Wang D Q, Hey J M, Nail S L
Process and Technology Development, Biological Products, Bayer Corporation, Berkeley, California 94701, USA.
J Pharm Sci. 2004 May;93(5):1253-63. doi: 10.1002/jps.20065.
Recombinant Factor VIII (rFVIII) and alpha-amylase were used as model proteins to examine the effect of freeze-drying process conditions on the long-term stability of these proteins as freeze-dried solids. The same sucrose/glycine formulation was used for all treatments. Three freeze-drying protocols were used-an "aggressive" and a "conservative" cycle that both produced pharmaceutically acceptable product, and a protocol that produced a collapsed matrix. For rFVIII, there was no difference in the biological activity versus the time profile for product freeze-dried under the three different conditions when stored at 5 or 25 degrees C. At 40 degrees C, however, the stability of the collapsed product appeared to be better than that of product freeze-dried with no collapse. Also, the level of residual moisture in the collapsed product was higher than that of the product with no collapse. For alpha-amylase, there was no significant difference in the stability profile at any of the temperatures over the time course of the study. The results support the conclusion that collapse is not necessarily detrimental to the long-term stability of freeze-dried proteins.
重组凝血因子VIII（rFVIII）和α-淀粉酶被用作模型蛋白，以研究冷冻干燥工艺条件对这些蛋白作为冻干固体的长期稳定性的影响。所有处理均使用相同的蔗糖/甘氨酸配方。采用了三种冷冻干燥方案——一种“激进”循环和一种“保守”循环，二者均产生了药学上可接受的产品，以及一种产生塌陷基质的方案。对于rFVIII，在5或25摄氏度储存时，在三种不同条件下冻干的产品，其生物活性与时间曲线没有差异。然而，在40摄氏度时，塌陷产品的稳定性似乎优于未塌陷的冻干产品。此外，塌陷产品中的残留水分水平高于未塌陷产品。对于α-淀粉酶，在研究的时间过程中，在任何温度下其稳定性曲线均无显著差异。这些结果支持以下结论：塌陷不一定对冻干蛋白的长期稳定性有害。
