Differences in crystallization behavior between quenched and ground amorphous ursodeoxycholic acid

To study the crystallization of ground and quenched ursodeoxycholic acid (UDCA) and to characterize their amorphous states.

Amorphous UDCA was prepared by grinding and also by rapid cooling of the melt. These samples were characterized by powder X-ray diffraction (XRD), near IR spectra and dynamic water sorption. The heat associated with crystallization was measured in an isothermal microcalorimeter at 25 degrees C at various relative humidities (RH) (50%-100%) and, in the presence of the vapour from a mixed solvent of ethanol and water (ethanol conc. 10%-100%). The specific surface area was calculated from krypton adsorption. Contact angles were measured by using a Wilhelmy plate to calculate the surface energy of the samples.

Ground and quenched samples yielded amorphous XRD patterns. Differential scanning calorimetry thermographs of the milled sample revealed that crystallization occurred at around 80 degrees C, whereas the quenched sample did not crystallize. Exposure to humid air did not result in crystallization of either amorphous sample during the microcalorimetric experiments. In the presence of ethanol vapour, the ground sample did, but the quenched sample did not, crystallize. The amount of water sorption into the quenched sample was larger than that of the ground sample at low RH. The surface energy of the quenched material was different to that of the ground. Peak shifts were observed in the NIR spectra at around 1450, 2100 nm, allowing differentiation between the ground and quenched samples.

It can be concluded that different molecular states of amorphous UDCA were obtained depending on the preparation method. The crystallisation of amorphous UDCA was related to the molecular state of disorder.