Extended release formulation of levetiracetam

Abstract

An extended release pharmaceutical composition of Levetiracetam with once a day dosage regime and the process of preparing it. The extended release tablet of Levetiracetam is with the 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 patients blood plasma, which comprises administering orally to a patient in need thereof, an extended release tablet that provides a peak blood plasma level of Levetiracetam in from about eight to about Sixteen hours. The core is prepared by Wet granulation, Dry granulation or Direct compression and optionally the tablet core is coated either in an coating pan or in and Fluidized bed system.

We claim: 
     
         1 . An extended release tablet of Levetiracetam with the 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. 
     
     
         2 . An extended release tablet of Levetiracetam with the core comprising from about 30% w/w to about 85% w/w of Levetiracetam and about 1% w/w to about 55% w/w water dispersible rate controlling polymer, and the tablet core has a functional coat of about 1% w/w to 15% w/w of core with the said functional coat comprising a combination of water non-dispersible and/or water dispersible polymer. 
     
     
         3 . An extended release formulation of Levetiracetam which 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 patients blood plasma, which comprises administering orally to a patient in need thereof, an extended release tablet that provides a peak blood plasma level of Levetiracetam in from about eight to about Sixteen hours. 
     
     
         4 . An extended release formulation according to  claim 1  wherein the tablet is comprised of from about 50% to 80% Levetiracetam by weight, about 20% to about 40% hydroxypropyl methylcellulose, by weight, and, optionally, from about 1% to about 5% by weight of Povidone. 
     
     
         5 . An extended release formulation according to  claim 1 , wherein the tablet core is comprised of from about 50% to 80% Levetiracetam by weight, about 20% to about 40% hydroxypropyl methylcellulose, by weight, and, optionally, from about 1% to about 5% by weight of Povidone and the core is coated with a functional coat comprising of ethyl cellulose and hydroxypropyl methylcellulose. 
     
     
         6 . An extended release formulation according to  claim 5  wherein the core is coated with from about 1% to about 12% of total formulation weight of film coating comprised of from about 70% to about 80% by weight of film coating of ethyl cellulose and from about 20% to about 30% by weight of film coating of hydroxypropyl methylcellulose. 
     
     
         7 . An extended release formulation according to  claim 5  wherein the core is coated with from about 1% to about 12% of total formulation weight of film coating comprised of from about 70% to about 80% by weight of film coating of ethyl cellulose, and from about 20% to about 30% by weight of film coating of Lactose. 
     
     
         8 . An extended release formulation of Levetiracetam having the following dissolution profile in USP Apparatus 1 (basket) at 100 rpm in purified water at 37.degree. C: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Time (hours) 
                   Average % Levetiracetam released 
                 
                     
                     
                 
                     
                 
                 
                 
                 
               
                     
                   2 
                   <35 
                 
                     
                   4 
                   35-75 
                 
                     
                   12 
                   >75 
                 
                     
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
               
            
           
         
       
     
     
         9 . An extended release formulation according to  claim 1  wherein the tablet is comprised of from about 61% to 73% Levetiracetam by weight, about 25% to about 35% hydroxypropyl methylcellulose, by weight, and, optionally, from about 1.1% to about 1.5% by weight of Povidone. 
     
     
         10 . An extended release formulation according to  claim 1  wherein the tablet core is comprised of from about 61% to 73% Levetiracetam by weight, about 25% to about 35% hydroxypropyl methylcellulose, by weight, and, optionally, from about 1.1% to about 1.5% by weight of Povidone and the core is coated with a functional coat comprising of ethyl cellulose and hydroxypropyl methylcellulose. 
     
     
         11 . An extended release formulation according to  claim 10  wherein the core is coated with from about 1.5% to about 4.8% of total formulation weight of film coating comprised of about 75% by weight of film coating of ethyl cellulose and about 25% by weight of film coating of hydroxypropyl methylcellulose. 
     
     
         12 . An extended release formulation according to  claim 1  wherein the functional film coating comprises 1-6% by weight of total weight. 
     
     
         13 . An extended release formulation according to  claim 1  wherein the film coating composition is comprised 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%. 
     
     
         14 . An extended release formulation according to  claim 1  wherein the core is prepared by Wet granulation, Dry granulation or Direct compression and optionally the tablet core is coated either in an coating pan or in and Fluidized bed system. 
     
     
         15 . An extended release formulation of Levetiracetam according to  claim 1  having the following dissolution profile in USP Apparatus 1 (basket) at 100 rpm in purified water at 37.degree. C: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Time (hours) 
                   Average % Levetiracetam released 
                 
                     
                     
                 
                     
                 
                 
                 
                 
               
                     
                   2 
                   10-35 
                 
                     
                   4 
                   35-75 
                 
                     
                   12 
                   >80 
                 
                     
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
               
            
           
         
       
     
     
         16 . An extended release formulation according to  claim 1  which is further coated with a hydrophilic polymer to improve its appearance, said polymer being in a ready mix form for example Opadry™.