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Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–l-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties

Ketoprofen–l-lysine salt (KLS) is a widely used nonsteroidal anti-inflammatory drug. Here, we studied deeply the solid-state characteristics of KLS to possibly identify new polymorphic drugs. Conducting a polymorph screening study and combining conventional techniques with solid-state nuclear magnet...

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Autores principales: Aramini, Andrea, Bianchini, Gianluca, Lillini, Samuele, Bordignon, Simone, Tomassetti, Mara, Novelli, Rubina, Mattioli, Simone, Lvova, Larisa, Paolesse, Roberto, Chierotti, Michele Remo, Allegretti, Marcello
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230491/
https://www.ncbi.nlm.nih.gov/pubmed/34200917
http://dx.doi.org/10.3390/ph14060555
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author Aramini, Andrea
Bianchini, Gianluca
Lillini, Samuele
Bordignon, Simone
Tomassetti, Mara
Novelli, Rubina
Mattioli, Simone
Lvova, Larisa
Paolesse, Roberto
Chierotti, Michele Remo
Allegretti, Marcello
author_facet Aramini, Andrea
Bianchini, Gianluca
Lillini, Samuele
Bordignon, Simone
Tomassetti, Mara
Novelli, Rubina
Mattioli, Simone
Lvova, Larisa
Paolesse, Roberto
Chierotti, Michele Remo
Allegretti, Marcello
author_sort Aramini, Andrea
collection PubMed
description Ketoprofen–l-lysine salt (KLS) is a widely used nonsteroidal anti-inflammatory drug. Here, we studied deeply the solid-state characteristics of KLS to possibly identify new polymorphic drugs. Conducting a polymorph screening study and combining conventional techniques with solid-state nuclear magnetic resonance, we identified, for the first time, a salt/cocrystal polymorphism of the ketoprofen (KET)–lysine (LYS) system, with the cocrystal, KET–LYS polymorph 1 (P1), being representative of commercial KLS, and the salt, KET–LYS polymorph 2 (P2), being a new polymorphic form of KLS. Interestingly, in vivo pharmacokinetics showed that the salt polymorph has significantly higher absorption and, thus, different pharmacokinetics compared to commercial KLS (cocrystal), laying the basis for the development of faster-release/acting KLS formulations. Moreover, intrinsic dissolution rate (IDR) and electronic tongue analyses showed that the salt has a higher IDR, a more bitter taste, and a different sensorial kinetics compared to the cocrystal, suggesting that different coating/flavoring processes should be envisioned for the new compound. Thus, the new KLS polymorphic form with its different physicochemical and pharmacokinetic characteristics can open the way to the development of a new KET–LYS polymorph drug that can emphasize the properties of commercial KLS for the treatment of acute inflammatory and painful conditions.
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spelling pubmed-82304912021-06-26 Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–l-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties Aramini, Andrea Bianchini, Gianluca Lillini, Samuele Bordignon, Simone Tomassetti, Mara Novelli, Rubina Mattioli, Simone Lvova, Larisa Paolesse, Roberto Chierotti, Michele Remo Allegretti, Marcello Pharmaceuticals (Basel) Article Ketoprofen–l-lysine salt (KLS) is a widely used nonsteroidal anti-inflammatory drug. Here, we studied deeply the solid-state characteristics of KLS to possibly identify new polymorphic drugs. Conducting a polymorph screening study and combining conventional techniques with solid-state nuclear magnetic resonance, we identified, for the first time, a salt/cocrystal polymorphism of the ketoprofen (KET)–lysine (LYS) system, with the cocrystal, KET–LYS polymorph 1 (P1), being representative of commercial KLS, and the salt, KET–LYS polymorph 2 (P2), being a new polymorphic form of KLS. Interestingly, in vivo pharmacokinetics showed that the salt polymorph has significantly higher absorption and, thus, different pharmacokinetics compared to commercial KLS (cocrystal), laying the basis for the development of faster-release/acting KLS formulations. Moreover, intrinsic dissolution rate (IDR) and electronic tongue analyses showed that the salt has a higher IDR, a more bitter taste, and a different sensorial kinetics compared to the cocrystal, suggesting that different coating/flavoring processes should be envisioned for the new compound. Thus, the new KLS polymorphic form with its different physicochemical and pharmacokinetic characteristics can open the way to the development of a new KET–LYS polymorph drug that can emphasize the properties of commercial KLS for the treatment of acute inflammatory and painful conditions. MDPI 2021-06-10 /pmc/articles/PMC8230491/ /pubmed/34200917 http://dx.doi.org/10.3390/ph14060555 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
Aramini, Andrea
Bianchini, Gianluca
Lillini, Samuele
Bordignon, Simone
Tomassetti, Mara
Novelli, Rubina
Mattioli, Simone
Lvova, Larisa
Paolesse, Roberto
Chierotti, Michele Remo
Allegretti, Marcello
Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–l-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties
title Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–l-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties
title_full Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–l-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties
title_fullStr Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–l-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties
title_full_unstemmed Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–l-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties
title_short Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–l-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties
title_sort unexpected salt/cocrystal polymorphism of the ketoprofen–lysine system: discovery of a new ketoprofen–l-lysine salt polymorph with different physicochemical and pharmacokinetic properties
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230491/
https://www.ncbi.nlm.nih.gov/pubmed/34200917
http://dx.doi.org/10.3390/ph14060555
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