En este documento se describe los aspectos basicos del proceso de garnualcion farmaceutica asi como una breve descripcion de cada una de ella

1. Presentation
Granulating
with Mike Tousey
“There is no replacement for experience”
experience”
Copyright© Techceuticals~2008 1
Objective
Common methods of granule formation for
tablet compression. This session will
provide a comprehensive, yet simple
explanation of typical granulation methods
used for pharmaceutical and nutritional
products for the purpose of tablet
manufacturing. The participant will gain
an understanding of methods of
granulating and equipment typically used
in today's manufacturing environments
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2. The Tablet
The Tablet is the final report card for how
well all previous operations performed
within the process.
Keep this objective in mind. There are
many really good process operators that
never really understand their role is to
make a good tablet, not just to complete a
function on a machine.
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Six Reasons to Granulate
There are six key reasons to granulate!
All six are based on the need to tablet or
encapsulate a product.
These six “reasons” are the key to
improving and optimization of an existing
blend or of individual ingredients.
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3. 1.To Improve Flow
Powder flow is important throughout the
entire tablet making process.
Weighing/Batching - accuracy
Milling- consistency
Blending- content uniformity
Granulating - repeatability
Tablet Compression – to meet the objectives
Flow performance is relative to speed and
capacity of the equipment
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2. Compressibility
Tablet Press speeds vary from 48 tablets
per minute to over 15,000 tablets per
minute.
The average press runs at 3000 tpm or 50
tablets per second.
The ability for a powder to compress
quickly is imperative.
The Press knows Weight, Thickness,
Speed…Hardness is a result.
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4. 3. Fines & Control Dust
Fine particles & dust are often the main
cause of poor flow, poor compression,
cross contamination, and poor content
uniformity.
Tablet compression and capsule filling
machines perform best with a particle size
distribution within a range of 40-200 mesh
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Particle Size Distribution
70
60
50
40
30
20
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0
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5. Fines
Large Particles Intermediates Fines
<20 Mesh 40-120 Mesh >200 Mesh
850 μm/.0331” 425-125 μm 75 μm/.0029”
10-20% .0165”-.0049” 10-20%
70-80%
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4. Control Segregation
Segregation means that powders are not
staying mixed and are separating. This
leads to content uniformity issues and
table weight & hardness control.
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6. 5. Density Control
Density variation
within a single
ingredient equates to
major problems with
tablet & capsule
manufacturing across
the board.
Bulk density variation
Each item in the above photo weighs
of ingredients within the same!
the blend is a recipe
for trouble. 11
6. Capture & fuse “Active”
There are 2 things “Actives and
Excipients” within a formulation.
Sometimes we granulate the entire blend
and other times we granulate individual
ingredients.
The Active Ingredient can represent a very
small percentage of the final formulation
or a very high percentage of the
formulation.
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7. Which Pathway?
Direct Compression
Wet Granulating
Dry Granulating
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Direct Compression
Why not just weigh the powder, mix it and put it on the tablet press?
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8. Granule Formation
Granules can be formed by
adding a liquid “Binder “
into the dry powder mass,
much like combining water,
milk or egg with flour when
cooking.
Granules can be formed
through dry compaction;
compaction;
some powders are sensitive to
liquid addition and high
temperatures from the drying
process.
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What is a Binder?
A binder is an “excipient” (non-active
ingredient) that forms a bridge and locks
particles together…aka a pharmaceutical
glue.
There are dry binders and wet Binders and
there are a few binders like “Avicel
PH102” by FMC that can work as a dry or
wet binder
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9. Wet Granulating
Pre-Blend
Wet Mass
Mill
Dry
Mill
Final Blend
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Dry Granulating
Dry Granulating is
also known as Roller
Compaction and
Slugging
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10. Process Pathways
Wet Granulation Dry Granulation Direct Blending
Pre-mix Pre-mix
Wet Massing Slugging/Chilsonating
Drying Milling
Milling Final Blending Charge and Blend
Powde rs
Final Blending
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5 Steps
There are 5 steps to follow which will help
to Determine if granulating is necessary
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11. 1. Is Direct Compression
Feasible?
If yes = Direct Compress
If no= The product must be Granulated
Many products are successful at a slow
speed on a tablet press, but not fast.
Can your product run as fast as the press
can go? If the answer is No, then your
product is non-optimized and is limited in
some way?
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2. Is the Blend Cohesive
If yes = Direct Compress
If no= The product must be Granulated
Products need to be cohesive (sticky). If
the answer is no something must be
added to help lock the particles together.
If products are too cohesive then we have
another problem which is commonly
referred to as “sticking & picking”.
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12. 3. Is the Flow acceptable?
If yes = Direct Compress
If no= The product must be Granulated
Flow is critical and it can change from
product variation, environmental changes,
and it can be impacted by time.
Good flow is like granulated sugar
Bad flow is like flour
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4. Is Content uniformity
acceptable?
If yes = Direct Compress
If no= The product must be Granulated
What is “content uniformity”?
Content Uniformity means that each and
every tablet has the same quantity of
ingredients within an acceptable range.
Is it possible to blend powders and then
have them come unblended? YES.
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13. 5. Is the Bulk Density
acceptable?
If yes = Direct Compress
If no= The product must be Granulated
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Granulate
If the answer to any of the above was YES
then the formula or ingredients within the
blend must be granulated.
Which method of granulation should you
choose? Wet or Dry Granulating?
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14. Summary
Remember that the purpose of Granulating is
to simply make a better tablet. If there is a
problem such as weight, hardness, thickness,
friability, appearance, disintegration,
dissolution, content uniformity, just to name
the major ones…then the need to granulate or
the need to improve they way you are
granulating must be carried out.
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Granulating series
Granulating Basics 101 – Dec 4th
Granulating 201 – Feb 26th
Granulating 301- April 23rd
If you would like to attend future
Granulating programs please email a
request for a discount coupon after this
presentation and we will email a 10%
discount coupon good for future sessions.
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15. Special Request
Please send photos and examples of
defects or examples of common problems
at your facility.
In return we will send you a free pass to a
future seminar.
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Questions and Thank You!
Open for Questions
If you don’t get the answer, email or call me to
discuss
Please join us next week for our QA/QC session
Thank You for joining me….Mike Tousey
Techceuticals
36 Persimmons Street, Suite 303
Bluffton, South Carolina, USA 29693-4519
Phone: 843 815 7441 Fax: 843 815 7446
E-mail: sales@techceuticals.com Web: www.techceuticals.com
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16. Thank You for attending today!
We hope you enjoyed today’s program
and will join us again soon.
If you need help, let the professionals at
Techceuticals bring their practical
solutions to your company! Ask us how
today!
Techceuticals
36 Persimmons Street, Suite 303
Bluffton, South Carolina, USA 29693-4519
Phone: 843 815 7441 Fax: 843 815 7446
E-mail: sales@techceuticals.com Web: www.techceuticals.com
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