US2021379050A1PendingUtilityA1

C-Met Modulator Pharmaceutical Compositions

80
Assignee: EXELIXIS INCPriority: Jul 16, 2010Filed: Aug 23, 2021Published: Dec 9, 2021
Est. expiryJul 16, 2030(~4 yrs left)· nominal 20-yr term from priority
A61K 9/2031A61K 9/2866A61K 9/2018A61K 9/28A61K 31/47A61K 9/2013A61K 31/33A61K 9/2054A61K 31/395A61K 9/2009A61K 9/2095A61K 31/435A61K 9/2833A61K 45/06A61K 31/00A61K 9/2004A61K 9/2893A61K 9/00
80
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

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

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A pharmaceutical composition comprising: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Ingredient 
                   (% w/w) 
                 
                     
                     
                 
                     
                 
                 
                 
                 
               
                     
                   Compound I 
                   31.68 
                 
                     
                   Microcrystalline Cellulose 
                   38.85 
                 
                     
                   Lactose anhydrous 
                   19.42 
                 
                     
                   Hydroxypropyl Cellulose 
                   3.00 
                 
                     
                   Croscarmellose Sodium 
                   3.00 
                 
                     
                   Total Intro-granular 
                   95.95 
                 
                     
                   Silicon dioxide, Colloidal 
                   0.30 
                 
                     
                   Croscarmellose Sodium 
                   3.00 
                 
                     
                   Magnesium Stearate 
                   0.75 
                 
                     
                   Total 
                   100.00 
                 
                     
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . A pharmaceutical composition comprising: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Ingredient 
                   (% w/w) 
                 
                     
                     
                 
                     
                   Compound I 
                   25.0-33.3 
                 
                     
                   Microcrystalline Cellulose 
                   q.s 
                 
                     
                   Hydroxypropyl Cellulose 
                   3 
                 
                     
                   Poloxamer 
                     0-3   
                 
                     
                   Croscarmellose Sodium 
                   6.0 
                 
                     
                   Colloidal Silicon Dioxide 
                   0.5 
                 
                     
                   Magnesium Stearate 
                    0.5-1.0  
                 
                     
                   Total 
                   100 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         3 . A pharmaceutical composition comprising: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                   Theoretical 
                 
                     
                     
                   Quantity (mg/unit 
                 
                     
                   Ingredient 
                   dose) 
                 
                     
                     
                 
                     
                 
                 
                 
                 
               
                     
                   Compound I 
                   100.0 
                 
                     
                   Microcrystalline Cellulose 
                   155.4 
                 
                     
                   PH-102 
                     
                 
                     
                   Lactose Anhydrous 60M 
                   77.7 
                 
                     
                   Hydroxypropyl Cellulose, 
                   12.0 
                 
                     
                   EXF 
                     
                 
                     
                   Croscarmellose Sodium 
                   24 
                 
                     
                   Colloidal Silicon Dioxide 
                   1.2 
                 
                     
                   Magnesium Stearate (Non- 
                   3.0 
                 
                     
                   Bovine) 
                     
                 
                     
                   Opadry Yellow 
                   16.0 
                 
                     
                   Total 
                   416 
                 
                     
                     
                 
             
                
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         4 . A pharmaceutical composition comprising:
 30-32 percent by weight of Compound I in at least one of the forms disclosed herein;   50-70 percent by weight of a filler;   2-4 percent by weight of a binder;   4-8 percent by weight of a disintegrant; and   0.2-0.6 percent by weight of a glidant; and 0.5-1 percent by weight of a lubricant.   
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein Compound I is the free base. 
     
     
         6 . The pharmaceutical composition of  claim 4 , wherein Compound I is a pharmaceutically acceptable salt. 
     
     
         7 . The pharmaceutical composition of  claim 4 , wherein Compound I is the malate salt. 
     
     
         8 . The pharmaceutical composition of  claim 4 , wherein Compound I is the L-, D-, or D,L malate salt, or mixtures thereof. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the Compound I malate salt is in amorphous, substantially amorphous, crystalline, or substantially crystalline form. 
     
     
         10 . The pharmaceutical composition of  claim 8 , wherein the Compound I malate salt is in crystalline or amorphous form. 
     
