Yoshioka S, Aso Y, Uchiyama M
National Institute of Hygienic Sciences, Tokyo, Japan.
J Pharm Sci. 1987 Oct;76(10):794-8. doi: 10.1002/jps.2600761009.
Nonisothermal prediction of drug stability based on direct nonlinear estimation of the shelf-life was compared with the isothermal approach. The reliability of the statistics for the estimates of the shelf-life (the time period required for a drug to degrade to 90% remaining at 25 degrees C) and activation energy obtained by the two methods was evaluated by the Monte Carlo method of computer simulations. The accuracy and precision of the estimates obtained by the nonisothermal method depended largely on the experimental conditions, such as experimental periods, sampling time, and temperature rise programs. The uncertainty of the estimates was determined mainly by the extents of drug degradation and temperature change achieved during the experiment. The nonisothermal method needed suitable experimental designs and precise assay methods of drug contents to provide reliable parameter estimates.
基于直接非线性估计保质期的药物稳定性非等温预测方法与等温方法进行了比较。通过计算机模拟的蒙特卡罗方法评估了两种方法获得的保质期估计值（药物在25摄氏度下降解至剩余90%所需的时间段）和活化能估计值的统计可靠性。非等温方法获得的估计值的准确性和精密度在很大程度上取决于实验条件，如实验周期、采样时间和升温程序。估计值的不确定性主要由实验过程中药物降解程度和温度变化幅度决定。非等温方法需要合适的实验设计和精确的药物含量测定方法来提供可靠的参数估计值。
