Extended delivery of cationic drugs from contact lenses loaded with unsaturated fatty acids

Abstract

This paper describes the use of surface-active anionic unsaturated fatty acids in commercial contact lenses to extend drug release duration and regulate delivery dosage. We studied the effect of oleic acid on the in vitro release kinetics of three cationic drugs, and two anionic drugs from silicone hydrogel contact lenses. The release duration of the cationic drugs: tetracaine hydrochloride, bupivacaine hydrochloride, and ketotifen fumarate was significantly extended from less than a day to more than a month because of the presence of oleic acid in the contact lenses. With a simple change in the fatty acid loading media, we could duplicate a similar efficacy by loading oleic acid in conventional non-silicone hydrogel contact lenses. The fitted effective diffusivity values of the three cationic drugs significantly decrease when the oleic acid weight % in the lenses is increased. By using two other unsaturated fatty acids, linoleic and α-linolenic acid, the release duration of ketotifen fumarate was also significantly extended in silicone hydrogel contact lenses. In contrast, the release of two anionic drugs, diclofenac sodium and flurbiprofen sodium, was accelerated for oleic acid modified lenses. These results show the dominating impact of coupling charge interactions between the drug and the fatty acid carrier molecules to precisely adjust delivery rate and dosage from a contact lens.