目的 制备24 h长时释放磷酸川芎嗪微孔渗透泵控释片。方法 根据不同时间累积释放度考察药物体外释放情况；利用单因素考察和正交试验设计，筛选出最佳处方。结果 单因素考察找出对16 h内体外累积释放度影响较为显著的因素：pH调节剂（枸橼酸钠、酒石酸钠）用量、聚乙二醇-400（PEG-400）用量、柠檬酸三乙酯（TEC）用量、包衣增重。采用L9（34）正交试验的优化实验，直观分析结果得到最优处方：按照两个最佳处方进行中试放大试验制备3批样品，其体外累计释放度曲线拟合结果符合零级模型，拟合度好（r=0.995 0），16 h累计释放度达85%以上。24 h释放结果批间相似因子（f2）为84～97，重现性好。结论 该处方制备工艺简单有效，所制磷酸川芎嗪微孔渗透泵片在16 h内零级释放特征显著，并可达到24 h的长时控释释药。
Objective To prepare the microporous osmotic pump controlled release tablets of Tetramethylpyrazine Phosphate for 24 hours. Methods The drug release condition in vitro was investigated by the cumulative release in different times; and its optimal prescription was revisited; the optimal prescription was selected by single factor investigation and orthogonal design. Results The significant influence factors to the cumulative release within 16 hours were found out by the single factor investigation:pH regulator (sodium citrate, sodium tartrate) dosage, polyethylene glycol-400 (PEG-400), triethyl citrate (TEC) dosage, the coating weight. Three batches of samples were prepared by pilot and amplification test according to the two optimal prescriptions. The results of the cumulative release curve fitting in vitro were in line with the zero-level model, and the fitting degree was good (r=0.995 0), the cumulative release rate was over 85% in 16 h. The inter batch similarity factor f2 was about 84-97 with good reproducibility about 24 h. Conclusion The preparation process of this prescription is simple and effective, and the preparation of tetramethylpyrazine phosphate microporous osmotic pump tablets had obvious zero-level release characteristics within 16 h, and can achieve long-term controlled release of drugs for 24 h.