Design of a Combined Modular and 3D-Printed Falling Film Solution Layer Crystallizer for Intermediate Purification in Continuous Production of Pharmaceuticals

Ind Eng Chem Res. 2021 Jul 21;60(28):10276-10285. doi: 10.1021/acs.iecr.1c00988. Epub 2021 Jul 12.

Abstract

A highly scalable combined modular and 3D-printed falling film crystallization device is developed and demonstrated herein; the device uses a small, complex, printed overflow-based film distribution part that ensures formation of a well-distributed heated liquid film around a modular, tubular residence time/crystallizer section, enabling extended residence times to be achieved. A model API (ibuprofen) and impurity (ibuprofen ethyl ester) were used as a test system in the evaluation of the novel crystallizer design. The proposed crystallizer was run using three operational configurations: batch, cyclical batch, and continuous feed, all with intermittent removal of product. Results were suitable for intermediate purification requirements, and stable operation was demonstrated over multiple cycles, indicating that this approach should be compatible with parallel semicontinuous operation for intermediate purification and solvent swap applications in the manufacture of drugs.