Preparation and characterization of Eudragit Retard nanosuspensions for the ocular delivery of cloricromene

The purpose of this study was to improve the stability ofcloricromene (AD6) in ophthalmic formulations and its drugavailability at the ocular level. To this end, AD6-loaded polymericnanoparticle suspensions were made using inert polymerresins (Eudragit RS100 and RL100). We modified thequasi-emulsion solvent diffusion technique by varying someformulation parameters (the drug-to-polymer ratio, the totaldrug and polymer amount, and the stirring speed). The chemicalstability of AD6 in the nanosuspensions was assessed bypreparing some formulations using (unbuffered) isotonicsaline or a pH 7 phosphate buffer solution as the dispersingmedium. The formulations were stored at 4°C, and the rate ofdegradation of AD6 was followed by high performance liquidchromatography (HPLC). The obtained nanosuspensionsshowed mean sizes and a positive surface charge (ζ-potential)that make them suitable for an ophthalmic application; theseproperties were maintained upon storage at 4°C for severalmonths. In vitro dissolution tests confirmed amodified releaseof the drug from the polymer matrixes. Nanosuspensions preparedwith saline solution and no or lower amounts of surfactant(Tween 80) showed an enhanced stability of the ester drugfor several months, with respect to an AD6 aqueous solution.Based on the technological results, AD6-loaded EudragitRetard nanoparticle suspensions appear to offer promise as ameans to improving the shelf life and bioavailability of thisdrug after ophthalmic application.