(656d) Underlying Mechanisms Leading to a Wet Milling Process Grinding Limit As a Function of Scale

Population balance equations (PBEs) are used to describe crystallizations and terminal milling processes frequently used in the pharmaceutical industry. A PBE accounts for the rate of generation and depletion of particles due to various mechanisms. Numerical schemes to solve integro-differential equations face specific mathematical and numerical challenges. In contrast, Monte Carlo simulations mimic events of a process using probabilistic tools to produce a snapshot of the population, from which particle size distributions may be reconstructed. Monte Carlo simulations are particularly suited for population balances that exhibit discrete elementary events that are inherently probabilistic (e.g., a crystal particle breaks into several fragments with prescribed probabilities; one unit of mass is deposited on the surface of a particle, a size-dependent dissolution event, etc.) [1].

In this work, we investigated the underlying phenomena that describe a terminal high-shear rotor-stator wet milling process where a polymorphic transformation takes place and particle size is controlled. Special attention will be paid to process scalability.

References

[1] Singh, M.; Ranade, V.; Shardt, O.; Matsoukas, T. Challenges and opportunities concerning numerical solutions for population balances: a critical review. J. Phys. A: Math. Theor. 55 (2022) 383002.