much importance to target drug delivery for both local and systematic treatment. Mostly the treatment efficacy depends on the technique by which the drug is delivered and optimum concentration reached, above or below this level leads to produce toxic or sub therapeutic action. Because of the high permeability and large absorptive surface area of lungs (approx 70-140 m2 in adult humans) and rich blood supply are encouraging or growing interests in developments in pulmonary drug delivery. The smaller airway and alveolar space accounts more than 95% of total lungs surface area and it is directly connected with the systematic circulation via the pulmonary capillary circulation. To deliver drugs into the pulmonary route, the most preferable devices are Dry powder inhalers. Chemotherapy of tuberculosis through inhalable drug delivery system is showing positive approach for eradicating Mycobacterium Tuberculosis by targeting both locally and systematically. This novel approach can maintain the drug concentration above therapeutic and below toxic levels for longer and longer duration with the different formulation development options like controlled or sustained drug delivery, mucoadhessive drug delivery. Nanometric range of anti tubercular drug loaded Nanoparticles or Nanospheres with different polymers and combination with any mucoadhessive polymers will offer excellent drug targeting and controlled release for longer duration of time. The drug loaded Nanospheres can make into inhalable dry powder Microparticulates by using inert carriers like mannitol, lactose monohydrate etc. So inhalable drug delivery is increasing interest in chemotherapy of tuberculosis.

BiographyVishnu Vardhan Reddy Beeram pursuing PhD from VIGNAN’S University, Vadlamudi, Guntur, Andhrapradesh, India. He has Completed Master of pharmacy in Pharmaceutics specialization form Rajiv Gandhi University of Health and Sciences, Bengaluru, Karnataka, India. He has published more than 10 papers in reputed scientific journals.

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Vishnu Vardhan Reddy Beeram et al., J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003




Accepted Abstracts



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J Pharm Drug Deliv Res 2015, 3:3http://dx.doi.org/10.4172/2325-9604.S1.003

Colon targeted delivery of the hydroxylase inhibitor dimethyloxallogylcine (DMOG) provides enhanced protection in a murine model of colitis Murtaza M Tambuwala1, Mario C Manresa2, Eoin P Cummins2, Ivan Coulter3 and Cormac T Taylor2

1University of Ulster, Northern Ireland2University College Dublin, Ireland3Sigmoid Pharma Inc., Ireland

Pharmacologic hydroxylase inhibition represents a potentially important new therapeutic approach to colitis. However, because of potential side effects associated with systemic delivery of hydroxylase inhibitors including unwanted regulation of angiogenic,

metabolic and erythropoeitic processes, it is desirable to develop new methods of delivery of such compounds to specific regions of the intestine in order to provide local therapeutic effects without systemic exposure. We have utilized an emulsion-based drug delivery system to attempt to achieve this goal. Initially, we demonstrated that the formulation of the hydroxylase inhibitor DMOG into a novel emulsion-based colon-specific delivery system was without effect upon the biological activity of the drug. The physical process of formulation of DMOG into the colon-specific drug delivery sphere system does not impact upon its biological activity. We next investigated whether formulated DMOG is delivered specifically to the colon when the beads are administered orally to mice. This was investigated by using transgenic mice which ubiquitously express the firefly luciferase gene under the control of a concatomer of NF-kappaB response elements (NRE) to assess NF-kappaB activity in vivo. Our results demonstrate that colon-targeted DMOG delivery resulted in an effective and selective elevation in basal NF-kappaB activity in the colon. We next investigated whether the therapeutic efficacy of colon-specific DMOG delivery in a murine model of DSS-induced colitis. Results from these experiments suggest those colon targeted DMOG beads are protective against experimental colitis in mice at a 40 fold lower dose as compared to systemic administration of DMOG. Our previous work has demonstrated that a significant proportion of the protective effects of DMOG observed in models of intestinal inflammation is a result of enhanced intestinal epithelial barrier function which diminishes the exposure of the mucosal immune system to luminal antigenic material.

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Development and evaluation of gastro retentive drug delivery system for a novel H2-receptor antagonist – LafutidineAbdul Aleem MohammedNajran University, KSA

Lafutidine a newly developed second generation histamine H2-receptor antagonist with its selective absorption from upper part of gastrointestinal tract and a biological half-life of 1.92±0.94 h makes it a suitable candidate for the development of gastroretentive

sustained release drug delivery system in order to enhance the bioavailability. The present work explored the development of multiple unit type oral floating microspheres using Eudragit S-100 as a polymer by solvent evaporation method. The prepared microspheres were evaluated for the micromeritic properties, floating behavior, entrapment efficiency, drug release kinetics and X-ray radiographic studies. The microspheres showed good flow properties and the particle size ranging from 51.72±3.01 to 92.43±5.34 µm. Scanning electron microscopy showed spherical size with porous surface. The entrapment efficiency was found to be 56.05±5.46 to 78.56±3.17. Floating microspheres showed good buoyancy (65.12±3.57 to 94.23±3.6) up to 20 hrs. X-ray radiographic studies also proved better retention in the stomach. Thus, it may be useful for prolonged drug release in stomach to improve the bioavailability and reduced dosing frequency.

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Preparation and in-vitro evaluation of Meloxicam co-ground mixturesAly NadaKuwait University, Kuwait

Meloxicam is a non-steroidal anti-inflammatory drug of the oxicam class, used to relieve the symptoms of dental pain, arthritis, primary dysmenorrhea, fever and as an analgesic, especially where there is an inflammatory component. Meloxicam inhibits

cyclooxygenase (COX) synthesis. This enzyme is responsible for converting arachidonic acid into prostaglandin H2. This is the first step in the synthesis of prostaglandins, which are mediators of inflammation. Meloxicam has been shown, especially at its low therapeutic dose, selectively to inhibit COX-2 over COX-1. The co-grinding technique, unlike the other solid dispersion techniques, was economically and environmentally desirable. In co-grinding approach, the use of toxic organic solvents could be easily avoided. Therefore, it was suitable for industrial manufacture on a large scale. Co-grinding of poorly water soluble drug (Meloxicam) particles with different hydrophilic polymers like PEG and / or PVP-K25 resulted in the formation of amorphous powders having enhanced drug solubility and dissolution properties , even if much smaller amount of hydrophilic polymers were used (MLX/hydrophilic polymers =1:1, w/w). According to percentage of drug dissolved, dissolution rate of MLX – PEG co-ground binary mixture prepared by ball mill or vibrational mill > MLX – PEG – PVP co-ground ternary mixture > MLX – PVP co-ground binary mixture > MLX – polymer physical mixture > MLX alone. As regards to the grinding techniques, co-ground mixtures prepared with ball mill has a relatively higher dissolution rate than those prepared with vibrational mill for all of the selected polymers at all of the employed ratios. An increase in the concentration of carrier in the co-ground blends resulted in an increase in the dissolution rate of MLX. The enhancement of dissolution of MLX from co-ground mixtures could be due to the reduction of crystalline nature of the drug in co-ground mixtures. Among all the prepared mixtures in this study, co-ground mixture of MLX and PEG in 1:4 ratio by ball mill showed the best results in terms of extent and rate of dissolution in water and phosphate buffer. This effect was not only due to particle size reduction, but also loss of crystalline nature of the drug during co-grinding. DSC and PXRD studies indicated that crystalline nature of drug was reduced after co-grinding with PEG and / or PVP as compared to their corresponding physical mixtures. SEM images showed that particle size of MLX was reduced after co-grinding with hydrophilic polymer PEG using ball mill.

