1 research outputs found
Similar but Different: The Case of Metoprolol Tartrate and Succinate Salts
The solid-state structure and behavior
of tartrate (MT-o) and succinate
(MS-m) metoprolol salts have been studied with a combined experimental
(X-ray diffraction by both single crystal and microcrystalline powder
and differential scanning calorimetry) and modeling approach (molecular
dynamics and molecular orbital calculations). In spite of their close
similarity at the molecular level in the corresponding crystal lattices,
calorimetric data suggest for MS-m a slightly greater cohesive energy.
In addition and more importantly, they show significantly different
“macroscopic” behaviors: MS-m undergoes a reversible
anisotropic lattice expansion/contraction upon temperature change
and once melted quickly recrystallizes to the starting crystal phase.
On the other hand, MT-o expands/contracts isotropically, and upon
cooling from the melt gives an amorphous solid, which, at ambient
conditions, takes 6 days to completely revert to the starting crystal
form. Both findings are relevant in the field of the pharmaceutical
drug development; i.e., when the phase purity of these active pharmaceutical
ingredients is assessed, discussed, and possibly related to drug product
formulations and manufacturing methods