Stable dosage forms of levomilnacipran

• US 8,481,598 B2
• Filed: 01/14/2011
• Issued: 07/09/2013
• 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: Surana, Rahul, Chhettry, Anil, Divi, Murali
• Primary Examiner(s): Carter, Kendra D
• Application Number:
  US13/006,993
• Publication Number:
  US 20110144210A1
• Time in Patent Office: 907 Days
• Field of Search: 514/620, 564/161, 564/190
• 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 method for treating major depressive disorder in a patient in need thereof, comprising administering to the patient about 120 mg/day of levomilnacipran or a pharmaceutically acceptable salt thereof in one or more sustained release oral dosage forms,

wherein the administering step provides a therapeutic blood plasma level of levomilnacipran or pharmaceutically acceptable salt thereof over approximately a twenty-four hour period to treat major depressive disorder in the patient, and

wherein the administering step provides an average maximum plasma concentration (C_max) between about 50 ng/mL and about 350 ng/mL of levomilnacipran or pharmaceutically acceptable salt thereof, an AUC_0-∞

between about 1000 ng·

hr/mL and about 9000 ng·

hr/mL and a T_max of at least 3 hours to the patient.

2. The method of claim 1, wherein the administering step comprises administering levomilnacipran hydrochloride.

3. The method of claim 1, wherein the administering step provides a mean T_max between about 4 hours and about 10 hours to the patient.

4. The method of claim 1, wherein the administering step provides a mean T_max of at least 3 hours and a mean AUC_0-∞

between about 5000 ng·

hr/mL and about 9000 ng·

hr/mL to the patient.

5. The method of claim 1, wherein the administering step provides a mean T_max of at least 3 hours and a mean AUG_0-∞

within ten percent of 5000 ng·

hr/mL to the patient.

6. The method of claim 1, wherein the administering step provides a mean T_max of at least 3 hours and a mean AUG_0-∞

within twenty percent of 5000 ng·

hr/mL to the patient.

7. The method of claim 1, wherein the administering step further comprises administering within the sustained-release oral dosage forms between about 0.001% and about 0.5% by weight of (1S,5R) 1-phenyl-3-azabicyclo[3-1-0]hexane-2-one relative to the amount of levomilnacipran or salt thereof.

8. The method of claim 1, wherein the administering step further comprises administering within the sustained-release oral dosage forms between about 0.001% and about 0.2% by weight of (1S,5R) 1-phenyl-3-azabicyclo[3-1-0]hexane-2-one relative to the amount of levomilnacipran or salt thereof.