Computer-aided design and scale-up of crystallization processes: Integrating approaches and case studies

Scaling up a crystallization process often results in significant changes to crystal size distribution (CSD), purity and morphology, which are key determinants of product quality and has implications for downstream operations such as filtration. This unwelcome observation results from the interplay between hydrodynamics and crystallization kinetics that scale in different ways. Computer-aided tools, such as process system engineering (PSE) software and computational fluid dynamics (CFD) simulations, offer a means to understand these interactions within system constraints and to use the insight thus gained to guide scale-up strategies. This article outlines approaches to scaling up crystallizers and how to develop new processes, showing how numerical simulations and other software tools can be used to address typical issues arising in each case.