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
"NOVEL POLYMORPHIC FORMS OF DAPOXETINE HYDROCHLORIDE."
Enaltec Labs Pvt. Ltd. an Indian Company, having its Registered Office at 17thFloor, Kesar Solitaire, Plot No.5 Sector-}9, 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.

NOVEL POLYMORPHIC FORMS OF DAPOXETINE HYDROCHLORIDE
FIELD OF THE INVENTION:
The present invention relates to novel polymorphic forms of dapoxetine hydrochloride. The present invention further relates to processes of preparing novel polymorphic forms of dapoxetine hydrochloride and pharmaceutical composition thereof.
BACKGROUND OF THE INVENTION:
Dapoxetine hydrochloride is chemically a hydrochloric acid salt of (S)-N, Af-dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l-amine and is known from U.S Patent No. 5,135,947 and is represented by a compound of structural formula I.

Dapoxetine (INN, brand name Priligy) is a short-acting selective serotonin reuptake inhibitor (SSRI) and is marketed for the treatment of premature ejaculation in men.
U.S Patent No. 5,135,947 does not describe crystallization of dapoxetine hydrochloride.
U.S Patent No. 5,292,962 and PCT Publication No. 2008/035358 962 describe crystallization of dapoxetine hydrochloride in isopropanol solvent.

Polymorphism, the occurrence of different crystal forms, is a property of some molecules and molecular complexes. A single molecule may give rise to a variety of crystalline forms having distinct crystal structures and physical properties like melting point, x-ray diffraction pattern, infrared absorption fingerprint, and solid state NMR spectrum. One crystalline form may give rise to thermal behavior different from that of another crystalline form. Thermal behavior can be measured in the laboratory by such techniques as capillary melting point, thermogravimetric analysis ("TGA"), and differential scanning calorimetry ("DSC") as well as by content of solvent in the crystalline form, which have been used to distinguish polymorphic forms.
The difference in the physical properties of different crystalline forms results from the orientation and intermolecular interactions of adjacent molecules or complexes in the bulk solid. Accordingly, polymorphs are distinct solids sharing the same molecular formula yet having distinct advantageous physical properties compared to other crystalline forms of the same compound or complex.
One of the most important physical properties of pharmaceutical compounds is their solubility in aqueous solutions, particularly their solubility in the gastric juices of a patient. For example, where absorption through the gastrointestinal tract is slow, it is often desirable for a drug that is unstable to conditions in the patient's stomach or intestine to dissolve slowly so that it does not accumulate in a deleterious environment. Different crystalline forms or polymorphs of the same pharmaceutical compounds can and reportedly do have different aqueous solubilities.
The discovery of new polymorphic forms and solvates 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.
The prior art processes of preparing dapoxetine hydrochloride does not described polymorphism of dapoxetine hydrochloride. The present applicant of the patent has surprisingly found that

dapoxetine hydrochloride can exhibit polymorphism and thus the invention relates to novel polymorphic forms of dapoxetine hydrochloride.
SUMMARY OF THE INVENTION:
A first aspect of the present invention is to provide a novel polymorphic form of dapoxetine hydrochloride hereinafter refer as crystalline form I.
A second aspect of the present invention is to provide a novel polymorphic form of dapoxetine hydrochloride hereinafter refer as crystalline form II.
A third aspect of the present invention is to provide an amorphous form of dapoxetine hydrochloride.
A fourth aspect of the present invention is to provide processes for preparing crystalline form I of dapoxetine hydrochloride.
A fifth aspect of the present invention is to provide processes for preparing crystalline form II of dapoxetine hydrochloride.
A sixth aspect of the present invention is to provide processes for preparing amorphous form of dapoxetine hydrochloride.
Another aspect of the present invention is to provide a process for preparing crystalline form I of dapoxetine hydrochloride comprising the steps of:
a. providing a solution of dapoxetine base in an alkyl acetate solvent,
b. treating a solution of dapoxetine base obtained from step a, with solution of hydrochloric
acid in alkyl acetate solvent at a temperature up to 20°C and
c. isolating crystalline form I of dapoxetine hydrochloride.

