Bhugra Chandan, Shmeis Rama, Krill Steven L, Pikal Michael J
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 North Eagleville Road, Storrs, Connecticut 06269, USA.
J Pharm Sci. 2008 Oct;97(10):4498-515. doi: 10.1002/jps.21324.
Stability of the amorphous state has been linked to molecular mobility of the matrix; however different techniques may capture different mobility substates. Our previous work suggested that two calorimetric techniques, Isothermal Microcalorimetry (TAM) and MDSC, measured different aspects of mobility with TAM measuring, in part, some faster modes of relaxation in addition to the modes mobilized at T(g). The aim of this work is to compare the relaxation times obtained using Thermally Stimulated Depolarization Current Spectroscopy (TSDC) with calorimetric mobility measured below T(g) and to determine if all measures of relaxation times below T(g) are consistent with relaxation times obtained above T(g) using Dielectric Spectroscopy (DRS). Model compounds were indomethacin, ketoconazole, nifedipine, flopropione, felodipine. For all compounds, relaxation times obtained using Thermal Windowing-TSDC technique below T(g) correlated well with relaxation times (tau) obtained above T(g) by DRS. At any given temperature below T(g), relaxation times measured depended upon the technique used and were in the following order TSDC < TAM < MDSC (tau). TSDC captures some faster relaxations not measured by calorimetric techniques, and therefore, different techniques give different measures of relaxation times below T(g). This information is important in understanding the relationships between mobility in the glassy solid and pharmaceutical stability.
非晶态的稳定性与基质的分子流动性有关；然而，不同的技术可能捕捉到不同的流动性亚状态。我们之前的工作表明，两种量热技术，等温微量热法（TAM）和调制式差示扫描量热法（MDSC），测量了流动性的不同方面，其中TAM部分测量了一些除了在玻璃化转变温度（Tg）时被激发的弛豫模式之外的更快弛豫模式。这项工作的目的是比较使用热刺激去极化电流光谱法（TSDC）获得的弛豫时间与在Tg以下测量的量热流动性，并确定Tg以下所有弛豫时间的测量值是否与使用介电光谱法（DRS）在Tg以上获得的弛豫时间一致。模型化合物为吲哚美辛、酮康唑、硝苯地平、氟丙酰、非洛地平。对于所有化合物，使用热窗口-TSDC技术在Tg以下获得的弛豫时间与通过DRS在Tg以上获得的弛豫时间（τ）相关性良好。在Tg以下的任何给定温度下，测量的弛豫时间取决于所使用的技术，并且按以下顺序排列：TSDC < TAM < MDSC（τ）。TSDC捕捉到了一些量热技术未测量到的更快弛豫，因此，不同的技术给出了Tg以下弛豫时间的不同测量值。这些信息对于理解玻璃态固体中的流动性与药物稳定性之间的关系很重要。
