High drug load tablet

Abstract

The present invention pertains to a high drug load tablet comprising as active ingredient Compound I of formula or a pharmaceutically acceptable salt thereof in an amount from about 30% to 80% in weight of the active moiety based on the total weight of the tablet.

1 . A small tablet comprising a pharmacologically effective amount of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide of formula (1) in the form of a monomesylate salt as the sole active drug: 
       
         
           
           
               
               
           
         
         in an amount from 30% to 80% by weight of the active moiety based on the total weight of the small tablet; and at least one disintegrant, wherein the at least one disintegrant is cross-linked polyvinlypyrrolidinone, wherein the small tablet is either 
         a small ovaloid tablet that is 10 to 20 mm in length, 5 to 10 mm in width and 4 to 8 mm in thickness or 
         a small round tablet that is 5 to 15 mm in diameter and 2 to 5 mm in thickness 
         and wherein the pharmacologically effective amount of the sole active moiety 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide is from 50 mg to 600 mg. 
       
     
     
         2 . A small tablet according to  claim 1 , wherein the sole active moiety is present in an amount from 50% to 80% of the active moiety by weight based on the weight of the small tablet. 
     
     
         3 . A small tablet according to  claim 1  wherein the 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide monomesylate salt is in the alpha crystalline form thereof. 
     
     
         4 . A small tablet according to  claim 1  wherein 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide monomesylate is in the beta crystalline form thereof. 
     
     
         5 . A small tablet according to  claim 1  further comprising at least one binder. 
     
     
         6 . The small tablet according to  claim 1  further comprising:
 at least one binder in an amount of 1% to 25% in weight based on the total weight of the small tablet; 
 at least one glidant in an amount of 0.5% to 3% in weight based on the total weight of the small tablet; and wherein the small ovaloid tablet comprises 400 mg of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide and the small round tablet comprises 100 mg of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide. 
 
     
     
         7 . A small tablet according to  claim 6  wherein the binder is selected from: microcrystalline cellulose, hydroxypropylcellulose and mixtures thereof. 
     
     
         8 . A small tablet according to  claim 6  wherein the glidant is selected from: colloidal silicon dioxide, colloidal anhydrous silica and mixtures thereof. 
     
     
         9 . A small tablet according to  claim 6  wherein the lubricant is magnesium stearate. 
     
     
         10 . A process for the preparation of a small tablet according to  claim 5 , which process comprises
 (a) forming an inner phase comprising
 (i) mixing the sole active drug 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide of formula (1)) in the form of monomesylate salt and at least one binder, wherein active moiety of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide is 30 to 80% on the total weight of the small tablet; 
 (ii) wet-granulating; 
   (b) forming an outer phase comprising
 (iii) mixing with at least one disintegrant, wherein the at least one disintegrant is cross-linked polyvinlypyrrolidinone; 
   to form a mixture; and   (c) forming a tablet by
 (iv) compressing the mixture obtained in step (iii). 
   
     
     
         11 . The process of  claim 10  further comprising coating the tablet formed in (iv) at a low temperature of between 30 and 40 degrees C.