Iontophoretic R-apomorphine delivery in combination with surfactant pretreatment: in vitro validation studies.
To validate the efficacy and controllability of a newly developed transdermal delivery system for R-apomorphine in combination with the surfactant pretreatment, iontophoresis was performed in three-chamber continuous-flow-through diffusion cells in vitro. The transdermal iontophoretic transport of R-apomorphine was examined with both human SC and freshly dermatomed human skin, at room temperature and at 32 degrees C. Furthermore, the relationship between current density and iontophoretic flux was investigated. By increasing the temperature from 22 to 32 degrees C, the iontophoretic transport rate of R-apomorphine in human SC was increased 1.9-fold. Also the iontophoretic flux increased linearly with the increase in the current density from 100 to 500 microA/cm(2). When using dermatomed human skin instead of SC, the iontophoretic flux at a current density of 500 microA/cm(2) was decreased from 362+/-45 to 259+/-30 nmol/cm(2)h, and the corresponding lag time was prolonged from 0.8 to 2.8h. In conclusion, the combination of non-occlusive pretreatment with the surfactant formulation and iontophoresis has shown to substantially increase the transdermal transport rate of R-apomorphine. A linear relationship between current density and R-apomorphine flux indicates that the iontophoretic delivery combined with surfactant pretreatment allows a controlled and individualised administration of R-apomorphine.
Li
Gai Ling
GL
Department of Pharmaceutical Technology, Leiden Amsterdam Centre for Drug Research, University of Leiden, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
Grossklaus
Arne
A
Danhof
Meindert
M
Bouwstra
Joke A
JA
D001058:Apomorphine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics
D004338:Drug Combinations; D013501:Surface-Active Agents; D001058:Apomorphine