Modelling and control of combined cooling and antisolvent crystallization processes

Although for decades nearly all pharmaceuticals have been purified by crystallization, there have been a disproportionate number of problems associated with the operation and control of these processes. This paper provides an overview of the recent advances in model-based and model-free (direct design) approaches to control the crystallization of pharmaceuticals, treating both antisolvent and cooling crystallization. A model-based combined technique which simultaneously controls the antisolvent addition rate and the cooling profile is presented. A population balance model of the combined cooling-antisolvent addition system is developed and a moments model is used in optimal control strategies with various objective functions. The simulation and experimental results show the advantages of the combined approach.