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The Physico-Chemical Properties of Glipizide: New Findings
The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal beh...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197375/ https://www.ncbi.nlm.nih.gov/pubmed/34073973 http://dx.doi.org/10.3390/molecules26113142 |
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author | Bruni, Giovanna Ghione, Ines Berbenni, Vittorio Cardini, Andrea Capsoni, Doretta Girella, Alessandro Milanese, Chiara Marini, Amedeo |
author_facet | Bruni, Giovanna Ghione, Ines Berbenni, Vittorio Cardini, Andrea Capsoni, Doretta Girella, Alessandro Milanese, Chiara Marini, Amedeo |
author_sort | Bruni, Giovanna |
collection | PubMed |
description | The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal behavior of glipizide, a hypoglycemic drug, was carried out with the aim of clarifying whether the recognition of its polymorphic forms can really be done on the basis of the endothermic peak that the literature studies attribute to the melting of the compound. A number of analytical techniques were used: thermal techniques (DSC, TGA), X-ray powder diffraction (XRPD), FT-IR spectroscopy and scanning electron microscopy (SEM). Great attention was paid to the experimental design and to the interpretation of the combined results obtained by all these techniques. We proved that the attribution of the endothermic peak shown by glipizide to its melting was actually wrong. The DSC peak is no doubt triggered by a decomposition process that involves gas evolution (cyclohexanamine and carbon dioxide) and formation of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which remains as decomposition residue. Thermal treatments properly designed and the combined use of DSC with FT-IR and XRPD led to identifying a new polymorphic form of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which is obtained by crystallization from the melt. Hence, our results put into evidence that the check of the polymorphic form of glipizide cannot be based on the temperature values of the DSC peak, since such a peak is due to a decomposition process whose Tonset value is strongly affected by the particle size. Kinetic studies of the decomposition process show the high stability of solid glipizide at room temperature. |
format | Online Article Text |
id | pubmed-8197375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81973752021-06-13 The Physico-Chemical Properties of Glipizide: New Findings Bruni, Giovanna Ghione, Ines Berbenni, Vittorio Cardini, Andrea Capsoni, Doretta Girella, Alessandro Milanese, Chiara Marini, Amedeo Molecules Article The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal behavior of glipizide, a hypoglycemic drug, was carried out with the aim of clarifying whether the recognition of its polymorphic forms can really be done on the basis of the endothermic peak that the literature studies attribute to the melting of the compound. A number of analytical techniques were used: thermal techniques (DSC, TGA), X-ray powder diffraction (XRPD), FT-IR spectroscopy and scanning electron microscopy (SEM). Great attention was paid to the experimental design and to the interpretation of the combined results obtained by all these techniques. We proved that the attribution of the endothermic peak shown by glipizide to its melting was actually wrong. The DSC peak is no doubt triggered by a decomposition process that involves gas evolution (cyclohexanamine and carbon dioxide) and formation of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which remains as decomposition residue. Thermal treatments properly designed and the combined use of DSC with FT-IR and XRPD led to identifying a new polymorphic form of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which is obtained by crystallization from the melt. Hence, our results put into evidence that the check of the polymorphic form of glipizide cannot be based on the temperature values of the DSC peak, since such a peak is due to a decomposition process whose Tonset value is strongly affected by the particle size. Kinetic studies of the decomposition process show the high stability of solid glipizide at room temperature. MDPI 2021-05-24 /pmc/articles/PMC8197375/ /pubmed/34073973 http://dx.doi.org/10.3390/molecules26113142 Text en © 2021 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 Bruni, Giovanna Ghione, Ines Berbenni, Vittorio Cardini, Andrea Capsoni, Doretta Girella, Alessandro Milanese, Chiara Marini, Amedeo The Physico-Chemical Properties of Glipizide: New Findings |
title | The Physico-Chemical Properties of Glipizide: New Findings |
title_full | The Physico-Chemical Properties of Glipizide: New Findings |
title_fullStr | The Physico-Chemical Properties of Glipizide: New Findings |
title_full_unstemmed | The Physico-Chemical Properties of Glipizide: New Findings |
title_short | The Physico-Chemical Properties of Glipizide: New Findings |
title_sort | physico-chemical properties of glipizide: new findings |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197375/ https://www.ncbi.nlm.nih.gov/pubmed/34073973 http://dx.doi.org/10.3390/molecules26113142 |
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