C-Met Modulator Pharmaceutical Compositions

Abstract

Pharmaceutical compositions and unit dosage forms comprising Compound (I) are disclosed.

1 - 30 . (canceled) 
     
     
         31 . A tablet pharmaceutical composition comprising Compound I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, and a filler, wherein Compound 1 is present in the pharmaceutical composition in an amount of from about 10 mg to about 200 mg. 
     
     
         32 . The tablet pharmaceutical composition of  claim 31 , wherein the filler is sodium starch glycolate, corn starch, talc, sucrose, dextrose, glucose, lactose, xylitol, fructose, sorbitol, calcium phosphate, calcium sulfate, microcrystalline cellulose, or mixtures thereof. 
     
     
         33 . The tablet pharmaceutical composition of  claim 32 , wherein the filler is present in an amount of from about 50 to about 70 percent by weight of the pharmaceutical composition. 
     
     
         34 . The tablet pharmaceutical composition of  claim 33 , wherein Compound I is present as the L-malate salt. 
     
     
         35 . A tablet pharmaceutical composition comprising Compound I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable filler, binder, disintegrant, glidant, and lubricant, and optionally a pharmaceutically acceptable coating, wherein Compound I is present in the pharmaceutical composition in an amount of from about 10 mg to about 200 mg. 
     
     
         36 . The pharmaceutical composition of  claim 35 , wherein Compound I is present as the L-malate salt. 
     
     
         37 . The pharmaceutical composition of  claim 36 , wherein the filler is sodium starch glycolate, corn starch, talc, sucrose, dextrose, glucose, lactose, xylitol, fructose, sorbitol, calcium phosphate, calcium sulfate, microcrystalline cellulose, or mixtures thereof. 
     
     
         38 . The tablet pharmaceutical composition of  claim 37 , wherein the filler is present in an amount of from about 50 to about 70 percent by weight of the pharmaceutical composition. 
     
     
         39 . The composition of  claim 36 , wherein the binder is acacia, alginic acid, carbomer, carboxymethylcellulose sodium, dextrin, ethylcellulose, gelatin, guar gum, hydrogenated vegetable oil (type I), hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, liquid glucose, magnesium aluminium silicate, maltodextrin, methylcellulose, polymethacrylates, povidone, pregelatinized starch, sodium alginate, starch, zein, or mixtures thereof. 
     
     
         40 . The composition of  claim 39 , wherein the binder is present in an amount of from about 2 to about 4 percent by weight of the pharmaceutical composition. 
     
     
         41 . The pharmaceutical composition of  claim 36 , wherein the disintegrant is alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminum silicate, methylcellulose, microcrystalline cellulose, polyacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, starch, or mixtures thereof. 
     
     
         42 . The pharmaceutical composition of  claim 36 , wherein the glidant is silicon dioxide. 
     
     
         43 . The pharmaceutical composition of  claim 36 , wherein the lubricant is magnesium stearate, stearic acid, talc, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, light mineral oil, magnesium stearate, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, zinc stearate, or mixtures thereof. 
     
     
         44 . The pharmaceutical composition of  claim 43 , wherein the lubricant is present in an amount of from about 0.5 to about 1.0 percent by weight of the pharmaceutical composition. 
     
     
         45 . The pharmaceutical composition of  claim 36 , wherein the optional film coating comprises Opadry Yellow. 
     
     
         46 . The pharmaceutical composition of  claim 45 , wherein the optional film coating comprises hypromellose, titanium dioxide, triacetin, and iron oxide yellow. 
     
     
         47 . A tablet pharmaceutical composition comprising Compound I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof and lactose, hydroxypropyl cellulose, croscarmellose sodium, and magnesium stearate, wherein Compound 1 is present in the pharmaceutical composition in an amount of from about 10 mg to about 200 mg. 
     
     
         48 . A tablet pharmaceutical composition comprising Compound I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, and a filler, a binder, a disintegrant, and a lubricant, wherein the tablet pharmaceutical composition is produced by a process comprising:
 1) Delumping unmilled Compound I; 
 2) Mixing Delumped Compound I with the filler to form a mixture; 
 3) Combining the mixture with the binder to form a binder solution; 
 4) Wet high shear granulating the binder solution to produce wet screened granules; 
 5) Fluid bed drying the wet screened granules to produce dried granules; 
 6) Blending the dried granules with the disintegrant to produce an extragranular blend; and 
 7) Lubricating the extragranular blend with a lubricant to produce a final blend. 
 
     
     
         49 . The tablet pharmaceutical composition of  claim 48 , wherein Compound I is present in the pharmaceutical composition in an amount of from about 10 mg to about 200 mg 
     
     
         50 . The tablet pharmaceutical composition of  claim 49 , wherein the filler comprises lactose, the binder comprises hydroxypropyl cellulose, the disintegrant comprises croscarmellose sodium, and the lubricant comprises magnesium stearate. 
     
     
         51 . The tablet pharmaceutical composition of  claim 50 , wherein the process further comprises:
 Tablet compressing the final blend to form an uncoated core tablet; and   Film coating the uncoated core tablet.