Rufloxacin eyedrops: effect of different formulations on ocular pharmacokinetics in rabbits.

PURPOSE: To evaluate the aqueous humor pharmacokinetics of rufloxacin in rabbits after topical administration of different formulations, and to individuate the ones showing the best pharmacokinetic profile. METHODS: Six formulations were instilled in rabbit eyes: two pH 7.2 suspensions of non-salified rufloxacin base, or zwitterion (RUF), one of which was viscosized with tamarind seed polysaccharide (TSP); two pH 7.2 solutions of RUF obtained using hydroxypropyl-beta-cyclodextrin (CD), one of which was viscosized with TSP; and two pH 5.0 solutions of rufloxacin hydrochloride (RUF-HCl ), one of which was viscosized with TSP. At different times after administration, samples of aqueous humor were withdrawn and analyzed by high-pressure liquid chromatography. The main pharmacokinetic parameters of RUF in the aqueous humor produced by the different formulations were calculated and statistical differences were assessed. RESULTS: The best results, in terms of aqueous humor bioavailability, were observed with two TSP-viscosized formulations: a solution of the hydrochloride (TSP/RUF-HCl) and a suspension of the base (TSP/RUF), followed by the non-viscosized solution of RUF-HCl. The formulations containing CD-solubilized RUF were much less effective. CONCLUSIONS: The present data confirm the significant availability-enhancing properties of tamarind seed polysaccharide, and indicate that solubilization of RUF with hydroxypropyl-beta-cyclodextrin (CD/RUF) results in decreased drug availability with respect to standard formulations. Two of the TSP-viscosized formulations (RUF suspension and RUF-HCl solution) produced aqueous humor RUF concentrations in the range of activity against Enterobacteriaceae and Pseudomonas aeruginosa, thus warranting further studies on applications of rufloxacin in ocular therapy.