Sustained Delivery of Olopatadine from Vitamin-E Loaded Contact Lenses

Abstract

Purpose: Topical antihistamines, such as olopatadine hydrochloride, an H1 receptor antagonist, are commonly prescribed for treating allergic conjunctivitis. Drug delivery via eye drops has many deficiencies including a short residence time due to tear drainage via the nasolacrimal duct, which results in a low bioavailability and potential for side effects. These deficiencies could be mitigated by a drug-eluting contact lens such as the recently approved ACUVUE^® THERAVISION™ WITH KETOTIFEN which is a daily disposable etafilcon, a drug-eluting contact lens with ketotifen (19 μg per lens). Here, we investigate the feasibility of designing a drug-eluting lens with sustained release of olopatadine for treating allergies using an extended wear lens. Methods: Nanobarrier depots composed of vitamin-E (VE) are formed through direct entrapment by ethanol-driven swelling. The drug-loaded lenses are characterized for transparency and water content. In vitro release is measured under sink conditions and fitted to a diffusion control release model to determine diffusivity and partition coefficient. Results: In vitro studies indicate that ACUVUE OASYS^® and ACUVUE TruEye™ lenses loaded with ∼0.3 g of VE/g of hydrogel effectively prolong olopatadine dynamics by 7-fold and 375-fold, respectively. Incorporation of VE into the lenses retains visible light transmission and other properties. Conclusion: The VE incorporation in commercial lenses significantly increases the release duration offering the possibility of antiallergy extended wear lenses.

Keywords: bioavailability; conjunctivitis; olopatadine hydrochloride; vitamin E.

FIG. 1.

Transmittance spectra of an 80 μm thick commercial ACUVUE^® OASYS^® and ACUVUE TruEye™ control lens and the modified version after VE (α-tocopherol) incorporation. Integration of VE into the lens matrix does not have an impact on transparency of the commercial lenses. VE, vitamin-E.

FIG. 2.

Dynamics of olopatadine transport during the release phase in commercial and modified ACUVUE OASYS (a, b) and ACUVUE TruEye (a, c) lenses. Data are presented as mean ± SD with n = 3. SD, standard deviation.

FIG. 3.

Dynamics of olopatadine transport during the release phase in commercial and modified ACUVUE OASYS (a) and ACUVUE TruEye (b) lenses plotted as a function of $\sqrt{t}$ to demonstrate diffusion control mechanism. Data are presented as mean ± SD with n = 3.

FIG. 4.

A scaling model proposed by Chauhan et al. used to predict the ratio of olopatadine release duration increase with respect to volume fraction of VE phase separated into the lens matrix. The solid lines are the best-fit results based on the scaling model presented for both commercial ACUVUE OASYS and ACUVUE TruEye lenses. Data are presented as mean ± SD with “n = 3.” The magnitude of error bars is small in comparison to the marker size.