Another aspect of the present invention is to provide a process for preparing crystalline form II of dapoxetine hydrochloride comprising the steps of:
a. providing a solution of dapoxetine base in an alkyl acetate solvent,
b. treating a solution of dapoxetine base obtained from step a, with solution of hydrochloric
acid in alkyl acetate solvent at a temperature of above 20°C and
c. isolating crystalline form II of dapoxetine hydrochloride.
Another aspect of the present invention is to provide a process for the preparation of dapoxetine hydrochloride amorphous form comprising the steps of:
a. providing a solution of crystalline dapoxetine hydrochloride in an organic solvent and
b. recovering dapoxetine hydrochloride in the amorphous form from the solution thereof by
the removal of the solvent by spray-drying or freeze-drying technique.
Another aspect of the present invention is to provide a process for the preparation of dapoxetine hydrochloride amorphous form comprising the steps of:
a. melting crystalline dapoxetine hydrochloride and
b. recovering dapoxetine hydrochloride in the amorphous form.
Another aspect of the present invention is to provide dapoxetine base in solid form.
Another aspect of the present invention is to provide novel polymorphic form of dapoxetine base hereinafter refer as crystalline form E.
Another aspect of the present invention is to provide solid dapoxetine base of white to off-white colour.
Another aspect of the present invention is to use of white to off-white colour solid dapoxetine base for the preparation of substantially pure dapoxetine hydrochloride.
Another aspect of the present invention is to provide a pharmaceutical composition comprising crystalline form I of dapoxetine hydrochloride.

Another aspect of the present invention is to provide a pharmaceutical composition comprising crystalline form II of dapoxetine hydrochloride.
Another aspect of the present invention is to provide a pharmaceutical composition comprising amorphous form of dapoxetine hydrochloride.
DETAIL DESCRIPTION OF THE INVENTION:
A crystalline form I of dapoxetine hydrochloride may be characterized by X-ray diffraction pattern having peaks at 6.1, 9.1, 9.4, 10.2, 10.6, 11.8, 12.2, 15.2, 17.0, 18.3, 19.4, 21.2, 21.5, 21.9, 22.7, 23.2, 23.6, 24.3, 24.6, 26.3, 28.2, 28.8, 30.3 ± 0.2 degrees two theta.
A crystalline form I of dapoxetine hydrochloride may be characterized by X-ray diffraction pattern as depicted in Figure 1.
A crystalline form I of dapoxetine hydrochloride may be characterized by X-ray diffraction pattern having following peaks:

Pos.
l°2Th.l Height
lets] Area
[cts*°2Th.] FWHM
f°2Th.] d-spacing
[A] . Rel. Int.
l%]
3.1555 269.66 46.72 0.1171 27.97663 13.15
6.1259 218.01 37.77 0.1171 14.41614 10.63
9.1784 784.09 155.26 0.1338 9.62740 38.25
9.4835 534.78 145.60 0.1840 9.31839 26.08
10.2358 644.46 127.61 0.1338 8.63514 31.43
10.6007 381.35 94.39 0.1673 8.33871 18.60
11.8528 541.42 80.41 0.1004 7.46047 26.41
12.2132 488.90 96.81 0.1338 7.24109 23.85

13.9369 54.18 8.05 0.1004 6.34915 2.64
15.2130 216.02 32.08 0.1004 5.81933 10.54
16.8299 942.33 233.25 0.1673 5.26371 45.96
17.0494 1495.67 222.13 0.1004 5.19645 72.95
17.9106 86.34 17.10 0.1338 4.94847 4.21
18.3055 274.12 81.42 0.2007 4.84261 13.37
18.8283 172.24 34.11 0.1338 4.70931 8.40
19.4628 1147.95 312.56 0.1840 4.55718 55.99
19.8845 197.14 48.80 0.1673 4.46148 9.62
20.5764 94.81 28.16 0.2007 4.31299 4.62
21.2968 853.55 147.89 0.1171 4.16870 41.63
21.5883 2050.16 456.71 0.1506 4.11306 100.00
21.9338 636.50 94.53 0.1004 4.04906 31.05
22.7109 715.06 159.29 0.1506 3.91223 34.88
23.2827 826.68 163.70 0.1338 3.81743 40.32
23.6954 820.16 162.40 0.1338 3.75186 40.00
24.3834 347.67 86.06 0.1673 3.64753 16.96
24.6686 223.64 44.29 0.1338 3.60601 10.91
25.1925 110.56 27.36 0.1673 3.53219 5.39
26.3247 206.98 40.98 0.1338 3.38279 10.10
27.4740 164.30 73.20 0.3011 3.24384 8.01
27.8962 93.75 13.92 0.1004 3.19569 4.57
28.2939 239.75 41.54 0.1171 3.15167 11.69
28.8211 283.78 56.19 0.1338 3.09521 13.84

