Porcine ear skin as a model for the assessment of transdermal drug delivery to premature neonates.
OBJECTIVE
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.
Sekkat
Nabila
N
School of Pharmacy, University of Geneva, CH-1211 Geneva 4, Switzerland.
Kalia
Yogeshvar N
YN
Guy
Richard H
RH
D000279:Administration, Cutaneous; D000367:Age Factors; D000818:Animals; D002110:Caffeine / Q000493:pharmacokinetics*; D004058:Diffusion; D004423:Ear; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D007478:Iontophoresis / Q000379:methods*; D008012:Lidocaine / Q000493:pharmacokinetics*; D023421:Models, Animal; D010539:Permeability; D010634:Phenobarbital / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D013552:Swine
D002110:Caffeine; D008012:Lidocaine; D010634:Phenobarbital