FIELD OF INVENTION The present invention relates to a process for the preparation of 2-[2-ethoxy-5-(4-ethyl-piperazine-l-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo [5,1-fJ [l,2,4]triazin-4-one hydrochloride trihydrate (Vardenafil hydrochloride trihydrate).
BACKGROUND OF THE INVENTION Vardenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) indicated for the treatment of erectile dysfunction. It is marketed as vardenafil monohydrochloride trihydrate under the brand name of LEVITRA® by Bayer Healthcare. Vardenafil is chemically known as 2-[2-ethoxy-5-(4-ethyl-piperazine-l-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-fJ[l,2,4]triazin-4-one, represented by the following structure formula:
U.S. Patent No. 6,362,178 discloses vardenafil and related compounds, its therapeutic uses as well as a process for its preparation for first time. The process for preparation of vardenafil described in U.S. Patent No. 6,362,178 is depicted in Scheme-I. It describes reaction of 2-[2-ethoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-fj[l,2,4]triazin-4-one with excess chlorosulfonic acid to provide 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo [ 1,5-fJ[ 1,2,4] triazin-2-yl) benzene-1-sulfonyl chloride as a colourless foam followed by reaction with N-ethyl piperazine using methylene chloride to give vardenafil base. Vardenafil base is purified from ether and then reacted with dil. aqueous hydrochloric acid to provide vardenafil monohydrochloride trihydrate.

Another process for the preparation of vardenafil is described in U.S. Patent No. 6,777,551 which discloses reaction of 2-[2-ethoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-fJ[l,2,4]triazin-4-one with concentrated sulphuric acid to provide 4-ethoxy-3 -(5 -methyl-4-oxo-7-propyl-3,4-dihydroimidazol [5,1 -f] [ 1,2,4] triazin-2-yl) benzenesulphonic acid, which is then reacted with thionyl chloride in the presence of catalytic amount of dimethyl formamide and subsequently with N-ethyl piperazine to give vardenafil base. Vardenafil base is reacted with aq. hydrochloric acid using acetone and water to provide vardenafil monohydrochloride trihydrate.

The above reported processes suffer from the drawback that they involve the isolation of the sulfonylchloride as an intermediate and use of hazardous reagent like concentrated sulphuric acid which leads to the formation of impurities.
WO2011079935 A2 discloses in-situ reaction of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo [ 1,5-f] [ 1,2,4]triazin-2-yl) benzene-1 -sulfonyl chloride with N-ethyl piperazine to give vardenafil base which is subsequently
*
reacted with citric acid to provide vardenafil citrate. The obtained vardenafil citrate salt is crystallized from rectified ethanol. Vardenafil citrate salt converted to vardenafil free base using aq. sodium hydroxide solution and then reacted with concentrated hydrochloric acid using acetone and water to provide vardenafil monohydrochloride trihydrate.

Indian application 1365/CHE/2010 discloses certain process related impurities including dimer and chloro impurity of formula VI & VII which are difficult to remove from the product.
It is desirable to remove impurities from the pharmaceutical product which may be harmful to patient. There is a need in the art for an improved, commercially viable and environmentally safer process for the preparation of

vardenafil or salts thereof having high yield and purity to overcome the drawbacks associated with the above processes.
SUMMARY OF THE INVENTION In an embodiment, the present invention provides a process for the preparation of vardenafil or its hydrochloride salt, comprising the steps of:
a) reacting 2-[2-ethoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-fJ[l,2,4] triazin-4-one of formula (II)
with chlorosulfonic acid to give compound of formula (III);
b) in-situ reacting the resulting 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,l-f][l,2,4]triazin -2-yl) benzene-1-sulfonyl chloride of formula (III) with N-ethyl piperazine to give vardenafil free base of formula (IV);

c) reacting vardenafil free base of formula (IV) with tartaric acid to give vardenafil hemitartrate salt of formula (V), optionally purifying vardenafil hemitartrate salt;
d) reacting vardenafil hemitartrate salt of formula (V) with a base to give vardenafil free base of formula (IV); and
e) reacting vardenafil free base of formula (IV) with hydrochloric acid to provide vardenafil hydrochloride, preferably vardenafil hydrochloride trihydrate (I).

