An investigation into water interactions with amorphous and milled salbutamol sulphate: the development of predictive models for uptake and recrystallization.

An investigation into the effect of water uptake on the glass transition of spray dried and milled salbutamol sulphate has been performed, with a particular view to exploring how the water uptake, T(g) value and recrystallization behaviour correlate. Samples of milled and spray dried drug were stored under controlled humidity conditions and the T(g) measured as a function of time. The T(g) was measured using modulated temperature differential scanning calorimetry (MTDSC) while the water content was measured using thermogravimetric analysis (TGA). A correlation was found between time of storage, water content and T(g) in that the samples showed time dependent equilibration with the storage environment (either gaining or losing water depending on the RH). The relationship between water content and stability, based on the concept of T(g) lowering, was modelled using the semi-empirical approach of Royall et al. (1999) as well as a derivation of the Kwei equation which allowed the interaction between the water and substrate to be accounted for. A method for predicting stability based on two simple DSC runs is proposed. In addition, we discuss the observation of a double glass transition for the spray dried samples.