Sustained Ophthalmic Delivery of Ketorolac Tromethamine from an ion activated In Situ gelling system

Abstract

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid pre-corneal 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 then undergo a sol-gel transition in the cul-de-sac. Hence, the purpose of the present work was to formulate and evaluate an ophthalmic delivery system for a nonsteroidal anti-inflammatory drug, Ketorolac tromethamine, based on the concept of ion activated in situ gelation. The sodium alginate was used in different concentrations (0.2-2.0 % w/v) as the gelling agent in combination with tamarind seed polysaccharide (TSP) (0.2-1.5 % w/v) which acted as a viscosity enhancing agent. Compatibility studies of the drug excipients were carried out using Differential Scanning Calorimetry (DSC). The prepared formulations were characterized for clarity, pH, antimicrobial efficacy, drug content, in vitro drug release and stability. In vitro release studies indicated that the sodium alginate / tamarind seed polysaccharide (TSP) solution retained the drug better than the sodium alginate or tamarind seed polysaccharide (TSP) solutions alone. The clarity, pH and drug content of the developed formulation were found to be satisfactory. The developed formulation was therapeutically efficacious, stable, non-irritant, and provided sustained drug release over an 8-h period. The formulation with benzalkonium chloride and edetate disodium improved the rate of corneal absorption but not the extent. The developed system is an alternative to conventional ophthalmic drops, patient compliance, industrially oriented and economical.