In another embodiment, the present invention provides a process for the preparation of vardenafil or its hydrochloride salt, comprising the steps of: a) reacting vardenafil free base of formula (IV)
with tartaric acid to give vardenafil hemitartrate salt of formula (V), optionally purifying vardenafil hemitartrate salt;
b) reacting vardenafil hemitartrate salt of formula (V) with base to give vardenafil free base of formula (IV); and

c) reacting vardenafil free base of formula (IV) with hydrochloric acid to provide vardenafil hydrochloride, preferably vardenafil hydrochloride trihydrate (I).
In yet another embodiment, the present invention provides a process for
preparing vardenafil or a pharmaceutically acceptable salt thereof in high purity
and yield by making a vardenafil hemitartrate salt having reduced amount of
impurities.
In yet another embodiment, the present invention provides a process for
the preparation of vardenafil or its tartrate salt, comprising the steps of:
a) reacting vardenafil free base of formula (IV)
with tartaric acid to give vardenafil hemitartrate salt of formula (V), optionally purifying vardenafil hemitartrate salt; and

b) reacting Vardenafil hemi tartrate salt of formula (V) with an aqueous solution of base to give Vardenafil free base of formula (IV). In yet another embodiment, the present invention provides a process for
preparing vardenafil or its hydrochloride salt, especially vardenafil hydrochloride
trihydrate having an improved impurity profile.
In yet another embodiment, the present invention provides a process for
preparing vardenafil or its hydrochloride salt, especially vardenafil hydrochloride
trihydrate substantially free of impurity of formula VI, VII and VIII.
DETAILED DESCRIPTION OF THE INVENTION As used herein, the phrase "vardenafil hydrochloride trihydrate substantially free of impurity" is means vardenafil hydrochloride trihydrate wherein the impurity of formula VI, VII and VIII is not more than 0.1% by HPLC.

The present invention avoids the isolation of 4-ethoxy-3-(5-methyl-4-oxo-
7-propyl-3,4-dihydro-imidazoi5,l-fJ[l,2,4]triazin-2-yl) benzene-1-sulfonyl-
chloride which may hydrolyse in water to sulfonic acid. The present invention encompass in-situ reaction of sulfonyl chloride with N-ethyl piperazine to provide vardenafil base which is also reacted in-situ with the tartaric acid to provide vardenafil hemitartrate salt having high purity and yield.
The present invention also provide a process for the preparation of vardenafil hemitartrate salt having relatively low content of one or more organic impurities compared to vardenafil salts known in the art. The content of chloro, dimer and bis-piperazine impurity of formula VI, VII & VIII can be controlled at a minimum level by preparing vardenafil hemitartrate salt and thereby obtaining vardenafil or a pharmaceutically acceptable salt thereof substantially free from impurities.
In one embodiment, the present invention provides a process for the preparation of vardenafil or its hydrochloride salt, comprising the steps of:
a) reacting 2-[2-ethoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-f][1,2,4]
triazin-4-one of formula (II)
with chlorosulfonic acid to give compound of formula (III);
b) in-situ reacting the resulting 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,l-f][l,2,4]triazin -2-yl) benzene-1-sulfonyl chloride of

formula (III) with N-ethyl piperazine to give vardenafil free base of formula (IV);
c) reacting vardenafil free base of formula (IV) with tartaric acid to give vardenafil hemitartrate salt of formula (V), optionally purifying vardenafil hemitartrate salt;
d) reacting vardenafil hemitartrate salt of formula (V) with an aqueous solution of base to give vardenafil free base of formula (IV);
e) reacting vardenafil free base of formula (IV) with hydrochloric acid to provide vardenafil hydrochloride, preferably vardenafil hydrochloride trihydrate (I).

Step a) involves reaction of 2-[2-ethoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-f][l,2,4] triazin-4-one of formula (II) with chlorosulfonic acid. This reaction may be carried out in presence of solvent. Solvents used in this step include, but are not limited to, hydrocarbons such as toluene, xylene; halogenated hydrocarbons such as dichloromethane, chlorobenzene, chloroform or mixtures thereof.
Step b) involves in-situ condensation of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,l-f][l,2,4]triazin -2-yl) benzene-1-sulfonyl chloride of formula (III) with N-ethyl piperazine in presence of solvent and optionally in presence of catalyst. Solvents used in this step include, but are not limited to, hydrocarbons such as toluene, xylene; halogenated hydrocarbons such as dichloromethane, chlorobenzene, chloroform or mixtures thereof. Catalyst can be selected from dimethylaminopyridine (DMAP), triethylamine (TEA) and N,N-diisopropylethylamine (DIPEA or Hunigs base).
Step c) involves reaction of vardenafil free base with tartaric acid in presence of solvent. Solvents used for this include, but are not limited to, alcohols such as methanol, ethanol, isopropanol or mixtures thereof. The reaction may be carried out at temperature ranging from 0°C to 150°C, preferably at reflux temperature. Vardenafil hemitartrate salt may be further purified from solvents selected from, but are not limited to, alcohols such as methanol, ethanol, isopropanol, n-butanol; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone; hydrocarbons such as toluene, xylene; halogenated hydrocarbons such as dichloromethane, ethylene dichloride, chlorobenzene, chloroform; polar

