Modeling and Computational Fluid Dynamics−Population Balance Equation−Micromixing Simulation of Impinging Jet Crystallizers

Abstract

Computational fluid dynamics (CFD), micromixing modeling, and the population balance equation (PBE) are coupled to simulate the crystal size distribution in a confined impinging jet crystallizer. For the antisolvent crystallization of lovastatin in confined impinging jets, the simulation results show varying degrees of inhomogeneity in the supersaturation and the nucleation and growth rates in the impinging jet crystallizer for different jet Reynolds numbers. The shape of the crystal size distribution and its variation with jet Reynolds number are consistent with experimental observations of unconfined impinging jets. The crystallization of l-histidine was also modeled to predict the crystal size distribution of stable and metastable polymorphs obtained from a confined impinging jet crystallizer. It is predicted how to adjust the inlet velocity to tailor the crystal size distribution, while the polymorph ratio remained relatively constant. The simulation results presented in this manuscript demonstrate the possibility of designing impinging jet crystallizers by modeling and simulation, to provide increased process understanding and reduce the experimental material required for design.