AMORPHOUS VILAZODONE HYDROCHLORIDE, A PROCESS FOR ITS
PREPARATION AND PHARMACEUTICAL COMPOSITIONS THEREOF
Field of the Invention
The present invention relates to amorphous vilazodone hydrochloride, its process of
preparation, and pharmaceutical compositions thereof.
Background of the Invention
Vilazodone hydrochloride is chemically described as 5-{4-[4-(5-cyano-lH-indol-3-
yl)butyl]piperazin-l-yl}-l-benzofuran-2-carboxamide hydrochloride of Formula I.
FORMULA I
Vilazodone hydrochloride is indicated for the treatment of major depressive disorder
(MDD).
Processes for the preparation of vilazodone hydrochloride and its various polymorphic
forms are described in U.S. Patent Nos. 5,532,241; 7,834,020; 7,981,894; and 7,381,726; U.S.
Publication Nos. 2011/0183994 and 2011/0190317; and European Patent Nos. EP 1 397 357 and
EP 0 648 767.
Summary of the Invention
The present invention relates to an amorphous vilazodone hydrochloride, its process of
preparation, and pharmaceutical compositions thereof.
Brief Description of the Drawings
Figure 1 depicts the X-ray Powder Diffraction Pattern (XRPD) of the amorphous vilazodone
hydrochloride obtained according to Example 1.
Figure 2 depicts the X-ray Powder Diffraction Pattern (XRPD) of the amorphous vilazodone
hydrochloride obtained according to Example 2.
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Figure 3 depicts the X-ray Powder Diffraction Pattern (XRPD) of the amorphous vilazodone
hydrochloride obtained according to Example 3.
Figure 4 depicts the X-ray Powder Diffraction Pattern (XRPD) of the amorphous vilazodone
hydrochloride obtained according to Example 4.
Figure 5 depicts the X-Ray Diffraction Pattern (XRPD) of the amorphous vilazodone
hydrochloride obtained according to Example 3 after storage at 25°C and 52% relative humidity
(RH) for 24 days.
Figure 6 depicts the Differential Scanning Calorimetry (DSC) of the amorphous vilazodone
hydrochloride obtained according to Example 2.
Figure 7 depicts the Differential Scanning Calorimetry (DSC) of the amorphous vilazodone
hydrochloride obtained according to Example 3.
Detailed Description of the Invention
A first aspect of the present invention provides an amorphous vilazodone hydrochloride.
The term "amorphous" refers to a solid without long-range crystalline order. The
amorphous form of a compound of Formula I of the present invention preferably contains less
than about 20% crystalline forms, more preferably less than 5% crystalline forms, and still more
preferably less than 1% or is essentially free of crystalline forms. "Essentially free of crystalline
forms" means that no crystalline polymorph forms can be detected within the limits of an X-ray
Powder Diffractometer.
The amorphous vilazodone hydrochloride prepared by the present invention may be
characterized by an X-ray Powder Diffraction Pattern (XRPD) as depicted in Figure 1, Figure 2,
Figure 3, or Figure 4. The amorphous vilazodone hydrochloride prepared by the present
invention may be further characterized by DSC data as depicted in Figures 6 and 7.
The amorphous vilazodone hydrochloride prepared by the present invention is stable and
does not convert to any other polymorphic form on storage at 25°C and 52% relative humidity
(RH) for 24 days as depicted by X-ray Powder Diffraction Pattern (XRPD) pattern similar to
Figure 5.
A second aspect of the present invention provides a process for the preparation of an
amorphous vilazodone hydrochloride wherein the process comprises:
a) obtaining a solution of vilazodone hydrochloride;
b) removing the solvent from the solution obtained in step a); and
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c) isolating amorphous vilazodone hydrochloride from the reaction mixture.
A solution of vilazodone hydrochloride can be obtained by treating vilazodone
hydrochloride with one or more solvents.
The term "solvent" includes any solvent or solvent mixture, for example, water, esters,
alkanols, halogenated hydrocarbons, ketones, ethers, polar aprotic solvents, or mixtures thereof.
The solvent may be selected from the group consisting of water, alkanol, esters, ketones,
ethers, polar aprotic solvents, or mixtures thereof. Examples of alkanols include those primary,
secondary, and tertiary alcohols having from one to six carbon atoms. Suitable alkanol solvents
include methanol, ethanol, n-propanol, 2-propanol, and butanol. Examples of ester solvents
include ethyl acetate, n-propyl acetate, isopropyl acetate, and n-butyl acetate. Examples of
ketones include acetone, methyl ethyl ketone, and the like. Examples of ethers include
tetrahydrofuran and the like. A suitable polar aprotic solvent includes N,N-dimethylformamide,
N,N-dimethylacetamide, dimethylsulphoxide, acetonitrile, and N-methylpyrrolidone. Examples
of halogenated hydrocarbons include dichloromethane, chloroform, and 1,2-dichloroethane. A
solvent may preferably be a mixture of water with alkanol, for example, a mixture of water with
methanol, ethanol, or 2-propanol.
Treating vilazodone hydrochloride with one or more solvents may include adding,
dissolving, slurrying, stirring, or a combination thereof. Vilazodone hydrochloride may be
treated with a solvent at a temperature of about 60°C to about 100°C, preferably at about 70°C
to about 80°C.
The solvent may be removed in step b) by using various drying techniques, for example,
spray drying, vacuum drying, freeze drying, or agitated thin film drying.
