Development of Continuous Anti-Solvent/Cooling Crystallization Process using Cascaded Mixed Suspension, Mixed Product Removal Crystallizers

Abstract

This paper describes a two-stage mixed-suspension, mixed-product removal (MSMPR) continuous crystallization developed for a pharmaceutical intermediate which uses anti-solvent and cooling to generate supersaturation. The results indicate that the stage in which anti-solvent is added has a significant influence on the final crystal properties, while purity and yield were nearly identical. The population balance model was employed to determine growth and nucleation kinetics through parameter estimation. With the incorporation of measured equilibrium distribution coefficients, the model was used to optimize crystal purity and yield of the product with respect to operating temperature and residence time.