Patel R A, Vasavada R C
School of Pharmacy, University of the Pacific, Stockton, California 95211.
Pharm Res. 1988 Feb;5(2):116-9. doi: 10.1023/a:1015996319406.
Effects of solubility, partition coefficient, and selected adjuvants (propylene glycol and Azone) on percutaneous penetration of isoproterenol HCl have been investigated using human cadaver skin. Isoproterenol was found to be stable (less than 1% decomposition) for 24 hr at 22 +/- 0.5 degrees C in the pH range 1 to 7 in the following solvents: water, normal saline, propylene glycol and a series of propylene glycol-water mixtures (10, 20, 40, and 60%; v/v); however, decomposition was significant beyond pH 8. In normal saline, the rate of decomposition increased significantly with an increase in temperature to 37 degrees C. The solubility of isoproterenol HCl decreased and its skin/vehicle partition coefficient increased with increasing proportions of propylene glycol in the vehicle, while the product of the solubility and partition coefficient appeared to plateau at 20% propylene glycol in water. Optimal penetration enhancing effects of Azone were seen when incorporated at a concentration of 1% (v/v) in the 20% (v/v) propylene glycol-water blend and, more significantly, when skin was pretreated with pure Azone for 60 min prior to application of the drug formulation.
使用人体尸体皮肤研究了溶解度、分配系数以及选定的佐剂（丙二醇和氮酮）对盐酸异丙肾上腺素经皮渗透的影响。发现盐酸异丙肾上腺素在22±0.5℃下于pH值1至7的以下溶剂中24小时内稳定（分解小于1%）：水、生理盐水、丙二醇以及一系列丙二醇-水混合物（10%、20%、40%和60%；v/v）；然而，在pH值大于8时分解显著。在生理盐水中，随着温度升高至37℃，分解速率显著增加。随着载体中丙二醇比例的增加，盐酸异丙肾上腺素的溶解度降低，其皮肤/载体分配系数增加，而溶解度和分配系数的乘积在水中丙二醇含量为20%时似乎达到平稳状态。当氮酮以1%（v/v）的浓度加入20%（v/v）的丙二醇-水混合物中时，观察到最佳的渗透增强效果，更显著的是，在施用药物制剂之前先用纯氮酮对皮肤预处理60分钟时。
