EVALUATION OF AMORPHOUS URSODEOXYCHOLIC ACID BY THERMAL METHODS

Purpose. The purpose of this study was to characterize the amorphous s tate of ursodeoxycholic acid (UDCA) samples by using isothermal microc alorimetry, X-ray diffraction, infrared (IR) spectroscopy and solid st ate carbon 13 nuclear magnetic resonance (C-13-NMR) spectroscopy, and to demonstrate the application of the thermal methods (microcalorimetr y and differential scanning calorimetry (DSC)) for studying the amorph ous state and clarifying the dissolution mechanism of UDCA. Methods. A morphous UDCA was prepared by grinding and rapid cooling of the melts. The heat of solution of UDCA was measured by an isothermal heat-condu ction twin microcalorimeter at 25.0 degrees C. Some physicochemical pr operties of amorphous UDCA were also studied. Results. The intensities of X-ray diffraction peaks of crystalline UDCA decreased with an incr ease in grinding time. The heat levels of solution of crystalline UDCA and UDCA ground for 1 min were endothermic, and became exothermic wit h an increase in grinding time. A good correlation was obtained betwee n the heat of solution and the heat of crystallization determined from the peak area in DSC. Although no significant difference was observed in X-ray diffraction patterns of amorphous UDCA prepared by the two m ethods, significant differences were recognized in DSC, IR and C-13-NM R, and the heat of solution indicated different values among the two s amples. The stability of amorphous UDCA samples stored under 74.5% rel ative humidity at 40 degrees C was found to depend upon the preparatio n methods. Conclusions. Different states of amorphous UDCA were obtain ed depending on the preparation method. The application of thermal met hods to evaluate the amorphous state was demonstrated. The mechanism o f dissolution of UDCA was discussed from the results of the heat of so lution examination.