(159c) Characterization of Novel Plug Flow Continuous Crystallizer
AIChE Annual Meeting
2024
2024 AIChE Annual Meeting
Separations Division
Plenary Session: Crystallization and Evaporation - Area 2B (Invited Talks)
Monday, October 28, 2024 - 1:58pm to 2:18pm
Process developers in the pharmaceutical industry lack a readily deployable, standardized, off-the-shelf continuous crystallization setup, abiding the low material requirements of early product development.1 The mixed-suspension-mixed-product-removal crystallizer (MSMPRC) offers the highest flexibility in terms of residence time and agitation intensity, making it the commonly used continuous crystallization platform. By operating a series of MSMPRCs, quasi plug flow behavior can be attained with narrower residence time distribution (RTD) enabling superior control over the
product’s critical quality attributes compared to a single stage. However, slurry transfer in continuous operation poses significant hurdles, particularly at the lab-scale, where the reduced size of the equipment’s transfer lines increases the risks of classification and clogging. In this study a novel stacked continuous crystallizer cascade is presented, hosting a series of ≥ 7 MSMPRCs (80 mL total volume) with a novel diaphragm driven slurry transfer not requiring transfer lines. RTD measurements reveal a nearly ideal mixing behavior throughout the cascade. Solids’ handling is assessed with different crystal size distributions (CSDs) of a model compound, to identify the size range for optimal performance. The results are evaluated by comparison with the tank in series model. Finally, proof-of-concept antisolvent crystallization experiments demonstrate the capability of the cascade to continuously manufacture solids with a narrow CSD and representative product extraction.
product’s critical quality attributes compared to a single stage. However, slurry transfer in continuous operation poses significant hurdles, particularly at the lab-scale, where the reduced size of the equipment’s transfer lines increases the risks of classification and clogging. In this study a novel stacked continuous crystallizer cascade is presented, hosting a series of ≥ 7 MSMPRCs (80 mL total volume) with a novel diaphragm driven slurry transfer not requiring transfer lines. RTD measurements reveal a nearly ideal mixing behavior throughout the cascade. Solids’ handling is assessed with different crystal size distributions (CSDs) of a model compound, to identify the size range for optimal performance. The results are evaluated by comparison with the tank in series model. Finally, proof-of-concept antisolvent crystallization experiments demonstrate the capability of the cascade to continuously manufacture solids with a narrow CSD and representative product extraction.
(1) Cote, A.; Erdemir, D.; Girard, K. P.; Green, D. A.; Lovette, M. A.; Sirota, E.; Nere, N. K.
Perspectives on the Current State, Challenges, and Opportunities in Pharmaceutical Crystallization
Process Development. Cryst Growth Des 2020, 20, 7568–758