STABLE DOSAGE FORMS OF LEVOMILNACIPRAN

• US 20110144210A1
• Filed: 01/14/2011
• Published: 06/16/2011
• Est. Priority Date: 11/06/2009
• Status: Active Grant

• Current Assignee: Forest Laboratories Holdings Limited (Abbvie Incorporated)
• Original Assignee: Forest Laboratories Holdings Limited (Abbvie Incorporated)
• Inventors: Divi, Murali, Surana, Rahul, Chhettry, Anil
• Granted Patent: US 8,481,598 B2
• Time in Patent Office: Days
• US Class Current: 514/620
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07C 231/00 Preparation of carboxylic acid amides
• CPC Class Codes: C07C 237/24 having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
• CPC Class Codes: C07C 2601/02 with a three-membered ring

Abstract

The present invention relates to stable dosage forms of levomilnacipran and pharmaceutically acceptable salts thereof. Processes for the preparation of these dosage forms and methods of using these dosage forms are also described.

Claims

1. A stable dosage form comprising levomilnacipran or a pharmaceutically acceptable salt thereof.

18. A method for treating major depressive disorder comprising administering the stable dosage form of claim 1 to a patient in need thereof.

21. A method for preparing the stable dosage form of claim 1, wherein the method comprises contacting an inert substrate with levomilnacipran or a pharmaceutically acceptable salt thereof and a dehydrated alcohol.

2. A stable dosage form comprising an active ingredient that comprises at least 98% by weight of levomilnacipran or pharmaceutically acceptable salt thereof.

3. The stable dosage form of claim 2, wherein the dosage form comprises an X-ray powder diffraction (XRD) pattern that comprises characteristic peaks at 12.0, 20.1 and 22.5±

0.2 degrees 2Ø

.

4. The stable dosage form of claim 3, wherein the XRD pattern further comprises a characteristic peak at 32.7±

0.2 degrees 2Ø

.

5. The stable dosage form of claim 3, wherein the XRD pattern further comprises a characteristic peak at 6.0±

0.2 degrees 2Ø

.

6. The stable dosage form of claim 2, wherein the dosage form comprises a XRD pattern that comprises characteristic peaks at 6.0, 12.0 and 20.1±

0.2 degrees 2Ø

.

7. The stable dosage form of claim 2, wherein the dosage form comprises about 0.001% to about 0.5% by weight of (1S,5R) 1-phenyl-3-azabicyclo[3-1-0]hexane-2-one.

8. The stable dosage form of claim 2, wherein the dosage form comprises about 0.001% to about 0.2% by weight of (1S,5R) 1-phenyl-3-azabicyclo[3-1-0]hexane-2-one.

9. The stable dosage form of claim 2, wherein the dosage form comprises about 45 wt. % to about 60 wt. % of the active ingredient, and about 30 wt. % to about 45 wt. % of an inert substrate or filler.

10. The stable dosage form of claim 2, wherein the dosage form comprises about 45 wt. % to about 60 wt. % the active ingredient;

about 30 wt. % to about 45 wt. % of an inert substrate or filler;

about 4 wt. % to about 10 wt. % of a binder; and

about 1 wt. % to about 5 wt. % of an anti-adherent or lubricant.

11. The stable dosage form of claim 2, wherein the dosage form comprises about 50 wt. % to about 60 wt. % of the active ingredient;

about 30 wt. % to about 40 wt. % of an inert substrate or filler;

about 4 wt. % to about 8 wt. % of a binder; and

about 1 wt. % to about 5 wt. % of an anti-adherent or lubricant.

12. The stable dosage form of claim 9, wherein the dosage form is an immediate-release oral dosage form.

13. The stable dosage form of claim 2, wherein the dosage form comprises about 40% to about 55% by weight of levomilnacipran or pharmaceutically acceptable salt thereof, about 5% to about 15% by weight of a release controlling agent, about 25% to about 40% by weight of an inert substrate, about 3% to about 10% by weight of a binder, about 3% to about 10% by weight of an anti-adherent, and about 0.1% to about 5% by weight of a plasticizer.

14. The stable dosage form of claim 13, wherein the dosage form is a modified-release oral dosage form.

15. The dosage form of claim 2, wherein the dosage form provides a dissolution rate of at least about 80% after about 6 hours to about 16 hours following entry into a use environment.

19. A method for treating major depressive disorder comprising administering the stable dosage form of claim 2 to a patient in need thereof.

22. A method for preparing the stable dosage form of claim 2, wherein the method comprises contacting an inert substrate with levomilnacipran or a pharmaceutically acceptable salt thereof and a dehydrated alcohol.

16. A stable dosage form comprising an active ingredient that comprises substantially pure levomilnacipran or pharmaceutically acceptable salt thereof, and about 0.01% to about 0.2% by weight of (1S,5R) 1-phenyl-3-azabicyclo[3-1-0]hexane-2-one, wherein the dosage form comprises an X-ray powder diffraction (XRD) pattern that comprises characteristic peaks at 12.0, 20.1 and 22.5±

0.2 degrees 2Ø

.

17. The stable dosage form of claim 16, wherein the dosage form comprises about 45 wt. % to about 60 wt. % of the active ingredient;

and about 4 wt. % to about 10 wt. % of a binder.

20. A method for treating major depressive disorder comprising administering the stable dosage form of claim 16 to a patient in need thereof.

23. A method for preparing the stable dosage form of claim 16, wherein the method comprises contacting an inert substrate with levomilnacipran or a pharmaceutically acceptable salt thereof and a dehydrated alcohol.