PAT-based design of agrochemical co-crystallization processes: a case-study for the selective crystallization of 1:1 and 3:2 co-crystals of p-toluenesulfonamide/triphenylphosphine oxide

K.A. Powell, D.M. Croker, C.D. Rielly, Z.K. Nagy

Research output: Contribution to journalArticle

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Abstract

In this study, the selective crystallization and characterization of the stoichiometric forms of the p-toluenesulfonamide/triphenylphosphine oxide (p-TSA-TPPO) co-crystal system in acetonitrile (MeCN) is demonstrated using batch and semi-batch crystallizers. In the batch study, both 1:1 and 3:2 p-TSA-TPPO were successfully isolated as pure forms. However, process variability was observed in a few experimental runs. To address the batch process variability issue, a control strategy was implemented using temperature cycling, aided by in situ process analytical technologies (PAT) to convert from 3:2 to 1:1 p-TSA-TPPO. In the semi-batch co-crystallization studies, the two molecular co-formers, p-TSA and TPPO, were dissolved in MeCN and pumped separately to the crystallizer. Changing the flow rates of the respective active ingredients allowed control over the co-crystallization outcome, and presents as a promising opportunity for development of a continuous co-crystallization process.

Original languageEnglish
Pages (from-to)95-108
Number of pages14
JournalChemical Engineering Science
Volume152
Early online date3 Jun 2016
DOIs
Publication statusPublished - 2 Oct 2016

Keywords

  • co-crystal
  • co-crystallization
  • process analytical technologies
  • stoichiometric

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