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 FORM OF VENLAFAXINE HYDROCHLORIDE AND PROCESS FOR THE PREPARATION THEREOF
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Towers, Bandra-Kurla Complex, Bandra
(East), Mumbai-400 051.
3. PREAMBLE TO THE DESCRIPTION
The present invention relates to novel polymorphic form of venlafaxine hydrochloride and a process for the preparation thereof.
The following specification particularly describes the invention and the manner in which it is to be performed.

4. DESCRIPTION
The present invention provides a novel polymorphic form of venlafaxine hydrochloride and a process for the preparation thereof.
Venlafaxine hydrochloride of the formula I is chemically known as (±)-1-[a-[(dimethylamino) methyl]-p-methoxybenzyl] cyclohexanol. Venlafaxine is indicated in the treatment of major depressive disorder.

venlafaxine hydrochloride FORMULA I
U.S. Patent number 4,535,186 disclosed a venlafaxine hydrochloride and its process for the preparation which involves reduction of 1-[cyano-(4-methoxyphenyl) methyl] cyclohexanol to corresponding 1-(2-amino-(4-methoxyphenyl) ethyl] cyclohexanol followed by converting it to venlafaxine.
Other methods u< preparing venlafaxine or its pharmaceutically acceptable salts are disclosed in U.S. Patent Nos. 5,043,466; 6,506,941; 6,620,960; 6,756,502; 7,141,697 and PCT Patent application Nos. WO 05/587796 and WO 06/35457
U.S. Patent No. 6,906,087 and U.S. Patent No. 7,045,661 discloses different polymorphic forms A, B, C and D of venlafaxine hydrochloride and processes for the preparation thereof.
U.S. Patent No^ 6,924,393 and U.S. Application US 2004/220278 discloses the processes for producing crystalline venlafaxine hydrochloride forms I, II, III and IV.
2

U.S. Patent No. 7,030,164 and U.S. Application 2006/074131 discloses anhydrous venlafaxine hydrochloride.
Different polymorphic forms of venlafaxine hydrochloride and process for their preparation are also disclosed in PCT patent application WO 2002/046140; WO 2003/042161; WO 2003/050074 and WO 2005/058796.
The present inventors have developed a venlafaxine hydrochloride in a novel polymorphic form referred as polymorphic form W, which is stable, consistently reproducible and useful to make pharmaceutical compositions. It was surprisingly found that in when venlafaxine hydrochloride was treated with water optionally in presence of class-Ill solvent, it is converted in a novel polymorphic form.
In one of the aspect of the present invention there is provided a novel polymorphic form W of venlafaxine hydrochloride having a characteristic XRD pattern as depicted in Figure I with the 2 theta values at 7.32, 12.60, 14.78, 16.22, 18.82, 20.26, 21.10 ± 0.2° 26.
In another aspect of the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of the venlafaxine hydrochloride polymorphic form W and one or more pharmaceutical acceptable excipient. The composition consisting polymorphic form W of venlafaxine hydrochloride is used in need of the patient for the treatment of major depressive disorder.
In another aspect of the invention the process of preparation of Venlafaxine hydrochloride polymorphic form W, which includes admixing water with venlafaxine hydrochloride wherein the mole ratio of venlafaxine hydrochloride and water is 1:0J5 to 1:1.5.
In another aspect of the invention the process of preparation of Venlafaxine hydrochloride polymorphic form W, which includes admixing water with
3

ventafaxine hyarocnloride in presence of class III solvents, wherein the venlafaxine hydrochloride and water mole ratio is 1:0.75 to 1:1.5.
Venlafaxine hydrochloride used as starting material can be prepared by the person skilled in the art through the teaching of US Patent No. 4,535,186. Venlafaxine hydrochloride obtained thereof was stirred with water at temperature at 35°C or less for 1-4 hours to get polymorphic form W optionally in presence of class III solvents such as acetone, isopropanol and the like. The term class III solvent has its ordinary meaning as defined in ICH harmonized tripartite guideline Class 3, Table 3, the less toxic solvents. Preferably the solvent is selected, in which Venlafaxine hydrochloride is practically insoluble. The term practically insoluble has its ordinary meanings as defined in United States Pharmacopoeia 2002. The water and venlafaxine hydrochloride mole ratio is 1:0.75 to 1:1.5.
Powder XRD of the samples was determined by Rigaku X-Ray diffractometer model ho. 2200-v Japan.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Example 1: Preparation of Polymorph "W" of Venlafaxine Hydrochloride
About 0.125 ml of water was added to 3.0 gm of venlafaxine hydrochloride. The obtained mass was stirred for three hours at room temperature. The resulting novel polymorph "W" of venlafaxine hydrochloride was isolated.
Yield: 2.85 gm.
4

Example 2: Preparation of Polymorph "W" of Venlafaxine Hydrochloride
About 0.25 ml of water was added to 3.0 gm of venlafaxine hydrochloride. The obtained mass was stirred for one hour at room temperature. The resulting novel polymorph "W" of venlafaxine hydrochloride was isolated. Yield: 2.80 gm.
Example 3: Preparation of Polymorph "W" of Venlafaxine Hydrochloride
3.0 gm of venlafaxine hydrochloride was suspended in 20 ml ethyl acetate. To the suspension 0.25 ml of water was added and mass was stirred for two hour at room temperature. The resulting novel polymorph "W" of venlafaxine hydrochloride was isolated from the reaction mass thereof. Yield: 2.9 gm.
5

WE CLAIM:
1. Novel polymorphic form "W" of Venlafaxine hydrochloride.
2. Venlafaxine hydrochloride of claim 1 having characteristics 2 theta values at 7.32, 12.60, 1478,16.22, 18.82, 20.26, 21.10 ± 0.2° 26.
3. A process of preparation of Venlafaxine hydrochloride polymorphic form W, which includes admixing water with venlafaxine hydrochloride. Wherein the mole ratio of venlafaxine hydrochloride and water is 1:0.75 to 1:1.5.
4. A process of preparation of Venlafaxine hydrochloride polymorphic form "W", which includes admixing water with venlafaxine hydrochloride in presence of class-Ill solvents, wherein the mole ratio of venlafaxine hydrochloride and water is 1:0.75 to 1:1.5.
5. A process of claim 3 & 4 where in admixing of water carried out at 20-25°C.
6. A process of claim 4 wherein water mixing is performed in presence of class III solvent in which venlafaxine is practically in soluble.
7. A process according to claim 6 wherein solvent is ethyl acetate.
6

8. A pharmaceutical composition comprising a therapeutically effective amount of Venlafaxine hydrochloride polymorphic form "W", and one or more pharmaceutically acceptable carriers, excipient or diluents.
Dated this 30th day of March, 2007 For Wockhardt Limited