1. Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts
- Author
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Kaxi Yu, Jie Shen, Jiyong Liu, Chiuyen Phan, and Guping Tang
- Subjects
Models, Molecular ,topology ,QH301-705.5 ,Hydrochloride ,Antineoplastic Agents ,Crystallography, X-Ray ,010402 general chemistry ,010403 inorganic & nuclear chemistry ,01 natural sciences ,Medicinal chemistry ,Article ,Catalysis ,Inorganic Chemistry ,chemistry.chemical_compound ,Biology (General) ,Physical and Theoretical Chemistry ,Solubility ,QD1-999 ,Protein Kinase Inhibitors ,Molecular Biology ,Spectroscopy ,Tetrahydrofuran ,hydrogen bond ,Aqueous solution ,Molecular Structure ,Hydrobromide ,Spectrum Analysis ,solubility ,Organic Chemistry ,Hydrogen Bonding ,General Medicine ,Liquid Crystals ,0104 chemical sciences ,Computer Science Applications ,Solvent ,Chemistry ,chemistry ,sorafenib ,Pyridinium ,Hydrate ,energy framework - Abstract
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.3H2O), 4-(4-{3-[4-chloro-3-(trifluoro-methyl)phenyl]ureido}phenoxy)-2-(N-methylcarbamoyl) pyridinium hydrochloride trihydrate, C21H17ClF3N4O3+·Cl−.3H2O (I), sorafenib hydrochloride monohydrate (Sor·HCl.H2O), C21H17ClF3N4O3+·Cl−.H2O (II), its solvated form (sorafenib hydrochloride monohydrate monotetrahydrofuran (Sor·HCl.H2O.THF), C21H17ClF3N4O3+·Cl−.H2O.C4H8O (III)), sorafenib hydrobromide (Sor·HBr), 4-(4-{3-[4-chloro-3-(trifluoro-methyl)phenyl]ureido}phenoxy)-2-(N-methylcarbamoyl) pyridinium hydrobromide, C21H17ClF3N4O3+·Br− (IV) and sorafenib hydrobromide monohydrate (Sor·HBr.H2O), C21H17ClF3N4O3+·Br−.H2O (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 P21/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.
- Published
- 2021
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