Abstract
Purpose: :
DuraSite®, a topical polymeric drug delivery system, has been successfully employed to formulate several ocular antibiotics and has shown superior pharmacokinetic profiles. The purpose of this study was to investigate the topical utility of DuraSite for the transport of bromfenac across different ocular tissues and compare this with XibromTM (bromfenac ophthalmic solution, 0.09%).
Methods: :
Bromfenac was formulated in DuraSite® at two different concentrations, namely, 0.045% and 0.09%. A single drop of either concentration was applied to the left eye of Dutch Belted rabbits while the same animal received the commercial preparation in the right eye (n=84). The bromfenac concentration in the aqueous humor of each eye was then measured at 0.5, 1, 2, 4, 8, 12, and 24 hours following administration. In a separate study, one drop of either 0.09% experimental or commercial bromfenac preparation was administered to rabbits t.i.d. for 14 days. Two hours after the last dose, various ocular tissues were harvested and assayed for bromfenac content. All analytical procedures used liquid chromatography atmospheric pressure ionization tandem mass spectrometry (LCMS).
Results: :
In single dose experiments, the aqueous AUC of 0.045% and 0.09% bromfenac in DuraSite was approximately 2 and 4-fold higher than that of commercial bromfenac ophthalmic solution, 0.09%, respectively. In multi-dose experiments, ocular tissue concentrations of bromfenac in sclera and choroid in the DuraSite group were approximately 3 times as high as the commercial formulation group.
Conclusions: :
. Formulations of bromfenac using DuraSite drug delivery system exhibit superior delivery kinetics to various ocular tissues when compared with the commercially available eye drop formulation for both anterior and posterior segments.