Effect of chitosan on in vitro release and ocular delivery of ofloxacin from erodible inserts based on poly(ethylene oxide)

The effects of chitosan hydrochloride (CH-HCl) on in vitro release of ofloxacin (OFX) from mucoadhesive erodible ocular :inserts and on the relevant ocular pharmacokinetics have been studied both to contribute evidence of the ability of CH-HCl to enhance transcorneal penetration of drugs and to increase the therapeutic efficacy of topically applied OFX. Circular inserts of 6 mm in diameter, 0.8-0.9 mm in thickness and 20 mg in weight, medicated with 0.3 mg drug, were prepared by powder compression. The addition of 10, 20 or 30% medicated CH-HCl microparticles, obtained by spray-drying, to formulations based on poly(ethylene oxide) of MW 900 kDa (PEO 900) or 2000 kDa (PEO 2000) produced changes in the insert microstructure which accelerated both insert erosion and OFX release from inserts. The effect was stronger with higher CH-HCl fractions. Of the CH-HCl-containing formulations based on either PEO 900 or PEO 2000, PEO 900-CH-HCl (9:1 w/w) was more suitable for a prolonged OFX release. Following insertion in the lower conjunctival sac of the rabbit's eye, such an insert produced no substantial increase of AUC(eff) (AUC in the aqueous humour for concentrations > MIC90%) with respect to inserts based on plain PEO; however, it produced a concentration peak in the aqueous significantly higher than that produced by any of the CH-HCl-free PEO inserts, and well higher than the MIC90%, for the more resistant ocular pathogens (7 mug/ml vs. 4 mug/ml). It has been argued that the increase was due to the ability of CH-HCl to enhance the transcorneal permeability of the drug. (C) 2002 Elsevier Science B.V. All rights reserved.