Ocular delivery of Flurbiprofen based on Eudragit� E-flurbiprofen complex dispersed in aqueous solution: preparation, characterization, in vitro corneal penetration and ocular irritation

QUINTEROS, DANIELA, ; TARTARA, LUIS, ; PALMA, SANTIAGO, ; MANZO, RUBEN ; AND ALLEMANDI, DANIEL.

JOURNAL OF PHARMACEUTICAL SCIENCES

JOHN WILEY & SONS INC

Lugar: New York; Año: 2014 vol. 103 p. 3859 - 3868

0022-3549

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-FBH 50 Cl 50 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 NaCl 0.9% increased the FB release through an ionic exchange, providing an optimal constant rate of delivery. Corneal FB permeation from 0.1% EU-FBH 50 -Cl 50 dispersed in 0.9% NaCl solution was substantially more effective compared to FB 0.1% solution, EU-FBH 50 -Cl 50 (Dex) or Tolerane � (a marketed formulation). This complex formulation was shown to be innocuous for rabbit ocular tissues, since no irritant effects were evidenced.