University of Toronto, Department of Chemical Engineering and Applied Chemistry, 200 College Street, Room 131, Toronto, Ontario M5S 3E5, Canada.
University of Toronto, Department of Chemical Engineering and Applied Chemistry, 200 College Street, Room 131, Toronto, Ontario M5S 3E5, Canada.
J Colloid Interface Sci. 2017 Jun 1;495:178-190. doi: 10.1016/j.jcis.2017.01.114. Epub 2017 Feb 1.
Fully dilutable microemulsions (μEs), used to design self-microemulsifying delivery system (SMEDS), are formulated as concentrate solutions containing oil and surfactants, without water. As water is added to dilute these systems, various μEs are produced (water-swollen reverse micelles, bicontinuous systems, and oil-swollen micelles), without the onset of phase separation. Currently, the formulation dilutable μEs follows a trial and error approach that has had a limited success. The objective of this work is to introduce the use of the hydrophilic-lipophilic-difference (HLD) and net-average-curvature (NAC) frameworks to predict the solubilisation features of ternary phase diagrams of lecithin-linker μEs and the use of these predictions to guide the formulation of dilutable μEs. To this end, the characteristic curvatures (Cc) of soybean lecithin (surfactant), glycerol monooleate (lipophilic linker) and polyglycerol caprylate (hydrophilic linker) and the equivalent alkane carbon number (EACN) of ethyl caprate (oil) were obtained via phase scans with reference surfactant-oil systems. These parameters were then used to calculate the HLD of lecithin-linkers-ethyl caprate microemulsions. The calculated HLDs were able to predict the phase transitions observed in the phase scans. The NAC was then used to fit and predict phase volumes obtained from salinity phase scans, and to predict the solubilisation features of ternary phase diagrams of the lecithin-linker formulations. The HLD-NAC predictions were reasonably accurate, and indicated that the largest region for dilutable μEs was obtained with slightly negative HLD values. The NAC framework also predicted, and explained, the changes in microemulsion properties along dilution lines.
可充分稀释的微乳液（μE），用于设计自微乳给药系统（SMEDS），是作为含有油和表面活性剂的浓缩溶液配制的，不含水。当向这些系统中加水进行稀释时，会产生各种μE（水膨胀反向胶束、双连续系统和油膨胀胶束），而不会发生相分离。目前，可稀释μE 的配方采用的是一种试错法，收效有限。本工作的目的是引入亲油-亲水差异（HLD）和净平均曲率（NAC）框架，以预测大豆磷脂-连接体μE 的三元相图的增溶特征，并利用这些预测来指导可稀释μE 的配方。为此，通过参考表面活性剂-油系统的相扫描，获得了大豆磷脂（表面活性剂）、甘油单油酸酯（亲脂性连接体）和辛酸甘油酯（亲水性连接体）的特征曲率（Cc）和乙基辛酸酯（油）的等效烷烃碳数（EACN）。然后，这些参数用于计算磷脂-连接体-乙基辛酸酯微乳液的 HLD。计算出的 HLD 能够预测相扫描中观察到的相变。然后，使用 NAC 拟合和预测盐度相扫描得到的相体积，并预测磷脂-连接体配方的三元相图的增溶特征。HLD-NAC 的预测相当准确，并表明具有略微负 HLD 值的区域可获得最大的可稀释μE 区域。NAC 框架还预测并解释了微乳液性质沿稀释线的变化。
