Pharmaceutical compositions comprising colloidal silicon dioxide

Abstract

The present invention provides a pharmaceutical composition comprising a macrolide solid dispersion, a disintegrant and colloidal silicon dioxide. The composition comprises 1 to 5% colloidal silicon dioxide by weight.

1 - 10 . (canceled) 
   
   
       11 . A pharmaceutical composition in the form of a dispersible tablet comprising a 40-O-(2-hydroxy)ethyl-rapamycin solid dispersion, a disintegrant comprising crosslinked polyvinylpyrrolidone and colloidal silicon dioxide, wherein the composition comprises 1 to 5% colloidal silicon dioxide by weight. 
   
   
       12 . A pharmaceutical composition according to  claim 11 , wherein crosslinked polyvinylpyrrolidone is in an amount of 10 to 30% by weight based on the total weight of the composition. 
   
   
       13 . A pharmaceutical composition according to  claim 11  or  12 , wherein crosslinked polyvinylpyrrolidone is in an amount of about 20% by weight based on the total weight of the composition. 
   
   
       14 . A pharmaceutical composition according to  claim 11  wherein 250 mg of the composition, when compressed using a force of 8 to 11 kN with a 9 mm die and standard flat punches, forms a tablet having a hardness of 35 to 80 N and a disintegration time of 3 minutes or less. 
   
   
       15 . A composition according to  claim 14  wherein 250 mg of the composition, when compressed using a compression force of 9.5 kN with a 9 mm die and standard flat punches, forms a tablet having a hardness of 40 to 66 N and a disintegration time of 3 minutes or less. 
   
   
       16 . A composition according to  claim 11 , wherein the tablet has a disintegration time of 90 seconds or less. 
   
   
       17 . A composition according to  claim 11  for use as an immunosuppressant. 
   
   
       18 . A process for producing a 40-O-(2-hydroxy)ethyl-rapamycin-containing dispersible tablet, comprising preparing a 40-O-(2-hydroxy)ethyl-rapamycin solid dispersion, mixing the 40-O-(2-hydroxy)ethyl-rapamycin solid dispersion with a disintegrant comprising crosslinked polyvinylpyrrolidone and colloidal silicon dioxide, wherein the composition comprises 1 to 5% colloidal silicon dioxide by weight to form a pharmaceutical composition and compressing the pharmaceutical composition to form the dispersible tablet. 
   
   
       19 . A process according to  claim 18 , wherein crosslinked polyvinylpyrrolidone is in an amount of about 10 to 30% by weight based on the total weight of the composition. 
   
   
       20 . A process according to  claim 18  or  19 , wherein crosslinked polyvinylpyrrolidone is in an amount of about 20% by weight based on the total weight of the composition.