Introduction: The sclera is considered the 'static barrier,' a main barrier for transscleral drug delivery. The characterization of passive and iontophoretic transport across the sclera in vitro is the first step toward our ability to predict transscleral drug delivery. Although previous studies have investigated this topic, the quantitative structure permeation relationships (QSPR) for passive and iontophoretic transscleral transport are not available.
Areas covered: This review evaluated previous results of transscleral passive and iontophoretic transport in vitro and examined QSPR for transscleral permeation of small permeants and macromolecules. Passive permeation data in the literature were compared with respective to the animal species employed in the studies. Data variability was investigated. Electrotransport theory and the mechanisms of iontophoresis were reviewed and used to analyze the iontophoresis data.
Expert opinion: QSPR was examined for passive transscleral permeation, showing correlations between logarithm of permeability coefficient and logarithm of molecular weight. Potential causes of data variability were proposed. QSPR were established for electroosmosis using the molecular weight of neutral permeants and for iontophoresis enhancement using the molecular weight and charge of ionic permeants. However, QSPR for charged macromolecules were empirical; iontophoretic flux enhancement was significantly smaller than Nernst-Planck model prediction due to complicating factors.
Keywords: Ocular delivery; diffusion; iontophoresis; quantitative structure permeation relationships (QSPR); sclera; transscleral.