Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts
Sorafenib (Sor) is an oral multi-kinase inhibitor, but its water solubility is very low. To improve its solubility, sorafenib hydrochloride hydrate, sorafenib hydrobromide and sorafenib hydrobromide hydrate were prepared in the mixed solvent of the corresponding acid solution, and tetrahydrofuran (T...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/6682 |
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| author | Chiuyen Phan Jie Shen Kaxi Yu Jiyong Liu Guping Tang |
| author_facet | Chiuyen Phan Jie Shen Kaxi Yu Jiyong Liu Guping Tang |
| author_sort | Chiuyen Phan |
| collection | DOAJ |
| description | Sorafenib (Sor) is an oral multi-kinase inhibitor, but its water solubility is very low. To improve its solubility, sorafenib hydrochloride hydrate, sorafenib hydrobromide and sorafenib hydrobromide hydrate were prepared in the mixed solvent of the corresponding acid solution, and tetrahydrofuran (THF). The crystal structures of sorafenib hydrochloride trihydrate (Sor·HCl.3H<sub>2</sub>O), 4-(4-{3-[4-chloro-3-(trifluoro-methyl)phenyl]ureido}phenoxy)-2-(<i>N</i>-methylcarbamoyl) pyridinium hydrochloride trihydrate, C<sub>21</sub>H<sub>17</sub>ClF<sub>3</sub>N<sub>4</sub>O<sub>3</sub><sup>+</sup>·Cl<sup>−</sup>.3H<sub>2</sub>O (I), sorafenib hydrochloride monohydrate (Sor·HCl.H<sub>2</sub>O), C<sub>21</sub>H<sub>17</sub>ClF<sub>3</sub>N<sub>4</sub>O<sub>3</sub><sup>+</sup>·Cl<sup>−</sup>.H<sub>2</sub>O (II), its solvated form (sorafenib hydrochloride monohydrate monotetrahydrofuran (Sor·HCl.H<sub>2</sub>O.THF), C<sub>21</sub>H<sub>17</sub>ClF<sub>3</sub>N<sub>4</sub>O<sub>3</sub><sup>+</sup>·Cl<sup>−</sup>.H<sub>2</sub>O.C<sub>4</sub>H<sub>8</sub>O (III)), sorafenib hydrobromide (Sor·HBr), 4-(4-{3-[4-chloro-3-(trifluoro-methyl)phenyl]ureido}phenoxy)-2-(N-methylcarbamoyl) pyridinium hydrobromide, C<sub>21</sub>H<sub>17</sub>ClF<sub>3</sub>N<sub>4</sub>O<sub>3</sub><sup>+</sup>·Br<sup>−</sup> (IV) and sorafenib hydrobromide monohydrate (Sor·HBr.H<sub>2</sub>O), C<sub>21</sub>H<sub>17</sub>ClF<sub>3</sub>N<sub>4</sub>O<sub>3</sub><sup>+</sup>·Br<sup>−</sup>.H<sub>2</sub>O (V) were analysed. Their hydrogen bond systems and topologies were investigated. The results showed the distinct roles of water molecules in stabilizing their crystal structures. Moreover, (II) and (V) were isomorphous crystal structures with the same space group P2<sub>1</sub>/n, and similar unit cell dimensions. The predicted morphologies of these forms based on the BFDH model matched well with experimental morphologies. The energy frameworks showed that (I), and (IV) might have better tabletability than (II) and (V). Moreover, the solubility and dissolution rate data exhibited an improvement in the solubility of these salts compared with the free drug. |
| first_indexed | 2024-03-10T10:10:45Z |
| format | Article |
| id | doaj.art-88a0b99a0ae5459bba9a5a5b68588107 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:10:45Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-88a0b99a0ae5459bba9a5a5b685881072023-11-22T01:14:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213668210.3390/ijms22136682Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib SaltsChiuyen Phan0Jie Shen1Kaxi Yu2Jiyong Liu3Guping Tang4Faculty of Chemical Technology–Environment, The University of Danang—University of Technology and Education, Danang 