TY - JOUR
T1 - A comprehensive spectroscopic study of the polymorphs of diflunisal and their phase transformations
AU - Pallipurath, Anuradha R.
AU - Civati, Francesco
AU - Sibik, Juraj
AU - Crowley, Clare
AU - Zeitler, J. Axel
AU - McArdle, Patrick
AU - Erxleben, Andrea
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/8/7
Y1 - 2017/8/7
N2 - 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.
AB - 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.
KW - Diflunisal
KW - Phase transformation
KW - Polymorphs
KW - Terahertz spectroscopy
UR - http://www.scopus.com/inward/record.url?scp=85020753820&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2017.06.020
DO - 10.1016/j.ijpharm.2017.06.020
M3 - Article
C2 - 28603011
AN - SCOPUS:85020753820
SN - 0378-5173
VL - 528
SP - 312
EP - 321
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -