A structured approach to cope with impurities during industrial crystallization development

Urwin, Stephanie J. and Levilain, Guillaume and Marziano, Ivan and Merritt, Jeremy M. and Houson, Ian and Ter Horst, Joop H. (2020) A structured approach to cope with impurities during industrial crystallization development. Organic Process Research and Development, 24 (8). pp. 1443-1456. ISSN 1083-6160 (https://doi.org/10.1021/acs.oprd.0c00166)

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Abstract

The perfect separation with optimal productivity, yield, and purity is very difficult to achieve. Despite its high selectivity, in crystallization unwanted impurities routinely contaminate a crystallization product. Awareness of the mechanism by which the impurity incorporates is key to understanding how to achieve crystals of higher purity. Here, we present a general workflow which can rapidly identify the mechanism of impurity incorporation responsible for poor impurity rejection during a crystallization. A series of four general experiments using standard laboratory instrumentation is required for successful discrimination between incorporation mechanisms. The workflow is demonstrated using four examples of active pharmaceutical ingredients contaminated with structurally related organic impurities. Application of this workflow allows a targeted problem-solving approach to the management of impurities during industrial crystallization development, while also decreasing resources expended on process development.

ORCID iDs

Urwin, Stephanie J. ORCID logoORCID: https://orcid.org/0000-0002-9092-0200, Levilain, Guillaume, Marziano, Ivan, Merritt, Jeremy M., Houson, Ian and Ter Horst, Joop H. ORCID logoORCID: https://orcid.org/0000-0003-0118-2160;
  • Item type:Article
    ID code:73374
    Dates:
    Date
    Event
    21 August 2020
    Published
    6 July 2020
    Published Online
    6 July 2020
    Accepted
    Keywords:impurity rejection, crystallisation, product purity, phase diagrams, workflows, Pharmacy and materia medica, Organic Chemistry, Physical and Theoretical Chemistry
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:29 Jul 2020 13:53
    Last modified:01 Feb 2023 03:15
    URI:https://strathprints.strath.ac.uk/id/eprint/73374
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