Freeze‐Drying of Proteins. Process, Formulation, and Stability.
Freeze‐Drying of Proteins. Process, Formulation, and Stability.
复制标题
蛋白质的冷冻干燥过程、配方和稳定性。
DOI：
10.1002/chin.199504315
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
M. Pikal
中科院分区：
文献类型：
--
作者：
M. Pikal
尽管冷冻干燥通常是生产治疗性蛋白质的首选方法，但蛋白质降解可能发生在过程中和/或储存期间。本文首先介绍了对过程控制至关重要的物理和工程原理，最后讨论了配方和稳定性之间的关系。通过在相关玻璃化转变温度以下快速冷冻和干燥至最佳残留水分（通常小于1%），最大限度地减少过程中降解。配方对工艺设计和稳定性都有重大影响，但稳定性增强的“机制”存在争议。初步得出结论：（a）冷冻过程中的稳定化主要是由于从蛋白质/水表面“排除”的溶质引起的蛋白质的热力学稳定性的增加;（B）干燥产物的稳定性通过在玻璃态载体中的固定化而增强。（c）干燥过程中的稳定性增强可能涉及固定化和“水替代”机制的方面。
Although freeze drying is often the process of choice for production of therapeutic proteins, protein degradation may occur in-process and/or during storage. This review begins with a presentation of physical and engineering principles critical to process control and concludes with a discussion of the relationship between formulation and stability. In-process degradation is minimized by rapid freezing and drying below the relevant glass transition temperature to the optimum residual moisture, which is normally less than 1%. Formulation has a major impact on both process design and stability, but "mechanisms" of stability enhancement are controversial. It is tentatively concluded that: (a) stabilization during freezing is largely due to the increase in thermodynamic stability of the protein caused by solutes that are "excluded" from the protein/aqueous surface; (b) stability of the dried product is enhanced by immobilization in a glassy (chemically inert) matrix; and (c) stability enhancement during drying may involve aspects of both the immobilization and the "water substitute" mechanisms.