Drug release dynamics from a three-layer composite contact lens in the vial, eye wear with blinking, and blister pack settings.

Abstract

In this work we design a multi-layer model of composite contact lens drug release. Such lenses have been designed by encapsulating drug-polymer films in contact lens hydrogels. Composite lenses can promote sustained discharge of drug and achieve near zero-order release kinetics, thus surpassing other ocular delivery methods that are limited by short residence times and an undesirable initial burst release. Our model is informed by in vivo data, and includes three coupled partial differential equation layers to simulate the composite lens. We mathematically investigate the effect of composite contact lens design characteristics on the time to 50% therapeutic drug release ($ t_{50} $) in the vial, eye, and blister pack settings. In the eye setting, we incorporate our prior model that considers the effect of many blinks on the pre- and post-lens tear film drug concentrations. We simulate drug cumulative release profiles and study the variability of $ t_{50} $ across: (1) the ratio of the drug-polymer film to hydrogel diffusion coefficients, (2) the centerline of the polymer film within the hydrogel, and (3) the polymer film thickness. In the blister pack setting, we study storage questions that may inform future commercial design. We find that the diffusion coefficient ratio strongly negatively affects $ t_{50} $ across all three settings, while the dependence of $ t_{50} $ on polymer centerline depends also on the diffusion coefficient ratio and the relative pre- and post-lens drug clearance rates in the eye wear setting. A relatively small blister pack loading concentration ($ < 5\% $ that of the drug-polymer film) is required to sustain 50% of the drug in the lens for one month. Our study reveals that optimal lens design depends on the desired drug delivery rates and lens wear conditions, and that geometric and material lens properties can be adjusted towards drug delivery performance goals. This work may help medical professionals better understand the mechanics of contact lens drug delivery and predict targeted tissue transport of ophthalmic drugs.

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