Developing a Systematic Design Approach to Tailor Crystal Size Distribution for Mixing-Sensitive Crystallization Processes

The design of crystallization processes becomes more complicated when mixing affects the final crystal product quality (e.g., crystal size distribution and polymorphic form). Such mixing effects are more apparent in antisolvent and reactive crystallizations, which involve the blending of different fluids, and in large-scale crystallizers, where homogeneity cannot be easily achieved. In this paper, we present the use of an integrated algorithm, which couples macromixing and micromixing models with the population balance equation, to model antisolvent crystallization in a stirred vessel and impinging jet crystallizers. The dependency of the crystal size distribution on the mixing speed and scale for a stirred vessel and the effects of jet velocity on the crystal size distribution and polymorphic form for an impinging jet crystallizer are numerically investigated. Eventually, the development of such computational tools would enable us to understand the interactions between hydrodynamics and the kinetics of crystallization in order to develop systematic design methodologies for crystallization processes.