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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 rate of silymarin (1), a 1-nanometer suspension (1-NS) was prepared by solvent precipitation combined with high pressure homogenization. The 1-NS average particle size and polydispersity index (PDI) were used as indexes to optimize the process and prescription by using single factor experiment and apices design-response surface method. The optimized formulation was as follows: 1 concentration of 4 g / L, concentration of PVP K30 of 1.3 g / L and sodium dodecyl sulfate concentration of 0.7 g / L; the obtained crude suspension under the pressure of 100 MPa Loop 12 times. Validation tests showed that the average particle size of 3 batches of 1-NS was (191.4 ± 1.35) nm and the PDI was 0.135 ± 0.003. To further improve stability, 1-NS was lyophilized by freeze-drying and the type and concentration of lyoprotectant was optimized. The results showed that 5% mannitol to protect the best. The average particle size of 1-NS lyophilized powder was (243.5 ± 2.8) nm and the PDI was 0.182 ± 0.018.1-NS. The lyophilized powder had a 90.5% dissolution rate at 60 min in water, while 1 physical mixture The dry powder was 48.6%, showing that the dissolution rate and extent of 1-NS lyophilized powder was significantly better than that of a 1-physical mixture.