FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule l3)
TITLE OF THE INVENTION:
NOVEL POLYMORPHIC FORM W-1 OF OLANZAPINE AND PROCESS FOR THE PREPARATION THEREOF
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Limited, D4-MIDC Area, Chikalthana,
Aurangabad - 431 210 (M.S.) INDIA.
3. PREAMBLE TO THE DESCRIPTION
The present invention relates to novel polymorphic Form W-1 of olanzapine 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 W-1 of olanzapine and a process for the preparation thereof.
Olanzapine of the formula I is chemically known as 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno [2,3-b][1,5]benzodiazepine. Olanzapine is indicated in the treatment of psychotic conditions including schizophrenia, schizophrenia-form diseases, and acute mania.

U.S. Patent No. 5,229,382 disclosed olanzapine synthesis by condensation of thienobenzodiazepine(4-amino-2-methyl-10H-thieno-[2,3-b]-[1,5] benzodiazepine) and N-methylpiperazine in a mixture of toluene and dimethylsulfoxide, which are high boiling organic solvents.
U.S. Patent No. 6,906,062 disclosed Form I of olanzapine and process for the preparation thereof. U.S. Patent No. 5,736,541 discloses Form II of olanzapine having a specific X-ray diffraction pattern.
U.S. Patent No. 5,703,232 and European Patent No. 733,634 disclosed solvates of anhydrous olanzapine with methanol, ethanol and isopropanol.
U.S. Patent No. 6,348,458 disclosed Form III, IV and V of olanzapine. U.S. Patent No. 6,020,487 discloses dihydrate Forms B, D and E of olanzapine.


U.S. Patent No. 6,740,753 disclosed Form X of olanzapine and process for preparation thereof.
U.S. Patent Application No. 2005/153954 discloses Form VI of olanzapine and process for preparation thereof.
PCT Patent Application WO 2002/18390 discloses monohydrate-l and dihydrate-I of olanzapine.
PCT Patent Application WO 2004/113346 discloses amorphous form of olanzapine and process for the preparation thereof.
Different polymorphic forms of olanzapine and process for their preparation are also disclosed in U.S. Patent Application Nos. 2004/0198721; 2004/0048854; 2005/0239772; 2005/0272720; 2006/0040920; 2007/0066602; 2007/0021605; 2007/007284 and PCT Patent Application Nos. 2004/056833; 2006/006185; 2006/025065; 2006/027800; 2006/030300.
The present inventors have developed an olanzapine in a novel polymorphic form referred as polymorphic Form W-1 that is stable, consistently reproducible and useful to make pharmaceutical compositions.
In one of the aspect of the present invention there is provided a novel polymorphic Form W-1 of olanzapine.
In an embodiment, a polymorphic Form W-1 of olanzapine is characterized by having a characteristic XRD pattern as depicted in Figure I with the 2 theta values at 6.42, 8.82, 12.92, 17.76 and 19.46 ± 0.2°. Powder XRD of the samples was determined by Rigaku X-Ray diffractometer model no. 2200-v Japan.

In another aspect of the present invention there is provided Form W-1 of
olanzapine having moisture content of about 5.0%w/w or less.
In yet another aspect there is provided a pharmaceutical composition that
includes a therapeutically effective amount of polymorphic Form W-1 of
olanzapine and one or more pharmaceutically acceptable carriers, excipients or
diluents.
In yet another aspect there is provided a process for the preparation of polymorphic Form W-1 of olanzapine, wherein the said process comprises of,
a) heating olanzapine in ketone solvent,
b) isolating the olanzapine in novel polymorphic Form W-1 from the reaction mass thereof.
Olanzapine used as starting material can be prepared by the person skilled in the art through the teaching of U.S. Patent No. 5,229,382.
The process of invention involves stirring of olanzapine in ketone solvent such as acetone, methyl ethyl ketone, methyl isobutyl ketone and the like or mixtures thereof at reflux temperature. Reaction mass is cooled gradually to 30- 40 °C and to this reaction mass added ether such as diethyl ether, isopropyl ether, t-butyl methyl ether, dioxane, tetrahydrofuran and the like or mixtures thereof. The novel polymorphic Form W-1 is then isolated from the reaction mass thereof.
The invention is further illustrated by the following example which is provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the invention.

Example Preparation of polymorphic Form W-1 of olanzapine
Olanzapine (10 g) and methyl ethyl ketone (50 ml) were heated to reflux under stirring for 30 minutes. The clear solution was obtained. The reaction mixture was cooled gradually to 30-35 °C. To this reaction mass t-butyl methyl ether is added and reaction mass was stirred for three hours at room temperature. Solid product was filtered and dried at 60 °C. Yield: 6.25 g Purity: 99.77%

WE CLAIM:
1. Novel polymorphic Form W-1 of olanzapine.
2. Polymorphic Form W-1 of olanzapine having a characteristic XRD pattern as depicted in Figure I.
3. Olanzapine of claim 1, having characteristics 2 theta values at 6.42, 8.82, 12.92, 17.76 and 19.46 ±0.2°.
4. A process for the preparation of Form W-1 of olanzapine wherein the said process comprises of,

a) heating olanzapine in ketone solvent,
b) isolated the novel polymorphic Form W-1 of olanzapine from the reaction mass thereof.

5. The process of claim 4, wherein ketone solvent is methyl ethyl ketone.
6. The process of claim 4, wherein olanzapine in novel polymorphic Form W-1 is isolated by precipitating reaction mass from ether solvent.
7. The process of claim 6, wherein ether solvent is t-butyl methyl ether.
8. Olanzapine Form W-1 having moisture content of about 5.0% w/w or less.


9. A pharmaceutical composition comprising a polymorphic Form W-1 of olanzapine and one or more pharmaceutically acceptable carriers, excipients or diluents.

Abstract
The present invention provides a novel polymorphic Form W-1 of olanzapine and a process for the preparation thereof.