注射用替加环素冻干工艺优化  

Optimization of Freeze-drying Process of Tigecycline for Injection

作　　者：任俊[1,2] 束余声[2] 欧宁[3] 许建国[2] 

机构地区：[1]南京医科大学药学院,江苏南京210029 [2]江苏省苏北人民医院药剂科,江苏扬州225001 [3]南京医科大学第一附属医院药剂科,江苏南京210029

出　　处：《中国医药工业杂志》2013年第11期1115-1119,共5页Chinese Journal of Pharmaceuticals

摘　　要：通过调整注射用替加环素在冻干过程中加入的冻干保护剂和溶液pH值，及预冻阶段和升华阶段导热油的温度，达到缩短冻干周期并提高制品稳定性的目的。所得最佳冻干工艺是在样品溶液中加入替加环素2倍处方量的乳糖，用1m01／L盐酸调至pH5．0～6．5，预冻阶段先降至共晶点附近（-10℃）保持约O．5h，然后降温至-40℃，维持1h；待样品完全冻结后再退火至-10℃保持0．5h，再降温至-40℃并维持2h；升华干燥阶段导热油温度设为8℃，并保持6．5h后再进行二次干燥（升温至40℃，维持4．5h）。所得制品中水分含量降低，稳定性提高，且冻干周期缩短至约20h。To shorten the freeze-drying cycle and improve the stability of tigecycline for injection, the kind and dosage of freeze-drying protective agent, the pH value of the solution and heat conducting oil temperature in pre-freezing and sublimation stage were optimized. The optimal freeze-drying process was to add lactose as the protectant with the amount of two times as much as tigecycline and adjust to pH 5.0 - 6.5 with 1 mol/L hydrochloric acid. Intermediate product should be keep for about 0.5 h at the vicinity of the eutectic point （-10 ℃） before cooled to -40 ℃, then the product should be keep for 1 h at -40 ℃. The next step was to heat the already frozen product to -10 ℃ and keep for 0.5 h. Subsequently, the temperature was decreased to -40 ℃ again and maintained for 2 h. Then the conducting oil temperature should be set at 8 ℃ for about 6.5 h before the temperature was elevated to 40 ℃ for 4.5 h. This improved freeze-drying process would significantly improve the stability of the final product and decrease the moisture content, and whereas reduce the freeze dryin~ period to about 20 h.

关 键 词：注射用替加环素 冻干工艺 冻干周期 工艺优化 

分 类 号：R944.11[医药卫生—药剂学]