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Multifunctional polymeric micelles for the simultaneous delivery of siRNA and chemotherapeutic agents: A promising strategy to reverse the drug resistance in the treatment of cancer Giuseppina SalzanoNortheastern University, USA

Since its discovery, small interfering RNAs (siRNA) have quickly crept into the biopharmaceutical research as a powerful tool for the treatment of different human diseases based on altered gene-expression. Despite promising data from pre-clinical studies,

concrete hurdles, still need to overcome to bring therapeutic siRNAs in clinic. With this in mind, we have reversibly modified siRNA with a phosphothioethanol (PE) portion via a reducible disulfide bond and incorporated the resulting siRNA-S-S-PE conjugate into nanosized polyethyelene glycol 2000-phosphatidyl ethanolamine (PEG2000-PE)-based polymeric micelles (PM). Then, we successfully co-incorporated in the same PM, an anti-survivin siRNA-S-S-PE conjugate and chemotherapeutic agent such as paclitaxel (PXL) for combined therapy. The developed nanopreparation showed high colloidal stability, high incorporation efficiency of both active agents, and small particle sizes compatible for parenteral administration. In an animal model of cancer, the micelles accumulate in distal tumors and delivered anti–survivin siRNA and PXL in sufficiently high amounts to mediate a potent and specific survivin downregulation and to improve anticancer activity as compared with single agents. In addition, survivin downregulation by anti–survivin siRNA/PXL PM mediated the sensitization of a resistant ovarian tumor to non-effective doses of PXL. Compared to conventional systems for siRNA delivery, we suggested a new type of platform that can respond to local stimuli, such as high levels of reductase in cancer cells, and release the siRNA free and active at the desired site. Moreover, the developed PM are suitable to incorporate different type of active agents for combined therapy.

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Novel tumor-targeted zein-based nanocarriers for co-delivery of anti-cancer drugs in breast cancer therapyAhmed O Elzoghby1, Sarah Laqany1, Sally Sabra1, Maged Helmy2, Maha El-Demellawy3, Medhat Haroun1, Salah Sheweita1 and Nazik Elgindy1

1Alexandria University, Egypt2Damanhur University, Egypt3City for Scientific Research & Technology Applications (SRTA-City), Egypt

Zein is a hydrophobic plant protein characterized by a good biodegradability and insoluble characteristics making it a good candidate for the development of biopolymeric nanoparticles for drug delivery. In this study, three types of zein nanocarriers

were developed for targeted delivery of poorly soluble anti-cancer drugs. First, zein nanospheres were successfully prepared via phase separation technique for co-delivery of exemestane and luteolin. Second, zein nanocapsules were successfully developed using spontaneous emulsification technique for co-delivery of exemestane and resveratrol. The developed drug-loaded zein nanospheres and nanocapsules demonstrated a suitable particle size (150-250 nm) and a negative zeta potential (above -30 mV) exhibiting a controlled drug release behavior. The surface of zein nanocarriers was successfully decorated with lactoferrin as a tumor-targeting ligand via electrostatic interaction. In the third part of this study, amphiphiliczein-lactoferrin co-polymeric micelles for co-delivery of rapamycin and wogonin were successfully developed. The chemical conjugation via carbodiimide-coupling technique was evidenced by NMR, IR and fluorescence spectroscopy while the core-shell structure of the micelles in aqueous solution was demonstrated by TEM. The drug-loaded self-assembled nanocarriers exhibited a nanometric size (100-250 nm) and a positive zeta potential (around +30 mV) in addition to high drug loading and a sustained release profile. The developed zein nanocarriers showed superior cytotoxicity and cellular uptake against MCF-7 breast cancer cells and powerful in vivo anti-tumor efficacy in breast cancer rat model compared to free drugs. Thereby, zein nanocarriers could evoke a new effective tumor-targeted delivery system to breast cancer by passive and active targeting.

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Simultaneous estimation of olmesartan Medoxomil and Indapamide in tablet dosage form by spectroscopic methodHasumati A Raj1, Rucha A Patel1, Meera V Lad1 and Richa A Dayaramani21Shree Dhanvantry Pharmacy College, India2Tolani Institute of Pharmacy, India

Olmesartan medoxomil and Indapamide combination is used in cardiac disease condition like Hypertension. Sustain release tablet formulation comprising Olmesartan medoxomil and Indapamide. Patent for formulation is patented in china by Ministry of

cardiovascular disease institute and patent for treatment for hypertension is patented in Japan. Olmesartan medoxomil was approved in USFDA on April, 2002 at New York and indapamide was approved in Lipha pharmaceutical institute on July 1998. Extensive literature survey related spectroscopy, high performance liquid chromatography, high performance thin layer chromatography, Reverse phase high performance liquid chromatography DAD method for estimation of Olmesartan medoxomil and Indapamide. Here thirteen analytical methods available for olmesartan medoxomil and twenty six analytical methods available for olmesartan medoxomil and its combination. And four analytical methods available for Indapamide, and nine analytical methods available for indapamide and its combination, seven analytical methods available for stability study for olmesartan, three analytical methods available for stability study for indapamide with other combination and no analytical method found for indapamide alone and for combination of olmesartan medoxomil and Indapamide, which indicates the need for analytical method development for Olmesartan medoxomil and Indapamide. Here attempt was made to develop and validate a sensitive, reproducible and specific spectroscopy method for Olmesartan medoxomil and Indapamide combination.

