Rufloxacin eyedrops: effect of different formulations on ocular pharmacokinetics in rabbits.
OBJECTIVE
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 At different times after administration, samples of aqueous humor were withdrawn and analyzed by high-pressure liquid chromatography.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.
Burgalassi
S
S
Department of Bioorganic Chemistry and Biopharmaceutics, University of Pisa, Pisa, Italy. burgal@farm.unipi.it
Cappello
B
B
Chetoni
P
P
Iervolino
M
M
Monti
D
D
Saettone
M F
MF
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D024841:Fluoroquinolones / Q000737:chemistry / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009883:Ophthalmic Solutions / Q000737:chemistry / Q000493:pharmacokinetics*; D011134:Polysaccharides / Q000493:pharmacokinetics; D015363:Quinolones / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D014783:Viscosity; D014822:Vitreous Body / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000493:pharmacokinetics
D000890:Anti-Infective Agents; D004337:Drug Carriers; D024841:Fluoroquinolones; D009883:Ophthalmic Solutions; D011134:Polysaccharides; D015363:Quinolones; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C060328:rufloxacin