This is advance method of tablet granulation technology.

1. FOAM GRANULATION TECHNOLOGY
PRESENTED BY
ALI SARTAJ
NIPER-HYD
18-01-2015 1

2. CONTENTS
• INTRODUCTION
• ADVANCED GRANULATION TECHNIQUES
• ADVANTAGES
• METHODOLOGY
• EQUIPMENTS
• APPLICATIONS
• FUTURE ASPECTS/CHALLENGES
• CASE STUDY
• REFERENCES
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3. INTRODUCTION
Powder particles are made to
adhere to form larger/multi
particle(.2-4mm)
Granules are either packed or
they mixed with other
excipients to form
tablet/capsule
Marketed product as a
Granule (Brufen Granules
600mg)
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4. NEED OF GRANULATION
1
•Increasing the bulk density of a product.
2
•Controlling the rate of drug release.
3
•Facilitating metering or volumetric dispensing.
4
•Improving product appearance.
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5. ADVANCED GRANULATION TECHNIQUES
Steam Granulation
Freeze Granulation
Technology(FGT)
Moisture Activated
Dry Granulation
(MADG)
Melt/Thermoplastic
Granulation
Foam Granulation
Thermal Adhesion
Granulation Process
(TAGP)
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6. FOAM GRANULATION-OVERVIEW
• In 2003, The DOW Chemical Company(Midland, MI) introduced foam
granulation technology.
• New approach of liquid delivery to create granules.
• Method of distributing the Foam binder through the powder.
• Alternative to the traditional application of atomized liquid spray in
pharmaceutical wet granulate on processes.
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7. FOAM GRANULATION-OVERVIEW
• Unlike spray granulation, the liquid binder is sent through a foam
generator and distributed to the powder bed as aqueous foam to
induce granulation.
• The inherently large surface areas of foams provide more efficient
particle coverage than may be achieved by conventional spray
technology.
• The technology has the capacity to produce a well-mixed granular
product of excipients and active ingredients with high consistency
in a relatively short span of time.
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8. ADVANTAGES
Foam
Granulation
Cost effective & Time
efficient
Improve process
robustness
No Spray
Nozzle
Water sensitive
Drugs
Uniform Binder
Distribution
No over
wetting
Less Water
Required
DISTRIBUTION OF BINDER AS AQUEOUS FOAM18-01-2015 8

9. METHOD
Required quantities
of drug, diluent or
disintegrant
Premixed
Addition of BINDER
to produce FOAM
Continuous
addition of FOAM
using CHOPPER and
IMPELLER
Collection of
granules after
attaining end point
Drying of Granules
in FBD Bowl
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10. EQUIPMENT REQUIRED
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International Journal of Pharmaceutical Frontier Research (IJPFR) 2(2)-2012: 68-79.

11. 18-01-2015 11
Typical equipment layout for foam granulation
showing: (1) Twin-screw extruder, (2) Powder
feed-port, (3) Gravimetric feeder for powder
excipients, (4) Side stuffer, (5) Mechanical foam-
generator, and (6) Foam feed-tube.
Drug Development and Industrial Pharmacy
2012; 38(7): 771–784
GRAL-600 Gral high shear granulator used in
manufacturing-scale up

12. INGREDIENTS USED
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CONTROLLED RELEASED NAPROXEN SODIUM FORMULATION
Naproxen Sodium 44%
METHOCEL K4MP CR, Hypromellose 2208
USP
30%
METHOCEL E6PLV, Hypromellose 2910
USP, Binder
1%
Fast Flow Lactose (FFL-316) 24.5%
Magnesium stearate 0.5%

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Drug dissolution results for a matrix controlled-
release formulation manufactured at lab-scale (10L),
pilot-scale (150L), and production-scale (600L) using
foam granulation technology. Tablets were prepared
at a low applied compression force (8.9kN) and a
high applied compression (26.7kN)
Drug dissolution results for an immediate release
formulation manufactured at lab-scale (10L), pilot-scale
(150L), and production-scale (600L) using foam
granulation technology. Tablets were prepared at a low
applied compression force (8.9kN) and a high applied
compression (26.7kN)
Scale-Up Trials of Foam Granulation Technology—High Shear
Pharm. Technol. 31 (4), 94–108 (2007).