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Telomerase enzyme as a molecular marker in hepatocellular carcinomaAllam E, El-Zayadi A, Ali A, Helal T, Hamdy H, Abou-Ghalia A and Elghazawy MConsultant, Egypt

Hepatocellular Carcinoma (HCC) is a common cause of death in Egypt and worldwide. Hepatitis C Virus (HCV) was proven to be the most important risk factor. Telomere hypothesis of cellular aging and tumorigenesis explains major part in pathogenesis

of HCC. So, in this study, we are aiming to investigate the use of telomerase enzyme in diagnosis of HCC. A group of 80 patients were divided into two groups, first group that has HCC and second group that has chronic HCV infection. Assay of telomerase enzyme activity was done in all patients using Telomere Repeat Amplification Protocol (TRAP–ELISA). This was correlated with full clinical, laboratory and histo-pathological evaluation of the patients. Results showed that telomerase activity was detected in 100% of HCC cases with a mean level of 136.75. On the other hand, telomerase activity was detected in 86.67% of HCV cases with a mean level of 16.38. There was a significantly higher telomerase activity in HCC group than HCV group (p value<0.001). Results also showed no correlation between enzyme level and tumor size, although higher levels were detected in late cases. Also the elevation of the enzyme levels in HCC with HCV infection compared to HCC cases without HCV (p<0.05) may predict more aggressive course of this cancer. The diagnostic validity test showed that best cut-off level of the enzyme is 9 with sensitivity of 98% and specificity of 60% and efficacy of 83.8%. In conclusion, assay of the Relative Telomerase Activity (RTA) may be a sensitive tumor molecular marker in diagnosis of HCC regardless sex, child class or tumor size. Finally, we recommend strict follow up of chronic liver patients with high RTA to detect any malignant transformation. Also, more studies are needed to study the validity of using serum RTA instead of tissue RTA to decrease the need of liver biopsy in HCC patients.

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PEGylated monoolein-based liquid crystalline nanoparticles of aloe-emodin: Optimization, in-vitro characterization and anticancer activity on human breast cancer cell lineMay S Freag,Yosra S R Elnaggar and Ossama Y AbdallahAlexandria University, Egypt

Aloe-emodin (AE) is a herbal drug with potential anticancer activity against many tumors. However, its hydrophobicity handicaps its efficient parenteral administration for chemotherapy. PEGylated Monoolein-based liquid crystalline nanoparticles (LCNPs)

of AE were first fabricated for enhanced water solubility and anti-tumoractivity.Optimization of various factors was performed based on particle size (PS) and zeta potential (ZP). Phase behaviour and physicochemical properties were characterized through polarized light microscopy, TEM, DSC, IR and XRD. Potential of PEGylation to reduce hemolytic toxicity of Monoolein was also assessed. Serum stability of LCNPs was evaluated in fetal bovine serum (FBS). Cytotoxicity and cellular uptake studies were assessed on MCF-7cell line. The fabricated PEGylated LCNPs showed PS of 190 nm ± 3.13 and ZP of -49.9±0.9 mV. PEGylation strategy could reduce MO hemolysis from 50% ±4.34 to 3%±1.04, and increase LCNPs stability. IC50 for AE-LCNPs was 3.18 and 4.3 folds lower compared to free AE after 24 and 48 hr, respectively. The cellular uptake of AE in LCNPs was about 3.21 folds higher than free AE after 24 hr incubation. In conclusion, PEGylated LCNPs could successfully enhance solubility, cellular uptake and cytotoxicity of AE and increase MO hemocompatibility, serving as a promising nanocarrier for efficient parenteral delivery of AE in cancer therapy.

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Development and evaluation of floatable and swellable controlled release gastroretentive dosage form of Sulpiride Mohammed KaleemullahManagement & Science University, Malaysia

The purpose of the present research was to design a gastroretentive dosage form based on floating and swelling principles that would enhance the bioavailability of sulpiride, a drug with a narrow absorption window in the upper gastrointestinal tract.

Gastroretentive tablets were prepared by direct compression method, using various amount of polyethylene oxide (PEO) and hydroxypropylmethyl cellulose (HPMC) as release retarding agents, citric acid and sodium bicarbonate as floating agents, and crospovidone, sodium starch glycolate, croscarmellose sodium and super porous hydrogel as swelling agents. The gastroretentive formulations were evaluated for physical characteristics, in vitro drug release, floating lag time, floating duration and swelling index. Formulation containing a combination of PEO-HPMC at 1:3 ratio was able to extend the drug release up to 24 hr and had the swelling index of 334.70%. Moreover, the addition of 10 mg of citric acid and 50 mg of sodium bicarbonate to the formulation achieved in vitro floating for 24 hr and 266 sec floating lag time. Furthermore, the addition of the croscarmellose sodium-superporous hydrogel combination (1:1 ratio) to the formulation yielded optimized formulation (F34) with the characteristics of high swelling index (823 %), sustained drug release up to 24 hr following first order release kinetic, floating for more than 24 hr, floating lag time less than one minute and stable for one year at 300C/65% RH. The optimized formulation (F34) consisted of sulpiride (11%), PEO (11%), HPMC (32%), croscarmellose sodium (16%), super porous hydrogel (16%), citric acid (2%) and sodium bicarbonate (11%). An isocratic HPLC-florescence method was validated for determination of sulpiride in rabbit plasma. The in vivo performance of the optimized gastroretentive formulation (F34) was evaluated in rabbits in comparison with a non-gastroretentive reference product (Dogmatil® capsule). The study was performed using a randomized, two-way crossover design. The optimized gastroretentive formulation (F34) showed a higher Tmax and AUC values but lower Cmax value than the non-gastroretentive reference product. In addition, the amount of drug released in vitro was correlated with the amount of drug absorbed in vivo. In conclusion, the bioavailability of sulpiride increased by 2.20 folds when formulated as gastroretentive dosage form compared to the non-gastroretentive reference product (Dogmatil® capsule).

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Anti-cancer screening of Asparagus africanus extractsO D Okolie, S S Mashele and I T MadunaCentral University of Technology, South Africa

The screening for active compounds from plants leads to the discovery of new medicinal drugs which have efficient protection and treatment roles against various diseases including cancer. In this study, methanol and dichloromethane extracts from the

roots of Asparagus africanus Lam. were tested against breast (MCF7), colon (HCT116) and prostate (PC3) cancer cell lines. Etoposide was used as a positive control. Total growth inhibition (TGI) of the cancer cells using the sulforhodamine B assay was determined to classify the extracts as inactive, weak, moderate or potent, and also the phytochemical properties of this plant were examined using quantitative method. The plant possesses some phytochemical constituents that show positive result, which give more questions to this research work. A. africanus extracts were inactive (TGI>50 µg/ml) against all the cell lines. The phytochemical screening of this plant shows positive result, which thereby raise questions for this plant to be tested with other type of cancer cell lines. However these results were inconclusive because the positive control was also inactive. More screening of the extracts with other cell lines and other positive standards may produce different results.

