Optimal Control of Antisolvent and Cooling Crystallization

Antisolvent crystallization;cooling crystallization;dual impinging jet;Y-mixer;paracetamol;Feedback Control

Zhou, Lifang ; Braatz ; Richard D.

关键词: Antisolvent crystallization;    cooling crystallization;    dual impinging jet;    Y-mixer;    paracetamol;    Feedback Control;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/18493/Zhou_Lifang.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Common quality requirements for crystallization products is so critical in the pharmaceutical industry, including the demands of the drug administration and customers (e.g. bioavailability, size uniformity, and polymorphic form) and the concern of the manufacturer for downstream processes such as filtration and drying (e.g. ability to flow). Because crystal size distribution (CSD) has a large effect on crystal properties, reproducible and optimal control of the CSD is of great importance.The first part of this thesis collected ATR-FTIR spectra and built a calibration model, whose regression coefficients were used along with ATR-FTIR spectra to measure the solubility of paracetamol in isopropanol-water solution at various temperatures and solvent ratios, also for further feedback control study. The second part simulated the process of feeding seeds produced by real-time antisolvent crystallization to cooling tank to decouple nucleation and growth. Optimization of the temperature profiles to achieve targeted crystal size distributions was presented as well.The overall contribution of the thesis is the development of a new process: the combination of antisovlent crystallization in dual impinging jet crystallizer and cooling crystallization in tank, which can be used to develop a continuous crystallization method in industry.