Process for preparating ivabradine hydrochloride form IV and methods of treatment of disease using ivabradine hydrochloride form IV
AssigneeUrquima, S.A.
InventorsRafael Prohens Lopez, Cristina Puigjaner Vallet, Rafael Barbas Canero, Jose Luis Del Rio Pericacho, Josep Marti Via
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Abstract
Ivabradine hydrochloride Form IV, its pharmaceutical composition, process for its preparation, and its use as therapeutically active ingredient and pharmaceutical compositions containing Ivabradine hydrochloride Form IV.
Claims17
A process for preparing ivabradine hydrochloride Form IV with a powder X-ray diffraction comprising the following degrees 2 theta (±0.2) peaks:
- 8.74, 15.55, 17.17, 19.89, and 24.29, wherein the X-ray diffraction is measured using a CuKα radiation, the process comprising:
- a) slurrying ivabradine hydrochloride in a solvent system comprising toluene, ethanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl acetate, isopropyl acetate and mixtures thereof;
- wherein said step of slurrying ivabradine occurs at a temperature of lower than 60° C. and the reaction time for said step of slurrying ivabradine is less than 48 h;
- and
- b) isolating the ivabradine hydrochloride Form IV.
A process for preparing ivabradine hydrochloride Form IV with a powder X-ray diffraction comprising the following degrees 2 theta (±0.2) peaks:
- 8.74, 15.55, 17.17, 19.89, and 24.29, wherein the X-ray diffraction is measured using a CuKα radiation, the process comprising:
- i) stirring a solution of ivabradine free base in a solvent system, wherein the solvent system comprises toluene, ethanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl acetate, isopropyl acetate and mixtures thereof;
- ii) maintaining the solution at a temperature lower than 60° C.;
- iii) adding a solution of hydrochloric acid to obtain ivabradine hydrochloride;
- iv) seeding with the ivabradine hydrochloride Form IV;
- v) isolating the ivabradine hydrochloride Form IV and
- vi) drying the isolated ivabradine hydrochloride Form IV under vacuum pressure and at a temperature between 45° C. and 70° C.
A method for the treatment of chronic stable angina pectoris in an adult with normal sinus rhythm, the method comprising administering an effective amount of ivabradine hydrochloride Form IV with a powder X-ray diffraction comprising the following degrees 2 theta (±0.2) peaks:
- 8.74, 15.55, 17.17, 19.89, and 24.29, wherein the X-ray diffraction is measured using a CuKα radiation.
A method for the treatment of chronic stable angina pectoris in coronary artery disease adults with normal sinus rhythm comprising administering to said adult an effective amount of ivabradine hydrochloride Form IV with a powder X-ray diffraction comprising the following degrees 2 theta (±0.2) peaks:
- 8.74, 15.55, 17.17, 19.89, and 24.29, wherein the X-ray diffraction is measured using a CuKα radiation.
Dependencies are inferred from the claim text.