DESC:FORM 2

THE PATENTS ACT 1970
(39 of 1970)
&
THE PATENTS RULE 2003

COMPLETE SPECIFICATION
(Section 10)

“EXTENDED RELEASE PHARMACEUTICAL COMPOSITIONS COMPRISING TOPIRAMATE”
Glenmark Pharmaceutical Limited
an Indian Company, registered under the Indian company’s Act 1957
having office at
Glenmark Pharmaceuticals Limited
B/2, Mahalaxmi Chambers,
22, Bhulabhai Desai Road,
Mumbai, 400026.
THE FOLLOWING SPECIFICATION DESCRIBES THE INVENTION
FIELD OF THE INVENTION
The present invention relates to extended release pharmaceutical compositions of Topiramate or a salt thereof. The invention also relates to processes for the preparation of such compositions and use thereof for treatment of seizures.

BACKGROUND OF THE INVENTION:
Topiramate is a well-known anti-convulsive agent chemically, it is 2,3:4,5-Di-O-isopropylidene-ß-D-fructopyranose sulfamate and has the following structural formula:

Topiramate is available as immediate release and extended release dosage forms in USA. Immediate release products are marketed by several companies in USA while extended release products are currently available as TROKENDI XR™ and QUDEXY XR™. Both of these products are once daily dosage form which provides prolonged drug release. TROKENDI XR™ capsules are administered intact, while QUDEXY XR™ can be administered intact as well as can be sprinkled on a spoonful of soft food.
PCT Appl. No. WO 2008061226 is directed to sustained-release compositions of topiramate comprising a sustained release component and an immediate component. Pharmaceutical compositions of this application are suitable for once a day administration.
PCT Appl. No. WO 2014143380 is directed to extended-release topiramate capsule that includes a capsule shell containing a single population of coated particles; wherein each coated particle includes a core and a coating thereon; wherein each particle core includes a homogeneous mixture comprising topiramate throughout its core; and wherein the coating includes one or more release controlling agent(s).
Extended release compositions are having advantage over conventional immediate release dosage forms. Extended release compositions reduces frequency of intakes and provide better patient compliance, they provide uniform drug release over prolonged time and reduces certain side effects. These types of compositions are generally preferred in patients suffering from seizure since patient need not to remember about repeated dose intake. Once a day administration of the dosage form is highly recommended for such patients, hence, there still remains a need of a pharmaceutical composition of topiramate which provides drug release for extended duration.
SUMMARY OF THE INVENTION:
In one general embodiment, the present invention provides an extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate.
In another embodiment, the present invention provides an extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate, wherein the two types of pellet populations can be either filled into capsules or compressed into tablet dosage forms.
In another embodiment, the present invention provides an extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate, wherein the first and the second pellet populations are filled into the capsules in 10:90 to 90:10 ratios.
In another embodiment, the present invention provides an extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate, wherein the first and the second pellet populations are filled into the capsules in 50:50 ratios.
In one more embodiment, the present invention provides an extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate, wherein the two types of pellet populations are having different compositions.
In another embodiment, the present invention provides an extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate, wherein the pharmaceutical composition exhibits a dissolution profile such that not more than 85% of drug is released after four hours when measured in TRIS buffer of pH 7.2 in basket apparatus having 100 rpm rotation.
In another embodiment, the present invention provides a stable extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate, wherein the two types of pellet populations are having different compositions.
In another embodiment, the present invention provides a stable extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate, wherein one pellet population comprising topiramate, 1-10 % by weight of ethyl cellulose and other pharmaceutically acceptable excipients, while other pellet population comprises topiramate, 5-15 % by weight of ethyl cellulose, talc and other pharmaceutically acceptable excipients.
In yet another embodiment, the present invention provides an extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate, wherein the two types of pellet populations are prepared separately and are either filled into capsules or compressed into tablet dosage forms.
In another embodiment, the present invention provides an extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate, wherein the two types of pellet populations are prepared separately employing a process that involves the steps of preparing the first pellet population by granulating topiramate with other excipients and coating them with a solution comprising controlled release polymers; preparing the second pellet population by granulating topiramate with other excipients and coating them with solution comprising controlled release polymers and other excipients and then filling the first and second type of pellet population in the capsule.
In one more embodiment, the present invention provides an extended release pharmaceutical composition of topiramate or a salt thereof comprising two types of pellet populations of topiramate, for treatment of seizures.