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Design and development of dual release oral reconstitutable suspension of Cefpodoxime proxetilMukesh kumar PatelB. M. Shah College of Pharmaceutical Education and Research, India

Objectives: The aim of present research work was undertaken with the objective of design and development of dual release oral reconstitutable suspension of Cefpodoxime proxetil for pediatric patients.

Experimental work: Pellets were prepared by extrusion – spheronization technique. Immediate release pellets were prepared and evaluated by using varying concentration of Sodium starch glycolate, Croscarmellose sodium and Crospovidone whereas sustained release pellets were prepared and evaluated by using different concentration of HPMC K100M, Eudragit RSPO & Kollidon SR. From the preliminary studies, optimize the batch of immediate release pellets and which are used for further preparation of dual release reconstitutable suspension but in SR pellets, optimization is carried out by using 32 factorial design in which HPMC K100M (X1) and Eudragit RSPO (X2) were selected as independent variables, while t50 (hr), t90 (hr), Q2 (%), and Q10 (%), were selected as dependent variable. Dissolution data were fitted to various kinetic models on drug release of SR pellets and optimize the SR pellet formulation for dual release oral reconstitutable suspension. The prepared dual release oral reconstitutable suspensions were evaluated for rheological and sedimentation behavior.

Results & Discussion: Result of preliminary studies of P1-P18 batches indicated that, Combination of sodium starch glycolate (5%) and Croscarmellose sodium (5%) containing P10 batch shows minimum disintegration time (22 sec), minimum wetting time (16 sec) and maximum % water absorption ratio (124.7%), desirable particle size (990 µm) and gave 98.7% drug release at the end of 2 hrs which are used for preparation of dual release reconstitutable suspension while results of statistical data was indicated that concentration of HPMC K100M and Eudragit RSPO had significant influence on Q2 (%), Q10 (%), t50 (hr) and t90 (hr). Form the study of factorial batches (F1-F9) of SR pellets, the optimized formulation (F6) showed 98.6% drug release at the end of 12 hrs with concentration of HPMC K100M (20%) and concentration of Eudragit RSPO (15%). SEM showed that optimized batch of IR pellets (P10 batch) and SR pellets (F6 batch) both were in spherical shape with smooth surface. The dissolution profile of optimize batch of SR pellet exhibits similarity factor (f2=86.36) and dissimilarity factor (f1=2.72) with theoretical release profile of Cefpodoxime proxetil. So, P10 batch of IR pellets and F6 batch of SR pellets were selected for the preparation of dual release oral reconstitutable suspension. Result of dissolution study of reconstitutable suspension indicated that there is no significant difference in % CPR on 1st day and after 15 day which indicates the stability of dual release reconstitutable suspension.

Conclusion: It was concluded that liquid pharmaceutical preparation for oral administration capable for providing a dual release of Cefpodoxime proxetil was successfully obtained and it was most suitable for pediatric patients due to reduce dosing frequency, masking the bitter taste of drug and increase patient compliance.

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Phase transformation in thiamine hydrochloride tablets: Influence on tablet microstructure, physical properties, and performanceParoma ChakravartyGenentech, Inc., USA

The objective of the study was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the

storage-induced phase transformation due to changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH HH transformation in tablets, within 30 h of storage at 40 °C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH–MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual and less dramatic changes in properties. The phase transformation and the complex inter-particulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior.

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Size and diffusion phenomena of cetyltrimethylammonium bromide /alcohol/water system in the presence of thymidine by dynamic light scatteringAjaya BhattaraiTribhuvan University, Nepal

In this paper precise measurements of Dynamic Light Scattering (DLS) of the effects of temperature, solvents (alcohols), water on the size and diffusion of CTAB reversed micelles in the thymidine/ CTAB/alcohol/ water system are reported. The concentrations of

CTAB were varied from 0.051 to 0.28 mol/L. Thymidine concentration in during auto-correlation function registration was the same in each solvent 0.001 mol/L. Water concentration in the studied systems was defined by R parameter according to relation: R=[H2O]/[CTAB]. DLS measurements were done at 298.15 and 308.15K. DLS experiment involved on detection two relaxation modes (fast and slow) in the systems containing CTAB reversed micelles, water, thymidine and solvents (methanol and Butanol). The DLS data clearly show the solvent influence as well as thymidine presence on CTAB reversed micelles size and consequently their diffusion coefficients.

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Formulation of iron-coated liposomes of SERM and design development of magnetic belt for the management of breast cancer during earlier stages and protection from invasive cancerPrashant S Khemariya SRK Pharmaceutical, India

Breast cancer remains the utmost common invasive cancer and the second leading cause of cancer mortality for women in the United States. Worldwide, breast cancer comprises 22.9% of all cancers (excluding non-melanoma skin cancers) in the women. It

is estimated that, globally, over 508,000 women died in 2011 due to breast cancer (Global Health Estimates, WHO 2013). Liposomes are attractive due to their unique opportunities together with negligible side effects not only in cancer but also in the treatment of other diseases. In this study, our aim is to develop combined prospective of iron-coated liposomes (of raloxifene hydrochloride) and design a magnetic belt (magnetism < 0.1 T) for the management of breast cancer during earlier stages and prevention from developing invasive cancer, and osteoporosis in post-menopausal women. Keeping this objective, the present systematic study was focused to design magnetic belt in shape of women’s breast that will contain few magnetic fires having enough magnetism to attract iron-coated liposomes only during oral administration of raloxifene hydrochloride, in order to overcome the poor bioavailability issue with the drug as well. Raloxifene or methanone, [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl]-[4-[2-(1-piperidinyl)ethoxy]phenyl] hydrochloride (a Selective Estrogen Receptor Modulator-SERM) is FDA approved drug and is used to decrease the chance of invasive breast cancer in post-menopausal women who have a high risk for developing the disease or who have osteoporosis. After oral administration of iron-coated liposomes, they will distribute throughout the body through the systemic circulation while the magnetic belt will be on the cancer site (breast). This belt results in accumulation of liposomes which will concentrate at the site of cancer because of the iron and magnet interaction. Ultimately, drug concentration and absorption will also enhance on the surrounding areas of cancerous cells where the cancerous cells will be denatured quickly.

