Theoretical and experimental studies on the internal mobility of two sulfonylurea agents: glibenclamide and glimepiride

Molecular dynamics of glibenclamide and glimepiride in their glassy state were studied by means of broadband dielectric spectroscopy. In both compounds we found a gamma-relaxation process, with nearly the same value of activation energy. Further, we were able to identify the origin of gamma relaxation by performing calculations within the framework of density functional theory. It was found that rotation of the chain end included cyclohexyl and neighboring carbonyl group is related to the observed mode in dielectric spectra. The calculated activation energy was only a few kJ per mole lower than the energies obtained from experiment. It is demonstrated that this fast gamma process is insensitive to pressure. Finally, another secondary mode in glibenclamide, predicted by computations, was confirmed from dielectric measurements at elevated pressure. Our calculations indicate that this mode should be pressure-sensitive.