Formation of two particular structures between β-cyclodextrin and bifonazole: β-cyclodextrin–bifonazole and (β-cyclodextrin)i–bifonazole (where 2 < i < 3)

Abstract

This paper deals with inclusion compound formation between β-cyclodextrin (β-CD) and bifonazole, an antimycotic hydrophobic imidazole derivative. High performance liquid chromatography (HPLC) was used in order to measure the solubility of this drug as a function of the quantity of cyclodextrin in the samples. According to the classification of Higuchi and Connors, an A type solubility diagram was obtained, revealing the formation of soluble inclusion compound(s). Differential scanning calorimetry (DSC) was used for the first time, in order to draw binary phase and Tammann diagrams between β-cyclodextrin and bifonazole. The experimental results demonstrated the formation of two binary compounds, β-cyclodextrin–bifonazole and (β-cyclodextrin)_i–bifonazole (where 2 < i < 3). The two compounds have been characterised using solid state nuclear magnetic resonance (NMR) spectroscopy. Different NMR spectra have been obtained, which indicate that the first compound is an inclusion compound and the second may be a crystallised compound, in which the bifonazole is not necessarily included in the cyclodextrin internal cavity.