Characterisation of moisture uptake effects on the glass transitional behaviour of an amorphous drug using modulated temperature DSC

The purpose of this study was to investigate the depression of the glass tr ansition temperature, T-g, of the protease inhibitor saquinavir in the firs t heating scan as a function of the quantity of sorbed water by the applica tion of modulated temperature differential scanning calorimetry (MTDSC). Sa mples of amorphous saquinavir were pretreated under various humidity condit ions and the quantity of sorbed water measured by thermogravimetric analysi s. MTDSC runs were performed using hermetically and non-hermetically sealed pans in order to determine the glass transition temperature. MTDSC allowed the separation of the glass transition from the enthalpic relaxation, ther eby allowing clear visualisation of T-g for amorphous saquinavir in the fir st heating scan. The plasticizing effects of water were assessed, with the depression in T-g related to the mole fraction of water sorbed via the Gord on-Taylor relationship. An expression has been derived which allows estimat ion of the water content which lowers the T-g to the storage temperature, t hereby considerably increasing the risk of recrystallisation. It is argued that this model may aid prediction of the optimal storage conditions for am orphous drugs. (C) 1999 Elsevier Science B.V. All rights reserved.