Ophthalmic delivery of sparfloxacin from in situ gel formulation for treatment of experimentally induced bacterial keratitis

• Published in: Drug testing and analysis Vol. 3; no. 2; p. 106
• Main Author: Nesseem, Demiana I
• Format: Journal Article
• Language: English
• Published: England 01.02.2011
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - analysis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - therapeutic use; Biological Availability; Carboxymethylcellulose Sodium - chemistry; Cornea - pathology; Corneal Ulcer - drug therapy; Corneal Ulcer - etiology; Corneal Ulcer - pathology; Delayed-Action Preparations - chemistry; Drug Delivery Systems - methods; Escherichia coli; Fluoroquinolones - administration & dosage; Fluoroquinolones - analysis; Fluoroquinolones - chemistry; Fluoroquinolones - pharmacokinetics; Fluoroquinolones - therapeutic use; Gels - chemistry; Hyaluronic Acid - chemistry; Male; Models, Animal; Poloxamer - chemistry; Rats; Rats, Inbred Strains; Rheology; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Staphylococcus aureus; Sterilization - methods; Treatment Outcome
• ISSN: 1942-7611
• DOI: 10.1002/dta.170

The objective of the present work was (1) to develop an in situ gelling ophthalmic delivery system by combining pluronic F127 and pluronic F68, with sparfloxacin; and (2) to examine the influence of incorporating a mucoadhesive polysaccharide such as sodium hyaluronate on the healing property due to bacterial keratitis. The formulations (F1-F6) were sterilized by gamma irradiated using Co(60) . Ultraviolet (UV) and infrared (IR) spectra studies were performed on sterilized and non-sterilized formulae. The formulations were evaluated for rheological characteristics, in vitro release behavior, and efficacy against induced bacterial conjunctivitis in rats' eyes. Moreover, histopathological evaluations were also done. All the samples passed sterility tests, and no change in physical appearance of the formulae due to gamma radiation was observed. The IR spectra of the formulae before and after sterilization showed similar peaks which confirmed that no ingredient was affected by gamma radiation. The formulations showed a flow index of 0.116-0.493 indicating pseudoplastic flow behavior. The release behavior of all formulae was non-Fickian anomalous release. The different formulae used to overcome the pathological alterations, produced by bacteria infections varied among each other depending on the duration of treatment; however, the effectiveness of formulation was arranged as F5, F4 and F3, respectively. The developed formulations were therapeutically efficacious, and provided sustained release of the drug over a 24-hour period. A better improvement in artificially induced bacterial conjunctivitis in rats' cornea was observed with the developed formulae; thus it can be considered as a viable alternative to conventional eye drops.