DESC:Field of the invention

The present invention provides a novel pure amorphous form of vilazodone hydrochloride, process for preparation, pharmaceutical compositions, and method of treating thereof.

Background of the invention

Vilazodone is 5-(4-[4-(5-cyano-1H-indol-3-yl) butyl] piperazin-1-yl) benzofuran-2-carboxamide and represented by formula (I).

The product is marketed in the form of Hydrochloride salt. The current pharmaceutical product containing this drug is being sold by Merck using the trade name Viibryd. Vilazodone is an SSRI antidepressant developed by Clinical Data for the treatment of major depressive disorder.

Vilazodone was first described in US patent 5532241. Example 4 of Said patent described process for preparing vilazodone by reacting 1-[4-{5-cyanoindol-3-yl) butyl]-4-{2-carboxybenzofuran-5-yl)-piprazine at first with 2-chloro-1-methylpyridinium methanesulfonate in N-methylpyrrolidine and then with dried ammonia. Customary working up gives the free base vilazodone. Which is further converted in to Vilazodone hydrochloride.

PCT publication no. WO2002102794A2 describes different polymorphs of Vilazodone hydrochloride, termed as form I to form XVI. WO2002102794A2 describes form XVI as amorphous form. The term "amorphous" means a solid without long-range crystalline order. However, the X-ray powder diffraction pattern of form XVI shows that the polymorph is not in its pure amorphous form but also comprises crystalline peaks. Therefore, it does not demonstrate the amorphous nature of the product. It is essentially a mixture of crystalline and amorphous form which is not a form of suitable choice.

Polymorphic purity is one of the important aspects in the development of any active pharmaceutical ingredients. An active pharmaceutical ingredient is always preferred to have consistency in terms of polymorphic purity. Therefore it is desirable to have either pure crystalline form or a substantially pure amorphous form.

Polymorphism is defined as "the ability of a substance to exist as two or more crystalline phases that have different arrangement and /or conformations of the molecule in the crystal lattice. Thus, in the strict sense, polymorphs are different crystalline forms of the same pure substance in which the molecules have different arrangements and / or configurations of the molecules". Different polymorphs may differ in their physical properties such as melting point, solubility, X-ray diffraction patterns, etc. Although those differences disappear once the compound is dissolved, they can appreciably influence pharmaceutically relevant properties of the solid form, such as handling properties, dissolution rate and stability. Such properties can significantly influence the processing, shelf life, and commercial acceptance of a polymorph. It is therefore important to investigate all solid forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form. Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC) and infrared spectrometry (IR).

Solvent medium and mode of isolation play very important role in obtaining a polymorphic form over the other.

It has been disclosed in the art that the amorphous forms in a number of drugs exhibit different dissolution characteristics and in some cases different bioavailability patterns compared to crystalline forms [Konne T., Chem. Pharm. Bull., 38, 2003-2007 (1990)]. For some therapeutic indications one bioavailability pattern may be favored over another.
The discovery of new polymorphic forms of a pharmaceutically useful compound provides a new opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for designing, for example, a pharmaceutical dosage form of a drug with a targeted release profile or other desired characteristic.

Accordingly, there remains a need in the art for a novel, stable and substantially pure amorphous form of Vilazodone hydrochloride. The present inventors have directed its research work to get the desired polymorphic purity.

Summary of the invention

The present inventors have now surprisingly and unexpectedly discovered a novel pure amorphous form of Vilazodone hydrochloride with high purity, adequate stability and good dissolution properties.
In one aspect, the present invention provides a novel, pure and stable amorphous form of Vilazodone hydrochloride.
In one aspect, the present invention provides a novel, pure and stable amorphous form of Vilazodone hydrochloride characterized by X-ray diffraction pattern as depicted in Figure- 1.
In another aspect, the present invention provides a pharmaceutical composition comprising amorphous Vilazodone hydrochloride of the present invention and one or more pharmaceutically acceptable excipients.
In another aspect, the amorphous Vilazodone hydrochloride disclosed herein for use in the pharmaceutical compositions of the present invention, wherein 90 volume-percent of the particles (D90) have a size of less than or equal to about 500 microns, specifically less than or equal to about 300 microns, more specifically less than or equal to about 200 microns, still more specifically less than or equal to about 100 microns, and most specifically less than or equal to about 15 microns.

