"An Amorphous Vilazodone Hydrochloride And Processes For Preparing Same"

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Abstract

Abstract: The present invention provided a process of preparing amorphous form of vilazodone hydrochloride from crystalline vilazodone hydrochloride by a simple precipitation process.

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FORM 2
THE PATENT ACT. 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
Title of the invention
"AN AMORPHOUS V1LAZODONE HYDROCHLORIDE AND PROCESSES FOR PREPARING SAME"
Enaltec Labs Pvt. Ltd. an Indian Company, having its Registered Office at 17'h floor Kesar Solitaire, Plot No.5 Sector-19, Sanpada. Navi Mumbai Maharashtra, India. Pin Code: 400705
1. The following specification particularly describes the invention and the manner in which it is to be performed.

AN AMORPHOUS VILAZODONE HYDROCHLORIDE AND PROCESSES FOR PREPARING SAME
FIELD OF THE INVENTION:
The present invention relate to substantially pure amorphous form of vilazodone hydrochloride. The present invention further relates to processes of preparing substantially pure amorphous form of vilazodone hydrochloride and pharmaceutical composition thereof.
BACKGROUND OF THE INVENTION:
Vilazodone hydrochloride is chemically 2-benzofurancarboxamide. 5-[4-[4-(5-cyano-lH-indol-3-yl) butyl]-1-piperazinyl]-, hydrochloride (1:1) and is known from U.S. Patent No. 5,532,241 and is represented by compound of structural formula I

Vilazodone hydrochloride has been approved in USA and sold in market under the proprietary name VIIBRYD. It is indicated for the treatment of major depressive disorder (MDD).
U.S. Patent No. 5.532,241 describes crystallization of vilazodone hydrochloride in 2-propanol and the resulting vilazodone hydrochloride obtained as mixture of amorphous and crystalline form.

U.S. Patent No. 7.834,020 describes fifteen polymorphic forms of vilazodone hydrochloride including an amorphous form. The disclosed crystalline polymorphic forms referred as form I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XIII, XIV, XV, XVI and their preparation methods
The vilazodone hydrochloride amorphous form i.e. form XVI described in the U.S. Patent No. 7.834,020 is also mixture of amorphous and crystalline form.
Accordingly there is a need in the art to develop substantially pure amorphous form of vilazodone hydrochloride and process of preparing substantially pure amorphous form of vilazodone hydrochloride.
SUMMARY OF THE INVENTION:
A first aspect of the present invention is to provide substantially pure amorphous form of
vilazodone hydrochloride.
A second aspect of the present invention is to provide processes of preparing substantially pure amorphous form of vilazodone hydrochloride.
A third aspect of the present invention is to provide a process of preparing substantially pure amorphous form of vilazodone hydrochloride comprising the steps of:
a. providing a solution of crystalline vilazodone hydrochloride in an organic solvent and
b. isolating substantially pure amorphous form of vilazodone hydrochloride thereof by the
removal of the solvent by spray-drying or freeze-drying technique.
A fourth aspect of the present invention is to provide a process of preparing substantially pure amorphous form of vilazodone hydrochloride comprising the steps of:
a. providing a solution of crystalline vilazodone hydrochloride in an organic solvent and
b. isolating substantially pure amorphous form of vilazodone hydrochloride thereof by the
method of slow crystallization.

Another aspect of the present invention is to provide a process of preparing substantially pure amorphous form of vilazodone hydrochloride comprising the steps of:
a. melting crystalline vilazodone hydrochloride and
b. isolating vilazodone hydrochloride in the substantially pure amorphous form.
Another aspect of the present invention is to provide a process of preparing amorphous form of vilazodone hydrochloride comprising the steps of:
a. providing a solution of crystalline vilazodone hydrochloride in an organic solvent,
b. flash cooling the solution obtained in step-a to about 10 to -50°C to form suspension, and
c. isolating amorphous form of vilazodone hydrochloride.
Another aspect of the present invention is to provide a pharmaceutical composition comprising substantially pure amorphous form of vilazodone hydrochloride.
DETAIL DESCRIPTION OF THE INVENTION:
A crystalline vilazodone hydrochloride used for the present invention may be prepared by methods known in the art such as those described in U.S. Patent No. 5,532,241 and 7,834,020 which are incorporated herein by reference only.
A solution of crystalline vilazodone hydrochloride in an organic solvent may be prepared by dissolving crystalline vilazodone hydrochloride in an organic solvent at a temperature in the range of 25°C to 80°C.
Alternatively, such a solution may be obtained directly from a reaction in which vilazodone hydrochloride is formed.
Examples of an organic solvent may include ketones, alcohols, esters, nitrites, halogenated aliphatic hydrocarbon solvents, ethers or mixtures thereof.
The ketone solvents may be selected from the group comprising of acetone, methyl ethyl ketone, methyl isobutyl ketone, dibutyl ketone, diethyl ketone, dipropyl ketone, diisopropyl ketone,

