薄荷醇和氮酮对甲硝唑在犬中体外透皮吸收的影响

Effect of menthol and Azone with on the transdermal delivery of metronidazole through the canine skin in vitro

关键词:  甲硝唑  薄荷醇  氮酮  透皮吸收  皮内摄取

Key words:  metronidazole  menthol  Azone  percutaneous absorption  cutaneous depots

摘要:

取下北京犬胸腰背部皮肤，-20℃保存。使用时，皮肤解冻固定在Franz透皮扩散仪上，保持恒速(200±1)r/min，恒温(35±0.5)℃。在扩散池中的皮肤角质层上加入2mL溶液载体含甲硝唑58.4μmol，以20%乙醇为溶剂，在预定时间点，取样1mL,采用HPLC方法测定各接受液中的药物量，透皮实验结束后，取下皮肤，测定皮肤中摄取的药物量。试验结果显示：与对照Ⅱ组相比，不同浓度的薄荷醇和氮酮对甲硝唑都有促渗作用，随着浓度的增加，其促渗作用也相应增加，5％氮酮促渗作用最明显(P<0.01)。对照Ⅱ组的促渗效果与对照Ⅰ相比差异显著(P<0.01)。此外，甲硝唑的透过量越大，皮内摄取量也大。说明，5%氮酮与20%乙醇联合使用，可作为甲硝唑局部和透皮吸收制剂的溶液载体。

Abstract:

Skin was harvested from the dorsal thoracolumbar region of female Pekingese after euthanasia and stored at -20℃ until required. The skin was defrosted and placed in the Franz-type diffusion cells. The stirring rate was maintained at (200±1)r/min and temperature was maintained at (35±0.5)℃. 2mL of donor solutions that contained 58.4μmol metronidazole in each formulation were applied to the stratum corneum (SC) surface of each skin sample with 20% ethanol to dissolve the menthol and Azone. Samples (1mL) were collected at predetermined time intervals. The diffused metronidazole in the receptor solution was quantified by using high performance liquid chromatography (HPLC). At the end of permeation experiment, the retained amount of metronidazole in the skin was also analyzed by HPLC. The results indicated that metronidazole permeation through canine skin was enhanced by different penetration enhancers in comparison with controlⅡ (P<0.01). The efficiency of the formulation to improve the transdermal delivery of metronidazole was concentration-dependent. 5% Azone significantly increased the flux of metronidazole (P<0.01). There was statistical difference controlⅡ and controlⅠ(P<0.01). The amount of metronidazole present in the skin increased as metronidazole percutaneous absorption increased. The present study suggests that 5% Azone with 20% ethanol may be used as potential vehicle for topical and transdermal delivery of metronidazole through canine skin.