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New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination

Since the formation of organic salts can improve the solubility, bioavailability, and stability of active pharmaceutical ingredients, the aim of this work was to prepare an organic salt of chlordiazepoxide with saccharin. To achieve this goal, the saccharin salt of chlordiazepoxide was obtained from...

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Autores principales: Lech, Anna, Garbacz, Patrycja, Sikorski, Artur, Gazda, Maria, Wesolowski, Marek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570060/
https://www.ncbi.nlm.nih.gov/pubmed/36233346
http://dx.doi.org/10.3390/ijms231912050
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author Lech, Anna
Garbacz, Patrycja
Sikorski, Artur
Gazda, Maria
Wesolowski, Marek
author_facet Lech, Anna
Garbacz, Patrycja
Sikorski, Artur
Gazda, Maria
Wesolowski, Marek
author_sort Lech, Anna
collection PubMed
description Since the formation of organic salts can improve the solubility, bioavailability, and stability of active pharmaceutical ingredients, the aim of this work was to prepare an organic salt of chlordiazepoxide with saccharin. To achieve this goal, the saccharin salt of chlordiazepoxide was obtained from a physical mixture of both components by grinding them with a small volume of solvent and by crystallizing them with complete evaporation of the solvent. The resulting salt was examined by methods such as Powder X-ray Diffraction (PXRD), Single Crystal X-ray Diffraction (SCXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FT-IR), and Raman spectroscopy. The results of the studies proved that saccharin salt of chlordiazepoxide crystallizes in the orthorhombic Pbca space group with one chlordiazepoxide cation and one saccharin anion in the asymmetric unit. In the crystal of the title compound, the chlordiazepoxide cation and the saccharin anion interact through strong N–H···O hydrogen bonds and weak C–H···O hydrogen bonds. The disappearance of the N–H band in the FT-IR spectrum of saccharin may indicate a shift of this proton towards chlordiazepoxide, while the disappearance of the aromatic bond band in the chlordiazepoxide ring in the Raman spectrum may suggest the formation of intermolecular hydrogen bonds between chlordiazepoxide molecules. The melting point of the salts differs from that of the starting compounds. Thermal decomposition of the salt begins above 200 °C and shows at least two overlapping stages of mass loss. In summary, the results of the research showed that the crystalline salt of the saccharin and chlordiazepoxide can be obtained by various methods: grinding with the addition of acetonitrile and crystallization from acetonitrile or a mixture of methanol with methylene chloride.
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spelling pubmed-95700602022-10-17 New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination Lech, Anna Garbacz, Patrycja Sikorski, Artur Gazda, Maria Wesolowski, Marek Int J Mol Sci Article Since the formation of organic salts can improve the solubility, bioavailability, and stability of active pharmaceutical ingredients, the aim of this work was to prepare an organic salt of chlordiazepoxide with saccharin. To achieve this goal, the saccharin salt of chlordiazepoxide was obtained from a physical mixture of both components by grinding them with a small volume of solvent and by crystallizing them with complete evaporation of the solvent. The resulting salt was examined by methods such as Powder X-ray Diffraction (PXRD), Single Crystal X-ray Diffraction (SCXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FT-IR), and Raman spectroscopy. The results of the studies proved that saccharin salt of chlordiazepoxide crystallizes in the orthorhombic Pbca space group with one chlordiazepoxide cation and one saccharin anion in the asymmetric unit. In the crystal of the title compound, the chlordiazepoxide cation and the saccharin anion interact through strong N–H···O hydrogen bonds and weak C–H···O hydrogen bonds. The disappearance of the N–H band in the FT-IR spectrum of saccharin may indicate a shift of this proton towards chlordiazepoxide, while the disappearance of the aromatic bond band in the chlordiazepoxide ring in the Raman spectrum may suggest the formation of intermolecular hydrogen bonds between chlordiazepoxide molecules. The melting point of the salts differs from that of the starting compounds. Thermal decomposition of the salt begins above 200 °C and shows at least two overlapping stages of mass loss. In summary, the results of the research showed that the crystalline salt of the saccharin and chlordiazepoxide can be obtained by various methods: grinding with the addition of acetonitrile and crystallization from acetonitrile or a mixture of methanol with methylene chloride. MDPI 2022-10-10 /pmc/articles/PMC9570060/ /pubmed/36233346 http://dx.doi.org/10.3390/ijms231912050 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
Lech, Anna
Garbacz, Patrycja
Sikorski, Artur
Gazda, Maria
Wesolowski, Marek
New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination
title New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination
title_full New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination
title_fullStr New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination
title_full_unstemmed New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination
title_short New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination
title_sort new saccharin salt of chlordiazepoxide: structural and physicochemical examination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570060/
https://www.ncbi.nlm.nih.gov/pubmed/36233346
http://dx.doi.org/10.3390/ijms231912050
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