CONTROL OF HYDRATES IN CONTINUOUS ANTISOLVENT COOLING CRYSTALLIZATION FOR A DRUG SYSTEM

Pharmaceutical manufacturing typically uses batch processing at multiple lo-cations. As a result production of a finished dosage form can require up to a total of 12 months with large inventories of intermediates at several stages. This enormous space-time demand is one of a myriad of reasons that has led to increased interest in continuous manufacturing (CM) of active pharmaceu-tical ingredients (APIs) and drug products. One aspect that needs to be addressed is the crystallization dynamics of hydrated drug forms in CM settings due to their vital impact on the physicochemical properties of APIs. This study focuses on the API mercaptopurine (6-MP), which is used for the treatment of the rare diseases, acute lymphoblastic leukemia (ALL) and Chron’s disease. 6-MP is administered in its monohydrate form, therefore, a thorough design of a continuous crystallization process is crucial to produce a drug product that meets regulatory standards. Solid state characterization of crystallized 6-MP was conducted by Raman spectroscopy and Powder X-Ray Diffraction. The study demonstrates that 6-MP monohydrate can be produced in a continuous crystallization setting by the choice of the sol-vent/antisolvent system with a yield of 96%.