In another aspect, the present invention further encompasses a process for preparing the highly pure and stable amorphous form of Vilazodone hydrochloride.
In another aspect of the present invention, a process is provided for preparation of a stable and substantially pure amorphous form of Vilazodone hydrochloride, which comprises:
a) Providing a solution of Vilazodone hydrochloride in a suitable solvent or a mixture of solvents capable of dissolving Vilazodone hydrochloride;
b) Optionally, filtering the solvent solution to remove any extraneous matter; and
c) Substantially removing the solvent from the solution to afford amorphous form of Vilazodone hydrochloride.
In another aspect of the present invention, suitable solvent in step (a) is selected from the group of formic acid, acetic acid and propionic acid, more preferably formic acid.

In another aspect of the present invention, a process is provided for preparation of a stable and substantially pure amorphous form of Vilazodone hydrochloride, which comprises:
a) Providing a solution of Vilazodone hydrochloride in formic acid;
b) Optionally, filtering the solvent solution to remove any extraneous matter; and
c) Substantially removing the solvent from the solution to afford amorphous form of Vilazodone hydrochloride.

In another aspect of the present invention, a process is provided for preparation of a stable and substantially pure amorphous form of Vilazodone hydrochloride, which comprises:
a) Providing a solution of Vilazodone free base in a suitable solvent or a mixture of solvents capable of dissolving Vilazodone;
b) Mixing with the solution of hydrochloric acid dissolved in the suitable solvent;
c) Optionally, filtering the solvent solution to remove any extraneous matter; and
d) Substantially removing the solvent from the solution to afford amorphous form of Vilazodone hydrochloride.

In another aspect of the present invention, suitable solvent in step (a) is selected from the group of formic acid, acetic acid and propionic acid, more preferably formic acid and suitable solvent in step (b) is selected from group comprising water, alcohols, ketones, chlorinated hydrocarbons, hydrocarbons, nitriles, esters, cyclic ethers, aliphatic ethers, polar aprotic solvents, and mixtures thereof. Preferable solvents are chlorinated hydrocarbons, ketones, alcohols and mixtures thereof, more preferably 2-propanol.

In another aspect of the present invention, a process is provided for preparation of a stable and substantially pure amorphous form of Vilazodone hydrochloride, which comprises:
a) Providing a solution of Vilazodone free base in formic acid;
b) Mixing with the solution of 2-propanol.HCl;
c) Optionally, filtering the solvent solution to remove any extraneous matter; and
d) Substantially removing the solvent from the solution to afford amorphous form of Vilazodone hydrochloride.

Unless otherwise indicated, the following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein.

The term "polymorphic form" refers to a crystal modification that can be characterized by analytical methods such as X-ray powder diffraction, IR-spectroscopy, differential scanning calorimetry (DSC) or by its melting point.

The term "amorphous" means a solid without long-range crystalline order. Amorphous form of Vilazodone hydrochloride in accordance with the present invention preferably contains less than about 10% crystalline forms of Vilazodone hydrochloride, more preferably less than 5% crystalline forms of Vilazodone hydrochloride, and still more preferably is essentially free of crystalline forms of Vilazodone hydrochloride. "Essentially free of crystalline forms of Vilazodone hydrochloride" means that no crystalline polymorph forms of Vilazodone hydrochloride can be detected within the limits of a powder X-ray diffractometer.

