Incorporating batch effects in the estimation of drug stability parameters using an Arrhenius model.

The nonlinear estimation of drug stability parameters (energy of activation Ea and shelf-life tY) by conventional approaches employs equations relating drug content determination C at time t and temperature T. The identification procedures lead to the determination of only one initial drug content C0 for several different experiments. However, it is well known that because of experimental concentration variation or of intentional modification of the experimental schedule, there are as many initial drug contents as experiments. For these reasons, a method which takes into account batch effects is proposed to determine stability parameters and also all initial drug contents C0j where j is the index of experiment in one step. This method is more accurate from a statistical viewpoint and is suitable for data treatment in pharmaceutical industries where the initial drug content of each batch entering the stability program can be checked a posteriori. The application of this method is shown on real kinetic data from the hydrolysis of acetylsalicylic acid (ASA).