Solid State Amorphization of β-Trehalose: A Structural Investigation Using Synchrotron Powder Diffraction and PDF Analysis

Abstract

International audienceWe have investigated the amorphization of β-trehalose by high energy milling using in situ and ex situ synchrotron powder diffraction and PDF analysis. From this analysis we show that amorphization takes place through a two-phase process involving an amorphous and a long-range ordered phase. The proportion and coherent domain size of the latter rapidly decrease with milling time until the whole sample appears amorphized. The PDF describing the local structure of the amorphous phase after two hours of milling is very close to that of a sample quenched from the liquid, and seems to continue to evolve for longer milling times. Their differences with the PDF expected for a rigid THL molecule confirm the existence of a conformational disorder of the torsion angles from the glycosidic linkage between the two cycles forming the molecule

Properties of Aqueous Trehalose Mixtures: Glass Transition and Hydrogen Bonding

“…To validate and compare the structure of trehalose in the glassy state in simulation and experiment, we further compared our results with the recently reported structure of pure trehalose in the glassy and crystalline states, as resolved using X-ray powder diffraction. 60 The structure was reported in terms of the pair distribution function, 61 defined as G̃ ( r ) = 4π r [ρ e ( r ) – ρ 0 e ], where ρ e ( r ) and ρ 0 e are the electron density at distance r and in the bulk, respectively. The calculation of the pair distribution function from simulations is performed using the relation, 61 where b i is the scattering power of the i th atom, taken here for comparison with the X-ray experiments as the number of electrons of the specified atom.…”

“…(D) Pair distribution function G̃ ( r ) for pure trehalose in the crystalline and glassy states of 100 wt % trehalose, derived from simulations and from experimentally reported data. 60 Data sets are shifted for clarity. (E and F) Simulated radial distribution function g ( r ) compared to X-ray guided EPSR simulation-derived function, as reported in ref ( 62 ), shown for TW correlations at two concentrations.…”

Monitoring a Mechanochemical Reaction Reveals the Formation of a New ACC Defect Variant Containing the HCO3– Anion Encapsulated by an Amorphous Matrix

“…13 Ball milling can induce an alloying of metals 14 or polymorph changes (e.g., a transformation from the anatase to the rutile phase of TiO2). 15 Similarly, organic compounds mixtures of organic and inorganic compounds 16 undergo structural changes during mechanochemical treatment. This is of particular interest for pharmaceuticals as the higher solubility of amorphous phases enhances the uptake of drugs with poor water solubility.…”

Using Milling to Explore Physical States: The Amorphous and Polymorphic Forms of Sulindac

“…Mechanical milling of powders is a usual process used in the course of drug formulation to reduce the particle size. However this process may also change the physical state of the end product [1][2][3] , leading sometimes to an amorphization [4][5][6][7][8][9][10] and sometimes to a polymorphic transformation [11][12][13][14][15] . It appears, that amorphizations mainly occur when milling is performed below the glass transition temperature (Tg) of the material while polymorphic transformations mainly occur when milling is performed above Tg [13,16,17] .…”