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Nanoparticulate systems for better delivery for anticancer and CNS active drugsR N SahaBITS Pilani Dubai Campus, UAE

Advancement in technology and insight of disease conditions, led to use of nanotechnology in better drug delivery, efficient therapeutic efficacy and better patient compliance. Study of nanoparticulate drug delivery systems, like polymer based

nanoparticles, solid-lipid nanoparticles, liposomal nanoparticles, showed promising results with several advantages over conventional or other particulate delivery systems. Studies with anticancer drugs, CNS active drugs and antiviral drugs produced modified and selective distribution, long term plasma circulation with controlled release for long term therapy. In vitro evaluation and characterization of the designed nanoparticles (NPs) showed that nature, amount and combination of materials used for design of nanoparticulate systems play important role of characters of NPs like size, zeta potential, polydispersity index and release profiles. They also play important role inlong term retention and high plasma drug concentration, modification of biodistribution. In pharmacokinetic and biodistribution studies in animal model showed selective but different distribution profiles based on nature and amount of carriers. Our group worked on some anticancer, antivirus and CNS active drugs and found long term plasma circulation and higher plasma drug concentration with respect to pure drug and thus reducing frequency of administration. Selective distribution were found to some organs/tissues and lower to other tissues. In vitro cell uptake study found to produce better cellular uptake and much lower IC50 values in case of NPs. Pharmacodynamic studies in animal model showed better therapeutic efficacy and longer survival period. Targeting index found to be enhanced in case of NPs. The findings suggest NPs are going to be future of novel drug delivery systems.

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Formulation and evaluation of nano-suspensions of CyclosporineRavikumar Patel, J K Patel and Y K PatelJodhpur National University, India

Background: Cyclosporine (CsA), a neutral hydrophobic cyclic peptide composed of 11 amino acid residues, is a 3rd generation immunosuppressant that has been used successfully in organ transplantation in humans since 1981. The aqueous solubility of CsA is very low i.e. 27.67 µg/ml at 250C because of which its oral bioavailability from its conventional dosage forms is very low. It also displays a considerable inter and intra-patient variability presumably due its poor and highly bile-dependent absorption as well as intestinal metabolism. Hence, it requires careful monitoring of blood levels.

Aim: To formulate and evaluate the nano-suspensions of cyclosporine.

Method: Formulation development of nano-suspension was done by trial and error method by different methods viz. solvent evaporation, high pressure homogenization and media milling.

Results: Solvent evaporation method gave a particle size of 1120 nm with 2.52% w/w of polyethylene glycol in dichloromethane, high pressure homogenizer method resulted a particle size of 1026 nm with 2.52% w/w of polyethylene glycol while media milling method gave a best particle size of 269.7 nm with 2.52% w/w of propylene glycol. Based on these results, media milling method was selected for further studies.

Discussion: The problem that occurred in solvent evaporation method was that after the evaporation of the solvent and during the addition of wetting agent in the drug solution, the separation of particles was observed while stirring and small clumps were seen. In the case of high pressure homogenization, it was observed that after completion of the two cycles there is blockage of the suspension in the piston gap. In order to avoid damage to the instrument and due to blockage of suspension, this method was not considered. Media milling method was selected. With the help of different wetting agents (polyethylene glycol 4000, polyethylene glycol 6000) and the stabilizers (poloxomer 407, poloxomer 188), different trials were made and the nano-suspensions were prepared. However, in these methods, the problem of sedimentation was observed. To avoid this problem, the particle size was reduced, but after 24 hours it showed sedimentation of 20-30% solids at the bottom. In order to reduce this, two more trials were made with the help of propylene glycol and different wetting agents and surfactants. In these trials, there was no sedimentation observed and the desired particle size was also achieved.

Conclusions: The nano-suspensions prepared with polaxomer 407 (which acts as a stabilizer) and propylene glycol (which is a surfactant) provided the particle size below 500 nm.

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Simultaneous estimation of Olmesartan Medoxomil and Indapamide in tablet dosage form by spectroscopic methodRucha A Patel1, Hasumati A Raj1, Meera V Lad1 and Richa A Dayaramani21Shree Dhanvantry Pharmacy College, India2Tolani Institute of Pharmacy, India

Olmesartan medoxomil and indapamide combination is used in cardiac disease condition like hypertension. Sustain release tablet formulation comprising olmesartan, medoxomil and indapamide. Patent for formulation is patented in china by Ministry of

cardiovascular disease institute and patent for treatment for hypertension is patented in Japan. Olmesartan medoxomil was approved in USFDA on April, 2002 at New York and indapamide was approved in Lipha pharmaceutical institute on July 1998. Extensive literature survey related spectroscopy, high performance liquid chromatography, high performance thin layer chromatography, Reverse phase high performance liquid chromatography DAD method for estimation of Olmesartan medoxomil and Indapamide. Here thirteen analytical methods available for olmesartan medoxomil and twenty six analytical methods available for olmesartan medoxomil and its combination. And four analytical methods available for Indapamide, and nine analytical methods available for indapamide and its combination, seven analytical methods available for stability study for olmesartan, three analytical methods available for stability study for indapamide with other combination and no analytical method found for indapamide alone and for combination of olmesartan medoxomil and Indapamide, which indicates the need for analytical method development for Olmesartan medoxomil and Indapamide. Here attempt was made to develop and validate a sensitive, reproducible and specific spectroscopy method for Olmesartan medoxomil and Indapamide combination.

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Development and characterization of in situ gel system for nasal delivery of Levodopa Reenu Yadav1, Abhay Asthana2, SK Yadav1, Akshat Sharma3 and Prabhat jain4

1IES College of Pharmacy, India 2MMCP, India 3LNCP, India

The objective of the present study was to develop a thermo sensitive in situ gel system based on chitosan (CS) and poly vinyl alcohol (PVA) for nasal delivery of Levodopa. The hydrogel was prepared by mixing the chitosan and poly vinyl alcohol. The

concentration of the components was optimized during formulation development. The prepared hydrogel was characterized for gelation temperature, gelation time, viscosity changes, degree of swelling, in vitro release and in vivo activity. The prepared hydrogel was liquid at room temperature while underwent thermal transition from solution below or at room temperature to non-flowing hydrogel when incubated at 37ºC within 12-15 minutes with increased viscosity. The in vitro release of levodopa from gel network was observed, the release of levodopa through gel network decreases upon increasing the chitosan concentration from 1 to 5%. Furthermore, the formulation when evaluated for their in vivo activity results indicates that the proposed thermo sensitive in situ gelling system has substantial potential as nasal delivery system for levodopa.