The term "pharmaceutically acceptable" means that which is useful in preparing a pharmaceutical composition that is generally non-toxic and is not biologically undesirable and includes that which is acceptable for veterinary use and/or human pharmaceutical use.
The term "pharmaceutical composition" is intended to encompass a drug product including the active ingredient(s), pharmaceutically acceptable excipients that make up the carrier, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients. Accordingly, the pharmaceutical compositions of the present invention encompass any composition made by admixing the active ingredient, active ingredient dispersion or composite, additional active ingredient(s), and pharmaceutically acceptable excipients.

The expression "pharmaceutically acceptable salt " is meant those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use.

As used herein, Dx means that X percent of the particles have a diameter less than a specified diameter D. Thus, a D90 or d(0.9) of less than 300 microns means that 90 volume-percent of the micronized particles in a composition have a diameter less than 300 microns. The term "micronization" used herein means a process or method by which the size of a population of particles is reduced.

As used herein, "Particle Size Distribution (P.S.D)" means the cumulative volume size distribution of equivalent spherical diameters as determined by laser diffraction in Malvern Master Sizer 2000 equipment or its equivalent. "Mean particle size distribution, i.e., D50" correspondingly, means the median of said particle size distribution.

By "substantially pure" is meant having purity greater than about 99%, specifically greater than about 99.5%, and more specifically greater than about 99.9% measured by HPLC.

The term "therapeutically effective amount" as used herein means the amount of a compound that, when administered to a mammal for treating a state, disorder or condition, is sufficient to effect such treatment. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the mammal to be treated.

The term "delivering" as used herein means providing a therapeutically effective amount of an active ingredient to a particular location within a host causing a therapeutically effective blood concentration of the active ingredient at the particular location. This can be accomplished, e.g., by topical, local or by systemic administration of the active ingredient to the host.

The term "buffering agent" as used herein is intended to mean a compound used to resist a change in pH upon dilution or addition of acid or alkali. Such compounds include, by way of example and without limitation, potassium metaphosphate, potassium phosphate, monobasic sodium acetate and sodium citrate anhydrous and dehydrate and other such material known to those of ordinary skill in the art.

The term "sweetening agent" as used herein is intended to mean a compound used to impart sweetness to a formulation. Such compounds include, by way of example and without limitation, aspartame, dextrose, glycerin, mannitol, saccharin sodium, sorbitol, sucrose, fructose and other such materials known to those of ordinary skill in the art.
The term "binders" as used herein is intended to mean substances used to cause adhesion of powder particles in granulations. Such compounds include, by way of example and without limitation, acacia alginic acid, tragacanth, carboxymethylcellulose sodium, polyvinylpyrrolidone, compressible sugar (e.g., NuTab), ethylcellulose, gelatin, liquid glucose, methylcellulose, povidone and pregelatinized starch, combinations thereof and other material known to those of ordinary skill in the art. If required, other binders may also be included in the present invention.

Exemplary binders include starch, polyethylene glycol, guar gum, polysaccharide, bentonites, sugars, invert sugars, poloxamers (PLURONIC(TM) F68, PLURONIC(TM)
Fl 27), collagen, albumin, celluloses in nonaqueous solvents, combinations thereof and the like. Other binders include, for example, polypropylene glycol, polyoxyethylene- polypropylene copolymer, polyethylene ester, polyethylene sorbitan ester, polyethylene oxide, microcrystalline cellulose, polyvinylpyrrolidone, combinations thereof and other such materials known to those of ordinary skill in the art. The term "diluent" or "filler" as used herein is intended to mean inert substances used as fillers to create the desired bulk, flow properties, and compression characteristics in the preparation of solid dosage formulations. Such compounds include, by way of example and without limitation, dibasic calcium phosphate, kaolin, sucrose, mannitol, microcrystalline cellulose, powdered cellulose, precipitated calcium carbonate, sorbitol, starch, combinations thereof and other such materials known to those of ordinary skill hi the art.

