Fast Determination of Phase Stability of Hydrates Using Intrinsic Dissolution Rate Measurements

The critical water activity (a(w,c)) at a fixed temperature and transition temperature (T-t) in water between an anhydrate and its corresponding hydrate determine their physical stability. Hence, their accurate determination enables the efficient development of robust crystallization processes and formulation of drugs. The commonly used methods for determining the two parameters are either labor- and material-intensive or cannot be accurately measured due to slow kinetics. Thus, a material-sparing and fast method is desirable for adoption in the early stage of drug development when the materials and time are limited. In this study, we show that intrinsic dissolution rate (IDR) measurement is a fast (a few days) and material-sparing (<1 g) method for accurate determination of a(w,c), T-t, as well as free energy, enthalpy, and entropy of hydration. Overall, the IDR measurement is an advantageous technique for characterizing the stability of pharmaceutical hydrates in an early stage of drug development.