Pharmaceutical exipient having improved compressibility

Abstract

A microcrystalline cellulose-based excipient having improved compressibility, whether utilized in direct compression, dry granulation or wet granulation formulations, is disclosed. The excipient is an agglomerate of microcrystalline cellulose particles and from about 0.1% to about 20% silicon dioxide particles, by weight of microcrystalline cellulose, wherein the microcrystalline cellulose and silicon dioxide are in intimate association with each other. The silicon dioxide utilized in the novel excipient has a particle size from about 1 nanometer to about 100 microns. Most preferably, the silicon dioxide is a grade of colloidal silicon dioxide. An extra low moisture excipient is provided which exhibits improved compressibility as compared to conventional microcrystalline cellulose, while providing a moisture content of of from about 0.5 to 2.5% LOD, preferably between about 0.5 and about 1.8%, more preferably between 0.8 and 1.5%, and most preferably between about 0.8 and about 1.2%.

1 . A method for preparing a tablet, comprising the steps of: 
 forming an aqueous slurry containing a mixture of microcrystalline cellulose in the form of a wet cake and silicon dioxide having a particle size from about 1 nm to about 100 μm;    drying said slurry to obtain an excipient comprising a plurality of agglomerated particles of microcrystalline cellulose in intimate association with said silicon dioxide, the amount of silicon dioxide being from about 0.1% to about 20% relative to the amount of microcrystalline cellulose, by weight;    mixing an active ingredient with said excipient in a ratio from about 1:99 to about 99:1 to obtain a mixture;    compressing said mixture into a tablet.    
     
     
         2 . The method of  claim 1 , wherein said silicon dioxide is colloidal silicon dioxide, and further comprising wet granulating said mixture prior to compressing said mixture into said tablet.  
     
     
         3 . (canceled)  
     
     
         4 . The method of  claim 1 , wherein said drying is accomplished via spray drying such that the resultant excipient particles have an average particle size from about 30 μm to about 250 μm.  
     
     
         5 . The method of  claim 1 , wherein the resultant excipient particles have a bulk density from about 0.2 g/ml to about 0.6 g/ml.  
     
     
         6 . (canceled)  
     
     
         7 . The method of  claim 2 , further comprising adding a further amount of said excipient to said wet granulated mixture, prior to compressing said mixture into a tablet.  
     
     
         8 . The method of  claim 1 , wherein said drying further comprises drying said slurry such that the resultant excipient particles have a moisture content of from about 0.5 to about 15%.  
     
     
         9 . The method of  claim 1 , wherein said drying further comprises drying said slurry such that the resultant excipient particles have a moisture content of from about 0.5 to about 2.5%.  
     
     
         10 . The method of  claim 1 , wherein said drying further comprises drying said slurry such that the resultant excipient particles have a moisture content of from about 0.5 to about 1.8%.  
     
     
         11 . The method of  claim 1 , wherein said drying further comprises drying said slurry such that the resultant excipient particles have a moisture content of from about 0.8 to about 1.5%.  
     
     
         12 . The method of  claim 1 , wherein said drying further comprises drying said slurry such that the resultant excipient particles have a moisture content of from about 0.8 to about 1.2%.  
     
     
         13 - 38 . (canceled)  
     
     
         39 . A method for preparing a tablet, comprising the steps of: 
 (a) forming an aqueous slurry of microcrystalline cellulose in the form of wet cake;    (b) forming an aqueous slurry of silicon dioxide having a particle size of from about 1 to about 100 μm;    (c) separately introducing said microcrystalline slurry and said silicon dioxide slurry separately into a drying apparatus for combination therein, to obtain an excipient comprising a plurality of agglomerated particles of microcrystalline cellulose in intimate association with said silicon dioxide, the amount of silicon dioxide being from about 0.1% to about 20% relative to the amount of microcrystalline cellulose, by weight;    (d) mixing an active ingredient with said excipient in a ratio of from about 1:99 to about 99:1 to obtain a mixture;    (e) compressing said mixture into a tablet.    
     
     
         40 . The method of  claim 39 , wherein said silicon dioxide is colloidal silicon dioxide, and further comprising wet granulating said mixture prior to compressing said mixture into said tablet.  
     
     
         41 . The method of  claim 39 , wherein said drying is accomplished via spray drying such that the resultant excipient particles have an average particle size from about 10 μm to about 1,000 μm.  
     
     
         42 . The method of  claim 39 , wherein said drying is accomplished via spray drying such that the resultant excipient particles have an average particle size from about 30 μm to about 250 μm.  
     
     
         43 . The method of  claim 39 , wherein the resultant excipient particles have a bulk density from about 0.2 g/ml to about 0.6 g/ml.  
     
     
         44 . The method of  claim 39 , wherein the resultant excipient particles have a bulk density of from about 0.35 g/ml to about 0.55 g/ml.  
     
     
         45 . The method of  claim 40 , further comprising adding a further amount of said excipient to said wet granulated mixture, prior to compressing said mixture into a tablet.  
     
     
         46 . The method of  claim 39 , wherein said drying further comprises drying such that the resultant excipient particles have a moisture content of from about 0.5 to about 15%.  
     
     
         47 . The method of  claim 39 , wherein said drying further comprises drying such that the resultant excipient particles have a moisture content of from about 0.5 to about 2.5%.  
     
     
         48 . The method of  claim 39 , wherein said drying further comprises drying such that the resultant excipient particles have a moisture content of from about 0.5 to about 1.8%.  
     
     
         49 . The method of  claim 39 , wherein said drying further comprises drying such that the resultant excipient particles have a moisture content of from about 0.8 to about 1.5%.  
     
     
         50 . The method of  claim 39 , wherein said drying further comprises drying such that the resultant excipient particles have a moisture content of from about 0.8 to about 1.2%.  
     
     
         51 . The method of  claim 1 , wherein said drying is accomplished via spray drying such that the resultant excipient particles have an average particle size from about 10 μm to about 1,000 μm.  
     
     
         52 . The method of  claim 51 , wherein the resultant excipient particles have a bulk density of from about 0.35 g/ml to about 0.55 g/ml.