Claims:Field of Invention

The present invention relates to a crystalline form of Lorcaserin Hydrochloride. In particular, the present invention directs to process for the preparation of a crystalline form of Lorcaserin Hydrochloride, has purity more than 99 % when measured by HPLC.

Background of the invention
Lorcaserin hydrochloride is a serotonin 2C receptor agonist for oral administration used for chronic weight management. It has the chemical name ((R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate, and has the structural formula I,

Formula I

In the United States, Lorcaserin hydrochloride (as hemihydrate) is marketed under the name BelviqTM.

Lorcaserin or a pharmaceutically acceptable salt was first described in U.S. Patent No. 6,953,787 with its process for the preparation. The process for the preparation also described in several patents, e.g. US patent Nos. US 8,546,379, US 7,977,329, US 8,367,657, US 8,168,624 and US 8,697,686.

Summary of the Invention

The present invention provides a crystalline form of Lorcaserin hydrochloride, compound of Formula I,

Formula I
has purity more than 99 % when measured by HPLC

The present invention also provides a process for the preparation of a crystalline form of Lorcaserin Hydrochloride, has purity more than 99 %, the process includes the steps of
a) dissolving Lorcaserin hydrochloride in acetonitrile,
b) heating the reaction mixture at suitable temperature.
c) adding isopropyl alcohol to the mixture of step b),
d) isolating crystalline form of Lorcaserin hydrochloride.

The present invention also provides the conversion of a crystalline form of Lorcaserin hydrochloride of present invention to other crystalline form of Lorcaserin hydrochloride.

Brief Description of the Drawings

Figure 1 shows an illustrative example of X-ray powder diffraction pattern of a crystalline form of Lorcaserin hydrochloride

Description of the Invention

For purposes of the present invention, the following terms are defined below.

The X-ray diffraction powder patterns of the present invention were obtained using a Bruker or PANalytical export Pro Powder X-ray Diffractometer at Cu Ka radiation, has the wavelength 1.54 Å.
In one aspect of the present invention provides a crystalline form of Lorcaserin hydrochloride, compound of Formula I,

Formula I
has purity more than 99 % when measured by HPLC.

In another aspect, the present invention provides a crystalline of Lorcaserin hydrochloride is characterized by its X-ray powder diffraction pattern substantially as shown in Figure 1.

In another aspect, the present invention provides a crystalline form of Lorcaserin hydrochloride, is characterized by X-ray diffraction pattern according to Figure 1, which is expressed in terms of 2 theta angles and obtained with a diffractometer equipped with a copper K a-radiation source, wherein said X-ray powder diffraction pattern includes two or more peaks selected from the group comprising of peaks with 2 theta angles of 12.83, 17.62, 19.71, 19.93, 21.14, 21.49, 22.15, 24.53, 25.18 and 25.83 ± 0.2º.

The XRPD characteristic peaks of the crystalline form of Lorcaserin hydrochloride, has purity more than 99 %, further defined from the Table 1:

Crystalline XRD Lorcaserin hydrochloride
2 Theta peaks d-spacing [Aº] Relative Intensity [%]
6.41 13.78 14.19
10.13 8.72 15.98
12.83 6.89 100.00
13.60 6.50 17.24
14.78 5.99 13.54
16.56 5.35 4.91
17.00 5.21 16.64
17.35 5.10 17.05
17.62 5.03 21.20
18.39 4.82 7.69
19.07 4.65 10.54
19.43 4.56 14.41
19.71 4.50 22.39
19.93 4.45 35.45
20.31 4.37 22.50
21.14 4.20 27.90
21.49 4.13 71.91
22.15 4.01 23.76
24.53 3.62 25.10
25.18 3.53 23.55
25.83 3.44 30.53
27.39 3.25 9.50
29.31 3.04 13.59
30.74 2.90 7.41
31.21 2.86 6.01
32.66 2.74 7.58

A crystalline form of Lorcaserin hydrochloride obtained by the process of the invention is stored at 25°C for a period of 3 months and no contamination of other polymorphic form has been observed.

In one another, aspect of the present invention provides the process for the preparation of a crystalline form of crude Lorcaserin hydrochloride, has purity more than 99 % when measured by HPLC, the process includes the steps of
a) dissolving Lorcaserin hydrochloride in acetonitrile,
b) heating the reaction mixture at suitable temperature,
c) adding isopropyl alcohol to the mixture of step b),
d) isolating crystalline form of Lorcaserin hydrochloride.

The present invention process involves the dissolving Lorcaserin hydrochloride in acetonitrile and heating at suitable temperature for a period of 30 minutes followed by addition of isopropyl alcohol. The reaction mixture is further heated at suitable temperature for a period of 15 minutes wherein suitable temperature is in between the range of 60°C to 70°C. Most preferably the suitable temperature is 70°C. The isolation of crystalline solid of Lorcaserin hydrochloride involves cooling the reaction mixture from step c) to temperature between the range of 25°C to 35°C and stirred for a period of 30 minutes followed by cooling at temperature between the range of 0°C to 5°C and maintained for period of 1 hour. The precipitate obtained is filtered and washed by chilled acetonitrile and dried under vacuum at temperature 60°C to obtain crystalline solid; wherein isolation is carried out by means of filtering and drying the reaction mass.

The present invention also provides the conversion of a crystalline form of Lorcaserin hydrochloride to other crystalline form of Lorcaserin hydrochloride.

The present invention is further illustrated by the following example, which does not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present application.
Example

Example-1: Preparation of Crystalline Lorcaserin hydrochloride

Charged acetonitrile (30 mL) in Lorcaserin hydrochloride (5.0 g) and heated at temperature 70°C for a period of 30 minutes followed by addition of isopropyl alcohol (1.0 ml). The reaction mixture was further heated at temperature 70°C for a period of 15 minutes. The reaction mixture was cooled to temperature 25°C to 35°C and stirred for a period of 30 minutes followed by cooling at temperature 0°C to 5°C and maintained for period of 1 hour. The precipitate obtained was filtered and washed by chilled acetonitrile and dried under vacuum at temperature 60°C to obtain titled compound in crystalline form.

Yield: 4 g
HPLC Purity: 99.3 %
, Description:1. A crystalline form of Lorcaserin hydrochloride, compound of Formula I,

Formula I
characterized by at least one of the following properties;
i. a powder X-ray diffraction pattern substantially in accordance with Figure 1;
ii. a powder X-ray diffraction pattern has peaks at about 12.83, 17.62, 19.71, 19.93, 21.14, 21.49, 22.15, 24.53, 25.18 and 25.83 ± 0.2º.

2. The crystalline form of claim 1, wherein crystalline form Lorcaserin hydrochloride can be converted in to any other crystalline or amorphous form of Lorcaserin hydrochloride.

3. A process for the preparation of crystalline form of Lorcaserin hydrochloride, has purity more than 99 % when measured by HPLC, the process comprises the steps of
a) dissolving Lorcaserin hydrochloride in acetonitrile,
b) heating the reaction mixture at suitable temperature,
c) adding isopropyl alcohol to the mixture of step b),
d) isolating crystalline form of Lorcaserin hydrochloride.

4. The process of claim 3, wherein the suitable temperature is in between the range of 60°C to 70°C.

5. The process of claim 3, wherein the suitable temperature is 70°C.

6. The process of claim 3, wherein isolation is carried out at temperature between the range of -5°C to 5°C.