PURPOSE: 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.
PURPOSE: 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.
Authors: Gai Ling Li; Ronald van der Geest; Laurence Chanet; Elske van Zanten; Meindert Danhof; Joke A Bouwstra Journal: J Control Release Date: 2002-11-07 Impact factor: 9.776