Hydrochloride salts of 8-[1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxymethyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one and preparation process therefor
View Patent ↗Disclosed are hydrochloride and tosylate crystalline salt forms of (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one, represented by Formula I and methods of preparing the same.
1. A crystalline Form I tosylate salt form of 8-[{(1R)-1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one (Formula I),
characterized by an x-ray powder diffraction pattern having peaks present at diffraction angles (in 2 θ±0.2) of: 9.4; 20.0; 21.0; and 25.3.
2. A crystalline Form II tosylate salt form of (5S,8S)-8-[{(1R)-1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one (Formula I),
characterized by an x-ray powder diffraction pattern having peaks present at diffraction angles (in 2 θ±0.2) of: 5.0; 10.0; 13.6; and 19.7.
3. A crystalline Form III tosylate salt form of (5S,8S)-8-[{(1R)-1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one (Formula I),
which is characterized by an x-ray powder diffraction pattern having peaks present at diffraction angles (in 2 θ±0.2) of: 6.3; 9.7; 20.2; and 22.2.
4. A crystalline Form IV tosylate salt form of (5S,8S)-8-[{(1R)-1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one (Formula I),
which is characterized by an x-ray powder diffraction pattern having peaks present at diffraction angles (in 2 θ±0.2) of: 6.1; 9.6; 20.9; and 22.0.
5. A pharmaceutical composition comprising the crystalline salt form of claim 1 and a pharmaceutically acceptable carrier optionally in combination with one or more additional therapeutic agents.
6. A pharmaceutical composition comprising the crystalline salt form of claim 2 and a pharmaceutically acceptable carrier optionally in combination with one or more additional therapeutic agents.
7. A pharmaceutical composition comprising the crystalline salt form of claim 3 and a pharmaceutically acceptable carrier optionally in combination with one or more additional therapeutic agents.
8. A pharmaceutical composition comprising the crystalline salt form of claim 4 and a pharmaceutically acceptable carrier optionally in combination with one or more additional therapeutic agents.
9. A method of treating or delaying the onset of nausea and/or emesis in a mammal which comprises administering to said mammal the crystalline salt form of claim 1 .
10. A method of treating or delaying the onset of nausea and/or emesis in a mammal which comprises administering to said mammal the crystalline salt form of claim 2 .
11. A method of treating or delaying the onset of nausea and/or emesis in a mammal which comprises administering to said mammal the crystalline salt form of claim 3 .
12. A method of treating or delaying the onset of nausea and/or emesis in a mammal which comprises administering to said mammal the crystalline salt form of claim 4 .
13. A method of treating or delaying the onset of chemotherapy-induced nausea and/or chemotherapy induced emesis in a mammal receiving chemotherapy, which comprises administering to said mammal the crystalline salt form of claim 1 .
14. The method of claim 13 further comprising contemporaneous administration of a chemotherapeutic agent.
15. A method of treating or delaying the onset of chemotherapy-induced nausea and/or chemotherapy induced emesis in a mammal receiving chemotherapy, which comprises administering to said mammal the crystalline salt form of claim 2 .
16. The method of claim 15 further comprising contemporaneous administration of a chemotherapeutic agent.
17. A method of treating or delaying the onset of chemotherapy-induced nausea and/or chemotherapy induced emesis in a mammal receiving chemotherapy, which comprises administering to said mammal the crystalline salt form of claim 3 .
18. The method of claim 17 further comprising contemporaneous administration of a chemotherapeutic agent.
19. A method of treating or delaying the onset of chemotherapy-induced nausea and/or chemotherapy induced emesis in a mammal receiving chemotherapy, which comprises administering to said mammal the crystalline salt form of claim 4 .
20. The method of claim 19 further comprising contemporaneous administration of a chemotherapeutic agent.