Febuxostat–<i>p</i>-Toluenesulfonic Acid Multi-Component Crystal: Characterization, Crystal Growth and Elucidation of the Salt/Co-Crystal Nature
The multi-component solid form of febuxostat (FEB) with <i>p</i>-toluenesulfonic acid was synthesized by solvent-drop grinding and cooling-evaporative crystallization and characterized by powder X-ray diffraction (XRPD), thermogravimetry (TGA), differential scanning calorimetry (DSC), an...
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MDPI AG
2023-05-01
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| author | Doriana T. Ungur Gustavo Santiso-Quinones Mihaela M. Pop Tudor L. Tamas Carmen Guguta Danny Stam Alice Mija Coca A. Iordache |
| author_facet | Doriana T. Ungur Gustavo Santiso-Quinones Mihaela M. Pop Tudor L. Tamas Carmen Guguta Danny Stam Alice Mija Coca A. Iordache |
| author_sort | Doriana T. Ungur |
| collection | DOAJ |
| description | The multi-component solid form of febuxostat (FEB) with <i>p</i>-toluenesulfonic acid was synthesized by solvent-drop grinding and cooling-evaporative crystallization and characterized by powder X-ray diffraction (XRPD), thermogravimetry (TGA), differential scanning calorimetry (DSC), and infrared spectroscopy (FT-IR). The multi-component form was stable after exposure at elevated temperature and relative humidity and powder dissolution measurements revealed five-fold aqueous solubility improvement relative to FEB. Additionally, the decrease in pH after dissolution suggests a potential for enhancing the drug absorption in the lower stomach. In the context of the regulatory requirements, the salt/co-crystal nature of the form was elucidated by a combination of crystallization process development and crystal growth, followed by SC-XRD and FT-IR. Despite the very weak basicity of the drug, crystal structure determination combined with spectroscopy analysis revealed salt formation by the transfer of the acidic proton from <i>p</i>-toluenesulfonic acid to FEB. Our study emphasizes the importance of the crystal structure knowledge in understanding the type of interactions present in multi-component crystals as well as complying with the specific regulatory requirements. |
| first_indexed | 2024-03-11T03:50:14Z |
| format | Article |
| id | doaj.art-e234c0ea69394a1a858abb476f93d09e |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-03-11T03:50:14Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-e234c0ea69394a1a858abb476f93d09e2023-11-18T01:00:48ZengMDPI AGCrystals2073-43522023-05-0113583610.3390/cryst13050836Febuxostat–<i>p</i>-Toluenesulfonic Acid Multi-Component Crystal: Characterization, Crystal Growth and Elucidation of the Salt/Co-Crystal NatureDoriana T. Ungur0Gustavo Santiso-Quinones1Mihaela M. Pop2Tudor L. Tamas3Carmen Guguta4Danny Stam5Alice Mija6Coca A. Iordache7Doctoral School in Integrative Biology, Faculty of Biology and Geology, “Babes-Bolyai” University, 400347 Cluj-Napoca, RomaniaCrystallise! AG, Hegenheimermattweg 167A, 4123 Allschwil, SwitzerlandTeraCrystal SRL, 67-103 Donat, 400293 Cluj-Napoca, RomaniaDepartment of Geology, Faculty of Biology and Geology, “Babes-Bolyai University”, 1 Kogălniceanu, 400084 Cluj-Napoca, RomaniaTechnobis Crystallization Systems BV, Pyrietstraat 2, 1812 SC Alkmaar, The NetherlandsEldico Scientific AG, Park Innovaare, 5234 Villiegen, SwitzerlandInstitute of Chemistry of Nice, UMR CNRS 7272, University Côte d’Azur, 06108 Nice, FranceTeraCrystal SRL, 67-103 Donat, 400293 Cluj-Napoca, RomaniaThe multi-component solid form of febuxostat (FEB) with <i>p</i>-toluenesulfonic acid was synthesized by solvent-drop grinding and cooling-evaporative crystallization and characterized by powder X-ray diffraction (XRPD), thermogravimetry (TGA), differential scanning calorimetry (DSC), and infrared spectroscopy (FT-IR). The multi-component form was stable after exposure at elevated temperature and relative humidity and powder dissolution measurements revealed five-fold aqueous solubility improvement relative to FEB. Additionally, the decrease in pH after dissolution suggests a potential for enhancing the drug absorption in the lower stomach. In the context of the regulatory requirements, the salt/co-crystal nature of the form was elucidated by a combination of crystallization process development and crystal growth, followed by SC-XRD and FT-IR. Despite the very weak basicity of the drug, crystal structure determination combined with spectroscopy analysis revealed salt formation by the transfer of the acidic proton from <i>p</i>-toluenesulfonic acid to FEB. Our study emphasizes the importance of the crystal structure knowledge in understanding the type of interactions present in multi-component crystals as well as complying with the specific regulatory requirements.https://www.mdpi.com/2073-4352/13/5/836febuxostat<i>p</i>-toluenesulfonic acidsalt/co-crystalSC-XRDFT-IR |
| spellingShingle | Doriana T. Ungur Gustavo Santiso-Quinones Mihaela M. Pop Tudor L. Tamas Carmen Guguta Danny Stam Alice Mija Coca A. Iordache Febuxostat–<i>p</i>-Toluenesulfonic Acid Multi-Component Crystal: Characterization, Crystal Growth and Elucidation of the Salt/Co-Crystal Nature Crystals febuxostat <i>p</i>-toluenesulfonic acid salt/co-crystal SC-XRD FT-IR |
| title | Febuxostat–<i>p</i>-Toluenesulfonic Acid Multi-Component Crystal: Characterization, Crystal Growth and Elucidation of the Salt/Co-Crystal Nature |
| title_full | Febuxostat–<i>p</i>-Toluenesulfonic Acid Multi-Component Crystal: Characterization, Crystal Growth and Elucidation of the Salt/Co-Crystal Nature |
| title_fullStr | Febuxostat–<i>p</i>-Toluenesulfonic Acid Multi-Component Crystal: Characterization, Crystal Growth and Elucidation of the Salt/Co-Crystal Nature |
| title_full_unstemmed | Febuxostat–<i>p</i>-Toluenesulfonic Acid Multi-Component Crystal: Characterization, Crystal Growth and Elucidation of the Salt/Co-Crystal Nature |
| title_short | Febuxostat–<i>p</i>-Toluenesulfonic Acid Multi-Component Crystal: Characterization, Crystal Growth and Elucidation of the Salt/Co-Crystal Nature |
| title_sort | febuxostat i p i toluenesulfonic acid multi component crystal characterization crystal growth and elucidation of the salt co crystal nature |
| topic | febuxostat <i>p</i>-toluenesulfonic acid salt/co-crystal SC-XRD FT-IR |
| url | https://www.mdpi.com/2073-4352/13/5/836 |
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