In Vitro and In Vivo Evaluation of the Chitosan Microparticulate Ocular Delivery System of Ketorolac Tromethamine

The microparticulate ocular delivery system for ketorolac tromethamine based on chitosan was prepared and characterized for particle size, morphology, entrapment efficiency, in vitro release and in vivo ocular antiinflammatory activity. Chitosan microparticles of ketorolac tromethamine were prepared by modified emulsification ionic gelation method, using sodium tripolyphosphate as the ionic cross linking agent. Particle size and morphology was assessed using optical microscopy. In vitro release was determined using shaker method. In vivo ocular anti inflammatory activity was determined in prostaglandin E₂-induced rabbit ocular inflammation model. The mean particle size and entrapment efficiency was found to decrease, while in vitro release was found to increase with decrease in the concentration of chitosan and sodium tripolyphosphate. The release of ketorolac tromethamine from prepared microparticles followed zero order kinetics. The inhibitory effect of ketorolac loaded microparticles against prostaglandin E₂ – induced polymorphonuclear leukocyte migration was found to be slow and sustained. In conclusion, chitosan microparticulate ocular suspension of ketorolac tromethamine can be used for prolonging the precorneal residence and sustaining the drug release.