Development and Characterization of a Single Stage Mixed-Suspension, Mixed-Product-Removal Crystallization Process with a Novel Transfer Unit

A continuously operated single stage mixed-suspension, mixed-product-removal (MSMPR) crystallizer using intermittent withdrawal via a dip pipe with combined pressure/vacuum was successfully developed for the manufacture of active pharmaceutical ingredients. Approximately 5.8% of the total operating volume was intermittently removed at a high velocity using vacuum. The transfer line was also periodically purged with nitrogen to ensure complete removal of residual solids. In situ process analytical technologies (focused beam reflective measurement (FBRM) and process video microscopy (PVM)) were successfully applied to monitor and characterize the MSMPR crystallization process. In this study, a cooling crystallization of paracetamol from an aqueous isopropyl alcohol solution was investigated. Experimental results indicate that the crystallization system was able to operate without any clogging issues for over 10 residence times, before which the system had approached steady state. Three different start-up st...