Physicochemical and Antifungal Properties of Clotrimazole in Combination with High-Molecular Weight Chitosan as a Multifunctional Excipient.

Chitosans represent a group of multifunctional drug excipients. Here, we aimed to estimate the impact of high-molecular weight chitosan on the physicochemical properties of clotrimazole-chitosan solid mixtures (CL-CH), prepared by grinding and kneading methods. We characterised these formulas by infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry, and performed in vitro clotrimazole dissolution tests. Additionally, we examined the antifungal activity of clotrimazole-chitosan mixtures against clinical Candida isolates under neutral and acid conditions. The synergistic effect of clotrimazole and chitosan S combinations was observed in tests carried out at pH 4 on Candida glabrata strains. The inhibition of C. glabrata growth reached at least 90%, regardless of the drug/excipient weight ratio, and even at half of the minimal inhibitory concentrations of clotrimazole. Our results demonstrate that clotrimazole and high-molecular weight chitosan could be an effective combination in a topical antifungal formulation, as chitosan acts synergistically with clotrimazole against non-albicans candida strains.