Polymorphs of bromfenac sodium and methods for preparing bromfenac sodium polymorphs

Patent metadata

Field	Value
Publication number	US-9045388-B2
Application number	US-201314026406-A
Country	US
Kind code	B2
Filing date	Sep 13, 2013
Priority date	Oct 15, 2009
Publication date	Jun 2, 2015
Grant date	Jun 2, 2015

Abstract

Different polymorphs of bromfenac sodium may be prepared and interconverted using crystallization/recrystallization, drying and/or hydration techniques.

First claim

What is claimed is:

1. A method of preparing bromfenac sodium Form III, comprising crystallizing or recrystallizing bromfenac sodium from a solvent mixture comprising: (1) water and 2-propanol; or (2) water, ethanol, toluene, and tert-butyl methyl ether.

2. The method of claim 1 , wherein the bromfenac sodium has been produced by hydrolysis of 7-(4-bromobenzoyl)indol-2-one and the solvent mixture is additionally comprised of at least one aromatic hydrocarbon and at least one anti-solvent.

3. The method of claim 2 , wherein the at least one aromatic hydrocarbon is selected from the group consisting of toluene and xylene.

4. The method of claim 2 , wherein the at least one anti-solvent comprises an alkylether.

5. The method of claim 2 , wherein the hydrolysis comprises treating the 7-(4-bromobenzoyl)indol-2-one with a sodium-containing base, and the solvent mixture and sodium-containing base are dearated prior to use.

6. The method of claim 1 , wherein the solvent mixture consists of water and 2-propanol.

7. The method of claim 6 , wherein the solvent mixture contains about 2 to about 8% v/v water.

8. The method of claim 1 , wherein the solvent mixture consists of water, ethanol, toluene, and tert-butyl methyl ether.

9. A method for converting a material selected from bromfenac sodium Form I, bromfenac sodium Form II or a mixture of bromfenac sodium Form I and bromfenac sodium Form II into bromfenac sodium Form III, comprising crystallizing or recrystallizing the material from a solvent mixture comprised of water and at least one of ethanol or 2-propanol.

10. The method of claim 9 , wherein the material consists of bromfenac sodium Form I.

11. The method of claim 9 , wherein the material consists of bromfenac sodium Form II.

12. The method of claim 9 , wherein the material consists of the mixture of bromfenac sodium Form I and bromfenac sodium Form II.

13. The method of claim 9 , wherein the solvent mixture consists of water and ethanol.

14. The method of claim 9 , wherein the solvent mixture consists of water and 2-propanol.

15. The method of claim 14 , wherein the crystallizing or recrystallizing step comprises adding the material to the solvent mixture then heating, followed by cooling to provide a thick slurry.

16. The method of claim 15 , wherein the heating step comprises heating to and maintaining at 60-70° C. under nitrogen for 1 hour and the cooling step comprises cooling to room temperature for 1 hour.

17. The method of claim 16 , further comprising filtering and washing the resulting thick slurry with 2-propanol and then drying under vacuum.

Assignees

• Johnson Matthey Plc

Inventors

• Matharu Saroop Singh
• Reddy Gurijala Venu
• Mencel James J
• Sun Xiaoyong

Classifications

• A61K31/196

  the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C225/22 Primary

  having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton · CPC title

• C07C221/00

  Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton · CPC title