Process for the preparation of levofloxacin hemihydrate

1. A process for the preparation of Levofloxacin hemihydrate comprising the steps of:

reacting (S)-(-)9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid with N-methyl piperazine in n-butanol at a temperature of 120° C. to 125° C.;

removing the n-butanol under vacuum at a temperature below 100° C.;

dissolving the residue in a mixture of toluene-chloroform and removing insolubles therefrom;

removing the toluene-chloroform mixture and adding isopropanol;

adding a pre-determined quantity of water and mixing for about 5 min to about 30 min;

cooling to a temperature of about 15° C. to about 35° C.; and

isolating and drying the product.

2. The process as claimed in claim 1 , wherein the mixture of toluene-chloroform is removed under vacuum below 60° C.

3. The process as claimed in claim 1 , wherein the crude Levofloxacin is isolated at 20° C. to 30° C.

4. The process as claimed in claim 1 , wherein the water is added at a temperature of between 60° C. to 90° C.

5. The process as claimed in claim 1 , wherein the pre-determined quantity of water added is equivalent to between 12% to 20% of the isopropanol.

6. The process as claimed in claim 1 , wherein the drying is carried out at a temperature of 45° C. to 85° C.

7. A process for the preparation of Levofloxacin hemihydrate free of Levofloxacin monohydrate, comprising the steps of:

providing an amount of (S)-(−)9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7-H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid;

suspending the same in n-butanol to form a first solution;

adding a molar excess amount of N-methyl piperazine to the first solution;

heating the first solution to a temperature substantially the same as the reflux temperature of the n-butanol;

removing the n-butanol at a temperature below 100° C. to form a residue;

washing the residue with a quantity of isopropanol to form a second solution;

heating the second solution to a temperature substantially the same as the reflux temperature of the second solution;

adding a pre-determined quantity of water to the second solution for a sufficient amount of time to form the Levofloxacin hemihydrate, wherein the amount of water added is equivalent to between about 12% to 20% of the quantity of isopropanol; and

isolating the Levofloxacin hemihydrate.

8. The process as claimed in claim 7 , further comprising the steps of:

dissolving the residue in a mixture of toluene-chloroform;

removing insolubles therefrom; and

removing the toluene-chloroform under vacuum below a temperature of about 60° C.

9. The process as claimed in claim 7 , wherein the amount of water added is added to the second solution at a temperature of between about 60° to 90° C.

10. The process as claimed in claim 7 , further comprising the step of drying the Levofloxacin hemihydrate at a temperature of between about 45° C. to 85° C.

11. The process as claimed in claim 7 , further comprising the step of drying the Levofloxacin hemihydrate at a temperature of between about 60° C. to 70° C.

12. The process as claimed in claim 7 , wherein the amount of water added is equivalent to 15% of the quantity of isopropanol.

13. The process as claimed in claim 7 , wherein the sufficient amount of time to form the Levofloxacin hemihydrate is between about 30 min and 4 hrs.