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Model-based solvent selection for integrated synthesis, crystallisation and isolation processes

Authors: Muhieddine, Mohamad H.; Jonuzaj, Suela; Viswanath, Shekhar K.; Armstrong, Alan; Galindo, Amparo; Adjiman, Claire S.;

Model-based solvent selection for integrated synthesis, crystallisation and isolation processes

Abstract

We present a systematic process-wide solvent selection tool based on computer-aided mixture/blend design (CAMbD) (Gani, 2004) for the integrated synthesis, crystallisation and isolation of pharmaceutical compounds. The method proposed simultaneously identifies the solvent and/or antisolvent mixture, mixture composition and process temperatures that optimise one or more key performance indicators. Additionally, the method entails comprehensive design specifications for the integrated process, such as the miscibility of the synthesis, crystallisation and wash solvents. The design approach is illustrated by identifying optimal solvent mixtures for the synthesis, crystallisation and isolation of mefenamic acid. Furthermore, a multi-objective CAMbD problem is formulated and shows that a mefenamic acid with purity of 98.8% can be achieved without significant loss of process performance in terms of the solvent E-factor.

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Keywords

Synthesis, crystallisation, isolation, CAMbD, mefenamic acid.

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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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impulse
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