Recent advances in crystallization control - An industrial perspective

Crystallization is the most important unit operation for the separation and purification of chemicals in the pharmaceutical and fine chemical industries. Crystallization processes in pharmaceutical active ingredient manufacturing have been traditionally a recipe-based operations, offering little scope for dynamic process control and improvement. With the change in regulatory climate from quality-by-testing (QbT) to quality-by-design (QbD) and with the advent of the process analytical technology (PAT) initiative, it is timely to examine the impact of such quality-based emphasis on crystallization control. In this paper, we review the important recent developments in the control of crystallization process, and discuss their feasibility and scope for implementation in industrial processes. The control methods to achieve different aspects of crystal product quality, including particle size distribution (PSD), crystal habit and polymorphic form, are discussed separately.