Method for manufacturing medicinal compounds containing dabigatran

Abstract

The invention relates to an improved process for preparing a new medicament formulation of the active substance dabigatran etexilate of formula I in the form of the methanesulphonic acid salt thereof, and this new medicament formulation as such.

1 . A process for preparing a suspension 4 of polymorph I of a methanesulphonic acid salt of dabigatran etexilate of formula I, 
       
         
           
           
               
               
           
         
         comprising the step of 
         mixing polymorph I of dabigatran etexilate methanesulphonate having a melting point of T mp. =180±3° C. (determined by DSC; heating rate: 10° C./min) with talc in a solution of hydroxypropylcellulose in isopropyl alcohol to form a suspension, 
         wherein of the suspension is formed at a temperature not exceeding 30° C. by a circulatory dispersal process. 
       
     
     
         2 . The process according to  claim 1 , wherein hydroxypropylcellulose is first dissolved in isopropyl alcohol to form the solution and then polymorph I of dabigatran etexilate methanesulphonate and talc are suspended in said solution. 
     
     
         3 . The process according to  claim 1 , wherein 0.05 to 0.5 kg dabigatran etexilate methanesulphonate is used per kilogram of isopropyl alcohol. 
     
     
         4 . The process according to  claim 1 , wherein 0.01 to 0.1 kg hydroxypropylcellulose is used per kilogram of isopropyl alcohol. 
     
     
         5 . The process according to  claim 1 , wherein 0.005 to 0.07 kg talc is used per kilogram of isopropyl alcohol. 
     
     
         6 . Suspension 4, made by the process according to  claim 1 . 
     
     
         7 . Suspension 4 according to  claim 6 , wherein the concentration of polymorph I of dabigatran etexilate methanesulphonate (active substance) is 10-25% (w/w). 
     
     
         8 . Suspension 4 according to  claim 6 , wherein the overall concentration of active substance, hydroxypropylcellulose and talc is 14-40% (w/w). 
     
     
         9 . (canceled) 
     
     
         10 . A process for preparing dabigatran etexilate methanesulphonate pellets 5, comprising the step of spraying suspension 4 according to  claim 6  onto isolated tartaric acid cores 3 by a fluidised bed method. 
     
     
         11 . The process for preparing dabigatran etexilate methanesulphonate pellets 5 according to  claim 10 , wherein the temperature of the pellets 3 is adjusted to 30-50° C. 
     
     
         12 . The process for preparing dabigatran etexilate methanesulphonate pellets 5 according to  claim 10 , wherein the temperature of the supply air is below 90° C. 
     
     
         13 . The process for preparing dabigatran etexilate methanesulphonate pellets 5 according to  claim 10  wherein the standardised spray rate at which the active substance suspension 4 is sprayed onto the tartaric acid pellets 3 is in the range from 4-45 g/min per kilogram of tartaric acid pellets 3 used. 
     
     
         14 . The process for preparing dabigatran etexilate methanesulphonate pellets 5 according to  claim 10 , wherein the standardised amount of supply air is in the range from 10-35 (m 3 /h) per kilogram of tartaric acid pellets 3 used. 
     
     
         15 . Dabigatran etexilate methanesulphonate pellets 5, made by a process according to  claim 10 . 
     
     
         16 . The process for preparing dabigatran etexilate methanesulphonate pellets 5 according to  claim 10 , wherein the temperature of the supply air is below 80° C. 
     
     
         17 . The process for preparing dabigatran etexilate methanesulphonate pellets 5 according to  claim 10 , wherein the temperature of the supply air is between 40°-80° C. 
     
     
         18 . The process for preparing dabigatran etexilate methanesulphonate pellets 5 according to  claim 10 , wherein the temperature of the supply air is between 55°-75° C.