29.1590 296.10 73.29 0.1673 3.06010 14.44
30.3099 218.39 64.87 0.2007 2.94648 10.65
30.9386 78.62 19.46 0.1673 2.88803 3.83
31.8475 178.66 61.91 0.2342 2.80765 8.71
33.2657 122.25 36.31 0.2007 2.69112 5.96
33.9828 113.12 33.60 0.2007 2.63595 5.52-
35.1421 75.30 14.91 0.1338 2.55160 3.67
36.2191 96.02 28.52 0.2007 2.47816 4.68
37.2696 163.13 64.60 0.2676 2.41069 7.96
37.6078 104.67 20.73 0.1338 2.38978 5.11
38.5463 110.79 32.91 0.2007 2.33373 5.40
39.2722 133.52 46.27 0.2342 2.29225 6.51
A crystalline form II of dapoxetine hydrochloride may be characterized by X-ray diffraction pattern having peaks at 18.4, 20.2, 22.3, 2.3.3, 24.8, 26.1, 27.2, 28.5, 29.0, 30.7, 31.6, 32.5, 33.1, 34.7, 35.6, 38.3 ± 0.2 degrees two theta.
A crystalline form II of dapoxetine hydrochloride may be characterized by X-ray diffraction pattern as depicted in Figure 2.
A crystalline form II of dapoxetine hydrochloride may be characterized by X-ray diffraction pattern having following peaks:

Pos. [°2Th.j Height
[cts] Area [cts*°2Th.] FWHM
l°2Th.] d-spacing
[A] Rel. Int.
[%]
18.4463 82.48 11.22 0.1020 4.80595 19.47
20.2155 76.47 8.32 0.0816 4.38917 18.05

22.3052 423.54 80.64 0.1428 3.98247 100.00
23.3144 128.32 13.96 0.0816 3.81231 . 30.30
24.8000 275.75 22.50 0.0612 3.58721 65.11
26.1547 83.62 13.65 0.1224 3.40439 19.74
27.2839 81.93 22.29 0.2040 3.26601 19.34
28.5435 187.27 61.13 0.2448 3.12468 44.22
29.0080 321.16 61.15 0.1428 3.07569 75.83
29.7533 36.48 11.91 0.2448 3.00032 8.61
30.7468 90.50 17.23 0.1428 2.90560 21.37
31.6966 46.81 5.09 0.0816 2.82067 11.05
32.5461 57.27 7.79 0.1020 2.74895 13.52
33.1870 86.48 9.41 0.0816 2.69731 20.42
33.3844 24.48 3.99 0.1224 2.68182 5.78
34.3430 44.22 4.81 0.0816 2.60912 10.44
34.7641 82.58 15.72 0.1428 2.57848 19.50
34.9712 49.60 5.40 0.0816 2.56368 11.71
35.6063 77.09 25.16 0.2448 2.51940 18.20
36.2363 23.81 7.77 0.2448 2.47702 5.62
36.7392 36.22 15.76 0.3264 2.44427 8.55
37.3791 20.52 4.46 0.1632 2.40388 4.84
38.3389 97.23 37.02 0.2856 2.34588 22.96
38.7719 29.76 8.09 0.2040 2.32067 7.03

A crystalline form E of dapoxetine base may be characterized by X-ray diffraction pattern having peaks at 10.9, 13.1, 17.4, 17.7, 18.6, 20.0, 21.7, 26.4, 28.1 ± 0.2 degrees two theta.
A crystalline form E of dapoxetine base may be characterized by X-ray diffraction pattern as depicted in Figure 4.
A crystalline form E of dapoxetine base may be characterized by X-ray diffraction pattern having following peaks:

