目的 制备大黄素纳米混悬剂（emodin nanosuspension，Emo-NS）及其冻干粉，并对其进行体外评价。方法 采用微型化介质研磨法制备Emo-NS，在单因素实验基础上，以粒径大小及多分散指数（poly dispersity index，PDI）为考察指标，考察氧化锆珠子体积、研磨速率及研磨时间的影响。采用冷冻干燥法固化，考察冻干保护剂对固化的影响。采用透射电子显微镜法（transmission electron microscopy，TEM）、差示扫描量热法（differential scanning calorimetry，DSC）、X射线衍射法（X-ray diffraction，XRD）、傅里叶变换红外光谱法（Fourier transform infrared spectroscopy，FT-IR）对Emo-NS进行表征，透析袋法评价其体外释放度。结果Emo-NS最佳处方为大黄素用量50 mg，泊洛沙姆407用量20 mg，氧化锆珠子体积5.9 mL，研磨速率1 390 r/min，研磨时间3.9 h；Emo-NS的平均粒径为（236.23±1.13）nm，PDI为0.205±0.011，均与Box-Behnken设计-响应面法预测值接近；ζ电位为（−31.22±1.34）mV。Emo-NS固化时的冻干保护剂确定为50 mg/mL的蔗糖。体外释放结果显示，Emo-NS冻干粉144 h累积释放率为（93.47±2.74）%，符合Ritger-Peppas释放模型。Emo-NS外貌为球形，DSC、XRD、FT-IR结果显示，Emo-NS冻干粉中大黄素以无定型状态分散于纳米混悬剂中或被稳定剂完全包裹，有利于其溶出。结论 将大黄素制备成Emo-NS，处方设计合理、制备工艺可行，显著提高了其体外溶出率。

Objective To prepare emodin nanosuspension (Emo-NS) and its lyophilized powder and perform in vitro evaluation. Methods Emo-NS was prepared by miniaturized media milling method, and the effects of zirconia bead volume, milling speed and milling time were investigated on a one-factor basis, with particle size and poly dispersity index (PDI) as the investigating indexes. Adopting freeze-drying method for curing, investigate the effect of freeze-drying protectant on curing. Transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR) were used to characterize the Emo-NS, and the dialysis bag method was used to evaluate its in vitro release. Results The optimal prescription of Emo-NS was 50 mg of emodin, 20 mg of poloxamer 407, zirconia beads volume of 5.9 mL, milling speed of 1 390 r/min, and milling time of 3.9 h. The average particle size was (236.23 ±1.13) nm, and the PDI was 0.205 ±0.011, which was close to that predicted by the Box-Behnken design-response surface method. The lyophilized protectant for curing was determined to be 50 mg/mL sucrose. The ζ potential was (−31.22 ±1.34) mV. The in vitro release results showed that the 144 h cumulative release of Emo-NS was (93.47 ±2.74)%, which was consistent with the Ritger-Peppas release model. The external appearance of Emo-NS was spherical, and the DSC, XRD, and FT-IR results showed that emodin in the Emo-NS was dispersed in nanosuspension in an amorphous state or was completely encapsulated by stabilizers, which was conducive to its dissolution. Conclusion The preparation of emodin into nanosuspension drug prescription was well-designed and feasible, which significantly improved its in vitro dissolution rate.

R283.6

国家中医药管理局高水平建设学科(zyyzdxk-2023272)