Systematic model-based dynamic optimization of a combined cooling and antisolvent multistage continuous crystallization process

A rigorous and systematic methodology was developed to optimize multistage combined cooling and antisolvent continuous MSMPR (mixed-suspension, mixed-product removal) crystallizers. The crystallization of aspirin (acetylsalicylic acid, ASA) in ethanol (solvent) and water (antisolvent) was used as a case study. A validated mathematical model of the system was firstly used to optimize the steady state performance followed by the development of several optimizations strategies aiming at the minimization of the start-up time using optimal dynamic profiles of antisolvent addition, cooling temperature, seeding flowrate and the combination of these decision variables. The start-up scenarios were also considered in the case of initially prefilled and empty vessels. Using the proposed dynamic optimization strategies, it was predicted that the start-up time can be reduced by up to 70%, which represents a significant gain in time, cost and environmental performance.