Novel impinging jet and continuous crystallizer design for rapid reactive crystallization of pharmaceuticals

Reactive crystallization is an important operation in the pharmaceutical industry for the production of the active pharmaceutical ingredients (APIs), but has not been as widely studied as cooling or anti-solvent crystallization. Reactive crystallization has many unique features that make them different from cooling or anti-solvent crystallization, even leading to some concepts and methods not directly applicable to the former. Literature survey reveals that previous research on reactive crystallization has mainly been conducted for inorganic materials which are known to be simpler than crystallization of organic molecules. The focus of this research project was to carry out research on the process design and optimization of organic reactive crystallization. The objective was to research on novel crystallizer designs that suit and take advantages of the features of reactive crystallization, and on advanced modeling and optimization techniques with the aim of manufacturing high quality products. Process analytical technology was used as a supporting tool to achieve the above stated objectives. The results showed that by using novel impinging jet design, the product had uniform size distribution and superior crystallinity. In addition, continuous process design can achieve a greater amount of product handling and reduce the batch-to-batch variation.