Sustained release pharmaceutical preparations and methods for producing the same

Abstract

An extended release tablet comprising a core including albuterol sulfate and extended release agent; and an extended release coating on the core to provide for sustained release of the albuterol sulfate.

1 . An extended release tablet comprising: 
 a core including albuterol sulfate and extended release agent; and    an extended release coating associated with the core to provide for sustained release of the albuterol sulfate.    
     
     
         2 . The extended release tablet according to  claim 1  wherein the extended release agent comprises a hydrophobic polymer.  
     
     
         3 . The extended release tablet according to  claim 2  wherein the hydrophobic polymer comprises ethyl cellulose.  
     
     
         4 . The extended release tablet according to  claim 1  wherein the extended release coating comprises hydrophobic polymer and hydrophilic polymer.  
     
     
         5 . The extended release tablet according to  claim 4  wherein the hydrophobic polymer comprises ethyl cellulose and the hydrophilic polymer comprises methyl cellulose.  
     
     
         6 . The extended release tablet according to  claim 1  wherein the extended release coating comprises ethyl cellulose and methyl cellulose, and the extended release agent comprises ethyl cellulose.  
     
     
         7 . The extended release tablet according to  claim 4  wherein the hydrophobic polymer and hydrophilic polymer of said extended release coating are present in a weight ratio of 55-65:45-35 of said hydrophobic polymer to said hydrophilic polymer.  
     
     
         8 . The extended release tablet according to  claim 7  wherein the hydrophobic polymer and hydrophilic polymer of said extended release coating are present in a weight ratio of 53:47 of said hydrophobic polymer to said hydrophilic polymer.  
     
     
         9 . The extended release tablet according to  claim 7  wherein the hydrophobic polymer and hydrophilic polymer of said extended release coating comprise ethyl cellulose and methyl cellulose, respectively.  
     
     
         10 . The extended release tablet according to  claim 8  wherein the hydrophobic polymer and hydrophilic polymer of said extended release coating comprise ethyl cellulose and methyl cellulose, respectively.  
     
     
         11 . The extended release tablet according to  claim 7  wherein the extended release coating has a weight of about 5 to 25 mg.  
     
     
         12 . The extended release tablet according to  claim 11  wherein the extended release coating has a weight of about 8 to 13 mg.  
     
     
         13 . The extended release tablet according to  claim 4  wherein ethanol is utilized as a solvent for preparing the core and the extended release coating.  
     
     
         14 . The extended release tablet according to  claim 1  wherein the core includes an anhydrous sulfate.  
     
     
         15 . The extended release tablet according to  claim 1  wherein the anhydrous sulfate comprises calcium sulfate.  
     
     
         16 . The extended release tablet according to  claim 1  wherein the core includes lactose monohydrate.  
     
     
         17 . The extended release tablet according to  claim 1  comprising an albuterol dissolution profile for a formulation containing 8 mg of albuterol of:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   2 nd  Hour 
                   Not more than 30% 
                 
                     
                   6 th  Hour 
                   50-75% 
                 
                     
                   10 th  Hour 
                   Not less than 75%. 
                 
                     
                     
                 
                     
                     
                 
             
                
                
               
               
                
                
                
                
                
               
            
           
         
       
     
     
         18 . The extended release tablet according to  claim 1  comprising an albuterol dissolution profile for a formulation containing 4 mg of albuterol of:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   2 nd  Hour 
                   Not more than 20% 
                 
                     
                   6 th  Hour 
                   45-70% 
                 
                     
                   10 th  Hour 
                   Not less than 75%. 
                 
                     
                     
                 
                     
                     
                 
             
                
                
               
               
                
                
                
                
                
               
            
           
         
       
     
     
         19 . The extended release tablet according to  claim 1  having bioequivalency to an albuterol sulfate osmotic device formulation.  
     
     
         20 . A diffusion controlled tablet for extended release of albuterol sulfate comprising albuterol sulfate in a diffusion controlled formulation structured and arranged to provide an albuterol dissolution profile for a formulation containing 8 mg of albuterol of:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   2 nd  Hour 
                   Not more than 30% 
                 
                     
                   6 th  Hour 
                   50-75% 
                 
                     
                   10 th  Hour 
                   Not less than 75%. 
                 
                     
                     
                 
                     
                     
                 
             
                
                
               
               
                
                
                
                
                
               
            
           
         
       
     
     
         21 . A diffusion controlled tablet for extended release of albuterol sulfate comprising albuterol sulfate in a diffusion controlled formulation structured and arranged to provide an albuterol dissolution profile for a formulation containing 4 mg of albuterol of:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   2 nd  Hour 
                   Not more than 20% 
                 
                     
                   6 th  Hour 
                   45-70% 
                 
                     
                   10 th  Hour 
                   Not less than 75%. 
                 
                     
                     
                 
                     
                     
                 
             
                
                
               
               
                
                
                
                
                
               
            
           
         
       
     
     
         22 . A diffusion controlled formulation for extended release of albuterol sulfate comprising albuterol sulfate in a diffusion controlled formulation structured and arranged to provide bioequivalency to an albuterol sulfate osmotic device formulation.  
     
     
         23 . The diffusion controlled formulation according to  claim 22  wherein bioequivalency is measured in a randomized, single dose, 2-way cross-over bioavailability study of healthy adult males under fasting conditions, based upon 36 individuals and plasma albuterol levels, for a formulation containing 4 mg of albuterol.  
     
     
         24 . The diffusion controlled formulation according to  claim 23  wherein In AUC 0-t is within 80-125% of 53074 pg·h/mL, In AUCinf is within 80-125% of 55606 pg·h/mL, and In Cmax is within 80-125% of 4383 pg/mL.  
     
     
         25 . The diffusion controlled formulation according to  claim 22  wherein bioequivalency is measured in a randomized, single dose, 3-way cross-over bioavailability study of healthy adult males under fed and fasting conditions, based upon 16 individuals and plasma albuterol levels, for a formulation containing 8 mg of albuterol.  
     
     
         26 . The diffusion controlled formulation according to  claim 25  wherein, for fed adult males, In AUC 0-t is within 80-125% of 106139 pg·h/mL, ln AUCinf is within 80-125% of 109692 pg·h/mL, and in Cmax is within 80-125% of 7149 pg/mL.  
     
     
         27 . The diffusion controlled formulation according to  claim 22  wherein bioequivalency is measured in a randomized, 2-way cross-over steady state bioavailability study of healthy adult males under fasting conditions, based upon 37 individuals and plasma albuterol levels, for a formulation containing 8 mg of albuterol.  
     
     
         28 . The diffusion controlled formulation according to  claim 27  wherein ln AUC O-T is within 80-125% of 1125573 pg·h/ml and In Cmax is within 80-125% of 14522 pg/mL.