The term "glidant" as used herein is intended to mean agents used in solid dosage formulations to improve flow-properties during tablet compression and to produce an anti-caking effect. Such compounds include, by way of example and without limitation, colloidal silica, calcium silicate, magnesium silicate, silicon hydrogel, cornstarch, talc, combinations thereof and other such materials known to those of ordinary skill in the art.

The term "lubricant" as used herein is intended to mean substances used in solid dosage formulations to reduce friction during compression of the solid dosage. Such compounds include, by way of example and without limitation, calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate, combinations thereof and other such materials known to those of ordinary skill in the art.

The term "disintegrant" as used herein is intended to mean a compound used in solid dosage formulations to promote the disruption of the solid mass into smaller particles which are more readily dispersed or dissolved. Exemplary disintegrants include, by way of example and without limitation, starches such as corn starch, potato starch, pregelatinized, sweeteners, clays, such as bentonite, macrocrystalline cellulose (e.g. Avicel(TM)), carsium (e.g. Amberlite(TM)), alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, tragacanth, combinations thereof and other such materials known to those of ordinary skill in the art.

The term "wetting agent" as used herein is intended to mean a compound used to aid in attaining intimate contact between solid particles and liquids. Exemplary wetting agents include, by way of example and without limitation, gelatin, casein, lecithin (phosphatides), gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glycerol monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers (e.g., macrogol ethers such as cetomacrogol 1000), polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, (e.g., TWEEN(TM)s), polyethylene glycols, polyoxyethylene stearates colloidal silicon dioxide, phosphates, sodium dodecylsulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, hydroxy! propylcellulose, hydroxypropylmethylcellulose phthalate, noncrystalline cellulose, magnesium aluminum silicate, triethanolamine, polyvinyl alcohol, and polyvinylpyrrolidone (PVP). Tyloxapol (a nonionic liquid polymer of the alkyl aryl polyether alcohol type) is another useful wetting agent, combinations thereof and other such materials known to those of ordinary skill in the art.

Brief Description of the Drawing
Figure 1 shows an X-ray diffraction pattern of novel pure amorphous form of vilazodone hydrochloride prepared by inventors.

Detailed description of the invention:

In one embodiment present invention provides novel pure amorphous form of vilazodone hydrochloride.
In another embodiment, the present invention further encompasses a process for preparing the highly pure and stable amorphous form of Vilazodone hydrochloride.

In another embodiment, the present invention provides a pharmaceutical composition comprising amorphous Vilazodone hydrochloride of the present invention and one or more pharmaceutically acceptable excipients.

In another embodiment, the amorphous Vilazodone hydrochloride disclosed herein for use in the pharmaceutical compositions of the present invention, wherein 90 volume-percent of the particles (D90) have a size of less than or equal to about 500 microns, specifically less than or equal to about 300 microns, more specifically less than or equal to about 200 microns, still more specifically less than or equal to about 100 microns, and most specifically less than or equal to about 15 microns.

According to one embodiment of the present invention, there is provided a stable and substantially pure amorphous form of Vilazodone hydrochloride. Amorphous form of Vilazodone hydrochloride is characterized by the following properties: a powder XRD pattern substantially in accordance with Figure 1. The X-ray powder diffraction pattern shows no peaks, thus demonstrating the amorphous nature of the product.

According to another embodiment of the present invention, a process is provided for preparation of a stable and substantially pure amorphous form of Vilazodone hydrochloride, which comprises:
a) Providing a solution of Vilazodone hydrochloride in a suitable solvent or a mixture of solvents capable of dissolving Vilazodone hydrochloride;
b) Optionally, filtering the solvent solution to remove any extraneous matter; and
c) Substantially removing the solvent from the solution to afford amorphous form of Vilazodone hydrochloride.

The process can produce amorphous Vilazodone hydrochloride in substantially pure form.

