Salt and crystalline forms thereof of a drug
View Patent ↗A crystalline form of a drug, ways to make it, compositions containing it and methods of treatment of diseases and inhibition of adverse physiological events using it are disclosed.
1. A process for making D-glucitol, 1-deoxy-1-(methylamino)-, 1-(6-amino-3,5-difluoropyridin-2-y1)-8-chloro-6-fluoro-1,4-dihydro-7-(3-hydroxyazetidin-1-y1)-4-oxo-3-quinolinecarboxylate salt comprising the steps of:
(1) combining 1-(6-amino-3,5-difluoropyridin-2-y1)-8-chloro-6-fluoro-1,4-dihydro-7-(3-hydroxyazetidin-1-y1)-4-oxo-3-quinolinecarboxylate and 1-deoxy-1-(methylamino)-D glucitol in a solvent to provide a mixture;
(2) filtering said mixture to provide a solid; and
(3) drying said solid to provide said D-glucitol, 1-deoxy-1-(methylamino)-, 1-(6-amino-3,5-difluoropyridin-2-y1)-8-chloro-6-fluoro-1,4-dihydro-7-(3-hydroxyazetidin-1-y1)-4-oxo-3-quinolinecarboxylate salt.
2. The process of claim 1 , wherein said solvent comprises water.
3. The process of claim 1 , wherein said solvent comprises an alcohol.
4. The process of claim 3 , wherein said alcohol is isopropanol.
5. The process of claim 4 , wherein said step of combining said 1-(6-amino-3,5-difluoropyridin-2-y1)-8-chloro-6-fluoro-1,4-dihydro-7-(3-hydroxyazetidin-1-y1)-4-oxo-3-quinolinecarboxylate and said 1-deoxy-1-(methylamino)-D-glucitol in a solvent to provide a mixture further comprises heating said mixture.
6. The process of claim 5 , wherein said heating comprises about 60 ° C.
7. The process of claim 5 , wherein said heating comprises about 45 ° C.
8. The process of claim 1 , wherein said step of combining said 1-(6-amino-3,5-difluoropyridin-2-y1)-8-chloro-6-fluoro-1,4-dihydro-7-(3-hydroxyazetidin-1-y1)-4-oxo-3-quinolinecarboxylate and said 1-deoxy-1-(methylamino)-D-glucitol in a solvent to provide a mixture further comprises heating said mixture and subsequently cooling said mixture.
9. The process of claim 8 , wherein said heating comprises about 60 ° C.
10. The process of claim 8 , wherein said heating comprises about 45 ° C.
11. The process of claim 8 , wherein said cooling comprises about 38 ° C.
12. The process of claim 8 , wherein said cooling comprises about 30 ° C.
13. The process of claim 12 , wherein said cooling comprises 30 ° C. ±5 ° C.
14. The process of claim 8 , wherein said cooling comprises about 0 ° C.
15. The process of claim 8 , wherein said cooling comprises cooling to about 38 ° C. and then cooling to about 0 ° C.
16. The process of claim 1 , wherein said step of filtering said mixture to provide said solid further comprises washing said solid.
17. The process of claim 16 , wherein said washing said solid is with an alcohol.
18. The process of claim 17 , wherein said alcohol is isopropanol.
19. The process of claim 1 , wherein said step of drying said solid to provide said D-glucitol, 1-deoxy-1-(methylamino)-, 1-(6-amino-3,5-difluoropyridin-2-y1)-8-chloro-6-fluoro-1,4-dihydro-7-(3-hydroxyazetidin-1-y1)-4-oxo-3-quinolinecarboxylate salt comprises reduced pressure.
20. The process of claim 1 , wherein said step of drying said solid to provide said D-glucitol, 1-deoxy-1-(methylamino)-, 1-(6-amino-3,5-difluoropyridin-2-y1)-8-chloro-6-fluoro-1,4-dihydro-7-(3-hydroxyazetidin-1-y1)-4-oxo-3-quinolinecarboxylate salt comprises heat.
21. The process of claim 20 , wherein said heat comprises about 50 ° C.
22. The process of claim 20 , wherein said heat comprises about 30 ° C.
23. The process of claim 20 , wherein said heat comprises about 30 ° C., followed by about 50 ° C.
24. The process of claim 1 , wherein the salt is crystalline.
25. The process of claim 24 , wherein the salt has substantial crystalline purity.
26. The process of claim 25 , wherein the salt has at least about 95% crystalline purity.
27. The process of claim 1 , wherein the salt has substantial chemical purity.
28. The process of claim 27 , wherein the salt is about 97% chemically pure.
29. The process of claim 27 , wherein the salt is about 98% chemically pure.
30. The process of claim 27 , wherein the salt is about 100% chemically pure.