Crystallization process monitoring and control using process analytical technology

In the past two decades, crystallization process understanding and development has been significantly improved by the use of process analytical technology methods. This chapter aims to give an overview of process analytical technology-based crystallization monitoring and control concepts. First a description of the available crystallization monitoring technologies is given, then control strategies for both batch and continuous processes are discussed. For batch crystallization processes, three feedback control methods, namely, control chart-based switching between nucleation and ripening steps, concentration or supersaturation control, automated direct nucleation control, and polymorphic feedback control are covered. Additionally, optimal solvent selection using process analytical technology as a polymorph control method is also discussed. The continuous crystallization monitoring and control related topics include automated direct nucleation control, polymorphic control, and encrustation monitoring.