US2003203025A1PendingUtilityA1

Sustained release oral formulations

49
Priority: Oct 1, 1998Filed: Mar 31, 2003Published: Oct 30, 2003
Est. expiryOct 1, 2018(expired)· nominal 20-yr term from priority
A61P 25/28A61K 9/2077A61K 9/5084A61K 9/2866A61K 9/2886A61K 9/5078A61K 31/27A61K 9/20
49
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Claims

Abstract

Pharmaceutical composition capable of releasing a therapeutically effective dose of active agent, e.g., rivastigamine, in a time-controlled manner.

Claims

exact text as granted — not AI-modified
1 . A pharmaceutical composition comprising 
 a first component comprising a first active agent dose wherein on contact with water 70 to 95% of said dose is released within 3 to 4 hours, and    a second component comprising a second active agent dose, a water soluble osmosis inducing agent and a water swellable excipient, said second component having a water permeable coating which, in use on contact with water, ruptures after a delay, and releases the active agent.    
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein the coating in the second component is a semi-permeable membrane.  
     
     
         3 . A pharmaceutical composition according to  claim 1  or  2  wherein the second component releases an effective dose of the active agent 6 to 12 hours after ingestion.  
     
     
         4 . A pharmaceutical composition according to any one of  claims 1  to  3  wherein the first component comprises a cellulose derivative coating.  
     
     
         5 . A pharmaceutical composition according to  claim 4  wherein the cellulose derivative coating comprises ethyl cellulose and hydroxypropyl methylcellulose.  
     
     
         6 . A pharmaceutical composition according to any one of  claims 1  to  3  wherein the first component comprises the active agent in a matrix.  
     
     
         7 . A pharmaceutical composition according to  claim 6  wherein in the first component the active agent is in a hydrophilic gel forming substance.  
     
     
         8 . A pharmaceutical composition according to  claim 7  wherein the hydrophilic gel forming substance is present in a ratio of 10 to 50% by weight of the first component.  
     
     
         9 . A pharmaceutical composition according to  claim 7  or  8  wherein the hydrophilic gel forming substance comprises hydroxypropylmethylcellulose having a viscosity of 100,000 mPa-s.  
     
     
         10 . A pharmaceutical composition according to any one of  claims 1  to  9  wherein the second component has the following release characteristics in water:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   time (minutes) 
                   amount (percentage) 
                 
                     
                     
                 
                     
                    0 
                   0-1 
                 
                     
                   120 
                   0-1 
                 
                     
                   180 
                   0-1 
                 
                     
                   240 
                    0-75 
                 
                     
                   300 
                    0-95 
                 
                     
                   360 
                   >99 
                 
                     
                     
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         11 . A pharmaceutical composition according to any one of  claims 1  to  10  wherein the active agent is rivastigmine.  
     
     
         12 . A pharmaceutical composition according to any one of  claims 1  to  11  comprising from 0.5 to 25% by weight of rivastigmine as active agent of the total composition.  
     
     
         13 . A pharmaceutical composition according to any one of  claims 1  to  12  wherein the second component comprises a second coating.  
     
     
         14 . A pharmaceutical composition comprising rivastigmine adapted so that in use on oral administration a therapeutically effective dose of rivastigmine is released only after 6 hours.  
     
     
         15 . A pharmaceutical composition capable of releasing on administration twice a therapeutically effective dose of rivastigmine at different intervals upon oral administration.  
     
     
         16 . A pharmaceutical oral controlled release tablet composition comprising rivastigmine.  
     
