School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China.
The Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China.
J Pharm Sci. 2021 Nov;110(11):3648-3658. doi: 10.1016/j.xphs.2021.07.013. Epub 2021 Jul 23.
Relationship between the stability of fat nano-emulsions and the incorporated drug at the molecular level are rarely known. Herein, fat nano-emulsions containing dihydropyridine drugs were prepared and the microstructure of their palisade layers were investigated.The prepared 1.0 mg/mL nimodipine nano-emulsion was found to contain 65.50% drug in the palisade layer. The increasing drug concentration led to a decrease-increase-decrease trend in centrifugal stability constant, particle size and proton nuclear magnetic resonance (H NMR) signal intensity of the lecithin trimethyl ammonium group in the nimodipine and felodipine nano-emulsions. The H NMR spectra of test solutions including nano-emulsions suggest that increasing drugs penetrated into the palisade layer, resulting in the lecithin arrangement from loose to tight, and then from monolayer to bilayer. Nimodipine and felodipine nano-emulsions showed two valley values at concentrations of 0.15 and 0.75 mg/mL, and 0.30 and 0.90 mg/mL respectively, which indicated that the nano-emulsion has two more stable states corresponding to the tightly arranged mono- and bi-palisade layer. These two concentrations are positively correlated with lipophilicity of nimodipine and felodipine. Further, nimodipine liposomes were prepared to validate the effect of drugs on the arrangement of lecithin in the palisade layer. H NMR characterizations of the liposomes showed a similar profile to that of nano-emulsions. These results demonstrated that the increasing drug concentration could cause a rearrangement of lecithin in the palisade layer, thus affecting emulsion stability.
脂肪纳米乳液中药物的稳定性与药物在分子水平上的关系很少被了解。本文制备了含有二氢吡啶类药物的脂肪纳米乳液，并研究了其栅栏层的微观结构。结果发现，制备的 1.0mg/mL 尼莫地平纳米乳液中，栅栏层中含有 65.50%的药物。随着药物浓度的增加，尼莫地平纳米乳液和非洛地平纳米乳液的离心稳定性常数、粒径和磷脂酰胆碱三甲铵基团的质子核磁共振（H NMR）信号强度呈先减小后增大再减小的趋势。包括纳米乳液在内的测试溶液的 H NMR 谱表明，随着药物不断进入栅栏层，磷脂的排列从松散变为紧密，然后从单层变为双层。尼莫地平纳米乳液和非洛地平纳米乳液在 0.15 和 0.75mg/mL，以及 0.30 和 0.90mg/mL 浓度处分别出现两个谷值，这表明纳米乳液有两种更稳定的状态，分别对应于紧密排列的单和双层栅栏层。这两个浓度与尼莫地平和非洛地平的亲脂性呈正相关。此外，还制备了尼莫地平脂质体以验证药物对磷脂在栅栏层中排列的影响。脂质体的 H NMR 特性与纳米乳液相似。这些结果表明，随着药物浓度的增加，会引起栅栏层中磷脂的重新排列，从而影响乳液的稳定性。
