灯盏花素纳米晶的制备及质量评价

Preparation and Quality Evaluation of Breviscapine Nanocrystals

目的:制备灯盏花素(BRE)纳米晶,并对其进行质量评价。方法:采用介质研磨法制备BRE纳米晶混悬液,以其粒径和多分散系数(PDI)为评价指标,对研磨介质的直径和用量、研磨时间、稳定剂种类和比例、BRE比例进行考察,筛选最优工艺和处方;以BRE纳米晶形态、色泽、粒径和PDI为评价指标,对加不同种类冻干保护剂(5%甘露醇、5%葡萄糖、5%乳糖)和不加冻干保护剂进行考察,筛选最优冻干保护剂;采用粒度分析仪、扫描电镜、X-射线粉末衍射法(XRPD)、差示扫描量热法(DSC)对以最优工艺和处方所制备的BRE纳米晶进行质量评价。结果:BRE纳米晶最优工艺及处方为氧化锆珠粒径0.6 mm、用量450 g,研磨时间为1 h,稳定剂为15%吐温80,BRE比例为25%,不添加冻干保护剂。所制得的BRE纳米晶为质地疏松、色泽均匀的黄色粉末,平均粒径为(283.10±3.08)nm,平均PDI为0.212±0.021,平均Zeta电位为(-38.48±0.39)mV;其为棒状晶型,分布均一且晶型稳定;20 min内累积溶出度为(90.37±1.22)%;在温度(40±2)℃、相对湿度(75±5)%条件下,避光放置3个月后稳定性良好。结论:BRE纳米晶的制备方法简单、可行,且所制得的BRE纳米晶稳定性、溶出度均良好。

OBJECTIVE: To prepare Breviscapine(BRE) nanocrystals, and to evaluate its quality. METHODS: BRE nanocrystal suspensions were prepared by media milling method. The diameter and amount of grinding beads,grinding time,type and ratio of stabilizer,BRE ratio were investigated to screen the optimal technology and formulation with particle size and polydispersity index(PDI) as evaluation indexes. Using morphology, color, particle size and PDI of BRE nanocrystals as evaluation index,different lyoprotectants(50% mannitol,5% glucose,5% lactose)and without lyoprotectant were investigated to screen the optimal lyoprotectant. Particle size analyzer, scanning electron microscope(SEM), X-Ray diffraction(XRPD),differential scanning calorimeter(DSC)were used to evaluate the quality of BRE nanocrystals which was prepared with the optimal technology and formulation. RESULTS:The optimal technology and formulation of BRE nanocrystals included that particle size of 0.6 mm zirconia beads with the amount of 450 g,grinding time of 1 h,stabilizer of 15% Tween-80,BRE ratio of 25%,without lyoprotectant. Prepared BRE nanocrystals were yellow powder with loose texture and uniform color. The average particle size of BRE nanocrystals was(283.10±3.08)nm,average PDI was(0.212±0.021)and average Zeta potential was(-38.48±0.39)mV.BRE nanocrystals were rod-like crystals,uniform in distribution and had no change in crystalline state. Accumulative dissolution of BRE nanocrystals were(90.37±1.22)% within 20 min. Under the condition of(40±2)℃ temperature and(75±5)% relative humidity, BRE nanocrystals remained stable after being kept away from light for 3 months. CONCLUSIONS: Established preparation method of BRE nanocrystals is simple and feasible. Prepared BRE nanocrystals show good stablility and dissolution.