Determination of fluidized bed granulation end point using near-infrared spectroscopy and phenomenological analysis.

Simultaneous real-time monitoring of particle size and moisture content by near-infrared spectroscopy through a window into the bed of a fluidized bed granulator is used to determine the granulation end point. The moisture content and particle size determined by the near-infrared monitor correlates well with off-line moisture content and particle size measurements. The measured particle size is modeled using a population balance approach, and the moisture content is shown to follow accepted models during drying. Given a known formulation, with predefined parameters for peak moisture content, final moisture content, and final granule size, the near-infrared monitoring system can be used to control a fluidized bed granulation by determining when binder addition should be stopped and when drying of the granules is complete. Copyright 2005 Wiley-Liss, Inc. and the American Pharmacists Association.