盐酸川芎嗪氯化钠注射液处方和制备工艺改进

Improvement of Formulation and Preparation Technology of Ligustrazine Hydrochloide and Sodium Chloride Injection

目的:在避免使用助溶剂的情况下解决盐酸川芎嗪氯化钠注射液长期放置后易析出细小白点、白块等可见异物问题。方法:选择柠檬酸钠作为本品pH调节剂,调节药液pH至4.0,使川芎嗪尽量以盐形式溶解于溶液中,对按改进处方制备的3批中试产品进行影响因素试验、长期稳定性和加速稳定性试验。结果:改进后处方为盐酸川芎嗪0.8 g,氯化钠9.0 g,加注射用水制成1 L,加适量10%枸橼酸和10%枸橼酸钠调节药液pH。3批中试产品在室温(25±2)℃留样24个月、加速试验(40±2)℃6个月及影响因素试验条件下,产品质量稳定,未出现细小白点、白块。结论:改进后处方与制备方法稳定可行。pH调节剂的变更未使药物物质基础发生改变,不影响药品的质量可控性、安全性和有效性,且药物稳定性更好。

Objective：To improve formulation and preparation technology of ligustrazine hydrochloide and sodium chloride injection.Method：With sodium citrate to adjust samples solution to pH 4.0,and try to make ligustrazine to form salt in injection,then long-term stability test,accelerated stability test and influencing factors test of three batches of pilot products was adopted,which were prepared by improving prescription.Result：Improved prescription was as following：ligustrazine hydrochloide 0.8 g,sodium chloride 9.0 g,added water for injection into 1 L,added a amount of 10% citric acid and 10% sodium citrate to adjust pH of samples solution.Under conditions of long-term stability test [24 months,room temperature of（25 ± 2） ℃ ],accelerated stability test [6 months,（40 ± 2） ℃] and influencing factors test,quality of three batches of test products was stable without tiny spots and white block.Conclusion：Improved formulation and preparation process were feasible and stable.Change of pH regulator was not change substance basis of drug and controllability,safety,efficacy of drug quality,and stability of samples got better.