aprotic solvents such as N,N-dimethylformamide (DMF), dimethyl acetamide (DMAc), dimethyl sulfoxide (DMSO); ethers such as tetrahydrofuran (THF); water or mixtures thereof.
Step d) involves reaction of vardenafil hemitartrate salt with base in presence of solvent to provide vardenafil free base. Solvents used in this step include, but are not limited to halogenated hydrocarbons such as dichloromethane, ethylene dichloride, chlorobenzene, chloroform; hydrocarbons such as toluene, xylene or mixture thereof. Base used in this step include, but are not limited to alkali or alkaline earth metal carbonate such as sodium carbonate, potassium carbonate; bicarbonate such as sodium bicarbonate, potassium bicarbonate; hydroxide such as sodium hydroxide, potassium hydroxide; organic base such as such as triethylamine, trimethylamine, diisopropylethylamine, tri-n-butylamine, or mixtures thereof.
Step e) involves the reaction of vardenafil free base with hydrochloric acid in presence of solvent to provide vardenafil hydrochloride trihydrate. Solvents used in this step include, but are not limited to, alcohols such methanol, ethanol, isopropanol; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone; water or mixtures thereof. Preferably, the reaction may be carried out with acetone, water and hydrochloric acid to provide vardenafil hydrochloride trihydrate.
In another embodiment, the present invention provides a process for the preparation of vardenafil or its hydrochloride salt, comprising the steps of: a) reacting vardenafil free base of formula (IV)
with tartaric acid to give vardenafil hemitartrate salt of formula (V), optionally purifying vardenafil hemitartrate salt;

b) reacting vardenafil hemitartrate salt of formula (V) with a base to give vardenafil free base of formula (IV); and
c) reacting vardenafil free base of formula (IV) with hydrochloric acid to provide vardenafil hydrochloride, preferably vardenafil hydrochloride trihydrate (I).
Vardenafil hemitartrate salt is reacted with base in presence of solvent to provide vardenafil free base. Vardenafil free base is reacted with hydrochloric acid in presence of solvent to provide vardenafil hydrochloride trihydrate. Vardenafil hydrochloride trihydrate obtained by the process of present invention

has improved impurity profile and substantially free of impurity of formula VI, VII and VIII. Vardenafil hydrochloride trihydrate obtained by present invention is preferred for pharmaceutical formulation, since it is substantially free of impurities.
In yet another embodiment, the present invention provides a process for preparing vardenafil or a pharmaceutically acceptable salt thereof in high purity and yield by making a vardenafil hemitartrate salt having reduced amount of impurities.
In yet another embodiment, the present invention provides a process for the preparation of vardenafil or its hemitartrate salt, comprising the steps of: a) reacting vardenafil free base of formula (IV)
with tartaric acid to give vardenafil hemitartrate salt of formula (V), optionally purifying vardenafil hemitartrate salt;
b) reacting vardenafil hemitartrate salt of formula (V) with a base to give vardenafil free base of formula (IV).

In order to obtain vardenafil hydrochloride trihydrate substantially free of impurities, reactions of vardenafil free base with various acids such as L(+)-tartaric acid, citric acid, succinic acid, oxalic acid, benzoic acid and malonic acid is carried out. Vardenafil hemitartrate salt obtained in a solid form and purification of vardenafil hemitartrate salt greatly enhanced the purity of the product obtained. Vardenafil hemitartrate salt may be purified from solvents selected from, but are not limited to, alcohols, ketones, hydrocarbons, halogenated hydrocarbons, polar aprotic solvents, ethers, water or mixtures thereof. The purification afforded vardenafil hemitartrate salt of high purity and the content of chloro, dimer and bis-piperazine impurity not more than 0.1% by HPLC. Vardenafil hemitartrate salt helps to obtain vardenafil hydrochloride trihydrate with improved impurity profile with the control of impurity of formula VI, VII and VIII at a minimum level.
In yet another embodiment, the present invention provides a process for preparing vardenafil hydrochloride trihydrate substantially free of impurity of formula VI, VII and VIII.
In yet another embodiment, the present invention provides a process tor preparation of vardenafil hydrochloride trihydrate as shown in Scheme-IV.

