Continuous Crystallization of Paracetamol (Acetaminophen) Form II: Selective Access to a Metastable Solid Form

Lauren R. Agnew, Thomas McGlone, Helen P. Wheatcroft, Amy Robertson, Anna R. Parsons, Chick C. Wilson

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51 Citations (SciVal)


The first continuous crystallization of a metastable polymorphic form of an active pharmaceutical ingredient is reported. Paracetamol form II, which displays enhanced solubility and compressibility in comparison to the stable form I, has been successfully crystallized in two continuous platforms: a continuous oscillatory baffled crystallizer and a mixed suspension mixed product removal (MSMPR) system, in the presence of the structurally similar molecule metacetamol as a template molecule. Samples from both crystallizers display high polymorphic purity and high solid phase purity, with the samples from the MSMPR in particular showing no evidence of the presence of a residual template molecule. The crystallization was found to be rapidly transferrable between the two continuous platforms. Samples produced display good stability with respect to the known form II to form I transition, reflecting the polymorphic selectivity achieved.

Original languageEnglish
Pages (from-to)2418-2427
Number of pages10
JournalCrystal Growth and Design
Issue number5
Publication statusPublished - 3 May 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics


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