Modeling-Aided Scale-Up of High-Shear Rotor–Stator Wet Milling for Pharmaceutical Applications

Abstract

This work describes a modeling-aided approach to scale-up high-shear rotor–stator wet milling processes for pharmaceutical applications. A population balance equation was used that applies known breakage distribution functions and specific breakage rate to provide valuable insight into the significance of different scale-up factors to predict milling performance as well as the importance of accounting for flow-induced breakage in recirculation configurations. Case studies involved the size reduction of platelike and rodlike organic crystalline compounds.