Solid dispersions of a erb2 (her2) inhibitor

Abstract

A solid dispersion of N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and processes for preparing the solid dispersion are provided herein. Also, a pharmaceutical composition comprising a solid dispersion of N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and uses thereof are provided herein.

What is claimed is: 
     
         1 . A solid dispersion comprising N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and a dispersion polymer, wherein the dispersion polymer is a methacrylate copolymer or a cellulosic polymer or cellulosic copolymer. 
     
     
         2 . The dispersion of  claim 1 , wherein the N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is amorphous. 
     
     
         3 . The dispersion of  claim 1 , wherein the N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is present in an amount of from about 0.1% to about 60% by weight relative to the dispersion polymer. 
     
     
         4 . The dispersion of  claim 1 , wherein the dispersion polymer is Eudragit L100. 
     
     
         5 . The dispersion of  claim 1 , wherein the dispersion polymer is neutral or basic. 
     
     
         6 . The dispersion of  claim 1 , wherein at least 95% the N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is in amorphous form. 
     
     
         7 . A pharmaceutical composition comprising the solid dispersion of  claim 1  and one or more pharmaceutically acceptable excipients. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein a disintegrant is a pharmaceutically acceptable excipient of the composition. 
     
     
         9 . The pharmaceutical composition of  claim 7 , wherein the solid dispersion ranges from about 25% to about 60% by weight. 
     
     
         10 . The pharmaceutical composition of  claim 8 , wherein the disintegrant ranges from about 0.1 to about 20 weight %. 
     
     
         11 . The pharmaceutical composition of  claim 8 , wherein the disintegrant is Crospovidone. 
     
     
         12 . The pharmaceutical composition of  claim 8 , wherein the disintegrant is sodium bicarbonate. 
     
     
         13 . The pharmaceutical composition of  claim 8 , wherein the disintegrant is Polyplasdone. 
     
     
         14 . A method for the treatment of ErbB2 positive non-small cell lung (NSCLC) cancer comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 7 . 
     
     
         15 . The method of  claim 14 , wherein the pharmaceutical composition is administered orally. 
     
     
         16 . The method of  claim 14 , wherein the pharmaceutical composition is administered in the form of a tablet. 
     
     
         17 . A method of treating or preventing a disease or disorder modulated by ErbB2, comprising administering to a subject in need of such treatment an effective amount of the pharmaceutical composition of  claim 7 .