Spernath Aviram, Aserin Abraham, Ziserman Lior, Danino Dganit, Garti Nissim
Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
J Control Release. 2007 Jun 22;119(3):279-90. doi: 10.1016/j.jconrel.2007.02.014. Epub 2007 Mar 1.
The present study evaluates the effect of a solubilized model drug, diclofenac sodium salt (diclofenac), in our unique new U-type microemulsion system embedded with phosphatidylcholine (PC) in terms of microstructure transformations, physical properties of the system (viscosity, electrical conductivity), droplet sizes and shapes, and nucleation and growth of the droplets. The physical properties are correlated to the permeability of diclofenac through Caco-2 monolayer cells. The major findings reported are: (1) systems that are rich in surfactant and contain minimal oil phase form a microemulsion that enables high solubilization of diclofenac (20 wt.% diclofenac in the oil and surfactant concentrate can be fully diluted with water); (2) PC presence at the interface does not affect the size of the O/W droplets, while the presence of diclofenac at the interface decreases the O/W droplet size by an average of 50%; (3) diclofenac seems to increase incorporation of PC into the W/O interface; (4) diclofenac affects the physical properties of the microemulsion increasing the viscosity of the W/O microemulsion system and completely changing the conductivity profile of the system upon water dilution; (5) cryo-TEM images indicate that above 70 wt.% water the droplets are spherical; (6) diclofenac permeability through Caco-2 monolayer cells increases when PC is embedded into the interface.
本研究评估了一种增溶的模型药物双氯芬酸钠盐（双氯芬酸）在我们独特的新型U型微乳液系统中的效果，该系统含有磷脂酰胆碱（PC），涉及微观结构转变、系统的物理性质（粘度、电导率）、液滴尺寸和形状以及液滴的成核和生长。这些物理性质与双氯芬酸通过Caco-2单层细胞的渗透率相关。报告的主要发现如下：（1）富含表面活性剂且油相含量最少的系统形成了一种微乳液，能够实现双氯芬酸的高增溶（油相和表面活性剂浓缩物中20 wt.%的双氯芬酸可以用水完全稀释）；（2）界面处PC的存在不影响O/W液滴的大小，而界面处双氯芬酸的存在使O/W液滴大小平均减小50%；（3）双氯芬酸似乎增加了PC向W/O界面的掺入；（4）双氯芬酸影响微乳液的物理性质，增加了W/O微乳液系统的粘度，并在用水稀释时完全改变了系统的电导率曲线；（5）冷冻透射电子显微镜图像表明，当水含量超过70 wt.%时，液滴呈球形；（6）当PC嵌入界面时，双氯芬酸通过Caco-2单层细胞的渗透率增加。