The term "substantially pure amorphous form of Vilazodone hydrochloride " refers to the amorphous form of Vilazodone hydrochloride having purity greater than about 98%, specifically greater than about 99%, more specifically greater than about 99.5% and still more specifically greater than about 99.9% (measured by HPLC).

The amorphous Vilazodone hydrochloride obtained by the process disclosed herein is stable, consistently reproducible and has good flow properties, and which is particularly suitable for bulk preparation and handling, and so, the amorphous Vilazodone hydrochloride obtained by the process disclosed herein is suitable for formulating Vilazodone hydrochloride.

The suitable solvent used in step-(a) is selected from the group comprising carboxylic acids, such as formic acid, acetic acid, propionic acid etc.

Step-(a) of providing a solution of Vilazodone hydrochloride includes dissolving Vilazodone hydrochloride in the solvent, or obtaining an existing solution from a previous processing step. Preferably the Vilazodone hydrochloride is dissolved in the solvent at a temperature of below about boiling temperature of the solvent used, more preferably at about 2O0C to about 1100C, and still more preferably at about 250C to about 800C.

The solution in step-(a) may also be prepared by reacting Vilazodone free base with Hydrochloric acid to produce a solution containing Vilazodone hydrochloride, or optionally subjecting the solution to usual work up such as washings, extractions etc., and dissolving the resulting Vilazodone hydrochloride in a suitable solvent at a temperature of below about boiling temperature of the solvent used, more preferably at 2O0C to about 1100C, and still more preferably at about 250C to about 800C.

The solution obtained in step-(a) may optionally be subjected to carbon treatment. The carbon treatment can be carried out by methods known in the art, for example by stirring the solution with finely powdered carbon at a temperature of below about 700C for at least 15 minutes, preferably at a temperature of about 250C to about 700C for at least 30 minutes; and filtering the resulting mixture through hyfio to obtain a filtrate containing Vilazodone hydrochloride by removing charcoal. Preferably, finely powdered carbon is an active carbon.

The solution obtained in step-(a) or step-(b) is optionally stirred at a temperature of about 300C to the reflux temperature of the solvent used for at least 20 minutes, and preferably at a temperature of about 400C to the reflux temperature of the solvent used from about 30 minutes to about 4 hours.

Removal of solvent in step-(c) is accomplished by, for example, substantially complete evaporation of the solvent, concentrating the solution and filtering the solid under inert atmosphere. Alternatively, the solvent may also be removed by evaporation.

Evaporation can be achieved at sub-zero temperatures by the lyophilisation or freeze- drying technique. The solution may also be completely evaporated in, for example, a pilot plant Rota vapor, a Vacuum Paddle Dryer or in a conventional reactor under vacuum above about 720 mm Hg by flash evaporation techniques by using an agitated thin film dryer ("ATFD"), or evaporated by spray drying.

The distillation process can be performed at atmospheric pressure or reduced pressure. Preferably the solvent is removed at a pressure of about 760 mm Hg or less, more preferably at about 400 mm Hg or less, still more preferably at about 80 mm Hg or less, and most preferably from about 30 to about 80 mm Hg.

The substantially pure amorphous Vilazodone hydrochloride obtained by the above process may be further dried in, for example, Vacuum Tray Dryer, Rotocon Vacuum Dryer, Vacuum Paddle Dryer or pilot plant Rota vapor, to further lower residual solvents.

The total purity of the amorphous Vilazodone hydrochloride obtained by the process disclosed herein is of greater than about 99%, specifically greater than about 99.5%, and more specifically greater than about 99.9% as measured by HPLC.

According to another aspect of the present invention, a process is provided for preparation of a stable and substantially pure amorphous form of Vilazodone hydrochloride, which comprises:
a) Providing a solution of Vilazodone free base in a suitable solvent or a mixture of solvents capable of dissolving Vilazodone;
b) Mixing with the solution of hydrochloric acid dissolved in the suitable solvent;
c) Optionally, filtering the solvent solution to remove any extraneous matter; and
d) Substantially removing the solvent from the solution to afford amorphous form of Vilazodone hydrochloride.

