This application claims priority to this Indian patent applications 2319/CHE/2012 filed on June 12, 2012 and 3779/CHE/2012 filed on September 12,2012.
FIELD OF THE INVENTION
The present invention relates to novel crystalline Forms of Vilazodone Hydrochloride, 5-
[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofurancarboxamide HC1,
denominated as Form-Al and Form-A2.
BACKGROUND OF THE INVENTION
Vilazodone Hydrochloride, 5 -[4- [4-(5 -cyano-1 H-indol-3 -yl)buty 1] -1 -piperaziny 1] -2-benzofurancarboxamide hydrochloride, having the Formula-I is approved, under the trade name VIIBRYD®, by the United States Food and Drug Administration. VIIBRYD® is indicated for the treatment of major depressive disorder.

Vilazodone hydrochloride was first disclosed in United States patent number US 5532241 and this patent does not disclose any polymorphic form of Vilazodone hydrochloride. The melting point of Vilazodone hydrochloride disclosed in this patent is in the range of 269-272° C.
United States patent number US 7834020 discloses pure crystals of Vilazodone hydrochloride forms like I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XIII, XIV, XV and XVI and amorphous form.

There is still a need in the art to prepare novel and stable crystalline forms of Vilazodone hydrochloride and the present invention provides novel and stable crystalline form of Vilazodone hydrochloride.
OBJECT AND SUMMARY OF THE INVENTION
Principle object of the present invention is to provide novel and stable crystalline Form-Al and Form-A2 of Vilazodone Hydrochloride, 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofurancarboxamide hydrochloride.
Another aspect of the present invention is to provide a process for the preparation of crystalline Form-Al and Form-A2 of Vilazodone Hydrochloride, 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofurancarboxamide hydrochloride.
BRIEF DESCRIPTION OF THE DRAWINGS
Further objects of the present invention together with additional features contributing thereto and advantages accruing there from will be apparent from the following description of preferred embodiments of the invention which are shown in the accompanying drawing figures wherein :
Figure 1: illustrates the powder X-ray diffraction pattern of crystalline Vilazodone
Hydrochloride Form-Al.
Figure 2: illustrates DSC thermogram of Vilazodone Hydrochloride Form-Al.
Figure 3: illustrates TGA of Vilazodone Hydrochloride Form-Al.
Figure 4: illustrates the powder X-ray diffraction pattern of crystalline Vilazodone
Hydrochloride Form-A2.
Figure 5: illustrates DSC thermogram of Vilazodone Hydrochloride Form-A2.
Figure 6: illustrates TGA of Vilazodone Hydrochloride Form-A2.

DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to stable crystalline Form-Al and Form-A2of Vilazodone
Hydrochloride, 5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-
benzofurancarboxamide HC1.
Instrumentation
Powder X-rav Diffraction fPXRD)
The said polymorph of the present invention is characterized by their X-ray powder diffraction pattern. Thus, the X-ray diffraction patterns of said polymorphs of the invention were measured on BRUKER DSDiscover powder diffractometer equipped with goniometer of 0/26 configuration and Lynx Eye detector. The Cu-anode X-ray tube was operated at 40kV and 30mA. The experiments were conducted over the 20 range of 2.0°-50.0°, 0.030° step size and 0.4 seconds step time.
Differential Scanning Calorimetry (DSC)
The DSC measurements were carried out on TA Q1000 of TA instruments. The experiments were performed at a heating rate of 20.0 °C/min over a temperature range of 30°C-330°C purging with nitrogen at a flow rate of 50ml/min. Standard aluminum crucibles covered by lids with pin holes were used.
Thermo gravimetric Analysis (TGA)
TGA/DTA was recorded using the instrument TA Q5000 IR of TA instruments. The experiments were performed at a heating rate of 10.0 °C/min over a temperature range of 30°C-350°C purging with nitrogen at a flow rate of 25ml/min.
The main aspect of the present invention is to provide a process for the preparation of Vilazodone hydrochloride comprising the steps of:
a) dissolving Vilazodone free base in C1-4 carboxylic acid,
b) adding hydrochloric acid source to the reaction mixture, and
c) isolating Vilazodone hydrochloride.

In one embodiment, C1-4 CAboxylic acid used in the present invention is acetic acid.
In one more embodiment, hydrochloric acid source is aqueous HO or alcoholic HC1 such
as Methanolic HC1, Ethanolic HC1, IPA HC1, preferably IPA HC1.
One aspect of the present invention is to provide Stable crystalline Form-Al of Vilazodone hydrochloride.
In one embodiment, crystalline Form-Al of Vilazodone hydrochloride is characterized by the Powder X-ray diffraction having characteristic peaks at 18.75, 21.0, 21.19 and 24.58(±) 0.2° 2-theta.
In another embodiment, crystalline Form-Al of Vilazodone hydrochloride is further characterized by the Powder X-ray diffraction having characteristic peaks at 9.00, 12.97, 14.47, 18.75, 21.0, 21.19,21.70, 22.03, 22.81, 23.57, 24.58, and 25.21(±) 0.2° 2-theta.
The crystalline Form-Al of Vilazodone hydrochloride is further characterized by the Powder X-ray diffraction as depicted in Figure 1.
The crystalline Form-Al of Vilazodone hydrochloride is further characterized by DSC thermogram as depicted in Figure 2.
The crystalline Form-Al of Vilazodone hydrochloride is further characterized by TGA as depicted in Figure 3.
Another aspect of the present invention is to provide a process for the preparation of crystalline Form-Al of Vilazodone hydrochloride comprising the steps of:
d) dissolving Vilazodone free base in CM carboxylic acid,
e) adding hydrochloric acid source to the reaction mixture, and
f) isolating crystalline Vilazodone hydrochloride Form-Al.
In one embodiment, CM carboxylic acid used in the present invention is acetic acid.

