注射用奥美拉唑钠可见异物和有关物质异常研究.doc

摘 要 研究背景：注射用奥美拉唑钠在储存过程中出现可见异物超标，有关物质上升过快问题。 研究目的：解决注射用奥美拉唑钠可见异物超标和有关物质上升过快问题，保证产品的安全性和稳定性。 研究方法：基于参照药品分析，首仿药品分析，文献查询分析，问题药品分析以及风险评估出的高风险因素和中风险因素，设计了低温充氮和室温无充氮条件下药液稳定性试验、丁基橡胶塞与奥美拉唑钠相容性试验、灭菌后胶塞残余水分对注射用奥美拉唑钠稳定性影响的试验，对奥美拉唑钠溶液稳定性、丁基橡胶塞相容性、冻干后水分和有关物质的相关性进行研究。 研究结果：和与注射用奥美拉唑钠有着良好的相容性；而与与注射用奥美拉唑钠的相容性差，不符合要求。冻干后产品水分会随着加速时间的延长而逐步上升，胶塞烘干越充分，水分上升速度会越慢。冻干后产品有关物质会随着加速时间的延长而逐步上升，胶塞热风干燥次数越多，有关物质上升速度会越快，反之，胶塞热风干燥次数越少，上升速度会越慢。胶塞干燥6个循环的批次，有关物质从0.2%上升到1.0%，而胶塞干燥0个循环的批次，有关物质仅从0.2%上升到0.6%。虽然有关物质会上升，但仍在质量标准允许的范围之内。 研究结论：在采取风险降低措施后，更新后的风险评估结果为低风险。关键词：奥美拉唑钠；可见异物；有关物质；胶塞；Study of visible particles out of specification and related substance abnormality of omeprazole sodium for injection Abstract Research background: The visible particles was out of specification and the related substance increased too fast during storage in Omeprazole sodium for injection. Research target: To solve the problem of visible particles out of specification and increased related substance to ensure the safety and stability of omeprazole sodium for injection. Research method: Based on Reference listed drug analysis, the first generic drug analysis, literature search, the problem drug analysis, high risk factors and medium risk factors through risk assessment, we designed three experiments to study the stability of the omeprazole sodium solution, the compatibility of rubber stoppers with omeprazole sodium, and the relationship between product moisture and related substance after lyophilization, which were the impact of low temperature and nitrogen headspace upon the omeprazole sodium solution stability, the compatibility of rubber stoppers and omeprazole sodium, and the impact of residual moisture released from rubber stoppers after moist heat sterilization upon the moisture and level of related substance . Research result: The omeprazole sodium solution was stable for 4 hours under protection of low temperature and nitrogen headspace, while the related substance increased quickly after 30 minutes without the pro