An energy-based population-balance approach to model granule growth and breakage in high-shear wet granulation processes |
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Authors: | Anish P Dhanarajan Rebanta Bandyopadhyay |
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Institution: | (1) Michigan Pharmaceutical Sciences, Pfizer Global R&D, Kalamazoo, MI;(2) Discovery Research, Dr. Reddy's Laboratories, Ltd, Bollaram Road, Miyapur, 500 049 Hyderabad, AP, India |
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Abstract: | A mathematical model of high shear wet granulation is proposed, where granule breakage, and not growth, is the dominant process.
The energy required for granule breakage is assumed to be provided by the impact of granules between themselves and the granulator
parts, and the extent of granule breakage determined by the balance between the impactenergy and the work of adhesion between
the agglomerating particles. A specific volume of dry powder per unit crack surface area was allowed to reattach to the surface
of broken granules to account for granule growth. To verify proposed model conditions, lactose monohydrate was granulated
with a relatively low amount (6%) of the binder phase, polyvinyl-pyrrolidone and water, and was added to the powder before
granulation.
The trend in granule size distribution during the experiment closely follwed the predicted model with an initial increase
in the weight fraction of the larger granules. This increase was possibly due to extensive breakage of weaker granules and
less extensive breakage, as if by attrition, of stronger granules, accompanied by the attachment of dry powder to the cracked
surfaces. Eventually, larger granules experience increased impact energy and break. When excess binder is added and, higher
volumes of powder reattach to the crack surface, more large granules form leading to granule overgrowth. This model highlights
the importance of the probability of impact per unit time interval (ie, the rate of impact), the strength of the granules
and the volume of powder that could attach to the cracked surface in high shear granulation processes where significant granule
breakage is encountered.
Published: August 10, 2007 |
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Keywords: | High shear granulation population blance model granule breakage |
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