Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783713222852870144 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8230491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT araminiandrea unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties AT bianchinigianluca unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties AT lillinisamuele unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties AT bordignonsimone unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties AT tomassettimara unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties AT novellirubina unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties AT mattiolisimone unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties AT lvovalarisa unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties AT paolesseroberto unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties AT chierottimicheleremo unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties AT allegrettimarcello unexpectedsaltcocrystalpolymorphismoftheketoprofenlysinesystemdiscoveryofanewketoprofenllysinesaltpolymorphwithdifferentphysicochemicalandpharmacokineticproperties |