title: Development of acetazolamide-loaded, pH-triggered polymeric nanoparticulate in situ gel for sustained ocular delivery: in vitro. ex vivo evaluation and pharmacodynamic study.
abstract: The objective of research was to develop a novel pH-triggered polymeric nanoparticulate in situ gel (NP-ISG) for ophthalmic delivery of acetazolamide (ACZ) to enhance the conjunctival permeation and precorneal residence time of the formulation by overcoming the limitations of protective ocular barriers. Nanoparticles (NP1--NP12) were developed by nanoprecipitation method and evaluated for pharmacotechnical characteristics including transmission electron microscopy. The optimized formulation, NP10 was dispersed in carbopol 934 P to form nanoparticulate in situ gels (NP-ISG1--NP-ISG5). NP-ISG5 was selected as optimized formulation on the basis of gelation ability and residence time. Ex vivo transcorneal permeation study exhibited significantly higher ACZ permeation from NP-ISG5 (74.50 ± 2.20 mg/cm(2)) and NP10 (93.5 ± 2.25 mg/cm(2)) than eye drops (20.08 ± 3.12 mg/cm(2)) and ACZ suspension (16.03 ± 2.14). Modified Draize test with zero score indicated nonirritant property of NP-ISG5. Corneal toxicity study revealed no visual signs of tissue damage. Further, NP-ISG5 when tested for hypotensive effect on intraocular pressure (IOP) in rabbits revealed that NP-ISG5 caused significant decrease in IOP (p < 0.05) in comparison to eye drops. Conclusively, NP-ISG5 may offer intensive management of glaucoma via higher permeation, prolonged precorneal residence time and sustained drug release along with higher in vitro efficacy, safety and patient compliance.
authors.affiliation: Department of Pharmaceutics, Rajiv Academy for Pharmacy, Chattikara , Mathura , India.
authors.forename: Jyotsana
authors.initials: J
authors.lastname: Singh
authors.forename: Gulshan
authors.initials: G
authors.lastname: Chhabra
authors.forename: Kamla
authors.initials: K
authors.lastname: Pathak
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003315:Cornea / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry; D005901:Glaucoma / Q000188:drug therapy; D006863:Hydrogen-Ion Concentration; D007429:Intraocular Pressure / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D010539:Permeability; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D013535:Suspensions / Q000008:administration & dosage / Q000145:classification
chemical_list: D003692:Delayed-Action Preparations; D005782:Gels; D009883:Ophthalmic Solutions; D011108:Polymers; D013535:Suspensions; D000086:Acetazolamide
keywords: Acetazolamide; Draize's test; in situ gel; intraocular pressure; nanoparticles; nanoprecipitation; transcorneal permeation