Sorafenib dimethyl sulphoxide solvate
The present invention provides dimethyl sulphoxide solvate of 4-(4-{3-[4-chloro-3 -(trifluoromethyl)phenyl]ureido}phenoxy)-N 2 -methylpyridine-2-carboxamide, process for its preparation, pharmaceutical composition comprising it and its use for the treatment of cancer. The present invention also provides a novel HPLC method for the identification, quantification and isolation of related substances of sorafenib.
1. Sorafenib dimethyl sulphoxide solvate of Formula III
characterized by X-ray diffraction peaks at d-spacing 5.20, 4.21, 4.16, 3.83 and 3.66 Å.
2. Sorafenib dimethyl sulphoxide solvate according to claim 1 further characterized by X-ray diffraction peaks at d-spacing 5.36, 4.47, 4.44, 3.26 and 3.14 Å.
3. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by X-ray diffraction pattern as depicted in FIG. 1 .
4. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by DSC thermogram having endotherms at about 123.69° C. and about 202.54° C.
5. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by DSC thermogram as depicted in FIG. 2 .
6. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by X-ray diffraction pattern as depicted in FIG. 1 and DSC thermogram as depicted in FIG. 2 .
7. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by TGA as depicted in FIG. 3 .
8. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by IR spectrum as depicted in FIG. 4 .
9. Sorafenib dimethyl sulphoxide solvate of Formula III having purity greater than 99% by HPLC.
10. A process for the preparation of sorafenib dimethyl sulphoxide solvate of Formula III
comprising contacting sorafenib free base of Formula I
with dimethyl sulphoxide.
11. The process according to claim 10 , wherein Sorafenib free base of Formula I is contacted with dimethyl sulphoxide at a temperature of about 15° C. to the reflux temperature of dimethyl sulphoxide.
12. A pharmaceutical composition comprising the sorafenib dimethyl sulphoxide solvate of Formula III according to claim 1 and one or more pharmaceutically acceptable carriers, diluents or excipients.