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To determine better drug delivery approaches: Pre-formulation and formulation studies of natural products analoguesSantosh P RavNational Institute of Pharmaceutical Education and Research, India

Nowadays, natural products based analogues are valuable and shows potent pharmacological activity but does not give expected drug delivery. The objective of this abstract is to perform some of the important pre-formulation and formulation studies of

New Chemical Entities (NCEs) to achieve the routes of enhancement. Prior to this, any screened NCEs will take part in clinical trial. It is mandatory to pass from physiochemical characterization and in-vivo / in-vitro stability profile of NCEs further to enter into drug delivery phase during intense preclinical studies. These are basic evaluation for physiochemical characterization such as aqueous stability, biorelevant media/solvent/pH solubility, degradation profile, partition coefficient, ionization constant, LogP/D, pKa, solid state characterization, polymorphism, thermal transformation, drug-excipient compatibility studies. In the next stage, development of analytical / bioanalytical methods, selection of compatible internal reference standard with NCEs at similar wavelength, formulation of dose for animal studies, bioavailability / toxicity/ metabolic studies and also comparison with authentic in-silico softwares are carried out which give some clues to get promising NCEs which may improve drug delivery approaches. It will help to provide regulatory relief and implementation in the drug delivery development and improve public safety standards.

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Pharmaceutical scale up for solid dosage formsShashank Tiwari1 and S P Mahapatra2 1Monad University, India2S S Medical College, India

Scale-up is defined as the process of increasing batch size. Scale-up of a process is viewed as a procedure for applying the same process to different output volumes. There is a subtle difference between these two definitions: batch size enlargement does not

always translate into a size increase of the processing volume. In mixing applications, scale-up is indeed concerned with increasing the linear dimensions from the laboratory to the plant size. On the other hand, processes exist (e.g., tableting) where the term ‘scale-up’ simply means enlarging the output by increasing the speed. To complete the picture, one should point out special procedures where an increase of the scale is counter-productive and ‘scale-down’ is required to improve the quality of the product. In moving from Research & Development (R&D) to production scale, it is sometimes essential to have an intermediate batch scale. This is achieved at the so-called pilot scale, which is defined as the manufacturing of drug product by a procedure fully representative of and simulating that used for full manufacturing scale. This scale also makes it possible to produce enough products for clinical testing and to manufacture samples for marketing. However, inserting an intermediate step between R&D and production scales does not, in itself, guarantee a smooth transition. A well-defined process may generate a perfect product both in the laboratory and the pilot plant and then fail quality assurance tests in production.

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Development of 5-fluorouracil enteric -coated nanoparticles for sustained and localized release and their in vitro characterization for treatment of colorectal cancerShashank Tummala and M N Satish KumarJSS College of Pharmacy, India

5-Fluorouracil is used in the treatment of colorectal cancer along with oxaliplatin as first line treatment, but it is still having lack of site specificity and poor therapeutic effect. Apart from that it exhibits toxic effects to healthy cells and decrease the drug availability

at colon region. These limitations were overcome by formulating them as enteric- coated chitosan polymeric nanoparticles as drug can be delivered directly to large bowel. The main reason for opting for enteric coating is due to its protection of drug at gastric pH. So the main objective was to prepare polymeric nanoparticles using chitosan with different ratios of polymer (1:1, 1:2, 1:3, 1:4) by solvent evaporation emulsification method. It was then characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), entrapment efficiency and particle size and further subjected to enteric coating. Dialysis bag technique was selected to determine drug in vitro release using various simulated fluids with pH (1.2, 4.5, 7.5, 7.0) to mimic the GIT tract. 5-FU nanoparticles with drug: polymer ratio of 1:2 and 1:3 has shown better particle size (149±1.28 nm and 138±1.01 nm respectively), entrapment efficiency (48.12±0.08% and 69.18±1.89 respectively). Comparative approach with non-enteric coated tablets shows a better drug release for 5-FU E1 after 4 h (initial burst release) followed by sustained release of 82% till 24 h, where as non enteric coated tablet released more than half the amount of the drug before reaching the colon area. So, these results conclude the usage of prepared nanoparticles as a potential drug delivery approach for the treatment of colorectal tumors.

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Porous carrier based multiparticulate technology for effective gastro-retention of therapeuticsSunil K JainGuru Ghasidas Vishwavidyalaya, India

Floating drug delivery system (FDDS) with extended residence time in the stomach could be of great importance for drugs with an absorption window in the upper small intestine. FDDS have been expected to remain floating in the gastric contents which

results in the enhancement of bioavailability as well as effective usage of the drugs. Floating microspheres are specially noticed due to their wide applicability in the targeting of various drugs to the stomach. These floating microspheres have the advantage that they stay buoyant and dispersed uniformly in the gastric fluid. Multiparticulate low-density particles further successfully prolongs the gastric retention time of various drugs. Low-density porous carriers have been used by researchers for formulation of FDDS. Porous carriers are low-density solids with an open or closed pore structure and offer large exposed surface area for drug loading. Examples of pharmaceutically exploited porous carriers include porous silicon dioxide (Sylysia®), polypropylene foam powder (Accurel®), porous calcium silicate (Florite®), magnesium aluminometa silicate (Neusilin®), porous ceramic, etc. Floating microspheres and floating granules of Repaglinide and Orlistat using low density calcium silicate (CS) as a porous carrier were developed. The designed formulations had shown good performance in terms of floating ability with excellent controlled release behavior. The relative bioavailability of Repaglinide loaded floating microspheres was also found to be raised about 3.17 times in contrast to that of the marketed tablet. Developed systems could serve as platform technology for future research on this domain. Future work in this direction should be targeted towards use of such porous carriers for the development of floating multiparticulate delivery systems. The coming years represent a critical time in this field as commercial applications of FDDS to be explored.

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Extraction, physicochemical characterization and evaluation of gum fraction of local myrrh (Commiphora myrrha) as binding agent in granule and tablet formulationsTaddese Mekonnen, Anteneh Belete and Tsige Gebre-MariamAddis Ababa University, Ethiopia

In modern pharmaceutical dosage forms, excipients often fulfill multi-functional roles such as modifying release, improvement of the stability and bioavailability of the active ingredient, enhancement of patient acceptability and ensure ease of manufacture.

New and improved excipients continue to be developed to meet these needs of advanced drug delivery systems. The objective of this study was to extract, characterize and evaluate myrrh gum as binding agent in granule and tablet formulations using paracetamol as a model drug in comparison with standard binders (PVP and Acacia). The gum fraction of myrrh was extracted, purified and characterized for its physicochemical properties. Batches of granules containing paracetamol were prepared using 2%, 5%, 7.5% and 10% w/w of myrrh gum and the reference binders. Tablets were evaluated for their mechanical and release properties. Result indicated myrrh gum exhibited high relative solubility in cold and hot water, low swelling power, acceptable moisture content, small total ash, no tannin and starch/dextrin content, mucilage with acidic pH and high viscosity, and excellent powder flow properties. Granules showed good particle size and size distribution, excellent flow and compressibility properties. The crushing strength, disintegration and dissolution times of the tablets increased with increased binder concentration while their friability decreased. All tablets passed standard specifications with respect to disintegration time, uniformity of weight, thickness, diameter, friability, hardness and tensile strength except friability at 2% binder and disintegration times at 10% myrrh gum and acacia. Comparison of the in vitro drug release showed tablets prepared with myrrh gum gave better drug release than acacia and comparable to PVP. This suggests that myrrh gum could be useful alternative binding agent especially when optimum mechanical strength and release required.

