Nanosponge-based hydrogel preparation of fluconazole for improved topical delivery

Abstract

Purpose: To develop polymeric nanosponge based hydrogel system of fluconazole (FZ) for improved delivery for topical application. Method: Six different nanosponge preparations of fluconazole were formulated by oil-in-water (o/w) emulsion solvent diffusion method using various drug to polymer (ethylcellulose, EC) ratios. Polyvinyl alcohol (PVA) and dichloromethane were used to prepare the aqueous and dispersed phases, respectively. The nanosponges (NS) were studied for entrapment efficiency, particle size, structural properties, size and appearance, and in vitro drug release. Furthermore, the hydrogel formulation was evaluated for ex vivo permeation characteristics. Results: Morphological studies revealed porous nanosized particles with the outer surface resembling orange peel. The nanosponges had particle size in the range of 220.2 ± 4.5 to 624.1 ± 10.4 nm. Release studies showed 43.9 ± 3.2 % drug release at 6 h, confirming the sustained release pattern of the drug-loaded nanosponges. Powder x-ray diffraction (PXRD) and Fourier transform infra-red (FTIR) analyses indicate complex formation in the nanosponge structure. Out of six nanosponge formulations prepared, F3 containing FZ and EC in the ratio of 1:0.7 showed optimum physicochemical and release characteristics and, therefore, was selected for hydrogel formulation. Kinetic analysis of the permeation data revealed a Higuchi diffusion pattern. Ex vivo permeation studies indicate that the hydrogel preparation displayed adequate drug permeation through rat abdominal skin. Conclusion: A nanosponge-loaded hydrogel of fluconazole for improved permeation of the drug through skin has been successfully developed. Safety and toxicity tests are required to ascertain its potential suitability for use in humans.