Bhattacharya Sisir, Suryanarayanan Raj
Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Pharm Sci. 2009 Sep;98(9):2935-53. doi: 10.1002/jps.21728.
In recent years, considerable effort has been directed towards correlating molecular mobility with the physical as well as chemical stability of amorphous pharmaceuticals. Global mobility (molecular motions associated with glass transition) has been the focus of most of these studies. However, in several instances, global mobility could not explain the instability. It is becoming recognized that local mobility (beta-relaxations), which is significant below the glass transition temperature, could be influencing stability. Generally, information on the mobility of an amorphous pharmaceutical below the glass transition temperature (T(g)) has been obtained by extrapolation of data from above T(g). Such studies, while providing information about overall mobility, are unsuitable for directly characterizing the local mobility. Our overall objective is to highlight the pharmaceutical significance of local motions in amorphous pharmaceuticals, primarily the Johari-Goldstein relaxations. The coupling model, which correlated the local motions with global mobility, has been discussed in order to emphasize the potential impact of local mobility on amorphous phase stability. The influence of additives including water on the local motions in an amorphous matrix, as in molecular dispersions, has been reviewed. Finally, we have provided a brief overview, including the strengths and limitations, of the common instrumental techniques used to characterize local motions.
近年来，人们付出了相当大的努力来关联分子流动性与无定形药物的物理及化学稳定性。整体流动性（与玻璃化转变相关的分子运动）一直是这些研究中的大部分的重点。然而，在一些情况下，整体流动性无法解释不稳定性。人们逐渐认识到，在玻璃化转变温度以下显著的局部流动性（β弛豫）可能会影响稳定性。一般来说，关于无定形药物在玻璃化转变温度（T(g)）以下的流动性信息是通过外推高于T(g)的数据获得的。这类研究虽然能提供有关整体流动性的信息，但并不适合直接表征局部流动性。我们的总体目标是强调无定形药物中局部运动的药学意义，主要是乔哈里 - 戈尔茨坦弛豫。讨论了将局部运动与整体流动性相关联的耦合模型，以强调局部流动性对无定形相稳定性的潜在影响。综述了包括水在内的添加剂对无定形基质（如分子分散体）中局部运动的影响。最后，我们简要概述了用于表征局部运动的常见仪器技术，包括其优点和局限性。
