RH‐Temperature Stability Diagram of the Dihydrate, β‐Anhydrate, and α‐Anhydrate Forms of Crystalline Trehalose

Trehalose crystals exhibit polymorphic, deliquescent, and hydrate-forming traits and can exist in dihydrate, β-anhydrate, or α-anhydrate (isomorphic desolvate) forms. The objective of this study was to identify the relative humidity (RH) and temperature boundaries for phase changes of these different trehalose crystal forms. The deliquescence points (RH0 s) of the anhydrate and dihydrate trehalose crystals were determined from 20 to 50 °C using a combination of water activity and dynamic vapor sorption measurement techniques. Increasing temperatures from 20 to 50 °C resulted in decreases in RH0 from 95.5% to 90.9% RH for the dihydrate and 69.9% to 62.0% RH for the β-anhydrate. The effects of temperature on the anhydrate-hydrate RH boundaries were also determined, using a combination of equilibration in controlled water activity solutions, powder X-ray diffraction, and Fourier-transform infrared spectroscopy techniques. Increasing temperatures resulted in increases in the anhydrate-hydrate RH boundaries. The irreversible β-anhydrate to dihydrate boundary increased from 44.9% to 57.8% RH, and the reversible α-anhydrate to dihydrate boundary increased from 10% to 25% RH, as temperature increased from 20 to 50 °C. This is the first report of an RH-temperautre stability map for crystalline trehalose. PRACTICAL APPLICATION: The manuscript addresses the issue of the physical stability and phase transformations of crystalline trehalose stored in different temperature and relative humidity environments. Unwanted hydrate formation or dehydration of crystal hydrates can lead to other undesirable water-solid interactions and/or physical modifications that have the potential to influence product quality and delivery traits. Therefore, this study identified relative humidity and temperature stability boundaries of the different trehalose crystal forms, using a variety of established and novel techniques to create a relative humidity-temperature stability map of crystalline trehalose from 20 to 50 °C.