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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...

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Autores principales: Bruni, Giovanna, Ghione, Ines, Berbenni, Vittorio, Cardini, Andrea, Capsoni, Doretta, Girella, Alessandro, Milanese, Chiara, Marini, Amedeo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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