In one more embodiment, hydrochloric acid source is IPA HC1, wherein HC1 in IPA HC1 is 0.8 to 1.4 mole ratio with respect to Vilazodone free base, preferably 0.9 to 1.1 mole ratio with respect to Vilazodone free base.
Another aspect of the present invention is to provide crystalline Form-A2 of Vilazodone hydrochloride.
In one embodiment, crystalline Form-A2 of Vilazodone hydrochloride is characterized by the Powder X-ray diffraction having characteristic peaks at 13.61, 18.73, 21.03, 24.67 and 29.09(±) 0.2° 2-theta.
In another embodiment, crystalline Form-A2 of Vilazodone hydrochloride is further characterized by the Powder X-ray diffraction having characteristic peaks at 8.70, 9.99, 10.59, 13.61, 14.86, 17.44, 18.73, 20.45, 21.03, 21.63, 24.67, 27.37, 29.09, and 30.12(±) 0.2° 2-theta.
The crystalline Form-A2 of Vilazodone hydrochloride is further characterized by the Powder X-ray diffraction as depicted in Figure 4.
The crystalline Form-A2 of Vilazodone hydrochloride is further characterized by DSC thermogram as depicted in Figure 5.
The crystalline Form-A2 of Vilazodone hydrochloride is further characterized by TGA as depicted in Figure 6.
Another aspect of the present invention is to provide a process for the preparation of crystalline Form-A2 of Vilazodone hydrochloride comprising the steps of:
a) dissolving Vilazodone free base in C1-4 carboxylic acid,
b) adding hydrochloric acid source to the reaction mixture, and
c) isolating crystalline Vilazodone hydrochloride Form-A2.

In one embodiment, CM carboxylic acid used in the present invention is acetic acid.
In one more embodiment, hydrochloric acid source is IPA HC1. Preferably 0.8 to 1.4 mole ratio of IPA HC1 with respect to Vilazodone free base is used for salt formation, most preferably 0.9 to 1.1 mole ratio with respect to Vilazodone free base. Vilazodone free base used in this invention is prepared by the prior art procedures for example disclosed in US 5532241.
Experimental procedure:
Example 1:
Process for the preparation of crystalline Vilazodone hydrochloride Form-Al.
Vilazodone free base (5g) was dissolved in acetic acid (50 ml) at ambient temperature. To the resultant mass IPA.HC1 (0.45g in 50ml) was added. The obtained mass was stirred for 2 hours. The product was filtered, washed with Isopropyl alcohol and dried at 70-75 °C to yield crystalline Vilazodone hydrochloride Form-Al.
Example 2:
Process for the preparation of crystalline Vilazodone hydrochloride Form-A2.
Vilazodone free base (1 g) was dissolved in acetic acid (10 ml). To the resultant mass IPA.HC1 (50ml) was added. The obtained mass was stirred for 2.5 hours. The product was filtered and dried at 70-75 °C to yield crystalline Vilazodone hydrochloride Form-
A2.

We claim:
1. A process for the preparation of Vilazodone hydrochloride comprising the steps
of:
a) dissolving Vilazodone free base in C1-4 carboxylic acid,
b) adding hydrochloric acid source to the reaction mixture, and
c) isolating Vilazodone hydrochloride.

2. The process according to claim 1, wherein CM carboxylic acid is acetic acid.
3. The process according to claim 1, wherein hydrochloric acid source is alcoholic HC1.
4. The process according to claim 3, wherein alcoholic HC1 is IPA HC1.
5. Crystalline Vilazodone hydrochloride Form-Al.
6. The crystalline Vilazodone hydrochloride Form-Al according claim 5, characterized by Powder X-ray diffraction having characteristic peaks at 18.75, 21.0, 21.19 and 24.58(±) 0.2° 2-theta.
7. The crystalline Vilazodone hydrochloride Form-Al according claim 5, characterized by Powder X-ray diffraction as depicted in Figure 1.
8. Crystalline Vilazodone hydrochloride Form-A2.
9. The crystalline Vilazodone hydrochloride Form-A2 according claim 8, characterized by the Powder X-ray diffraction having characteristic peaks at 13.61, 18.73, 21.03,24.67 and 29.09(±) 0.2° 2-theta.
10. The crystalline Vilazodone hydrochloride Form-A2 according claim 8, characterized by Powder X-ray diffraction as depicted in Figure 4.