A PAT Approach to Enhance Process Understanding of Fluid Bed Granulation Using In-line Particle Size Characterization and Multivariate Analysis

Abstract

The purpose of this study was to achieve improved process understanding of fluid bed granulation using in-line particle size analyzer in conjunction with multivariate methods. The combined use of process analyzers and multivariate tools provides a useful means to drug development within the framework of quality by design utilizing process analytical technology. The evaluation of in-line monitoring manufacturability quality attributes, particle size, and particle size distribution, was conducted using the Parsum probe which is based on spatial filtering technique. Several granulation batches were manufactured and monitored using a commercial-scale fluid bed granulator. Reference measurements by offline Malvern MasterSizer showed good agreement with those by Parsum at end-of-spray phase. Multivariate/batch statistical process control methods were used to evaluate batch process performance, batch-to-batch variation and develop potential control strategy. The results indicated that the Parsum analyzer is a viable tool for in-line particle size characterization and improved process understanding in combination with multivariate tools.