GranulatingGranulatingwith Mike Touseywith Mike Tousey
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ObjectiveObjective
Common methods of granule formation for Common methods of granule formation for tablet compression. This session will tablet compression. This session will provide a comprehensive, yet simple provide a comprehensive, yet simple explanation of typical granulation methods explanation of typical granulation methods used for pharmaceutical and nutritional used for pharmaceutical and nutritional products for the purpose of tablet products for the purpose of tablet manufacturing. The participant will gain manufacturing. The participant will gain an understanding of methods of an understanding of methods of granulating and equipment typically used granulating and equipment typically used in today's manufacturing environmentsin today's manufacturing environments
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The TabletThe Tablet
The Tablet is the final report card for how The Tablet is the final report card for how well all previous operations performed well all previous operations performed within the process.within the process.Keep this objective in mind. There are Keep this objective in mind. There are many really good process operators that many really good process operators that never really understand their role is to never really understand their role is to make a good tablet, not just to complete a make a good tablet, not just to complete a function on a machine.function on a machine.
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Six Reasons to GranulateSix Reasons to Granulate
There are six key reasons to granulate!There are six key reasons to granulate!All six are based on the need to tablet or All six are based on the need to tablet or encapsulate a product.encapsulate a product.These six These six ““reasonsreasons”” are the key to are the key to improving and optimization of an existing improving and optimization of an existing blend or of individual ingredients.blend or of individual ingredients.
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1.To Improve Flow1.To Improve Flow
Powder flow is important throughout the Powder flow is important throughout the entire tablet making process.entire tablet making process.
Weighing/Batching Weighing/Batching -- accuracyaccuracyMillingMilling-- consistencyconsistencyBlendingBlending-- content uniformitycontent uniformityGranulating Granulating -- repeatabilityrepeatabilityTablet Compression Tablet Compression –– to meet the objectivesto meet the objectives
Flow performance is relative to speed and Flow performance is relative to speed and capacity of the equipmentcapacity of the equipment
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2. Compressibility2. Compressibility
Tablet Press speeds vary from 48 tablets Tablet Press speeds vary from 48 tablets per minute to over 15,000 tablets per per minute to over 15,000 tablets per minute.minute.The average press runs at 3000 tpm or 50 The average press runs at 3000 tpm or 50 tablets per second.tablets per second.The ability for a powder to compress The ability for a powder to compress quickly is imperative.quickly is imperative.The Press knows Weight, Thickness, The Press knows Weight, Thickness, SpeedSpeed……Hardness is a result.Hardness is a result.
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3. Fines & Control Dust3. Fines & Control Dust
Fine particles & dust are often the main Fine particles & dust are often the main cause of poor flow, poor compression, cause of poor flow, poor compression, cross contamination, and poor content cross contamination, and poor content uniformity.uniformity.Tablet compression and capsule filling Tablet compression and capsule filling machines perform best with a particle size machines perform best with a particle size distribution within a range of 40distribution within a range of 40--200 mesh200 mesh
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Particle Size DistributionParticle Size Distribution
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40
50
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FinesFines
Large Particles
<20 Mesh 850 μm/.0331”
10-20%
Fines
>200 Mesh75 μm/.0029”
10-20%
Intermediates
40-120 Mesh425-125 μm
.0165”-.0049”
70-80%
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4. Control Segregation4. Control Segregation
Segregation means that powders are not Segregation means that powders are not staying mixed and are separating. This staying mixed and are separating. This leads to content uniformity issues and leads to content uniformity issues and table weight & hardness control.table weight & hardness control.
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5. Density Control5. Density Control
Density variation Density variation within a single within a single ingredient equates to ingredient equates to major problems with major problems with tablet & capsule tablet & capsule manufacturing across manufacturing across the board. the board. Bulk density variation Bulk density variation of ingredients within of ingredients within the blend is a recipe the blend is a recipe for trouble.for trouble.
There are 2 things There are 2 things ““Actives and Actives and ExcipientsExcipients”” within a formulation.within a formulation.Sometimes we granulate the entire blend Sometimes we granulate the entire blend and other times we granulate individual and other times we granulate individual ingredients.ingredients.The Active Ingredient can represent a very The Active Ingredient can represent a very small percentage of the final formulation small percentage of the final formulation or a very high percentage of the or a very high percentage of the formulation.formulation.
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Which Pathway?Which Pathway?
Direct Compression Direct Compression Wet GranulatingWet GranulatingDry GranulatingDry Granulating
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Direct CompressionDirect Compression
Why not just weigh the powder, mix it and put it on the tablet press?
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Granule FormationGranule Formation
Granules can be formed by Granules can be formed by adding a liquid adding a liquid ““BinderBinder ““into the dry powder mass, into the dry powder mass, much like combining water, much like combining water, milk or egg with flour when milk or egg with flour when cooking.cooking.Granules can be formed Granules can be formed through through dry compactiondry compaction; ; some powders are sensitive to some powders are sensitive to liquid addition and high liquid addition and high temperatures from the drying temperatures from the drying process.process.
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What is a Binder?What is a Binder?