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Transdermal drug delivery and patient monitoring using hydrogel-based microneedles Thakur R R SinghQueens University Belfast, UK

Here we describe unique microneedle arrays prepared from crosslinked polymers which contain no drug themselves. Instead, they rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch-

type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilised, resist hole closure while in place and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically-modulated delivery is also a unique feature. Since we have also shown that these microneedles efficiently imbibe skin interstitial fluid, employing them in blood-free therapeutic drug monitoring is another important potential application. This technology has the potential to greatly increase the range of type of drug deliverable transdermally and enhance therapeutic monitoring, with ensuing benefits for industry, healthcare providers and, ultimately, patients.

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Physico-chemical and physic-mechanical characterization of polypeptide-k: A phyto-insulin for oral deliveryVarun Garg, Puneet Kaur, Sachin Kumar Singh and Monica GulatiLovely Professional University, India

Polypeptide-k is an anti-diabetic protein isolated from dried seeds of the ripened fruits of Momordica charantia. In last one decade, extensive research has been carried out on polypeptide-k to explore its potential applications in the treatment of diabetes

mellitus. It is widely marketed in combination or alone in the form of tablets in Malaysian as well as Indian markets. However, the physic-chemical and physico-mechanical properties of the drug remain unexplored hitherto. Our study, for the first time, reports the vital preformulation parameters of the peptide molecule. The knowledge of these parameters will not only support the formulation development and evaluation but will also help in compiling the monograph of this peptide drug.

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Nanoplatforms for cancer targeting and image-guided drug deliveryWeibo CaiUniversity of Wisconsin–Madison, USA

The Molecular Imaging and Nanotechnology Laboratory at the University of Wisconsin - Madison is mainly focused on three areas: 1) development of multimodality molecular imaging agents; 2) nanotechnology and its biomedical applications; and 3)

molecular therapy of cancer. In this talk, I will present our recent work on molecular imaging and image-guided drug delivery of cancer with peptides, proteins, and a variety of nanomaterials. The primary imaging techniques used in these studies are positron emission tomography (PET), optical imaging, and magnetic resonance imaging (MRI). Three of the major molecular targets that we are investigating are CD105 (i.e. endoglin), VEGFR, and integrin αvβ3. The nanomaterials that will be discussed in this presentation include nano-graphene oxide, zinc oxide nanomaterials, micelles, silica-based nanoparticles, magnetic nanoparticles, among many others.

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Formation of phytosome containing silymarin using thin layer-hydration technique aimed for oral deliveryWina Maryana, Diky Mudhakhir and Heni Rachmawati Institut Teknologi Bandung, Indonesia

Silymarin is a unique flavonoid complex isolated from milk thistle (Silybum marianum) and has been widely used as hepatoprotective agent. Orally administered silymarin will be absorbed rapidly and only 20-50% of silymarin will be absorbed

through gastrointestinal tract, resulting on its low bioavailability. Those limitations are due to its poorly soluble either in water and oil and its low intestinal permeability. This study was aimed to develop silymarin-loaded phytosomes to improve silymarin bioavailability with sufficient safety and stability. This system consists of silymarin-phospholipid complex prepared by solvent evaporation method, which was incorporated to formed phytosome shape vesicles using thin layer method with various concentration and molar ratio of silymarin and phospholipid. Phytosome vesicles size was reduced using probe sonication. The result demonstrated that formula with 2% silymarin-phospholipid complex and molar ratio of 1:5 showed the best physical properties with mean vesicle diameter of 133.53±8.76 nm, polydispersity index of 0.34±0.08, entrapment efficiency of 97.17±2.41 %, loading capacity of 12.18±0.30%, and good stability after freeze thaw stability test. Analysis of FTIR spectroscopy and DSC was confirmed the presence of physical and chemical interactions between silymarin and phospholipid complex. Well formed and discrete vesicles of phytosome were revealed by Transmission Electron Microscopy, drug content, and freeze thaw stability test.

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siRNA-based targeted gene therapies in cancer: Targeting EF2-kinase in solid tumors Bulent OzpolatThe University of Texas-MD Anderson Cancer Center, USA

After recent discovery, the use of small interfering RNA (siRNA) has rapidly become a powerful tool for silencing oncogenes and holds promise as a novel class of therapeutics in cancer. siRNA based therapeutic intervention can be uses especially for those

targets that cannot be targeted by small inhibitors or for “non drugable” targets. However, successful clinical applications and in vivo delivery of the siRNA-based therapeutics to primary and metastatic tumors remains as a great challenge. We recently identified eEF2-kinase in solid tumorssuch as breast and pancreatic cancer developed tumor targeting nanoliposomes that can target siRNA in vivo into tumor cells more effectively than regular liposomes, leading to significant and robust target gene silencing for about a week in breast, ovarian and prostate cancers animal models. Overall, our preclinical studies demonstrated that highly specific targeting of genes promoting cell proliferation, survival, tumor growth, invasion ad progression including EF2-kinase (Ef2K) and Bcl-2, EphA2 genes by liposomal siRNA nanotherapeutics significantly inhibited tumor growth in breast, ovarian and prostate cancers, respectively, as well as hematological tumor models such as lymphoma. Our data suggest that siRNA based nanotherapies have potential as novel class of systemic therapies for various cancers and provide the proof of concept and the impetus for translational studies for Phase I clinical trials in patients.

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Preparation of Rapamycin and methyl-β-cyclodextrin complexes using a single-step, organic solvent-free supercritical fluid process: An approach to enhance the solubility and dissolution propertiesShashi Ravi Suman Rudrangi, Vivek Trivedi, Bruce D Alexander and Stephen R WicksUniversity of Greenwich, UK

The purpose of this study was to evaluate a single-step, organic solvent-free supercritical fluid process for the preparation of rapamycin-methyl-β-cyclodextrin complexes with an express goal to enhance the dissolution properties of rapamycin. The

complexes were prepared by supercritical carbon dioxide processing, co-evaporation, freeze drying and physical mixing. The prepared complexes were then analyzed by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, solubility and dissolution studies. Computational molecular docking studies were performed to study the formation of molecular inclusion complexation of rapamycin with methyl-β-cyclodextrin. Rapamycin exists in a highly crystalline solid form. Physical mixing of rapamycin and methyl-β-cyclodextrin appeared not to reduce the degree of crystallinity of the drug. The co-evaporated and freeze dried complexes had a lower degree of crystallinity than the physical mix; however the lowest degree of crystallinity was achieved in complexes prepared by supercritical carbon dioxide processing method. All the binary mixtures with Me-β-CD exhibited a faster and greater extent of drug dissolution than the drug alone. Products obtained by the supercritical carbon dioxide processing method exhibited the highest apparent drug dissolution. Information obtained from the characterization tests suggest complete complexation or amorphization of rapamycin and Me-β-CD prepared by supercritical carbon dioxide processing method. Therefore, a solid inclusion method using supercritical carbon dioxide carrier proved to be a novel and useful complexation method for rapamycin into Me-β-CD. Furthermore, since this method has no toxic solvent residue, products obtained by this method should provide minimal side effects in humans, compared to those obtained by techniques, which require the use of perilous organic solvents.