The suitable solvent used in step-(b) is selected from the group comprising water, alcohols, ketones, chlorinated hydrocarbons, hydrocarbons, nitriles, esters, cyclic ethers, aliphatic ethers, polar aprotic solvents, and mixtures thereof. Preferable solvents are chlorinated hydrocarbons, ketones, alcohols and mixtures thereof, more preferably more preferably 2-propanol.
Exemplary alcohol solvents include, but are not limited to, C1 to C8 straight or branched chain alcohol solvents such as methanol, ethanol, propanol, butanol, amyl alcohol, hexanol, and mixtures thereof. Specific alcohol solvents are methanol, ethanol, isopropyl alcohol, and mixtures thereof, and most specific alcohol solvent is isopropyl alcohol.
Exemplary ketone solvents include, but are not limited to, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone and the like, and mixtures thereof.
Exemplary nitrile solvents include, but are not limited to, acetonitrile, propionitrile and the like, and mixtures thereof.
Exemplary ester solvents include, but are not limited to, ethyl acetate, isopropyl acetate, and the like and mixtures thereof.
Exemplary chlorinated hydrocarbon solvents include, but are not limited to, methylene chloride, ethyl dichloride, chloroform, carbon tetrachloride, and mixtures thereof. Specific chlorinated hydrocarbon solvent is methylene chloride.
Exemplary cyclic ether solvents include, but are not limited to, tetrahydrofuran, dioxane, and the like, and mixtures thereof.
Exemplary aliphatic ether solvents include, but are not limited to, diethyl ether, diisopropyl ether, monoglyme, diglyme and the like, and mixtures thereof.
Exemplary hydrocarbon solvents include, but are not limited to, n-pentane, n-hexane, n-heptane and isomers thereof, cyclohexane, toluene and xylene and the like, and mixtures thereof.
Exemplary polar aprotic solvents include, but are not limited to, N,N-dimethylformaniide, N,N- dimethylacetamide, dimethylsulfoxide, and mixtures thereof.

In one embodiment, the substantially pure amorphous Vilazodone hydrochloride disclosed herein for use in the pharmaceutical compositions of the present invention, wherein 90 volume-percent of the particles (D90) have a size of less than or equal to about 500 microns, specifically less than or equal to about 300 microns, more specifically less than or equal to about 200 microns, still more specifically less than or equal to about 100 microns, and most specifically less than or equal to about 15 microns.
In another embodiment, the particle sizes of substantially pure amorphous Vilazodone hydrochloride can be achieved by a mechanical process of reducing the size of particles which includes any one or more of cutting, chipping, crushing, milling, grinding, micronizing, trituration or other particle size reduction methods known in the art, to bring the solid state forms the desired particle size range.

According to another aspect of the present invention, there is provided a method for treating a patient suffering from depressive disorders, anxiety disorders, bipolar disorders, mania, dementia, substance-related disorders, sexual dysfunctions, eating disorders, obesity, fibromyalgia, sleeping disorders, psychiatric disorders, cerebral infarct, tension, for the therapy of side-effects in the treatment of hypertension, cerebral disorders, chronic pain, acromegaly, hypogonadism, secondary amenorrhea, premenstrual syndrome and undesired puerperal lactation.

According to another aspect of the present invention, there is provided pharmaceutical compositions comprising amorphous Vilazodone hydrochloride prepared according to processes of the present invention in any of its embodiments and one or more pharmaceutically acceptable excipients.

According to another aspect of the present invention, there is provided a process for preparing a pharmaceutical formulation comprising combining amorphous Vilazodone hydrochloride prepared according to processes of the present invention in any of its embodiments, with one or more pharmaceutically acceptable excipients.

