The doctoral dissertations of the former Helsinki University of Technology (TKK) and Aalto University Schools of Technology (CHEM, ELEC, ENG, SCI) published in electronic format are available in the electronic publications archive of Aalto University - Aaltodoc.

The Use of Ion-Exchange Fibers in Controlled Transdermal Iontophoretic Drug Delivery

Marja Vuorio

Dissertation for the degree of Doctor of Science in Technology to be presented with due permission of the Department of Chemical Technology for public examination and debate in Auditorium KE 2 (Komppa Auditorium) at Helsinki University of Technology (Espoo, Finland) on the 9th of October, 2004, at 12 o'clock noon.

Overview in PDF format (ISBN 951-22-7262-8)   [206 KB]
Dissertation is also available in print (ISBN 951-22-7261-X)


Transdermal iontophoresis is a method where the movement of ionic drugs (and sometimes also neutral drug molecules) across skin is enhanced using an externally applied potential difference. Iontophoretic devices contain three distinct components; 1) the drug reservoir which contains one electrode, the polarity chosen depends on the charge of the drug, 2) the return electrode and 3) the electronic controller. In this study ion-exchange fibers were investigated as a drug reservoir material for iontophoretic device.

The parameters affecting the drug release from the ion-exchange fibers without applied current were studied experimentally and theoretically modeled using five model drugs and four different ion-exchange fibers. It was found that lipophilic drugs were retained more strongly and for longer in the fibers than hydrophilic drugs. The hydrophilic drugs were also released more readily from fibers containing strong ion-exchange groups, whereas the lipophilic drugs attached more strongly to strong ion-exchange groups and released more easily from the weak ion-exchange groups. The salt concentration and the choice of the salt also had an effect; when using equimolar amounts of sodium chloride at lower salt concentrations, more drug was released. Incorporation of calcium chloride in the bathing solution increased considerably both the drug release rate and the total amount of drug released when compared to sodium chloride alone.

The drug release from the fibers were studied in vitro and in vivo using iontophoresis. Due to significantly different release properties, tacrine and metoprolol were chosen for screening of their suitability for this kind of iontophoretic system, using an in-house designed in vitro cell. It was found that the rate of tacrine release from the device could be controlled by adjusting the salt concentration and the current density used but the rate of metoprolol release could not be controlled this way. A semi-quantitative and pragmatic interpretation of the results also showed that it should be possible to manufacture a transdermal iontophoretic patch to delivery tacrine. It was also determined in vivo that clinically relevant plasma concentrations of tacrine could be achieved in a human volunteer using an in-house designed and manufactured iontophoretic transdermal drug delivery patch.

This thesis consists of an overview and of the following 5 publications:

  1. Jaskari Tarja, Vuorio Marja, Kontturi Kyösti, Urtti Arto, Manzanares José A. and Hirvonen Jouni, 2000. Controlled transdermal iontophoresis by ion-exchange fiber. Journal of Controlled Release 67, numbers 2-3, pages 179-190. © 2000 Elsevier Science. By permission.
  2. Jaskari Tarja, Vuorio Marja, Kontturi Kyösti, Manzanares José A. and Hirvonen Jouni, 2001. Ion-exchange fibers and drugs: an equilibrium study. Journal of Controlled Release 70, numbers 1-2, pages 219-229. © 2001 Elsevier Science. By permission.
  3. Kankkunen Tarja, Sulkava Raimo, Vuorio Marja, Kontturi Kyösti and Hirvonen Jouni, 2002. Transdermal iontophoresis of tacrine in vivo. Pharmaceutical Research 19, number 5, pages 705-708.
  4. Vuorio Marja, Manzanares José A., Murtomäki Lasse, Hirvonen Jouni, Kankkunen Tarja and Kontturi Kyösti, 2003. Ion-exchange fibers and drugs: a transient study. Journal of Controlled Release 91, number 3, pages 439-448. © 2003 Elsevier Science. By permission.
  5. Vuorio Marja, Murtomäki Lasse, Hirvonen Jouni and Kontturi Kyösti, 2004. Ion-exchange fibers and drugs: a novel device for the screening of iontophoretic systems. Journal of Controlled Release 97, number 3, pages 485-492. © 2004 Elsevier Science. By permission.

Keywords: controlled release, ion-exchange, iontophoresis, ion-exchange fibers

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© 2004 Helsinki University of Technology

Last update 2011-05-26