Ke Wen-Ting, Lin Shyr-Yi, Ho Hsiu-O, Sheu Ming-Thau
Graduate Institute of Pharmaceutical Sciences, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC.
J Control Release. 2005 Feb 2;102(2):489-507. doi: 10.1016/j.jconrel.2004.10.030.
Attempts were to develop microemulsion systems using medium chain triglyceride, deionized water, and TPGS as surfactant for the oral delivery of protein drugs or poorly water-soluble drugs. Phase diagrams were constructed to elucidate the phase behavior of systems composed of Captex 300 and water with D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) as main surfactant, polysorbates (Tween 20, Tween 40, Tween 60 and Tween 80) as adjuvant surfactants, and polyethylene glycols (PEG 400 and PEG 600) and polyols (ethanediol, 1,2-propanediol, 1,3-propanediol, 1,3-butanediol, 1,4-butanediol and glycerin) as cosurfactants. The ratios of TPGS to Tweens, PEGs or polyols (K(m)) were set at 4/1, 2/1, 1/1, 1/2, and 1/4. The phase diagram for H(2)O/Captex 300/TPGS system reveals that when TPGS was used as a sole surfactant, it is not capable of producing isotropic solutions of water and oil over a wide range of the compositions. H(2)O/Captex 300/TPGS/Tweens systems with various K(m), regardless of the adjuvant surfactant used were capable of producing an isotropic phase. The extension of microemulsion phase and the presence and extension of the gel phase were found to be dependent on the surfactant mixture. The phase diagrams of H(2)O/Captex 300/TPGS systems using polyols as cosurfactants demonstrate that the types of polyols have a slight effect on the region of existence of the microemulsions. Comparison between the isotropic regions for the polyols system reveals that as the relative concentration of polyols increase, the isotropic region decrease in size. This decrease is towards the S(mix)-water axis indicating that as the relative concentration of polyols increases the maximum amount of oil solubilized decreases. The gel region decreased in size with the increase of polyols weight ratio. All polyols do not solubilized Captex 300 without using TPGS as surfactant.
人们尝试开发以中链甘油三酯、去离子水和TPGS作为表面活性剂的微乳剂系统，用于口服递送蛋白质药物或水溶性差的药物。构建相图以阐明由Captex 300和水组成的系统的相行为，该系统以D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）作为主要表面活性剂，聚山梨酯（吐温20、吐温40、吐温60和吐温80）作为辅助表面活性剂，聚乙二醇（PEG 400和PEG 600）和多元醇（乙二醇、1,2-丙二醇、1,3-丙二醇、1,3-丁二醇、1,4-丁二醇和甘油）作为助表面活性剂。TPGS与吐温、PEG或多元醇的比例（K(m)）设定为4/1、2/1、1/1、1/2和1/4。H(2)O/Captex 300/TPGS系统的相图显示，当TPGS用作唯一表面活性剂时，它不能在很宽的组成范围内产生水和油的各向同性溶液。具有不同K(m)的H(2)O/Captex 300/TPGS/吐温系统，无论使用何种辅助表面活性剂，都能够产生各向同性相。发现微乳相的扩展以及凝胶相的存在和扩展取决于表面活性剂混合物。使用多元醇作为助表面活性剂的H(2)O/Captex 300/TPGS系统的相图表明，多元醇的类型对微乳存在区域有轻微影响。多元醇系统各向同性区域之间的比较表明，随着多元醇相对浓度的增加，各向同性区域的尺寸减小。这种减小是朝着S(mix)-水轴的方向，表明随着多元醇相对浓度的增加，增溶的油的最大量减少。凝胶区域的尺寸随着多元醇重量比的增加而减小。如果不使用TPGS作为表面活性剂，所有多元醇都不能增溶Captex 300。
