Preparation of in situ-forming ophthalmic gels of ciprofloxacin in hydrochloride for the treatment of bacterial conjunctivitis:: In vitro and in vivo studies

Sol-to-gel systems of ciprofloxacin hydrochloride were prepared utilizing the phase transition properties of hydroxy propyl methyl. cellulose K 15 M grade (HPMC) and carbopol 934. The sol-to-gel systems were sterilized by gamma radiation and/or filtration. The sol-to-gel systems were evaluated for rheological characteristics, in vitro release behavior, microbial efficacy, in vivo release behavior, and efficacy against induced bacterial conjunctivitis in rabbits' eyes. Concentration in aqueous humor was determined and stability studies were carried out as per the ICH guidelines. The system passed the test for sterility. The sol-to-gel system exhibited a zero-order drug release pattern over 24 h in in vitro release studies. The drug was active against selected microorganisms in microbial efficacy studies. Better improvement in artificially induced bacterial conjunctivitis in rabbits' eyes was observed in animals treated with the sol-to-gel system compared with marketed eye drops. Drug concentration in aqueous humor was greater than the minimum inhibitory concentration (MIC 90) against selected microorganisms. The shelf-life of the product was >2 years. (C) 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association.