     
         11 . The pharmaceutical composition of  claim 4 , wherein the filler is selected from the group consisting of sodium starch glycolate, corn starch, talc, sucrose, dextrose, glucose, lactose, xylitol, fructose, sorbitol, calcium phosphate, calcium sulfate, calcium carbonate, and microcrystalline cellulose, or mixtures thereof. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the filler is comprises lactose and microcrystalline cellulose. 
     
     
         13 . The pharmaceutical composition of  claim 2 , wherein the binder is selected from the group consisting of 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, and zein, or mixtures thereof. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the binder is hydroxypropyl cellulose. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the disintegrant is selected from the group consisting of 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, and starch, or mixtures thereof. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the disintegrant is croscarmellose sodium. 
     
     
         17 . The pharmaceutical composition of  claim 4 , wherein the glidant is colloidal silicon dioxide. 
     
     
         18 . The pharmaceutical composition of  claim 4 , wherein the lubricant is selected from the group consisting of magnesium stearate, Lubritab®, stearic acid, and talc, or mixtures thereof. 
     
     
         19 . The pharmaceutical composition of  claim 4 , wherein the lubricant is magnesium stearate. 
     
     
         20 . The pharmaceutical composition of  claim 4 , further comprising a film coating. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein the film coating comprises Opadry Yellow. 
     
     
         22 . The pharmaceutical formulation of  claims 1 - 4  which is a tablet formulation. 
     
     
         23 . A pharmaceutical composition comprising: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                     
                   Weight/Weight 
                 
                     
                   Component 
                   Percent 
                 
                     
                     
                 
                     
                   Compound I 
                    25-29  
                 
                     
                   Microcrystalline Cellulose 
                   q.s. 
                 
                     
                   Lactose Anhydrous 
                    40-44  
                 
                     
                   Hydroxypropyl Cellulose 
                     2-4   
                 
                     
                   Croscarrnellose Sodium 
                     2-8   
                 
                     
                   Colloidal Silicon Dioxide 
                   0.1-0.4 
                 
                     
                   Magnesium Stearate 
                   0.7-0.9 
                 
                     
                   Total 
                   100 
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         24 . The pharmaceutical composition of  claim 22 , further comprising a film coating. 
     
     
         25 . The pharmaceutical composition of  claim 24 , wherein the film coating comprises Opadry yellow. 
     
     
         26 . A method for treating cancer, comprising administering to a patient in need of such treatment a pharmaceutical composition of  claim 1 - 4  or  23 , alone or in combination with another therapeutic agent. 
     
     
         27 . The method of  claim 26 , wherein the cancer is selected from the group consisting of pancreatic cancer, kidney cancer, liver cancer, prostate cancer, gastric cancer, gastroesophageal cancer, melanoma, lung cancer, breast cancer, thyroid cancer, and astrocytic tumors. 
     
     
         28 . The method of  claim 27 , wherein the cancer is pancreatic cancer, hepatocellular carcinoma (HCC), renal cell carcinoma, castration-resistant prostate cancer (CRPC), gastric or gastroesophageal junction cancer, melanoma, small cell lung cancer (SCLC), ovarian cancer, primary peritoneal or fallopian tube carcinoma, estrogen receptor positive breast cancer, estrogen receptor/progesterone receptor/HER2-negative (triple-negative) breast cancer, inflammatory (regardless of receptor status) breast cancer, non-small cell lung cancer (NSCLC), or medullary thyroid cancer. 
     
     
         29 . A process for manufacturing a pharmaceutical composition comprising Compound I, comprising the steps of:
 a. Delumping unmilled Compound I;   b. Premixing the delumped Compound I with microcrystalline cellulose, anhydrous lactose, and croscarmellose sodium to form a binder solution;   c. Wet high shear granulation of the binder solution to produce wet granules;   d. Wet screening of the wet granules to produce wet screened granules;   e. Fluid bed drying of the wet screened granules to produce dried granules;   f. Dry milling of the dried granules to produce dried milled granules;   g. Blending the dried milled granules with colloidal silicon and croscarmellose to produce an extragranular Wend;   h. Lubricant blending of the extragranular blend and magnesium stearate to produce a final blend; and   i. Tablet compression of the final blend to form an uncoated core tablet.   
     
     
         30 . The process of  claim 29 , further comprising the step of film coating of the uncoated core tablet.

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.