Inclusion complexes of Fluconazole with methylated-betacyclodextrin: influence on physicochemical properties of theguest molecule

The increase in the incidence of fungal infections and fungal resistance has prompted the research for better therapeutic strategies such as the optimization and improvement of existing antifungal drugs. Fluconazole, one of the most used and well-tolerated antifungal drugs has a series of drawbacks hampering the obtention of an optimal therapeutic response. Complexation with cyclodextrins represents a very-well known approach for improvement of pharmaceutical profile of drugs. The present study aims to obtain and to evaluate the solid inclusion complexes of fluconazole with methylated beta-cyclodextrin, as preliminary experiments in formulation of improved pharmaceutical product of fluconazole. The differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray powder diffractometry were used to characterize the binary systems between fluconazole and methylated-beta-cyclodextrin. The encapsulation of fluconazole into methylated-betacyclodextrin cavity resulted in modifications of the physicochemical properties of the antifungal agent. The formation of the fluconazole-cyclodextrin inclusion complex was confirmed by thermal and spectral methods. Based on the experimental data, a real interaction in solid state between the antifungal agent and cyclodextrin was proved, leading us to propose the kneading product in 1:1 molar ratio for future development of improved pharmaceutical formulation containing fluconazole.