Morphological and Structural Properties of Amorphous Lactulose Studied by Scanning Electron Microscopy, Polarized Neutron Scattering, and Molecular Dynamics Simulations

Abstract

Morphological and structural properties of amorphous disaccharide lactulose (C12H22O11), obtained by four different amorphisation methods (milling, quenching of the melt form, spray-drying and freeze-drying) are investigated by scanning electron microscopy, polarised neutron scattering and molecular dynamics simulations. While major differences on the morphology of the different amorphous samples are revealed by scanning electron microscopy images, only subtle structural differences have been found by polarised neutron scattering. Microstructure of the milled sample appears slightly different from the others amorphised materials with the presence of remaining crystalline germs which are not detected by X-ray diffraction. Quantitative phase analysis shows that these remaining crystallites are present in a ratio between 1-4%, and their size remains between 20-30 nm despite a long milling time of about 8 hours. The impact of the change in tautomeric concentrations on the physical properties of lactulose in the amorphous state has been investigated from molecular dynamics simulations. It is suggested that chemical differences between lactulose tautomers could be at the origin of small structural differences detected by polarised neutron scattering.

Impact of Amorphization Methods on the Physicochemical Properties of Amorphous Lactulose

“…However, it is worth noticing that subtle structural differences between the different amorphous states were detected by neutron diffraction investigations. These results are reported in detail in ref .…”

Impact of Low Concentration of Strongly Hydrogen-Bonded Water Molecules on the Dynamics of Amorphous Terfenadine: Insights from Molecular Dynamics Simulations and Dielectric Relaxation Spectroscopy

“…The amount of water content and water uptake are also highly dependent on the processes used to generate the amorphous solids. In practice, it can be produced by many different routes: (i) the classical thermal quench from the liquid state, , (ii) the mechanical route (compression and milling) occurring entirely in the solid state, − and (iii) the solvent removal processes (freeze-drying and spray-drying) requiring the dissolution of the compound in a solvent. − It is well recognized that water uptake can be particularly important for amorphous solids obtained by milling since this technique intrinsically increases the specific surface area of the materials. , Water content might also be important in some freeze-dried or spray-dried systems since they are first dissolved in water before imposing subsequent freezing and drying stages to systems. − …”