Levofloxacin loaded gelrite-cellulose polymer based sustained ocular drug delivery: formulation, optimization and biological study

Abstract

Abstract In the present work, levofloxacin in situ gel formulation was developed using gelrite as a gelling agent in combination with hydroxy propyl methyl cellulose. The developed formulations were evaluated for physicochemical parameters, in vitro release, ex vivo transcorneal study, sterility testing, antimicrobial efficacy, ocular irritation study, histopathological and stability evaluation. The in vitro drug release study showed the extended drug release up to 12 h, and the best fit kinetic model was found to be Peppas model (R 2=0.9654), suggesting a Fickian diffusion process. The developed formulations showed optimized physicochemical results for all parameters. The optimized formulation showed therapeutically efficacious antimicrobial activity. Hens egg test-chorioallantoin membrane assay (HET-CAM) showed a mean score of 0.33 up to 24 h, which indicated the non-irritant property of the developed formulation. This non-irritant and stable in situ gel formulation of levofloxacin was found to be promising and safe for use as ocular delivery. The degradation rate constant and shelf life of developed optimized formulation (F14) were found to be low (1.213×10-4 at 25°C) and 2.14 years, respectively. This renders them favorable for ocular use as they would gel once in contact with the tear fluid, thus reducing nasolacrimal drainage, but would thin upon shearing, preventing ocular irritation and therefore induced lacrimation.