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.
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
Tarja
T
Kankkunen
Inkeri
I
Huupponen
Katri
K
Lahtinen
Mats
M
Sundell
Kenneth
K
Ekman
Kyösti
K
Kontturi
Jouni
J
Hirvonen
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