Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 31 4 2025 10 11 Preparation, Pharmaceutical Characterization, In-Vitro Release Kinetics, and Antifungal Efficacy Investigation of Fluconazole Niosomal Hydrogel 440 451 10.34172/PS.025.42799 EN Mohammad Amin Raeisi Estabragh https://orcid.org/0000-0001-5992-1654 Hossein Pardakhty Abbas Pardakhty https://orcid.org/0000-0002-1848-5961 Journal Article 10.34172/PS.025.42799 2025 06 05 2025 08 02 Background: Lipid vesicular systems can enhance the penetration of antifungal drugs like fluconazole in topical applications. Niosomes, composed of non-ionic surfactants and cholesterol, are a key type of lipid vesicles. Methods: Fluconazole (FL) niosomes were prepared using thin film hydration with varying ratios of Span®/Tween®/cholesterol. Their morphological characteristics, particle size, physical stability, encapsulation efficiency (EE%), cumulative drug release, and kinetics were assessed. The optimal formulation was then combined with a gel base, and its physicochemical and pharmaceutical properties were examined. Antifungal efficacy against Candida albicans (ATCC: 10231) was evaluated compared to free drug solutions. Results: All formulations exhibited encapsulation efficiencies over 50%, with the Span60/Tween60/cholesterol blend (45/45/10 mole%) achieving the highest efficiency (70.2%). Following the Higuchi model, this formulation released 55.4% of FL over four hours. The gel formulations showed good physical stability, particularly the one with 1% carboxymethyl cellulose, which was suitable for topical application due to its pseudoplastic and thixotropic properties. In-vitro minimum inhibitory concentration (MIC) values against Candida albicans were recorded as 16 μg/mL (solution), 2 μg/mL (niosomal suspension), and 4 μg/mL (niosomal gel). Conclusion: A stable and locally applicable FL niosomal gel can be formulated, potentially enhancing effectiveness and reducing microbial resistance to FL as indicated by antifungal activity results in-vitro.