DETAILED DESCRIPTION OF THE INVENTION:
The present invention provides extended release pharmaceutical compositions of topiramate or a salt thereof, wherein the composition comprising two types of pellet populations.
The pharmaceutical compositions of the present invention are suitable for administration as solid oral dosage forms namely tablets or capsules and are suitable for once daily administration.
The pharmaceutical composition of the present invention comprises two types of pellet populations which have different compositions and are prepared separately and either filled in capsules or compressed into tablet dosage form.
As used herein, the term `topiramate` is used in broad sense to include not only the topiramate per se but also its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs and pharmaceutically acceptable prodrugs thereof, and also its various crystalline and amorphous forms.
As used herein, the term ‘two types of pellet populations’ relates to two types of pellets or beads which have different compositions and are manufactured separately. The two pellet populations also differ significantly in terms of in-vitro dissolution profile. One pellet population releases less than 50% of topiramate in two hours while other population releases more than 50 % of topiramate in two hours.
As used herein, the term ‘stable pharmaceutical composition’ relates to the pharmaceutical composition that retains at least 90% of initial drug content after storage at 40 °C and 75 % relative humidity for at least six months. Total impurity content of the stable pharmaceutical composition is less than 5% after storage at 40 °C and 75 % relative humidity for at least six months.
The two types of pellet composition as per the invention comprise topiramate, controlled release polymers and pharmaceutically acceptable excipients.

Suitable controlled release polymers include, but are not limited to, hydrophilic or hydrophobic materials or combinations thereof.
Suitable hydrophilic materials may include one or more of cellulose derivatives, polysaccharides, a polyacrylate, polyvinyl alcohol or polyvinyl pyrrolidone, carbopols, polyethylene oxides, magnesium aluminum silicate, modified starch derivatives or a derivative of such hydrophilic polymers or combinations thereof.

Suitable cellulose derivatives may include one or more of methylcellulose, ethyl cellulose, hydroxymethyl cellulose, different viscosity grades of hydroxypropyl methylcellulose, hydroxy propyl cellulose, hydroxyethylcellulose, carboxymethyl cellulose or a combination thereof.

The polysaccharides suitable for the purposes of the present invention may include one or more of gums both natural and modified (semi-synthetic) like alginates, Karaya, Guar, Locust bean, xanthan gum, gellan gum, welan gum, rhamsan gum and dextran.

Suitable hydrophobic material may include one or more of waxes, ethylcellulose, copolymer of acrylic acid and methacrylic acid esters, polyethylene, polyamide, polyvinyl acetate, glycerol monostearate, stearylalcohol, glyceryl behenate or mixtures thereof.

Suitable wax material may include one or more of an amorphous wax, an anionic wax, an anionic emulsifying wax, a bleached wax, a carnauba wax, a cetyl esters wax, a beeswax, hydrogenated castor oil, hydrogenated vegetable oil, a cationic emulsifying wax, a cetrimide emulsifying wax, an emulsifying wax, glyceryl behenate, a microcrystalline wax, a nonionic wax, a nonionic emulsifying wax, a paraffin, a petroleum wax, a spermaceti wax, a white wax, a yellow wax, and combinations comprising one or more of the foregoing waxes. These and other suitable waxes are known to those having skill in the art.

Other pharmaceutically acceptable excipients for use in the pharmaceutical composition of present invention may include one or more diluents, fillers/bulking agents, binders, disintegrant, lubricants, glidants, sweeteners/taste masking agents, colorants and flavors.
Suitable diluents/fillers or bulking agents include, but are not limited to, microcrystalline cellulose, di- or tri-basic calcium phosphate, crystalline cellulose, powdered cellulose, calcium carbonate, calcium sulphate, magnesium silicate, magnesium trisilicate, magnesium aluminium metasilicate (Neusilin), kaolin, starch, starch derivatives, magnesium carbonate, magnesium oxide and co-processed insoluble excipients.

