目的 制備24 h長時釋放磷酸川芎嗪微孔滲透泵控釋片。方法 根據(jù)不同時間累積釋放度考察藥物體外釋放情況；利用單因素考察和正交試驗設(shè)計，篩選出最佳處方。結(jié)果 單因素考察找出對16 h內(nèi)體外累積釋放度影響較為顯著的因素：pH調(diào)節(jié)劑（枸櫞酸鈉、酒石酸鈉）用量、聚乙二醇-400（PEG-400）用量、檸檬酸三乙酯（TEC）用量、包衣增重。采用L₉（3⁴）正交試驗的優(yōu)化實驗，直觀分析結(jié)果得到最優(yōu)處方：按照兩個最佳處方進(jìn)行中試放大試驗制備3批樣品，其體外累計釋放度曲線擬合結(jié)果符合零級模型，擬合度好（r=0.995 0），16 h累計釋放度達(dá)85%以上。24 h釋放結(jié)果批間相似因子（f₂）為84～97，重現(xiàn)性好。結(jié)論 該處方制備工藝簡單有效，所制磷酸川芎嗪微孔滲透泵片在16 h內(nèi)零級釋放特征顯著，并可達(dá)到24 h的長時控釋釋藥。

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.