Extended release formulation of levetiracetam

Abstract

The present invention relates to extended release pharmaceutical compositions of Levetiracetam and processes for preparing the same. The extended release tablet of Levetiracetam is with a core comprising of Levetiracetam and water dispersible rate controlling polymer, and the tablet core is optionally functional coated comprising a combination of water non-dispersible and/or water dispersible polymer. It provides extended therapeutically effective plasma levels over a twenty four hour period with diminished incidences of neuropsychiatric adverse events by eliminating the troughs and peaks of drug concentration in a patient's blood plasma. The composition also exhibits no food effect.

We claim: 
     
         1 . An extended release tablet of Levetiracetam comprising from about 30% to about 85% w/w of the tablet of Levetiracetam and about 1% to about 50% w/w of the tablet of a water dispersible rate controlling polymer, which exhibits no adverse food effect. 
     
     
         2 . An extended release tablet formulation according to  claim 1 , wherein said tablet exhibiting a value of (AUC fed )/(AUC fasted ) of at least 0.80 with a lower 90% confidence limit of at least 0.75. 
     
     
         3 . An extended release tablet formulation according to  claim 1 , wherein said tablet is coated with a functional coat of about 1% to 15% w/w of the tablet weight comprising a combination of a water non-dispersible polymer and a water dispersible polymer. 
     
     
         4 . An extended release tablet formulation according to  claim 1 , wherein when orally administered to a patient in need thereof provides a peak plasma level of Levetiracetam in from about eight to about sixteen hours and provides extended therapeutically effective plasma levels over a twenty four hour period with diminished incidences of neuropsychiatric adverse events by eliminating the troughs and peaks of drug concentration in vivo. 
     
     
         5 . An extended release tablet according to  claim 1 , wherein the tablet is comprised of from about 50% to 80% Levetiracetam w/w of the tablet and about 20% to about 40% w/w of the tablet hydroxypropyl methylcellulose. 
     
     
         6 . An extended release tablet according to  claim 5 , wherein the tablet further comprises about 1% to about 5% w/w of the tablet povidone. 
     
     
         7 . An extended release tablet according to  claim 6 , wherein the tablet is coated with a functional coat comprising ethyl cellulose, hydroxypropyl methylcellulose and polyethylene glycol. 
     
     
         8 . An extended release tablet according to  claim 1 , wherein the tablet is coated with a functional coat of about 1% to about 12% w/w of the tablet weight, said functional coat comprising of from about 70% to about 80% w/w of the functional coat of ethyl cellulose, from about 20% to about 30% w/w of the functional coat of hydroxypropyl methylcellulose and from 10 to about 20% w/w of the functional coat of polyethylene glycol. 
     
     
         9 . An extended release tablet according to  claim 1  wherein the tablet is coated with a functional coat of about 1% w/w to about 12% w/w of the tablet weight, said functional coat comprising of from about 70% to about 80% w/w of the functional coat of ethyl cellulose and from about 20% to about 30% w/w of the functional coat of lactose. 
     
     
         10 . An extended release tablet according to  claim 1  having the following dissolution profile in USP Apparatus 1 (basket) at 100 rpm in purified water at 37° C.: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Time (hours) 
                   Average % Levetiracetam released 
                 
                     
                     
                 
                     
                 
                 
                 
                 
               
                     
                   2 
                   <35 
                 
                     
                   4 
                   35-75 
                 
                     
                   12 
                   >75 
                 
                     
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
               
            
           
         
       
     
     
         11 . An extended release tablet according to  claim 1 , wherein the tablet is comprised of from about 61% to 73% w/w of the tablet levetiracetam and about 25% to about 35% w/w of the tablet. hydroxypropyl methylcellulose 
     
     
         12 . An extended release tablet according to  claim 11 , wherein the tablet further comprises from about 1.1% to about 1.5% w/w of the tablet povidone. 
     
     
         13 . An extended release tablet according to  claim 11 , wherein the tablet is coated with a functional coat of about 1.0% to about 6.0% w/w of the tablet, said functional coat comprising of about 75% w/w of the functional coat of ethyl cellulose and about 25% w/w of the functional coat of hydroxypropyl methylcellulose. 
     
     
         14 . An extended release tablet according to  claim 11 , wherein the tablet is coated with a functional coat comprising of ethyl cellulose, hydroxypropyl methylcellulose and polyethylene glycol. 
     
     
         15 . An extended release tablet according to  claim 1 , wherein said tablet is coated with a functional coat of about 1-6% w/w of the tablet. 
     
     
         16 . An extended release tablet according to  claim 15 , wherein the functional coat comprises of ethyl cellulose having a 44.0-51.0% content of ethoxy groups and hydroxypropyl methylcellulose having viscosity of 2-6 cps at 2% aqueous solution with a methoxy content of 28.0-30.0% and a hydroxypropoxy group content of 7.0-12.0%. 
     
     
         17 . An extended release tablet according to  claim 1 , wherein the tablet is prepared by wet granulation, dry granulation or direct compression. 
     
     
         18 . An extended release tablet according to  claim 1 , wherein the tablet is prepared by wet granulation, dry granulation or direct compression and the core is coated either in a coating pan or in a fluidized bed system. 
     
     
         19 . The extended release tablet of  claim 1  wherein the hydrophilic polymer is in the form of Opadry ready mix.