| abstract |
The present invention relates to impurities having genotoxic effects (eg (C 1 -C 5 ) alkanyl methanesulfonate) and residual solvents known as potential precursors thereof (eg (C 1 -C 5 ) alkanols or lower Crystalline anhydrous polymorphic form of the compound (S) -2- [4- (2-fluorobenzyloxy) benzylamino] propane, which is structurally determined as Form A substantially free of esters with alkanoic acids)) It relates to a novel process for the preparation and / or purification of amide salts in high yield and very high enantiomer and chemical purity. The method (I) preparing and / or crystallizing the salt from water, acetone, an aliphatic ketone of 4 to 5 carbon atoms or a mixture thereof with water; or (ii) converting the solid salt into (a) water, (b) Slurry with water and acetone or a mixture of aliphatic ketones of 4-5 carbon atoms, (c) acetone, an aliphatic ketone of 4-5 carbon atoms or mixtures thereof; or (iii) solid salt When the resulting product is wholly or partially composed of crystalline hemihydrate pseudopolymorphic Form H crystals, this product is removed by removing water. Product to anhydrous Form A crystals; Including that. Ralfinamide methanesulfonate, or its crystalline hemihydrate pseudopolymorph Form H of its R-enantiomer, is a crystalline anhydrous polyhydride that does not contain impurities and / or residual solvents known as precursors thereof that have the genotoxic effects described above. It shows a physicochemical profile that is a useful intermediate for obtaining Form A and provides significant advantages in the design and development of solid dosage forms, particularly modified release formulations. |