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 COMPRISING TOPIRAMATE 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 comprising Topiramate or salt thereof in admixture with pharmaceutically acceptable excipients and a method for the preparation of said composition wherein the composition is prepared by wet granulation method.
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 comprising Topiramate or salt thereof in admixture with pharmaceutically acceptable excipients and a method for the preparation of said composition wherein the composition is prepared by wet granulation method.
Topiramate is a sulfamate-substituted monosaccharide. Chemically Topiramate is 2,3:4,5-Di-O-isopropylidene-b-D-fructopyranose sulfamate (Formula I). It is commercially available under the trade name of TOPAMAX®. Topiramate is indicated for the treatment of (a) Monotherapy Epilepsy (b) Adjunctive Therapy Epilepsy and (c) Migraine.

US Patent No. 4,513,006 discloses Sulfamate of formula that cover Topiramate.
US Application No. 2004258758 discloses a nanoparticulate topiramate composition along with a stabilizer & a method for the preparation of the same.
US Application No. 2004156901 and European Patent No. EP1066027 discloses a solid dosage formulation of topiramate and process for producing the solid dosage formulation.
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US Application No. 2005069587 discloses drug compositions comprising a pharmaceutical agent and a solubilizing agent. It also discloses drug compositions and dosage forms comprising topiramate and methods of treatment using said topiramate drug compositions and dosage forms.
US Application No. 20050175696 and PCT application WO2005065647 discloses a coating of granules with hydrophilic polymer & an osmotic drug delivery system.
US Application No. 2005175697 discloses drug compositions comprising topiramate and a solubilizing agent. Also discloses osmotic drug delivery system for topiramate.
PCT Application WO2006009403 discloses sustained-release topiramate preparation and a method for producing the same.
PCT Application WO2004054547 discloses a bi-or multi-phasic tablet comprising hygroscopic gum material.
US Application 20040053853 discloses a pharmaceutical composition comprising polymorph, solvate, hydrate, dehydrate, co-crystal, anhydrous, or amorphous form of topiramate and a pharmaceutical^ acceptable excipient or diluent.
While working on the Topiramate formulation, it has been surprisingly observed by the present inventors that scale up and scale down topiramate formulation can be easily prepared by wet granulation, dry granulation or direct compression method but when look a like formulation comprising 200 mg of Topiramate were prepared by dry granulation or direct compression, lead to processing problems during compression like sticking and capping. It was also found that look a like formulation can be easily prepared by wet granulation method and processing problems like sticking and capping were overcomed. The present inventors while
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working on Topiramate formulation have surprisingly found that the pharmaceutical composition comprising Topiramate or salt thereof can be prepared by wet granulation method and the said method provides
• Ease of manufacturing
• Reduced manufacturing time
• Overcome processing problems during compression like sticking and capping in look a like formulation
• A stable formulation
• A formulation that is comparable in all respects to conventional formulations of Topiramate.
The formulation of the present invention comprises 10 - 500 mg of Topiramate or salt thereof along as an active ingredient. The Pharmaceutical composition comprises in parts by weight from about 30% to about 60% topiramate, from about 10% to about 45% lactose monohydrate, from about 10% to about 40% microcrystalline cellulose, from about 0.5% to about 2.5 % Sodium starch glycolate, from about 1% to about 5% Povidone K-30 alongwith other pharmaceutically acceptable excipients.
One of the aspects of the present invention provides a pharmaceutical composition comprising 10 mg to 500 mg of Topiramate or salt thereof alongwith pharmaceutically acceptable excipients wherein the said composition is prepared by wet granulation method.
In yet another aspect of present invention there is provided a pharmaceutical composition comprising in parts by weight from about 30% to about 60% topiramate, from about 10% to about 45% lactose monohydrate, from about 10% to about 40% microcrystalline cellulose, from about 0.5% to about 2.5 % Sodium starch glycolate, from about 1% to about 5% Povidone K-30.
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The pharmaceutical composition comprises of Topiramate as an active ingredient. The scale-up and scale-down formulation of topiramate can be prepared by wet granulation, dry granulation, or direct compression method whereas look a like formulation can be prepared by wet granulation method. The wet granulation method involves the step of granulating Topiramate, Lactose monohydrate, microcrystalline cellulose and Sodium starch glycolate with a solution of Povidone K-30. The dried granules are lubricated and compressed to form tablet using suitable tooling.
The compressed tablets may be optionally coated with functional coat that rapidly disintegrates or dissolves in water or the environment of use. The coat may be a conventional sugar or polymeric film coating, which is applied in a coating pan or by conventional spraying techniques. Preferred materials for the coat are commercially available under the OPADRY tradename. Generally, the coat surrounding the core will comprise from about 1 to 5% preferably about 2 to 3% based on the total weight of the tablet.
The pharmaceutical composition can be granule, powder, sachet, capsule or compressed to form tablets. The pharmaceutical composition is meant for oral administration.
The pharmaceutical composition comprises of pharmaceutically acceptable excipients comprises of diluent, binder, disintegrant, lubricant, glidant and the like.
The suitable diluents may be one or more of microcrystalline cellulose, mannitol, starch, lactose monohydrate, pregelatinized starch, sodium starch glycolate and the like.
The suitable binder may be one or more of sugars, gums, low molecular weight hydroxypropyl methylcellulose, polyvinyl pyrrolidone, hydroxypropyl cellulose,
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Povidone K-30, potato starch, wheat starch and corn starch, gum tragacanth, acacia gum and gelatin, purified water and the like.
The suitable disintegrant may be one or more of microcrystalline cellulose, croscarmellose sodium, crospovidone, sodium starch glycolate and the like.
The suitable lubricants may be selected from a group comprising one or more of mineral oils, vegetable oils and glyceryl esters of fatty acids wherein mineral oils, vegetable oils and glyceryl esters of fatty acids comprises hydrogenated vegetable oil, hydrogenated castor oil, light mineral oil, glycerol monostearate, glycerol monobehenate, glyceryl behenate, glyceryl palmitostearate and the like.
The suitable glidant may be one or more of colloidal silicon dioxide, talc or 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.
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EXAMPLES 1 - 3
Table 1: Composition of Topiramate tablets (25 mg, 100 mg and 200 mg)