Suitable binders may include polyvinylpyrrolidone, lactose, starches, modified starches, sugars, gum acacia, gum tragacanth, guar gum, pectin, wax binders, microcrystalline cellulose, methylcellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, copolyvidone, gelatin and sodium alginate, preferably polyvinylpyrrolidone.
Suitable disintegrants include, but are not limited to, Veegum (highly refined isomorphous silicate), crospovidone, cellulose, kaolin, crosslinked carboxy methyl cellulose (e.g., AcDiSol), microcrystalline cellulose (e.g., Avicel PH101 & PH102), crosslinked polyvinyl pyrrolidone (e.g., Kollidon CL), and mixtures thereof. Preferred disintegrants among these disintegrants include crosslinked carboxy methyl cellulose (e.g., AcDiSol), microcrystalline cellulose (e.g., Avicel PH101 & PH102), crosslinked polyvinyl pyrrolidone (e.g., Kollidon CL), and mixtures thereof.
Suitable plasticizers include, but are not limited to, castor oil, diacetylated monoglycerides, dibutyl sebacate, diethyl phthalate, glycerin, polyethylene glycol, propylene glycol, triacetin, and triethyl citrate.
Suitable lubricants and glidants include, but are not limited to, stearic acid and its derivatives or esters like sodium stearate, magnesium stearate and calcium stearate and the corresponding esters such as sodium stearyl fumarate; talc and colloidal silicon dioxide.

Suitable colorants include, but are not limited to non-water soluble lake pigments, aluminium lake red neutral pigments, yellow ferric oxide, red ferric oxide, black iron oxide and the like.

The extended release pharmaceutical composition of the present invention comprises two types of pellet populations of topiramate, wherein the two types of pellet populations are having different composition and are prepared separately employing a process that involves the steps of preparing the first pellet population using topiramate, controlled release polymers and pharmaceutically acceptable excipient; preparing the second pellet population using topiramate, controlled release polymers and pharmaceutically acceptable excipient and filling the first and second type of pellet population in capsule.
Throughout this specification it is to be understood that the words "comprise" and "include" and variations such as "comprises", "comprising", "includes", "including" are to be interpreted inclusively, unless the context requires otherwise. That is, the use of these words may imply the inclusion of an element or elements not specifically recited.
The invention is further illustrated by the following examples which are provided to be exemplary of the invention and do not limit the scope of the invention. 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
A. PREPARATION OF FIRST PELLET POPULATION
TABLE 1: Pellet Set 1
Sr. No. Ingredients Quantity (%w/w)
Core pellet
1. Topiramate 25-75
2. Microcrystalline cellulose 15-50
3. Hydroxypropyl methyl cellulose 1-10
4. Water q.s.
Functional coating
5. Ethyl cellulose 1-10
6. Hydroxypropyl methyl cellulose 0.5-5
7. Polyethylene glycol 1-5
8. Absolute alcohol q.s.
9. Purified water q.s.
TOTAL WEIGHT 100

PROCEDURE:
i. Topiramate, microcrystalline cellulose and hydroxypropyl cellulose are sifted through suitable mesh and mix together to prepare dry mix.
ii. Mixture is granulated with water and wet mass is extruded through screen to obtain pellets.
iii. The pellets obtained are dried.
iv. Ethyl cellulose is dissolved in Ethanol/water to obtain clear solution.
v. To this solution polyethylene glycol is added to obtain coating solution
vi. The core pellets of step (iii) are taken in Fluid bed processor and are coated with the functional coating solution of step (v) till desired coating weight gain is achieved.

