Use of real‐time FT‐IR monitoring of a pharmaceutical compound under stress atmospheric conditions to characterize its solid‐state degradation kinetics

The use of online FT‐IR is described for investigating the degradation kinetics of the solid amorphous pharmaceutical compound, fosaprepitant dimeglumine (FD), under stress storage conditions (i.e., high temperature, T, and humidity, % RH). It is found that under conditions of elevated T and % RH, the kinetics are denucleation rate limited for the deliquescence of the amorphous FD solid, based on the high quality fits obtained to the authors' dispersive kinetic model for that mechanism. At elevated T and low % RH, it is found that a classical, first‐order hydrolysis mechanism for the degradation of FD (which forms crystalline aprepitant, AP) significantly contributes to the overall conversion rate. That mechanism is similar to the one observed previously for the solution‐phase hydrolysis of FD. Appropriate kinetic models are proposed for the FD‐to‐AP conversion under all of the experimental conditions investigated in this work. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 42: 25–36, 2010