The aim of this work is to demonstrate that uncontrolled initial moisture content in microcrystalline cellulose (MCC) can profoundly affect high shear wet granulation (HSWG) process. We show that granule tabletability is reduced by approximately 50% when initial moisture content in MCC increases from 0.9% to 10.5% while all other processing parameters remain unchanged. An important observation is that granule tableting performance deteriorates significantly when initial moisture content increases from 2.6% to 4.9%, which is considered normal variation in moisture content for typical MCC (3-5%). The deteriorated tabletability is largely caused by increased granule size. On the other hand, granule flowability improves continuously with increasing initial moisture content in MCC. The improved flowability is mainly a result of granule size enlargement. Clearly, moisture content of raw materials for a HSWG process must be carefully monitored and controlled to ensure a robust manufacturing process as required by the quality-by-design principle.
Bibliographical noteFunding Information:
This work is supported by a grant from the Dane O. Kildsig Center for Pharmaceutical Processing Research (CPPR) and University of Minnesota (Grant-in-aid).
Copyright 2012 Elsevier B.V., All rights reserved.
- High shear wet granulation
- Microcrystalline cellulose
- Moisture content