Pharmacokinetics and anti-inflammatory activity in rabbits of a novel indomethacin ophthalmic solution.
The formulation of aqueous ophthalmic solutions containing indomethacin (IND) presents serious problems due to poor solubility and stability of the drug. The purpose of this study was to evaluate a novel 0.1% IND formulation containing a poly(oxyethylene)-poly(oxypropylene) block copolymer (poloxamer 407) as solubilizer. This formulation was evaluated for stability, bioavailability and anti-inflammatory activity in comparison with an ophthalmic IND solution currently on the market. The experimental solution, tested for IND stability at different temperatures, compared favorably with the commercial solution. In rabbits, it produced significantly higher IND levels in the aqueous humor and, in an immunogenic uveitis model, it induced a comparatively faster resolution of the symptoms, as determined by inflammation scores and by IOP measurements. The data indicate poloxamer 407 as a potentially valuable nonirritating, solubilizing and stabilizing agent for indomethacin.
Chetoni
P
P
Department of Bioorganic Chemistry and Biopharmaceutics, University of Pisa, Italy. chetonip@farm.unipi.it
Panichi
L
L
Burgalassi
S
S
Benelli
U
U
Saettone
M F
MF
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000494:pharmacology; D001082:Aqueous Humor / Q000378:metabolism*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004341:Drug Evaluation; D004355:Drug Stability; D006358:Hot Temperature; D007213:Indomethacin / Q000493:pharmacokinetics* / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics / Q000494:pharmacology; D020442:Poloxamer / Q000494:pharmacology; D011817:Rabbits; D012710:Serum Albumin, Bovine; D014018:Tissue Distribution; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009883:Ophthalmic Solutions; D020442:Poloxamer; D012710:Serum Albumin, Bovine; D007213:Indomethacin