B. PREPARATION OF SECOND PELLET POPULATION
TABLE 2: Pellet Set 2
Sr. No. Ingredients Quantity (%w/w)
Core pellet
1. Topiramate 25-75
2. Microcrystalline cellulose 15-50
3. Hydroxypropyl methyl cellulose 1-10
4. Water q.s.
Functional coating
5. Ethyl cellulose 5-15
6. Hydroxypropyl methyl cellulose 1-5
7. Polyethylene glycol 1-5
8. Talc Micronized 0.01-5
9. Aluminium lake red 0.01-5
10. Absolute alcohol q.s.
11. Purified water q.s.
TOTAL WEIGHT 100

PROCEDURE:
i. Topiramate, microcrystalline cellulose and hydroxypropyl cellulose are shifted through suitable mesh and mix together to prepare dry mix.
ii. Mixture is granulated with water and wet mass is extruded through screen to obtain spheres.
iii. The pellets obtained are dried.
iv. Ethyl cellulose is dissolved in Ethanol/water to obtain clear solution.
v. To this solution polyethylene glycol, Aluminium Lake red and Talc are added to obtain the coating solution.
vi. The core pellets of step (iii) are taken in Fluid bed processor and are coated with the functional coating solution of step (v) till desired coating weight gain is achieved.

C. PREPARATION OF FINAL COMPOSITION
PROCEDURE:
i. The coated pellets of first population and second populations are mixed together in required amount.
ii. The mixed pellet populations are lubricated with talc.
iii. The lubricated coated pellet populations comprising the two types of pellet population are filled in capsules to obtain the final dosage form.

EXAMPLE 2
A. PREPARATION OF CORE PELLET
Core pellets comprising Topiramate are prepared as below:
Sr. No. Ingredients Quantity (%w/w)
1. Topiramate 45-55
2. Microcrystalline cellulose 30-40
3. Hydroxypropyl methyl cellulose 1-10
4. Water q.s.

The core pellets are divided into two portions which form the first pellet population and second pellet population.
B. PREPARATION OF COATING SOLUTION
Two different coating solutions were prepared to coat the two pellet populations prepared in step A. The coating solutions were prepared as below:
B.1 Preparation of first coating solution
Sr. No. Ingredients Quantity (%w/w)
1. Ethocel 10 cps 1-10
2. HPMC E5 0.1-3
3. PEG 6000 0.1-3
4. Absolute alcohol qs
5. Purified water qs

B.2 Preparation of second coating solution
Sr. No. Ingredients Quantity (%w/w)
1. Ethocel 10 cps 1-10
2. HPMC E5 0.1-3
3. PEG 6000 0.1-3
4. Talc micronized 0.01-1
5. Al Lake red 0.01-0.1
6. Absolute alcohol qs
7. Purified water qs

C. COATING OF CORE PELLETS
(i) The first pellets are coated with a first coating solution to achieve a weight gain of 8% based on core pellet weight.
Ingredients (%w/w)
Core Composition
Topiramate 45-55
Microcrystalline cellulose 30-40
Hydroxypropyl methyl cellulose 1-10
Purified water qs
Functional Coating 8%
Ethocel 10 cps 1-10
HPMC E5 0.1-3
PEG 6000 0.1-3
Absolute alcohol qs
Purified water qs

(ii) The second pellets are coated with the second coating solution to achieve a weight gain of 12% based on core pellet weight.
Ingredients (%w/w)
Core Composition
Topiramate 45-55
Microcrystalline cellulose 30-40
Hydroxypropyl methyl cellulose 1-10
Purified water qs
Functional Coating 12%
Ethocel 10 cps 1-10
HPMC E5 0.1-3
PEG 6000 0.1-3
Talc 0.01-1
Al lake red 0.01-0.1
Absolute alcohol qs
Purified water qs

D. LUBRICATION
The first and second coated pellets are separately lubricated with talc.
E. MIXING & FILLING OF TWO PELLET POPULATION IN A CAPSULE
The first and second lubricated pellets are then mixed in a 1: 1 weight ratio and are filled into a capsule
Final composition
Sr. No. Ingredients Quantity (%w/w)
Composition of core pellet
1. Topiramate 45-55
2. Microcrystalline cellulose 30-40
3. Hydroxypropyl methyl cellulose 1-10
4. Water q.s.
Composition of Functional Coated Pellet
5. Ethocel 10 cps 1-10
6. HPMC E5 0.1-3
7. PEG 6000 0.1-3
8. Talc 0.01-1
9. Al Lake red 0.01-0.1
10. Absolute alcohol qs
11. Purified water qs
Lubrication
12. Talc 0.01-1

