Goto S, Nakata K, Miyakawa T, Zhang W, Uchida T
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yakugaku Zasshi. 1991 Nov;111(11):702-8. doi: 10.1248/yakushi1947.111.11_702.
A stable water/liquid paraffin system water-in-oil-in-water (W/O/W) multiple emulsion was prepared by the two-step procedure of emulsification using a variety of nonionic emulsifying agents, such as Span 80 and Tween 20. After comparison of the releasing properties of such water soluble drugs as cefadroxil, cephradine, 4-aminoantipyrine and antipyrine which were entrapped separately in the inner aqueous phase of the W/O/W multiple emulsion, a large difference was observed. It was ascertained that the difference in these releasing properties was due to no physical rupture by the microscopic observation and the results of the release test of W/O/W multiple emulsion with two kinds of drugs entrapped simultaneously in an inner aqueous phase. This reason was presumed to be dependent on permeation in the oily phase of the drug itself. It was proved that the differences of releasing properties tended to depend on the molecular weight and were closely related to the drug concentration of outer aqueous phase of W/O/W multiple emulsion containing the drug in both aqueous phases prepared as an experimental model. Therefore, two possible mechanisms for the releasing of drugs in W/O/W multiple emulsion may be interpreted as follows: the first is that the mixed and inversed micelles formed by Span 80 and Tween 20 agents in the oily phase act as a carrier of drugs, and the second is that drug molecules diffuse through small pore existing in very thin lamella of the emulsifying agents partially formed in the oil layer owing to the fluctuation of the thickness.
采用两步乳化法，使用多种非离子乳化剂（如司盘80和吐温20）制备了稳定的水/液体石蜡体系的水包油包水（W/O/W）多重乳液。在比较头孢羟氨苄、头孢拉定、4-氨基安替比林和安替比林等水溶性药物分别包裹在W/O/W多重乳液内水相后的释放特性时，观察到了很大差异。通过显微镜观察以及同时在内部水相中包裹两种药物的W/O/W多重乳液的释放试验结果，确定这些释放特性的差异是由于没有物理破裂。推测其原因取决于药物本身在油相中的渗透。结果证明，释放特性的差异往往取决于分子量，并且与作为实验模型制备的在两个水相中都含有药物的W/O/W多重乳液外水相中的药物浓度密切相关。因此，W/O/W多重乳液中药物释放的两种可能机制可以解释如下：第一种是司盘80和吐温20试剂在油相中形成的混合反胶束充当药物载体，第二种是由于厚度波动，药物分子通过油层中部分形成的乳化剂超薄片层中存在的小孔扩散。
