Improving Workflow for Modeling of High-Shear Rotor-Stator Wet Milling for Pharmaceutical Applications

Wet milling is an important unit operation for the size reduction of pharmaceutical powders. The benefits of wet milling to the pharmaceutical industry relies on its ability to control particle size distributions (PSDs) while managing containment concerns and avoiding dry powder handling of potent active pharmaceutical ingredients (APIs). Due to the high-value nature of APIs, a trial-and-error experimentally-driven scale-dependent approach to obtain optimal milling conditions would not be cost-effective.

The use of modeling-aided scale-up of high-shear rotor-stator wet milling processes using a standardized population balance equation (PBE) approach has been reported by this group in the past.^1-2 In this work, recent model improvements as well as the creation of templates for easy data collection and the actions taken to improve the workflow will be discussed. A few case studies from early to late phase small molecules and multiple scales of mills from lab to manufacturing will be used to exemplify the approach.

¹ Luciani et al. PBE-Aided Design of Slurry Milling Process to Reduce Particle Size of Intermediate and Active Pharmaceutical Ingredients, AIChE Annual Meeting 2012 (366b)

² Luciani et al. PBE-Aided Design of Slurry Milling Process to Reduce Particle Size of Intermediate and Active Pharmaceutical Ingredients. Org. Process Res. Dev., 2015, 19 (5), 582–589