     
         17 . A pharmaceutical composition comprising Rivastigmine having the following release characteristics in water:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   time (minutes) 
                   amount (percentage) 
                 
                     
                     
                 
                     
                    30 
                    1-40 
                 
                     
                    60 
                   10-60 
                 
                     
                   120 
                   40-80 
                 
                     
                   180 
                   60-90 
                 
                     
                   240 
                   65-95 
                 
                     
                   300 
                   70-99 
                 
                     
                   360 
                   75-99 
                 
                     
                   420 
                   >80 
                 
                     
                     
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         18 . A controlled release, oral pharmaceutical composition containing rivastigmine having the following release characteristic in water or artificial stomach juices:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   time (minutes) 
                   amount (percentage) 
                 
                     
                     
                 
                     
                    30 
                    1-8 
                 
                     
                    60 
                   15-25 
                 
                     
                   120 
                   45-70 
                 
                     
                   180 
                   75-90 
                 
                     
                   240 
                   92-95 
                 
                     
                   300 
                   95-98 
                 
                     
                   360 
                   97-99 
                 
                     
                   420 
                   >99 
                 
                     
                     
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         19 . A controlled release, oral pharmaceutical composition containing rivastigmine having the following release characteristic in water or artificial stomach juices:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   time (minutes) 
                   amount (percentage) 
                 
                     
                     
                 
                     
                    30 
                    5-25 
                 
                     
                    60 
                   25-45 
                 
                     
                   120 
                   50-70 
                 
                     
                   180 
                   65-80 
                 
                     
                   240 
                   70-90 
                 
                     
                   300 
                   75-95 
                 
                     
                   360 
                   80-90 
                 
                     
                   420 
                   85-95 
                 
                     
                   480 
                   85-95 
                 
                     
                     
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         20 . A controlled release, oral pharmaceutical composition containing rivastigmine having the following release characteristic in water or artificial stomach juices:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   time (minutes) 
                   amount (percentage) 
                 
                     
                     
                 
                     
                    30 
                   25-40 
                 
                     
                    60 
                   45-65 
                 
                     
                   120 
                   65-85 
                 
                     
                   180 
                   75-95 
                 
                     
                   240 
                   75-96 
                 
                     
                   300 
                   85-97 
                 
                     
                   360 
                   87-98 
                 
                     
                   420 
                   90-98 
                 
                     
                   480 
                   90-99 
                 
                     
                     
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         21 . A controlled release, oral pharmaceutical composition containing rivastigmine wherein in use 50 to 80% of said rivastigmine is released in artificial stomach juices within 3 hours.  
     
     
         22 . A composition according to any one of  claims 16  to  21  comprising coated particles.  
     
     
         23 . A composition according to any one of  claims 16  to  22  comprising coated pellets.  
     
     
         24 . A composition according to  Claim 22  or  23  wherein the coating comprises a cellulose derivative.  
     
     
         25 . A composition according to  claim 24  wherein the cellulose derivative comprises ethyl cellulose and hydroxypropyl methylcellulose.  
     
     
         26 . A pharmaceutical composition according to  claim 16  or  17  wherein rivastigmine is in a hydrophilic swellable substance.  
     
     
         27 . A pharmaceutical composition according to  claim 26  wherein the hydrophilic swellable substance comprises hydroxypropylmethylcellulose 100,000 cps.  
     
     
         28 . A pharmaceutical oral controlled release tablet composition comprising rivastigmine having the following release characteristic in water or artificial stomach juices:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   time (minutes) 
                   amount (percentage) 
                 
                     
                     
                 
                     
                    30 
                   28-35 
                 
                     
                    60 
                   40-55 
                 
                     
                   120 
                   58-75 
                 
                     
                   180 
                   70-90 
                 
                     
                   240 
                   80-95 
                 
                     
                   300 
                   88-98 
                 
                     
                   360 
                   >92 
                 
                     
                     
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         29 . A pharmaceutical oral controlled release tablet composition comprising rivastigmine wherein in use 60 to 90% of said rivastigmine is released in artificial stomach juices within 3 hours.  
     
     
         30 . Use of rivastigmine and excipients as defined in any one of  claims 1  to  29  in the manufacture of a medicament for the treatment of patients with mild to moderately severe Dementia of the Alzheimer's type by oral administration.  
     
     
         31 . A pharmaceutical composition comprising a core coated with two films, the first Inner film being a semi-permeable to water or body fluids film applied directly on said core and comprising cellulose acetate, the second outer film being a permeable to water or body fluids film comprising ethylcellulose.

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