Malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer
Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclo-propane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.
1 - 15 . (canceled)
16 . A solid dosage form of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide, malate salt for oral administration, wherein said salt is admixed with pharmaceutically acceptable excipients comprising a filler, a binder, a disintegrating agent, and a lubricant.
17 . The solid dosage form of claim 16 , wherein the malate salt is the (DL)-malate salt.
18 . The solid dosage form of claim 17 , wherein the malate salt is the (L)-malate salt.
19 . The solid dosage form of claim 18 , wherein the (L)-malate salt is in an amount of from about 5% to about 75% by weight of the solid dosage form.
20 . The solid dosage form of claim 19 , wherein the filler is lactose.
21 . The solid dosage form of claim 20 , wherein the binder is a cellulose derivative.
22 . The solid dosage form of claim 21 , wherein the disintegrant is croscarmellose sodium.
23 . The solid dosage form of claim 22 , wherein the lubricant is magnesium stearate.
24 . The solid dosage form of claim 23 , wherein said salt is crystalline.
25 . The solid dosage form of claim 16 , wherein said salt is amorphous.
26 . The solid dosage form of claim 24 , which is a tablet.
27 . A solid dosage form of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide, malate salt for oral administration, wherein said salt is crystalline, and wherein said salt is admixed with pharmaceutically acceptable excipients comprising a filler, a binder, a disintegrating agent, and a lubricant.
28 . The solid dosage form of claim 27 , wherein the malate salt is the (DL)-malate salt.
29 . The solid dosage form of claim 28 , wherein the malate salt is the (L)-malate salt.
30 . The solid dosage form of claim 29 , wherein the (L)-malate salt is in an amount of from about 5% to about 75% by weight of the solid dosage form.
31 . The solid dosage form of claim 30 , wherein the filler is lactose.
32 . The solid dosage form of claim 31 , wherein the binder is a cellulose derivative.
33 . The solid dosage form of claim 32 , wherein the disintegrant is croscarmellose sodium.
34 . The solid dosage form of claim 33 , wherein the lubricant is magnesium stearate.
35 . The solid dosage form of claim 34 , which is a tablet.