Thermal behavior of ursodeoxycholic acid in urea: Identification of anomalous peak in the thermal analysis

The objective of this study was to clarify the thermal behavior of ursodeox ycholic acid (UDCA) in mixtures with urea. Physical mixtures of UDCA and ur ea in various ratios were prepared, and the thermal analysis of these sampl e mixtures was investigated using conventional differential scanning calori metry (DSC) and variable-temperature powder X-ray diffractometry (VTXRD). T he hot-stage microscopy (HSM) and powder X-ray diffractometry (PXRD) were u sed as complementary techniques. From the DSC results of all sample mixture s, it was,found that there was no endothermic peak at the melting temperatu re of intact UDCA crystals. The DSC thermograms of each ratio showed only t he endothermic peak at about 136 degreesC due to the melt of urea and the a nomalous endothermic peak at about 155 degreesC-157 degreesC. The VTXRD stu dy revealed that the crystals of urea completely disappeared at a temperatu re of 140 degreesC. At this temperature, it was identified that the VTXRD p attern obtained was of UDCA crystals. The crystalline peaks gradually decre ased in intensity at a temperature of 150 degreesC. When the temperature wa s up to 160 degreesC, the identical crystalline peaks of UDCA crystals comp letely disappeared. It was concluded that the anomalous endothermic peak at 155 degreesC-157 degreesC was the peak due to the dissolution of UDCA crys tals in the surrounding melted urea.