methyl butyl ketone, methyl propyl ketone, methyl isopropyl ketone, ethyl isopropyl ketone or mixture(s) thereof.
The alcohol solvents may be selected from the group comprising of methanol, ethanol, propanol, isopropanol. butanol. isobutanol, t-butanol. pentanol or mixture(s) thereof.
The ester solvents may be selected from the group comprising of ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, tertiary butyl acetate, pentyl acetate or mixture(s) thereof.
The nitrile solvents may be selected from the group comprising of acetonitrile. propionitrile or mixture(s) thereof.
The halogenated aliphatic hydrocarbon solvents may be selected from the group comprising of dichJoromethane, dichloroethane. chloroform, carbon tetrachloride or mixture(s) thereof.
The ether solvents may be selected from the group comprising of tetrahydrofuran. dioxane, diethyl ether, diisopropyl ether, dibutyl ether, methyl tertiary butyl ether, methyl ethyl ether, methyl isobutyl ether or mixture(s) thereof.
A solution of crystalline vilazodone hydrochloride in an organic solvent may be flash cooled to quickly decrease the temperature of solution to about 10 to -50°C to get suspension.
The resulting suspension may be stirred for a period of 30 minutes to 6 hours at a temperature to about 10 to -50°C to get amorphous form of vilazodone hydrochloride.
An amorphous form of vilazodone hydrochloride may be isolated by the steps of filtration, centrifugation, washing, drying or the combinations thereof.
The amorphous form of vilazodone hydrochloride may be optionally further dried under vacuum at a temperature in the range of 40°C to 60°C for a period of 1 hour to 8 hours to obtain amorphous form of vilazodone hydrochloride with desired residual solvent content.

EXAMPLES:
In the following examples, the preferred embodiments of the present invention are described only by way of illustrating the processes of the invention. However, these are not intended to limit the scope of the present invention in any way.
Example 1: Preparation of amorphous form of vilazodone hydrochloride.
Crystalline vilazodone hydrochloride (lOgm) was added isopropanol (30ml) and the resulting reaction mixture was then heated to about 65°C to get clear solution. The clear solution was immediately cooled to about 0°C over 10 minutes to get suspension. The resulting suspension was stirred at 0°C for 30 minutes. The product thus obtained was filtered and washed with isopropanol (10ml) and dried under vacuum at 40-45°C for 8 hours to get title compound. Yield; 9.2gm Purity: 99.9% (By HPLC)
Example 2: Preparation of amorphous form of vilazodone hydrochloride.
Crystalline vilazodone hydrochloride (lOgm) was added ethanol (40ml) and the resulting
reaction mixture was then heated to about 60°C to get clear solution. The clear solution was
immediately cooled to about 0°C over 10 minutes to get suspension. The resulting suspension
was stirred at 0°C for 30 minutes. The product thus obtained was filtered and washed with
ethanol (10ml) and dried under vacuum at 40-45°C for 6 hours to get title compound.
Yield: 9.3gm
Purity: 99.9% (By HPLC)

WE CLAIM:
1. A process of preparing amorphous form of vilazodone hydrochloride comprising the
steps of:
a. providing a solution of crystalline vilazodone hydrochloride in an organic solvent.
b. flash cooling the solution obtained in step-a to about 10 to -50°C to form
suspension, and
c. isolating amorphous form of vilazodone hydrochloride.
2. The process according to claim no. 1 wherein, a solution of crystalline vilazodone hydrochloride in an organic solvent is prepared by dissolving crystalline vilazodone hydrochloride in an organic solvent at a temperature in the range of 25°C to 80°C.
3. The process according to claim nos. 1 and 2 wherein, an organic solvent is selected from the group comprising of ketones, alcohols, esters, nitriles, halogenated aliphatic hydrocarbon solvents, ethers or mixtures thereof.
4. The process according to claim no. 3 wherein, ketone solvent is selected from the group comprising of acetone, methyl ethyl ketone, methyl isobutyl ketone, dibutyl ketone, diethyl ketone, dipropyl ketone, diisopropyl ketone, methyl butyl ketone, methyl propyl ketone, methyl isopropyl ketone, ethyl isopropyl ketone or mixture(s) thereof; The alcohol solvent is selected from the group comprising of methanol, ethanol, propanol, isopropanol, butanol, isobutanol, t-butanol, pentanol or mixture(s) thereof; The ester solvent is selected from the group comprising of ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, tertiary butyl acetate, pentyl acetate or mixture(s) thereof; The nitrile solvent is selected from the group comprising of acetonitrile, propionitrile or mixture(s) thereof; The halogenated aliphatic hydrocarbon solvent is selected from the group comprising of dichloromethane, dichloroethane, chloroform, carbon tetrachloride or mixture(s) thereof; The ether solvent is selected from the group comprising of tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, dibutyl ether, methyl tertiary butyl ether, methyl ethyl ether, methyl isobutyl ether or mixture(s) thereof.

5. The process according to claim no. 1 wherein, a solution of crystalline vilazodone hydrochloride in an organic solvent is flash cooled to quickly decrease the temperature of solution to about 10 to -50°C to get suspension.
6. The process according to claim no. 5, wherein resulting suspension is stirred for a period of 30 minutes to 6 hours at a temperature to about 10 to -50°C to get amorphous form of vilazodone hydrochloride.
7. The process according to claim no. 1 wherein, an amorphous form of vilazodone hydrochloride is isolated by the steps of filtration, centrifugation, washing, drying or the combinations thereof.
8. The process according to claim no. 7 wherein, an amorphous form of vilazodone hydrochloride is optionally further dried under vacuum at a temperature in the range of 40°C to 60°C for a period of 1 hour to 8 hours to obtain amorphous form of vilazodone hydrochloride with desired residual solvent content.

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