Pretreatment with a water-based surfactant formulation affects transdermal iontophoretic delivery of R-apomorphine in vitro.
OBJECTIVE
To further increase the transdermal transport rate of R-apomorphine, a nonocclusive pretreatment with an aqueous surfactant formulation in combination with iontophoresis was explored in vitro.


METHODS
The human stratum corneum was pretreated nonocclusively with formulations composed of laureth-3 oxyethylene ether (C12EO3), laureth-7 oxyethylene ether (C12EO7), and cholesterol sulfate (CSO4) prior to iontophoresis. The effect on the flux of the following parameters was examined: the composition, the charge, and the applied amount of surfactant formulations.


RESULTS
The iontophoretic flux of R-apomorphine was appreciably increased by pretreatment with surfactant formulations. A formulation containing C12EO3/C12EO7/CSO4 at a molar ratio of 70:30:5 was very stable and increased the iontophoretic flux of R-apomorphine from 92.2 +/- 13.9 nmol/cm2 x h to 181.5 +/- 22.6 nmol/cm2 x h. When further increasing the negative charge of this formulation the iontophoretic transport rate was slightly inhibited. A dose of 40 microL/cm2 of the formulation with a total surfactant concentration of 5% (w/w) was sufficient for a maximum enhancing effect.


CONCLUSIONS
The results obviously show that nonocclusive pretreatment with the surfactant formulation enhances the iontophoretic transport of R-apomorphine, and is a promising approach to achieve therapeutic concentrations of R-apomorphine.
Department of Pharmaceutical Technology, Leiden Amsterdam Centre for Drug Research, University of Leiden, PO Box 9502, 2300 RA, Leiden, The Netherlands.
Gai Ling
GL
Li
Meindert
M
Danhof
Peter M
PM
Frederik
Joke A
JA
Bouwstra
D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D001058:Apomorphine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods*; D010300:Parkinson Disease / Q000188:drug therapy*; D019999:Pharmaceutical Solutions / Q000493:pharmacokinetics; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D013501:Surface-Active Agents / Q000737:chemistry / Q000493:pharmacokinetics*
D000277:Adjuvants, Pharmaceutic; D003692:Delayed-Action Preparations; D019999:Pharmaceutical Solutions; D013501:Surface-Active Agents; D000077423:Polidocanol; D011092:Polyethylene Glycols; D001058:Apomorphine