Issue 13, 2019

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

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

Supplementary files

Article information

Article type
Paper
Submitted
24 8月 2018
Accepted
16 10月 2018
First published
16 10月 2018
This article is Open Access
Creative Commons BY-NC license

CrystEngComm, 2019,21, 2105-2118

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

L. Nicoud, F. Licordari and A. S. Myerson, CrystEngComm, 2019, 21, 2105 DOI: 10.1039/C8CE01428K

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