Pharmacokinetic differences between ocular inserts and eyedrops

Controlled release ocular inserts have been found to increase the amount of drug which is absorbed into the aqueous humour when compared to eyedrops. Systemic absorption following delivery using a controlled release insert has been found to be dependent on the release rate of the insert. The objective of this study was to determine if ocular inserts affect drug absorption into other ocular tissues such as the conjunctiva and iris-ciliary body. Ocular absorption studies were performed using albino rabbits and ethylene-vinyl acetate controlled release devices containing timolol maleate. A compartmental model previously developed to simulate ocular absorption following eyedrop administration was modified and used to simulate these experiments. The conjunctival absorption coefficient calculated by the model and the AUC of the conjunctiva per mumol of delivered drug were found to be 2.7 and 42 times higher, respectively, for the ocular insert as compared to eyedrop administration. The increased conjunctiva absorption was likely the result of reduced tear mixing, which caused a high local concentration of timolol between the insert and the conjunctiva. The AUC of the iris-ciliary body per mumol of delivered drug was found to be 24 times higher for the ocular inserts as compared to eyedrop administration. The AUC of the iris-ciliary body was found to be 1.4 times higher than the AUC of the aqueous humour for eyedrop administration, but 9 times greater for delivery via the ocular inserts. Thus, the increased absorption into the iris-ciliary body and aqueous humour observed for ocular inserts is partially the result of an increase in the amount of drug which enters these tissues via penetration across the conjunctiva and sclera.