Augmented local skin accumulation efficiency of sertaconazole nitrate via glycerosomal hydrogel: Formulation, statistical optimization, ex vivo performance and in vivo penetration

Abstract

This study aimed at formulating Sertaconazole nitrate (SZ), in a suitable glycerosomes based topical formulation that offers deep skin penetration and high local skin accumulation efficiency. SZ Glycerosomes were prepared using thin-film hydration technique according to a 24 full factorial design. Studied factors were Phosphatidylcholine (PhC) amount, Brij® L4: PhC ratio, glycerol concentration, and method of further treatment either sonication or freezing and thawing. The power of the design for each response was calculated before design implementation. Suitable models were elucidated for studied responses and their validity was checked. An optimized formula (O-GL) was numerically optimized using Design expert software®. The O-GL had suitable characterization with entrapment efficiency of 80.6 ± 2.9%, particle size of 418 ± 11 nm, polydispersity index of 0.452 ± 0.27, and zeta potential of −52.6 ± 0.6 mV. This O-GL was incorporated in a hydrogel (O-GL hydrogel). This O-GL hydrogel showed superior ex-vivo deposition in rat skin (Local accumulation efficiency: 55.1 ± 7.9) compared to O-GL (14.9 ± 1.1) and Dermofix® cream (marketed product) (13.1 ± 0.8). It also showed deep in-vivo penetration that reached deep dermal skin layers. Thus, the proposed formula (O-GL hydrogel) is promising for SZ topical delivery. It achieved deep skin penetration and high local skin accumulation efficiency for the effective treatment of fungal infections.