Model-Based Systematic Design and Analysis Approach for Unseeded Combined Cooling and Antisolvent Crystallization (CCAC) Systems

A novel model-based systematic analysis and design approach for unseeded combined cooling and antisolvent crystallization (CCAC) processes has been proposed and evaluated for the crystallization of aspirin in ethanol–water mixture. The approach can be easily implemented in practice using automated lab reactors, and gives the optimal times for the start of a linear cooling profile or constant antisolvent addition rate. According to the proposed analysis, based on the sensitivity of the solubility surface, the simplified operating procedures should either belong to cooling first or antisolvent first strategy, depending on whether the initial solution locates at temperature sensitive region or antisolvent concentration sensitive region. The proposed approach can be used to produce operating surfaces based on which the performance of combined cooling and antisolvent crystallization systems can be understood and operating strategies rapidly designed depending on the initial concentration, solvent composition and desired yield.