Perspectives on Rotor Stator Wet Milling: Scaledown, Scaleup, Operations and Applications

Rotor stator wet milling is a versatile, scalable and portable method for manipulating the particle size and physical attributes of pharmaceutical APIs, intermediates and reagents, and can be utilized for a variety of applications. An overview of the theory for particle size reduction via wet milling will be provided, along with some general guidance on setup, operational parameters. Scaleup/scaledown issues (attrition, undesired annealing, reproducibility) and examples of novel applications will be presented by use of case studies, including the following: Particle size distribution modification by combination of terminal wet milling and heat/cool annealing; improving reaction kinetics and conversion efficiency by wet milling of a reagent to degranulate and expose fresh interfaces to solution phase; pushing the boundaries of rotor-stator wet milling with higher tip speed operations; and use of wet mills in sterile operations or for potent compounds, to reduce exposure risk and bioburden associated with dry powder processing.