Improved stability and release control of levodopa and metaraminol using ion-exchange fibers and transdermal iontophoresis.
Achievement of controlled drug delivery and stability of drugs during storage is a problem also in transdermal drug delivery. The objective of this study was to determine, whether an easily oxidized drug, levodopa, could be stabilized during storage using pH-adjustment and ion-exchange fibers. Controlled transdermal delivery of the zwitterionic levodopa was attempted by iontophoresis and ion-exchange fiber. Ion-exchange kinetics and transdermal permeation of a cationic (presumably more stable) model drug, metaraminol, were compared to the corresponding data of levodopa. Levodopa was rapidly oxidized in the presence of water, especially at basic pH-values. At acidic pH-values the stability was improved significantly. Ion-exchange group and the pH had a clear effect on the release of both the levodopa and metaraminol from the ion-exchange fiber. The adsorption/release kinetics of metaraminol were more easily controllable than the corresponding rate and extent of levodopa adsorption/release. Iontophoretic enhancement of drug permeation across the skin was clearly more significant with the positively charged metaraminol than with the zwitterionic levodopa. Ion-exchange fibers provide a promising alternative to control drug delivery and to store drugs that are degraded easily.
Kankkunen
Tarja
T
Department of Pharmacy, Pharmaceutical Technology Division and Viikki Drug Discovery Technology Center, University of Helsinki, PO Box 56, 00014, Helsinki, Finland. tarja.jaskari@helsinki.fi
Huupponen
Inkeri
I
Lahtinen
Katri
K
Sundell
Mats
M
Ekman
Kenneth
K
Kontturi
Kyösti
K
Hirvonen
Jouni
J
D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007475:Ion Exchange Resins; D007478:Iontophoresis; D007980:Levodopa / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008680:Metaraminol / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D010084:Oxidation-Reduction; D012869:Skin Absorption
D003692:Delayed-Action Preparations; D007475:Ion Exchange Resins; D007980:Levodopa; D008680:Metaraminol