DRY GRANULATIONMANUFACTURING 1007

Prepared By: Geraldo GarciaPrepared By: Geraldo Garcia Pharmaceutical QA/QCPharmaceutical QA/QC AAPSAAPS

Prepared For: Victor ShulmanPrepared For: Victor Shulman Manufacturing InstructorManufacturing Instructor AAPS AAPS

DRY GRANULATION PROCESSDRY GRANULATION PROCESS

• Dry granulation may be used if the materials have sufficient inherent binding or cohesive properties to form granules.

• Dry granulation refers to the process of granulating without the use of liquids.• There are two dry granulation methods used in the pharma industry: slugging and roll

compaction.

Drug A d ju v a n t

S c re e n

Blend Pellet G r in d

L u b ric a n ts C

Tablet B le n d

C o m p re s s

DRY GRANULATION PROCESS SCHEMATIC DIAGRAMDRY GRANULATION PROCESS SCHEMATIC DIAGRAM

Slugging (Old Method)Slugging (Old Method)

• material to be granulized is first made into a large compressed mass or "slug" typically by way of a tablet press using large flat-faced tooling.

Disadvantages of SluggingDisadvantages of Slugging

• single batch processing• frequent maintenance changeover • poor process control • poor economies of scale • low manufacturing output per hour • excessive air and sound pollution, • increased use of storage

containers, • more energy and time required to

produce 1 Kg of slugs than 1 Kg of roller compact

Aspirin SluggingAspirin Slugging

Slugging Tablet Press (Tablet Press Company) Slugging Tablet Press (Tablet Press Company)

• material particles are consolidated and densified by passing the material between two high-pressure rollers.

• densified material from a roller compactor is then reduced to a uniform granule size by milling.

• capable of handling a large amount of material in a short period of time

• Invented by Francis Xavier Chilson

Roller Compactor / Chilsonator (New Method)Roller Compactor / Chilsonator (New Method)

Roller CompactorsRoller Compactors

Hutt Roller Hutt Roller compactorcompactor

Roller OrientationRoller Orientation

A. Horizontal orientation In horizontal roll orientation the loss of material due to bypass is high as compared to other designsB. Vertical orientation Loss of un-compacted material is minimal in vertical orientation due to independence of feed to gravitational forcesC. Incline orientation (position between horizontal and vertical) The use of inclined roll orientation decreases bypass from 15-20% to 7%

1: Filling hopper, 2: Feeding auger/screw feeder, 2’: Screw feeder, 3: Tamping auger, 4:Rolls, 5: Flake crusher, 6: Granulator, 7 and 8: Two stage diagonal granulation system using coarse and fine granulator, respectively. 

• The roll orientation plays significant role in generation and minimization of bypass.

Variables of Roller CompactionVariables of Roller Compaction

• In the slip or entry region powder starts to move but at a speed slower than the roll speed, thus indicating that slips occur therefore termed “slips”.

• The nip region starts at a roll angle α, (nip angle), when the wall velocity of the powder becomes equal to that of the rolls.

• The release region starts when the roll gap starts to increase again and its size depends on the stored elastic strains in the compact, release rate of compact,t and the roll speed.

Schematic of the main regions during roller compactionSchematic of the main regions during roller compaction

roll pressurehorizontal/vertical feed screw speed

roller gap

roll speed

screen size

Requirements for Roller CompactionRequirements for Roller Compaction

• adequate supply of the powder to the nip region and entire conveying of powder entering from nip region into the narrowest part of the roll gap.

• uniform distribution of the compaction pressure over the whole roll-gripped mass.

• adequate, effective, and uniform de-aeration of powder mass via vacuum before it reaches the nip region.

• material to be processed should be compressible, should have consistent increase in density with force, suitable for milling operation and recompression.

Advantages of dry granulation:Advantages of dry granulation:• Useful for heat or moisture sensitive materials.• Less equipment and space than that required by wet granulation.• Improve tablet disintegration since it does not involve the use of water so it increases water-uptake ability of the disintegrant.• This method is of value in the production of certain dosage forms as effervescent tablets.

Disdvantages of dry granulation:Disdvantages of dry granulation:•Requires high duty machine if compared with direct compaction•Since it is dry process, more dust is produced which may contaminate other drug

In my opinion:In my opinion:I prefer dry granulation because it is:I prefer dry granulation because it is:•economical,economical,•use less spaceuse less space•it eliminates addition of moisture and heat which contributes to the product’s degradationit eliminates addition of moisture and heat which contributes to the product’s degradation•Mechanical strength of the product in more uniformMechanical strength of the product in more uniform•Machine is easy to maintain after operationMachine is easy to maintain after operation

When to Use Dry Granulation?When to Use Dry Granulation?

• this method is used when direct compression is not applicable (e.g., large-dose or poor compressibility drugs)

• when wet granulation cannot be used (e.g., drugs sensitive to heat or moisture). • Vitamins and effervescent tablets are examples of products prepared by dry granulation.

DRY GRANULATION PROCESS VIDEODRY GRANULATION PROCESS VIDEO

Text References:• Miller RW. Roller Compaction Technology. In: Handbook of Pharmaceutical Granulation

Technology, Parikh, Marcel Dekker Inc., New York, 1997: 81, 99-150.• Teng Y, Qiu Z and Wen H. Systematical Approach of Formulation and Process Development

Using Roller Compaction. Eur. J Pharm Sci 2009; 73(2): 219-229. • Kleinebudde P. Roll Compaction/Dry granulation: Pharmaceutical Applications.Eur J Pharm

Biopharm 2004; 58; 317-326.• Hariharan M, Wowchuk C, Nkansah P, Gupta VK. Effect of Formulation Composition on the

Properties of Controlled Release Tablets Prepared by Roller Compaction. Drug Dev’t. Ind Pharm 2004; 30: 565-572.

• Funakoshi Y, Asogawa TSE. The Use of a Novel Roller Compactor with a Concave-convex Roller Pair to Obtain Uniform Compacting Pressure. Drug Dev Ind Pharm1977; 3: 555-573

• Bozic DZ, Dreu Rand Vrecer F. Influence of Dry Granulation on Compactibility and Capping Tendency of Macrolide Antibiotic Formulation. Int J Pharm 2008; 357: 44-54.

Video and Picture Attachments:

• Internet Google Images

• You Tube – Animation Video Dry Granulation Process