Moxifloxacin loaded microspheres-composed gel for controlled release and enhanced penetration in ocular tissues: In vitro, ex vivo and in vivo proof of concept

Abstract

Microspheres-enriched ocular gels are proposed in this work for the loading of a model quinolone antibiotic of broad-spectrum - moxifloxacin hydrochloride (MXF) - as an approach to achieve a controlled release profile and enhance drug's bioavailability in ocular milieu. MXF is a synthetic fluoroquinolone antibacterial agent used for treatment of ocular diseases caused by strains of aerobic gram positive and gram-negative bacteria, besides others. MXF-loaded Eudragit RS microspheres were prepared by emulsion solvent evaporation method, as previously described by us. Optimized microspheres were characterized and then formulated in an ocular gel. Hydrophilic polymeric base HPMC K100 was used as gelling agent. Ocular gel enriched with microspheres was evaluated for its physicochemical parameters, in vitro drug release, ex vivo corneal and scleral permeation and bioadhesion, in vivo primary eye irritation and in vivo efficacy study. The developed MXF microspheres dispersed in an ocular gel showed an in vitro drug release over a period 12 h, improved corneal and scleral penetration and increased therapeutic efficacy with a reduced administration frequency which may contribute to increase patient's compliance to ocular treatment.