Drug delivery to the neonatal and premature pediatric populations is very challenging. This research assessed the potential of delivering midazolam by transdermal iontophoresis as an alternative strategy in pediatric therapy. In vitro experiments used intact and tape-stripped porcine skin as models for the skin barrier function of full-term and premature newborns, respectively. Midazolam transdermal transport was significantly enhanced by applying higher currents, increasing the formulation pH, and optimizing the drug’s mole fraction in the vehicle. When the skin barrier was decreased to half of its baseline competence, the passive permeation of midazolam increased by approximately 60-fold; and complete stratum corneum removal led to an additional 20-fold enhancement in permeation. Iontophoresis retained control of the drug transport trough partially compromised skin. However, a very high passive contribution undermined the iontophoretic control when the barrier was fully compromised. Overall, midazolam delivery could be rate-controlled by iontophoresis in most circumstances, and therapeutically useful fluxes could be achieved.
Original languageEnglish
Pages (from-to)137-143
Number of pages7
JournalEuropean Journal of Pharmaceutical Sciences
Early online date5 Dec 2018
Publication statusPublished - 1 Feb 2019


  • Iontophoresis
  • Midazolam
  • Passive diffusion
  • Pediatric drug delivery
  • Skin barrier function
  • Transdermal drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science


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