Stable dosage forms of levomilnacipran

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.

What is claimed is: 
     
         1 . A stable dosage form comprising levomilnacipran or a pharmaceutically acceptable salt thereof. 
     
     
         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. 
     
     
         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. 
     
     
         18 . A method for treating major depressive disorder comprising administering the stable dosage form of  claim 1  to a patient in need thereof. 
     
     
         19 . A method for treating major depressive disorder comprising administering the stable dosage form of  claim 2  to a patient in need thereof. 
     
     
         20 . A method for treating major depressive disorder comprising administering the stable dosage form of  claim 16  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. 
     
     
         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. 
     
     
         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.