文档介绍：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:低温充氮气保护的奥美拉唑钠溶液在配制后4小时内都处于稳定状态,。欧洲来源胶塞A和欧洲来源胶塞B与注射用奥美拉唑钠有着良好的相容性;而亚洲来源胶塞C与亚洲来源胶塞D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,%%,而胶塞干燥0个循环的批次,%%。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:药液的低温充氮保护对奥美拉唑钠溶液稳定性的有着十分重要的影响。丁基橡胶塞是影响注射用奥美拉唑钠可见异物的重要因素之一。全真空压塞后胶塞内部的残余水分会逐渐被吸收到奥美拉唑钠冻干粉中,从而导致产品水分进一步升高。灭菌后胶塞残余水分对奥美拉唑钠冻干粉的稳定性产生重要影响。如果水分长期维持于过低水平,则产品有关物质会在储存期内快速升高。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, patibility 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, patibility of rubber stoppers and omeprazole sodium, and the impact of residual moisture released from rubber stoppers after moist heat sterilization upon