title: Development, in vitro and in vivo characterization of Eudragit RL 100 nanoparticles for improved ocular bioavailability of acetazolamide.
abstract: Glaucoma is characterized by increased intra ocular pressure (IOP) which results in blindness if left untreated. Acetazolamide (ACZ) is used to treat glaucoma since long back. Since it is a Class IV drug [According to Biopharmaceutics Classification System (BCS)], so its topical delivery results in poor ocular bioavailability. Objective of the present study is to increase the topical ocular bioavailability and to sustain the release of drug for longer time. ACZ-loaded Eudragit® RL 100 nanoparticle suspension (ACZ-E-NPs) was prepared by the nanoprecipitation method. Ratio of organic to aqueous phase and composition of organic phase were altered to get the best formulation. Formulations prepared with acetone and methanol as organic phase were smallest in size. EE was in the range of 57.8% to 68.5%. According to drug release study almost all the formulations released 80% of drug in 8 h duration. The kinetics of drug release showed that the drug release pattern followed Higuchi's model (highest R2 values) and further it was fitted to the Korsemeyer-Peppas model, which showed the release was as per Fickian diffusion. IOP lowering effects of plain drug solution and ACZ-E-NPs were compared in adult male albino rabbits with a Riester Tonometer. The data revealed that the ACZ-E-NPs lower the IOP for longer time and of higher magnitude also. The difference was significant (p<0.001). Short-term stability study showed that none of the formulations was having remarked difference in their physicochemical properties after 6 months of storage at various temperatures.
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi , Jharkhand , India .
authors.forename: Parmanand
authors.initials: P
authors.lastname: Verma
authors.forename: Roop Narayan
authors.initials: RN
authors.lastname: Gupta
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Jha
authors.forename: Ravishankar
authors.initials: R
authors.lastname: Pandey
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000180:Acrylic Resins / Q000737:chemistry*; D060433:Administration, Ophthalmic; D000818:Animals; D001682:Biological Availability; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D005901:Glaucoma / Q000188:drug therapy; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D008956:Models, Chemical; D053758:Nanoparticles; D010316:Particle Size; D011817:Rabbits; D013696:Temperature; D013997:Time Factors
chemical_list: D000180:Acrylic Resins; D002257:Carbonic Anhydrase Inhibitors; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C050528:Eudragit RS; D000086:Acetazolamide