title: Transdermal iontophoresis of rotigotine: influence of concentration, temperature and current density in human skin in vitro.
abstract: Iontophoretic transport of rotigotine across human stratum corneum (HSC) was studied in vitro in side by side diffusion cells according to the following protocol: 6 h of passive diffusion, 9 h of iontophoresis followed by 5 h of passive diffusion. A current density of 0.5 mA cm(-2) was applied. The parameters studied were the influence of the rotigotine concentration in donor phase and the influence of the molecular weight of the co-ions. To this end, Na(+) was replaced by tetra ethyl ammonium (TEA(+)) or tetra butyl ammonium (TBA(+)) (both at pH 5 and 6). In addition, the influence of the acceptor phase temperature (32 degrees C versus room temperature), the replacement of HSC by dermatomed human skin (DHS), and the relation between drug transport and current density were examined. The estimated steady-state flux (Flux(ss)) gradually increased with the drug concentration in the donor phase in a linear manner. The flux was also linearly correlated with the applied current density providing a convenient approach to individual dose titration. The use of TEA(+) as co-ion increased the rotigotine iontophoretic flux significantly, while TBA(+) did not. Replacing HSC by DHS reduced the iontophoretic rotigotine transport, while an increase in temperature to 32 degrees C increased the rotigotine flux. The maximum Flux(ss) achieved was around 80 nmol cm(-2) h(-1) indicating that by means of iontophoresis, a therapeutic level of rotigotine might be achieved with a reasonable patch size.
authors.affiliation: Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, University of Leiden, P.O. Box 9502, Einsteinweg 55, 2300 RA Leiden, The Netherlands.
authors.forename: Akhmad Kharis
authors.initials: AK
authors.lastname: Nugroho
authors.forename: Gailing
authors.initials: G
authors.lastname: Li
authors.forename: Arne
authors.initials: A
authors.lastname: Grossklaus
authors.forename: Meindert
authors.initials: M
authors.lastname: Danhof
authors.forename: Joke A
authors.initials: JA
authors.lastname: Bouwstra
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods*; D008875:Middle Aged; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D013696:Temperature; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine