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 COMPOSITIONS OF ESZOPICLONE OR SALTS
THEREOF
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: D-4, M.I.D.C. Area, Chikalthana, Aurangabad - 431210,
(M.S.) INDIA.
3. PREAMBLE TO THE DESCRIPTION
The present invention provides a pharmaceutical composition comprising eszopiclone or salt thereof along with cyclodextrins or derivatives thereof and one or more pharmaceutically acceptable excipients.
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 comprising eszopiclone or salt thereof along with cyclodextrins or derivatives thereof and one or more pharmaceutically acceptable excipients.
Eszopiclone is a nonbenzodiazepine hypnotic agent that is a pyrrolopyrazine derivative of the cyclopyrrolone class. Its molecular weight is 388.81, and its empirical formula is C17H17CIN6O3. Eszopiclone has a single chiral center with an (S)configuration, and its structural formula is:

O
/ ^
VC-N N-ChL
S ^
US Patent No 6,319,926 provides a method for improving sleep quality or time comprising the step of administering an effective quantity of zopiclone, or a pharmaceutically acceptable salt thereof, in the form of its dextrorotatory isomer and essentially free of its levorotatory isomer.
US Patent No 6,444,673 describe a pharmaceutical composition comprising an effective amount of the dextrorotatory isomer, essentially free of the levorotatory isomer of zopiclone, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
US Patent No 6,864,257 provides method of inducing an effect selected from the group consisting of a hypnotic effect, a sedative effect and a tranquilizing effect, comprising administering to the human an effective quantity of zopiclone, or a
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pharmaceutically acceptable salt thereof, in the form of its dextrorotatory isomer and essentially free of its levorotatory isomer.
Eszopiclone poses problems of low solubility, leading to decreased dissolution of drug and hence low bioavailability.
It was noticed by the present inventors while working on the eszopiclone formulation that use of cyclodextrin results in increased solubility, significant increase in percent drug release of eszopiclone and hence improved bioavailability of eszopiclone.
One of the aspects of the present invention provides a pharmaceutical composition comprising eszopiclone or salt thereof along with cyclodextrins or derivatives thereof and one or more pharmaceutically acceptable excipients.
In another aspect of the present invention there is provided a pharmaceutical composition comprising eszopiclone or salt thereof along with cyclodextrins or derivatives thereof and one or more pharmaceutically acceptable excipients, wherein eszopiclone is present in admixture with cyclodextrins or derivatives thereof.
In yet another aspect of the present invention there is provided a pharmaceutical composition comprising eszopiclone or salt thereof along with cyclodextrins or derivatives thereof and one or more pharmaceutically acceptable excipients, wherein eszopiclone is present in the form of complex with cyclodextrins or derivatives thereof.
The pharmaceutical composition of the present invention can be present in the form of one or more of monolayered tablets, bilayered tablets, tablet in tablet, caplet, minitablet, capsules, tablet in capsule, granules in capsules, pellets, pellets in capsules, powder and other dosage forms suitable for oral administration.

Suitable cyclodextrin derivatives may be one or more of hydroxypropyl~p-cyclodextrin, (3-cyclodextrin, a-cyclodextrin, hydroxypropyl- a-cyclodextrin.
The pharmaceutical composition comprises of pharmaceutical^ acceptable excipients wherein excipients may include fillers, lubricants, disintegrants, and glidants.
Suitable filler may be one or more of, microcrystalline cellulose, mannitol, calcium phosphate, calcium sulfate, kaolin, dry starch, powdered sugar.
Suitable lubricant may be one or more of magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumarate, hydrogenated vegetable oil, glyceryl behenate.
Suitable glidant may be one or more of colloidal silicon dioxide, talc or cornstarch.
Suitable disintegrant may be one or more of starch, croscarmellose sodium, crospovidone, and sodium starch glycolate.
The pharmaceutical composition of the present invention can be prepared by mixing eszopiclone with cyclodextrin and other excipients, granulating the dry-mix, then wet mass is dried, resultant mass passed through mesh to get desired size of granules. The granules are then mixed with lubricant, disintegrant, glidant or a mixture thereof, and the mixture is finally compressed.
The complex of eszopiclone and cyclodextrin can be prepared by various processes including solvent evaporation, kneading, spray drying, colloidal milling, high speed mixing, trituration or simple mixing. The eszopiclone can be present in an amount relative to the cyclodextrin, such that a molar ratio between the
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eszopiclone and the cyclodextrin is from about 1:1 to 1:10. eszopiclone or salt thereof may be added to the formulation in the form of complex.
Exterior portion of cyclodextrin being hydrophiiic allows the cyclodextrin to form inclusion complexes with eszopiclone and which can then be dissolved in water.
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.
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Example-1 Table-1 Composition for Eszopiclone Tablets (1 mg)

