FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule13)
1. TITLE OF THE INVENTION:
PHARMACEUTICAL COMPOSITION OF QUETIAPINE OR SALT 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 provides a pharmaceutical composition of quetiapine or salt thereof wherein the composition comprises of quetiapine and an insoluble binder in admixture with pharmaceutically acceptable carrier.
The following specification particularly describes the invention and the manner in which it is to be performed.

4. DESCRIPTION
The present invention provides a pharmaceutical composition of quetiapine or salt thereof wherein the composition comprises of quetiapine and an insoluble binder in admixture with pharmaceutically acceptable carrier.
Quetiapine is a psychotropic agent belonging to a chemical class of dibenzothiazepine derivatives. Quetiapine is thought to exert its antipsychotic effects primarily via antagonism of the dopamine D2 receptor the serotonin 5HT2 receptor. It is commercially available as fumarate salt under the trade name of Seroquel®. It is chemically 2-[2-(4-dibenzo [b,f\ [1,4]thiazepin-11 -yl-1 -piperazinyl)ethoxy]-ethanol fumarate (2:1) (Formula I). Quetiapine is indicated for the treatment of acute manic episodes associated with bipolar disorder and schizophrenia.
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us Patent No. 4,879,288 discloses a dibenzothiazepine compound (Quetiapine), its preparation and use for antidopaminergic activity, for example as an antipsychotic or neuroleptic.
European Patents EP 240,228 and EP 282,236 disclose a dibenzothiazepine compound (Quetiapine), its preparation and use for antidopaminergic activity.
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US Patent No 5,948,437 disclose a sustained release formulation of quetiapine or a pharmaceutical^ acceptable salt thereof.
US Patent Application 2005158383 discloses dosage forms of quetiapine and its salts, particularly quetiapine hemifumarate including wax dosage forms, press-coat dosage forms, and sprinkle dosage forms. The invention also provides sustained release and pulsed release dosage forms of quetiapine and its salts.
US Patent No 6,599,897 and US Patent No 7,022,692 discloses granule formulation of quetiapine and pharmaceutically acceptable salt thereof using freely or very water-soluble binder in the granule formulation of quetiapine.
The use of freely water soluble or very water soluble binder in the formulation of quetiapine is well known in the prior art. The present inventors while working on the quetiapine formulation have now surprisingly found that when insoluble binder is used to prepare quetiapine formulation, it provides excellent binding, faster disintegration and results in a stable formulation. Moreover, the insoluble binder is compatible with quetiapine or salt thereof and other pharmaceutically acceptable carrier.
In one of the aspects of present invention there is provided a pharmaceutical composition comprising quetiapine or salt thereof and an insoluble binder in admixture with filler, disintegrant, lubricant and optionally other pharmaceutically acceptable carrier.
The pharmaceutical composition comprises of quetiapine or salt thereof as an active ingredient, wherein quetiapine can be present in the form of quetiapine fumarate in an immediate release form.
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The immediate release dosage form containing quetiapine or salt thereof includes solid oral dosage forms such as granules, sachets, tablets, mini tablets, capsules, powder or pellets.
Pharmaceutically acceptable carrier can be filler, lubricant, glidant, disintegrant and the like. The filler may be one or more of Avicel PH 101, Avicel PH 102, lactose, dibasic dicalcium phosphate dihydrate and dicalcium phosphate monohydrate. The lubricants may be one or more of talc, magnesium stearate, calcium stearate, polyethylene glycol, hydrogenated vegetable oils, stearic acid, sodium stearyl fumarate and sodium benzoate. The glidant may be one or both of colloidal silicon dioxide and talc or magnesium stearate. The disintegrant may be one or more of croscarmellose sodium, crospovidone and sodium starch glycolate.
The term insoluble binder in the present invention refers to the binder that does not dissolve in water but it may swell in water. The insoluble binder may be one or more of L-HPC (Low substituted hydroxypropyl cellulose), starch, ethyl cellulose, polyacrylate, Alginic acid, hydrogenated vegetable oil, magnesium aluminum silicate, sodium alginate and the like.
The pharmaceutical composition can be prepared by dry granulation, wet granulation or direct compression. Quetiapine or salt thereof is blended with an insoluble binder like L-HPC and one or more pharmaceutically acceptable carrier, which includes a mixture of lactose, microcrystalline cellulose, and dibasic calcium phosphate. The blend is granulated by dry or wet granulation. The granules are then blended with one or more pharmaceutically acceptable carrier that includes one or more of magnesium stearate, talc, L-HPC and sodium starch glycolate. This blend is compressed to form a tablet.
The compressed tablets may optionally be coated with a color coat that rapidly disintegrates or dissolves in water or the environment of use. The color coat may
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be a conventional sugar or polymeric film coating, which is applied in a coating pan or by conventional spraying techniques. Preferred materials for the color coat are commercially available under the OPADRY tradename. Generally, the color coat surrounding the core will comprise from about 1 to 5% preferably about 2 to 3% based on the total weight of the tablet.
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
Table 1: Composition of Quetiapine fumarate tablets.

