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Crystallization Solvent Design Based on a New Quantitative Control Model of Crystal Morphology
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  • Shiyang Chai,
  • Enhui Li,
  • Lei Zhang,
  • Jian Du,
  • Qingwei Meng
Shiyang Chai
Dalian University of Technology

Corresponding Author:[email protected]

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Enhui Li
Dalian University of Technology
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Lei Zhang
Dalian University of Technology
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Jian Du
Dalian University of Technology
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Qingwei Meng
Dalian University of Technology
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Abstract

Solution crystallization is an important separation unit operation in active pharmaceutical ingredient (API) production. Solvent is one of the important factors affecting crystal morphology. How to select/design suitable crystallization solvents is still one of the most urgent problems in the crystallization field. In this paper, a framework for crystallization solvent design based on the developed quantitative control model of crystal morphology is proposed. First, molecular dynamics is used to predict the crystal morphology in solvents. Next, nine solvent descriptors are selected. Then, the quantitative relationship between crystal aspect ratio and solvent descriptors is developed. Subsequently, Computer-Aided Molecular Design (CAMD) method is integrated with the developed quantitative control model. The crystallization solvent design problem is expressed as a Mixed-Integer Non-Linear Programming (MINLP) model, which is solved by the decomposition algorithm. Finally, the crystallization solvent design framework is applied to two cases: benzoic acid and ibuprofen, and experimental verification is implemented.
19 May 2021Submitted to AIChE Journal
19 May 2021Submission Checks Completed
19 May 2021Assigned to Editor
26 May 2021Reviewer(s) Assigned
07 Jul 2021Editorial Decision: Revise Major
11 Aug 20211st Revision Received
16 Aug 2021Submission Checks Completed
16 Aug 2021Assigned to Editor
17 Aug 2021Reviewer(s) Assigned
19 Sep 2021Editorial Decision: Revise Minor
24 Sep 20212nd Revision Received
24 Sep 2021Submission Checks Completed
24 Sep 2021Assigned to Editor
26 Sep 2021Reviewer(s) Assigned
05 Oct 2021Editorial Decision: Accept