Li Gai Ling, Danhof Meindert, Frederik Peter M, Bouwstra Joke A
Department of Pharmaceutical Technology, Leiden Amsterdam Centre for Drug Research, University of Leiden, PO Box 9502, 2300 RA, Leiden, The Netherlands.
Pharm Res. 2003 Apr;20(4):653-9. doi: 10.1023/a:1023211219118.
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.
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.
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.
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.
为进一步提高R-阿扑吗啡的经皮转运速率，在体外研究了使用水性表面活性剂制剂结合离子电渗疗法进行非封闭预处理的效果。
在离子电渗疗法之前，用人角质层对由月桂醇聚醚-3（C12EO3）、月桂醇聚醚-7（C12EO7）和硫酸胆固醇（CSO4）组成的制剂进行非封闭预处理。研究了以下参数对通量的影响：表面活性剂制剂的组成、电荷和用量。
用表面活性剂制剂预处理可显著提高R-阿扑吗啡的离子电渗通量。摩尔比为70:30:5的C12EO3/C12EO7/CSO4制剂非常稳定，可使R-阿扑吗啡的离子电渗通量从92.2±13.9 nmol/cm²·h提高到181.5±22.6 nmol/cm²·h。当进一步增加该制剂的负电荷时，离子电渗转运速率略有抑制。总表面活性剂浓度为5%（w/w）的制剂剂量为40 μL/cm²时足以产生最大增强效果。
结果明显表明，用表面活性剂制剂进行非封闭预处理可增强R-阿扑吗啡的离子电渗转运，是实现R-阿扑吗啡治疗浓度的一种有前景的方法。
