de Smidt J H, Offringa J C, Crommelin D J
Department of Pharmaceutics, Faculty of Pharmacy, Utrecht University, The Netherlands.
J Pharm Sci. 1991 Apr;80(4):399-401. doi: 10.1002/jps.2600800424.
Bile salts increase the apparent solubility of lipophilic poorly water-soluble drugs like griseofulvin. In this study, the dissolution kinetics of griseofulvin in solutions of bile salts (sodium taurocholate and sodium cholate) were investigated. A rotating disk apparatus was chosen to monitor dissolution kinetics; it well-defined hydrodynamic conditions allowed for analysis of the behavior of bile salt micelles under different conditions. Griseofulvin solubility and dissolution rate increased with increasing bile salt concentration in the dissolution medium. The enhancement of the dissolution rate was not linearly related to the solubility increase, as diffusional transport of the solubilized drug proved to be less efficient than transport of the unsolubilized ("free") drug. The dissolution process proved to be controlled by convective diffusion. An analysis of the data with the phase separation model provided results for the micellar diffusion coefficient comparable with literature data obtained with different techniques.
胆盐可增加亲脂性、水溶性差的药物(如灰黄霉素)的表观溶解度。在本研究中,对灰黄霉素在胆盐(牛磺胆酸钠和胆酸钠)溶液中的溶解动力学进行了研究。选用旋转圆盘装置监测溶解动力学;其明确的流体动力学条件有助于分析不同条件下胆盐胶束的行为。在溶解介质中,灰黄霉素的溶解度和溶解速率随胆盐浓度的增加而增加。溶解速率的提高与溶解度的增加并非线性相关,因为已增溶药物的扩散传输效率低于未增溶(“游离”)药物的传输效率。结果表明,溶解过程受对流扩散控制。用相分离模型对数据进行分析,得到的胶束扩散系数结果与用不同技术获得的文献数据相当。