变温加速法解析阿司匹林降解反应的动力学参数

Using nor-isothermal method on kinetic parameters of degradation of aspirin

目的:采用变温加速法测定药物降解反应的动力学参数。并与等温加速法相比较,考察该方法的准确性。方法:以阿司匹林为模型药物,在设定的实验条件下,从温度变化过程中药物的残存率与时间的关系入手,根据化学动力学的原理,采用非线性最小二乘法解析其降解反应的动力学参数Ea及A。结果:阿司匹林的降解反应属准一级反应。在pH 2、pH 4和pH 6的条件下,采用变温加速法求得阿司匹林的降解反应的Ea分别是:16.13、18.19和23.87 kJ/mol(升温速率为5℃/h和10℃/h的平均值),等温加速法测得的Ea分别为16.12、18.01和23.93 kJ/mol。结论:采用变温加速法与等温加速法测得的药物降解反应的动力学参数基本一致。与等温加速法相比,变温加速法测定药物的稳定性具有迅速、可靠、简便、用样量少等特点。

Objective： To study the kinetic parameters of degradation of aspirin by the nor-isothermal method （and Compare with isothermal method） , To researched the accuracy and credibility of the method, Methods： Aspirin was used as a model drug. Under certainly experiment conditions, the stability of aspirin was studied by the nor-isothermal method which was defined as a linear relationship between time and temperature. The value of activation energy （ Ea ） and frequency factors （ A ） were calculated by applying the nonlinear least-square method. Results：The degradation of aspirin was attributed to pseudo first order reaction. The Ea values calculated by the nor-isothermal method were 16. 13 （pH 2） ,18.19 （pH 4） and 23.87（pH 6） kJ/mol （the mean values of Ea at 5 ℃/h and 10 ℃/h） respectively. The corresponding isothermal method values were 16. 12 （ pH 2） , 18.01 （ pH 4 ） and 23.93 （ pH 6） kJ/mol respectively. Condusion：The results indicated that the kinetic parameter determined by the nor-isothermal method was in good accord with that of isothermal method. These results indicated that the nor-isothermal method described in this study could be adequately used for the stability study and was a rapid and accurate method for the determination of kinetic parameters.