No Ingredients Example 1Qty/tab(mg) Example 2Qty/tab(mg) Example 3Qty/tab(mg)
1 Topiramate 25 100 200
2 Lactose monohydrate 30 120 40
3 Microcrystalline cellulose 19 76 76
4 Sodium starch glycolate 1 4 4
5 Povidone K-30 2.5 10 10
6 Purified Water q.s. q.s. q.s.
7 Sodium starch glycolate 1 4 4
8 Colloidal silicon dioxide 0.5 2 2
9 Magnesium Stearate 1 4 4
Core Tablet weight 80 320 340
10 OpadryYS-1 -7003 White 2 — ~
11 Opadry Light Yellow — — —
12 Opadry Yellow — 8 ~
13 Opadry Salmon — — 8.5
Coated Tablet weight 82.0 328.0 348.5
Procedure: The pharmaceutical analgesic compositions mentioned in examples 1 to 3 is prepared by sifting individually and then blending Topiramate, Lactose monohydrate, Microcrystalline cellulose and Sodium starch glycolate followed by granulating the blend with solution of Povidone K-30 in Purified Water. The obtained granules are mixed with Sodium starch glycolate and Colloidal silicon dioxide, and then lubricated with magnesium stearate. The lubricated granules are compressed to form a tablet using suitable tooling. The obtained tablet is optionally coated with dispersion of Opadry.
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WE CLAIM:
1. A pharmaceutical composition comprising 10 mg to 500 mg of Topiramate or salt thereof alongwith pharmaceutically acceptable excipients wherein the said composition is prepared by wet granulation method.
2. A pharmaceutical composition comprising in parts by weight from about 30% to about 60% topiramate, from about 10% to about 45% lactose monohydrate, from about 10% to about 40% microcrystalline cellulose, from about 0.5% to about 2.5 % Sodium starch glycolate, from about 1% to about 5% Povidone K-30.
3. A pharmaceutical composition as per claim 1, wherein pharmaceutically acceptable excipients is selected from a group comprising of one or more of diluent, filler, binder, disintegrant, lubricant, glidant.
4. A pharmaceutical composition as per claim 1 and 2, wherein the said composition is powder, granule, sachet, capsule, tablet
5. A pharmaceutical composition as per claim 1 and 2, wherein the said composition is meant for oral administration

oated this 31st day of August, 2006 For Wockhardt Limited
(Mandat)Kodgule)
Authorized Signatory
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