Kawakami Kohsaku, Oda Naohiko, Miyoshi Kyoko, Funaki Takeshi, Ida Yasuo
Developmental Research Laboratories, Shionogi & Co. Ltd., 12-4 Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan.
Eur J Pharm Sci. 2006 May;28(1-2):7-14. doi: 10.1016/j.ejps.2005.11.012. Epub 2006 Jan 6.
The solubilization behavior of a poorly soluble model drug, phenytoin (PHT), under combined use of surfactants (sodium dodecyl sulfate (SDS), Tween 80) and cosolvents (dimethylacetoamide (DMA), ethanol, poly(ethylene glycol) 400 (PEG), glycerol) was examined. The solubility of PHT in the aqueous surfactant solutions increased linearly with increase of the surfactant concentration. The solubility of PHT in water-cosolvent mixtures roughly followed the log-linear model, which is widely accepted to explain the solubilization behavior of poorly soluble compounds in water-cosolvent mixtures, except for the case of glycerol, in which the solubility was minimal at 10% (w/v) of glycerol. When the cosolvents were added to the aqueous surfactant solutions, their effect on the solubility depended on the combination of the surfactant and the cosolvent. The most striking increase in solubility was observed with DMA, regardless of the type of surfactant. When ethanol was added, an increase in the solubility was observed with the Tween 80 solution, while a dramatic decrease was found with the SDS solution. The addition of glycerol or PEG to the surfactant solutions had only a minor impact on the solubility. These solubilization behaviors of PHT in the surfactant-cosolvent mixtures were partially explained by the solubility model introduced in our previous paper [Kawakami, K., Miyoshi, K., Ida, Y., 2004. Solubilization behavior of poorly soluble drugs with combined use of Gelucire 44/14 and cosolvent. J. Pharm. Sci. 93, 1471-1479]. Addition of the cosolvents to the surfactant solutions generally offered only a small advantage from the viewpoint of improving solubility because of the decrease in the solubilization capacity of the micelles.
考察了难溶性模型药物苯妥英（PHT）在表面活性剂（十二烷基硫酸钠（SDS）、吐温80）和助溶剂（二甲基乙酰胺（DMA）、乙醇、聚乙二醇400（PEG）、甘油）联合使用时的增溶行为。PHT在表面活性剂水溶液中的溶解度随表面活性剂浓度的增加呈线性增加。PHT在水 - 助溶剂混合物中的溶解度大致遵循对数线性模型，该模型被广泛用于解释难溶性化合物在水 - 助溶剂混合物中的增溶行为，但甘油的情况除外，在10%（w/v）甘油时溶解度最小。当将助溶剂添加到表面活性剂水溶液中时，它们对溶解度的影响取决于表面活性剂和助溶剂的组合。无论表面活性剂类型如何，DMA对溶解度的增加最为显著。添加乙醇时，吐温80溶液的溶解度增加，而SDS溶液的溶解度则显著降低。向表面活性剂溶液中添加甘油或PEG对溶解度的影响较小。PHT在表面活性剂 - 助溶剂混合物中的这些增溶行为部分地由我们之前论文[Kawakami, K., Miyoshi, K., Ida, Y., 2004. Solubilization behavior of poorly soluble drugs with combined use of Gelucire 44/14 and cosolvent. J. Pharm. Sci. 93, 1471 - 1479]中引入的溶解度模型进行了解释。从改善溶解度的角度来看，由于胶束增溶能力的降低，向表面活性剂溶液中添加助溶剂通常仅提供很小的优势。
