Novel pharmaceutical composition

Abstract

The invention pertains to dispersible tablets comprising as active ingredient N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide, methanesulfonate salt, processes for preparing the same, and processes for using the same.

What is claimed is: 
     
         1 . A dispersible tablet comprising (a) Compound A, (b) hypromellose, and (c) at least one pharmaceutically acceptable excipient suitable for the preparation of tablets, wherein the Compound A is present in an amount of from 5% to 40% in weight based on the total weight of the tablet. 
     
     
         2 . The dispersible tablet according to  claim 1 , wherein hypromellose is present in about 1% to about 13% in weight based on the total weight of the tablet. 
     
     
         3 . The dispersible tablet according to  claim 2 , wherein hypromellose is present in about 5% to about 10% in weight based on the total weight of the tablet. 
     
     
         4 . The dispersible tablet according to  claim 3 , wherein hypromellose has nominal viscosity between 4 mPa s to 6 mPa s, preferably 5 mPa s, as measured at 20° C. for a 2% by weight in water, and a 28% to 30% methoxyl substitution. 
     
     
         5 . The dispersible tablet according to  claim 3 , wherein hypromellose has viscosity of between 80 mPa s to 120 mPa s, preferably 100 mPa s, as measured at 20° C. for a 2% by weight in water, and 19% to 24% methoxyl substitution. 
     
     
         6 . The dispersible tablet according to  claim 1 , wherein the tablet has a disintegration time, measured according to the disintegration test of the European Pharmacopoeia 2.9.1,disintegration time of tablets in water at 15° C. to 25° C., of 3 minutes or less. 
     
     
         7 . The dispersible tablet according to  claim 1 , wherein the tablet has a hardness of mean value, measured according to the resistance to crushing of tablets test of the European Pharmacopoeia 2.9.8, of not more than 55N. 
     
     
         8 . The dispersible tablet according to  claim 1  wherein the pharmaceutically acceptable excipients comprise:
 (i) at least one filler in a total amount of about 35% to 70% in weight based on the total weight of the tablet, 
 (ii) at least one disintegrant in a total amount of about 2.5% to 13% in weight based on the total weight of the tablet, 
 (iii) at least one lubricant in a total amount of about 0.1% to 2% in weight based on the total weight of the tablet, and 
 (iv) at least one glidant in a total amount of about 0.1% to 2.5% in weight based on the total weight of the tablet. 
 
     
     
         9 . The dispersible tablet according to  claim 8 , wherein the fillers are mannitol and microcrystalline cellulose. 
     
     
         10 . The dispersible tablet according to  claim 9 , wherein mannitol and microcrystalline cellulose is present in a weight by weight ratio of about 2.5:1 to 2:1. 
     
     
         11 . The dispersible tablet according to  claim 8 - 10 , wherein the disintegrant is crospovidone. 
     
     
         12 . The dispersible tablet according to  claim 11 , wherein crospovidone is present in about 5% to 10% in weight based on the total weight of the tablet. 
     
     
         13 . The dispersible tablet according to any one of  claims 8 - 12 , wherein the glidant is colloidal silicon dioxide. 
     
     
         14 . The dispersible tablet according to any one of  claims 8 - 13 , wherein the lubricant is magnesium stearate. 
     
     
         15 . A method of administering the dispersible tablet according to  claim 1  to a patient in need of said composition which comprises (i) combining the composition with an aqueous medium (ii) allowing the composition to disperse in the aqueous medium to form a dispersion and (iii) ingesting the dispersion. 
     
     
         16 . The dispersible tablet according to  claim 1  for use in the treatment of cancer. 
     
     
         17 . The dispersible tablet according to  claim 16  for use in treatment of cancer, wherein the cancer is a BRAF-mutation positive solid tumor. 
     
     
         18 . A process for the preparation of the dispersible tablet according to  claims 1 - 14 , which comprises
 (i) mixing the Compound A and at least one pharmaceutically acceptable excipient;   (ii) granulating the mixture obtained in (i);   (iii) mixing the granulates obtained in (ii) with at least one pharmaceutically acceptable excipient to form a mixture; and   (iv) compressing the mixture obtained in step (iii) to form a tablet.   
     
     
         19 . A process according to  claim 18 , wherein the granulation step (ii) is dry granulation. 
     
     
         20 . A process according to  claim 19 , wherein dry granulation is with roller compaction with a granulating mill.