Augmentation of antifungal activity of fluconazole using a clove oil nanoemulgel formulation optimized by factorial randomized D-optimal design.

In the present study, fluconazole (FLU) showed the highest solubility in clove oil and was selected as the oil phase for the FLU-loaded nanoemulsion (FLU-NE). Among the studied cosurfactants, Labrafac was better than ethanol at providing globules with acceptable sizes and a lower polydispersity index (PDI) when Tween 80 was the surfactant. This optimized FLU-NE was thermodynamically stable. Furthermore, FLU-NE stored at 40 ± 2 °C and 75 ± 5% relative humidity for 6 months demonstrated good stability. The FLU-NE was converted to a FLU-loaded nanoemulsion gel (FLU-NEG) using 2% w/v sodium carboxymethyl cellulose. The FLU-NEG was acceptable in terms of visual appearance and spreadability. Rheological studies revealed pseudoplastic behavior for FLU-NEG. The viscosity of FLU-NEG decreased when the applied rpm was increased. FLU-NEG showed greater drug release than that from a FLU-GEL formulation. Furthermore, the FLU release from FLU-NEG followed the Higuchi model. The results from the in vitro antifungal evaluation of FLU-NEG on Candida albicans ATCC 76615 strain confirmed the increase in the antifungal activity of FLU by clove oil. Significant differences were observed in the zones of inhibition produced by FLU-NEG compared to those produced by the blank nanoemulsion gel (B-NEG), fluconazole suspension (FLU-SUS), and nystatin samples. Thus, the increase in the antifungal activity of FLU using clove oil as the oil phase in its nanoemulsion formulation was quite evident from our results. Therefore, the developed FLU-NEG could be considered a potential candidate for further preclinical and clinical studies.