Physical stability and relaxation of amorphous indomethacin.
The alpha- and beta-relaxation processes in amorphous indomethacin have been studied by using differential scanning calorimetry. The beta-process has been detected as a small endothermic peak that emerges before the glass transition step when reheating samples previously annealed in the temperature region -20 to +5 degrees C. The activation energy of the beta-process is approximately 57 kJ mol(-1), and shows an increase with increasing temperature as it approaches the glass transition region. In the glass transition region, the effective activation energy of relaxation decreases with increasing temperature from 320 to 160 kJ mol(-1). Heat capacity measurements have allowed for the evaluation of the cooperatively rearranging region in terms of the linear size (3.4 nm) and the number of molecules (90). The beta-relaxation fades below -30 degrees C, which provides a practical estimate for the lower temperature limit of physical instability in indomethacin. It is demonstrated experimentally that nucleation of indomethacin takes place in the temperature region of the beta-relaxation.
Vyazovkin
Sergey
S
Department of Chemistry, University of Alabama at Birmingham, 901 South 14 Street, Birmingham, Alabama 35294, USA. vyazovkin@uab.edu
Dranca
Ion
I
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D007213:Indomethacin / Q000737:chemistry*; D015394:Molecular Structure; D013816:Thermodynamics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin