Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–<span style="font-variant: small-caps">l</span>-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties
Ketoprofen–<span style="font-variant: small-caps;">l</span>-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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/6/555 |
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| author | Andrea Aramini Gianluca Bianchini Samuele Lillini Simone Bordignon Mara Tomassetti Rubina Novelli Simone Mattioli Larisa Lvova Roberto Paolesse Michele Remo Chierotti Marcello Allegretti |
| author_facet | Andrea Aramini Gianluca Bianchini Samuele Lillini Simone Bordignon Mara Tomassetti Rubina Novelli Simone Mattioli Larisa Lvova Roberto Paolesse Michele Remo Chierotti Marcello Allegretti |
| author_sort | Andrea Aramini |
| collection | DOAJ |
| description | Ketoprofen–<span style="font-variant: small-caps;">l</span>-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. |
| first_indexed | 2024-03-10T10:31:42Z |
| format | Article |
| id | doaj.art-ddf1013b611f43b3a11a79951ad46ca0 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T10:31:42Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-ddf1013b611f43b3a11a79951ad46ca02023-11-21T23:39:10ZengMDPI AGPharmaceuticals1424-82472021-06-0114655510.3390/ph14060555Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–<span style="font-variant: small-caps">l</span>-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic PropertiesAndrea Aramini0Gianluca Bianchini1Samuele Lillini2Simone Bordignon3Mara Tomassetti4Rubina Novelli5Simone Mattioli6Larisa Lvova7Roberto Paolesse8Michele Remo Chierotti9Marcello Allegretti10Research and Early Development, Dompé Farmaceutici S.p.A., 67100 L’Aquila, ItalyResearch and Early Development, Dompé Farmaceutici S.p.A., 67100 L’Aquila, ItalyResearch and Early Development, Dompé Farmaceutici S.p.A., 80131 Napoli, ItalyDepartment of Chemistry and NIS Centre, University of Torino, 10125 Torino, ItalyResearch and Early Development, Dompé Farmaceutici S.p.A., 80131 Napoli, ItalyResearch and Early Development, Dompé Farmaceutici S.p.A., 20122 Milano, ItalyResearch and Early Development, Dompé Farmaceutici S.p.A., 80131 Napoli, ItalyDepartment of Chemical Science and Technology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Chemical Science and Technology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Chemistry and NIS Centre, University of Torino, 10125 Torino, ItalyResearch and Early Development, Dompé Farmaceutici S.p.A., 67100 L’Aquila, ItalyKetoprofen–<span style="font-variant: small-caps;">l</span>-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.https://www.mdpi.com/1424-8247/14/6/555ketoprofen–<span style="font-variant: small-caps">l</span>-lysine saltcocrystalsaltpolymorphismfaster-release formulation |
| spellingShingle | Andrea Aramini Gianluca Bianchini Samuele Lillini Simone Bordignon Mara Tomassetti Rubina Novelli Simone Mattioli Larisa Lvova Roberto Paolesse Michele Remo Chierotti Marcello Allegretti Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–<span style="font-variant: small-caps">l</span>-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties Pharmaceuticals ketoprofen–<span style="font-variant: small-caps">l</span>-lysine salt cocrystal salt polymorphism faster-release formulation |
| title | Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen–Lysine System: Discovery of a New Ketoprofen–<span style="font-variant: small-caps">l</span>-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–<span style="font-variant: small-caps">l</span>-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–<span style="font-variant: small-caps">l</span>-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–<span style="font-variant: small-caps">l</span>-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–<span style="font-variant: small-caps">l</span>-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 span style font variant small caps l span lysine salt polymorph with different physicochemical and pharmacokinetic properties |
| topic | ketoprofen–<span style="font-variant: small-caps">l</span>-lysine salt cocrystal salt polymorphism faster-release formulation |
| url | https://www.mdpi.com/1424-8247/14/6/555 |
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