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

OAI: oai:purehost.bath.ac.uk:publications/f51a1e9a-9472-4409-b910-1d5143dc3a37 • DOI: https://doi.org/10.1016/j.ijpharm.2017.06.020

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.

diflunisal Phase transformation polymorphs Terahertz Spectroscopy /dk/atira/pure/subjectarea/asjc/3000/3003 name=Pharmaceutical Science