注射用灯盏花素调配方法优化及其在不同溶媒中稳定性的研究

Optimization of mixture method about breviscapine for injection and its stability in different kinds of solvent

目的确定注射用灯盏花素的最佳调配方法,考察其在不同溶媒中的稳定性。方法采用正交实验的方法优选注射用灯盏花素的最佳溶解方法;高效液相色谱法(HPLC)测定在25℃下,0、2、4、6、8 h时,不同溶媒输液中注射用灯盏花素的主成分野黄芩苷的含量变化,同时测定输液中pH和微粒的变化。结果注射用灯盏花素最佳调配工艺为20 mg粉针加入3 mL灭菌注射用水溶于西林瓶中,以1 200 r/min频率振荡2 min;室温下,注射用灯盏花素在250 mL 0.9%氯化钠、5%葡萄糖、葡萄糖氯化钠输液中8 h内主成分含量稳定,不溶性微粒和pH均符合要求;在250 mL 10%葡萄糖输液中8 h内含量较稳定,在第4小时时pH<5,第8小时时不溶性微粒数超过药典标准。结论临床使用时,将注射用灯盏花素使用最佳调配方法溶解后,选用50 mL 0.9%氯化钠,5%葡萄糖或者葡萄糖氯化钠溶液作为稀释溶媒,并且8 h内使用。

Objective To optimize the mixture method of breviscapine for injection,and to investigate their stability in different solvents.Methods The orthogonal test was adopted to choose the optimum dissolution method.High performance liquid chromatography(HPLC)was adopted to measure the content changes of scutellarin,the main constituent of breviscapine for injection,in different solvents at 0,2,4,6,8 h at the temperature of 25℃.Meanwhile the changes in pH values and particles of the solvents were determined.Results The optimal mixture method of breviscapine for injection was as follows:3 mL sterile water for injection was added to 20 mg powder-injection in the vial,which was shaken for 2 min with the frequency of 1 200 r/min.At room temperature,the main constituents of breviscapine were stable within 8 h in 250 mL 0.9%sodium chloride solution,5%glucose solution and glucose and sodium chloride solution.The pH value and the unsolvable particles conformed to requirements.The contents were stable in 250 mL 10%glucose solution at 8 h.The pH value was below 5 at 4 h and the number of unsolvable particles at 8 h exceeded the standard of Chinese pharmacopoeia.Conclusion It is recommended that in clinical use,after breviscapine is dissolved in accordance with the optimal solvent method,50 mL 0.9%sodium chloride solution,5%glucose solution or glucose sodium chloride solution can be used as diluent.And the injection needs to be used within 8h.