Pos.
[°2Th.] Height [cts] Area
[cts*°2Th.] FWHM
[02Th.] 1 d-spacing ReF. Int.
6.5991 713.69 88.33 0.0836 13.38336 2.90
9.2982 401.71 39.77 0.0669 9.50368 1.63
9.8706 74.38 11.05 0.1004 8.95376 0.30
10.9211 24265.77 3003.13 0.0836 8.09474 98.62
11.8226 29.58 4.39 0.1004 7.47946 0.12
13.1508 1581.76 313.21 0.1338 6.72689 6.43
15.1781 29.07 7.20 0.1673 5.83264 0.12
15.8302 57.00 8.47 0.1004 5.59383 0.23
16.5830 455.76 78.97 0.1171 5.34153 1.85
17.2484 1244.55 92.42 0.0502 5.13695 5.06
17.4022 3778.40 374.09 0.0669 5.09189 15.36
17.7008 6282.44 933.02 0.1004 5.00665 25.53
18.4379 3132.25 232.59 0.0502 4.80812 12.73
18.6515 11836.60 2929.80 0.1673 4.75355 48.11
19.0339 459.39 102.34 0.1506 4.65891 1.87

19.3858 4.89 0.73 0.1004 4.57511 0.02
19.8160 3254.73 241.68 0.0502 4.47675 13.23
20.0640 24605.14 3654.16 0.1004 4.42197 100.00
20.9471 336.00 49.90 0.1004 4.23750 1.37
21.4482 228.91 34.00 0.1004 4.13961 0.93
21.7368 2260.06 335.65 0.1004 4.08530 9.19
22.4562 966.08 215.21 0.1506 3.95602 3.93
22.9248 308.79 30.57 0.0669 3.87622 1.26
23.1422 1040.80 297.25 0.1428 3.84029 4.23
23.8378 63.18 10.31 0.0816 3.72978 0.26
24.0867 623.85 178.17 0.1428 3.69179 2.54
24.4156 164.25 26.81 0.0816 3.64280 0.67
24.8572 161.13 26.30 0.0816 3.57908 0.65
26.1986 1252.78 255.57 0.1020 3.39879 5.09
26.4697 14897.52 3039.09 0.1020 3.36459 60.55
27.0381 586.04 95.64 0.0816 3.29513 2.38
27.6563 179.06 36.53 0.1020 3.22287 0.73
28.0547 1534.33 187.80 0.0612 3.17800 6.24
28.1495 1876.19 229.65 0.0612 3.16751 7.63
28.8660 20.78 3.39 0.0816 3.09050 0.08
29.2218 179.00 21.91 0.0612 3.05367 0.73
29.7227 734.19 239.64 0.1632 3.00334 2.98
30.4607 36.30 11.85 0.1632 2.93223 0.15
31.3438 166.22 20.34 0.0612 2.85161 0.68

32.4632
11.28 5.52 0.2448 2.75579 0.05
33.1882 102.21 16.68 0.0816 2.69723 0.42
33.9167 25.84 5.27 0.1020 2.64094 0.11
34.0368 117.74 19.22 0.0816 2.63189 0.48
34.2198 314.50 76.99 0.1224 2.61824 1.28
34.8907 40.89 10.01 0.1224 2.56941 0.17
35.1207 245.57 30.06 0.0612 2.55311 1.00
35.4014 794.88 194.59 0.1224 2.53350 3.23
36.0175 40.15 9.83 0.1224 2.49157 0.16
37.7430 100.33 24.56 0.1224 2.38153 0.41
38.1220 51.39 20.97 0.2040 2.35872 0.21
38.5043 17.20 5.61 0.1632 2.33618 0.07
39.1239 36.10 10.31 0.1428 2.30060 0.15
The dapoxetine base used in the present invention may be formed by methods known in the art such as those described in U.S.Patent nos. 5,135,947; 5,292,962; and PCT Publication No. 2008/035358 962 which are incorporated herein by reference only.
The dapoxetine base obtained by following the prior-art processes may be purified by treating a solution of dapoxetine in an ether solvent or aromatic hydrocarbon solvents with charcoal at a temperature in the range of 20°C to 60°C.
The examples of 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, petroleum ether or mixture(s) thereof.
The examples of aromatic hydrocarbon solvents may be selected from the group comprising of benzene, toluene, cresol or xylene.

