Vyazovkin Sergey, Dranca Ion
Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. vyazovkin@ uab.edu
J Phys Chem B. 2007 Jun 28;111(25):7283-7. doi: 10.1021/jp0700027. Epub 2007 May 27.
Differential scanning calorimetry has been used to study glassy indomethacin aged at 0 and -10 degrees C for periods of time up to 109 and 210 days, respectively. The results demonstrate the emergence of a small melting peak of the alpha-polymorph after aging for 69 days at 0 degrees C and for 147 days at -10 degrees C (i.e., approximately 55 degrees C below the glass-transition temperature) that provides evidence of nucleation occurring in the temperature region of the beta-relaxation. The evolution of an endothermic recovery peak temperature features a plateau at longer annealing times that suggests that the glass has made significant progress toward reaching the supercooled liquid state. It has been found that the melting peaks become detectable after the recovery peak has reached the plateau. The results highlight the importance of studying physical aging in the temperature region of the beta-relaxation as a means of evaluating the physical stability of amorphous pharmaceutical materials.
差示扫描量热法已用于研究在0℃和-10℃下分别老化长达109天和210天的玻璃态吲哚美辛。结果表明，在0℃老化69天和在-10℃老化147天（即比玻璃化转变温度低约55℃）后，出现了α-晶型的小熔融峰，这证明了在β-弛豫温度区域发生了成核现象。吸热恢复峰温度的演变在较长的退火时间呈现出一个平台期，这表明玻璃态已在向过冷液态转变方面取得了显著进展。已发现，在恢复峰达到平台期后，熔融峰变得可检测到。这些结果突出了研究β-弛豫温度区域内物理老化作为评估无定形药物材料物理稳定性手段的重要性。
