Enhance of trascorneal permeation using novel eudragit-flurbiprofen complexes

QUINTEROS, DANIELA; TARTARA, LUIS IGNACIO; PALMA SANTIAGO; MANZO, RUBEN HILARIO; ALLEMANDI DANIEL

Córdoba

Congreso; 1era Reunión Internacional de Ciencias Farmacéuticas; 2010

Facultad de Ciencias Químicas - UNC

INTRODUCTION This work was carried out in the framework of a project concerning the development of new ophthalmic drug delivery systems. It is based on the properties of Polymethacrylates (Eudragit®, Eu)-drug complexes, which are able to increase the aqueous compatibility of low solubility drug. The aim of the work was the assessment of physico-chemical, pharmaceutical and biopharmaceutical properties of these complexes. Flurbiprofeno (Fl) was selected as active and Eudragit®-Fl complexes were formulated in aqueous solution, which was subjected to transcorneal permeation assays as well as the evaluation of its potential ocular irritation in rabbits. MATERIALS Eu-Fl complexes, containing Fl 0.1%, were formulated using 5% dextrose and saline solutions as vehicles. As comparison a commercial product (Tolerane®) and Fl 0,01% aqueous solution (control) were studies METHODS Properties such as osmolality, partition coeficient, pH, electrokinetic potential, solubility were measured an analysed. Drug release and transcorneal permeation assays were performed in bicompartmental diffusion cells. The potential ocular irritancy and/or damaging effects of the formulations were evaluated using a slightly modified version of the Draize test and inspection of histological sections of cornea. RESULTS The Eu-Fl complex solutions were transparent, stable, with high and positive electrokinetic potential (+35 - +55mV). A high proportion of Fl associated to the Eu by ionic condensation was corroborated. As consequence, an increase of the solubility of Fl was observed in pHs where it exhibits low aqueous solubility. The kinetics of permeation through rabbit cornea of 4 formulations showed similar tendency than those obtained in the release assays. The comparative analysis of Fl release and permeation rates showed that solutions containing Eu-Fl50 NaCl 0.9% promoted Fl permeation faster than expected. These systems produced slight irritation characterized by a discrete to moderate vessel congestion of the conjunctiva, without corneal or intraocular injury. CONCLUSIONS Eu-Fl complexes, vehiculized in aqueous solutions, showed an increment in drug permeation through rabbit cornea, especially in saline solutions. Two factors would the responsible for this effect. By one side, Fl apparent solubility was augmented as consequence of complexation. On the other side, the presence of anionic ions (i.e. Cl-) promoted Fl release from the complexes as consequence of the activation of an ionic interchange process. Finally, the use of these formulations seem to be promissory since have shown to be practically no aggressive for ocular mucosa