摘要
目的探讨生产稳定及高质量的注射用托拉塞米处方及制备工艺。方法通过筛选辅料及占比确定注射用托拉塞米处方,通过对配液温度和pH,脱炭工艺及过滤材料、灌装容器、冻干参数的考察,确定注射用托拉塞米的制备工艺。结果最佳处方为托拉塞米(10 mg)、碳酸氢钠(20 mg)、甘露醇(100 mg)。配制温度控制为15~25℃,药液采用5%氢氧化钠调节pH值至9.0,同时存放于10℃以下;采用0.45μm+0.22μm聚醚砜滤膜进行过滤,选用5 ml或10 ml无色低硼硅玻璃管制注射剂瓶,丁基溴橡胶塞进行封装。最终冻干工艺制品条件为:-40℃,预冻3 h;导热油升温至0℃,保温40~60 h;导热油升温至20℃,保温6~8 h;最终制品在35℃,保温6~8 h。高效液相色谱法检测202009031、202009032、202009033批样品含量分别为100.21%,100.83%、99.82%。202009031样品在长期试验、加速试验,水分结果有所增加,其他考察指标无明显变化;202009032和202009033样品在长期试验、加速试验期间,有关物质略有增加,水分结果有所增加,但均在限度范围内,其他考察指标无明显变化。结论本处方及工艺制备的注射用托拉塞米,质量稳定,可行性好,适合工业化大生产。
Objective To explore the formulation and preparation process of Torasemide Injection with high quality and stability.Methods The formulation of Torasemide Injection was determined by screening excipents and proportion.The preparation process of torasemide for injection was determined by investigating the temperature of liquid mixing and pH,decarbonization process and filtration material,filling container and freeze-parameters.Results The best prescriptions were Torasemide(10 mg),Sodium Bicarbonate(20 mg),Mannitol(100 mg).The preparation temperature is controlled at 15-25℃,and the pH value of the liquid was adjusted to 9.0 by 5%sodium hydroxide,and stored below 10℃at the same time.Polyethersulfone membrane was used for filtration with 0.45μm+0.22μm.Colorless low-borosilicate glass controlled injection bottle 5 ml or 10 ml,butyl bromine rubble plug for packaging.The optimum freeze-drying process conditions was that products were pre-frozen for 3 hours at-40℃.The heat conducting oil was heated to 0℃for 40-60 hours.The heat conducting oil was heated to 20℃for 6-8 hours.The final product was kept at 35℃for 6-8 hours.The contents of 202009031,202009032 and 202009033 samples were 100.21%,100.83%and 99.82%respectively by high performance liquid chromatography.During months long-term test and accelerated test,the moisture content of 202009031 samples increased,but all of them were within the limit,and other inspection indexes did not change significantly.During months long-term test and accelerated test of 202009032 and 202009033 samples,the related substances increased slightly and the moisture content increased slightly,but all of them were within the limits,and the other indexes did not change significantly.Conclusion The Torasemide Injection prepared by this prescription and process has stable quality,good feasibility and suitable for industrial production.
作者
李朴超
王小文
唐海
朱柏儒
刘全礼
LI Puchao;WANG Xiaowen;TANG Hai;ZHU Boru;LIU Quanli(College of Pharmacy,Baotou Medical College,Inner Mongolia Autonomous Region,Baotou014040,China;Tasly Research Institute Jiangsu Tasly Diyi PHarmaceutical Co.,Ltd.,Tianjin300410,China)
出处
《中国当代医药》
CAS
2022年第25期40-44,共5页
China Modern Medicine
关键词
托拉塞米
处方筛选
工艺参数
质量研究
Torasemide
Prescription screening
Process parameters
Study of quality