Formulation and Evaluation of in Situ Ocular Gel of Ketorolac Tromethamine

Abstract

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid precorneal elimination of the drug may be overcome by the use of in situ gel-forming systems that are instilled as drops into the eye and undergo a sol–gel transition in the cul-de-sac. Hence, the purpose of the present studies was to formulation and evaluation of an ophthalmic delivery system for a nonsteroidal anti-inflammatory drug, ketorolac tromethamine, based on the concept of thermo-sensitive, pH-sensitive, ion sensitive, in situ gelation. These gelling systems involve the use of poloxamer 407 and poloxamer 188, (thermo-sensitive polymer), carbopol 934 and carbopol 980 (pH-sensitive polymer), gelrite (ion sensitive polymer) was used as gelling agent and HPMC K4M was used as viscosity-enhancing agent. It was found that the optimum concentration of poloxamer 407 solution for the thermo-sensitive in situ gel forming delivery systems was 20% (w/w), carbopol 980 solution for the pH-sensitive in situ gel forming delivery systems was 0.3% (w/w) and gelrite solution for the ion-sensitive in situ gel forming delivery systems was 0.50% (w/w). In vitro drug release studies showed that the formulation released drug over a period of 8 hours with formulation KT-T71 (gelrite 0.50% w/v/HPMC K4M 0.2% w/v) showing the highest drug release of 95.29% of ketorolac tromethamine. Formulation (KT-T71) showed zero order drug release. Formulations (KT-T23, KT-T57, and KT-T71) used to determine the in vivo eye irritation studies (as per draize test) using six male rabbits. The formulations were found to be non-irritating with no ocular damage. The results demonstrated that the gelrite /HPMC K4M mixture can be used as an in situ gelling vehicle to enhance the ocular bioavailability and patient compliance. The prepared formulation was stable, non-irritant and provided sustained release of the drug over an 8-h period. The developed system is thus a viable alternative to conventional eye drops.