Process modelling, design and technoeconomic Liquid-Liquid Extraction (LLE) optimisation for comparative evaluation of batch vs. continuous pharmaceutical manufacturing of atropine
Process modelling, design and technoeconomic Liquid-Liquid Extraction (LLE) optimisation for comparative evaluation of batch vs. continuous pharmaceutical manufacturing of atropine
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DOI：
10.1016/j.compchemeng.2018.12.028
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发表时间：
2019-05
期刊：
影响因子：
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通讯作者：
Samir Diab;Nikolaos Mytis;A. Boudouvis;Dimitrios I. Gerogiorgis
中科院分区：
文献类型：
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作者：
Samir Diab;Nikolaos Mytis;A. Boudouvis;Dimitrios I. Gerogiorgis
与目前占主导地位的批量生产方法相比，连续制药（CPM）可以通过潜在的运营和经济效益彻底改变工业效率。过程建模和优化是有价值的快速设计空间的评估和最佳工艺设计配置的说明，没有昂贵和耗时的实验活动。本文追求总成本最小化通过非线性优化不同的分离设计方案的阿托品，一个产品的巨大的社会重要性。该研究认为，一个证明连续流合成，反应动力学参数估计反应器设计，并说明了随后的批次与连续液-液萃取（LLE）的产品纯化的比较分析，使用公布的分配系数数据和MABAC模型的三元液-液平衡。最初的优化结果表明，甲苯是最好的连续液液平衡溶剂，在可接受的材料效率下，在考虑的两个工厂容量下实现最低的总成本，并且相对于用于不同溶剂回收的分批液液平衡设计，实现最大的总成本节约。
Continuous Pharmaceutical Manufacturing (CPM) can revolutionise industrial efficiency via potential operational and economic benefits over currently dominant batch methods. Process modelling and optimisation are valuable towards rapid design space evaluation and elucidation of optimal process design configurations, without expensive and time-consuming experimental campaigns. This paper pursues total cost minimisation via nonlinear optimisation of different separation design options for atropine, a product of great societal importance. The study considers a demonstrated continuous flow synthesis, presents reaction kinetic parameter estimation towards reactor design, and illustrates a comparative analysis of the subsequent batch vs. continuous liquid–liquid extraction (LLE) for product purification, using published partition coefficient data and UNIFAC-modelled ternary liquid–liquid equilibria. Original optimisation results show that toluene is the best continuous LLE solvent, attaining the lowest total costs at both plant capacities considered and the greatest total cost savings with respect to the batch LLE design for varying solvent recovery, at acceptable material efficiencies.