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FOAM

GRANULATION
PRESENTED BY
Long Island University

NIKHIL KUMAR NARRA

11/8/2011

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Content:

Introduction Why Do We Need Granulation? Mechanism of Foam Granulation Benefits Applications Conclusion Personal opinion References

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INTRODUCTION
Definition:
In addition to active ingredients, formulations are complex
mixtures of diluents, binders, disintegrants, surface active agents, glidants, lubricants, colorants, coating substances, surfactants and many other raw materials that impart different properties to the final solid dosage product.

The process of reducing a substance to very small pieces

(granules). Granulation is required to impart improved technical properties to a substance, to prevent sintering (adhesion) and increase friability, to make it possible to use small portions of a material, and to facilitate loading and transporting.

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GRANULAR MATERIALS
A granular material is a collection of distinct macroscopic particles,
such as sand in an hourglass or peanuts in a container.

The evolution of the particles follows Newton's equations, with

repulsive forces between particles that are non-zero only when there is a contact between particles. tremendous amount of complex behavior, much of which has not yet been satisfactorily explained. They behave differently than solids, liquids, and gases which has led many to characterize granular materials as a new form of matter. then the large scale state of the system depends on the angle of the plane.

Although granular materials are very simple to describe they exhibit a

For example, if a granular material is heaped on an inclined plane,

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Contin.
For large angles the granular material flows like a non-Newtonian
liquid. For small angles the granular material will behave like a solid and remain stationary.

The value of the critical angle between these phases depends on

the preparation history, and the transition between the phases is a manifestation of the glass transition. granular materials interesting are inelastic collisions and the unimportance of temperature.

From a small scale point of view, the characteristics that make

Because collisions between particles are inelastic then the energy

of a granular material is a dynamic quantity, and because the particles that make up a granular materials are macroscopic then temperature does not produce significant motion.

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WHY DO WE NEED GRANULATION ?

Granulation is carried out for various reasons,
one of those is to prevent the segregation of the constituents of powder mix. Segregation is due to differences in the size or density of the component of the mix. tend to concentrate at the base of the container with the larger and/or less dense ones on the top. An ideal granulation will contain all the constituents of the mix in the correct proportion in each granule and segregation of granules will not occur.
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Normally, the smaller and/or denser particles

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Foam Granulation
In 2003, The Dow Chemical Company (Midland,
MI) introduced foam technology for delivering aqueous binder systems in high-shear and fluidbed wet granulation applications. solution tank and high-shear granulator to introduce the binder as a foam rather than spraying or pouring in binder onto a moving powder bed.

A foam generator can be set up with a binder

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Foamed Binder Granulation Set Up

Binder Solution Tank

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Foam Generator

High Shear Granulator

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What was the motivation to develop a new granulation technology versus conventional granulation techniques ?
The significant problem in the spray granulation is the uniform
distribution of the liquid/binder combination evenly throughout a moving powder bed. It may appear to be uniform when spraying, but it doesn't always happen. preferentially grab the water in the granulating liquid and sometimes this would interfere with its uniform distribution enlargement

They have hydrophilic polymers in their formulations that tend to

Foam granulation uses less liquid to achieve the same extent of size Reduces drying and manufacturing time in the granulation stage due
to lower liquid requirements

Faster addition rates, and improved process control Selection of nozzle can be eliminated
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Contin.
Simplified scale up can be achieved by reducing the number of
variables.

Foam granulation also increases manufacturing flexibility for water

sensitive drugs and low dose drugs

Most recently hapgood and melvin compared the physical and

mechanical properties of granules and tablets made by foam granulation and spray granulation for three high drug load formulation. pore size when using foam or spray granulation, but there were differences in the mechanical properties of the tablets.

They found no major difference in the granule surface area or granule

When the granules contained a high loading of brittle drug, the

plasticity of granules was higher when foam granulation was used, possibly due to improved surface coverage of the liquid binder on the brittle drug particles.

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some of the unique challenges and applications of using foam granulation ?

We have found that most people are using it for new
applications and some are looking at it as replacement for current methods, especially because of potential cost savings. for ex : The technology does not use nozzle systems.

The technology also has been helpful in some cases where

there may be difficulty in scaling up a process because of over-wetting and the number of nozzle systems that may need to be used. Foam technology has been proven to scale very easily for both immediate release and matrix controlled-release products.
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Contin.
The technology also uses less water per granulation,
which means less drying time and less impact on the environment.

This technology appears to help solve the issues that

people have been having with wet granulation of highly water-soluble and even very poorly water soluble drugs. and over granulated products.

These issues include areas of concentrated over wetting The technology seems to provide a better and a wider
endpoint in which to granulate to even with some very difficult actives that we work with, including natural ingredients in the nutritional supplement industry.

