Mathematical Modeling, Design, and Optimization of a Multisegment Multiaddition Plug-Flow Crystallizer for Antisolvent Crystallizations

• DOI: 10.1021/acs.oprd.5b00110
• Publication Date: 2015-09-11T10:23:55Z
• Authors: Qinglin Su; Brahim Benyahia; Zoltan K. Nagy; Chris D. Rielly
• Keywords: 02 engineering and technology; 0210 nano-technology

In the pharmaceutical industries, the requirements of rapid process development and scalable design have made the tubular crystallizer a promising platform for continuous manufacturing and crystallization processes, capable of replacing conventional capital- and labor-intensive batch operations. This paper takes a process systems engineering (PSE) approach to the optimal design of a continuous antisolvent addition crystallizer to deliver the most promising product qualities, such as the crystal size distribution. A multisegment multiaddition plug-flow crystallizer (MSMA-PFC) is considered as an example of a continuous antisolvent crystallization process, in which the total number, location, and distribution of antisolvent additions are to be optimized. First-principles dynamic and steady-state mathematical models for the MSMA-PFC are presented, based on example kinetic models for nucleation and growth of paracetamol crystallizing in acetone, with water as the antisolvent. The performances of different cry...