caa a22 4500 477125743 CHVBK 20180405111649.0 cr unu---uuuuu 170330e19970601xx s 000 0 eng 10.1023/A:1012114825513 doi (NATIONALLICENCE)springer-10.1023/A:1012114825513 Evaluation of Amorphous Ursodeoxycholic Acid by Thermal Methods [Elektronische Daten] [Etsuo Yonemochi, Yasuhiko Ueno, Takao Ohmae, Toshio Oguchi, Shin-ichiro Nakajima, Keiji Yamamoto] Purpose. The purpose of this study was to characterize the amorphous state of ursodeoxycholic acid (UDCA) samples by using isothermal microcalorimetry, X-ray diffraction, infrared (IR) spectroscopy and solid state carbon 13 nuclear magnetic resonance (13C-NMR) spectroscopy, and to demonstrate the application of the thermal methods (microcalorimetry and differential scanning calorimetry (DSC)) for studying the amorphous state and clarifying the dissolution mechanism of UDCA. Methods. Amorphous UDCA was prepared by grinding and rapid cooling of the melts. The heat of solution of UDCA was measured by an isothermal heat-conduction twin microcalorimeter at 25.0°C. Some physicochemical properties of amorphous UDCA were also studied. Results. The intensities of X-ray diffraction peaks of crystalline UDCA decreased with an increase in grinding time. The heat levels of solution of crystalline UDCA and UDCA ground for 1 min were endothermic, and became exothermic with an increase in grinding time. A good correlation was obtained between 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 methods, significant differences were recognized in DSC, IR and 13C-NMR, and the heat of solution indicated different values among the two samples. The stability of amorphous UDCA samples stored under 74.5% relative humidity at 40°C was found to depend upon the preparation methods. Conclusions. Different states of amorphous UDCA were obtained depending on the preparation method. The application of thermal methods to evaluate the amorphous state was demonstrated. The mechanism of dissolution of UDCA was discussed from the results of the heat of solution examination. Plenum Publishing Corporation, 1997 ursodeoxycholic acid nationallicence amorphous nationallicence powder X-ray diffraction nationallicence thermal analysis nationallicence 13C-NMR nationallicence Yonemochi Etsuo Faculty of Pharmaceutical Sciences, Chiba University, 1−33 Yayoi-cho, 263, Inage-ku, Chiba, Japan aut Ueno Yasuhiko Faculty of Pharmaceutical Sciences, Chiba University, 1−33 Yayoi-cho, 263, Inage-ku, Chiba, Japan aut Ohmae Takao Faculty of Pharmaceutical Sciences, Chiba University, 1−33 Yayoi-cho, 263, Inage-ku, Chiba, Japan aut Oguchi Toshio Faculty of Pharmaceutical Sciences, Chiba University, 1−33 Yayoi-cho, 263, Inage-ku, Chiba, Japan aut Nakajima Shin-ichiro Hospital Pharmacy, Yamanashi Medical University, 409-38, Tamaho-cho, Yamanashi, Japan aut Yamamoto Keiji Faculty of Pharmaceutical Sciences, Chiba University, 1−33 Yayoi-cho, 263, Inage-ku, Chiba, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 798-803 0724-8741 14:6<798 1997 14 11095 https://doi.org/10.1023/A:1012114825513 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012114825513 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yonemochi Etsuo Faculty of Pharmaceutical Sciences, Chiba University, 1−33 Yayoi-cho, 263, Inage-ku, Chiba, Japan aut NATIONALLICENCE 700 1- Ueno Yasuhiko Faculty of Pharmaceutical Sciences, Chiba University, 1−33 Yayoi-cho, 263, Inage-ku, Chiba, Japan aut NATIONALLICENCE 700 1- Ohmae Takao Faculty of Pharmaceutical Sciences, Chiba University, 1−33 Yayoi-cho, 263, Inage-ku, Chiba, Japan aut NATIONALLICENCE 700 1- Oguchi Toshio Faculty of Pharmaceutical Sciences, Chiba University, 1−33 Yayoi-cho, 263, Inage-ku, Chiba, Japan aut NATIONALLICENCE 700 1- Nakajima Shin-ichiro Hospital Pharmacy, Yamanashi Medical University, 409-38, Tamaho-cho, Yamanashi, Japan aut NATIONALLICENCE 700 1- Yamamoto Keiji Faculty of Pharmaceutical Sciences, Chiba University, 1−33 Yayoi-cho, 263, Inage-ku, Chiba, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 798-803 0724-8741 14:6<798 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer