S W Friedrich | PubMed Health

PubMed1996

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.

Absorption↗

PubMed1993

Theoretical corneal permeation model for ionizable drugs.

The primary route into the eye for many drugs is transcorneal permeation. A better understanding of the mechanisms involved in transcorneal permeation could lead to improvements in drug dosage forms or the development of drug delivery devices which enhance the ocular bioavailability of drugs. A corneal permeation model has been developed which can be used to study the mechanisms involved in corneal permeation. The model uses five compartments in series to simulate the tear film, epithelium, stroma, endothelium and aqueous humour. These tissues were assumed to be adequately represented by plane sheet barriers of physiological thickness. The tear film was assumed to be perfectly mixed and the stroma completely stagnant. Due to inadequate knowledge of the hydrodynamics of the aqueous humour, both stagnant and perfectly mixed extremes were studied. The four routes of drug loss which were considered the most significant and therefore included in the model were lacrimal drainage, conjunctival absorption, aqueous drainage and iris-ciliary body absorption. The equilibrium that can exist between the ionic and non-ionic forms of a drug was found to be an important step in the mechanism of transcorneal permeation. Including the equilibrium condition in the model resulted in aqueous humour drug levels that were over 50 times higher than the levels predicted by a model which did not use the equilibrium mechanism. A relationship between the lipophilicity of each of the two drug forms and its permeability in each layer of the cornea was used in the model. The model was used to predict aqueous humour drug concentrations resulting from a constant release of timolol into the tear film or from the application of timolol, levobunolol and pilocarpine eyedrops. The model produced transient aqueous humour drug levels that closely followed experimental in vivo data from literature. Using the model, it was also possible to predict the amount of instilled drug that is lost through each of the four elimination routes of the eye.

Absorption↗