Importance of the noncorneal absorption route in topical ophthalmic drug delivery.

TLDR

Transcorneal permeation has traditionally been the main route for topically applied ophthalmic drugs, yet alternate noncorneal pathways have received little attention and may be crucial for drugs poorly absorbed across the cornea due to their physicochemical properties. The study aims to determine the significance of noncorneal absorption for drugs poorly absorbed across the cornea because of their physicochemical properties. The authors developed an in vivo system to quantify the contribution of noncorneal absorption to intraocular drug levels following topical administration. The results demonstrated that noncorneal absorption significantly contributes to intraocular drug penetration, bypasses the anterior chamber, involves conjunctiva/sclera penetration, and is not explained by systemic reentry or local vasculature, with inulin confirming the route for poorly absorbed high‑molecular‑weight substances.

Abstract

Transcorneal permeation has traditionally been the mechanism by which topically applied ophthalmic drugs are believed to gain access to the internal ocular structures. Relatively little attention has been given to alternate routes by which drugs may enter the eye. A system has been developed which allowed the investigation in vivo of the contribution of noncorneal absorption to intraocular drug levels after topical dosing. Using timolol and inulin as probe drugs, it was shown that the noncorneal absorption route may contribute significantly to drug penetration into intraocular tissues. Furthermore, results demonstrated that drugs absorbed by the noncorneal route appeared to enter certain intraocular tissues by a mechanism which bypasses the anterior chamber. These studies suggested that intraocular penetration via noncorneal routes involves penetration of drug across the conjunctiva/sclera. Neither reentry from the general circulation after drug absorption into the blood or drug delivery by the local vasculature accounted for the observed results. In terms of topical ophthalmic drug delivery, the noncorneal absorption route may be important for drugs that are poorly absorbed across the cornea due to their physical-chemical properties. We have demonstrated this using inulin as a model for a poorly absorbed, high molecular weight substance.