程序变温法确定药物降解反应级数

通过电子计算机模拟程序升温加速试验,从理论上阐明了常规的程序升温法不能确定药物降解反应级数的原因是因为同一组数据可由不同的反应级数和活化能的组合所拟合;解决这一问题的关键是在一个变温程序中包含升温和降温部分;据此提出了一种新的程序变温方法(程序升降温法)。利用这种方法,可以真正做到只通过一次程序变温加速试验,就获得包括反应级数在内的药物降解的动力学参数,且确定反应级数的能力与恒温法相近似。

DETERMINATION OF RATE ORDER FOR DEGRADATION OF DRUGS WITH NONISOTHERMAL STABILITY ESPERIMENT

By a theoretical investigation of simulated nonisothermal data, the inability to determine the rate order for degradation of drugs with ordinary nonisothermal experiment was discussed. Results indicate that both rate order n and activation energy E can change the curvature of the c-t curve and the change caused by higher n can be compensated by higher E in ordinary nonisothermal experiments. That means a suitable E can always be assessed to fit each of the definite n (0, 1, or 2 in our study) very well. As a result, a same set of c-t data can be well fitted by different combinations of n and E. This is why the rate order cannot be assessed in ordinary nonisothermal experiments. To overcome this deficiency, it is important that there have both temperature rising and lowering parts in one nonisothermal experiment. A new heating model, temperature rising and lowering program, was presented. With this new heating model, the kinetic parameters, including the rate order, can be obtained in one nonisothermal stability experiment. The ability of the new heating model to determine rate order is almost the same as that of isothermal experiments.