The purified dapoxetine base (hereinafter refer as crystalline form E) may be isolated by concentrating the resulting solution of under reduced pressure at a temperature below 45 °C.
The purification of dapoxetine base in an ether solvent or aromatic hydrocarbon solvent may be carried out more than one time.
A solution of dapoxetine base in an alkyl acetate solvent may be formed by dissolving dapoxetine base in an alkyl acetate solvent at a temperature in the range of 20°C to 30°C.
The examples of alkyl acetate 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 solution of dapoxetine base in alkyl acetate solvent may be treated with solution of hydrochloric acid in an alkyl acetate solvent at a temperature in the range of 0°C to 30°C to get a solution of dapoxetine hydrochloride an alkyl acetate solvent.
The hydrochloric acid solution in an alkyl acetate solvent may contain hydrochloric acid in the range of 5% weight / weight to 15% weight / weight.
The crystalline form I of dapoxetine hydrochloride may be formed by stirring the solution of dapoxetine hydrochloride in an alkyl acetate solvent at a temperature in the range of -15°C to 20°C for a period of 30 minutes to 6 hours.
The crystalline form I of dapoxetine hydrochloride may be isolated by the steps of filtration, centrifugation, washing, drying or the combinations thereof.
The isolated crystalline form I of dapoxetine hydrochloride may be dried at a temperature in the range of 40°C to 150°C for a period of 2 hours to 8 hours under reduced pressure.

The crystalline form II of dapoxetine hydrochloride may be formed by stirring the solution of dapoxetine hydrochloride in an alkyl acetate solvent at a temperature in the range of 21 °C to 55°C for a period of 30 minutes to 6 hours.
The crystalline form II of dapoxetine hydrochloride may be isolated by the steps of filtration, centrifugation, washing, drying or the combinations thereof.
The isolated crystalline form II of dapoxetine hydrochloride may be dried at a temperature in the range of 40°C to 150°C for a period of 2 hours to 8 hours under reduced pressure.
A solution of crystalline dapoxetine hydrochloride in organic solvents may be prepared by dissolving crystalline dapoxetine hydrochloride in an organic solvent at a temperature in the rangeof 25°C to30°C.
Alternatively, such a solution may be obtained directly from a reaction in which dapoxetine hydrochloride is formed.
Examples of organic solvent may include ketones, alcohols, esters, nitriles, 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 dichloromethane, 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.
The solvent may be removed from the solution by a technique which includes, for example, spray drying and freeze drying.
In one aspect, dapoxetine hydrochloride amorphous form may be recovered from the solution using a spray drying technique. A Mini-Spray Dryer (Model: Buchi 190, Switzerland) can be used. The Buchi 190 Mini-Spray Dryer operates on the principle of nozzle spraying in a parallel flow, i.e., the sprayed product and the drying gas flow in the same direction. The drying gas can be air or inert, gases such as nitrogen, argon and carbon dioxide.
In another aspect, dapoxetine hydrochloride amorphous form may be recovered from the solution using a freeze drying technique. A freeze dryer (Model; Virtis Genesis SQ Freeze Dryer) can be used in this technique. The Virtis Genesis SQ Freeze Dryer operates on the principle of lyophilization, i.e., a process of stabilizing initially wet materials (aqueous solution or suspensions) by freezing them, then subliming the ice while simultaneously desorbing some of the bound moisture (primary drying). Following removal of the ice, desorption may be continued (secondary drying). This process may be carried out under vacuum.
The spray drying may be accomplished using a spray dryer which operates on the principle of nozzle spraying in a parallel flow, i.e., the sprayed product and the drying gas flow in the same direction. The drying gas can be air or one or more inert gases such as nitrogen, argon, and carbon dioxide. Moreover, the product obtained may be further or additionally dried to achieve

the desired moisture values. For example, the product may be further or additionally dried in a tray drier, dried under vacuum and/or in a Fluid Bed Dryer
The crystalline dapoxetine hydrochloride may be melted at a temperature in the range of 150°C to 180°C.
The dapoxetine hydrochloride amorphous form may be recovered by the steps of cooling and milling of melted dapoxetine hydrochloride. The milling of melted dapoxetine hydrochloride may be carried out in a clay mortar and pestle.
The cooling of melted dapoxetine hydrochloride may be carried out up to the temperature in the range of 20-30°C.
The dapoxetine hydrochloride amorphous form obtained by the present invention may be additionally dried at a temperature in the range of 40°C to 150°C for 2 hours to 8 hours.
The term "substantially pure dapoxetine hydrochloride" described herein referred to dapoxetine hydrochloride having more than 99% purity as determined by HPLC technique.
The pharmaceutical composition of dapoxetine hydrochloride comprising crystalline form I of dapoxetine hydrochloride and pharmaceutically acceptable excipients.
The pharmaceutical composition of dapoxetine hydrochloride comprising crystalline form II of dapoxetine hydrochloride and pharmaceutically acceptable excipients.
The pharmaceutical composition of dapoxetine hydrochloride comprising amorphous form of dapoxetine hydrochloride and pharmaceutically acceptable excipients.
BRIEF DESCRIPTION OF THE DRAWING:

