Innovative Niosomal In Situ Gel for Sustained Ocular Delivery of Terbinafine Hydrochloride
摘要
Conventional ophthalmic antifungal formulations often exhibit rapid precorneal elimination and limited ocular bioavailability, necessitating frequent dosing. The present study aimed to develop a niosomal thermoresponsive in situ gel formulation of terbinafine hydrochloride for sustained ocular delivery. Terbinafine-loaded niosomes were prepared using Span 60 and cholesterol and optimized using a 3² factorial design. The optimized formulation exhibited high entrapment efficiency (89.9 ± 0.16%), a mean vesicle size of 492 ± 0.13 nm, and a polydispersity index of 0.284, indicating uniform vesicle distribution. The optimized niosomes were incorporated into a poloxamer-based thermoresponsive in situ gel exhibiting gelation at 37.1 ± 0.5 °C and pseudoplastic rheological behaviour suitable for ocular administration. The developed formulation demonstrated sustained drug release with a t₉₀ value of approximately 717 min and enhanced ex vivo permeation, achieving nearly 90% drug diffusion within 10 h. In vivo ocular pharmacokinetic studies in rabbits showed an increase in AUC₀–8h from 169.1 to 305.8 ng·h/mL and prolonged mean residence time from 2.83 to 3.76 h compared with the drug solution. The formulation was well tolerated in ocular irritation studies and retained antifungal activity against Candida albicans. These findings suggest that the integration of niosomal vesicles with thermoresponsive in situ gel systems may provide a promising strategy for sustained ocular delivery of terbinafine hydrochloride.