An investigation of the polymorphism of a potent nonsteroidal anti-inflammatory drug flunixin

Hao Liu, Xing Yang, Shanyu Wu, Mingtao Zhang, Sean Parkin, Shuang Cao, Tonglei Li, Faquan Yu, Sihui Long

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5 Scopus citations


Flunixin [2-(3-trifluoromethyl-2-methyl-phenylamino)-nicotinic acid, FLX], a potent nonsteroidal anti-inflammatory drug widely used in veterinary medicine, was found to exist in at least two crystal forms (I and II), in contrast to clonixin [2-(3-chloro-2-methyl-phenylamino)-nicotinic acid, CLX], which exists in four solvent-free forms and multiple solvates. Form I was harvested from a variety of solvents and characterized by single-crystal X-ray diffraction, PXRD, FT-IR, and Raman spectroscopy. Its crystal structure is sustained on the strong acid-pyridine hydrogen bond. Form II was generated by thermal treatment of form I. Other aspects of this polymorphic system were investigated both experimentally and theoretically. Quantum chemistry calculations were performed to shed light on the lack of polymorphism from solution-phase crystallization. Conformational scan of the dihedral angle C2-N7-C8-C9 (τ) revealed two stable conformations, one with τ near 170°, and the other near 70°, corresponding to the molecule in the crystal. Hirshfeld analysis accounted for the major intermolecular interactions contributing to the overall stability of the crystal.

Original languageEnglish
Pages (from-to)448-457
Number of pages10
Issue number3
StatePublished - 2020

Bibliographical note

Funding Information:
SL thanks the Natural Science Foundation of Hubei Province for financial support (2014CFB787). HL acknowledges the sponsorship from the Innovation Fund of the Graduate School (CX2018003). TL is grateful to NSF for supporting this work (DMR1006364). SP is grateful to the NSF MRI program (CHE0319176 and CHE1625732).

Publisher Copyright:
This journal is © The Royal Society of Chemistry.

ASJC Scopus subject areas

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


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