Technoeconomic Evaluation of Multiple Mixed Suspension-Mixed Product Removal (MSMPR) Crystallizer Configurations for Continuous Cyclosporine Crystallization,Organic Process Research & Development

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Technoeconomic Evaluation of Multiple Mixed Suspension-Mixed Product Removal (MSMPR) Crystallizer Configurations for Continuous Cyclosporine Crystallization
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2017-09-22 00:00:00 , DOI: 10.1021/acs.oprd.7b00225
Samir Diab ₁ , Dimitrios I. Gerogiorgis ₁

Affiliation

Continuous crystallization using Mixed Suspension-Mixed Product Removal (MSMPR) crystallizers has been demonstrated as a feasible method for implementing continuous separations in pharmaceutical manufacturing processes. This work conducts a steady-state process modeling and simulation study of the continuous cooling crystallization of cyclosporine, comparing processes with and without solids recycle for their technoeconomic viability. The model describes population balance equations, crystallization kinetics, and process mass balances to compare attainable crystallization and plantwide yields of different process configurations. Total cost components using an established economic analysis methodology are compared for varying numbers of crystallizers, operating temperatures, total crystallizer cascade residence times and API feed concentrations. Economic analyses and the calculation of normalized cost components with respect to total crystallizer volumes identify the process without recycle as the most economically viable option, achieving the lowest total costs and low E-factors for pharmaceutical processes. The sensitivity of total costs to the selected total residence times for economic analyses highlights the need for rigorous comparison methodologies. This work identifies the need for technoeconomic optimization studies of continuous crystallization processes to establish the optimal design of manufacturing campaigns prior to further development.

中文翻译：

连续环孢菌素结晶的多种混合混悬液去除（MSMPR）结晶器配置的技术经济评估

使用混合悬浮混合产品去除（MSMPR）结晶器进行连续结晶已被证明是在制药生产过程中实现连续分离的一种可行方法。这项工作进行了环孢素的连续冷却结晶的稳态过程建模和仿真研究，比较了有或没有固体再循环的工艺在技术经济上的可行性。该模型描述了种群平衡方程，结晶动力学和过程质量平衡，以比较不同过程配置可获得的结晶和全厂产量。使用确定的经济分析方法对总成本构成进行比较，以分析不同数量的结晶器，操作温度，总结晶器级联停留时间和API进料浓度。制药过程中的电子因子。对于经济分析，总成本对选定总停留时间的敏感性凸显了对严格比较方法的需求。这项工作确定了对连续结晶过程进行技术经济优化研究的需要，以便在进一步开发之前确定制造活动的最佳设计。

更新日期：2017-09-23

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