注射用5-氮杂胞苷的制备及质量研究  

Preparation and quality evaluation of 5-azacytidine for injection

作　　者：黄雅菲 HUANG Yafei(Department of Pharmacy,the People′s Hospital of Lishui District of Nanjing,Nanjing 211200,China)

机构地区：[1]南京市溧水区人民医院药剂科,江苏南京211200

出　　处：《沈阳药科大学学报》2023年第10期1284-1290,共7页Journal of Shenyang Pharmaceutical University

基　　金：南京药学会-常州四药医院药学会科研基金项目(2018YX018);南京药学会-天晴医院药学会科研基金项目(Q2019010);江苏省药学会-天晴医院药学基金项目(Q202054)。

摘　　要：目的采用冷冻干燥工艺制备注射用5-氮杂胞苷,并对其质量进行评价。方法通过对5-氮杂胞苷溶液的稳定性研究确定最佳溶液配制温度。根据样品外观确定预冻工艺参数。根据样品温度和干燥时间采用析因实验设计优化一次干燥过程中隔板温度和真空度。根据水分、有关物质结果确定二次干燥的温度及时间。根据优化的冻干工艺参数制备3批注射用5-氮杂胞苷,并与参比制剂进行对比研究。结果5-氮杂胞苷溶液对温度极其敏感,需在(4±2)℃条件下配制,在6 h内药物较为稳定;采用反复冻结法,降温速率为0.5~1℃·min^(-1),退火温度-10℃及保持时间为2 h,冻干得到的注射用5-氮杂胞苷外观均匀、无鳞片状。通过实验优化得到最佳一次干燥工艺参数为:隔板温度为20℃,真空度为60 Pa,在该工艺参数范围内进行操作,冻干时间明显缩短;二次干燥温度为30℃,干燥时间为40 h,产品水分与有关物质均可以达到与参比制剂相似;三批自制注射用5-氮杂胞苷的检测指标与参比制剂相似或一致。结论本研究作者按照优化的冷冻干燥工艺参数制备注射用5-氮杂胞苷,可以得到与参比制剂质量一致的制剂产品。Objective To prepare 5-azacytidine for injection and evaluate its quality.Methods The stability of 5-azacytidine solution under different temperature conditions was determined.The pre-freezing process parameters were determined according to the appearance of the lyophilization products.Using the products temperature and drying time as indicators,the factorial experiment design was used to optimize the shelf temperature and vacuum during the primary drying process.According to the moisture content and the level of related substances,the shelf temperature and drying time of the secondary drying were determined.Three batches of 5-azacytidine for injection were prepared with optimized lyophilization parameters,and quality comparison was conducted with reference products.Results The 5-azacytidine solution was stable at(4±2)℃for 6 hours.The freezing process adopted the repeated freezing method,the cooling rate was 0.5-1℃·min^(-1),the annealing temperature and holding time were-10℃and 2 h,respectively.The primary drying process parameters obtained through experimental optimization as followed:the shelf temperature of 20℃,the vacuum of 60 Pa.The 5-azacytidine for injection was produced under the freeze-drying process parameters,the freeze-drying time was significantly shortened,and the product appearance was full.The moisture content and related substances of 5-azacytidine for injection could be similar to the reference preparation under secondary drying temperature of 30℃and the drying time of 40 h.The quality of 5-azacytidine for injection was similar or consistent with the reference preparation.Conclusion The 5-azacytidine for injection was prepared according to the optimized freeze-drying process parameters,and the product quality could be consistent with the reference preparation.

关 键 词：注射用5-氮杂胞苷 冷冻干燥 预冻 一次干燥 二次干燥 质量评价 

分 类 号：R94[医药卫生—药剂学]