(762c) Process Dynamics of Continuous Cooling Crystallization of Carbamazepine in a Mixed Suspension Mixed Product Removal (MSMPR) System
- Conference: AIChE Annual Meeting
- Year: 2017
- Proceeding: 2017 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
Thursday, November 2, 2017 - 4:05pm-4:30pm
The continuous cooling crystallization of carbamazepine (CBZ) in ethanol in a multi-stage MSMPR system is used as the case study. FBRM and Raman spectroscopy are implemented for on-line monitoring. Various startup conditions are evaluated to determine the optimal scenario for the continuous system of interest. The impact of disturbances on the process dynamics and state of operation are evaluated by implementing pulse or step changes to the temperature, flowrate, feed solution concentration, and polymorphic form. Slurry samples for all experiments are obtained and characterized by off-line HPLC, laser diffraction and XRPD before and after the disturbances. The on-line and off-line data obtained are used to characterize the effect on crystal properties (i.e. size and form) and process parameters (i.e. solution concentration). Moreover, simulation studies for the crystallization process are conducted using population balance models to further understand the impact of process disturbances on quality attributes for the continuous cooling crystallization of CBZ.
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