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Rapid batch addition of foam to granulate

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Torque profile of high shear granulation comparing spray and foam binder
addition with a controlled release naproxen sodium formulation granulated
to a common endpoint
November 2004

16. MECHANISM
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Foam(Shown in shadow) dispersion during powder bumping flow
Chemical Engineering Research and Design 89(2011) 526-536

17. MECHANISM
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Foam(Shown in shadow) dispersion during powder roping flow
Chemical Engineering Research and Design 89(2011) 526-536

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Conceptualized recti-linear view of foam
addition to the twin screw extruder at
the site of the side stuffer unit.
Powder Technology 228 (2012) 339–348

19. FOAM GRANULATION vs WET GRANULATION
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FOAM BINDER LIQUID BINDER
Acceptable granulation at 6% and 11%
binder concentration
Acceptable granulation only at 11%
concentration
Low axial compression preferred,
otherwise excessive aggregation
observed
High axial compression required,
otherwise lactose excited as a few
large, wet lumps within a matrix of dry
powder
Exiting granule temperature largely
insensitive to process (less than 40°C in
all cases
Very high granule temperatures
occurred (reaching as high 90°C at high
axial compression conditions)
Pharmaceutical Technology 37 (2013) 68-72

20. FOAM GRANULATION vs WET GRANULATION
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Chemical Engineering Science 64 (2009), 2826-2836 A cross-sectional view of the twin-screw extruder-
Powder excipients (in blue) shows the differences in
configuration used for (a) directly injecting liquids
versus (b) introducing foamed binder into the
granulation process.
Pharmaceutical Technology 37 (2013) 68-72

21. FOAM GRANULATION vs WET GRANULATION
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Initial stages of foam penetration (left) and drop penetration (right)into a static powder bed
Chem. Eng. Res. Design 89 (5), 526-536 (2011).

22. APPLICATIONS
Reduce over-wetting and Number of Nozzle system
Ease of Scale – up for both IR and Matrix controlled release products
Less water usage - Reduced Drying Time and Less burden on Environment
Good carrier of components even very low concentration
Solve the issues related to Highly water-soluble Drug or very poorly soluble drugs
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23. APPLICATION
some very difficult actives that we work
with, including natural ingredients in
the nutritional supplement industry.
Is any
technique
suitable?
YES, Foam granulation
technology which gives
better and wider End
point
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24. CURRENT SCENARIO
1. Dow Wolff Cellulosics, part of The Dow Chemical Company, has
signed a commercial contract with Bristol-Myers Squibb to use
Dow's foam granulation technology in the development and
manufacture of tablets for clinical and commercial use.
2. Concern to Patent for is to fine tune the technology for coating of
tablets using foam technology rather than conventional spraying.
3. The pharmaceutical industry is very conservative when it comes to
new applications and new technologies. This technique has become
better but it always takes time- Challenge
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25. FUTURE ASPECTS
The selection of the most appropriate
granulation process (conventional wet or
foam) to improve a drug product's
manufacturability can be guided by
knowledge of the intrinsic mechanical
properties of the drug.
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WET Granulation FOAM Granulation

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Optical microscopy pictures of PARACETAMOL particle morphology. Pure material (P),
Wet granulation (W), and Foam granulation (F).

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Optical microscopy pictures of aspirin particle morphology. Pure
material (P),wet granulation (W), and foam granulation (F).

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Optical microscopy pictures of metformin particle morphology. Pure
material (P), Wet granulation (W), and Foam granulation (F).

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Particle size distributions for (A) APAP, (B) aspirin, and (C)
metformin, conventional Wet granulation vs. Foam granulation.

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CONCLUSION

35. CONCLUSION
BETTER
DISTRIBUTION OF
DRUG EVEN OF mg
QUANTITY
IMPROVE PHASICAL
CHARACTERISTICS
(PATIENT’S
COMPLIANCE)
APPLICABLE FOR
HIGH SOLUBLE AS
WELL VERY POORLY
SOLUBLE DRUGS
COMMERCIAL
VALUE
DEPEND ON
INTRINSIC
PROPERTIES OF
DRUG
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36. REFERENCES
 International Journal of Pharmaceutical Frontier Research (IJPFR) 2(2)-2012: 68-79.
 Drug Development & Industrial Pharmacy 38(7)-2012: 771-784.
 Chemical Engineering Research and Design 89(2011): 526-536.
 Pharmaceutical Technology 37(2013): 68-72.
 Powder Technology 228(2012): 339–348.
 Chemical Engineering Science 64(2009): 2826-2836.
 Chem. Eng. Res. Design 89(5)-2011: 526-536
 Pharm. Technol. 31(4)-2007 94–108
 POWDER TECHNOLOGY 195(2009):15-24
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38. NOW SEMINAR IS OPEN FOR DISCUSSION
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FOAM
GRANULATION ?