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Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape

Any time the pharmaceutical industry develops a new drug, potential polymorphic events must be thoroughly described, because in a crystalline pharmaceutical solid, different arrangements of the same active pharmaceutical ingredient can yield to very different physicochemical properties that might be...

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Autores principales: Acebedo-Martínez, Francisco Javier, Alarcón-Payer, Carolina, Frontera, Antonio, Barbas, Rafael, Prohens, Rafel, Di Crisci, Milena, Domínguez-Martín, Alicia, Gómez-Morales, Jaime, Choquesillo-Lazarte, Duane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706418/
https://www.ncbi.nlm.nih.gov/pubmed/34959421
http://dx.doi.org/10.3390/pharmaceutics13122140
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author Acebedo-Martínez, Francisco Javier
Alarcón-Payer, Carolina
Frontera, Antonio
Barbas, Rafael
Prohens, Rafel
Di Crisci, Milena
Domínguez-Martín, Alicia
Gómez-Morales, Jaime
Choquesillo-Lazarte, Duane
author_facet Acebedo-Martínez, Francisco Javier
Alarcón-Payer, Carolina
Frontera, Antonio
Barbas, Rafael
Prohens, Rafel
Di Crisci, Milena
Domínguez-Martín, Alicia
Gómez-Morales, Jaime
Choquesillo-Lazarte, Duane
author_sort Acebedo-Martínez, Francisco Javier
collection PubMed
description Any time the pharmaceutical industry develops a new drug, potential polymorphic events must be thoroughly described, because in a crystalline pharmaceutical solid, different arrangements of the same active pharmaceutical ingredient can yield to very different physicochemical properties that might be crucial for its efficacy, such as dissolution, solubility, or stability. Polymorphism in cocrystal formulation cannot be neglected, either. In this work, two different cocrystal polymorphs of the non-steroidal anti-inflammatory drug niflumic acid and caffeine are reported. They have been synthesized by mechanochemical methods and thoroughly characterized in solid-state by powder and single crystal X-ray diffraction respectively, as well as other techniques such as thermal analyses, infrared spectroscopy and computational methods. Both theoretical and experimental results are in agreement, confirming a conformational polymorphism. The polymorph NIF–CAF Form I exhibits improved solubility and dissolution rate compared to NIF–CAF Form II, although Form II is significantly more stable than Form I. The conditions needed to obtain these polymorphs and their transition have been carefully characterized, revealing an intricate system.
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spelling pubmed-87064182021-12-25 Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape Acebedo-Martínez, Francisco Javier Alarcón-Payer, Carolina Frontera, Antonio Barbas, Rafael Prohens, Rafel Di Crisci, Milena Domínguez-Martín, Alicia Gómez-Morales, Jaime Choquesillo-Lazarte, Duane Pharmaceutics Article Any time the pharmaceutical industry develops a new drug, potential polymorphic events must be thoroughly described, because in a crystalline pharmaceutical solid, different arrangements of the same active pharmaceutical ingredient can yield to very different physicochemical properties that might be crucial for its efficacy, such as dissolution, solubility, or stability. Polymorphism in cocrystal formulation cannot be neglected, either. In this work, two different cocrystal polymorphs of the non-steroidal anti-inflammatory drug niflumic acid and caffeine are reported. They have been synthesized by mechanochemical methods and thoroughly characterized in solid-state by powder and single crystal X-ray diffraction respectively, as well as other techniques such as thermal analyses, infrared spectroscopy and computational methods. Both theoretical and experimental results are in agreement, confirming a conformational polymorphism. The polymorph NIF–CAF Form I exhibits improved solubility and dissolution rate compared to NIF–CAF Form II, although Form II is significantly more stable than Form I. The conditions needed to obtain these polymorphs and their transition have been carefully characterized, revealing an intricate system. MDPI 2021-12-13 /pmc/articles/PMC8706418/ /pubmed/34959421 http://dx.doi.org/10.3390/pharmaceutics13122140 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
Acebedo-Martínez, Francisco Javier
Alarcón-Payer, Carolina
Frontera, Antonio
Barbas, Rafael
Prohens, Rafel
Di Crisci, Milena
Domínguez-Martín, Alicia
Gómez-Morales, Jaime
Choquesillo-Lazarte, Duane
Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape
title Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape
title_full Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape
title_fullStr Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape
title_full_unstemmed Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape
title_short Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape
title_sort novel polymorphic cocrystals of the non-steroidal anti-inflammatory drug niflumic acid: expanding the pharmaceutical landscape
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706418/
https://www.ncbi.nlm.nih.gov/pubmed/34959421
http://dx.doi.org/10.3390/pharmaceutics13122140
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