Morphological and Structural Properties of Amorphous Lactulose Studied by Scanning Electron Microscopy, Polarized Neutron Scattering, and Molecular Dynamics Simulations.
Morphological and structural properties of amorphous disaccharide lactulose (C12H22O11), obtained by four different amorphization methods (milling, quenching of the melt form, spray-drying, and freeze-drying), are investigated by scanning electron microscopy, polarized 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 polarized neutron scattering. Microstructure of the milled sample appears slightly different from the other amorphized 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 and 4%, and their size remains between 20 and 30 nm despite a long milling time of about 8 h. 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 polarized neutron scattering.
['Ngono|Frederic|F|0000-0001-7880-5907', 'Cuello|Gabriel J|GJ|', 'Jiménez-Ruiz|Monica|M|0000-0002-9856-807X', 'Willart|Jean-Francois|JF|0000-0002-7911-3918', 'Guerain|Mathieu|M|', 'Wildes|Andrew R|AR|', 'Stunault|Anne|A|', 'Hamoudi-Ben Yelles|Cherifa-Mounira|CM|', 'Affouard|Frederic|F|0000-0001-8429-6416']
D002152:Calorimetry, Differential Scanning D003460:Crystallization D003890:Desiccation D004339:Drug Compounding D004355:Drug Stability D005612:Freeze Drying D007536:Isomerism D007792:Lactulose D008855:Microscopy, Electron, Scanning D056004:Molecular Dynamics Simulation D009502:Neutrons D010316:Particle Size D011208:Powders D014961:X-Ray Diffraction
structure molecular dynamics simulation milling spray-drying freeze-drying crystallites amorphous sugar neutron diffraction quenching melt