Characterization of inclusion complexes between bifonazole and different cyclodextrins in solid and solution state

Abstract

The aim of this study is to confirm the formation of inclusion complexes between bifonazole (BFZ) and different cyclodextrin (CD) derivatives. BFZ, an imidazole antifungal derivative, is a very hy-drophobic compound, which is a major drawback in obtaining topical pharmaceutical formulations with optimal bioavailability. CDs may increase local drug delivery by enhancing the drug release and/or per-meation. Several native and derivatized CD derivatives were tested in the experiments. The binary sys-tems between BFZ and CDs were prepared in two molar ratios by physical mixing methods. The physico-chemical properties of these complexes were studied by differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy methods. The results showed favorable molecular interaction between the components in solid state and in solution. 1H NMR-CD titrations and molecular modeling study showed that the most stable complex was obtained when using γ-CD. The Job's method and 2D NMR spectroscopy support the 2: 1 stoichiometry of the BFZ: γ-CD complex.