No. Ingredients Qty/ tablet (mg)
1. Quetiapine Fumarate 345.00
2. Lactose monohydrate 100.00
3. Microcrystalline Cellulose 170.00
4. Dibasic Dicalcium phosphate dihydrate 90.00
5. L-HPC 15.00
6. Sodium Starch Glycolate 22.50
7. Magnesium Stearate 7.50
COATING
8. Opadry White 22.50 mg
TOTAL 772.50
Procedure: The Intragranular material comprising Quetiapine Fumarate, Lactose monohydrate, Microcrystalline Cellulose, Dibasic Dicalcium phosphate dihydrate and L-HPC were sifted individually and then mixed using a suitable blender. The
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blend was granulated with purified water, dried in fluidised bed and obtained granules were mixed with presifted extragranular material comprising Sodium Starch Glycolate and Magnesium Stearate. The obtained blend was compressed using a suitable tooling to form a tablet that is optionally coated with dispersion of opadry.
EXAMPLE 2
Table 2: Composition of Quetiapine fumarate tablets.

No. Ingredients Qty/ tablet (mg)
1. Quetiapine Fumarate 345.00
2. Lactose monohydrate 100.00
3. Microcrystalline Cellulose 170.00
4. Dibasic Dicalcium phosphate dihydrate 90.00
5. Starch 15.00
6. Sodium Starch Glycolate 22.50
7. Magnesium Stearate 7.50
COATING
8. Opadry White 22.50 mg
TOTAL 772.50
Procedure: The Intragranular material comprising Quetiapine Fumarate, Lactose monohydrate, Microcrystalline Cellulose, Dibasic Dicalcium phosphate dihydrate and starch were sifted individually and then mixed using a suitable blender. The blend was granulated with water, dried in fluidised water and obtained granules were mixed with presifted extragranular material comprising Sodium Starch Glycolate and Magnesium Stearate. The obtained blend was compressed using a suitable tooling to form a tablet that is optionally coated with dispersion of opadry.
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EXAMPLE 3
Table 3: Composition of Quetiapine fumarate tablets.

No. Ingredients Qty/ tablet (mg)
1. Quetiapine Fumarate 345.00
2. Lactose monohydrate 100.00
3. Microcrystalline Cellulose 177.50
4. Dibasic Dicalcium phosphate dihydrate 90.00
5. L-HPC 22.50
6. Sodium Starch Glycolate 7.50
7. Magnesium Stearate 7.50
COATING
8. Opadry White 22.50 mg
TOTAL 772.50
Procedure: The Intragranular material comprising Quetiapine Fumarate, Lactose monohydrate, Microcrystalline Cellulose, Dibasic Dicalcium phosphate dihydrate and part of L-HPC were sifted individually and then mixed using a suitable blender. The blend was granulated with purified water, dried in fluidised bed and obtained granules were mixed with presifted extragranular material comprising Sodium Starch Glycolate, part of L-HPC and Magnesium Stearate. The obtained blend was compressed using a suitable tooling to form a tablet that is optionally coated with dispersion of opadry.
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EXAMPLE 4
Table 4: Composition of Quetiapine fumarate tablets.

No. Ingredients Qty/ tablet (mg)
1. Quetiapine Fumarate 345.00
2. Lactose monohydrate 190.00
3. Microcrystalline Cellulose 162.50
4. L-HPC 15.00
6. Sodium Starch Glycolate 22.50
7. Talc 7.50
8. Magnesium Stearate 7.50
COATING
9. Opadry white 22.50 mg
TOTAL 772.50
Procedure: The Intragranular material comprising Quetiapine Fumarate, Lactose monohydrate, Microcrystalline Cellulose and L-HPC were sifted individually and then mixed using a suitable blender. The blend was granulated with purified water, dried in fluidised bed and obtained granules were mixed with presifted extragranular material comprising Sodium Starch Glycolate, talc and Magnesium Stearate. The obtained blend was compressed using a suitable tooling to form a tablet that is optionally coated with dispersion of opadry.
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WE CLAIM:
1. A pharmaceutical composition comprising quetiapine or salt thereof and an insoluble binder in admixture with filler, disintegrant, lubricant and optionally other pharmaceutically acceptable carrier.
2. A pharmaceutical composition of claim 1 wherein quetiapine is present in the form of quetiapine fumarate.
3. A pharmaceutical composition of claim 1 wherein insoluble binder comprises one or more of Low substituted hydroxypropyl cellulose (L-HPC), polyacrylate, Alginic acid, hydrogenated vegetable oil, magnesium aluminum silicate, sodium alginate, starch, ethyl cellulose and the like.
4. A pharmaceutical composition of claim 1 wherein insoluble binder is L-HPC or starch.
5. A pharmaceutical composition of claim 1 wherein pharmaceutically acceptable carrier is selected from a group comprising one or more of filler, disintegrant, lubricant, glidant and the like.
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6. A pharmaceutical composition of claim 1 is a solid oral dosage form wherein the dosage form is tablet, capsule, granule, powder, sachet or pellet.
7. A method of treating one or more mood disorders and bipolar disorder which comprises administering an effective amount of a pharmaceutical composition as defined in claim 1 to a patient in need thereof.

.TH

Dated this 28th day of June, 2006

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For Wockhardt Limited
(Yatendra Kumar) Authorized Signatory