a College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences , St. John's University , Queens , NY , USA.
b Celgene Corporation , Summit , NJ , USA.
Drug Dev Ind Pharm. 2018 Jun;44(6):895-901. doi: 10.1080/03639045.2017.1419365. Epub 2017 Dec 26.
The objective of the study was to develop a self-microemulsifying drug delivery system (SMEDDS), also known as microemulsion preconcentrate, for oral delivery of five poorly water-soluble nutraceuticals or bioactive agents, namely, vitamin A, vitamin K2, coenzyme Q, quercetin and trans-resveratrol. The SMEDDS contained a 1:1 mixture (w/w) of Capmul MCM NF (a medium chain monoglyceride) and Captex 355 EP/NF (a medium chain triglyceride) as the hydrophobic lipid and Tween 80 (polysorbate 80) as the hydrophilic surfactant. The lipid and surfactant were mixed at 50:50 w/w ratio. All three of the SMEDDS components have GRAS or safe food additive status. The solubility of nutraceuticals was determined in Capmul MCM, Captex 355, Tween 80, and the SMEDDS (microemulsion preconcentrate mixture). The solubility values of vitamin A palmitate, vitamin K2, coenzyme Q, quercetin, and trans-resveratrol per g of SMEDDS were, respectively, 500, 12, 8, 56, and 87 mg. Appropriate formulations of nutraceuticals were prepared and filled into hard gelatin capsules. They were then subjected to in vitro dispersion testing using 250 mL of 0.01 N HCl in USP dissolution apparatus II. The dispersion test showed that all SMEDDS containing nutraceuticals dispersed spontaneously to form microemulsions after disintegration of capsule shells with globule size in the range of 25 to 200 nm. From all formulations, except that of vitamin K2, >80-90% nutraceuticals dispersed in 5-10 min and there was no precipitation of compounds during the test period of 120 min. Some variation in dispersion of vitamin K2 was observed due to the nature of the material used (vitamin K2 pre-adsorbed onto calcium phosphate). The present report provides a simple and organic cosolvent-free lipid-based SMEDDS for the oral delivery of poorly water-soluble nutraceuticals. Although a 50:50 w/w mixture of lipid to surfactant was used, the lipid content may be increased to 70:30 without compromising the formation of microemulsion.
本研究的目的是开发一种自微乳药物传递系统（SMEDDS），也称为微乳预浓缩物，用于口服递送五种疏水性营养物或生物活性药物，即维生素 A、维生素 K2、辅酶 Q、槲皮素和反式白藜芦醇。SMEDDS 含有 Capmul MCM NF（中链单甘油酯）和 Captex 355 EP/NF（中链甘油三酯）的 1:1 混合物（w/w）作为疏水性脂质和 Tween 80（聚山梨酯 80）作为亲水性表面活性剂。脂质和表面活性剂以 50:50w/w 的比例混合。所有三种 SMEDDS 成分均具有 GRAS 或安全食品添加剂状态。在 Capmul MCM、Captex 355、Tween 80 和 SMEDDS（微乳预浓缩物混合物）中测定营养物的溶解度。每克 SMEDDS 中维生素 A 棕榈酸酯、维生素 K2、辅酶 Q、槲皮素和反式白藜芦醇的溶解度分别为 500、12、8、56 和 87mg。制备了适当的营养物配方并填充到硬明胶胶囊中。然后，将它们在 USP 溶解仪 II 中的 250mL0.01N HCl 中进行体外分散测试。分散测试表明，所有含有营养物的 SMEDDS 在胶囊壳崩解后均自发分散形成微乳液，液滴大小在 25 至 200nm 范围内。除了维生素 K2 之外，所有配方在 5-10 分钟内分散了>80-90%的营养物，并且在 120 分钟的测试期间没有化合物沉淀。由于所用材料的性质（维生素 K2 预先吸附在磷酸钙上），观察到维生素 K2 分散的一些变化。本报告提供了一种简单的、无有机共溶剂的基于脂质的 SMEDDS，用于口服递送疏水性营养物。尽管使用了 50:50w/w 的脂质与表面活性剂混合物，但可以将脂质含量增加到 70:30，而不会影响微乳液的形成。