A binder is an A binder is an ““excipientexcipient”” (non(non--active active ingredient) that forms a bridge and locks ingredient) that forms a bridge and locks particles togetherparticles together……aka a pharmaceutical aka a pharmaceutical glue.glue.There are dry binders and wet Binders and There are dry binders and wet Binders and there are a few binders like there are a few binders like ““Avicel Avicel PH102PH102”” by FMC that can work as a dry or by FMC that can work as a dry or wet binderwet binder
Dry Granulating is Dry Granulating is also known as Roller also known as Roller Compaction and Compaction and SluggingSlugging
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Wet Granulation Dry Granulation Direct Blending
Pre-mix Pre-mix
Wet Massing Slugging/Chilsonating
Drying Milling
Milling Final Blending Charge and Blend Powders
Final Blending
Process PathwaysProcess Pathways
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5 Steps 5 Steps
There are 5 steps to follow which will help There are 5 steps to follow which will help to Determine if granulating is necessaryto Determine if granulating is necessary
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1. Is Direct Compression 1. Is Direct Compression Feasible?Feasible?
If yes = Direct CompressIf yes = Direct CompressIf no= The product must be GranulatedIf no= The product must be GranulatedMany products are successful at a slow Many products are successful at a slow speed on a tablet press, but not fast.speed on a tablet press, but not fast.Can your product run as fast as the press Can your product run as fast as the press can go? If the answer is No, then your can go? If the answer is No, then your product is nonproduct is non--optimized and is limited in optimized and is limited in some way?some way?
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2. Is the Blend Cohesive2. Is the Blend Cohesive
If yes = Direct CompressIf yes = Direct CompressIf no= The product must be GranulatedIf no= The product must be GranulatedProducts need to be cohesive (sticky). If Products need to be cohesive (sticky). If the answer is no something must be the answer is no something must be added to help lock the particles together.added to help lock the particles together.If products are too cohesive then we have If products are too cohesive then we have another problem which is commonly another problem which is commonly referred to as referred to as ““sticking & pickingsticking & picking””..
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3. Is the Flow acceptable?3. Is the Flow acceptable?
If yes = Direct CompressIf yes = Direct CompressIf no= The product must be GranulatedIf no= The product must be GranulatedFlow is critical and it can change from Flow is critical and it can change from product variation, environmental changes, product variation, environmental changes, and it can be impacted by time.and it can be impacted by time.Good flow is like granulated sugar Good flow is like granulated sugar Bad flow is like flourBad flow is like flour
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4. Is Content uniformity 4. Is Content uniformity acceptable?acceptable?
If yes = Direct CompressIf yes = Direct CompressIf no= The product must be GranulatedIf no= The product must be GranulatedWhat is What is ““content uniformitycontent uniformity””??Content Uniformity means that each and Content Uniformity means that each and every tablet has the same quantity of every tablet has the same quantity of ingredients within an acceptable range.ingredients within an acceptable range.Is it possible to blend powders and then Is it possible to blend powders and then have them come unblended? YES.have them come unblended? YES.
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5. Is the Bulk Density 5. Is the Bulk Density acceptable?acceptable?
If yes = Direct CompressIf yes = Direct CompressIf no= The product must be GranulatedIf no= The product must be Granulated
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GranulateGranulate
If the answer to any of the above was YES If the answer to any of the above was YES then the formula or ingredients within the then the formula or ingredients within the blend must be granulated.blend must be granulated.Which method of granulation should you Which method of granulation should you choose? Wet or Dry Granulating?choose? Wet or Dry Granulating?
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SummarySummary
Remember that the purpose of Granulating is Remember that the purpose of Granulating is to simply make a better tablet. If there is a to simply make a better tablet. If there is a problem such as weight, hardness, thickness, problem such as weight, hardness, thickness, friability, appearance, disintegration, friability, appearance, disintegration, dissolution, content uniformity, just to name dissolution, content uniformity, just to name the major onesthe major ones……then the need to granulate or then the need to granulate or the need to improve they way you are the need to improve they way you are granulating must be carried out.granulating must be carried out.
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Granulating seriesGranulating series
Granulating Basics 101 Granulating Basics 101 –– Dec 4Dec 4thth
Granulating 201 Granulating 201 –– Feb 26thFeb 26thGranulating 301Granulating 301-- April 23April 23rdrd
If you would like to attend future If you would like to attend future Granulating programs please email a Granulating programs please email a request for a discount coupon after this request for a discount coupon after this presentation and we will email a 10% presentation and we will email a 10% discount coupon good for future sessions.discount coupon good for future sessions.
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Special RequestSpecial Request
Please send photos and examples of Please send photos and examples of defects or examples of common problems defects or examples of common problems at your facility.at your facility.In return we will send you a free pass to a In return we will send you a free pass to a future seminar.future seminar.
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Questions and Thank You!Questions and Thank You!
Open for QuestionsOpen for QuestionsIf you donIf you don’’t get the answer, email or call me to t get the answer, email or call me to discussdiscussPlease join us next week for our QA/QC sessionPlease join us next week for our QA/QC sessionThank You for joining meThank You for joining me…….Mike Tousey.Mike Tousey
36 Persimmons Street, Suite 303Bluffton, South Carolina, USA 29693-4519Phone: 843 815 7441 Fax: 843 815 7446
Thank You for attending today!Thank You for attending today!
We hope you enjoyed todayWe hope you enjoyed today’’s program s program and will join us again soon. and will join us again soon.
If you need help, let the professionals at If you need help, let the professionals at Techceuticals bring their practical Techceuticals bring their practical solutions to your company! Ask us how solutions to your company! Ask us how today!today!
36 Persimmons Street, Suite 303Bluffton, South Carolina, USA 29693-4519Phone: 843 815 7441 Fax: 843 815 7446
