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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/13/12/2140 |
| _version_ | 1827670262909239296 |
|---|---|
| author | Francisco Javier Acebedo-Martínez Carolina Alarcón-Payer Antonio Frontera Rafael Barbas Rafel Prohens Milena Di Crisci Alicia Domínguez-Martín Jaime Gómez-Morales Duane Choquesillo-Lazarte |
| author_facet | Francisco Javier Acebedo-Martínez Carolina Alarcón-Payer Antonio Frontera Rafael Barbas Rafel Prohens Milena Di Crisci Alicia Domínguez-Martín Jaime Gómez-Morales Duane Choquesillo-Lazarte |
| author_sort | Francisco Javier Acebedo-Martínez |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T03:19:35Z |
| format | Article |
| id | doaj.art-89dbc99e9187492d9c72e36752169efa |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:19:35Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-89dbc99e9187492d9c72e36752169efa2023-11-23T10:06:27ZengMDPI AGPharmaceutics1999-49232021-12-011312214010.3390/pharmaceutics13122140Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical LandscapeFrancisco Javier Acebedo-Martínez0Carolina Alarcón-Payer1Antonio Frontera2Rafael Barbas3Rafel Prohens4Milena Di Crisci5Alicia Domínguez-Martín6Jaime Gómez-Morales7Duane Choquesillo-Lazarte8Laboratorio de Estudios Cristalográficos, IACT, CSIC-Universidad de Granada, Avda. de las Palmeras 4, 18100 Armilla, SpainServicio de Farmacia, Hospital Universitario Virgen de las Nieves, 18014 Granada, SpainDepartment of Chemistry, Universitat de les Illes Balears, Crta de Valldemossa km 7.5, 07122 Palma de Mallorca, SpainUnitat de Polimorfisme i Calorimetria, Centres Científics i Tecnològics, Universitat de Barcelona, Baldiri Reixac 10, 08028 Barcelona, SpainUnitat de Polimorfisme i Calorimetria, Centres Científics i Tecnològics, Universitat de Barcelona, Baldiri Reixac 10, 08028 Barcelona, SpainLaboratorio de Estudios Cristalográficos, IACT, CSIC-Universidad de Granada, Avda. de las Palmeras 4, 18100 Armilla, SpainDepartment of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, SpainLaboratorio de Estudios Cristalográficos, IACT, CSIC-Universidad de Granada, Avda. de las Palmeras 4, 18100 Armilla, SpainLaboratorio de Estudios Cristalográficos, IACT, CSIC-Universidad de Granada, Avda. de las Palmeras 4, 18100 Armilla, SpainAny 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.https://www.mdpi.com/1999-4923/13/12/2140cocrystal polymorphismniflumic acidcaffeineNSAIDsmechanochemical synthesis |
| spellingShingle | Francisco Javier Acebedo-Martínez Carolina Alarcón-Payer Antonio Frontera Rafael Barbas Rafel Prohens Milena Di Crisci Alicia Domínguez-Martín Jaime Gómez-Morales Duane Choquesillo-Lazarte Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape Pharmaceutics cocrystal polymorphism niflumic acid caffeine NSAIDs mechanochemical synthesis |
| 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 | cocrystal polymorphism niflumic acid caffeine NSAIDs mechanochemical synthesis |
| url | https://www.mdpi.com/1999-4923/13/12/2140 |
| work_keys_str_mv | AT franciscojavieracebedomartinez novelpolymorphiccocrystalsofthenonsteroidalantiinflammatorydrugniflumicacidexpandingthepharmaceuticallandscape AT carolinaalarconpayer novelpolymorphiccocrystalsofthenonsteroidalantiinflammatorydrugniflumicacidexpandingthepharmaceuticallandscape AT antoniofrontera novelpolymorphiccocrystalsofthenonsteroidalantiinflammatorydrugniflumicacidexpandingthepharmaceuticallandscape AT rafaelbarbas novelpolymorphiccocrystalsofthenonsteroidalantiinflammatorydrugniflumicacidexpandingthepharmaceuticallandscape AT rafelprohens novelpolymorphiccocrystalsofthenonsteroidalantiinflammatorydrugniflumicacidexpandingthepharmaceuticallandscape AT milenadicrisci novelpolymorphiccocrystalsofthenonsteroidalantiinflammatorydrugniflumicacidexpandingthepharmaceuticallandscape AT aliciadominguezmartin novelpolymorphiccocrystalsofthenonsteroidalantiinflammatorydrugniflumicacidexpandingthepharmaceuticallandscape AT jaimegomezmorales novelpolymorphiccocrystalsofthenonsteroidalantiinflammatorydrugniflumicacidexpandingthepharmaceuticallandscape AT duanechoquesillolazarte novelpolymorphiccocrystalsofthenonsteroidalantiinflammatorydrugniflumicacidexpandingthepharmaceuticallandscape |