Lactulose: a model system to investigate solid state amorphization induced by milling.

In this paper, we show that crystalline lactulose can be amorphized directly in the solid state by mechanical milling. Moreover, compared to similar materials, the amorphization kinetics of lactulose is found to be very rapid and the amorphous state thus obtained appears to be very stable against recrystallization upon heating. These features make lactulose a model compound for this type of solid state transformation. The ease of crystalline lactulose to be amorphized upon milling is explained by comparing elastic constants of lactulose with those of several other disaccharides. These constants have been determined by molecular dynamics simulations. The paper also shows how isothermal dissolution calorimetry can be used effectively for the determination of amorphization kinetics during grinding when the usual characterization techniques (DSC and powder X-ray diffraction) fail.