Tea Tree Oil-Based Sertaconazole Nitrate Organogels: Optimized Topical Delivery for Enhanced Antifungal Efficacy

Introduction: This study focused on developing a topical organogel system using Sertaconazole Nitrate (SN) and Tea Tree Oil (TTO) to enhance localized antifungal delivery. The aim was to improve skin deposition, drug release, and overall therapeutic effectiveness while minimizing systemic absorption and potential side effects. Methods: A Box-Behnken Design (BBD) was applied to optimize the formulation based on three key responses: Viscosity (VS), Spreadability (SP), and Drug Content (DC). The independent var-iables included Tea Tree Oil, Carbopol-934 (CP), and Polyethylene Glycol-400 (PEG). Opti-mized formulations were assessed for pH, rheological behavior, in vitro and ex vivo drug release, zeta potential, antifungal activity, skin irritation, and histopathological effects. Results: Formulations exhibited pH values between 6.11 ± 0.01 and 6.70 ± 0.03, indicating good skin compatibility. Viscosity ranged from 0.38 ± 0.11 to 0.50 ± 0.24 Pa.s, spreadability from 19.80 ± 1.02 to 26.75 ± 1.03 g.cm/s, and drug content between 92.45 ± 1.21% and 98.95 ± 1.7%. The optimized Sertaconazole Nitrate Organogel (SNO) achieved 99.16 ± 0.11% in vitro drug re-lease and 98.1 ± 1.50% ex vivo release within 24 hours. Minimal systemic absorption (1.64 ± 0.15%) confirmed localized drug delivery. The zeta potential was -27.90 mV, indicating stable dispersion. The antifungal efficacy was confirmed by a 2 cm inhibition zone against Candida al-bicans and Trichophyton rubrum, which outperformed the plain gel, marketed product, and SN alone. No signs of irritation or tissue damage were observed in skin histology. Discussion: The optimized formulation effectively delivered Sertaconazole Nitrate to the targeted skin layers, demonstrating superior antifungal activity and excellent physicochemical characteris-tics. The combination of TTO and SN provided enhanced therapeutic outcomes with a reduced risk of systemic side effects. The negative surface charge and appropriate rheological properties further supported its stability and usability as a topical preparation. Conclusion: The developed Sertaconazole nitrate-Tea Tree Oil organogel proved to be a safe, ef-fective, and non-invasive option for treating dermal fungal infections, with enhanced localized delivery and promising antifungal performance.