Stoichiometric and Non-Stoichiometric Hydrates of Brucine.

The complex interplay of temperature and water activity (a(w)) / relative humidity (RH) on the solid form stability and transformation pathways of three hydrates (HyA, HyB and HyC), an isostructural dehydrate (HyA(dehy) ), an anhydrate (AH) and amorphous brucine has been elucidated and the transformation enthalpies quantified. The dihydrate (HyA) shows a non-stoichimetric (de)hydration behavior at RH < 40% at 25 °C and the removal of the water molecules results in an isomorphic dehydrate structure. The metastable dehydration product converts to AH upon storage at driest conditions or to HyA if exposed to moisture. HyB is a stoichiometric tetrahydrate. The loss of the water molecules causes HyB to collapse to an amorphous phase. Amorphous brucine transforms to AH at RH < 40% RH and a mixture of hydrated phases at higher RH values. The third hyrdate (HyC) is only stable at RH ≥ 55% at 25 °C and contains 3.65 to 3.85 mole equivalent of water. Dehydration of HyC occurs in one step at RH < 55% at 25 °C or upon heating and AH is obtained. The AH is the thermodynamically most stable phase of brucine at RH < 40% at 25 °C. Depending on the conditions, temperature and a(w), each of the three hydrates becomes the thermodynamically most stable form. This study demonstrates the importance of applying complimentary analytical techniques and appropriate approaches for understanding the stability ranges and transition behavior between the solid forms of compounds with multiple hydrates.