胶塞处理过程对易吸潮类冻干制品的水分有影响—以乳糖为例介绍.doc

摘 要 存放过程中，由于胶塞中的水分有可能会转移到冷冻干燥制品中，从而胶塞的水分会对冷冻干燥制品的水分含量造成影响。胶塞中释放的水分可能会对冷冻干燥制品的质量造成不良影响。 本研究的目的是评估处理过程和存放条件对胶塞水分含量的影响。胶塞在使用前，会进行清洗和灭菌。这些处理过程，尤其是灭菌处理会增加胶塞的水分含量，增加的幅度与胶塞的材质有密切关系。对于易吸潮类冷冻干燥制品，在存放过程中，这些被吸收的水分会从胶塞中释放出来然后转移至产品中。因此，需要一个合适的干燥过程来将胶塞的水分干燥至可以接受的水平。 胶塞水分研究的内容包括胶塞的材质，灭菌温度和时间，干燥温度和时间，存放的包装和条件，冷冻干燥对胶塞水分含量的影响以及水分从胶塞中转移至乳糖模型冷冻干燥品。结果证明胶塞在灭菌过程中会吸收大量的水分。为了得到水分较低的胶塞，需要在105oC条件下干燥至少4小时。干燥结束后，在室温存放条件下，胶塞的水分会迅速重新平衡。胶塞中的水分在冷冻干燥过程不会解吸附出来。 在进行水分含量对冷冻干燥制品稳定性影响的风险评估时，制品性质和灌装量都是很重要的因素。对于易吸潮的制品，尤其是低灌装量或小规格的制品，胶塞水分含量的控制尤其重要。 最后，胶塞中的水分转移至冷冻干燥制品的多少取决于初始胶塞的水分含量。为了减少水分带来的稳定性问题，有必要选择合适的胶塞以及对胶塞进行合适的处理和保存。 The Conditions of Stopper Processing Can Implicate the Water Content of Hygroscopic Lyophilized Products: A study with Lactose Stopper moisture content can have a significant impact on the water content of lyophilized drug products due to the potential of moisture transfer from stopper to product during storage. Moisture released from rubber stoppers may adversely affect the quality of lyophilized product during storage. The purpose of this study was to evaluate the effect of processing and storage condition on the moisture content of rubber stopper. Prior to its application, a rubber stopper is washed and steam sterilized. These processes, especially the process of steam sterilization, increase the moisture content of the rubber stopper and the moisture uptake can vary greatly depending on the rubber formulation. A sufficient drying cycle is needed to dry stoppers to an acceptable moisture level. The stopper moisture studies included the effect of rubber formulation，steam sterilization time, drying time and temperature, storage method and conditions, lyophilization and moisture transfer from stopper to a modellyophile of lactose. Results indicated that stoppers absorbed significant amount of moisture during sterilization. To achieve final moisture content at a lower level，stoppers required at least 4 h of drying at 105℃. After drying, stopper moisture levels equilibrated rapidly to am