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.