Ocular transport model for ophthalmic delivery of timolol through p-HEMA contact lenses

Abstract

Approximately 90% of all ophthalmic drug formulations are now applied as eye drops. While eye drops are convenient and well accepted by patients, approximately 95% of the drug contained in the drops is lost due to absorption through the conjunctiva or through tear drainage. Ophthalmic drug delivery via contact lenses should be more effective than drops because it increases the residence time of the drug in the eye, thus leading to a larger fractional intake of the drug through the cornea. While a number of in vivo and some in vitro experiments have been conducted to design and test ophthalmic drug delivery through contact lenses, little quantitative data exists for bioavailability, i.e., the fractional corneal uptake of the drug. In this paper we combine in vitro experiments with modeling to investigate the delivery of timolol, a drug commonly used to treat glaucoma, to the eyes. The in vitro experiments were conducted to create a transport model for releasing the drug from p-HEMA contact lenses. The transport model includes drug adsorption on the polymer and drug diffusion in bulk water. Experiments were conducted at three different cross-linker levels, and the transport parameters were determined for each case. The transport model was then incorporated into a model for the release of the drug from the contact lens into the pre- and post-contact lens tear films and the subsequent corneal uptake. Results show that at least 20% of the timolol entrapped in the lens will enter the cornea, which is much larger than the fractional uptake for drug delivery through drops.