The following examples are provided only for the purpose of illustrating certain specific aspects of the present invention and should not be considered as limiting the scope or spirit of the invention in any manner.
Example 1 Preparation of 2-[2-ethoxy-5-(4-ethyl-piperazine-l-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-f] [l,2,4]triazin-4-one hemi tartrate
2-(2-Ethoxyphenyl)-5-methyl-7-propy-3H-imidazo [5,l-fJ[l,2,4]triazin-4-one (100 g) was added portion wise into chlorosulfonic acid (200 ml) at 25-35°C within 2-3 h. The reaction mass was stirred at 25-35°C for 3h. In another flask, a 2000 ml mixture of dichloromethane: water (1:1) was cooled to 10-20°C. After the completion of reaction, the reaction mixture was poured into a cooled mixture of dichloromethane: water (1:1). Reaction mixture was allowed to warm at 25-35°C and stirred for 30 min. Separate the organic layer and washed with water (500 ml x 3). N-Ethyl piperazine (42.04 g) was added drop wise to the organic

layer at 25-35°C. Reaction mixture was stirred for 2 h. After the completion of reaction, 5 % sodium bicarbonate solution was added to the reaction mixture and stirred for 5-10 min. Organic layer was separated and washed with 5% sodium bicarbonate solution (1000 ml) followed by water (1000 ml). Organic layer was distilled out below 50°C. The residue was stirred with isopropyl alcohol (200 ml) at 40-50°C for 5-10 min. and then distilled out under vacuum below 50°C. Isopropyl alcohol (1500 ml) and L(+) tartaric acid (48.08 g) was added to the obtained residue and heated to reflux for 1 h. Reaction mass was allowed warm at r.t. and stirred for 1 h. The reaction mixture was filtered and washed with isopropyl alcohol (50 ml x 2). The solid was dried at 25-35°C for 2 h and then at 45-55°C for 8 h to give the title product (134 g). Yield: 74.0 % HPLC Purity: 99.53 % Content of tartaric acid: 13.88 % Content of chloro & dimer impurity: 0.04 % Content of bis-piperazine impurity: 0.22 %
Example 2 Purification of 2-[2-ethoxy-5-(4-ethyl-piperazine-l-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-f][lj2,4]triazin-4-one hemi tartrate
A mixture of 2-[2-ethoxy-5-(4-ethyl-piperazine-l-sulfonyl)-phenyl]-5-methyl-7-
propyl-3H-imidazo[5,l-f][l,2,4]triazin-4-one hemi tartrate (130 g) and methanol
(650 ml) was heated to 60-70°C for 1 h. The Reaction mass was cooled to 0-10°C
and stirred for 1 h. The Resulting solid was filtered off and washed with chilled
methanol (65 ml x 2). The solid was dried at 25-35°C for 2 h and then at 45-55°C
for 8 h to give the title product (117 g).
Yield: 90.0 %
HPLC Purity: 99.83 %
Content of tartaric acid: 12.91 %
Content of chloro & dimer impurity: Not detected
Content of bis-piperazine impurity: 0.04 %

