目的 基于质量源于设计(QbD)理念优化穿心莲内酯(And)固体脂质纳米粒(And-SLNs).方法 采用热熔乳化-高压均质法制备And-SLNs.以And-SLNs的包封率、粒径分布为评价指标,首先应用Plackett-Burman实验设计筛选出对And-SLNs性质影响显著的处方和工艺变量,然后对筛选出的变量应用Box-Behnken效应面法进一步优化.采用Malvern粒度仪测定And-SLNs的粒径分布和Zeta电位,透射电镜考察其形态;并考察And-SLNs的体外释药行为.结果 And-SLNs的包封率为(91.4±3.7)%,粒径为(258.4±42.1)nm,Zeta电位为(-36.1±3.4)mV,透射电镜显示And-SLNs粒径均一,呈球状分布,48 h累积释放度为52.4%.结论 在And-SLNs开发过程中应用QbD理念优化是可行的.

Objective The aim of this investigation was to use a quality by design (QbD) approach to optimize andrographolide solid lipid nanoparticles (And-SLNs). Methods The And-SLNs were prepared by melt-emulsion and followed by high pressure homogenization methods. The And-SLNs with ideal encapsulation efficiency (EE) and particle size distribution were used various experimental statistical design modules. Plackett-Burman design for independent variables was first conducted to prescreen various formulation and process variables during the development of SLNs. Selected primary variables were further optimized by Box-Behnken design. The particle size distribution, Zeta potential, morphology, and in vitro drug release behavior of And-SLNs were studied by Malvern Particle Size Analyzer and Transmission Electron Microscope (TEM), respectively. Results The EE, particle size, and Zeta potential of And-SLNs were found to be (91.4 ± 3.7)%, (258.4 ± 42.1) nm, and (-36.1 ± 3.4) mV, respectively. The And-SLNs were found to be small and spherical with uniform particle size and smooth surface as seen in TEM. The in vitro accumulated release of And reached up to 52.4% within 48 h. Conclusion This study demonstrates that the QbD approach could optimize the formulation and process variables to achieve favorable responses for And-SLNs.

陕西省教育厅科学研究计划项目(2013JK0816);陕西省中药制药重点学科资助(10080)