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

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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., 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:09 Oct 2021 00:59
      URI:https://strathprints.strath.ac.uk/id/eprint/73374
    CORE (COnnecting REpositories)