A comprehensive spectroscopic study of the polymorphs of diflunisal and their phase transformations

Anuradha R. Pallipurath, Francesco Civati, Juraj Sibik, Clare Crowley, J. Axel Zeitler, Patrick McArdle, Andrea Erxleben

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Understanding phase transitions in pharmaceutical materials is of vital importance for drug manufacturing, processing and storage. In this paper we have carried out comprehensive high-resolution spectroscopic studies on the polymorphs of the non-steroidal anti-inflammatory drug diflunisal that has four known polymorphs, forms I–IV (FI–FIV), three of which have known crystal structures. Phase transformations during milling, heating, melt-quenching and exposure to high relative humidity were investigated using Raman and terahertz spectroscopy in combination with differential scanning calorimetry and X-ray powder diffraction. The observed phase transformations indicate the stability order FIII > FI > FII, FIV. Furthermore, crystallization experiments from the gas phase and from solution by fast evaporation of different solvents were carried out. Fast evaporation of an ethanolic solution below 70 °C was identified as a reliable and convenient method to obtain the somewhat elusive FII in bulk quantities.

Original languageEnglish
Pages (from-to)312-321
Number of pages10
JournalInternational Journal of Pharmaceutics
Issue number1-2
Early online date8 Jun 2017
Publication statusPublished - Aug 2017



  • Diflunisal
  • Phase transformation
  • Polymorphs
  • Terahertz spectroscopy

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Pallipurath, A. R., Civati, F., Sibik, J., Crowley, C., Zeitler, J. A., McArdle, P., & Erxleben, A. (2017). A comprehensive spectroscopic study of the polymorphs of diflunisal and their phase transformations. International Journal of Pharmaceutics, 528(1-2), 312-321. https://doi.org/10.1016/j.ijpharm.2017.06.020