Development of acetazolamide-loaded, pH-triggered polymeric nanoparticulate in situ gel for sustained ocular delivery: in vitro. ex vivo evaluation and pharmacodynamic study. (September 2014)

• Record Type: Journal Article
• Authors: Singh, Jyotsana; Chhabra, Gulshan; Pathak, Kamla
• Is Part Of: Drug development and industrial pharmacy. Volume 40:Number 9(2014:Sep.)
• Page Start: 1223
• Page End: 1232
• Publication Date: 2014-09
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.3109/03639045.2013.814061
• Languages: English
• ISSNs: 0363-9045

Abstract

<abstract> <title>Abstract</title> <p>The objective of research was to develop a novel pH-triggered polymeric nanoparticulate <italic>in situ</italic> 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 <italic>in situ</italic> gels (NP-ISG1--NP-ISG5). NP-ISG5 was selected as optimized formulation on the basis of gelation ability and residence time. <italic>Ex vivo</italic> transcorneal permeation study exhibited significantly higher ACZ permeation from NP-ISG5 (74.50 ± 2.20 mg/cm<sup>2</sup>) and NP10 (93.5 ± 2.25 mg/cm<sup>2</sup>) than eye drops (20.08 ± 3.12 mg/cm<sup>2</sup>) 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 (<italic>p</italic> < 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 <italic>in vitro</italic> efficacy, safety and patient compliance.</p> </abstract>