CRYSTALLINE MODIFICATIONS OF METHYL (3Z)-3-{(4-{METHYL(4-METHYLPIPERAZIN-1-YL)ACETYLAMINO}PHENYL)AMINO(PHENYL)METHYLIDENE}-2-OXO-2,3-DIHYDRO-1H-INDOLE-6-CARBOXYLATE SALTS AND METHODS OF PREPARATION THEREOF

摘要

The present solution relates to crystalline modifications of methyl (3Z)-3-{[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)amino](phenyl)methylidene}-2-oxo-2,3-dihydro-1H-indole-6-carboxylate salts of Formula I, wherein HX represents at least one acid component, preferably methanesulfonic acid, p-toluenesulphonic acid, L-tartaric acid, maleic acid, acetic acid and phosphoric acid. Another solution also relates to the processes for the preparation thereof as well as said use thereof in pharmaceutically acceptable compositions. Use of said crystalline forms of intedanib and manufactured salts in the preparation of methyl (3Z)-3-{[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)amino](phenyl)methylidene}-2-oxo-2,3-dihydro-1H-indole-6-carboxylate in the form of any pharmaceutically acceptable salt thereof is also object of this invention.;