In this study, the effect of dehydration conditions (air temperature and relative humidity) on the stability of ampicillin trihydrate was investigated. Firstly, the material was characterized. The results of gravimetric experiments provided the conditions where the trihydrate transforms into the anhydrate. The analysis of X-ray diffractometry patterns, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and Scanning Electron Microscopy (SEM) results allowed to confirm that the material used in this study is the ampicillin trihydrate. Secondly, the dehydration rate was found to increase strongly with ambient air temperature and to decrease with air relative humidity. The degradation of the trihydrate ampicillin (quantified by the HPLC method) during storage was activated by losing water molecules. This phenomenon has been explained by the enthalpy-entropy compensation phenomena. The measured evolutions of ampicillin trihydrate amount with time during dehydration for all considered ambient conditions were found to be well represented by the First order chemical kinetic model. The parameters of this equation were correlated to temperature and relative humidity by a simple expression which could be a possible mathematical representation of the ampicillin’s degradation curves. This kind of simple degradation curve fitting equation can be very helpful for the modelling and optimal control of pharmaceutically active components drying processes.