Effect of glass transition temperature on the stability of lyophilized formulations containing a chimeric therapeutic monoclonal antibody
Effect of glass transition temperature on the stability of lyophilized formulations containing a chimeric therapeutic monoclonal antibody
复制标题
DOI：
10.1023/a:1012144810067
复制
发表时间：
1997-05-01
影响因子：
3.7
通讯作者：
DalMonte, PR
中科院分区：
文献类型：
--
作者：
Duddu, SP;DalMonte, PR
目的。本研究的目的是强调了解主要由糖和蛋白质组成的冻干无定形固体的玻璃化转变温度T-g在解释加速稳定性数据中的重要性。用DSC和介电弛豫光谱测量了玻璃化转变温度。用排粒径色谱法监测固体状态下蛋白质的聚集。蔗糖配方（T-g近似于59℃）在60℃下储存时发生了明显的聚集，而海藻糖配方（T-g近似于80℃）在60℃下是稳定的。蔗糖配方在60℃下观察到的不稳定性可归因于其T-g（近似于59℃）接近测试温度。蛋白质/糖比的增加对蔗糖和海藻糖配方的T(g)s有增加作用，但增加的程度不同。由于配方在其保质期内以玻璃态存在，在玻璃态（40℃）下产生的加速稳定性数据可能比在更高温度（60℃）下产生的数据更好地预测配方的相对稳定性，其中一种配方处于玻璃态，而另一种配方接近或高于其T-g。
Purpose. The purpose of this study is to highlight the importance of knowing the glass transition temperature, T-g, of a lyophilized amorphous solid composed primarily of a sugar and a protein in the interpretation of accelerated stability data.Methods. Glass transition temperatures were measured using DSC and dielectric relaxation spectroscopy. Aggregation of protein in the solid state was monitored using size-exclusion chromatography.Results. Sucrose formulation (T-g similar to 59 degrees C) when stored at 60 degrees C was found to undergo significant aggregation, while the trehalose formulation (T-g similar to 80 degrees C) was stable at 60 degrees C. The instability observed with sucrose formulation at 60 degrees C can be attributed to its T-g (similar to 59 degrees C) being close to the testing temperature. Increase in the protein/sugar ratio was found to increase the T(g)s of the formulations containing sucrose or trehalose, but to different degrees.Conclusions. Since the formulations exist in glassy state during their shelf-life, accelerated stability data generated in the glassy state (40 degrees C) is perhaps a better predictor of the relative stability of formulations than the data generated at a higher temperature (60 degrees C) where one formulation is in the glassy state while the other is near or above its T-g.