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Form Selection of Concomitant Polymorphs: A Case Study Informed by Crystallization Kinetics Modeling
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  • Weiwei Tang,
  • Yufeng Quan,
  • Junbo Gong,
  • Jingkang Wang,
  • Qiuxiang Yin,
  • Tonglei Li
Weiwei Tang
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Yufeng Quan
Tianjin University
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Junbo Gong
Tianjin University
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Jingkang Wang
Tianjin University
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Qiuxiang Yin
Tianjin University
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Tonglei Li
Purdue University System
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Abstract

Molecular mechanisms and process kinetics of crystallizing concomitant polymorphs remain poorly understood. Solvent-mediated phase transformation is often mistaken as concomitant crystallization, mainly due to the two processes sharing similar kinetic profiles. Herein, we developed a population balance model to simulate a concomitant crystallization process of two polymorphs of tolfenamic acid (TFA). The kinetic modeling aims to better understand concomitant crystallization and help guide form selection of such a molecular system. Crystallization kinetics of ethanolic TFA solutions were uncovered from induction time measurements, as well as seeded and unseeded crystallization experiments. Both experimental and simulation results demonstrate that the stable form I crystallizes concomitantly with the metastable form II. The faster growing form II results in an intermediate decline in the kinetic profile of form I composition in crystallized samples, a characteristic feature of the concomitantly crystallized system. A four-quadrant scheme of attainable polymorph outcome was simulated under various crystallization conditions.

Peer review status:UNDER REVIEW

18 Feb 2020Submitted to AIChE Journal
21 Feb 2020Submission Checks Completed
21 Feb 2020Assigned to Editor
16 Mar 2020Reviewer(s) Assigned
02 Jul 2020Editorial Decision: Revise Major
04 Aug 20201st Revision Received
01 Sep 2020Submission Checks Completed
01 Sep 2020Assigned to Editor
03 Sep 2020Reviewer(s) Assigned