462030 Characterization of an Integrated Continuous Cooling Crystallization Process with an in-Situ Wet Mill System for Particle Size Reduction

Wednesday, November 16, 2016: 4:15 PM
Cyril Magnin III (Parc 55 San Francisco)
David Acevedo1, Vamsi Krishna Kamaraju2,3, Brian Glennon2,3 and Zoltan K. Nagy1, (1)School of Chemical Engineering, Purdue University, West Lafayette, IN, (2)APC Ltd., Dublin, Ireland, (3)School of Chemical & Bioprocess Engineering, University College Dublin, Dublin 4, Ireland

Crystallization is one of the critical unit operations during the production of an active pharmaceutical ingredient or a pharmaceutical intermediate. Control of crystal attributes such as size and size distribution are critical not only to the efficiency of the downstream operations but also to the final drug product. Size reduction can be achieved by dry or wet milling operations. The integration of an insitu wet mill and continuous mixed suspension mixed product removal crystallizer (MSMPR) is studied in this work for cooling crystallization of Paracetamol from an aqueous isopropanol mixture. During this study, the impact of various operational conditions of both continuous insitu mill and MSMPR unit on the product properties is evaluated. The paper demonstrates that the MSMPR operational conditions (i.e. residence time, operational temperature) significantly impact the achievable steady state product characteristics. In addition, the influence of insitu mill operating conditions (i.e. rotor speed) on critical product and process qualities attributes such as particle size distribution, mean particle size, and yield. Towards this end, breakage kernels were evaluated and validated through a parameter estimation routine using the experimental data. The specific breakage rate considering magma density and rotor speed showed higher accuracy between the various kernels.

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See more of this Session: Modeling and Control of Crystallization
See more of this Group/Topical: Separations Division