Isolation of the amorphous vilazodone hydrochloride in step c) comprises a common
isolation technique such as evaporation, evaporation under vacuum, cooling, extraction, one or
more washings, crystallization, precipitation, filtration, filtration under a vacuum, decantation
and centrifugation, or a combination thereof.
A third aspect of the present invention provides a pharmaceutical composition
comprising an amorphous vilazodone hydrochloride and a carrier.
A fourth aspect of the present invention provides a method of treating or preventing
major depressive disorder (MDD) comprising a step of administering to a patient in need thereof
of a therapeutically effective amount of amorphous vilazodone hydrochloride.
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XRPD of the samples were determined by using a Panalytical X'Pert Pro X-Ray Powder
Diffractometer in the range 3-40 degree 2 theta and under a tube voltage and current of 45 Kv
and 40 mA, respectively. Copper radiation of wavelength 1.54 angstrom and Xceletor detector
was used.
In the following section, embodiments are described by way of examples to illustrate the
process of invention. Several variants of these examples would be evident to persons ordinarily
skilled in the art.
EXAMPLES
Example 1: Preparation of Amorphous Vilazodone Hydrochloride
Vilazodone hydrochloride (5.0 g) was dissolved in methanol (125 mL) and water (15
mL) at 80°C. The reaction mixture was filtered and spray dried under the following conditions:
Air Inlet Temperature: 100°C
Air Outlet Temperature: 52°C
The solid so obtained was collected from the spray dryer and dried in a vacuum tray drier
at 55°C for 4 hours to obtain the title compound having an XRPD pattern as depicted in Figure
1.
Yield: 1.52 g
Example 2: Preparation of Amorphous Vilazodone Hydrochloride
Vilazodone hydrochloride (2.5 g) was dissolved in 2-propanol (125 mL) and water (125
mL) at 80°C. The reaction mixture was filtered and spray dried under the following conditions:
Air Inlet Temperature: 130°C
Air Outlet Temperature: 66°C
The solid so obtained was collected from the spray dryer and dried in a vacuum tray drier
at 55°C for 4 hours to obtain the title compound having an XRPD pattern as depicted in Figure
2.
Yield: 2.08 g
Example 3: Preparation of Amorphous Vilazodone Hydrochloride
Vilazodone hydrochloride (5.12 g) was dissolved in ethanol (125 mL) and water (125
mL) at 71°C. The reaction mixture was filtered and spray dried under the following conditions:
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Air Inlet Temperature: 120°C
Air Outlet temperature: 65°C
The solid so obtained was collected from the spray dryer and dried in a vacuum tray drier
at 55°C for 4 hours to obtain the title compound having an XRPD pattern as depicted in Figure
3.
Yield: 2.32 g
Example 4: Preparation of Amorphous Vilazodone Hydrochloride
Vilazodone hydrochloride (0.6 g) was dissolved in methanol (60 mL) and water (5 mL)
at 70°C. The solvent was quickly distilled on a Buchi Roto vapor under the following
conditions:
Temperature: 70°C
Rotations per minute: 200
Pressure: 55 mbar
The solid so obtained was collected from the Buchi Rotovapor and dried in a vacuum
tray drier at 55°C for 4 hours to obtain the title compound having an XRPD pattern as depicted
in Figure 4.
Yield: 0.46 g

WE CLAIM:
1. Amorphous vilazodone hydrochloride.
2. Amorphous vilazodone hydrochloride according to claim 1 which is characterized by X
ray powder diffraction pattern (XRPD) pattern as depicted in Figures 1, 2, 3, or 4.
3. Amorphous vilazodone hydrochloride according to claim 1 which is characterized by
DSC data as depicted in Figure 6 or 7.
4. Amorphous vilazodone hydrochloride according to claim 1 which contains less than
about 20% crystalline forms.
5. Amorphous vilazodone hydrochloride according to claim 1 which is essentially free of
crystalline forms.
6. Stable amorphous vilazodone hydrochloride.
7. The stable amorphous vilazodone hydrochloride according to claim 6 which does not
convert to any other polymorphic form on storage at 25°C and 52% relative humidity
(RH) for 24 days.
8. The stable amorphous vilazodone hydrochloride according to claim 6 which is
characterized by the X-ray Powder Diffraction Pattern (XRPD) pattern as depicted in
Figure 5 on storage at 25°C and 52% relative humidity (RH) for 24 days.
9. A process for the preparation of amorphous vilazodone hydrochloride wherein the
process comprises:
a) obtaining a solution of vilazodone hydrochloride;
b) removing the solvent from the solution obtained in step a); and
c) isolating amorphous vilazodone hydrochloride from the reaction mixture.
10. The process according to claim 9, wherein the solution of vilazodone hydrochloride is
obtained by treating the vilazodone hydrochloride with one or more solvents.
11. The process according to claim 10, wherein the solvent is selected from the group
consisting of water, alkanol, esters, ketones, ethers, polar aprotic solvents, or mixtures
thereof.
12. The process according to claim 10, wherein the solvent is a mixture of water with
methanol, ethanol, or 2-propanol.

13. The process according to claim 9, wherein the solvent is removed in step b) by using
drying techniques.
14. A pharmaceutical composition comprising an amorphous vilazodone hydrochloride and a
carrier.
15. A method of treating or preventing a major depressive disorder (MDD) comprising a step
of administering to a patient in need thereof of a therapeutically effective amount of an
amorphous vilazodone hydrochloride.