Dissolution behavior of a poorly water soluble compound in the presence of Tween 80
Dissolution behavior of a poorly water soluble compound in the presence of Tween 80
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DOI：
10.1023/a:1023493821302
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发表时间：
2003-05-01
影响因子：
3.7
通讯作者：
Babu, SR
中科院分区：
文献类型：
--
作者：
Chen, LR;Wesley, JA;Babu, SR
目的。研究吐温 80 阻碍 CI-1041（一种游离形式的难溶于水的化合物）溶解的机制。方法。对 CI-1041 在 0.1 N HCl 和不同浓度的 Tween 80 中的散装粉末和固有溶出度 (ID) 进行了分析。对溶解实验的残留固体进行了表征。测定了吐温 80 在 0.1 N HCl 中的表面张力和临界胶束浓度 (CMC)。结果。 CI-1041 在 0.1 N HCl 中经历溶剂介导转化为其氯化物盐 (CS)。 CI-1041 颗粒表面的 CS 涂层可将 ID 率降低 20 至 30 倍。当0.1 N HCl中的Tween 80浓度低于0.5 mg/ml时，CS形成速率随着Tween 80浓度的增加而增加。 0.1 N HCl 中的吐温 80 浓度高于 0.5 mg/ml 时，观察到相反的趋势。 0.5 mg/ml Tween 80 的趋势变化与 Tween 80 在 0.1 N HCL 中的 CMC 大致一致。结论。作者提出了由 Tween 80 介导的以下机制。在 CMC 以下，添加 Tween 80 导致的表面张力降低，增加了不溶性 CS 的成核速率，导致在 CI-1041 游离形式的表面上形成 CS。这反过来又通过减少化合物释放到溶液中来降低溶解速率。在 CMC 之上，表面张力降低对 CS 成核及其形成的影响可能会被其他因素抵消，例如粘度增加或表面活性剂在晶体表面上的吸附。
Purpose. To investigate the mechanism by which Tween 80 impedes the dissolution of CI-1041, a poorly water-soluble compound in its free form.Methods. Bulk powder and intrinsic dissolution (ID) of CI-1041 in 0.1 N HCl with various concentrations of Tween 80 were conducted. The residual solids of the dissolution experiments were characterized. The surface tension and the critical micellar concentration (CMC) of Tween 80 in 0.1 N HCl were determined.Results. CI-1041 underwent solvent mediated conversion to its chloride salt (CS) in 0.1 N HCl. The coating of the CS on the surface of the CI-1041 pellet decreased the ID rate 20 to 30 fold. When the Tween 80 concentration in 0.1 N HCl was below 0.5 mg/ml, the CS formation rate increased with increasing Tween 80 concentration. Above 0.5 mg/ml of Tween 80 in 0.1 N HCl, opposite trend was observed. The change in trend at 0.5 mg/ml Tween 80 coincided approximately with the CMC of Tween 80 in 0.1 N HCL.Conclusions. The authors propose the following mechanism mediated by Tween 80. Below CMC, reduced surface tension caused by addition of Tween 80 increases the rate of nucleation of insoluble CS, causing the formation of CS on the surface of the CI-1041 free form. This, in turn, decreases the dissolution rate by decreasing the release of compound into solution. Above CMC, the effect of reduced surface tension on the CS nucleation and therefore its formation may be negated by other factors, such as an increase in viscosity or adsorption of surfactant on the crystal surface.