摘要
目的制备以甘草酸为稳定剂的水飞蓟素纳米混悬剂(silymarin nanosuspension,SM-NS),并考察体外释放特性和电荷稳定机制。方法用高速剪切-高压均质法制得SM-NS,用冷冻干燥法制成SM-NS冻干粉并进行理化特性表征和体外释放特性评价。从离子强度,pH值的角度对SM-NS进行了稳定机制研究。结果稳定剂甘草酸(GA)用量为0.15%,制备工艺为剪切速率19000 r/min、剪切时间4 min、均质压力100 MPa、均质次数12次,冻干保护剂为甘露醇,其用量3%,制得的SM-NS冻干粉平均粒径为(516.4±10.4)nm,多分散指数(PDI)为0.260±0.046;体外释放结果表明SM-NS冻干粉的溶出速率和溶解度显著提高;电荷稳定机制研究表明甘草酸能提供良好的电荷稳定作用,抗环境冲击能力较强。结论SM-NS是一种潜在的安全性高的新型纳米药物,其通过甘草酸的电荷稳定作用显著提高水飞蓟素的溶解度及稳定性。
Objective To prepare silymarin nanosuspension(SM-NS) with glycyrrhizic acid as stabilizer, and investigate the in vitro release characteristics and charge stabilization mechanism. Methods SM-NS was prepared by high-speed shear-high pressure homogenization method. SM-NS lyophilized powder were prepared by freeze-drying method and characterized by physical and chemical characterization and in vitro release. The stability mechanism of SM-NS was studied from the ionic strength and pH value. Results The dosage of glycyrrhizic acid(GA) was 0.15%. The preparation process was shear rate of 19 000 r/min, shear time of 4 min, homogenization pressure of 100 MPa, homogenization times of 12 times, and lyoprotectant was mannitol 3%, the average particle size of SM-NS lyophilized powder was(516.4 ± 10.4) nm, PDI was(0.260 ± 0.046);The in vitro release results showed that the dissolution rate and solubility of SM-NS lyophilized powder were significantly higher than the physical mixture;The study of charge stability mechanism showed that licorice acid can provide good charge stabilization and strong resistance to environmental impact. Conclusion SM-NS is a potential and new nano-drug with high safety, which is formed by the charge stability of GA to significantly improve the solubility and stability of silymarin.
作者
唐海龙
李小芳
龙家英
邓茂
谢龙
廖艳梅
TANG Hai-long;LI Xiao-fang;LONG Jia-ying;DENG Mao;XIE Long;LIAO Yan-mei(Key Laboratory of Research and Utilization of Chinese Medicinal Resources in Sichuan Province,Key Laboratory Breeding Base of Co-founded by Sichuan Province and Ministry of Science and Technology,Key Laboratory of Standardization of Chinese Herbal Medicine of Ministry of Education,College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)
出处
《中草药》
CAS
CSCD
北大核心
2020年第4期971-977,共7页
Chinese Traditional and Herbal Drugs
基金
四川省科技厅项目(2019YFS0113)
国家中医药管理局项目(2018ZYO3O02)。
关键词
纳米混悬剂
水飞蓟素
甘草酸
制备工艺
稳定机制
高速剪切-高压均质技术
释放特性
冷冻干燥法
溶解度
稳定性
nanosuspension
silymarin
glycyrrhizic acid
preparation process
stabilization mechanism
high-speed shear-high pressure homogenization
release characteristics
freeze-drying method
solubility
stability
