A novel nanoparticles impregnated ocular insert for enhanced bioavailability to posterior segment of eye: In vitro, in vivo and stability studies

The present investigation was carried out to demonstrate with the help of in vitro and in vivo studies that nano particles impregnated ocular inserts effectively delivers significant concentration of drug to the posterior segment of eye after topical administration for treatment of glaucoma. Drug loaded Nanoparticles and their ocular insert have been reported to reduce side effects of orally administered Acetazolamide. Eudragit NPs were prepared by the solvent diffusion nanoprecipitation technique. The prepared NPs were evaluated for various parameters such as particle size, zeta potential, % entrapment efficiency, % drug loading, DSC, FTIR, TEM and stability studies. Ocular inserts of NPs were prepared by solvent casting method. The prepared ocular inserts were evaluated for thickness, content uniformity, folding endurance, disintegration time, morphology and stability study. The NPs and ocular inserts were evaluated for in-vitro drug diffusion study, ex-vivo trans-corneal permeability study, in-vivo ocular tolerability and intra ocular pressure (IOP) reduction study. The optimized batch was stable for a period of 3 months in lyophilized form. The optimized formulations had size range of 367 nm +/- 8 nm, zeta potential around +7 mV +/- 13 mV and 51.61% +/- 3.84% entrapment efficiency with 19% +/- 1,40% drug loading. The ex-vivo trans-corneal study showed higher cumulative corneal permeation, flux across corneal tissue (2.460 +/- 0.028 mu g/ml) and apparent corneal permeability (8.926 x 10(-6) cm(2)/s & 3.863 x 10(-6) cm(2)/s) from drug loaded Eudragit NPs and Ocular inserts as compared to drug solution (0.671 +/- 0.020 mu g/ml & 3.166 x 10(-6) cm(2)/s). In-vivo study showed the Eudragit NPs and ocular insert produced significant (P < 0.001) lowering in intra ocular pressure compared with the solution of free drug after 3 h of topical ocular administration. Plain Eudragit NPs caused no inflammation and/or discomfort in rabbit eyes and neither affected the intra ocular pressure establishing their safety and non irritancy. (C) 2016 Elsevier B.V. All rights reserved.