Development and validation of a two-dimensional population balance model for a supercritical CO2 antisolvent batch crystallization process

In this study, a two-dimensional population balance model with solvent removal kinetics has been developed to predict the dynamic behavior of carbamazepine form II crystals produced by a supercritical CO2 antisolvent batch crystallization process. The model was simulated and validated using experimental crystal size distribution data (CSD). The model was able to accurately predict the behavior of CSD with a change in process operating conditions. The model was also applied to study the time evolution of aspect ratio, average crystal length, and solute concentration in the solution. Finally, solvent removal kinetics were modeled to evaluate the solvent content and drying temperature of the drying gas during the solvent removal process. The developed mathematical model and the presented results suggest the ability of the discussed approach to make suitable model predictions, which can significantly reduce the number of experimental trials required for process design, optimization, and control. (c) 2020 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.