摘要
为提高水飞蓟素(1)的溶出度,采用溶剂沉淀法结合高压均质法制备1纳米混悬剂(1-NS)。以1-NS平均粒径和多分散指数(PDI)为指标,采用单因素试验和星点设计-效应面法优化工艺和处方。所得优化处方为:1浓度为4 g/L,聚维酮(PVP)K30浓度为1.3 g/L,十二烷基硫酸钠浓度为0.7 g/L;所得粗混悬剂在100 MPa压力下循环12次。验证试验表明,3批1-NS的平均粒径为(191.4±1.35)nm,PDI为0.135±0.003。为进一步提高稳定性,采用冷冻干燥法将1-NS冻干,并优化了冻干保护剂种类和浓度。结果显示,以5%甘露醇的保护效果最好。1-NS冻干粉再分散后的平均粒径为(243.5±2.8)nm,PDI为0.182±0.018。1-NS冻干粉在水中60 min时的溶出率达90.5%,而1物理混合物冻干粉为48.6%,可见1-NS冻干粉的溶出速度和程度明显优于1物理混合物。
To improve the dissolution of silymarin （1）, the 1 nanosuspension （1-NS） was prepared by solvent precipitation method combined with high pressure homogenization method. The process and formulation parameters were optimized by single factor test and central composite design-response surface methodology with average particle size and polydispersion index （PDI） as the indexes. The optimal formulation was as follows： the concentrations of 1, polyvidone （PVP） K30 and sodium dodecylsulfate were 4, 1.3 and 0.7 g/L, respectively. Then the crude suspension was treated at homogeneous pressure of 100 MPa with 12 cycles. The results of validation test showed that the average particle size and PDI values of three batches of the optimal 1-NS were （191.4±1.35） nm and 0.135±0.003. Then the 1-NS was freezedried to further improve the stability. The type and concentration of cryoprotectants were also optimized. The results showed that the mannitol with the concentration of 5 % had the best protective effect among the tested cryoprotectants. The average particle size and PDI values of the reconstituted 1-NS freeze-dried powder were （243.5±2.8）nm and 0.182± 0.018. The dissolution at 60 min of the freeze-dried powders of 1-NS and the physical mixture of 1 in water were 90.5 % and 48.6 %, which indicating a significant increase in the rate and extent of dissolution.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2016年第9期1165-1170,共6页
Chinese Journal of Pharmaceuticals
基金
四川省科技厅“苗子工程”重点项目(2016RZ0037)
四川省教育厅项目(15ZA0094、16ZB0118)
关键词
水飞蓟素
纳米混悬剂
冷冻干燥
再分散性能
粒度分布
溶出度
silymarin
nanosuspension
freeze-drying
redispersibility
particle size distribution
dissolution
