Activation energies for the decomposition of pharmaceuticals and their application to predicting hydrolytic stability in drug discovery

The stability of drug-like molecules is one of the most important areas of the drug development process and Arrhenius studies can be used in order to predict the stability of compounds by performing forced degradation studies at elevated temperatures and then extrapolating the data to room temperature. Analysis of the activation energies calculated from 166 Arrhenius experiments performed on drug-like molecules in solution, using temperatures up to 90 °C, indicates that the mean activation energy for these degradations is 98.6 kJ/mol (23.6 kcal/mol). The impact on the predicted half-lives of employing different activation energies is discussed.