Coupled-Batch Preferential Crystallization of Imeglimin Propionate on a 200 g Scale

The application of coupled-batch preferential crystallization (CB-PC) for the propionate salt of the active pharmaceutical ingredient imeglimin is demonstrated herein. Process conditions were chosen based on metastable zone width measurements, and an apparatus with 500 mL-sized crystallization vessels was constructed. A series of CB-PC experiments on an increasing scale were run, and observations on scaling up were made throughout, including the effect of the seeding method, productivity over time, and physical limits of the apparatus. The series culminated in two successive runs each on a 200 g scale, in which the mother liquor from the first run was recycled to the second.