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Iontophoretic delivery of selected antiparkinsonian agents in vitro

Tomasz Giller ,  Maria B. Delgado-Charro 

University of Bath, Claverton Down, Bath 27AY, United Kingdom


An efficient pharmacological treatment of Parkinson’s disease remains a still unsolved problem. The specificity of the disease enforces frequent dose adjustment and employment of complex dose regimes. Oral antiparkinsonian drugs suffer from a marked first pass effect, and a variable absorption in the gastrointestinal tract. In this work we show that the transdermal route can be an advantageous alternative to the standard oral treatment.

Transdermal iontophoretic delivery of six drugs: pramipexole (PMP), piribedil (PIR), selegiline (SEL), trihexyphenidyl (THP), entacapone (ETC) and pergolide (PER) was performed, using side-by-side diffusion cells. Dermatomed pig skin, and human full-thickness skin were employed as membrane models. Samples of receptor solution were analyzed for the drug and electro-osmotic marker content, via HPLC and LCMS. The influence of formulation parameters on the transdermal drug flux was studied. Namely, the effects of: donor solution pH; donor drug concentration in both, single-ion and co-ion situation; current intensity, drug ionization; and electroosmosis were investigated. Also, the water mobility of ionized drugs and their octanol-water distribution coefficient was measured.

Iontophoresis significantly enhanced the transport of all the drugs, with respect to passive diffusion. Iontophoretic fluxes were proportional to the intensity of the current applied for all the substances examined. This confirms that iontophoresis could allow easy dose individualization. Single-ion fluxes were independent of the drug molar concentration for all the drugs. Drug fluxes dropped markedly with the pH; this was probably due to the increased competition offered by the very mobile hydrogen ions (H+), and reduced skin cation permselectivity. Iontophoretic fluxes usually decreased as competing co-ions were introduced in the donor. However, two distinct behaviours were observed: for one group of drugs fluxes and transport numbers were linearly proportional to mole fraction; while for the other group, only the initial raise in mole fraction resulted in increasing flux. Iontophoretic fluxes took longer to stabilize across full thickness human skin, and were lower than across dermatome pig skin.

Briefly, the best candidates for iontophoretic delivery were pramipexole, selegiline, and piribedil. Trihexyphenidyl, entacapone and pergolide are poor candidates and probably would require patches of impractical size.


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Related papers

Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Tomasz Giller
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-04-06 23:27
Revised:   2010-04-06 23:27