Formulation and evaluation of chitosan-coated ketoconazole-loaded ethosomal gel by Box–Behnken design

The research work aimed to evaluate the chitosan-coated ketoconazole-loaded ethosomal gel using a Box–Behnken design approach to increase bioavailability and reduce dose-related toxicity. In the design of experiment (DoE)-based formulation optimization, the independent variables were soy lecithin, Tween 80, and ethanol, while the dependent variables were particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), and cumulative percentage drug release (CDR). The design was a three-factor, three-level Box–Behnken design (BBD). The optimized ketoconazole (KCZ)-loaded ethosomes predicted by Design-Expert software (Version 13) consisted of 399.9 mg of soya lecithin, 4.73 ml of ethanol, and 300 µl of Tween 80, which were prepared by the cold method. According to characterization investigations, the mean particle size was 184.9 ± 6.21 nm, the zeta potential was −12.9 mV, the PDI was 0.230 ± 0.07, and the percentage of entrapment efficiency was 78.45 ± 3.5%. The observed CDR was 81.93 ± 5.6% at 24 h, exhibiting a sustained drug release profile. The optimized formulation was coated with chitosan to form a gel, with a pH of 5.5 and a viscosity of 9780 cps. In the in vitro antifungal study, the maximum zone of inhibition after 72 h, shown by chitosan-coated KCZ-loaded ethosomal, was 23.5 ± 5.3 mm. Edema was seen up to 72 h following the application of chitosan-coated KCZ-loaded ethosomes, but there was no indication of erythema in the in vivo skin irritation assay. The results showed that this formulation showed good potential for antifungal activity against Candida albicans.