Purpose

This work evaluates the probability and impact of using high-temperature accelerated aging for determining shelf life based on reaction mechanism changes.

Method

Simulations are made to calculate the probability of a significant error in determining shelf life based on high-temperature stability data. Published distributions of activation energies and varied transition temperatures (T_x, the temperature where both processes are equally involved) to calculate shelf impacts from mechanism changes using high temperature data to assign long-term shelf life.

Results

High-temperature mechanism changes with respect to individual degradation products rarely occur when using accelerated stability studies. Even in the uncommon scenario of a mechanism change with temperature, the probability of there being a practical error in a shelf life determination from using these data is calculated to be less than 25%. High temperature modeling does bring a prediction risk when there is either a phase change or secondary degradation.

Conclusion

High temperature data can reliably be used to determine long-term shelf life in most cases. Changes of mechanism with temperature rarely occur and when they do, most often they will not result in a longer shelf life assigned than will ultimately be observed.

中文翻译：

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高温机制变化：使用药物加速老化模型的意义

目的

这项工作评估了使用高温加速老化根据反应机制变化确定保质期的可能性和影响。

方法

进行模拟以计算根据高温稳定性数据确定保质期时出现重大错误的概率。发布了活化能和不同转变温度（T _x，两个过程同等参与的温度）的分布，以使用高温数据计算机制变化对保质期的影响，以分配长期保质期。

结果

当使用加速稳定性研究时，单个降解产物的高温机制变化很少发生。即使在机制随温度变化的罕见情况下，使用这些数据确定保质期时出现实际错误的概率也低于 25%。当存在相变或二次降解时，高温建模确实会带来预测风险。

结论

在大多数情况下，高温数据可以可靠地用于确定长期保质期。机制随温度的变化很少发生，即使发生，大多数情况下也不会导致指定的保质期比最终观察到的更长。