PURPOSE: The purpose of this study was (i) to validate differentially tape-stripped, porcine skin as an in vitro model for the evaluation of transdermal drug delivery (TDD) to premature neonates, (ii) to determine whether the model could estimate neonatal skin permeability as a function of postconceptional age (PCA), and (iii) to demonstrate that iontophoretic delivery permits precise control of drug input independent of skin barrier function. METHODS: Passive permeation of caffeine, phenobarbital, and lidocaine across tape-stripped porcine skin barriers was measured. Iontophoretic delivery of lidocaine across skins with different barrier competencies was also evaluated. RESULTS: For all drugs, passive permeation correlated with skin barrier function; that is, with transepidermal water loss (TEWL): Jss = A x exp[B x TEWL]. Combining this result with a previously derived dependence of TEWL upon the PCA of premature neonates in vivo allowed a relative value of Jss to be predicted for a given PCA. Comparison of these predictions showed excellent agreement with experimental data reported for diamorphine. Iontophoretic lidocaine delivery was precisely controllable independent of barrier competency. CONCLUSIONS: Porcine skin, in vitro, differentially tape-stripped to specific barrier competencies, is a useful model to explore TDD in premature neonates. The potential for iontophoresis to provide improved dose control and adjustment, irrespective of skin barrier maturity, is established.
PURPOSE: The purpose of this study was (i) to validate differentially tape-stripped, porcine skin as an in vitro model for the evaluation of transdermal drug delivery (TDD) to premature neonates, (ii) to determine whether the model could estimate neonatal skin permeability as a function of postconceptional age (PCA), and (iii) to demonstrate that iontophoretic delivery permits precise control of drug input independent of skin barrier function. METHODS: Passive permeation of caffeine, phenobarbital, and lidocaine across tape-stripped porcine skin barriers was measured. Iontophoretic delivery of lidocaine across skins with different barrier competencies was also evaluated. RESULTS: For all drugs, passive permeation correlated with skin barrier function; that is, with transepidermal water loss (TEWL): Jss = A x exp[B x TEWL]. Combining this result with a previously derived dependence of TEWL upon the PCA of premature neonates in vivo allowed a relative value of Jss to be predicted for a given PCA. Comparison of these predictions showed excellent agreement with experimental data reported for diamorphine. Iontophoretic lidocaine delivery was precisely controllable independent of barrier competency. CONCLUSIONS: Porcine skin, in vitro, differentially tape-stripped to specific barrier competencies, is a useful model to explore TDD in premature neonates. The potential for iontophoresis to provide improved dose control and adjustment, irrespective of skin barrier maturity, is established.
Authors: Eman Abd; Shereen A Yousef; Michael N Pastore; Krishna Telaprolu; Yousuf H Mohammed; Sarika Namjoshi; Jeffrey E Grice; Michael S Roberts Journal: Clin Pharmacol Date: 2016-10-19