Hur Inyoung, Casas-Orozco Daniel, Laky Daniel, Destro Francesco, Nagy Zoltan K
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 4797 USA.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
Chem Eng Sci. 2024 Mar 5;285. doi: 10.1016/j.ces.2023.119534. Epub 2023 Dec 9.
In this work dynamic models of the continuous crystallization, filtration, deliquoring, washing, and drying steps are introduced, which are developed in the open-source pharmaceutical modeling tool PharmaPy. These models enable the simulation and digital design of an integrated continuous two-stage crystallization and filtration-drying carousel system. The carousel offers an intensified process that can manufacture products with tailored properties through optimal design and control. Results show that improved crystallization design enhances overall process efficiency by improving critical material attributes of the crystal slurry for downstream filtration and drying operations. The digital design of the integrated process achieves enhanced productivity while satisfying multiple design and product quality constraints. Additionally, the impact of model uncertainty on the optimal operating conditions is investigated. The findings demonstrate the systematic process development potential of PharmaPy, providing improved process understanding, design space identification, and optimized robust operation.
在这项工作中，引入了连续结晶、过滤、脱液、洗涤和干燥步骤的动态模型，这些模型是在开源制药建模工具PharmaPy中开发的。这些模型能够对集成连续两阶段结晶和过滤-干燥转盘系统进行模拟和数字化设计。该转盘提供了一个强化过程，通过优化设计和控制，可以生产具有定制特性的产品。结果表明，改进的结晶设计通过改善晶体浆料的关键材料属性，用于下游过滤和干燥操作，从而提高了整体工艺效率。集成工艺的数字化设计在满足多个设计和产品质量约束的同时，提高了生产率。此外，还研究了模型不确定性对最佳操作条件的影响。研究结果证明了PharmaPy的系统工艺开发潜力，提供了更好的工艺理解、设计空间识别和优化的稳健操作。
