离子导入与促渗剂对双氯芬酸钠凝胶经皮吸收的影响

Transdermal delivery of diclofenac sodium gel after iontophoresis

目的 :考察离子导入和经皮渗透促渗剂月桂氮酮对双氯芬酸钠凝胶经皮吸收的促渗透作用。方法 :以聚乙烯醇、羧甲基纤维素钠、羟丙基甲基纤维素等高分子材料制备双氯芬酸钠凝胶 ,通过家兔在体被动扩散、月桂氮酮预处理、离子导入、月桂氮酮预处理加离子导入 4种方法 ,考察其血药浓度变化 ,并用扫描电镜观察不同处理对皮肤的影响。结果 :双氯芬酸钠凝胶在家兔体内被动扩散其血药浓度无法测得 ,月桂氮酮预处理后血药浓度时间曲线下面积 (0 h～ 7h)是 8.4μg· ml- 1 · h- 1 ,而离子导入、月桂氮酮预处理加离子导入后双氯芬酸钠血药浓度时间曲线下面积分别为 2 .7和 15 .4μg· ml- 1 · h- 1 。扫描电镜结果显示 ,电场及月桂氮酮对皮肤角质层并未引起明显的损伤。结论 :双氯芬酸钠凝胶家兔在体实验结果表明 ,月桂氮酮预处理和离子导入对促进双氯芬酸钠的经皮渗透有协同作用 。

Objective: To observe the in vivo effect of combined iontophoresis and laurocapram pretreatment on transdermal delivery of diclofenac sodium gel. Methods: Diclofenac sodium gel was prepared using polyvinyl alcohol, carboxymethylcellulose sodium and hydroxypropylmethyl cellulose. The diclofenac blood level in rabbits was measured in four groups: passive diffusion, laurocapram pretreatment, iontophoresis (current density controlled at 0.3 mA/cm 2) and combined laurocapram pretreatment and iontophoresis. Rabbit stratum corneum of each of the four groups was examined using a scanning electron microscope. Results: Diclofenac blood concentration in the passive diffusion group was undetectable. The diclofenac blood concentration area under the curve vs. time was 8.4 μl·ml -1 ·h -1 in the laurocapram pretreatment group, 2.7 μl·ml -1 ·h -1 in the iontophoresis group and 15.4 μl·ml -1 ·h -1 in the combination group. There was no detectable damage observed by scanning electron mic roscopy to the stratum corneum after iontophoresis or laurocapram pretreatment. Conclusion: The combination of iontophoresis and laurocapram pretreatment appears to enhance transdermal delivery of diclofenac sodium gel wi thout significant skin damage.