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Solid-State Study of the Structure, Dynamics, and Thermal Processes of Safinamide Mesylate—A New Generation Drug for the Treatment of Neurodegenerative Diseases
[Image: see text] 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 crystal...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728732/ https://www.ncbi.nlm.nih.gov/pubmed/34856803 http://dx.doi.org/10.1021/acs.molpharmaceut.1c00779 |
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author | Pawlak, Tomasz Oszajca, Marcin Szczesio, Małgorzata Potrzebowski, Marek J. |
author_facet | Pawlak, Tomasz Oszajca, Marcin Szczesio, Małgorzata Potrzebowski, Marek J. |
author_sort | Pawlak, Tomasz |
collection | PubMed |
description | [Image: see text] 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 P2(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 P2(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 P2(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. |
format | Online Article Text |
id | pubmed-8728732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-87287322022-01-05 Solid-State Study of the Structure, Dynamics, and Thermal Processes of Safinamide Mesylate—A New Generation Drug for the Treatment of Neurodegenerative Diseases Pawlak, Tomasz Oszajca, Marcin Szczesio, Małgorzata Potrzebowski, Marek J. Mol Pharm [Image: see text] 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 P2(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 P2(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 P2(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. American Chemical Society 2021-12-03 2022-01-03 /pmc/articles/PMC8728732/ /pubmed/34856803 http://dx.doi.org/10.1021/acs.molpharmaceut.1c00779 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Pawlak, Tomasz Oszajca, Marcin Szczesio, Małgorzata Potrzebowski, Marek J. Solid-State Study of the Structure, Dynamics, and Thermal Processes of Safinamide Mesylate—A New Generation Drug for the Treatment of Neurodegenerative Diseases |
title | Solid-State Study of the Structure, Dynamics, and
Thermal Processes of Safinamide Mesylate—A New Generation Drug
for the Treatment of Neurodegenerative
Diseases |
title_full | Solid-State Study of the Structure, Dynamics, and
Thermal Processes of Safinamide Mesylate—A New Generation Drug
for the Treatment of Neurodegenerative
Diseases |
title_fullStr | Solid-State Study of the Structure, Dynamics, and
Thermal Processes of Safinamide Mesylate—A New Generation Drug
for the Treatment of Neurodegenerative
Diseases |
title_full_unstemmed | Solid-State Study of the Structure, Dynamics, and
Thermal Processes of Safinamide Mesylate—A New Generation Drug
for the Treatment of Neurodegenerative
Diseases |
title_short | Solid-State Study of the Structure, Dynamics, and
Thermal Processes of Safinamide Mesylate—A New Generation Drug
for the Treatment of Neurodegenerative
Diseases |
title_sort | solid-state study of the structure, dynamics, and
thermal processes of safinamide mesylate—a new generation drug
for the treatment of neurodegenerative
diseases |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728732/ https://www.ncbi.nlm.nih.gov/pubmed/34856803 http://dx.doi.org/10.1021/acs.molpharmaceut.1c00779 |
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