Design and optimization of naringenin-loaded organogels for topical management of bacterial infections.

Bacterial skin infections are increasingly complicated by antimicrobial resistance, and naringenin, a citrus flavanone with membrane disrupting antibacterial activity, is limited in topical use by poor aqueous solubility and low dermal penetration. The present work was undertaken to develop and optimize naringenin loaded organogels for topical antibacterial application using a systematic quality by design approach. Naringenin loaded organogels were prepared by the hot emulsification technique and optimized through a 32 full factorial design in which glyceryl monostearate (10 to 20% w/w) and Capryol™ PGMC (5 to 15% w/w) concentrations were varied. The formulations were characterized for gel strength, viscosity, spreadability, drug content, drug excipient compatibility by FTIR, in vitro drug release, release kinetics, antibacterial activity and accelerated stability. The pH values (6.12 to 6.42) were suitable for topical application and the drug content was high (96.8 to 99.1%). Gel strength (42.6 to 92.2 g) and viscosity (3842.6 to 9922.3 cps) increased with glyceryl monostearate concentration, whereas spreadability (16.5 to 29.6 g · cm/s) decreased. Response surface methodology identified MF5, containing 15% w/w glyceryl monostearate and 10% w/w Capryol™ PGMC, as the optimized formulation, with experimental values for gel strength (78.5 g), viscosity (6082.4 cps) and drug release at 12 h (89.74%) closely matching the predicted values (relative error below 2.5%). The optimized formulation followed zero order release kinetics (R2 = 0.9859) with a non Fickian diffusion mechanism (n = 0.79), retained antibacterial activity against Escherichia coli and Staphylococcus aureus, and remained stable under accelerated conditions for three months. Optimized naringenin loaded organogel exhibited favorable physiochemical properties with an sustained in-vitro drug release and antibacterial activity against Escherichia coli and Staphylococcus aureus. The optimized formulation showed reduced antibacterial activity under the same experimental conditions when compared with the standard ciprofloxacin, and showed to release the antibiotic continuously from the organogel matrix. By using the factorial design approach, an optimized formulation having reproducible quality attributes and acceptable physicochemical stability after accelerated storage was achieved.