(504c) Impact of Multiple Antisolvent Addition Points in a Tower Crystallizer

Process developers in the pharmaceutical industry lack readily deployable, standardized, off-the-shelf continuous crystallization setups, abiding the low material requirements of early product development.¹ To address this need a novel tower crystallizer (TWC) was first introduced in 2024.² The design consisted of seven tanks, simulating a vertically aligned cascade of mixed suspension, mixed product removal crystallizers (MSMPRCs) with a total volume of 80 mL. The slurry is transferred by a diaphragm-driven mechanism that eliminates the need for transfer lines, typically causing challenges in traditional lab-scale MSMPRCs.² The initial study also demonstrated ideal residence time distribution (RTD) characteristics and a proof-of-concept antisolvent crystallization process.²

In this work, we present a continuous crystallization strategy of multiple points of antisolvent addition along the TWC. The process performance is evaluated based on critical quality attributes of the crystallized active pharmaceutical ingredient, e.g., crystal size distribution and morphology. The results are benchmarked against a traditional lab-scale MSMPRC setup of equivalent volume to elucidate the impact of the TWC configuration on crystallization behavior.

References

(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, 7568–7581. DOI:10.1021/acs.cgd.0c00847.

(2) Aprile, G.; Pandit, A. V.; Albertazzi, J.; Vetter, T.; Viano, R.; Milani, L.; Adamo, A.; Myerson, A. S.; Stelzer, T. Residence Time Distribution Characterization and Proof-of-Concept of a Novel Stacked 7-Stage Continuous Crystallizer Cascade with Diaphragm-Driven Slurry Transfer. Ind. Eng. Chem. Res. 2024. DOI:10.1021/acs.iecr.4c02153.