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Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue
Glasdegib is a recently approved drug for the treatment of acute myeloid leukemia. It is formulated and marketed in monomaleate salt form. In our investigation, we were able to prepare a glasdegib dimaleate form, which could, in theory, exist in double-salt form or as a mixture of salt and co-crysta...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9415664/ https://www.ncbi.nlm.nih.gov/pubmed/36015269 http://dx.doi.org/10.3390/pharmaceutics14081641 |
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author | Peklar, Boris Perdih, Franc Makuc, Damjan Plavec, Janez Cluzeau, Jérôme Kitanovski, Zoran Časar, Zdenko |
author_facet | Peklar, Boris Perdih, Franc Makuc, Damjan Plavec, Janez Cluzeau, Jérôme Kitanovski, Zoran Časar, Zdenko |
author_sort | Peklar, Boris |
collection | PubMed |
description | Glasdegib is a recently approved drug for the treatment of acute myeloid leukemia. It is formulated and marketed in monomaleate salt form. In our investigation, we were able to prepare a glasdegib dimaleate form, which could, in theory, exist in double-salt form or as a mixture of salt and co-crystal species. Therefore, the obtained crystals of glasdegib dimaleate were characterized via (15)N ssNMR and single-crystal X-ray diffraction, which revealed that the obtained glasdegib dimaleate exists in double-salt form. This is a surprising finding based on the pK(a) values for glasdegib and maleic acid. Furthermore, we fully characterized the new dimaleate form using thermal analyses (DSC and TGA) and spectroscopy (IR and Raman). Finally, the physicochemical properties, such as solubility and chemical stability, of both forms were determined and compared. |
format | Online Article Text |
id | pubmed-9415664 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94156642022-08-27 Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue Peklar, Boris Perdih, Franc Makuc, Damjan Plavec, Janez Cluzeau, Jérôme Kitanovski, Zoran Časar, Zdenko Pharmaceutics Article Glasdegib is a recently approved drug for the treatment of acute myeloid leukemia. It is formulated and marketed in monomaleate salt form. In our investigation, we were able to prepare a glasdegib dimaleate form, which could, in theory, exist in double-salt form or as a mixture of salt and co-crystal species. Therefore, the obtained crystals of glasdegib dimaleate were characterized via (15)N ssNMR and single-crystal X-ray diffraction, which revealed that the obtained glasdegib dimaleate exists in double-salt form. This is a surprising finding based on the pK(a) values for glasdegib and maleic acid. Furthermore, we fully characterized the new dimaleate form using thermal analyses (DSC and TGA) and spectroscopy (IR and Raman). Finally, the physicochemical properties, such as solubility and chemical stability, of both forms were determined and compared. MDPI 2022-08-06 /pmc/articles/PMC9415664/ /pubmed/36015269 http://dx.doi.org/10.3390/pharmaceutics14081641 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Peklar, Boris Perdih, Franc Makuc, Damjan Plavec, Janez Cluzeau, Jérôme Kitanovski, Zoran Časar, Zdenko Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue |
title | Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue |
title_full | Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue |
title_fullStr | Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue |
title_full_unstemmed | Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue |
title_short | Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue |
title_sort | glasdegib dimaleate: synthesis, characterization and comparison of its properties with monomaleate analogue |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9415664/ https://www.ncbi.nlm.nih.gov/pubmed/36015269 http://dx.doi.org/10.3390/pharmaceutics14081641 |
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