Abstract
A mechanistic understanding of the over-granulation problem during high shear wet granulation (HSWG) process can guide efficient development of robust formulation and manufacturing process. Using microcrystalline cellulose (MCC) as a model compound, we demonstrate that size enlargement is an important mechanism for over-granulation in HSWG. A higher granulation water level results in larger granules and lower tabletability. With increasing water, granules enlarge sharply when water level is higher than 65%. Granule tabletability deteriorates with increasing granule size and becomes over-granulated when more than 70% water is used. For a batch of over-granulated granule that is ground and sieved, tabletability of the sieved fractions decreases with increasing granule size. The tabletability of the finest fraction (45-90 μm) is nearly four times that of the largest fraction (300-425 μm). These results show that size reduction can be an effective strategy to address the problem of over-granulation.
Original language | English (US) |
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Pages (from-to) | 3322-3325 |
Number of pages | 4 |
Journal | Journal of Pharmaceutical Sciences |
Volume | 99 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2010 |
Bibliographical note
Funding Information:This work is supported by a grant from the Dane O. Kildsig Center for Pharmaceutical Processing Research.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
Keywords
- Granule size
- High shear wet granulation
- Microcrystalline cellulose
- Over-granulation