Binary mixtures of flufenamic acid and its chloro, difluoromethyl and fluoromethyl analogues; incorporation and distribution in flufenamic acid crystals
Loading...
Files
Published Version
Supplementary data
Date
2026-07-06
Authors
Bourke, Timothy
Chiarella, Renato A.
Moynihan, Humphrey A.
Journal Title
Journal ISSN
Volume Title
Publisher
Royal Society of Chemistry
Published Version
Abstract
Impurities are a common feature of pharmaceutical process chemistry. For example, fluorine-containing drug substances are often found to have the corresponding desfluoro compounds as impurities which are difficult to remove by crystallization. Analogues of flufenamic acid in which the trifluoromethyl group was replaced by difluoromethyl, fluoromethyl or chloro groups were synthesized and examined as examples of such impurities. Investigation of the extent of incorporation and behaviour by PXRD and DSC were consistent with crystal lattice level substitution of flufenamic acid molecules with analogous impurities. Use of methanol or acetonitrile as crystallization solvent resulted in efficient incorporation of the impurities into flufenamic acid crystals. Examination of the distribution of the impurities within flufenamic acid crystals by partial dissolution methods showed that impurity inclusion was occurring throughout the crystal growth process. In each of the impurities studied, the trifluoromethyl group of flufenamic acid was replaced by a group with similar electronic and steric properties. Consideration of the crystal structure of the flufenamic acid polymorph obtained, i.e., form III, suggested that replacement of flufenamic acid molecules by those impurities could be accommodated within the flufenamic acid form III crystal lattice.
Description
Keywords
Binary mixtures , Flufenamic acid , [Chemistry]
Citation
Bourke, T, Chiarella, R A & Moynihan, H A 2026, 'Binary mixtures of flufenamic acid and its chloro, difluoromethyl and fluoromethyl analogues; incorporation and distribution in flufenamic acid crystals', CrystEngComm, pp. 1-12. https://doi.org/10.1039/d6ce00346j