A simulation study with statistical evaluation for the determination of non-isothermal kinetics conditions in drugs stability.

Non-isothermal degradations were applied to carry out simulation studies to analyse the influence of some factors on the accuracy and precision of stability parameters of drugs, to establish the best work conditions in experimental studies of stability using non-isothermal methodology. These factors were: random error added, sampling frequency, heating model, extent of drug degradation, amplitude of temperature range and mean temperature. Simulation studies were realized for a first-order degradation process. A weighted non-linear regression was used to determine the stability parameters which were statistically evaluated. An ANOVA analysis and post hoc comparisons tests were made to determine the statistical significance of the influence of each factor studied on the central value and on the precision of stability parameters of drugs. Univariant general linear model allowed to establish quantitatively the effect of the variability of the factors studied on the variability on the precision of the kinetic parameters. It was found that the influence of the studied factors was not statistically significant (p>0.05) on the activation energy (E(a)) and shelf-life (t(90)) values. Nevertheless, four of the six analysed factors influenced with statistical significance on the precision of the shelf-life according the following decreasing order of importance: random error added, extent of drug degradation, amplitude of temperature range and heating model.