alexa Effect of chitosan and of N-carboxymethylchitosan on intraocular penetration of topically applied ofloxacin.
Pharmaceutical Sciences

Pharmaceutical Sciences

Pharmaceutica Analytica Acta

Author(s): Di Colo G, Zambito Y, Burgalassi S, Nardini I, Saettone MF

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Abstract The effects of chitosan hydrochloride (Ch-HCl) and of N-carboxymethylchitosan (CMCh), formulated in ophthalmic solutions, on the ocular pharmacokinetics of ofloxacin were studied in rabbits. The carboxymethylation of a chitosan of high molecular mass (1460 kDa) and deacetylation degree (89.9\%) introduced 0.84 N-carboxymethyl groups per repeating unit. Aqueous solutions containing 1\% (w/v) of either polymer showed a pseudoplastic rheologic behaviour, and, when instilled in rabbit eyes, produced no irritation. The kinetics of drug disappearance from tear fluid and the profiles of drug concentration in the aqueous humour versus time were determined and interpreted in the light of a pharmacokinetic model and of drug-polymer binding. Ch-HCl significantly enhanced intraocular drug penetration with respect to an isoviscous drug solution containing poly(vinyl alcohol) and to commercial ofloxacin eyedrops. This effect, which resulted in about 190\% increase of the peak concentration in the aqueous, was ascribed to an increased corneal permeability. The polyanionic CMCh failed to enhance intraocular drug penetration. It nevertheless increased precorneal drug retention in virtue of its viscosity and of ofloxacin binding. Consequently, the residence time at concentrations higher than the MIC90 and the bioavailability of the antibiotic in the aqueous were increased by about 150 and 240\%, respectively, with respect to the reference vehicle. This article was published in Int J Pharm and referenced in Pharmaceutica Analytica Acta

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