Crystalline forms of Gatifloxacin
The present invention relates to a process for purification of novel polymorphic form of Gatifloxacin which comprises dissolving Gatifloxacin in about 15-50 volumes of methanol, removing insolubles if any, adding organic base to the solution, maintaining the solution at temperature of 30° C. to 70° C., for about 20 min to 4 hrs, followed by gradual cooling and maintaining the reaction mass to −10 to 20° C. for about 1-4 hrs, isolation and drying at temperature of about 45° C. to 65° C.
1. A crystalline form of Gatifloxacin (form-X) that exhibits characteristic XRD-peaks expressed in 2θ at 7.8, 8.8, 9.8, 10.3, 11.8, 12.8, 13.7, 14.2, 14.9, 17.3, 17.7, 18.2, 19.2, 19.8, 20.6, 21.2, 23.9, 26.0 and 28.6 ± 0.2 degrees.
2. A crystalline form of Gatifloxacin (form-Y) that exhibits characteristic XRD-peaks expressed in 2θ at 5.1, 6.2, 7.8, 9.1, 9.8, 10.4, 12.9, 13.6, 14.3, 17.3, 17.7, 18.3, 18.8, 19.6, 20.7, 21.1, 23.4, 23.9, 24.4, 25.4, 25.9 and 26.6 ± 0.2 degrees.
3. A crystalline form of Gatifloxacin (form-Z) that exhibits characteristic XRD-peaks expressed in 2θ at 7.3, 8.7, 9.5, 11.2, 12.1, 12.8, 14.0, 14.8, 15.3, 16.0, 19.2, 21.0, 21.6, 23.2, 24.0, 24.4, 25.9 and 26.6 ±0.2 degrees.
4. A process for the preparation of Gatifloxacin Form-X comprising the steps:
dissolving Gatifloxacin in methanol,
removing insolubles if any,
adding an organic base,
maintaining the reaction mixture at an appropriate temperature,
cooling the reaction mixture to −10° C. to 20° C.,
maintaining the reaction mixture at that temperature for 1 hr to 4 hrs,
isolating and drying the product.
5. A process as claimed in claim 4 , wherein the volume of methanol for dissolution of Gatifloxacin is 15 to 50 volumes, with respect to Gatifloxacin.
6. A process as claimed in claim 4 or 5 , wherein Gatifloxacin is dissolved in methanol at a temperature in between 45° C. and reflux temperature.
7. A process as claimed in claim 4 , wherein the addition of the organic base is carried out at a temperature from 30° C. to 70° C.
8. A process as claimed in claim 4 , wherein the organic base is triethyl amine or diisopropyl ethylamine.
9. A process as claimed in claim 4 , wherein the maintenance temperature of the reaction mass is between 30° C. and 70° C.
10. A process as claimed in claim 4 , wherein the drying temperature is between 45° C. and 65° C.
11. A process for the preparation of novel crystalline Gatifloxacin Form-Y comprising the steps:
dissolving Gatifloxacin in methanol,
removing insolubles if any,
concentrating the reaction mass under reduced pressure,
cooling the reaction mass to a temperature of −20° C. to 10° C.,
maintaining the reaction mixture at −20° C. to 10° C. for 30 min to 4 hrs,
isolating and drying the product.
12. A process as claimed in claim 11 , wherein the volume of methanol for dissolution of Gatifloxacin is 15 to 50 volumes with respect to Gatifloxacin.
13. A process as claimed in claims 11 or 12 , wherein Gatifloxacin is dissolved in methanol at a temperature of 45° C. to reflux temperature.
14. A process as claimed in claim 11 , wherein the reaction mass is concentrated to one half to one third of the original volume.
15. A process as claimed in claim 11 , wherein the drying temperature is between 45° C. and 65° C.
16. A process for the preparation of novel crystalline Gatifloxacin Form-Z comprising the steps:
dissolving Gatifloxacin in methanol,
removing insolubles if any,
cooling the reaction mixture to a temperature of −10° C. to 10° C.,
maintaining the reaction mixture at −10° C. to 10° C. for 30 min. to 4 hrs,
isolating and drying the product.
17. A process as claimed in claim 16 , wherein the volume of methanol for dissolution of Gatifloxacin is 15 to 50 volumes, with respect to Gatifloxacin.
18. A process as claimed in claim 16 , wherein the dissolution of Gatifloxacin in methanol is at a temperature of 30° C. to 70° C.,.
19. A process as claimed in claim 16 , wherein the drying temperature is 45° C. to 65° C.
20. A process as claimed in claim 18 , wherein dissolution of Gatifloxacin in methanol is at the reflux temperature of the solvent.
21. A process as claimed in any one of claims 5 , 12 , and 17 , wherein the volume of methanol for dissolution of Gatifloxacin is 20 to 35 volumes with respect to Gatifloxacin.
22. A process as claimed in claim 9 , wherein the maintenance temperature of the reaction mass is the reflux temperature of the solvent.