Analysis of release kinetics of ocular therapeutics from drug releasing contact lenses: Best methods and practices to advance the field

Arianna Tieppo, Aarika C. Boggs, Payam Pourjavad, Mark E. Byrne

    Research output: Contribution to journalArticle

    30 Scopus citations

    Abstract

    Several methods have been proposed to achieve an extended and controlled release of ocular therapeutics via contact lenses; however, the experimental conditions used to study the drug release vary greatly and significantly influence the release kinetics. In this paper, we examine variations in the release conditions and their effect on the release of both hydrophilic and hydrophobic drugs (ketotifen fumarate, diclofenac sodium, timolol maleate and dexamethasone) from conventional hydrogel and silicone hydrogel lenses. Drug release was studied under different conditions, varying volume, mixing rates, and temperature. Volume had the biggest effect on the release profile, which ironically is the least consistent variable throughout the literature. When a small volume (2-30. mL) was used with no forced mixing and solvent exchange every 24. h, equilibrium was reached promptly much earlier than solvent exchange, significantly damping the drug release rate and artificially extending the release duration, leading to false conclusions. Using a large volume (200-400. mL) with a 30. rpm mixing rate and no solvent exchange, the release rate and total mass released was significantly increased. In general, the release performed in small volumes with no force mixing exhibited cumulative mass release amounts of 3-12 times less than the cumulative release amounts in large volumes with mixing. Increases in mixing rate and temperature resulted in relatively small increases of 1.4 and 1.2 times, respectively in fractional mass released. These results strongly demonstrate the necessity of proper and thorough analysis of release data to assure that equilibrium is not affecting release kinetics. This is paramount for comparison of various controlled drug release methods of therapeutic contact lenses, validation of the potential of lenses as an efficient and effective means of drug delivery, as well as increasing the likelihood of only the most promising methods reaching in vivo studies.

    Original languageEnglish (US)
    Pages (from-to)305-313
    Number of pages9
    JournalContact Lens and Anterior Eye
    Volume37
    Issue number4
    DOIs
    StatePublished - Aug 2014

    All Science Journal Classification (ASJC) codes

    • Ophthalmology
    • Optometry

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