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: GALANTAMINE COMPOSITIONS
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, which comprises of galantamine or salt thereof along with sugar alcohols and other pharmaceutically acceptable excipients.
The following specification particularly describes the invention and the manner in which it is to be performed.
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4. Description
The present invention provides a pharmaceutical composition, which comprises of galantamine or salt thereof along with sugar alcohols and other pharmaceutically acceptable excipients.
Galantamine hydrobromide is a reversible, competitive acetylcholinesterase inhibitor. It has an empirical formula of C17H21NO3 »HBr and a molecular weight of 368.27. Its chemical name is (4aS, 6R, 8aS)-4a, 5,9,10,11, 12-hexahydro-3-methoxy-11-methyl-6H- benzofuro [3a, 3,2-ef][2] benzazepin-6-ol hydrobromide. Galantamine hydrobromide is a white to almost white powder and is sparingly soluble in water. It is indicated for the treatment of mild to moderate dementia of the Alzheimer's type. Its structural formula is:

US Patent No 4,663,318 (the '318 Patent) and European equivalent EP236684B1 discloses method of treating Alzheimer's disease using galantamine or an analogue or a pharmaceutically acceptable acid addition salt thereof.
US Patent No 6,099,863 (the '863 Patent) and European equivalent EP915701B1 discloses a fast-dissolving tablet for oral administration comprising galantamine hydrobromide (1:1) and a pharmaceutically acceptable carrier, characterized in that said carrier comprises a spray-dried mixture of lactose
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monohydrate and microcrystalline cellulose (75:25) as a diluent, and an insoluble or poorly soluble cross-linked polymer disintegrant.
US Patent No 6,358,527 (the '527 patent) also discloses a fast-dissolving tablet for oral administration comprising galantamine hydrobromide (1:1) and a pharmaceutically acceptable carrier, characterized in that said carrier comprises a spray-dried mixture of lactose monohydrate and microcrystalline cellulose (75:25) as a diluent, and an insoluble or poorly soluble cross-linked polymer disintegrant and compressing the mixture into tablets; and optionally film-coating the tablet.
US Application 20050142193 (the '193 Application) discloses galantamine formulations substantially free of microcrystalline cellulose, lactose, and/or starch.
US Application 2005191349 (the '349 Application) discloses fast dissolve galantamine formulation wherein the formulation exhibits a dissolution profile such that after 0.5-hour less than about 75% of the galantamine or galantamine salt is released.
PCT Patent Application WO2005/051489 discloses fast dissolving tablet of galantamine hydrobromide and a pharmaceutically acceptable carrier characterized in that the said carrier comprises a spray dried mixture of lactose monohydrate and microcrystalline cellulose (75:25) and water- soluble disintegrant or simple blend of lactose monohydrate and microcrystalline cellulose as a diluent and a water- soluble disintegrant or poorly soluble /insoluble disintegrant or anhydrous lactose as diluent and poorly soluble or insoluble cross-linked polymer and processes for preparation thereof.
The present inventors have now surprisingly found that when mannitol is used in formulation, it provides fast release of galantamine from tablet which is comparable to that obtained with fast dissolving tablets of galantamine. The
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present inventors noticed that without using costly special grade carriers like Cellactose (Coprocessed lactose and microcrystalline cellulose), which have been used in prior art reported fast dissolving tablets, fast release of galantamine can be achieved using simply mannitol, which is otherwise cheap and also the commonly used excipient in tablet formulations.
One of the aspects of the present invention provides a pharmaceutical composition, which comprises of galantamine or salt thereof along with sugar alcohols and other pharmaceutically acceptable excipients.
The pharmaceutical composition comprises of blending galantamine hydrobromide with other ingredients in a non-shear blender and the final blend may be formulated as tablet, capsule and pellets.
The pharmaceutical composition comprising galantamine or salt thereof wherein galantamine is present as galantamine hydrobromide.
The pharmaceutical composition comprises of sugar alcohols wherein sugar alcohols may be selected from a group comprising one or more of mannitol, lactitol, maltitol, sorbitol and the like.
The pharmaceutical composition comprises of pharmaceutically acceptable excipients wherein excipients may include fillers, lubricants, disintegrants, and glidants.
Suitable filler may be selected from a group comprising one or more of, microcrystalline cellulose, calcium phosphate, calcium sulfate, kaolin, dry starch, powdered sugar and the like.
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Suitable lubricants may be selected from a group comprising one or more of magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumarate and the like.
Suitable glidants may be one or more of colloidal silicon dioxide, talc or cornstarch and the like.
Suitable disintegrant may be one or more of starch, croscarmellose sodium, crosspovidone, sodium starch glycolate and the like.
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 galantamine hydrobromide tablets.

S.No Ingredients Quantity/tablet (mg)
1. Galantamine hydrobromide 5.126
2. Microcrystalline cellulose 21.83
3. Mannitol 32.74
4. Colloidal silicon dioxide 0.15
5. Talc 0.63
6. Crospovidone 1.89
7. Magnesium stearate 0.63
Total 63
8. Opadry coating 1.5
Total 64.5
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Procedure: Galantamine hydrobromide and microcrystalline cellulose are sifted and mixed in non-shear blender. Mannitol, colloidal silicon dioxide, talc, crospovidone are sifted and mixed with above blend in non-shear blender and lubricated with magnesium stearate. Final blend is compressed into tablets using suitable tooling. Tablets are coated with aqueous dispersion of opadry.
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WE CLAIM:
1. A pharmaceutical composition, which comprises of galantamine or salt thereof along with sugar alcohols and other pharmaceutically acceptable excipients.
2. A pharmaceutical composition according to claim 1, wherein galantamine or salts thereof is present as galantamine hydrobromide.
3. A pharmaceutical composition according to claim 1, wherein sugar alcohols are selected from a group comprising one or more of mannitol, lactitol, maltitol, sorbitol and the like.
4. A pharmaceutical composition according to claim 3, wherein sugar alcohol is mannitol.
5. A pharmaceutical composition of claim 1, wherein pharmaceutically acceptable excipients are fillers, lubricants, disintegrants, glidants
Dated this 31st day of August, 2006 For Wockhardt Limited
(Mandar Kodgule) Authorized Signatory
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