Polymorphs of bromfenac sodium and methods for preparing bromfenac sodium polymorphs

• US 9,061,968 B2
• Filed: 09/13/2013
• Issued: 06/23/2015
• Est. Priority Date: 10/15/2009
• Status: Active Grant

• Current Assignee: Macfarlan Smith (Hong Kong) Ltd. (Johnson Matthey PLC)
• Original Assignee: Johnson Matthey PLC
• Inventors: Matharu, Saroop Singh, Reddy, Gurijala Venu, Mencel, James J., Sun, Xiaoyong
• Primary Examiner(s): BROOKS, CLINTON A
• Application Number:
  US14/026,389
• Publication Number:
  US 20140011880A1
• Time in Patent Office: 648 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07C 221/00 Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
• CPC Class Codes: C07C 225/22 having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
• CPC Class Codes: C07C 227/22 from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
• CPC Class Codes: C07C 227/42 Crystallisation
• CPC Class Codes: C07C 229/42 with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains

Abstract

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

Claims

1. Bromfenac sodium, characterized by a powder x-ray diffraction pattern having main peaks expressed as 2-theta at about 16.5, 18.5, 20.7, 34.1, 11.3, 14.4, 17.3, 19.4, 21.0, 22.7, 29.0, 31.8, and 36.1 degrees.

2. A method for making a pharmaceutical formulation comprising formulating the bromfenac sodium in accordance with claim 1 and at least one excipient to provide the pharmaceutical formulation.

3. A method for reducing inflammation comprising administering the pharmaceutical formulation made by the process of claim 2 to an eye of a human patient in need of such treatment, wherein the pharmaceutical formulation is an ophthalmic composition.

4. The method of claim 3, wherein the pharmaceutical formulation does not contain more than 0.15% AUC of any process impurity of bromfenac sodium degradation product.

5. The method of claim 3, wherein the pharmaceutical formulation contains less than 100 ppm aluminum, boron, and manganese in total and less than 30 ppm of each of these elements.

6. A vial containing the pharmaceutical formulation made by the process according to claim 2.

7. Bromfenac sodium in accordance with claim 1, characterized by an XRPD d-spacing/% intensity pattern in accordance with that shown in Table D.

8. Bromfenac sodium, characterized by a powder x-ray diffraction pattern exhibiting main peaks in accordance with those shown in FIG. 6.

9. A method for making a pharmaceutical formulation comprising formulating the bromfenac sodium in accordance with claim 8 and at least one excipient to provide the pharmaceutical formulation.

10. The method of claim 9, wherein the pharmaceutical formulation is a liquid.

11. The method of claim 10, wherein the liquid is a solution.

12. The method of claim 10, wherein the at least one excipient comprises a water soluble polymer.

13. The method of claim 10, wherein the crystalline form of bromfenac sodium consists essentially of bromfenac sodium Form II.

14. The method of claim 10, wherein the pH of the formulation is about 7.5 to 8.5.

15. The method of claim 9, wherein the pharmaceutical formulation is a suspension.

16. The method of claim 11, wherein the formulated crystalline form of bromfenac sodium is dissolved in the solution in an amount from about 0.01% to about 5% by weight.

17. The method of claim 10, wherein the at least one excipient is selected from the group consisting of at least one of carriers, solvents, preservatives, stabilizers, surfactants, pH adjusting agents, diluents, and fillers.

18. The method of claim 9, wherein the at least one excipient comprises a preservative, a chelating agent, a pH-adjusting agent, a water soluble polymer, a sulfite, a buffer system, and water.

19. The method of claim 18, wherein the pH-adjusting agent comprises sodium hydroxide, the water soluble polymer comprises polyvinyl pyrrolidone, the sulfite comprises sodium sulfite, and the buffer system comprises boric acid and sodium borate.

20. The method of claim 19, wherein the chelating agent comprises sodium edetate.

21. A method for reducing inflammation comprising administering the pharmaceutical formulation made by the process of claim 9 to an eye of a human patient in need of such treatment, wherein the pharmaceutical formulation is an ophthalmic composition.

22. The method of claim 21, wherein the ophthalmic composition is in the form of an eye drop.

23. The method of claim 21, wherein the inflammation is a result of an operative procedure or surgery.

24. A method for reducing pain comprising administering the pharmaceutical formulation made by the process of claim 9 to an eye of a human patient in need of such treatment, wherein the pharmaceutical formulation is an ophthalmic composition.

25. The method of claim 24, wherein the ophthalmic composition is in the form of an eye drop.

26. The method of claim 24, wherein the inflammation pain is a result of a surgery.

27. The method of claim 16, wherein the surgery is cataract or refractive surgery.

28. A vial containing the pharmaceutical formulation made by the process according to claim 9.