Abstract

Purpose:Most eye diseases are treated with topical application of eye drops. The poor bioavailability and therapeutic response exhibited by these conventional eye drops due to rapid precorneal elimination of the drug may be overcome by the use of in situ gelling systems that are instilled as drops into the eye and undergo a sol-to-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 pH-triggered in situ gelation. Methods:Polyacrylic acid (Carbopol^® 934) was used as the gelling agent in combination with hydroxypropylmethylcellulose (Methocel K4M) 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, drug content, sol-to-gel transition by scanning electron microscopy (SEM), in vitro and in vivo drug release, ocular irritation and stability. Results: 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. Conclusions: The developed formulation is a viable alternative to conventional eye drops by virtue of its ability to enhance bioavailability through its longer precorneal residence time and ability to produce sustained drug release. Also important factor is the ease of instillation and the reduced frequency of instillation resulting in better patient acceptance.

Keywords:  In situ gelation   Sustained ophthalmic delivery   Carbopol^®   934   Ketorolac tromethamine