!H NMR (DMSO-d6)8: 0.904-0.956 (6H, q), 1.310-1.344 (3H, t), 1.684-1.777 (2H, m), 2.308-2.362(2H, q), 2.448 (4H, s), 2.481-2.52 (3H, m), 2.808-2.845 (2H, t), 2.910 (4H, s), 4.191-4.243 (2H, q), 4.265 (1H, s), 7.382-7.404 (1H, d), 7.839-7.878 (2H, m)
XPRD (20): 5.21, 8.11, 10.13, 10.45, 14.33, 15.45, 16.12, 16.70, 18.53, 20.85, 21.07,21.96,23.24,23.52,23.94 & 24.77 ± 0.2
Example 3
Preparation of 2-[2-ethoxy-5-(4-ethyl-piperazine-l-sulfonyl)-phenyl]-5-
methyl-7-propyl-3H-imidazo[5,l-f][lj2,4]triazin-4-one hydrochloride
trihydrate
A solution of sodium bicarbonate (4.47 g) in water (100 ml) was added at 25-
35°C to heterogeneous reaction mixture of 2-[2-ethoxy-5-(4-ethyl-piperazine-l-
sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-fj[l,2,4]triazin-4-one hemi
tartrate (20 g) in dichloromethane (100 ml) within 0.5 to 1 h. Reaction mixture
was allowed to stir at 25-35°C for 1 h and then separate the organic layer, washed
with water (40 ml) and distilled out organic layer under vacuum below 50°C. The
residue was stirred with acetone (20 ml) at 40-50°C for 10-15 min. and then
distilled out under vacuum below 50°C. Acetone (60 ml) and water (2 ml) was
added to the obtained residue. Hydrochloric acid (3.32 ml) was added dropwise to
the reaction mass. Stir the clear solution of the reaction mass at 25-35°C for 1 h
and then at 0-5°C for 2 h. The resulting solid was filtered and washed with chilled
acetone (10 ml x 2). The solid was dried at 25-3 5°C in air tray drying to give the
title product (17.4 g).
Yield: 84.61 %
HPLC Purity: 99.95 %
Chloride content: 6.56 % w/w (on anhydrous basis)
Water Content: 9.54 % w/w
Content of chloro & dimer impurity: Not detected
Content of bis-piperazine impurity: Not detected

!H NMR (DMSO-de) 8: 0.914-0.951 (3H, t), 1.193-1.228 (3H, t), 1.320-1.355 (3H, t), 1.699-1.792 (2H, m), 2.327 (3H, s), 2.781-2.863 (4H, m), 3.087-3.103 (4H, m), 3.495-3.523(2H, d), 3.795-3.826 (2H, d), 4.205-4.257 (2H, q), 7.426-7.451 (1H, m), 7.930-7.952 (2H, m) 10.931 (1H, s), 11.793 (1H, s)
Example 4 Preparation of 2-[2-ethoxy-5-(4-ethyl-piperazine-1 -sulfony l)-pheny 1] -5-methyl-7-propyl-3H-imidazo[5,l-f] [l,2,4]triazin-4-one citrate
A solution of citric acid (1.96 g) in methanol (10 ml) was added to a mixture of
vardenafil base (5 g) and methanol (25 ml) at 50°C. Reaction mixture was stirred
at 50°C for 15 min. and then allowed to warm at 25-35°C and continue stirred for
2 h. The resulting solid was filtered, washed with methanol (5 ml) and dried at
50°C to give the title product (5.3 g).
Yield: 76.0 %
HPLC purity: 99.31%
Content of dimer & chloro impurity: 0.35 %
Content of bis-piperazine impurity: Not detected
Example 5 Preparation of 2-[2-ethoxy-5-(4-ethyl-piperazine-l-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-f] [l,2,4]triazin-4-one succinate
A solution of succinic acid (1.20 g) in a mixture of acetone & water (25 ml)
(9.5:0.5) was added to a mixture of vardenafil base (5 g) in acetone & water (25
ml) (9.5:0.5) at 50°C. Reaction mixture was stirred at 50°C for 15 min. and then
allowed to warm at 25-3 5 °C and continue stirred for 2 h. Reaction mixture was
cooled to 0-10°C & stirred for 1 h. The resulting solid was filtered, washed with a
mixture of acetone & water (5 ml) (9.5:0.5) and dried at 50°C to give the title
product (4.6 g).
Yield: 74.0 %
HPLC purity: 99.56 %
Content of chloro & dimer impurity: 0.14 %
Content of bis-piperazine impurity: 0.02 %

Example 6 Preparation of 2-[2-ethoxy-5-(4-ethyl-piperazine-l-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-f][l,2,4]triazin-4-one oxalate
A mixture of vardenafil base (6.35 g) and oxalic acid dihydrate (1.60 g) in
isopropanol (50 ml) was heated to reflux at 85°C for 1 h. The reaction mixture
was allowed to warm at 25-35°C and continue stirred for 1 h. The resulting solid
was filtered, washed with isopropanol (3ml * 2) and dried at 50°C to give the title
product (6.53 g). The solid was purified from isopropanol (25 ml) at reflux
temperature to give to the title product (5.40 g).
Yield: 67.66%
HPLC purity: 99.03 %
Content of chloro & dimer impurity: 0.21 %
Content of bis-piperazine impurity: 0.26 %
Example 7 Preparation of 2-[2-ethoxy-5-(4-ethyl-piperazine-l-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,l-f] [l,2,4]triazin-4-one benzoate
A mixture of vardenafil base (6.30 g) and benzoic acid (1.60g) in isopropanol (50 ml) was heated to reflux at 85°C for 1 h. The reaction mixture was allowed to warm at 25-35°C and continue stirred for 1 h. The resulting solid was filtered, washed with isopropanol (3 ml x 2) and dried at 50°C to give the title product (6.53 g). The solid was purified from isopropanol (25 ml) at reflux temperature to give to the title product (4.0 g). Yield: 51.0%

