Determination of rate order for degradation of drugs with nonisothermal stability experiment.

The inability of ordinary nonisothermal experiments to determine the rate order (n) of drug degradation is discussed on the basis of a theoretical study of simulated nonisothermal data. In ordinary nonisothermal experiments, using either r or sigma(C[experiment] C[compute])2 as the measure of goodness of fit, the rate order cannot be assessed because the same set of c-t data can be well fitted by different combinations of estimates for n and the activation energy (E). Hence, a new nonisothermal heating-and-cooling model is introduced as a revision, in which sigma(C[experiment] C[compute])2 changes significantly with various kinetic models. Therefore, all the kinetic parameters, including the rate order, can be obtained in one nonisothermal stability experiment. Furthermore, the ability to determine rate order is significantly affected by the extent of drug degradation and experimental error, though not by sampling frequency or temperature change. To demonstrate the applicability of the heating-and-cooling model, the stability and rate order of degradation of vitamin C tablets was studied by this method.