Pharmaceutical compositions comprising afatinib

Abstract

The present invention relates to a tablet comprising Afatinib or a pharmaceutically acceptable salt thereof, wherein the tablet is obtained by direct compression. The present invention further relates to a process for manufacturing a tablet of the invention as well as the use of the tablet of the invention.

1 . A tablet comprising afatinib or a pharmaceutically acceptable salt thereof and lactose, wherein the tablet is obtained by direct compression without a granulation step. 
     
     
         2 . The tablet according to  claim 1 , wherein the lactose comprises lactose monohydrate. 
     
     
         3 . The tablet according to  claim 2 , wherein the lactose monohydrate has a D 90  of 150 to 500 μm. 
     
     
         4 . The tablet according to  claim 1  comprising crystalline afatinib dimaleate. 
     
     
         5 . The tablet according to  claim 4  comprising crystalline afatinib dimaleate of Form A, Form B, Form C, Form D, Form E, Form F, Form G, Form H, Form I, Form J, Form K, Form L, or Form M. 
     
     
         6 . The tablet according to  claim 4  comprising crystalline afatinib dimaleate of Form A or Form L. 
     
     
         7 . The tablet according to  claim 1 , comprising: 
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   Crystalline afatinib dimaleate 
                   1 to 50%  
                   w/w 
                 
                     
                   Lactose monohydrate 
                   20 to 90%  
                   w/w 
                 
                     
                   Microcrystalline cellulose 
                   1 to 40% 
                   w/w 
                 
                     
                   Crospovidone  
                   0.5 to 15% 
                   w/w 
                 
                     
                   Colloidal silicon dioxide 
                   0.1 to 5% 
                   w/w 
                 
                     
                   Magnesium stearate 
                   0.5 to 10%  
                   w/w 
                 
                     
                   Hydroxypropyl methylcellulose 
                   2 to 5% 
                   w/w 
                 
                     
                   based coating 
                 
                     
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         8 . A batch of tablets, each comprising a therapeutically effective amount of afatinib or a pharmaceutically acceptable salt thereof and lactose, wherein the tablets are obtained by direct compression without a granulation step, and the therapeutically effective amount of afatinib or pharmaceutically acceptable salt thereof intended for each tablet so obtained is specified by a label claim. 
     
     
         9 . The batch according to  claim 8 , wherein the lactose comprises lactose monohydrate. 
     
     
         10 . The batch according to  claim 9 , wherein the lactose monohydrate has a D 90  of 150 to 500 μm. 
     
     
         11 . The batch according to  claim 8 , wherein the afatinib or the pharmaceutically acceptable salt thereof comprises afatinib dimaleate of crystalline Form A, Form B, Form C, Form D, Form E, Form F, Form G, Form H, Form I, Form J, Form K, Form L, or Form M. 
     
     
         12 . The batch according to  claim 8 , wherein the uniformity of the afatinib or the pharmaceutically acceptable salt thereof in the tablets is at least 99% of the label claim. 
     
     
         13 . The batch according to  claim 8 , wherein the uniformity of the afatinib or the pharmaceutically acceptable salt thereof in the tablets is at most 103% of the label claim. 
     
     
         14 . The batch according to  claim 8 , wherein the uniformity of the afatinib or the pharmaceutically acceptable salt thereof in the tablets is within 99%-103% of the label claim. 
     
     
         15 . A process for manufacturing a tablet, the process comprising:
 (i) providing a mixture of afatinib or a pharmaceutically acceptable salt thereof and lactose;   (ii) combining the mixture of step (i) with at least one lubricant; and   (iii) compressing the lubricated mixture of step (ii) to form the tablet, wherein a granulation step is not performed in the process.   
     
     
         16 . The process according to  claim 15 , wherein the lactose comprises lactose monohydrate. 
     
     
         17 . The process according to  claim 16 , wherein the lactose monohydrate has a D 90  of 150 to 500 μm. 
     
     
         18 . The process according to  claim 15 , wherein the afatinib or pharmaceutically acceptable salt thereof comprises crystalline afatinib dimaleate. 
     
     
         19 . The process according to  claim 15 , wherein the afatinib or pharmaceutically acceptable salt thereof comprises afatinib dimaleate of crystalline Form A, Form B, Form C, Form D, Form E, Form F, Form G, Form H, Form I, Form J, Form K, Form L, or Form M. 
     
     
         20 . The process according to  claim 15 , wherein the tablet comprises: 
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   Crystalline afatinib dimaleate 
                   1 to 50% 
                   w/w 
                 
                     
                   Lactose monohydrate 
                   20 to 90%  
                   w/w 
                 
                     
                   Microcrystalline cellulose 
                   1 to 40% 
                   w/w 
                 
                     
                   Crospovidone 
                   0.5 to 15% 
                   w/w 
                 
                     
                   Colloidal silicon dioxide 
                   0.1 to 5% 
                   w/w 
                 
                     
                   Magnesium stearate 
                   0.5 to 10%  
                   w/w 
                 
                     
                   Hydroxypropyl methylcellulose 
                   2 to 5% 
                   w/w 
                 
                     
                   based coating