title: A novel nanoparticles impregnated ocular insert for enhanced bioavailability to posterior segment of eye: In vitro, in vivo and stability studies.
abstract: The present investigation was carried out to demonstrate with the help of in vitro and in vivo studies that nanoparticles 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 3months in lyophilized form. The optimized formulations had size range of 367nm±8nm, zeta potential around +7mV±1.3mV 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±0.028μg/ml) and apparent corneal permeability (3.926×10-6cm2/s & 3.863×10-6cm2/s) from drug loaded Eudragit NPs and Ocular inserts as compared to drug solution (0.671±0.020μg/ml & 3.166×10-6cm2/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 3h 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.
authors.affiliation: Drug Delivery Research Laboratory, Centre of relevance and Excellence in NDDS, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, India.
authors.forename: Lalaji V
authors.initials: LV
authors.lastname: Rathod
authors.affiliation: Drug Delivery Research Laboratory, Centre of relevance and Excellence in NDDS, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, India.
authors.forename: Rakhee
authors.initials: R
authors.lastname: Kapadia
authors.affiliation: Drug Delivery Research Laboratory, Centre of relevance and Excellence in NDDS, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, India. Electronic address: dr_krutikasawant@rediffmail.com.
authors.forename: Krutika K
authors.initials: KK
authors.lastname: Sawant
mesh_terms: D000086:Acetazolamide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D003315:Cornea; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006041:Goats; D007429:Intraocular Pressure / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011817:Rabbits
chemical_list: D004343:Drug Implants; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D000086:Acetazolamide
keywords: Acetazolamide; Eudragit NPs; Glaucoma treatment; Nanoprecipitation; Ocular drug delivery; Ocular inserts