Melt Crystallization for Paracetamol Polymorphism

Alexander G. Shtukenberg, Melissa Tan, Leslie Vogt-Maranto, Eric J. Chan, Wenqian Xu, Jingxiang Yang, Mark E. Tuckerman, Chunhua T. Hu, Bart Kahr

Research output: Contribution to journalArticlepeer-review


Trimorphic paracetamol, one of the most commonly used analgesic and antipyretic drugs, has been a model system for studying transformations among phases of molecular crystalline materials. During crystallization from the melt and the glass above 0 °C, three new polymorphs of paracetamol (N-acetyl-para-aminophenol or acetaminophen) were discovered, doubling the number of known ambient forms. The crystal structure of one new form was solved using a combination of powder X-ray diffraction and computational techniques. Growth kinetics became anomalous near the glass transition: As temperature decreased, growth rate increased; this rare and poorly understood phenomenon is commonly identified as the glass-to-crystal (GC) growth mode. In addition, two polymorphs displayed optical evidence of helicoidal morphologies, a characteristic of at least 25% of molecular crystals, that has been resistant to a universal explanation.

Original languageEnglish (US)
Pages (from-to)4070-4080
Number of pages11
JournalCrystal Growth and Design
Issue number7
StatePublished - Jul 3 2019

ASJC Scopus subject areas

  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics


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