DEVELOPMENT AND EVALUATION OF HP-β-CD COMPLEXATION BASED NOVEL OPHTHALMIC GEL FORMULATION OF NEPAFENAC

Nepafenac is an analgesic and anti-inflammatory drug, used in post-operative ocular pain and presently available in the market in the form of 0.1% ophthalmic suspension eye drop due to aqueous insolubility of the drug. The present formulation is not only poor patient compliant due to suspension form but also suffers from a short corneal residence and inadequate ocular bioavailability. The objective of the present research work is to enhance the aqueous solubility of lipophilic drug nepafenac and develop its ocular gel formulation for overcoming the drawbacks of the presently marketed product. The 10% w/v HP-β-CD solution was used to formulate nepafenac in solution form, which resulted in 57.14 fold solubility enhancement of nepafenac in water, facilitating the development of nepafenac eye drop-in solution form. To enhance the pre-corneal residence of the formulation, the drug solution was incorporated into the hydrogel base, i.e. gellan gum capable of ion-activated sol-to-gel transformation in the ocular environment while sodium hyaluronate forms gel that exists in slightly viscous flowable form. The developed formulation was evaluated for their physical appearance, drug content, pH, osmolality, in-vitro gelation property, in-vitro drug release, and ex-vivo trans-corneal drug permeation and all the studied parameters were found satisfactory and acceptable. Trans-corneal drug permeation study revealed that there was approximately 1.38 and 1.48 times enhancement in the drug permeation flux during 24 h study for developed in-situ gel and preformed gel, respectively, as compared to the marketed conventional product.