Solid-State Study of the Structure, Dynamics, and Thermal Processes of Safinamide MesylateA New Generation Drug for the Treatment of Neurodegenerative Diseases

Safinamide mesylate
(SM), the pure active pharmaceutical
ingredient (API) recently used in Parkinson disease treatment, recrystallized
employing water–ethanol mixture of solvents (vol/vol 1:9) gives
a different crystallographic form compared to SM in Xadago
tablets. Pure SM crystallizes as a hemihydrate in the
monoclinic system with the P21 space group.
Its crystal and molecular structure were determined by means of cryo
X-ray crystallography at 100 K. SM in the Xadago tablet
exists in anhydrous form in the orthorhombic crystallographic system
with the P212121 space group. The water migration and thermal processes in the crystal
lattice were monitored by solid-state NMR spectroscopy, differential
scanning calorimetry, and thermogravimetric analysis. SM in Xadago in the high-humidity environment undergoes phase transformation
to the P21 form which can be easily reversed
just by heating up to 80 °C. For the commercial form of the API,
there is also a reversible thermal transformation observed between Z′ = 1 ↔ Z′ = 3 crystallographic
forms in the 0–20 °C temperature range. Analysis of molecular
motion in the crystal lattice proves that the observed conformational
polymorphism is forced by intramolecular dynamics. All above-mentioned
processes were analyzed and described employing the NMR crystallography
approach with the support of advanced theoretical calculations.