Transscleral Ocular Drug Delivery of Crystalline Drug Formulation Using Triamcinolone Acetonide as a Prototype

Abstract

Purpose: : To characterize the pharmacokinetics of triamcinolone acetonide in various ocular tissues in a rabbit model following a single sub Tenon injection of 40mg with decantation.

Methods: : Three rabbits at each time points (3 hours, 1 day, 3 days, 7 days, 14 days, 21 days, and 28 days) received sub Tenon injection of triamcinolone acetonide (40mg in 0.4 ml). The animals were sacrificed at the designated time points and the eye globes were snap frozen and dissected into aqueous, iris-ciliary body, vitreous, retina, and choroid. Blood sample were also collected from each rabbit before sacrifice. The concentrations of triamcinolone acetonide in the various ocular tissues and blood sample were analyzed using high-phase liquid chromatography (HPLC).

Results: : Triamcinolone acetonide concentration followed a mono exponential decrease over the study period in all studied ocular tissues. The concentrations decreased rapidly during the first three days then followed by a slower tapering during the rest of the observed time period. Triamcinolone acetonide concentration was significantly higher in the choroid than in the other tissues and triamcinolone acetonide concentration in the vitreous was the lowest. Triamcinolone acetonide in the choroid had the highest coefficient of logarithmic regression, indicating the rapid TA clearance which was 1.75 times more rapidly than triamcinolone acetonide in vitreous and 2 times more rapidly than triamcinolone acetonide in aqueous. Triamcinolone acetonide half-life in choroid was 5 days and in aqueous was 10 days. Triamcinolone acetonide was detectable in all blood samples during the whole study period with very low levels.

Conclusions: : Triamcinolone acetonide clearance from the intraocular tissues after sub Tenon administration follows a mono exponential model. Triamcinolone acetonide was cleared the most in choroid and retina, indicating choroid and retina serve as barriers for Triamcinolone acetonide transport from sub Tenon space to the vitreous. Triamcinolone acetonide can be detected in all the intraocular tissues for at least 28 days after a 40mg sub Tenon injection. This suggests the feasibility of other crystalline compounds for transscleral ocular drug delivery.

Keywords: retina • vitreous • choroid