A Meta-Analysis of In Vitro Release of Hydrophilic Therapeutics from Contact Lenses Using Mathematical Modeling

Background/Objectives: A meta-analysis was conducted to study the in vitro release of hydrophilic therapeutics from contact lenses, loaded using the soaking method. Fifty-three experiments were studied that measure the cumulative release of therapeutics from (mostly) commercial contact lenses placed in a vial. Methods: A mathematical model and a parameter-fitting algorithm are presented to estimate the diffusion coefficient (D) and 50% therapeutic release time (T50) of all the experimental lens-therapeutic combinations. Statistical methods were used to analyze the relationships between lens materials, therapeutic properties, and predicted parameter values (D and T50). Results: The mathematical framework was validated against previous studies. It was found that lens water content directly and moderately influences the estimated diffusion coefficient. More specifically, the median diffusivity of silicone hydrogel (SH) contact lenses was statistically different from that of conventional hydrogel (CH) lenses. The dependencies of other lens and therapeutic properties on diffusivity were complex, with special cases studied to elicit dependencies. A predictive tool was constructed to estimate the logarithm of 50% therapeutic release time (log(T50)), given the lens water content and the therapeutic molecular volume and density. Conclusions: The conducted meta-analysis found that the kinetic release of therapeutics from contact lenses depends on the properties of both the contact lens and therapeutics. The statistical model explained 64% of the variability of the log(T50) and can be used in the preliminary stages of contact lens drug delivery development.