Phase Transitions and Anisotropic Mechanical Response in a Waterrich Trisaccharide Crystal

Abstract

Appreciating the mechanical response of molecular crystals in different hydration states is remarkable, and that under variable temperature conditions is hitherto unknown. We herein report the dehydration-driven anisotropic mechanical properties of raffinose pentahydrate (RF5W) single crystals as a function of temperature (T) using nanoindentation. The major face (011), with the initial loss of lattice water and the subsequent formation of defects, experienced a monotonous decrease in the hardness (H) and elastic modulus (E). Nonetheless, in the intermediate range of T, the minor face (002) exhibited a transient increase in the H and E due to dehydration-induced local structural rearrangements and the formation of slightly denser molecular packing and interactions. Beyond 65 °C, with the further loss of lattice water, the formation of defects predominates and interrupts the long-range ordering. The crystal–amorphous transformation leads to a drastic drop in the mechanical parameters. The optical and electron microscopy makes apparent observations on the expulsion of water from the crystal interior and the ensuing crystal surface transformations. The crystal hydrates are pervasive in drug formulations and could undergo dehydration to diminish the shelf life of a drug formulation. The mechanical response consequent to dehydration-driven crystal–amorphous transformation in an archetypal crystal hydrate highlights the probable ramifications on the pharmaceutical formulations.