Potential of iontophoresis as a drug delivery method for midazolam in pediatrics.
Iontophoresis
Midazolam
Passive diffusion
Pediatric drug delivery
Skin barrier function
Transdermal drug delivery
Journal
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Titre abrégé: Eur J Pharm Sci
Pays: Netherlands
ID NLM: 9317982
Informations de publication
Date de publication:
01 Feb 2019
01 Feb 2019
Historique:
received:
20
08
2018
revised:
12
11
2018
accepted:
29
11
2018
pubmed:
7
12
2018
medline:
29
5
2019
entrez:
4
12
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30503379
pii: S0928-0987(18)30526-8
doi: 10.1016/j.ejps.2018.11.035
pii:
doi:
Substances chimiques
Hypnotics and Sedatives
0
Midazolam
R60L0SM5BC
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
137-143Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.