Population Balance Model Development Verification and Validation of Cooling Crystallization of Carbamazepine

• DOI: 10.1021/acs.cgd.0c00434
• Publication Date: 2020-06-23T14:08:20Z
• Authors: Yiqing C. Liu; David Acevedo; Xiaochuan Yang; Sean Naimi; Wei-Lee Wu; Naresh Pavurala; Zoltan K. Nagy; Thomas F. O’Connor
• Keywords: Supersaturation

Using process modeling to understand dynamics and potentially explore the design space of a crystallization is difficult because its complex nature with many factors at play, such as initial concentration, supersaturation, seeding strategy, flow pattern. In this work, systematic approach applied sequentially estimate growth nucleation rate cooling carbamazepine various conditions in batch operation. Different formulations kinetic expressions are tested model discrimination exercise obtain best fit most confidence form. Then, based on risk, determined by purpose obtained model, verification validation activities applied. The verified validated predict concentration D50 for specific strategy mechanisms, including both growth, highly dependent seed PSD. A brief discussion also given transferring batch-developed continuous operations response growing interest development. It found that can be transferred where supersaturation solid similar those during experimentation. Because interactive effects kinetics, it reasonable conclude order infer transferable experimental must wide enough cover potential operating space.