We claim:
1. A process for preparation of vardenafil or its hydrochloride salt, comprising the steps of:
a) reacting 2-[2-ethoxy-phenyl]-5-methyl-7-propyI-3H-imidazo[5,l-fJ[l,2,4] triazin-4-one of formula (II)
with chlorosulfonic acid to give compound of formula (III);
b) in-situ reacting the resulting 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,l-f][l,2,4]triazin -2-yl) benzene-1-sulfonyl chloride of formula (III) with N-ethyl piperazine to give vardenafil free base of formula (IV);
c) reacting vardenafil free base of formula (IV) with tartaric acid to give vardenafil hemitartrate salt of formula (V), optionally purifying vardenafil hemitartrate salt;

d) reacting vardenafil hemitartrate salt of formula (V) with a base to give vardenafil free base of formula (IV); and
e) reacting vardenafil free base of formula (IV) with hydrochloric acid to provide vardenafil hydrochloride, preferably vardenafil hydrochloride trihydrate (I).
2. The process according to claim 1, wherein step c) is carried out in presence of organic solvent such as alcohol selected from methanol, ethanol, isopropanol or mixtures thereof.

3. The process according to claim 1, wherein purification of vardenafil
hemitartrate salt carried out in solvent selected from the group consisting of
alcohols such as methanol, ethanol, isopropanol, n-butanol; ketones such as
acetone, methyl ethyl ketone, methyl isobutyl ketone; hydrocarbons such as
toluene, xylene; halogenated hydrocarbons such as dichloromethane, ethylene
dichloride, chlorobenzene, chloroform; polar aprotic solvents such as N,N-
dimethylformamide (DMF), dimethyl acetamide (DMAc), dimethyl sulfoxide
(DMSO); ethers such as tetrahydrofuran (THF) or mixtures thereof.
The process according to claim 1, wherein base used in step d) is selected from the group consisting of alkali or alkaline earth metal carbonate such as sodium carbonate, potassium carbonate; bicarbonate such as sodium bicarbonate, potassium bicarbonate; hydroxide such as sodium hydroxide, potassium hydroxide; organic base such as triethylamine, trimethylamine, diisopropylethylamine, tri-n-butylamine, or mixtures thereof.
The process according to claim 1, wherein step d) is carried out in presence of organic solvent selected from the group consisting of halogenated hydrocarbons such as dichloromethane, ethylene dichloride, chlorobenzene, chloroform; hydrocarbons such as toluene, xylene or mixtures thereof.
The process according to claim 1, wherein step e) is carried out in presence of solvent selected from the group consisting of alcohols such methanol, ethanol, isopropanol; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone; water or mixtures thereof.
7. The process of claim 1, wherein the vardenafil hydrochloride trihydrate
prepared is substantially free of impurity of formula VI, VII and VIII.
8. A process for the preparation of vardenafil or salts thereof, comprising the steps
of:

a) reacting vardenafil free base of formula (IV)
with tartaric acid to give vardenafil hemitartrate salt of formula (V), optionally purifying vardenafil hemitartrate salt;
b) reacting vardenafil hemitartrate salt of formula (V) with base to give vardenafil free base of formula (IV); and
c) reacting vardenafil free base of formula (IV) with hydrochloric acid to provide vardenafil hydrochloride, preferably vardenafil hydrochloride trihydrate (I).

8. A process for the preparation of vardenafil or salts thereof, comprising the steps of:
a) reacting vardenafil free base of formula (IV)
with tartaric acid to give vardenafil hemitartrate salt of formula (V), optionally purifying vardenafil hemitartrate salt; and
b) reacting vardenafil hemi tartrate salt of formula (V) with an aqueous solution of base to give vardenafil free base of formula (IV).

10. Vardenafil hydrochloride trihydrate substantially free of impurity of formula VI, VII and VIII.