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The evaluation of supercritical fluid technology as a preparative technique for the manufacture of Flurbiprofen-methyl-β-cyclodextrin inclusion complexes: An approach to enhance the solubility and dissolution propertiesShashi Ravi Suman Rudrangi, Vivek Trivedi, Bruce D Alexander and Stephen R WicksUniversity of Greenwich, UK

The aim of this study was to enhance the apparent solubility and dissolution properties of flurbiprofen through inclusion complexation with cyclodextrins. Especially, the efficacy of supercritical fluid technology as a preparative technique for

the manufacture of flurbiprofen-methyl-β-cyclodextrin inclusion complexes was evaluated. The complexes were prepared by supercritical carbon dioxide processing and were evaluated by solubility, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy and in vitro dissolution studies. Computational molecular docking studies were conducted to study the possibility of molecular arrangement of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin. The studies support the formation of stable molecular inclusion complexes between the drug and cyclodextrin in a 1:1 stoichiometry. The results obtained from different analytical studies suggest complete complexation or amorphisation of flurbiprofen and methyl-β-cyclodextrin binary samples prepared by supercritical carbon dioxide processing. In vitro dissolution studies showed that the dissolution properties of flurbiprofen were significantly enhanced by the binary mixtures prepared by supercritical carbon dioxide processing. The amount of flurbiprofen released from drug alone was very low with 1.11±0.09% dissolving at the end of 60 min while the binary mixtures processed by supercritical carbon dioxide at 45°C and 200 bar released 99.39±2.34% of the drug at the end of 30 min. The study demonstrated the single step, organic solvent-free supercritical carbon dioxide process as a promising approach for the preparation of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin in solid state. The preliminary data suggests that the complexation of flurbiprofen with methyl-β-cyclodextrin will lead to better therapeutic efficacy.

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Hollow calcium carbonate nanoparticles as pH-sensitive targeted delivery carriers in cancer therapyAnjala W Bulathge1, M M M G P G Mantilaka and R M G RajapakseUniversity of Peradeniya, Sri Lanka

pH sensitive drug delivery systems can achieve targeted drug delivery and systemic control release. The studies in this area have been increased in recent years and more attention has been devoted to develop new methods for the preparation of new drug

delivery systems especially in cancer therapy. Among the metal based anti-cancer drugs, copper complexes have shown remarkable potential in cancer therapy. Therefore, the aim of this study is to synthesize a pH-sensitive calcium carbonate-encapsulated copper bis-(8-hydroxyquinoline) anti-cancer drug delivery system starting from naturally occurring dolomite. In this novel research, first, copper bis-(8-hydroxyquinoline) is synthesized using copper(II) chloride dihydrate and 8-hydroxyquinoline as the reactants. The drug was loaded to the preformed hollow structures of precipitated calcium carbonate (PCC) by physisorption method. Hollow structures of PCC were suspended in prepared solution of Copper bis-(8-hydroxyquinoline) dissolved in Dimethylformamide (DMF). It was moderately stirred for five days. PCC products were collected by centrifugation followed by washing with acetone to remove the DMF. The obtained product was characterized using XRD, XRF and FTIR studies. XRD and FTIR studies revealed that copper bis-(8-hydroxyqunoline) incorporated inside the CaCO3 hollow PCC product. The release of drug is monitored in vitro in the pH values of 2.0, 4.0, 6.0 and 8.0. According to results, within first four hours, the cumulative release shows 100% in pH 2 and pH 4. However, no release is observed in pH 8 for 120 hours. Therefore, it is a good indication that the encapsulated drug releases at the pH trigger point. pH differences can be found at the subcellular level, late endosomes and lysosomes have much lower pH, in the range 4.5–5.5 . Due to high rate of glycolysis, tumors exhibit pH value 5.7 while the pH value of normal tissue is 7.4. This pH gradient is very important in internalization of drugs. Therefore this has potential applications in effective cancer therapy.

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Formulation design and development of solid self-micro-emulsifying drug delivery system (S-SMEDDS) for Bosentan monohydrateLokesh Narsineni1, 2 and Rahul Bhaskar1, 3

1Lovely Professional University, India2University of Waterloo, Canada3Wockhardt Research Centre, India

Liquid self-emulsifying system is prepared by employing Quality by Design (QbD) using D-optimal mixture design. Solubility of bosentan monohydrate is determined in long chain and medium chain triglycerides, surfactants and co-surfactants. Optimal

mixture design is used for setting various levels of constraints for the excipient concentrations in preparing liquid SMEDDS and response surfaces such as globule size, polydispersity index, dissolution efficiency and time for 85% drug release (t85%) are evaluated. Optimized batch containing bosentan monohydrate 62.5 mg, capmul MCM (10.38%), labrasol/cremophor EL 1:1 (56.0%), transcutol P (33.62%) is predicted by the design which is validated by droplet size, PDI, dissolution efficiency and t85% . Solid powder form is prepared by adsorbing liquid SMEDDS onto solid carrier material neusilin US2. In vitro dissolution studies, comparative dissolution profiles of prepared solid SMEDDS and marketed preparation ‘BOSENTAS’ are carried out and reported. Ex vivo permeation study using chicken intestine showed improved permeability up to 0.0649 µg/cm2/min. Droplet morphology and solid state characteristics are determined using TEM, XRD and SEM. Zeta potential of the system was found to be -1.89 mV. Reconstituted S-SMEDDS had droplet size of 77.97 nm compared to liquid SMEDDS droplet size which was 47.00 nm. TEM images revealed the spherical shape and least globule size while XRD peaks reveal the transformation of crystalline polymorph A2 state of drug to amorphous state in S-SMEDDS. SEM images validate the integrity in shape. This study demonstrates a strategic way for development of S-SMEDDS for a drug with low solubility by QbD approach.

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