Immediate release tablet

Abstract

A new oral IR formulation in solid form for a low molecular weight thrombin inhibitor having pH dependant dissolution, characterized in that the formulation comprises a filler or a combination of fillers having disintegrant properties in an amount higher than 35% w/w of the formulation.

1 . An oral immediate release formulation in solid form, comprising: 
 (a) a low molecular weight peptide-based thrombin inhibitor having pH dependent solubility and a particle size of less than 300 μm, wherein the thrombin inhibitor is selected from the group consisting of inogatran, melagatran and (glycine, N-[1-cyclohexyl-2-[2-[[[[4-[(hydroxyimino)aminomethyl]-phenyl]methyl]amino]carbonyl]-1-azetidinyl]-2-oxoethyl]-, ethyl ester, [S-(R*,S*)]-), and    (b) a filler or a combination of fillers selected from the group consisting of microcrystalline cellulose, microfine cellulose, cross-linked sodium carboxymethyl cellulose, cross-linked hydroxypropyl cellulose, pregelatinized starch, maize starch, potato starch, rice starch and wheat starch in an amount higher than 35% w/w of the formulation.    
     
     
         2 . The oral formulation according to  claim 1 , wherein the formulation optionally contains a sugar, a disintegrant, a binder and/or a lubricant.  
     
     
         3 . The oral formulation according to  claim 1 , wherein the thrombin inhibitor has a particle size of less than 150 μm.  
     
     
         4 . The oral formulation according to  claim 1 , further comprising mannitol.  
     
     
         5 . The oral formulation according to  claim 1 , wherein microcrystalline cellulose constitutes 50-90% (w/w) of the formulation.  
     
     
         6 . The oral formulation according to  claim 4 , mannitol constitutes 0-15% (w/w) of the formulation.  
     
     
         7 . The oral formulation according to  claim 1 , wherein the thrombin inhibitor is (glycine, N-[1-cyclohexyl-2-[2-[[[[4-[(hydroxyimino)aminomethyl]-phenyl]methyl]amino]carbonyl]-1-azetidinyl]-2-oxoethyl]-, ethyl ester, [S-(R*,S*)]-).  
     
     
         8 - 12 . (canceled)  
     
     
         13 . The oral formulation according to  claim 1 , wherein the thrombin inhibitor has a particle size of less than 80 μm.  
     
     
         14 . The oral formulation according to  claim 1 , further comprising a binder.  
     
     
         15 . The oral formulation according to  claim 14 , wherein the binder constitutes up to 15% (w/w) of the formulation.  
     
     
         16 . The oral formulation according to  claim 14 , wherein the binder is a polyvinylpyrrolidone.  
     
     
         17 . The oral formulation according to  claim 1 , wherein the thrombin inhibitor constitutes 1-35% (w/w) of the formulation.  
     
     
         18 . A process for the preparation of the oral immediate release pharmaceutical formulation according to  claim 1 , comprising preparing the formulation by direct compression or by wet granulation techniques.  
     
     
         19 . A method for the treatment of thromboembolism comprising administering, to a mammal in need thereof, a therapeutically effective amount of an oral immediate release formulation according to  claim 1 .  
     
     
         20 . A method for inhibiting thrombin in a mammal, comprising administering to said mammal a therapeutically effective amount of an oral immediate release formulation according to  claim 1.