1H NMR spectroscopic characterization of inclusion complexes of tolfenamic and flufenamic acids with β-cyclodextrin

The complexation between the anionic forms of tolfenamic acid and flufenamic acid with β-cyclodextrin was investigated in solution by 1D and 2D proton NMR spectroscopy. The stoichiometry of the complexes was determined by the method of continuous variation using the chemical induced shifts of both the host and guest protons. An analysis of the spectroscopic data revealed that simultaneous inclusion of both rings of tolfenamic and flufenamic acids occur, giving rise each to two isomeric 1:1 complexes. The view of a bimodal binding between these two drugs and β-cyclodextrin was also supported by ROESY experiments. Using a rough approximation, we have estimated the association constants order of magnitude of the 1:1 complexes.

• We report the complexation process between tolfenamic and flufenamic acid with β-CD.
• Induced chemical shifts variation and ROESY spectra sustain a bimodal complexation.
• The entrance of both aromatic rings occurs through the secondary rim of the β-CD.
• The microscopic association constants order of magnitude was evaluated.