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Using PAT to Tune Mill Processes: Optimizing the Particle Size Distribution of APIs

Kippax PG.

RDD Europe 2009. Volume 1, 2009: 73-82.

Abstract:

The Quality by Design (QbD) and Process Analytical Technology (PAT) initiatives have provided an opportunity for the pharmaceutical industry to re-evaluate manufacturing science, through the application of a risk-based approach to developing product specifications. One area which has received much attention is that of particle size control. This paper demonstrates the application of laser diffraction based particle size analysis to improve the understanding of mill processes, which results in improved product consistency. The importance of the selection of an appropriate sampling point for size analysis within the process is described, along with the differences between ‘in-line’ and ‘on-line’ sampling methods. The application of laser diffraction is then described for process optimization studies where raw material consistency, mill feed rate and the mill operating conditions are shown to be important. These case studies demonstrate how real-time particle size data can enable the root causes of process variability to be identified.