Topical felbinac loaded cubosomal hydrogel for promising treatment of inflammatory pain

Abstract

An attempt was made to formulate felbinac-loaded cubosomes to treat inflammatory pain. Cubosomes were prepared by the emulsification method in two stages; formulation of cubosomes and then conversion to hydrogel. Optimization technique was applied to get cubosomes by considering independent variables namely, glyceryl monooleate (GMO) and Poloxamer 407, in the range of 1.5 to 2.5 g and 0.5 to 2 w/w %, respectively. The effect of these variables was studied on particle size and drug release. Further, formulations were also characterized to get drug content and entrapment efficiency. Optimized formulation was incorporated into Carbopol 934 gel base to generate hydrogel and evaluated for spreadability, in-vitro diffusion, and anti-inflammatory activity by using carrageenan-induced rat paw edema model. Drug release, entrapment efficiency and drug content of nine formulations ranged from 70.62 ± 1.28 to 93.55 ± 2.35% within 24 h, 91.17 ± 1.12 to 91.89 ± 2.11%, and 21.82 ± 1.21 to 38.81 ± 0.87%, respectively. Transmission electron microscopy revealed well discrete, cubic, and spherical-shaped cubosomes. The zeta potential and particle size of the optimized formulation were 50 ± 1.31 mV and 332.5 ± 13.65 nm respectively. The drug release of optimized formulation was 89.58 ± 2.36% within 24 h. Cubosome hydrogel exhibited good spreadability and slow drug diffusion (88.45 ± 2.28% within 24 h) owing to the viscous nature of the gel. The studies of anti-inflammatory activity suggestive of a notable decrease in paw edema observed after 1 h, which persisted for up to 24 h following treatment with cubosome hydrogel. Felbinac gel (without cubosomes) showed anti-inflammatory action till 6 h with comparatively less reduction in edema. Histopathology of cubogel revealed significant reduction in edema and polymorphonuclear infiltration. Cubogel demonstrated good anti-inflammatory effect and could be a good choice of topical formulation to treat inflammatory pain.