Pharmaceutical formulation

Abstract

The present invention relates to a pharmaceutical composition of 8-chloro-5-methyl-1-[4-(2-pyridyloxy)cyclohexyl]-4,6-dihydro-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine, a process for the preparation thereof and its use in the treatment of diseases.

1 . A pharmaceutical composition comprising a compound of formula I, 
       
         
           
           
               
               
           
         
       
     
     
         2 . A peroxid-free pharmaceutical composition comprising the compound of formula I 
       
         
           
           
               
               
           
         
       
     
     
         3 . The pharmaceutical composition according to  claim 1 , comprising the compound of formula I in a kernel, in particular 5±1% by weight of the compound of formula I, more particular 5% by weight of the compound of formula I. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , further comprising at least one of the following compounds in the kernel:
 ii) disintegrant,   iii) filler,   iv) glidant and   v) lubricant.   
     
     
         5 . The pharmaceutical composition according to  claim 1 , further comprising the kernel consisting of:
 i) compound of formula I as defined in  claim 1     ii) disintegrant,   iii) filler,   iv) glidant and   v) lubricant.   
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein
 i) the disintegrant is croscarmellose sodium, in particular 5±1 croscarmellose sodium, more particular 5% by weight croscarmellose sodium   ii) the filler is mannitol and/or starch, in particular 85±3% by weight filler, more particular 70% by weight mannitol and 15% by weight starch,   iii) the glidant is colloidal anhydrous silica, in particular 2±1% by weight colloidal anhydrous silica, more particular 2% by weight colloidal anhydrous silica, and   iv) the lubricant is sodium stearyl fumarate, in particular 3±1% by weight sodium stearyl fumarate, more particular 3% by weight sodium stearyl fumarate.   
     
     
         7 . The pharmaceutical composition according to  claim 1 , further comprising a film coating system, in particular a film coating system comprising:
 i) a coating agent,   ii) a colourant,   iii) a plasticizer,   iv) an anti-tacking agent, and   v) a coating vehicle.   
     
     
         8 . The pharmaceutical composition according to  claim 7 , wherein
 i) the coating agent is polyvinyl alcohol, in particular 40±2% by weight polyvinyl alcohol, more particular 40% by weight polyvinyl alcohol,   ii) the first colourant is titanium dioxide, in particular 23±2% by weight titanium dioxide, more particular 22.8% by weight titanium dioxide,   iii) the second colourant is aluminum (2E)-3-oxo-2-(3-oxo-5-sulfo-1H-indol-2-ylidene)-1H-indole-5-sulfonic acid, in particular 2±1% by weight (2E)-3-oxo-2-(3-oxo-5-sulfo-1H-indol-2-ylidene)-1H-indole-5-sulfonic acid, more particular 2.2% by weight (2E)-3-oxo-2-(3-oxo-5-sulfo-1H-indol-2-ylidene)-1H-indole-5-sulfonic acid,   iv) the plasticizer is Macrogol/PEG 3350, in particular 20.2±2% by weight Macrogol/PEG 3350, more particular 20.2% by weight Macrogol/PEG 3350,   v) the anti-tacking agent is talc, in particular 14.8±1% by weight talc, more particular 14.8% by weight talc, and   vi) the coating vehicle is purified water.   
     
     
         9 . The pharmaceutical composition according to  claim 1 , wherein the kernel according to any one of  claims 1 - 5  is film coated with a 3% by weight of a film coating system according to any one of  claims 6 - 7  based on the kernel weight. 
     
     
         10 . The pharmaceutical composition according to  claim 1  as described below 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Kernel 
                   mg 
                 
                     
                     
                 
                     
                 
                 
                 
                 
               
                     
                   a compound of formula 1 
                   10.00 
                 
                     
                   Mannitol 
                   140 
                 
                     
                   Maize Starch 
                   30 
                 
                     
                   Croscarmellose Sodium 
                   10 
                 
                     
                   Silica, Colloidal Anhydrous 
                   4 
                 
                     
                   Sodium Stearyl Fumarate 
                   6 
                 
                     
                   Film Coating System 
                     
                 
                     
                   Polyvinyl Alcohol 
                   2.40 
                 
                     
                   Titanium Dioxide/Aluminum (2E)-3-oxo- 
                   1.3692/0.1308 
                 
                     
                   2-(3-oxo-5-sulfo-1H-indol-2-ylidene)- 
                     
                 
                     
                   1H-indole-5-sulfonic acid 
                     
                 
                     
                   Macrogol/PEG 3350 
                   1.21 
                 
                     
                   Talc 
                   0.89 
                 
                     
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         11 . A process to produce the pharmaceutical composition as described in  claim 1 , in particular a process comprising the following steps
 i) blend the compound of formula I, maize starch, colloidal anhydrous silica in Container 1,   ii) sieve blend the mixture of i) having a screen size approximately 1.5 mm into Container 2,   iii) add mannitol and croscarmellose sodium to Container 2 and blend,   iv) sieve blend the mixture of iii) having a screen size approximately 1.5 mm into Container 1,   v) add pre-sieved sodium stearyl fumarate having a screen size approximately 0.5 mm into Container 1 and blend,   vi) compress the blend of v) into tablet kernels, and   vii) prepare the film-coating system, and   viii) spray it onto the kernels.   
     
     
         12 . The pharmaceutical composition as described in  claim 1  for use in the treatment of the core social and communication deficits of patients with autism spectrum disorder. 
     
     
         13 . A dispersible tablet of a pharmaceutical composition as described in  claim 1 . 
     
     
         14 . The invention as described hereinabove.