Modified release formulations of memantine oral dosage forms

Abstract

The present invention provides pharmaceutical compositions given once daily containing at least one therapeutically active ingredient selected from the group consisting of memantine and a pharmaceutically acceptable salt of memantine, and a pharmaceutically acceptable polymeric matrix carrier. The dosage forms of the invention sustain the release of the therapeutically active agent from about 4 to about 24 hours when said dosage form is exposed to aqueous solutions. following entry of said form into a use environment, wherein said dosage form has a dissolution rate of more than about 80% after passage of about 6 hours to about 12 hours following said entry into said use environment.

What is claimed: 
     
         1 . A modified release solid oral dosage form comprising:
 (a) at least one therapeutically active ingredient selected from the group consisting of memantine and a pharmaceutically acceptable salt of memantine, and   (b) a pharmaceutically acceptable polymeric carrier substantially contributing to the modification of the release of said active ingredient,   
       said dosage form sustaining release of said therapeutically active agent from about 4 hours to about 24 hours following entry of said form into a use environment, wherein said dosage form has a dissolution rate of more than about 80% after passage of about 6 hours to about 12 hours following said entry into said use environment. 
     
     
         2 . The modified release solid oral dosage form according to  claim 1 , wherein said active ingredient is memantine hydrochloride. 
     
     
         3 . The modified release solid oral dosage form according to  claim 1 , wherein the dissolution rate of more than about 80% is achieved after about 12 hours. 
     
     
         4 . The modified release solid oral dosage form of  claim 3 , comprising the active ingredient in an amount within the range of from about 1.0% w/w to about 20% w/w. 
     
     
         5 . The modified release solid oral dosage form according to  claim 1 , wherein the dissolution rate of more than about 80% is achieved after about 6 hours. 
     
     
         6 . The modified release solid oral dosage form of  claim 5 , wherein the active ingredient is present in amounts ranging from about 1.0% w/w to about 35% w/w. 
     
     
         7 . The modified release solid oral dosage form of  claim 1 , wherein the polymeric carrier is a polymeric matrix. 
     
     
         8 . The modified release solid oral dosage form of  claim 7 , wherein the polymeric matrix is a swellable matrix and comprises hydroxypropyl methylcellulose. 
     
     
         9 . The modified release solid oral dosage form of  claim 8 , wherein the dissolution rate of more than about 80% is achieved after about 12 hours, and wherein the hydroxypropyl methylcellulose is present in amounts from about 50% w/w to about 80% w/w. 
     
     
         10 . The modified release solid oral dosage form of  claim 8 , wherein the dissolution rate of more than about 80% is achieved after about 6 hours, and wherein the hydroxypropyl methylcellulose is present in amounts from about 20% w/w to about 70% w/w. 
     
     
         11 . The modified release solid oral dosage form of  claim 1 , further comprising a filler. 
     
     
         12 . The modified release solid oral dosage form of  claim 11 , wherein the filler is lactose monohydrate. 
     
     
         13 . The modified release solid oral dosage form of  claim 12 , wherein the dissolution rate of more than about 80% is achieved after about 12 hours, and the lactose monohydrate is present in an amount from about 5% w/w to about 50% w/w. 
     
     
         14 . The modified release solid oral dosage form of  claim 12 , wherein the dissolution rate of more than about 80% is achieved after about 6 hours, and the lactose monohydrate is present in amounts from about 5% w/w to about 75% w/w. 
     
     
         15 . The modified release solid oral dosage form of  claim 11 , wherein the filler is microcrystalline cellulose. 
     
     
         16 . The modified release solid oral dosage form of  claim 15 , wherein the microcrystalline cellulose is present in an amount from about 5% w/w to about 80% w/w. 
     
     
         17 . The modified release solid oral dosage form of  claim 11 , wherein the filler is dicalcium phosphate. 
     
     
         18 . The modified release solid oral dosage form of  claim 17 , wherein the dicalcium phosphate is present in an amount from about 7% w/w to about 40% w/w. 
     
     
         19 . The modified release solid oral dosage form of  claim 1 , further comprising a lubricant. 
     
     
         20 . The modified release solid oral dosage form of  claim 19 , wherein the lubricant is magnesium stearate. 
     
