Kemken J, Ziegler A, Müller B W
Department of Pharmaceutics and Biopharmaceutics, Christian-Albrecht-University, Kiel, FRG.
Pharm Res. 1992 Apr;9(4):554-8. doi: 10.1023/a:1015856800653.
Transdermal absorption of drugs is limited by the stratum corneum, which serves as a diffusion barrier. This barrier might be overcome by enhancing the thermodynamic activity of the drug vehicle. Thermodynamic activity is particularly high in supersaturated systems because it is directly correlated with the degree of saturation. Since supersaturated systems are not stable, they were formed in situ by application of water-free microemulsion bases. These water-free microemulsion bases saturated with the drug were applied to New Zealand albino rabbits with an occlusive patch. Occlusion leads to water uptake from the skin due to hydratation and changes the microemulsion base into a microemulsion. The microemulsion will become supersaturated as a result of decreasing solubility of the drug with increasing water content. The pharmacodynamic effect of the model drug bupranolol in vivo was investigated over a 10-hr time period. The in vitro solubility of bupranolol was examined with respect to the water content. The solubility vs water content curves were compared to the effect vs time curves. The microemulsions and their individual components were studied, and the effect vs time curves were inversely correlated with the solubility vs water content curves.
药物的经皮吸收受角质层限制，角质层起着扩散屏障的作用。可通过提高药物载体的热力学活性来克服这一屏障。在过饱和系统中，热力学活性特别高，因为它与饱和度直接相关。由于过饱和系统不稳定，所以通过应用无水微乳基质原位形成过饱和系统。将用药物饱和的这些无水微乳基质用封闭贴剂应用于新西兰白化兔。封闭会因水合作用导致皮肤吸水，并使微乳基质转变为微乳。随着含水量增加药物溶解度降低，微乳将变得过饱和。在10小时时间段内研究了模型药物布普洛尔在体内的药效学作用。考察了布普洛尔相对于含水量的体外溶解度。将溶解度与含水量曲线与效应与时间曲线进行比较。对微乳及其各个组分进行了研究，效应与时间曲线与溶解度与含水量曲线呈负相关。
