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

摘要

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-Cl-50 dispersed in 0.9% NaCl solution was substantially more effective compared with 0.1% FB solution, EU-FBH50-Cl-50(Dex), or Tolerane((R)) (a marketed formulation). This complex formulation was shown to be innocuous for rabbit ocular tissues because no irritant effects were evidenced. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3859-3868, 2014