Field of the Invention
The present invention relates to novel polymorph-N of Ivabradine hydrochloride and process for its preparation.
Back ground of the Invention
The chemical structure of Ivabradine hydrochloride, 3-{3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl] methyl}(methyl)amino]-propyl}-7,8-dimethoxy-l ,3,4,5-tetrahydro-2H-3-benzazepin-2-one hydrochloride as shown in formula (I):Ivabradine is a novel medication used for the symptomatic management of stable angina pectoris. It is classified as a cardiotonic agent.
The preparation and therapeutic use of Ivabradine and its pharmaceutically acceptable salts are first described in EP 0534859 and US 5,296,482.
Ivabradine Hydrochloride exists in several polymorphic forms i.e., I, II, IV, X, Z, K, C, S, a, P, y, 5, yd, Pd and 5d. These forms are disclosed in US 8,541,405, CN 103183639, US 9,139,531, WO 2011/098582, US 9,120,755, CN 103012269, CN 103864690, US 7,176,197, US 7,361,649, US 7,361,650, US 7,358,240, US 7,361,651, US 7,361,652 and US 7,384,932.
The USFDA recommends that applicants for drug product registration investigate whether the drug substance can exist in polymorphic forms; this is discussed in the agency's draft guidance for industry entitled "ANDAs: Pharmaceutical Solid Polymorphism," which was published in December 2004. Therefore, it is always desirable to identify as many polymorphic forms as possible, in connection with the product development.
OBJECTS OF THE INVENTION
The primary object of the invention is to provide a novel polymorph of Ivabradine hydrochloride.
Another object of the invention is to provide a process for the preparation of novel polymorph of Ivabradine hydrochloride.

Summary of the Invention
In one aspect, the present invention relates to novel polymorph-N of Ivabradine hydrochloride.
In another aspect, there is provided novel polymorph-N of Ivabradine hydrochloride characterized h X-ray powder diffraction spectrum having peaks at 8.60,9.08, 11.65, 14.60, 15.29, 16.73,17.20,18.2' 18.89, 19.64, 20.31, 21.02, 21.58, 22.26, 22.67, 23.39, 23.97, 24.55, 26.37, 27.07, 27.69, 29.31, 30.2: 31.18, 32.44, 33.70, 35.20, 35.57, 39.12, 41.56, 42.32, 43.87, 45.77 ° 20.
In further aspect, there is also provide a process for the preparation of novel polymorph-N of Ivabradir hydrochloride comprising the steps of:
a) suspend Ivabradine hydrochloride in n-butyl acetate and n-hexane;
b) heat the above suspension to 60-65 °C;
c) add methanol to obtain the clear solution;
d) slowly cool the above solution to 25-30 °C;
e) further cooled the above solution to 15- 20 °C and maintained for 2 hours under stirring;
f) filter the crystals and wash with chilled n-butyl acetate;
g) dry the crystals under vacuum.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure -1 represents X-ray Diffraction spectrum of polymorph-N of Ivabradine hydrochloride. Figure -2 is a table showing the X-ray powder diffraction peaks and calculated d-values for th polymorph-N of Ivabradine hydrochloride. Figure -3 represents DSC of the polymorph-N of Ivabradine hydrochloride.
DETAILED DESCRIPTION OF THE INVENTION
Ivabradine hydrochloride of formula (I) can be prepared by any conventional methods known in th prior art.
The process for the preparation of novel polymorph-N of Ivabradine hydrochloride comprising the step of:
a) suspend Ivabradine hydrochloride in n-butyl acetate and n-hexane;
b) heat the above suspension to 60-65 °C;
c) add methanol to obtain the clear solution;
d) slowly cool the above solution to 25-30 °C;
e) further cooled the above solution to 15- 20 °C and maintained for 2 hours under stirring;
f) filter the crystals and wash with chilled n-butyl acetate;
g) dry the crystals under vacuum.

The XRD and DSC are shown in the Figures 1-3. The novel form of Ivabradine hydrochloride is characterized by X-ray powder diffraction spectrum having principal peaks at 8.60, 9.08, 11.65, 14.60, 15.29, 16.73, 17.20, 18.24, 18.89, 19.64,20.31,21.02,21.58,22.26,22.67,23.39,23.97,24.55,26.37, 27.07, 27.69, 29.31, 30.25, 31.18, 32.44, 33.70, 35.20, 35.57, 39.12, 41.56, 42.32, 43.87, 45.77 ° 20.
The present invention provides novel polymorphs of Ivabradine hydrochloride, from the group consisting of solvents: Diphenyl ether, methyl tetrahydrofuran, 2-methoxy ethanol, petroleum ether, cyclopentyl methyl ether, isopropyl or isobutyl acetate, methanol, hexane and mixtures thereof.
EXAMPLES
Example 1: Preparation of Ivabradine Hydrochloride Form N.
To Ivabradine hydrochloride (5.0 grams, 0.0099 moles) added n-butyl acetate (33.3 mL) and n-hexane (0.5 mL, 0.1 volume) resulting suspension heated to 60-65° C. To the suspension added methanol (6.6 mL) and clear solution observed. The solution slowly cooled to 25-30 °C and further cooled to 15-20 °C and stirred for 2 hours. The resulting crystals filtered off and washed with chilled n-butyl acetate (5 mL), followed by drying under vacuum. Yield: 3.5 grams, 70%.

Claims
We Claim:
1. A compound of Ivabradine hydrochloride polymorph-N.
2. The Ivabradine hydrochloride polymorph-N according to claim 1, having X-ray powder diffraction comprising peaks at 8.60, 9.08, 11.65, 14.60, 15.29, 16.73, 17.20, 18.24, 18.89, 19.64, 20.31, 21.02, 21.58, 22.26, 22.67, 23.39, 23.97, 24.55, 26.37, 27.07, 27.69, 29.31, 30.25, 31.18, 32.44, 33.70, 35.20, 35.57, 39.12, 41.56, 42.32, 43.87, 45.77 ° 29.
3. Ivabradine hydrochloride polymorph-N according to claim 1, having an X-ray diffraction pattern in accordance with Figure - 1.
4. Ivabradine hydrochloride polymorph-N according to claim 1, having a Differential Scanning
Calorimetry curve substantially in accordance with Figure - 3.
5. A process for the preparation of novel polymorph-N of Ivabradine hydrochloride, which comprises
the steps of:
a) suspend Ivabradine hydrochloride in n-butyl acetate and n-hexane;
b) heat the above suspension to 60-65 °C;
c) add methanol to obtain the clear solution;
d) slowly cool the above solution to 25-30 °C;
e) further cooled the above solution to 15- 20 °C and maintained for 2 hours under stirring;
f) filter the crystals and wash with chilled n-butyl acetate;
g) dry the crystals under vacuum.