目的 制备川芎嗪（Lig）双羟萘酸盐（Lig-PAM）缓释纳米混悬剂（Lig-PAM-NSps），并考察其体外释放特性。方法 采用难溶性盐技术制备Lig-PAM，并对其理化性质进行表征。采用微型介质研磨法制备Lig-PAM-NSps，以平均粒径、多分散指数（PDI）、稳定系数（SI）为评价指标综合加权评分，通过单因素和正交试验优化处方工艺参数，对制备的Lig-PAM-NSps进行表征，并考察其稳定性及体外药物释放情况。结果 Lig与PAM以物质的量为1∶1制备的Lig-PAM复合率为（97.48±0.04）%，与Lig相比，Lig-PAM在水和模拟体液中的溶解度分别降低了95.50%和77.39%；傅里叶红外光谱（FT-IR）和X射线粉末衍射（XRD）表明Lig与PAM形成了Lig-PAM。经正交试验优化后，按最佳处方工艺制得Lig-PAM-NSps的平均粒径为（585±5）nm，PDI为0.328±0.015，SI为0.928±0.012；扫描电镜显示Lig-PAM-NSps呈大小分布均一的圆球形，粒径在600 nm左右，且在60 d内物理稳定；体外释放结果表明48 h内Lig-PAM-NSps与Lig溶液相比具有明显的缓释作用，并呈现一级释药特征[ln（1－Q）=0.153 67 t+80.458 14，r=0.99826]。结论 Lig-PAM-NSps制备工艺稳定，在体外可缓慢释放Lig。

Objective To prepare ligustrazine pamoate (Lig-PAM) sustained-release nanosuspension (Lig-PAM-NSps) and determine its in vitro release characteristics. Methods Lig-PAM was prepared by hydrophobic salt formation method and its physicochemical properties were characterized. Then, Lig-PAM-NSps was prepared by miniaturized medium grinding method. The prescription and preparation process of Lig-PAM-NSps were optimized by the single factor and orthogonal experiment with average particle size, polydispersity index (PDI) and stability coefficient (SI) as indicators. Lig-PAM-NSps was characterized, and its stability and in vitro release was also investigated. Results The compound ratio of Lig-PAM prepared by Lig and PAM in the amount of 1:1 was (97.48±0.04)%. Compared with Lig, the solubilities of Lig-PAM in water and simulated body fluids were decreased by 95.50% and 77.39%, respectively. Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XRD) showed that the Lig and PAM formed Lig-PAM. The optimum prescription size of Lig-PAM-NSps was (585±5) nm, PDI was (0.328±0.015) and SI was (0.928±0.012). The scanning electron microscopy (SEM) showed that Lig-PAM-NSps was spherical with uniform size distribution, and the particle size was about 600 nm and its physical stability was good within 60 d. The results of in vitro release showed that Lig-PAM-NSps had obvious sustained-release effect compared with Lig solution within 48 h, and showed the first-order release characteristics[ln(1-Q)=0.153 67 t + 80.458 14, r=0.998 26]. Conclusion The preparation progress of Lig-PAM-NSps is stable and can release Lig slowly in vitro.

R283.6

四川省科技厅应用基础研究（2019YJ0661）；四川省科技创新苗子工程（2019061）；四川省教育厅高校科研创新团队项目（17TD0010）