Figure 1 illustrates a powder X-ray diffraction pattern of dapoxetine hydrochloride crystalline form I.
Figure 2 illustrates a powder X-ray diffraction pattern of dapoxetine hydrochloride crystalline form II.
Figure 3 illustrates a powder X-ray diffraction pattern of dapoxetine hydrochloride amorphous form.
Figure 4 illustrates a powder X-ray diffraction pattern of dapoxetine base crystalline form E.
XRD diffraction measurement was performed on X-Ray powder diffractometer Bruker D8
Advance powder diffractometer with the detector Lynxeye (Bruker). The analysis conditions
were as follows:
Scan range [°2-theta]: 2-39.98;
Scan mode: continuous;
Step size [°2-theta]: 0.0170°;
Scan step time[s]: 51.04 seconds;
Sample spin: 15 rpm;
Sample holder: glass;
Measurement Temperature [°C]: 25
Anode Material: Cu
K-AIpha [A]: 1.54060
Prior to analysis, the samples were gently ground by means of mortar and pestle in order to obtain a fine powder. The sample might be mixed with n-dodecane in order to avoid the environment contamination by airborne particles coming from the powder. The ground sample or its suspension with n-dodecane was adjusted into a cavity of the sample holder and the surface of the sample was smoothed by means of a cover glass.

EXAMLES:
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: Purification of dapoxetine base
Crude dapoxetine (50gm) was dissolved in diethyl ether (1000ml) at 25°C and resulting solution
was added charcoal (30gm) and stirred the for 1 hour at 25°C. The resulting solution was filtered,
washed with diethyl ether (50ml) and then concentrating resulting filtrate under reduced pressure
below 45°C to get title compound.
Yield: 42.5gm
Purity: 99.98% (By HPLC)
XRD: As depicted in Figure 4
Example 2: Preparation of crystalline form I of dapoxetine hydrochloride
Dapoxetine base obtained from example 1 (lOgm) was dissolved in ethyl acetate (100ml) at 25-30°C and then it was cooled to 5-10°C. The resulting solution was then added hydrochloric acid solution in ethyl acetate (30ml, 8% weight / weight) drop wise within 1 hour at 5-10°C and the resulting reaction mixture was stirred for 1 hour at 5-10°C. The resulting solids were filtered, washed with chilled ethyl acetate (10ml) and dried at 45-50°C for 4 hours to get title compound. Yield: ll.Ogm Purity: 99.98% (By HPLC) XRD: As depicted in Figure 1
Example 3: Preparation of crystalline form II of dapoxetine hydrochloride
Dapoxetine base obtained from example 1 (lOgm) was dissolved in ethyl acetate (100ml) at 25-30°C and resulting solution was added a solution of hydrochloric acid gas (30ml, 8% weight / weight) in ethyl acetate drop wise within 1 hour at 25-30°C and the resulting reaction mixture was stirred for 1 hour at 25-30°C. The resulting solids were filtered, washed with chilled ethyl acetate (10ml) and dried at 45-50°C for 4 hours to get title compound. Yield: ll.lgm

Purity: 99.95% (By HPLC) XRD: As depicted in Figure 2
Example 4: Preparation of amorphous form of dapoxetine hydrochloride.
Crystalline dapoxetine hydrochloride (lOgm) was placed in to an oven at 180°C for 45 minutes.
The melted dapoxetine hydrochloride was cooled to 25°C and then it was milled in a clay mortar
and pestle to get title compound.
Yield: 9.8 gm
Purity: 99.94% (By HPLC)
Example 5: Preparation of amorphous form of dapoxetine hydrochloride.
Crystalline dapoxetine hydrochloride (lOgm) was dissolved in isopropanol (60ml) at 25-30°C.
The clear solution was subjected to spray drying in a mini spray dryer at an inlet temperature of
60°C and an outlet temperature of 40°C with a feed rate of 15 ml/minute. Dapoxetine
hydrochloride in an amorphous form was thus isolated.
Yield: 9.5 gm
Purity: 99.97% (By HPLC)

