(233v) Development and Optimization of a Mixed Suspension Mixed Product Removal (MSMPR) Crystallization Process Incorporating Wet-Milling
- Conference: AIChE Annual Meeting
- Year: 2016
- Proceeding: 2016 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
- Time: Monday, November 14, 2016 - 3:15pm-5:45pm
The work presented herein solves the fouling and classification issues encountered for one of Takedaâ??s APIs by adding wet-milling to the first stage of an MSMPR crystallizer. The API studied was found to be characterized by slow nucleation kinetics resulting in a prolonged wash out period. During this period, large (>1mm) particles were formed that were unable to be transferred leading to classification issues, build up of supersaturation and severe fouling.
The high shear imparted by the wet-mill was found to control particle size and increase both primary and secondary nucleation rates. This reduced supersaturation and therefore fouling and encrustation. The wet-mill was incorporated in the first stage of the cascade which was then experimentally optimized investigating factors such as solvent composition, types and materials of construction of the impeller, wet-mill rotational speed, wet-mill turnover numbers, residence time and start-up methods. Finally, a multi-stage system was developed to optimize productivity.