A structured approach to cope with impurities during industrial crystallization development

Stephanie J. Urwin, Guillaume Levilain, Ivan Marziano, Jeremy M. Merritt, Ian Houson, Joop H. Ter Horst

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Abstract

The perfect separation with optimal productivity, yield and purity is very difficult to achieve. Despite its high selectivity, in crystallisation unwanted impurities routinely contaminate a crystallisation 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 crystallisation. 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 crystallisation development, whilst also decreasing resources expended on process development.
Original languageEnglish
Number of pages14
JournalOrganic Process Research and Development
Early online date6 Jul 2020
DOIs
Publication statusE-pub ahead of print - 6 Jul 2020

Keywords

  • impurity rejection
  • crystallisation
  • product purity
  • phase diagrams
  • workflows

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