Optimal start-up strategies of a combined cooling and antisolvent multistage continuous crystallization process

A model-based optimization methodology was developed to systematically address all possible optimal start-up scenarios of a multistage combined cooling and antisolvent continuous MSMPR (mixed-suspension, mixed-product removal) crystallizer. The crystallization of aspirin (acetylsalicylic acid, ASA) in ethanol (solvent) and water (antisolvent) was used as a case study. A steady state optimization was firstly conducted to optimize the crystallizer design and operating conditions and set-up the reference trajectories. The discretised profiles of the jacket temperatures, antisolvent flowrates and seeding policies, which includes the seed flowrates, loading and mean size, were used as decision vectors for the dynamic optimization problem. Scenarios with single and combined decision vectors were addressed and analysed in start-up situations involving prefilled or empty vessels. The impact of simplified optimization and operating procedures or refined discretization schemes were also addressed. It was shown that several options may provide comparable performance and the start-up time can be improved by nearly 80% in the case of combined decision vectors involving all possible decision vectors.