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目的:基于质量源于设计(QbD)理念设计和开发重楼总皂苷固体脂质纳米粒。方法:根据重楼总皂苷固体脂质纳米粒剂型及给药特点确立了目标产品概况,并根据理论知识和实际经验,通过风险评估工具确定影响固体脂质纳米粒制剂学性质的关键性变量。首先应用Plackett-Burman试验筛选出对重楼总皂苷固体脂质纳米粒制剂学性质影响显著的关键变量,然后对筛选出的变量应用Box-Behnken效应面法进一步优化。评价重楼总皂苷固体脂质纳米粒的粒径分布、多聚分散系数(PdI)、Zeta电位、微观形态等理化性质,考察固体脂质纳米粒体外释药情况。结果:最佳处方和制备工艺为:单硬脂酸甘油酯浓度为5.5%,大豆磷脂浓度为8.0%,均质次数为6次,固定药物浓度为5.0%,表面活性剂种类为吐温80,均质压力为600 bar,均质温度为65℃。采用优化后处方工艺制得的重楼总皂苷固体脂质纳米粒平均粒径为(116.5±32.1)nm,PdI为0.198±0.018,Zeta电位为(-23.6.5±0.9)mV,透射电镜显示固体脂质纳米粒呈球状分布,体外释放结果表明具有缓释效果,24 h累积释药为63.5%。结论:运用QbD理念设计和开发重楼总皂苷固体脂质纳米粒切实可行,能确保产品质量符合要求。
Objective: To design and develop a total saponin solid lipid nanoparticles based on the QbD concept. Methods: The target product profile was established based on the solid lipid nanoparticle formulations and the administration characteristics of the total saponin solid preparation. Based on the theoretical knowledge and practical experience, risk assessment tools were used to determine the key variables affecting the properties of the solid lipid nanoparticles preparation. Firstly, Plakeyt-Burman test was used to screen out the key variables influencing the preparation properties of the total saponin solid lipid nanoparticles. The Box-Behnken response surface method was used to optimize the selected variables. The particle size distribution, PdI, Zeta potential and microscopic morphology of the total saponin solid lipid nanoparticles of Rhizoma Paridis were evaluated. The drug release characteristics of solid lipid nanoparticles were investigated. Results: The optimal prescription and preparation process were as follows: the concentration of glycerol monostearate was 5.5%, the concentration of soybean phospholipid was 8.0%, the number of homogenization was 6 times, the concentration of fixed drug was 5.0%, the surfactant type was Tween 80 , Homogenization pressure 600 bar, homogenization temperature 65 ℃. The average particle size of the total saponin solid lipid nanoparticles was (116.5 ± 32.1) nm, the PdI was 0.198 ± 0.018 and the Zeta potential was (-23.6.5 ± 0.9) mV. The results of transmission electron microscopy Solid lipid nanoparticles were spherical, the release results in vitro showed a sustained release effect, cumulative release of 24 h was 63.5%. Conclusion: It is practicable to design and develop the total saponin solid lipid nanoparticles using QbD concept to ensure that the product quality meets the requirements.