(392c) Investigation of Particle Size Reduction Mechanisms in Rotor Stator Wet Mills

Rotor stator wet milling has emerged as an alternative to traditional dry milling to reduce particle size while eliminating the processing hazards associated with dust generation. Currently, published fundamental investigations to understand particle size reduction of pharmaceutical compounds during wet milling are limited. In this study, a lab scale fundamental investigation for how the particle size reduction mechanism (shear vs. particle-particle/particle-wall collisions) is related to the scale-up correlations of tip speed and shear frequency is explored for a variety of API compounds with differing morphologies. For each API compound, the lab scale milling parameters were varied by changing rotor rotational speed and rotor/stator configuration. The particle size was measured real-time using focused beam reflectance measurement (FBRM) and correlated to spot slurry samples analyzed by light scattering. The benefit of a fundamental understanding of this technology will aid in building a platform to translate lab scale development to the pilot plant and, subsequently, the manufacturing scale.