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Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid
The preparation of new active pharmaceutical ingredient (API) multicomponent crystal forms, especially co-crystals and salts, is being considered as a reliable strategy to improve API solubility and bioavailability. In this study, three novel imidazole-based salts of the poorly water-soluble salicyl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891694/ https://www.ncbi.nlm.nih.gov/pubmed/31731746 http://dx.doi.org/10.3390/molecules24224144 |
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author | Martins, Inês C. B. Al-Sabbagh, Dominik Meyer, Klas Maiwald, Michael Scholz, Gudrun Emmerling, Franziska |
author_facet | Martins, Inês C. B. Al-Sabbagh, Dominik Meyer, Klas Maiwald, Michael Scholz, Gudrun Emmerling, Franziska |
author_sort | Martins, Inês C. B. |
collection | PubMed |
description | The preparation of new active pharmaceutical ingredient (API) multicomponent crystal forms, especially co-crystals and salts, is being considered as a reliable strategy to improve API solubility and bioavailability. In this study, three novel imidazole-based salts of the poorly water-soluble salicylic acid (SA) are reported exhibiting a remarkable improvement in solubility and dissolution rate properties. All structures were solved by powder X-ray diffraction. Multiple complementary techniques were used to solve co-crystal/salt ambiguities: density functional theory calculations, Raman and (1)H/(13)C solid-state NMR spectroscopies. In all molecular salts, the crystal packing interactions are based on a common charged assisted (+)N-H((SA)) [Formula: see text] O(−)((co-former)) hydrogen bond interaction. The presence of an extra methyl group in different positions of the co-former, induced different supramolecular arrangements, yielding salts with different physicochemical properties. All salts present much higher solubility and dissolution rate than pure SA. The most promising results were obtained for the salts with imidazole and 1-methylimidazole co-formers. |
format | Online Article Text |
id | pubmed-6891694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68916942019-12-12 Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid Martins, Inês C. B. Al-Sabbagh, Dominik Meyer, Klas Maiwald, Michael Scholz, Gudrun Emmerling, Franziska Molecules Article The preparation of new active pharmaceutical ingredient (API) multicomponent crystal forms, especially co-crystals and salts, is being considered as a reliable strategy to improve API solubility and bioavailability. In this study, three novel imidazole-based salts of the poorly water-soluble salicylic acid (SA) are reported exhibiting a remarkable improvement in solubility and dissolution rate properties. All structures were solved by powder X-ray diffraction. Multiple complementary techniques were used to solve co-crystal/salt ambiguities: density functional theory calculations, Raman and (1)H/(13)C solid-state NMR spectroscopies. In all molecular salts, the crystal packing interactions are based on a common charged assisted (+)N-H((SA)) [Formula: see text] O(−)((co-former)) hydrogen bond interaction. The presence of an extra methyl group in different positions of the co-former, induced different supramolecular arrangements, yielding salts with different physicochemical properties. All salts present much higher solubility and dissolution rate than pure SA. The most promising results were obtained for the salts with imidazole and 1-methylimidazole co-formers. MDPI 2019-11-15 /pmc/articles/PMC6891694/ /pubmed/31731746 http://dx.doi.org/10.3390/molecules24224144 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Martins, Inês C. B. Al-Sabbagh, Dominik Meyer, Klas Maiwald, Michael Scholz, Gudrun Emmerling, Franziska Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid |
title | Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid |
title_full | Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid |
title_fullStr | Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid |
title_full_unstemmed | Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid |
title_short | Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid |
title_sort | insight into the structure and properties of novel imidazole-based salts of salicylic acid |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891694/ https://www.ncbi.nlm.nih.gov/pubmed/31731746 http://dx.doi.org/10.3390/molecules24224144 |
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