Effect of product temperature during primary drying on the long-term stability of lyophilized proteins
Effect of product temperature during primary drying on the long-term stability of lyophilized proteins
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DOI：
10.1080/10837450701563459
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发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Rapaud, Michel
中科院分区：
文献类型：
--
作者：
Passot, Stephanie;Fonseca, Fernanda;Rapaud, Michel
我们的目的是研究在低于和高于Tg'（冷冻浓缩相的玻璃化转变温度）的产品温度下进行初级干燥对冻干蛋白质长期稳定性的影响。选择两种在所用填充剂的性质上不同的保护介质（无定形或结晶）。通过使用搁板温度和腔室压力的各种组合进行几个冻干循环，以在初级干燥期间获得不同的产品温度值。在冻干后以及在VC和25 ℃下储存6个月后测量蛋白质的抗原活性。储存6个月后，无论保护介质如何，两种毒素的抗原活性损失从在低于Tg'的产品温度下进行初级干燥时的0%增加到在高于Tg'的产品温度下进行初级干燥时的25%。部分结晶体系的使用使得可以承受高的初级干燥温度（高于Tg '）。然而，当包括蛋白质和稳定分子的无定形相变为粘性状态时，冻干蛋白质的保质期可能缩短。
Our objective was to investigate the effect of performing primary drying at product temperatures below and above Tg' (glass transition temperature of the freeze-concentrated phase) on the long-term stability of lyophilized proteins. Two protective media differing in the nature of the bulking agent used (amorphous or crystalline) were selected. Several lyophilization cycles were performed by using various combinations of shelf temperature and chamber pressure to obtain different values of product temperature during primary drying. The antigenic activity of the proteins was measured after lyophilization and after 6 months of storage at VC and 25 degrees C. After 6 months of storage and regardless of the protective medium, the losses of antigenic activity of both toxins increased from 0% when primary drying was performed at a product temperature lower than Tg' and to 25% when the product temperature was higher than Tg'. The use of partially crystalline systems makes it possible to withstand high primary drying temperatures (above Tg'). However, the shelf life of lyophilized proteins may be decreased when the amorphous phase including the protein and the stabilizing molecule changes to the viscous state.