S.No. Ingredients Qty/Tab (%w/w)
1 Eszopiclone cyclodextrin
complex eq. to 1 to 3 mg of
(With beta cyclodextrinActive
complex)
2 Microcrystalline Cellulose 5-40%
3 DCP Anhydrous 5-60%
4 Croscarmellose sodium 2-10%
5 Hypromellose 1-10%
6 Purified Water q.s
7 Lactose Monohydrate 2-60%
8 Dibasic Calcium Phosphate 5-40%
9 Croscarmellose sodium 2-10%
10 Colloidal Silicon Dioxide 0.25-2.5%
11 Magnesium Stearate 0.25-2%
Procedure:
Slurry of cyclodextrin is prepared by continuous stirring with water and to this eszopiclone is added. This slurry is then dried. The residual mass is passed through mesh to obtain a homogenous blend. Geometricaliy mixing of eszopiclone complex and DCP passed through mesh and mix with presifted microcrystalline cellulose, croscarmellose sodium and hypromellose dry mix the above blend in rapid mixer granulator then granulate with purified water, the obtained wet mass dried in fluidized bed granulator, passed through mesh to get granules of desired size. Siftings of dibasic calcium phosphate, lactose monohydrate, colloidal silicon dioxide and croscarmellose sodium through mesh and blended. Then granules are lubricated with magnesium stearate and final blend is compressed in to tablets using suitable tooling and optionally coating with aqueous dispersion of Opadry.
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Example-2 Table-2 Composition for Eszopiclone Tablets (1 mg)

S.No. Ingredients Qty/Tab <%w/w)
1 Eszopiclone cyclodextrin complex*(With hydroxy propyl beta cyclodextrin complex) eq. to 1 to 3 mg of Active
2 Microcrystalline Cellulose 5-40%
3 DCP Anhydrous 5-60%
4 Croscarmellose sodium 2-10%
5 Hypromellose 1-10%
6 Purified Water* qs
7 Lactose Monohydrate 2-60%
8 Dibasic Calcium Phosphate 5-40%
9 Croscarmellose sodium 2-10%
10 Colloidal Silicon Dioxide 0.25-2.5%
11 Magnesium Stearate 0.25-2%
Procedure:
The Inclusion complex is prepared by kneading the eszopiclone along with the cyclodextrin and purified water and subsequent drying to get the complex. Geometrically mixing of eszopiclone complex and DCP then passed through mesh and mix with presifted microcrystalline cellulose, croscarmellose sodium and hypromellose, dry mix the above blend in rapid mixer granulator then granulate with purified water, the obtained wet mass dried in fluidized bed granulator, passed through mesh to get granules of desired size. Sittings of dibasic calcium phosphate, lactose monohydrate, colloidal silicon dioxide and croscarmellose sodium through mesh and blended. Then granules are lubricated with magnesium stearate and final blend is compressed in to tablets using suitable tooling and optionally coating with aqueous dispersion of opadry.
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WE CLAIM:
1) A pharmaceutical composition comprising eszopiclone or salt thereof along with cyclodextrins or derivatives thereof and one or more pharmaceutical^ acceptable excipients.
2) A pharmaceutical composition comprising eszopiclone or salt thereof along with cyclodextrins or derivatives thereof and one or more pharmaceutically acceptable excipients, wherein eszopiclone is present in admixture with cyclodextrins or derivatives thereof.
3) A pharmaceutical composition comprising eszopiclone or salt thereof along with cyclodextrins or derivatives thereof and one or more pharmaceutically acceptable excipients, wherein eszopiclone is present in the form of complex with cyclodextrins or derivatives thereof.
4) The pharmaceutical composition of claim 1, 2 or 3 comprises one or more of monolayered tablets, bilayered tablets, tablet in tablet, caplet, minitablet, capsules, tablet in capsule, granules in capsules, pellets, pellets in capsules, powder and other dosage forms suitable for oral administration.
5) The pharmaceutical composition of claim 1, 2 or 3, wherein the cyclodextrins comprises one or more of hydroxypropyl-β-cyclodextrin, β-cyclodextrin, a-cyclodextrin, hydroxypropyl-a-cyclodextrin.
6) The pharmaceutical composition of claim 1, 2 or 3, wherein eszopiclone and cyclodextrin are present in a molar ratio of about 1:1 to 1:10.
7) The pharmaceutical composition of claim 1, 2, or 3, wherein pharmaceutically acceptable excipients comprises one or more of fillers, lubricants, disintegrants, and glidants.
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8) The pharmaceutical composition of claim 7, wherein fillers comprises one ,or more of microcrystalline cellulose, calcium phosphate, calcium sulfate, kaolin, dry starch and powdered sugar.
9) The pharmaceutical composition of claim 7, wherein lubricants comprises one or more of magnesium stearate, zinc stearate, cafcium stearate, stearic acid and sodium stearyl fumarate.
10) The pharmaceutical composition of claim 7, wherein disintegrants
comprises one or more of starch, croscarmellose sodium, crospovidone,
and sodium starch glycolate.
Dated this '" day of June, 2008 For Wockhardt Limited
(MandarKodgule) Authorized signatory
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