Characterization of a Hydrate–Dehydrate System with Critical Transitions in the Typical Range of Processing and Storage Conditions

Abstract

The use of water in pharmaceutical processing, along with the ubiquitous presence of water in the environment make the study and characterization of pharmaceutical hydrates a subject of particular interest to the quality of the in-process material as well as on the performance of the final product. Many drug compounds produce crystalline hydrates. The temperature and humidity conditions used during the processing, handling and storage of pharmaceutical products has an important effect on the dynamics of hydration and dehydration pertaining to hydrate formation. The key to such dynamics is the energetics of the interaction of water with the drug molecule in forming the hydrate. Such an effect can be probed in practice through studies of hydration as a function of temperature and water activity. We present a case study where the energetics of hydration are such that the system can turn into one of three crystalline forms by small changes in temperature or relative humidity, near the typical ambient conditions. The example illustrates how characterization techniques can be integrated to create a phase diagram showing the conditions leading to different hydrated or dehydrated forms.