Preparation and Transformation of Solid Glass Solutions of Clotrimazole to Nanosuspensions with Improved Physicochemical and Antifungal Properties

Purpose Evaluating the feasibility of two-step preparation of clotrimazole solid glass solutions for improving its physicochemical properties, intrinsic dissolution, and antifungal activity. Methods Co-grinding with selected coformers including vitamin C and L-arginine was employed to form co-amorphous dispersions; then, a polymeric carrier was added to form a homogenous glass solution. The solid solutions were converted to nanosuspensions after reconstitution and ultrasonication. The dispersions were characterized for equilibrium solubility, intrinsic dissolution, particle size, and zeta potential. Solid state characterization was carried out using differential scanning calorimetry, X-ray powder diffraction, and Infrared spectroscopy. The antifungal activity was evaluated using candida albicans species. Results Equilibrium solubility indicated superb increase in clotrimazole solubility (more than 289 times) from glass solutions compared to pure crystalline drug. The intrinsic dissolution data showed 64% ± 0.34 of drug released within 15 min, and complete dissolution was obtained in 45 min. The ideal formula showed nanosized particles after dispersion in water (225 nm), optimum zeta potential (20.20 µV), and polydispersity index (0.35). Solid state characterization showed shortened peaks and diffraction lines of the glass solutions compared to parent components. The biological activity of the reconstituted nanosuspension showed decreased minimum inhibitory concentration by 50% and increased area of growth inhibition zones of candida albicans by more than 28% compared to drug solution. Conclusions These findings suggest that solid glass solutions and its derived nanosuspensions of clotrimazole with ascorbic acid and polyvinyl pyrrolidone could be a valuable solution for maximizing drug bioavailability.