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Polymorph control in batch seeded crystallizers. A case study with paracetamol

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Abstract

Controlling crystal polymorphism is crucial in the manufacturing of pharmaceuticals. In this work, we combine experimental characterization (including online imaging, infrared and Raman spectroscopy) with population balance modeling to investigate polymorph formation in batch seeded crystallizers considering paracetamol as a model system. We show that seeding the crystallizer with the target polymorph (here form II) does not necessarily lead to the intended polymorphic outcome. It is found that a decrease in temperature and in the stirring speed both allow improving the yield–purity trade-off thanks to a decrease in the nucleation rate of form I. The temperature leading to the most productive process is shown to be strongly dependent on the target polymorphic purity, namely the optimal temperature decreases with increasing purity specifications.

Graphical abstract: Polymorph control in batch seeded crystallizers. A case study with paracetamol

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Publication details

The article was received on 24 Aug 2018, accepted on 16 Oct 2018 and first published on 16 Oct 2018


Article type: Paper
DOI: 10.1039/C8CE01428K
Citation: CrystEngComm, 2019, Advance Article
  • Open access: Creative Commons BY-NC license
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    Polymorph control in batch seeded crystallizers. A case study with paracetamol

    L. Nicoud, F. Licordari and A. S. Myerson, CrystEngComm, 2019, Advance Article , DOI: 10.1039/C8CE01428K

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