Trehalose amorphization and recrystallization Original Research Article

The stability of the amorphous trehalose prepared by using several procedures is presented and discussed. Amorphization is shown to occur by melting (Tm = 215 °C) or milling (room temperature) the crystalline anhydrous form TRE-β. Fast dehydration of the di-hydrate crystalline polymorph, TRE-h, also produces an amorphous phase. Other dehydration procedures of TRE-h, such as microwave treatment, supercritical extraction or gentle heating at low scan rates, give variable fractions of the polymorph TRE-α, that undergo amorphization upon melting (at lower temperature, Tm = 130 °C). Additional procedures for amorphization, such as freeze-drying, spray-drying or evaporation of trehalose solutions, are discussed. All these procedures are classified depending on the capability of the undercooled liquid phase to undergo cold crystallization upon heating the glassy state at temperatures above the glass transition temperature (Tg = 120 °C). The recrystallizable amorphous phase is invariably obtained by the melt of the polymorph TRE-α, while other procedures always give an amorphous phase that is unable to crystallize above Tg. The existence of two different categories is analyzed in terms of the transformation paths and the hypothesis that the systems may exhibit different molecular mobilities.