Yet another embodiment of the present invention is directed to pharmaceutical compositions comprising at least a therapeutically effective amount of substantially pure amorphous Vilazodone hydrochloride of the present invention. Such pharmaceutical compositions may be administered to a mammalian patient in any dosage form, e.g., liquid, powder, elixir, injectable solution, etc. Dosage forms may be adapted for administration to the patient by oral, buccal, parenteral, ophthalmic, rectal and transdermal routes or any other acceptable route of administration. Oral dosage forms include, but are not limited to, tablets, pills, capsules, troches, sachets, suspensions, powders, lozenges, elixirs and the like.
The pure amorphous Vilazodone hydrochloride of the present invention may also be administered as suppositories, ophthalmic ointments and suspensions, and parenteral suspensions, which are administered by other routes. The dosage forms may contain amorphous Vilazodone hydrochloride of the present invention as is or, alternatively, may contain amorphous Vilazodone hydrochloride of the present invention as part of a composition. The pharmaceutical compositions may further contain one or more pharmaceutically acceptable excipients. Suitable excipients and the amounts to use may be readily determined by the formulation scientist based upon experience and consideration of standard procedures and reference works in the field, e.g., the buffering agents, sweetening agents, binders, diluents, fillers, lubricants, wetting agents and disintegrants described hereinabove.
Capsule dosages will contain amorphous Vilazodone hydrochloride of the present invention within a capsule which may be coated with gelatin. Tablets and powders may also be coated with an enteric coating. The enteric-coated powder forms may have coatings containing at least phthalic acid cellulose acetate, hydroxypropylmethyl cellulose phthalate, polyvinyl alcohol phthalate, carboxy methyl ethyl cellulose, a copolymer of styrene and maleic acid, a copolymer of methacrylic acid and methyl methacrylate, and like materials, and if desired, they may be employed with suitable plasticizers and/or extending agents. A coated capsule or tablet may have a coating on the surface thereof or may be a capsule or tablet comprising a powder or granules with an enteric-coating. Tableting compositions may have few or many components depending upon the tableting method used, the release rate desired and other factors. For example, the compositions of the present invention may contain diluents such as cellulose-derived materials like powdered cellulose, macrocrystalline cellulose, microfine cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose salts and other substituted and unsubstituted celluloses; starch; pregelatinized starch; inorganic diluents such calcium carbonate and calcium diphosphate and other diluents known to one of ordinary skill in the art. Yet other suitable diluents include waxes, sugars (e.g. lactose) and sugar alcohols like mannitol and sorbitol, acrylate polymers and copolymers, as well as pectin, dextrin and gelatin.
Other excipients contemplated by the present invention include binders, such as acacia gum, pregelatinized starch, sodium alginate, glucose and other binders used in wet and dry granulation and direct compression tableting processes; disintegrants such as sodium starch glycolate, crospovidone, low-substituted hydroxypropyl cellulose and others; lubricants like magnesium and calcium stearate and sodium stearyl fumarate; flavorings; sweeteners; preservatives; pharmaceutically acceptable dyes and glidants such as silicon dioxide.

The following examples are provided to enable one skilled in the art to practice the invention and are merely illustrate the process of this invention. However, it is not intended in any way to limit the scope of the present invention.
The products of the following Examples 1-3 each gave a powder X-ray diffraction pattern in Figures 1. The products had a shelf life suitable for commercial use and were suitable for rapid absorption after oral administration.

EXAMPLES
Example 1
Process for preparing amorphous Vilazodone hydrochloride
Vilazodone hydrochloride (2.Og) was dissolved in formic acid (10 ml) to obtain clear solution. The solvents were removed completely under vacuum at 400C and then dried for 12 hours to give 2.0 g of Vilazodone hydrochloride in amorphous form.

Example 2
Process for preparing amorphous Vilazodone hydrochloride
Vilazodone hydrochloride (2.Og) was dissolved in formic acid (10 ml) to obtain clear solution. The resulting clear solution was concentrated to dryness using laboratory spray dryer to give 2.0 g of Vilazodone hydrochloride in amorphous form.

