Development and Evaluation of a Ciclopirox Olamine-Loaded Nanoemulgel for Topical Antifungal Delivery

Abstract

Background and Aim: Superficial fungal infections of the skin are among the most common dermatological disorders worldwide, particularly in tropical and humid regions, and are associated with substantial morbidity, recurrence, and impaired quality of life. Conventional topical formulations of Ciclopirox Olamine (CPO) suffer from limited penetration across the stratum corneum, inadequate retention at the site of action, and the need for frequent application, which may compromise patient compliance and therapeutic outcomes. The present study was undertaken to develop and evaluate a CPO-loaded nanoemulgel intended to for enhanced dermal delivery, prolong skin residence time, and improve antifungal efficacy in topical therapy. Methods: Preformulation studies included determination of ?max, construction of a calibration curve in phosphate-buffered saline (PBS) pH 5.5, and drug excipient compatibility assessment by Fourier transform infrared spectroscopy (FTIR). Equilibrium solubility of CPO was determined in various oils, surfactants, and co-surfactants, and pseudo-ternary phase diagrams were constructed at different Smix ratios by the aqueous titration method. Nine nanoemulsion batches (F1–F9) were prepared by spontaneous emulsification and optimized with respect to globule size, polydispersity index (PDI), and zeta potential. The optimized nanoemulsion was incorporated into a Carbopol 940 gel base to obtain the nanoemulgel, which was evaluated for pH, viscosity, spreadability, drug content, in vitro drug release through a dialysis membrane using Franz diffusion cells, and in vitro antifungal activity against Candida albicans. Accelerated stability studies were carried out as per ICH guidelines (40 ± 2 °C / 75 ± 5% RH) for three months. All experiments were performed in triplicate (n = 3) and results are expressed as mean ± SD. Statistical analysis was performed using [software name/version] with one-way ANOVA followed by Tukey’s HSD post hoc test; p < 0.05 was considered statistically significant. Results: CPO exhibited the highest solubility in oleic acid, Tween 80, and PEG 400, which were accordingly selected as the oil, surfactant, and co-surfactant. The optimized nanoemulsion (F5) showed a globule size of 92.4 ± 3.1 nm, PDI of 0.214 ± 0.02, and zeta potential of -28.6 ± 1.2 mV. The corresponding nanoemulgel demonstrated skin-compatible pH (6.2–6.5), suitable viscosity, good spreadability, and drug content close to 99%. In vitro release followed the Korsmeyer–Peppas model with anomalous (non-Fickian) transport and achieved 96.8 ± 2.1% cumulative release at 12 h, significantly higher than the marketed CPO cream (70.3 ± 2.2%, p < 0.05). The nanoemulgel produced a significantly larger zone of inhibition against C. albicans than the marketed cream and plain drug dispersion (p < 0.05). FTIR confirmed the absence of drug–excipient interaction, and the formulation remained physically and chemically stable over three months under accelerated conditions. Conclusion: The developed Ciclopirox Olamine nanoemulgel is a stable, efficacious, and patient-friendly topical delivery system that markedly enhances drug release and antifungal activity relative to conventional CPO formulations, with potential to reduce dosing frequency and improve therapeutic outcomes in superficial fungal infections, warranting further evaluation in appropriate in vivo and clinical studies.

KEYWORDS: Ciclopirox olamine; Nanoemulsion; Nanoemulgel; Topical antifungal therapy; Franz diffusion cell; Candida albicans; ICH stability; Korsmeyer-Peppas kinetics.