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Binder dispersion and nucleation in mixergranulators

Nucleation experiments in this study show that foam delivery tends to
create a narrower nuclei size distribution during the early stage of wet granulation process compared to spray delivery at the same processing conditions, demonstrating the potential of foam granulation in achieving improved binder distribution. properties and powder flow conditions in the granulator

For foam delivery, the nuclei formation is influenced by the foam The experiments show that the narrowest nuclei size distribution is

obtained by granulating with high-quality foam and intensive powder mixing conditions. intensively agitated powder. The interactions of foam quality and the powder flow pattern are discussed and two distinct wetting and nucleation mechanisms are proposed under bumping flow, a low-quality foam tends to induce localised wetting and nucleation. The wetting and nucleation is foam drainage controlled. Under roping flow, foam will be dispersed by the motion of the agitated powder. The wetting and nucleation is mechanical dispersion controlled.

Coarser nuclei are formed when low-quality foam is dispersed in a less

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Evaluating foam binder performance in high shear granulation

To investigate performance differences between
conventional spray v/s foamed polymeric binder addition methods, the following CR naproxen sodium system was developed for a high shear granulation study.

1. Naproxen sodium (44%) 2. METHOCEL K4MP CR, Hypromellose 2208 USP

(30%)

3. METHOCEL E6PLV, Hypromellose 2901 USP,

binder (1%)
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4. FFL-316 (24.5%)

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Torque profiles show faster processing, lower water requirements

The foam system achieved common endpoint torque in 40% less time than the spray addition method. The foam method also required 40% less water for the granulation step. 11/8/2011 1515

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Reproducible particle size distributions and fewer fines

Here, Two trials for the foam system yielded quite similar particle size distributions. Even more important, the foam addition method yielded significantly lower levels of particles smaller than 140 mesh (105 microns).

It strongly suggests that the very rapid and thorough particle wetting by the foam allows small particles to adhere to larger particles in the early stages of granulation, Long Island University 11/8/2011 1616

Comparable tablet physical properties

Physical properties were quite similar for the foam and spray systems. Physical property testing generally showed tablet crushing strengths within one standard deviation of each other. Tablet thicknesses were also very similar. 11/8/2011 1717

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Applications
The Use of Starch 1500 as a Binder and Disintegrant in foam
Granulation

Colorcon's unique manufacturing process results in the most effective

functional balance for Starch 1500. Due to the low solution viscosity, binding and disintegration properties, Starch 1500 allows for process flexibility. This flexibility includes the ability to dry-blend Starch 1500 with other ingredients before adding water, or dispersing a portion in cold water. formulation and the process used, as well as the desired finished dosage characteristics.

The choice of where to add the starch excipient depends greatly on the

Dry Addition

The cold water soluble fraction of Starch 1500 provides unique benefits for

the granulation process. The main advantage is that it can be dry blended with other ingredients and granulation can be accomplished by the addition of water. slurries. The approach is similar to using fully pregelatinized starches,

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Conclusion
Foam granulation gives excellent stability and a broader
operating window than standard liquid injection.

Uniformly wetted particles were found with foamed binder

addition, which minimizing heat build-up in the exiting granulates and allowed lower binder solution concentrations to be used than possible by direct liquid injection to the extruder. processing. Overall, foam binder processing is easier, faster and allows ease of handling of drug compounds even at lower concentration.

The dilute binder solutions are easy to handle in

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Personal Opinion
This new technology allows for fast, simple and cost
effective granulation and could minimize issue associated with conventional process. cost foam generator, the manufacturing process uses less water than traditional wet granulation process. process so that it can reduce the nozzle difficulties.

Without modifying the exiting equipment and using a low

And my opinion is that it can be also used in many coating

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References
P. Sheskey et al., "Foam Technology: The Development of
a Novel Technique for the Delivery of Aqueous Binder Systems in High-Shear and Fluid-Bed Wet-Granulation Applications," poster presented at AAPS Annual Meeting and Exposition, Salt Lake City, UT, Oct. 26-30, 2003.

P. Sheskey et al., "Scale-Up Trials of Foam Granulation

TechnologyHigh Shear," Pharm. Technol. 31 (4), 94108 (2007).

"Niro Pharma Systems History,

Various papers presented at Advances in Wet Granulation Technology for Solid Oral Dosage Forms, AAPS Pharmaceutical Technologies Summer Conference, Lansdowne, VA, USA, 813 June 2003. Long Island University 11/8/2011 2121

References
M. Bardin, P.C. Knigh and J.P.K. Seville, Powder
Technol., 140, 169175 (2004). 30(8), 831845 (2004).

C.M. Keary and P.J. Sheskey, Drug Dev. Ind. Pharm., T. Hlinak, Am. Pharm. Rev., 3(4), 3336 (2000). M. Yasumura and K. Ashihara, Pharm. Technol. Japan,
12(9), 12791289 (1996).

E. Russo, Pharm. Technol., 8(11), 4656 (1984). K. Ashihara and M. Yasumura, Kagaku Kogaku, 60(3),
180182 (1996).

P. Sheskey, C. Long Island University

Keary and D. Clark, 11/8/2011 poster presented at 2222 the 2006 Annual Meeting and Exposition of the

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