Solvent usage is a major source of environmental waste in pharmaceutical industry. The current paradigm shift toward continuous manufacturing in pharmaceutical industry has renewed the interest in continuous crystallization, which offers the prospect of easy solvent recycling. However, the selection of solvents for an integrated crystallization processes is nontrivial due to the likely trade-off between optimal solvent properties for crystallization and solvent separation and recycling. A systematic approach for the simultaneous optimization of process conditions and solvent selection for continuous crystallization including solvent recycling is presented. A unified perturbed-chain statistical associating fluid theory model framework is applied to predict thermodynamic properties related to solubility and vapor-liquid equilibrium, which is integrated with a process model. A continuous mapping procedure is adopted to solve the optimization problem effectively. A case study based on continuous antisolvent crystallization of paracetamol with solvent separation via flash demonstrates the approach. © 2017 American Institute of Chemical Engineers AIChE J, 2017

中文翻译：

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使用PC-SAFT进行连续结晶和溶剂回收的集成溶剂和工艺设计

溶剂的使用是制药行业环境废物的主要来源。当前制药业向连续生产的范式转变重新引起了人们对连续结晶的兴趣，这为容易回收溶剂提供了希望。然而，由于用于结晶的最佳溶剂性质与溶剂分离和再循环之间的可能折衷，因此对于整体结晶过程的溶剂选择是不平凡的。提出了一种同时优化工艺条件和选择溶剂以进行连续结晶（包括溶剂循环利用）的系统方法。应用统一的扰动链统计缔合流体理论模型框架来预测与溶解度和气液平衡有关的热力学性质，与流程模型集成在一起。采用连续映射程序可以有效地解决优化问题。基于对乙酰氨基酚的连续反溶剂结晶以及通过闪蒸分离溶剂的案例研究证明了该方法。©2017美国化学工程师学会AIChE的Ĵ，2017年