FLUCONAZOLE ENCAPSULATED SPANLASTIC IN-SITU GEL FOR OCULAR DELIVERY: FORMULATION, OPTIMIZATION AND CHARACTERIZATION

Abstract

The development of effective ocular drug delivery systems remains a significant challenge due to anatomical and physiological barriers that limit drug bioavailability. This study presents the formulation and evaluation of fluconazole-loaded spanlastic in-situ gel to enhance drug retention time and therapeutic efficacy for ophthalmic applications. Spanlastics are elastic vesicular carriers, were prepared by using ethanol injection method and optimized for particle size, zeta potential, and entrapment efficiency. The edge activators selected for the preparation were Tween 80, Tween 20, and Polyvinyl alcohol (PVA) with Span 80. FTIR and DSC analyses were performed for drug excipient compatibility check. Optimized spanlastic preparation was incorporated into a thermosensitive in-situ gel matrix of Poloxamer 407. Final optimized in-situ gel preparation was evaluated for appearance, pH, gelation temperature, in vitro release and ex vivo permeation across excise goat cornea. Among the nine formulations developed, formulation F1 (Span 80: Tween 80 at 65:35 w/w) exhibited optimal characteristics and was shown particle size of 168.3 nm, zeta potential of −21.27 mV, and entrapment efficiency of 87.3%. FTIR and DSC analyses confirmed drug-excipient compatibility. In vitro drug release studies showed 55.10% and 76.25% release in 5 hr from fluconazole loaded spanlastic and fluconazole suspension respectively. The in-situ gel preparation was developed for F1 spanlastic formulation and the rheological evaluation revealed the suitable gelation temperature (35 ± 1°C). Ex vivo permeation studies showed a 65.21% drug permeation from spanlastics in-situ gel which was significantly higher than the 42.2% observed with fluconazole loaded Poloxamer 407 gel. Therefore, fluconazole loaded spanlastic in-situ gel could offers a promising alternative for ocular antifungal therapy with sustained drug release, enhanced corneal permeation, and improved therapeutic outcomes. Further in-vivo studies are warranted to validate clinical efficacy and long-term safety.