Pharmaceutical composition for the treatment of cancer

Abstract

The present invention pertains to a pharmaceutical composition comprising the compound of the formula (I) in a high concentration and at least one pharmaceutically acceptable excipient, the use of the composition for the treatment of hyper-proliforative diseases, such as cancer, either as a sole agent, or in combination with other anti-cancer therapies, and the process for preparing of said composition.

1 . A pharmaceutical composition comprising 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-phenoxy}-pyridine-2-carboxylic acid methyl amide, its solvates, hydrates, pharmaceutically acceptable salts, or a combination thereof as active agent in a portion of at least 40% by weight of the composition and at least one pharmaceutically acceptable excipient. 
     
     
         2 . The pharmaceutical composition of  claim 1  comprising the active agent in a portion of at least 55% by weight of the composition. 
     
     
         3 . The pharmaceutical composition of any of  claim 2  wherein the active agent is the p-toluenesulfonic acid salt of 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-phenoxy}-pyridine-2-carboxylic acid methyl amide. 
     
     
         4 . The pharmaceutical composition of  claim 3  comprising the active agent in a portion of at least 55% by weight of the composition. 
     
     
         5 . The pharmaceutical composition of  claim 3  comprising the active agent in a portion of at least 75% by weight of the composition. 
     
     
         6 . The pharmaceutical composition of  claim 5  wherein the />-toluenesulfonic acid salt of 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-phenoxy}-pyridine-2-carboxylic acid methyl amide exists for at least 80% in the stable polymorph I. 
     
     
         7 . The pharmaceutical composition of  claim 1  comprising the active agent in a portion of at least 40%, a filler in a portion of from 0 to 60%, a disintegrant in a portion of from 0 to 15%, a binder in a portion of from 0 to 15%, a lubricant in a portion of from 0 to 2% and a surfactant in a portion of from 0 to 5% by weight of the composition. 
     
     
         8 . The pharmaceutical composition of  claim 7  comprising the ̂-toluenesulfonic acid salt of 4{4-[3-(4-chloro-3-trifiuoromethylphenyl)-ureido]-phenoxy}-pyridine-2-carboxylic acid methyl amide in a portion of at least 55%, microcrystalline cellulose as a filler in a portion of from 0 to 60%, croscarmellose sodium as a disintegrant in a portion of from 0 to 15%, hypromellose as a binder in a portion of from 0 to 15%, magnesium stearate as a lubricant in a portion of from 0 to 2% and sodium lauryl sulfate as a surfactant in a portion of from 0 to 5% by weight of the composition. 
     
     
         9 . The pharmaceutical composition of  claim 8  for oral administration. 
     
     
         10 . The pharmaceutical composition of  claim 9  is solid oral dosage form. 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . The pharmaceutical composition of  claim 1  wherein the active agent is micronized. 
     
     
         14 . The pharmaceutical composition of  claim 13  comprising water in an amount of less than or equal to 6% by weight of the composition. 
     
     
         15 . The pharmaceutical composition of  claim 14  in combination with one or more cytotoxic agents, signal transduction inhibitors, or with other anti-cancer agents or therapies, as well as with admixtures and combinations thereof. 
     
     
         16 . A process for manufacturing a pharmaceutical composition of  claim 14  wherein the active agent is blended with at least one pharmaceutically acceptable excipient. 
     
     
         17 . The process of  claim 16  wherein:
 a) the active agent and at least one pharmaceutically acceptable excipient are wet granulated, 
 b) the granulate is blended with the lubricant and optionally with one or more further pharmaceutically acceptable excipient, 
 c) the post blend granulate is subdivided into single units, 
 d) and the product of step c) is optionally coated with one or more further pharmaceutically acceptable excipients. 
 
     
     
         18 . The process of  claim 17  wherein the product of step c) is a tablet, capsule or sachet. 
     
     
         19 . The process of  claim 18  wherein the product of step c) is coated with one or more further pharmaceutically acceptable excipients 
     
     
         20 . The process of  claim 16  wherein the active agent and at least one pharmaceutically acceptable excipient are blended without granulation and directly compressed to tablets or filled into capsules or sachets. 
     
     
         21 . The process of  claim 16  wherein the active agent anlone or the active agent and at least one pharmaceutically acceptable excipient are treated by a dry granulation method and then compressed to tablets or filled into capsules or sachets. 
     
     
         22 . Method for using the pharmaceutical composition of  claim 1  to treat mammalian hyper-proliferative disorders, including cancer.