TY - JOUR
T1 - Local mobility in amorphous pharmaceuticals - Characterization and implications on stability
AU - Bhattacharya, Sisir
AU - Suryanarayanan, Raj
PY - 2009/9
Y1 - 2009/9
N2 - 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 (β-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 (Tg) has been obtained by extrapolation of data from above Tg. 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.
AB - 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 (β-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 (Tg) has been obtained by extrapolation of data from above Tg. 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.
KW - Amorphous
KW - Crystallization
KW - Lyophilization
KW - Mobility
KW - Physical characterization
KW - Solid dispersion
KW - Stability
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U2 - 10.1002/jps.21728
DO - 10.1002/jps.21728
M3 - Article
C2 - 19499564
AN - SCOPUS:68949132727
SN - 0022-3549
VL - 98
SP - 2935
EP - 2953
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 9
ER -