550000, VietnamDepartment of Chemistry, Zhejiang University, Hangzhou 310028, ChinaDepartment of Chemistry, Zhejiang University, Hangzhou 310028, ChinaDepartment of Chemistry, Zhejiang University, Hangzhou 310028, ChinaDepartment of Chemistry, Zhejiang University, Hangzhou 310028, ChinaSorafenib (Sor) is an oral multi-kinase inhibitor, but its water solubility is very low. To improve its solubility, sorafenib hydrochloride hydrate, sorafenib hydrobromide and sorafenib hydrobromide hydrate were prepared in the mixed solvent of the corresponding acid solution, and tetrahydrofuran (THF). The crystal structures of sorafenib hydrochloride trihydrate (Sor·HCl.3H<sub>2</sub>O), 4-(4-{3-[4-chloro-3-(trifluoro-methyl)phenyl]ureido}phenoxy)-2-(<i>N</i>-methylcarbamoyl) pyridinium hydrochloride trihydrate, C<sub>21</sub>H<sub>17</sub>ClF<sub>3</sub>N<sub>4</sub>O<sub>3</sub><sup>+</sup>·Cl<sup>−</sup>.3H<sub>2</sub>O (I), sorafenib hydrochloride monohydrate (Sor·HCl.H<sub>2</sub>O), C<sub>21</sub>H<sub>17</sub>ClF<sub>3</sub>N<sub>4</sub>O<sub>3</sub><sup>+</sup>·Cl<sup>−</sup>.H<sub>2</sub>O (II), its solvated form (sorafenib hydrochloride monohydrate monotetrahydrofuran (Sor·HCl.H<sub>2</sub>O.THF), C<sub>21</sub>H<sub>17</sub>ClF<sub>3</sub>N<sub>4</sub>O<sub>3</sub><sup>+</sup>·Cl<sup>−</sup>.H<sub>2</sub>O.C<sub>4</sub>H<sub>8</sub>O (III)), sorafenib hydrobromide (Sor·HBr), 4-(4-{3-[4-chloro-3-(trifluoro-methyl)phenyl]ureido}phenoxy)-2-(N-methylcarbamoyl) pyridinium hydrobromide, C<sub>21</sub>H<sub>17</sub>ClF<sub>3</sub>N<sub>4</sub>O<sub>3</sub><sup>+</sup>·Br<sup>−</sup> (IV) and sorafenib hydrobromide monohydrate (Sor·HBr.H<sub>2</sub>O), C<sub>21</sub>H<sub>17</sub>ClF<sub>3</sub>N<sub>4</sub>O<sub>3</sub><sup>+</sup>·Br<sup>−</sup>.H<sub>2</sub>O (V) were analysed. Their hydrogen bond systems and topologies were investigated. The results showed the distinct roles of water molecules in stabilizing their crystal structures. Moreover, (II) and (V) were isomorphous crystal structures with the same space group P2<sub>1</sub>/n, and similar unit cell dimensions. The predicted morphologies of these forms based on the BFDH model matched well with experimental morphologies. The energy frameworks showed that (I), and (IV) might have better tabletability than (II) and (V). Moreover, the solubility and dissolution rate data exhibited an improvement in the solubility of these salts compared with the free drug.https://www.mdpi.com/1422-0067/22/13/6682sorafenibhydrogen bondtopologyenergy frameworksolubility |
| spellingShingle | Chiuyen Phan Jie Shen Kaxi Yu Jiyong Liu Guping Tang Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts International Journal of Molecular Sciences sorafenib hydrogen bond topology energy framework solubility |
| title | Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts |
| title_full | Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts |
| title_fullStr | Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts |
| title_full_unstemmed | Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts |
| title_short | Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts |
| title_sort | hydrogen bonds topologies energy frameworks and solubilities of five sorafenib salts |
| topic | sorafenib hydrogen bond topology energy framework solubility |
| url | https://www.mdpi.com/1422-0067/22/13/6682 |
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