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. © 2005 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:604-612, 2005