Open AccessSolid-State Study of the Structure, Dynamics, and Thermal Processes of Safinamide Mesylate─A New Generation Drug for the Treatment of Neurodegenerative Diseases
Author(s) -
T. Pawlak,
Marcin Oszajca,
Małgorzata Szczesio,
Marek J. Potrzebowski
Publication year - 2021
Publication title -
molecular pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 127
eISSN - 1543-8392
pISSN - 1543-8384
DOI - 10.1021/acs.molpharmaceut.1c00779
Subject(s) - orthorhombic crystal system , monoclinic crystal system , crystal structure , differential scanning calorimetry , crystallography , polymorphism (computer science) , thermogravimetric analysis , chemistry , materials science , organic chemistry , thermodynamics , gene , genotype , biochemistry , physics
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 P 2 1 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 P 2 1 2 1 2 1 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 P 2 1 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.