Example 3
Process for preparing amorphous Vilazodone hydrochloride
Formic acid (500ml) and vilazodone base (100g) and 20%w/w hydrochloric acid were mixed at 20-30oC under stirring. Activated carbon (5.0g) was added and reaction mass was stirred for 30-45 minutes at 30-35oC. The reaction mass was filtered hot and washed with hot (30-35oC) Formic acid (100ml). The spray dryer aspirator was set at 1400 rpm (vacuum at 50-120mm), inlet temperature 125-130oC, and air pressure at 3-4 Kg /cm2 and feed pump rate of 2-3 rpm. Then filtrate was spray dried. The material was unloaded and dried in VTD at 85-90oC for 20-24 hours.

Example 4
Process for preparing amorphous Vilazodone hydrochloride
Formic acid (500ml) and vilazodone base (100g) and IPA.HCl were mixed at 20-30oC under stirring. Activated carbon (5.0g) was added and reaction mass was stirred for 30-45 minutes at 30-35oC. The reaction mass was filtered hot and washed with hot (30-35oC) Formic acid (100ml). The spray dryer aspirator was set at 1400 rpm (vacuum at 50-120mm), inlet temperature 125-130oC, and air pressure at 3-4 Kg /cm2 and feed pump rate of 2-3 rpm. Then filtrate was spray dried. The material was unloaded and dried in VTD at 85-90oC for 20-24 hours.
,CLAIMS:1. A process for preparation of a stable and substantially pure amorphous form of Vilazodone hydrochloride, which comprises:
a) Providing a solution of Vilazodone hydrochloride in a suitable solvent or a mixture of solvents capable of dissolving Vilazodone hydrochloride;
b) Optionally, filtering the solvent solution to remove any extraneous matter; and
c) Substantially removing the solvent from the solution to afford amorphous form of Vilazodone hydrochloride.

2. A process according to claim 1, wherein, suitable solvent in step (a) is selected from the group of formic acid, acetic acid and propionic acid, more preferably formic acid.

3. A process for preparation of a stable and substantially pure amorphous form of Vilazodone hydrochloride, which comprises:
a) Providing a solution of Vilazodone hydrochloride in formic acid;
b) Optionally, filtering the solvent solution to remove any extraneous matter; and
c) Substantially removing the solvent from the solution to afford amorphous form of Vilazodone hydrochloride.

4. A process for preparation of a stable and substantially pure amorphous form of Vilazodone hydrochloride, which comprises:
a) Providing a solution of Vilazodone free base in a suitable solvent or a mixture of solvents capable of dissolving Vilazodone;
b) Mixing with the solution of hydrochloric acid dissolved in the suitable solvent;
c) Optionally, filtering the solvent solution to remove any extraneous matter; and
d) Substantially removing the solvent from the solution to afford amorphous form of Vilazodone hydrochloride.

5. A process according to claim 4 wherein, suitable solvent in step (a) is selected from the group of formic acid, acetic acid and propionic acid, more preferably formic acid.

6. A process according to claim 4 wherein, and suitable solvent in step (b) is selected from group comprising water, alcohols, ketones, chlorinated hydrocarbons, hydrocarbons, nitriles, esters, cyclic ethers, aliphatic ethers, polar aprotic solvents, and mixtures thereof. Preferable solvents are chlorinated hydrocarbons, ketones, alcohols and mixtures thereof.

7. A process is provided for preparation of a stable and substantially pure amorphous form of Vilazodone hydrochloride, which comprises:
a) Providing a solution of Vilazodone free base in formic acid;
b) Mixing with the solution of aqueous HCl;
c) Optionally, filtering the solvent solution to remove any extraneous matter; and
d) Substantially removing the solvent from the solution to afford amorphous form of Vilazodone hydrochloride.