Process intensification of atorvastatin calcium crystallization for target polymorph development via continuous combined cooling and antisolvent crystallization using an oscillatory baffled crystallizer.

In this paper, continuous crystallization of Atorvastatin calcium (ASC) using a continuous oscillatory baffled crystallizer (COBC) has been investigated. Like most API manufacturing, ASC is manufactured batchwise and the pure API is recovered via batch combined cooling and antisolvent crystallization (CCAC) process, which has the challenges of low productivity, wide crystal size distribution (CSD) and sometimes polymorphic form contamination. To overcome the limitations of the batch crystallization, continuous crystallization of ASC was studied in a NiTech (United Kingdom) DN15 COBC, manufactured by Alconbury Weston Ltd.