Pikal M J, Shah S
Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana 46285.
Pharm Res. 1991 Mar;8(3):365-9. doi: 10.1023/a:1015801817259.
Enhanced iontophoretic transport using pulsed DC is usually explained by citing the observed decrease in skin resistance caused by an increase in AC pulse frequency at very small currents. Alternately, it has been suggested that the "on-to-off" nature of pulsed DC imparts an "impact energy" to the fluid, thereby increasing transport. This report provides a test of these mechanisms for enhanced delivery via pulsed iontophoresis. The DC resistance of hairless mouse skin during continuous and pulsed DC iontophoresis is measured as a function of time for selected pulse frequencies and duty cycles using current densities ranging from 0.1 to 1.0 mA/cm2. As a test of the impact energy mechanism, the iontophoretic transport of 14C-glucose measured with pulsed DC is compared with similar data obtained previously using continuous DC. It is suggested that pulsed current can yield lower resistance and enhanced drug delivery provided that (a) the "steady-state" current during the "on" phase of the pulse is very small and (b) the frequency is low enough to allow depolarization of the skin during the "off" phase of the pulse. The glucose transport results suggest that the "impact energy" concept does not apply to iontophoresis.
使用脉冲直流电增强离子电渗转运通常是通过引用在非常小的电流下交流脉冲频率增加导致皮肤电阻下降来解释的。另外，有人提出脉冲直流电的“开-关”性质会给流体赋予“冲击能量”，从而增加转运。本报告对这些通过脉冲离子电渗法增强递送的机制进行了测试。使用0.1至1.0 mA/cm²的电流密度，针对选定的脉冲频率和占空比，测量无毛小鼠皮肤在连续和脉冲直流电离子电渗过程中的直流电阻随时间的变化。作为对冲击能量机制的测试，将用脉冲直流电测量的¹⁴C-葡萄糖的离子电渗转运与先前使用连续直流电获得的类似数据进行比较。结果表明，只要（a）脉冲“开启”阶段的“稳态”电流非常小，且（b）频率足够低，以便在脉冲“关闭”阶段皮肤能够去极化，脉冲电流就能产生更低的电阻并增强药物递送。葡萄糖转运结果表明“冲击能量”概念不适用于离子电渗法。