WE CLAIM:
1. A compound which is a crystalline form I of dapoxetine hydrochloride having substantially the same X-ray diffraction pattern as depicted in Figure 1 and characterized by X-ray diffraction pattern having peaks at 6.1, 9.1, 9.4, 10.2, 10.6, 11.8, 12.2, 15.2, 17.0, 18.3, 19.4, 21.2, 21.5, 21.9, 22.7, 23.2, 23.6, 24.3, 24.6, 26.3, 28.2, 28.8, 30.3 ± 0.2 degrees two theta.
2. A process for preparing crystalline form I of dapoxetine hydrochloride comprising the steps of:
b. treating a solution of dapoxetine base obtained from step a, with solution of
hydrochloric acid in alkyl acetate solvent at a temperature up to 20°C and
c. isolating crystalline form I of dapoxetine hydrochloride.
3. The process according to claim nos. 2 wherein, solution of dapoxetine base in an alkyl acetate solvent is formed by dissolving dapoxetine base in an alkyl acetate solvent such as ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, tertiary butyl acetate, pentyl acetate or mixture(s) thereof at a temperature in the range of 20°C to 30°C and treating solution of dapoxetine base in an alkyl acetate solvent with solution of hydrochloric acid in an alkyl acetate solvent contains hydrochloric acid in the range of 5% weight / weight to 15% weight / weight at a temperature in the range of 0°C to 30°C to get a solution of dapoxetine hydrochloride an alkyl acetate solvent.
4. The process according to claim no. 2 wherein, crystalline form I of dapoxetine hydrochloride is formed by stirring the solution of dapoxetine hydrochloride in an alkyl acetate solvent at a temperature in the range of-15°C to 20CC for a period of 30 minutes to 6 hours and isolated by the steps of filtration, centrifugation, washing and drying at a temperature in the range of 40°C to 150°C for a period of 2 hours to 8 hours under reduced pressure.
5. A compound which is a crystalline form II of dapoxetine hydrochloride having substantially the same X-ray diffraction pattern as depicted in Figure 2 and characterized by X-ray diffraction pattern having peaks at 18.4, 20.2, 22.3, 23.3, 24.8, 26.1, 27.2, 28.5, 29.0, 30.7, 31.6, 32.5, 33.1, 34.7, 35.6, 38.3 + 0.2 degrees two theta.

6. A process for preparing crystalline form II of dapoxetine hydrochloride comprising the
steps of:
a. providing a solution of dapoxetine base in an alkyl acetate solvent,
b. treating a solution of dapoxetine base obtained from step a, with solution of
hydrochloric acid in alkyl acetate solvent at a temperature of above 20°C and
c. isolating crystalline form II of dapoxetine hydrochloride.
7. The process according to claim no. 6 wherein, crystalline form II of dapoxetine hydrochloride is formed by stirring the solution of dapoxetine hydrochloride in an alkyl acetate solvent at a temperature in the range of 21°C to 55°C for a period of 30 minutes to 6 hours and isolated by the steps of filtration, centrifugafion, washing and drying at a temperature in the range of 40°C to 150°C for a period of 2 hours to 8 hours under reduced pressure.
8. A compound which is an amorphous form of dapoxetine hydrochloride having substantially the same X-ray diffraction pattern as depicted in Figure 3.
9. A process for the preparation of dapoxetine hydrochloride amorphous form comprising the steps of:
a. providing a solution of crystalline dapoxetine hydrochloride in an organic solvent
and
b. recovering dapoxetine hydrochloride in the amorphous form from the solution
thereof by the removal of the solvent by spray-drying or freeze-drying technique.
10. A compound which is a crystalline form E of dapoxetine base having substantially the
same X-ray diffraction pattern as depicted in Figure 4 and characterized by X-ray
diffraction pattern having peaks at 10.9, 13.1, 17.4, 17.7, 18.6, 20.0, 21.7, 26.4, 28.1 ±
0.2 degrees two theta.