Hirvonen J, Rytting J H, Paronen P, Urtti A
Department of Pharmaceutical Technology, University of Kuopio, Finland.
Pharm Res. 1991 Jul;8(7):933-7. doi: 10.1023/a:1015824100788.
The effectiveness of the penetration enhancers, dodecyl N,N-dimethylamino acetate (DDAA) and Azone, on pretreated human epidermis for the permeation of model drugs, indomethacin, 5-fluorouracil, and propranolol-HCl, was studied in in vitro diffusion cells. Snakeskin (Elaphe obsoleta) and rabbit pinna skin were compared as possible models for human skin. The drug concentrations were analyzed by HPLC. With all skins and all model drugs, DDAA increased drug permeability at least as well as Azone, and in most cases it was a more effective permeation enhancer. The relative permeation improvements in human skin, snakeskin, and rabbit skin were 10- to 20-, 5- to 50-, and 20- to 120-fold, respectively. Tritiated water served as an indicator of skin condition. Its penetration in the skin samples was independent of the drugs used, and both penetration enhancers significantly increased the flux of tritiated water through all skins. Thus, DDAA and Azone significantly increased the permeation of lipophilic and hydrophilic model compounds. Rabbit pinna skin was a poor model for human skin in vitro, while snakeskin was much closer to human skin in terms of transdermal permeability. In most cases drug permeability decreased in the order rabbit much greater than human greater than or less than snake.
在体外扩散池中，研究了渗透促进剂十二烷基N，N - 二甲基氨基乙酸酯（DDAA）和氮酮对预处理过的人表皮中模型药物吲哚美辛、5 - 氟尿嘧啶和盐酸普萘洛尔渗透的有效性。比较了蛇皮（王锦蛇）和兔耳廓皮肤作为人皮肤的可能模型。通过高效液相色谱法分析药物浓度。对于所有皮肤和所有模型药物，DDAA至少与氮酮一样能提高药物渗透性，并且在大多数情况下它是一种更有效的渗透促进剂。在人皮肤、蛇皮和兔皮中相对渗透改善分别为10至20倍、5至50倍和20至120倍。氚标记水用作皮肤状况的指标。其在皮肤样品中的渗透与所用药物无关，并且两种渗透促进剂均显著增加了氚标记水通过所有皮肤的通量。因此，DDAA和氮酮显著增加了亲脂性和亲水性模型化合物的渗透。兔耳廓皮肤在体外是人皮肤的较差模型，而蛇皮在透皮渗透性方面更接近人皮肤。在大多数情况下，药物渗透性按兔皮远大于人皮大于或小于蛇皮的顺序降低。