     
         21 . The modified release solid oral dosage form of  claim 20 , wherein the dissolution rate of more than about 80% is achieved after about 12 hours, and wherein the magnesium stearate is present in an amount within the range from about 0.8% w/w to about 1.2% w/w. 
     
     
         22 . The modified release solid oral dosage form of  claim 20 , wherein the dissolution rate of more than about 80% is achieved after about 6 hours, and wherein the magnesium stearate is present in an amount within the range from about 0.4% w/w to about 0.6% w/w. 
     
     
         23 . The modified release solid oral dosage form of  claim 1 , further comprising one or more components selected from the group consisting of carriers, excipients, anti-adherants, fillers, stabilizing agents, binders, colorants, glidants, and lubricants. 
     
     
         24 . A modified release solid oral dosage form, comprising
 (a) between about 2.5% w/w and about 20.0% w/w of memantine hydrochloride;   (b) between about 68% w/w and about 77% w/w of hydroxypropyl methyl cellulose;   (c) between about 6.9% w/w and about 15% w/w of lactose monohydrate;   (d) between about 0.8% w/w and about 1.3% w/w of fumed silica;   (e) between about 3.0% w/w and about 5.0% w/w of talc; and   (f) between about 0.9% w/w and about 1.1% w/w of magnesium stearate;   
       wherein the dissolution rate of memantine hydrochloride of more than about 80% is achieved after about 12 hours. 
     
     
         25 . A modified release solid oral dosage form, comprising:
 (a) between about 5% w/w and about 35% w/w of memantine hydrochloride;   (b) between about 54% w/w and about 65% w/w of hydroxypropyl methyl cellulose;   (c) between about 7% w/w and about 24% w/w of lactose monohydrate;   (d) between about 0.8% w/w and about 1.3% w/w of fumed silica;   (e) between about 3.0% w/w and about 5.0% w/w of talc; and   (f) between about 0.4% w/w and about 0.6% w/w of magnesium stearate;   
       wherein the dissolution rate of memantine hydrochloride of more than about 80% is achieved after about 6 hours. 
     
     
         26 . A modified release solid oral dosage form, comprising:
 (a) between about 5% w/w and about 35% w/w of memantine hydrochloride;   (b) between about 54% w/w and about 65% w/w of hydroxypropyl methyl cellulose;   (c) between about 7% w/w and 40% w/w of microcrystalline cellulose;   (d) between about 0.8% w/w and about 1.3% w/w of fumed silica;   (e) between about 3.0% w/w and about 5.0% w/w of talc; and   (f) between about 0.4% w/w and about 0.6% w/w of magnesium stearate;   
       wherein the dissolution rate of memantine hydrochloride of more than about 80% is achieved after about 6 hours. 
     
     
         27 . A modified release solid oral dosage form, comprising:
 (a) between about 5% w/w and about 35% w/w of memantine hydrochloride;   (b) between about 54% w/w and about 65% w/w of hydroxypropyl methyl cellulose;   (c) between about 7% w/w and 40% w/w of dicalcium phosphate;   (d) between about 0.8% w/w and about 1.3% w/w of fumed silica;   (e) between about 3.0% w/w and about 5.0% w/w of talc; and   (f) between about 0.4% w/w and about 0.6% w/w of magnesium stearate;   
       wherein the dissolution rate of memantine hydrochloride of more than about 80% is achieved after about 6 hours. 
     
     
         28 . The modified release solid oral dosage form of one of  claims 24 - 27  wherein said modified release solid oral dosage form is a tablet. 
     
     
         29 . The modified release solid oral dosage form of  claim 1 , wherein the dissolution rate exhibited by said modified release solid oral dosage form after about 1 hour is at least about 10% and up to about 35%. 
     
     
         30 . The modified release solid oral dosage form of  claim 1 , wherein the dissolution rate exhibited by said modified release solid oral dosage form after about 2 to about 6 hours is at least about 30% and up to about 60%. 
     
     
         31 . The modified release solid oral dosage form of  claim 1 , wherein said modified release solid oral dosage form is administered once-a-day. 
     
     
         32 . A method for treating a disorder selected from the group consisting of mild, moderate and severe Alzheimer's dementia, and neuropathic pain, wherein the method comprises administering a modified release solid oral dosage form of  claim 1 .