Methods for the preparation of Ivabradine sulfate and form I crystal thereof

A method for preparing a form I crystal of Ivabradine sulfate comprising:

• heating a mixture of arbitrary or amorphous forms of Ivabradine sulfate and one or more moderate polar organic solvents to dissolve the arbitrary or amorphous forms of Ivabradine sulfate
• stirring and/or laying and cooling the mixture to crystallization;
• and
• filtering and washing, and then drying at a drying temperature in a range of 40˜80° C. in vacuum;
• wherein the crystal being characterized in that using CuKα radiation to obtain X-ray diffraction patterns represented by 2θ angles and interplanar crystal spacing (d value), the obtained X-ray diffraction patterns comprise characteristic peaks at 4.76 (18.55), 14.18 (6.24), 16.14 (5.49), 16.94 (5.23), 18.1 (4.88), 19.12 (4.64), 20.04 (4.43), 20.42 (4.35), 21.70 (4.09), 22.56 (3.94), and 23.80 (3.74).

A method for preparing a form I crystal of Ivabradine sulfate comprising:

• dissolving one or more of arbitrary and amorphous forms of Ivabradine sulfate in a solvent comprising methanol;
• concentrating the solvent to obtain an amorphous oil;
• heating the amorphous to dissolve the amorphous oil in a second solvent composition comprising one or more polar organic solvents;
• stirring and/or laying and cooling the second solvent mixture to crystallization;
• and
• filtering and washing, and then drying at a drying temperature in a range of 40˜80° C. in vacuum;
• wherein the crystal being characterized in that using CuKα radiation to obtain X-ray diffraction patterns represented by 2θ angles and interplanar crystal spacing (d value), the obtained X-ray diffraction patterns comprise characteristic peaks at 4.76 (18.55), 14.18 (6.24), 16.14 (5.49), 16.94 (5.23), 18.1 (4.88), 19.12 (4.64), 20.04 (4.43), 20.42 (4.35), 21.70 (4.09), 22.56 (3.94), and 23.80 (3.74).

A method for preparing a form I crystal of Ivabradine sulfate comprising:

• dissolving Ivabradine and sulfuric acid at a mole ratio of approximately 1:1 in a solvent composition comprising a moderate polar organic solvent to form a mixture;
• mixing and stirring and/or laying the mixture to crystallization;
• and
• filtering and washing, and then drying at a drying temperature in a range of approximately 40˜80° C. in vacuum;
• wherein the crystal being characterized in that using CuKα radiation to obtain X-ray diffraction patterns represented by 2θ angles and interplanar crystal spacing (d value), the obtained X-ray diffraction patterns comprise characteristic peaks at 4.76 (18.55), 14.18 (6.24), 16.14 (5.49), 16.94 (5.23), 18.1 (4.88), 19.12 (4.64), 20.04 (4.43), 20.42 (4.35), 21.70 (4.09), 22.56 (3.94), and 23.80 (3.74).