A Natural Triterpenoid Saponin as Multifunctional Stabilizer for Drug Nanosuspension Powder
A Natural Triterpenoid Saponin as Multifunctional Stabilizer for Drug Nanosuspension Powder
复制标题
天然三萜皂苷作为药物纳米混悬剂的多功能稳定剂
DOI：
10.1208/s12249-017-0756-7
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发表时间：
2017-10-01
影响因子：
3.3
通讯作者：
Yang, Ming
中科院分区：
文献类型：
--
作者：
Chen, Yingchong;Liu, Yang;Yang, Ming
本研究的目的是制备一种新型的天然三萜皂苷修饰的药物纳米混悬剂，并对其稳定性和重现性进行评价。一种难溶性药物（穿心莲内酯（AGE））被用作模型药物。以GZ为天然稳定剂，通过均质法制备了平均粒径为487 nm的AGE纳米混悬剂（AGE-NS），并通过冷冻干燥法将其转化为干燥的AGE纳米混悬剂粉末（AGE-NP）。结果表明，GZ能够阻止AGE纳米晶的聚集，并且冷冻干燥的AGE-NP可以容易地再分散回AGE-NS。这与GZ具有界面性质（37.02 ± 0.29 N/m）和静电效应（−43.6 ± 0.9 mV），并能将AGE纳米晶捕获到其网络结构中的特殊性质有关。与以海藻糖为基质形成剂的AGE-NP/GZ相比，AGE-NP/GZ冻干物表现出优异的性能。粉末X射线衍射结果表明，GZ没有改变AGE的结晶状态。AGE-NP/GZ的溶出度（99.87%）明显高于粗AGE（42.35%）。本研究表明GZ可作为一种新型的多功能稳定剂用于药物纳米混悬剂的制备，为难溶性药物的进一步剂型开发提供了有希望的基础。
The objective of this study is to prepare a novel drug nanosuspension modified by a natural triterpenoid saponin (glycyrrhizin (GZ)) and evaluate its stability and redispersibility. A poorly soluble drug (andrographolide (AGE)) was used as a model drug. AGE nanosuspensions (AGE-NS) using GZ as natural stabilizer with mean particle size of 487 nm were firstly prepared by homogenization and converted into dried AGE nanosuspension powder (AGE-NP) by freeze-drying. It was found that GZ was able to prevent the aggregation of AGE nanocrystals and the freeze-dried AGE-NP could easily redisperse back to AGE-NS. It was related with special properties of GZ that possessed the interfacial property (37.02 ± 0.29 N/m) and electrostatic effect (−43.6 ± 0.9 mV) and could entrap AGE nanocrystals into its network structure. The freeze-dried AGE-NP/GZ exhibited excellent performance, compared with those combined with trehalose as matrix formers. The powder X-ray diffraction result demonstrated that GZ did not alter the AGE crystal state. The dissolution of AGE-NP/GZ (99.87%) was significantly enhanced, compared with the coarse AGE (42.35%). This study demonstrated that GZ could be used as a novel multifunctional stabilizer for production of drug nanosuspensions and provided a promising basis for further formulation development of poorly soluble drug.