Gamma-crystalline form of ivabradine hydrochloride, a process for its preparation and pharmaceutical compositions containing it

• US 20060194963A1
• Filed: 02/22/2006
• Published: 08/31/2006
• Est. Priority Date: 02/28/2005
• Status: Active Grant

• Current Assignee: Les Laboratoires Servier (Servier Sas)
• Original Assignee: Les Laboratoires Servier (Servier Sas)
• Inventors: Damien, Gerard, Auguste, Marie-Noelle, Horvath, Stephane
• Granted Patent: US 7,361,650 B2
• Time in Patent Office: Days
• US Class Current: 540/523
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 223/16 Benzazepines; Hydrogenated benzazepines
• CPC Class Codes: H04L 51/212 using filtering or selective blocking
• CPC Class Codes: H04L 51/214 using selective forwarding

Abstract

A γ-Crystalline form of ivabradine hydrochloride of formula (I): characterised by its powder X-ray diffraction data. Medicinal products containing the same which are useful as bradycardics.

Claims

1. A γ

-Crystalline form of ivabradine hydrochloride of formula (I);

2. A process for the preparation of the γ

-crystalline form of ivabradine hydrochloride of claim 1, wherein a mixture of ivabradine hydrochloride and 2-ethoxyethanol, a mixture of ivabradine hydrochloride, 2-ethoxyethanol and water, or a mixture of ivabradine hydrochloride, ethanol and water is heated until dissolution is complete and is then cooled until crystallisation is complete, and the product thus obtained is collected by filtration.

3. The process of claim 2, wherein the solution of ivabradine hydrochloride is seeded during the cooling step.

4. A pharmaceutical composition comprising as active ingredient the γ

-crystalline form of ivabradine hydrochloride of claim 1, in combination with one or more pharmaceutically acceptable, inert, non-toxic carriers.

5. A method for treating or preventing a condition requiring a bradycardic, such method comprising administering to a living animal body, including a human, a therapeutically effective amount of a γ

-crystalline form of ivabradine hydrochloride of claim 1.

6. A method for treating or preventing clinical situations of myocardial ischaemia and/or a condition involving rhythm disturbances, such method comprising administering to a living animal body, including a human, a therapeutically effective amount of a γ

-crystalline form of ivabradine hydrochloride of claim 1.

7. The method of claim 6, wherein the clinical situation of myocardial ischaemia is selected from angina pectioris and myocardial infarct and associated rhythm disturbances.

8. The method of claim 6, wherein the condition involving rhythm disturbances is selected from supra ventricular rhythm disturbances and heart failure.