Abstract

The aim of the study is to design, optimize and characterize an ophthalmic in situ gelling system of an antibacterial agent, ofloxacin using polyacrylic acid (PAA) as the gelling agent along with Noveon^® AA-1 USP Polycarbophil as a viscosity enhancer.  A 3² full factorial design was applied for the optimization of the final formulation. The effect of independent variables was evaluated using dependent variables, that is, gel strength, bioadhesion force, viscosity and in vitro drug release profile of the formulation. Polynomial regression equations and surface plots were used to relate the dependent and independent variables. The desirability function was employed in order to determine the best batch which was then evaluated for an in vivo antimicrobial efficacy, effect of sterilization, ocular irritation and accelerated stability studies. From the factorial design, it was found that the optimum values of the responses could be obtained at medium levels of polyacrylic acid and Noveon^® AA-1 USP Polycarbophil (0.5/0.5%w/w respectively). The formulation retained antimicrobial efficacy, showed insignificant effect over sterilization and found non irritant to the corneal surface confirmed by microscopy of the corneal mucosal membrane compared with reference marketed formulation. Conclusively, the optimized formulation was found to be stable, therapeutically efficacious and providing sustained release of the drug over an 8 h period even after accelerated stability study over three months. The developed system is thus a viable alternative to conventional ophthalmic formulations.

Key words: In situ gel, ofloxacin, factorial design, poly(acrylic acid) (PAA), Noveon^®AA-1 USP polycarbophil.