目的 制备田蓟苷纳米混悬剂冻干粉缓释片，并研究影响缓释片药物释放的因素及缓释片的释药机制。方法 采用高压均质法制备田蓟苷纳米混悬剂，乳糖-甘露醇（3：1）作为冻干保护剂制备冻干粉末。以HPMC作为骨架材料进一步制备成田蓟苷纳米混悬剂冻干粉缓释片，单因素考察骨架材料HPMC K4M和HPMC K15M比例及其用量、PEG 4000用量和硬脂酸镁用量对缓释片体外释药的影响，正交试验得出最佳处方。结果 田蓟苷纳米混悬剂平均粒径及Zeta电位分别为（164.41±9.72）nm和（-37.21±2.38）mV；冻干粉复溶后平均粒径及Zeta电位分别为（211.83±11.26）nm和（-31.66±2.92）mV。正交试验优化后的最佳处方为骨架材料HPMC K4M和HPMC K15M用量比为2：1，用量为40 mg，释放速率调节剂PEG 4000用量为20 mg，硬脂酸镁用量为片质量的0.5%。田蓟苷纳米混悬剂冻干粉缓释片体外释药行为符合Higuchi释药模型：M_t/M_∞=0.286 8 t^1/2-0.073 8，r²=0.981 4，在12 h内的累积释放度达到92.36%，释药机制为扩散与骨架溶蚀并存。结论 田蓟苷纳米混悬剂冻干粉缓释片制备工艺重复性良好，可有效控制田蓟苷纳米粒在体外缓慢释放。

Objective To prepare sustained-release tablets of tilianin nanosuspension lyophilized powder. The factors that might influence drug release and release mechanism were studied in present study. Methods High pressure homogenization method was used to prepare tilianin nanosuspension. Lactose and mannitol (3:1) were employed as freeze-drying protective agent to prepare lyophilized powder. HPMC was used as framework material to prepare sustained-release tablets of tilianin nanosuspension lyophilized powder. Based on single factor test, the effects of proportion and amounts of HPMC K4M and HPMC K15, amounts of PEG 4000 and magnesium stearate on in vitro drug release of sustained-release tablets were investigated. Orthogonal test was designed to gain the optimum prescription. Results The particle size and zeta potential of tilianin nanosuspension were (164.41 ±9.72) nm and (-37.21 ±2.38) mV, respectively. The particle size and zeta potential of re-dispersed freeze-drying products were (211.83 ±11.26) nm and (-31.66 ±2.92) mV, respectively. The optimum prescription was as follow:the proportion and amounts of HPMC K4M and HPMC K15 were 2:1 and 40 mg, amounts of PEG 4000 was 20 mg, and amounts of magnesium stearate were 0.5%. Sustained release tablets of tilianin nanosuspension were well accorded with Higuchi kinetics model. The equation was M_t/M_∞=0.286 8 t^1/2-0.073 8, r²=0.981 4. And the cumulative release could achieve 92.36% in 12 h. The drug release from the tablets was controlled by diffusion and degradation of the matrix. Conclusion The preparation technology of sustained release tablets of tilianin nanosuspension lyophilized powder has good reproducibility. This sustained release tablets could control the release of tilianin nanosuspension in a slow characteristic.

R283.6

国家科技重大专项（2018ZX09201009-002-009）