7 - Modeling of milling processes via DEM, PBM, and microhydrodynamics

Abstract

This chapter presents various modeling approaches used for the simulation and design of wet and dry milling processes in pharmaceutical industry. After introducing the milling process and its salient features, we report the state-of-the-art modeling techniques including microhydrodynamic models, discrete element method (DEM), and population balance model (PBM), and their integrated use in a multiscale framework. The discussion of theory is followed by two major cases studies: one on the application of a microhydrodynamic model to the preparation of poorly water-soluble drug nanosuspensions in a wet media mill and another on the application of a multiscale DEM–PBM approach to ball milling. The former case study demonstrates how microhydrodynamic models can guide the design of wet media milling processes, whereas the latter case study demonstrates how one can judiciously combine particle scale–ensemble scale–process scale models to simulate the evolution of particle size distribution during dry milling.