Transdermal iontophoresis of rotigotine: influence of concentration, temperature and current density in human skin in vitro.
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.
Nugroho
Akhmad Kharis
AK
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.
Li
Gailing
G
Grossklaus
Arne
A
Danhof
Meindert
M
Bouwstra
Joke A
JA
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*
D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine