Ocular Delivery of Flurbiprofen Based on Eudragit® E-Flurbiprofen Complex Dispersed in Aqueous Solution: Preparation, Characterization, In Vitro Corneal Penetration, and Ocular Irritation

Abstract

A novel ophthalmic formulation based on the ionic complexation between Eudragit E 100 (EU) and flurbiprofen (FB) is proposed. The selected complex composition, named EU–FBH50Cl50, had the basic groups of EU completely neutralized with equal molar amounts of FB and HCl. This complex, obtained in the solid state, exhibited a high aqueous compatibility producing a colloidal dispersion with a high positive electrokinetic potential, in which more than 99% of FB was ionically condensed with EU. In bicompartimental Franz cells, FB diffusion from the complex was very slow. However, dispersion in 0.9% NaCl increased the FB release through an ionic exchange, providing an optimal constant rate of delivery. Corneal FB permeation from 0.1% EU–FBH50–Cl50 dispersed in 0.9% NaCl solution was substantially more effective compared with 0.1% FB solution, EU–FBH50–Cl50(Dex), or ToleraneR (a marketed formulation). This complex formulation was shown to be innocuous for rabbit ocular tissues because no irritant effects were evidenced.