Bakatselou V, Oppenheim R C, Dressman J B
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Pharm Res. 1991 Dec;8(12):1461-9. doi: 10.1023/a:1015877929381.
The ability of sodium taurocholate to increase the initial dissolution rate of five steroids was studied in terms of effects on solubility, wetting, and diffusion coefficient. For all compounds, wetting effects predominated over solubilization effects at bile salt concentrations representative of the fasted state. For hydrocortisone, triamcinolone, betamethasone, and dexamethasone, this trend also continued at the higher bile salt concentrations typical of the fed state. Bile salts solubilized these compounds by a factor of two or less, and diffusivity changes were negligible at bile salt concentrations up to 30 mM. For the more lipophilic danazol, the wetting effects were small and of importance only at premicellar levels of bile salt. At higher concentrations, the increase in solubility was the predominant factor. Incorporation into micelles appeared to decrease the diffusivity slightly, but this was important only at bile salts concentrations of 15 mM or higher. In conclusion, it appears that even within a series of structurally related compounds the mechanism by which bile salts mediate increases in dissolution rate can differ considerably.
就对溶解度、润湿性和扩散系数的影响而言，研究了牛磺胆酸钠提高五种甾体药物初始溶解速率的能力。对于所有化合物，在代表禁食状态的胆汁盐浓度下，润湿性影响超过增溶作用。对于氢化可的松、曲安西龙、倍他米松和地塞米松，在代表进食状态的较高胆汁盐浓度下，这种趋势也持续存在。胆汁盐使这些化合物的溶解度增加不到两倍，在胆汁盐浓度高达30 mM时，扩散率变化可忽略不计。对于亲脂性更强的达那唑，润湿性影响较小，仅在胆汁盐的亚胶束水平时才重要。在较高浓度下，溶解度增加是主要因素。纳入胶束似乎会使扩散率略有降低，但这仅在胆汁盐浓度为15 mM或更高时才重要。总之，似乎即使在一系列结构相关的化合物中，胆汁盐介导溶解速率增加的机制也可能有很大差异。
