Potential of iontophoresis as a drug delivery method for midazolam in pediatrics.


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
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

137-143

Informations de copyright

Copyright © 2018 Elsevier B.V. All rights reserved.

Auteurs

Asma Djabri (A)

Department of Pharmacy and Pharmacology, University of Bath, Claverton Down BA2 7AY, UK. Electronic address: Asma.Djabri@gstt.nhs.uk.

Richard H Guy (RH)

Department of Pharmacy and Pharmacology, University of Bath, Claverton Down BA2 7AY, UK. Electronic address: R.H.Guy@bath.ac.uk.

M Begoña Delgado-Charro (MB)

Department of Pharmacy and Pharmacology, University of Bath, Claverton Down BA2 7AY, UK. Electronic address: B.Delgado-Charro@bath.ac.uk.

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Classifications MeSH