CLAIMS:

1. An extended release composition comprising two populations of coated pellets of topiramate in a ratio of about 10: 90 to about 90:10; wherein said two population of coated pellets comprises a core and an extended release coating and wherein the two population of coated pellets differ in their composition and process of making.
2. The composition of claim 2 wherein the ratio of the two populations of extended release pellets of topiramate is about 50:50
3. An extended release composition of claim 1 wherein the two populations of coated pellets comprises the first pellet population and a second pellet population wherein:
(a) the first coated pellet population comprises
(i) a core comprising about 25%-75% w/w topiramate, about 15%-50%
w/w of a filler, about 1%-10% w/w of a binder, about 1%-10% w/w of a
disintegrant.
(ii) an extended release coating comprising about 1%-10% w/w of a
controlled release polymer, about 0.1%-5% w/w of a plasticizer.
(b) the second coated pellet population comprises
(i) a core comprising about 25%-75% w/w topiramate, about 15%-50%
w/w of a filler, about 1%-10% w/w of a binder, about 1%-10% w/w of a
disintegrant.
(ii) an extended release coating comprising about 5%-15% w/w of a
controlled release polymer, about 0.1%-5% w/w of a plasticizer, about
0.01%-1% w/w of a glidant, and about 0.01-1% w/w of a colorant.
4. The composition according to claim 3 wherein the filler comprises microcrystalline cellulose, di- or tri-basic calcium phosphate, crystalline cellulose, powdered cellulose, calcium carbonate, calcium sulphate, magnesium silicate, magnesium trisilicate, magnesium aluminium metasilicate, kaolin, starch, starch derivatives, magnesium carbonate, magnesium oxide and co-processed insoluble excipients
5. The composition according to claim 3 wherein the binder comprises polyvinylpyrrolidone, lactose, starches, modified starches, sugars, gum acacia, gum tragacanth, guar gum, pectin, wax binders, microcrystalline cellulose, methylcellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, copolyvidone, gelatin and sodium alginate, preferably polyvinylpyrrolidone.
6. The composition according to claim 3 wherein the disintegrant comprises highly refined isomorphous silicate, crospovidone, cellulose, kaolin, crosslinked carboxy methyl cellulose, microcrystalline cellulose, crosslinked polyvinyl pyrrolidone, and mixtures thereof.
7. The composition according to claim 3 wherein the plasticizer comprises castor oil, diacetylated monoglycerides, dibutyl sebacate, diethyl phthalate, glycerin, polyethylene glycol, propylene glycol, triacetin, and triethyl citrate
8. The composition according to claim 3 wherein the controlled release polymer comprises one or more of cellulose derivatives, one or more of methylcellulose, ethyl cellulose, hydroxymethyl cellulose, different viscosity grades of hydroxypropyl methylcellulose, hydroxy propyl cellulose, hydroxyethylcellulose, carboxymethyl cellulose, polysaccharides, gums both natural and semi-synthetic like alginates, Karaya, Guar, Locust bean, xanthan gum, gellan gum, welan gum, rhamsan gum and dextran, a polyacrylate, polyvinyl alcohol or polyvinyl pyrrolidone, carbopols, polyethylene oxides, magnesium aluminum silicate, modified starch derivatives or a derivative of such hydrophilic polymers, one or more of waxes, ethylcellulose, copolymer of acrylic acid and methacrylic acid esters, polyethylene, polyamide, polyvinyl acetate, glycerol monostearate, stearylalcohol, glyceryl behenate or combinations thereof
9. The composition according to claim 3 wherein the glidant comprises stearic acid and its derivatives or esters like sodium stearate, magnesium stearate and calcium stearate and the corresponding esters such as sodium stearyl fumarate; talc and colloidal silicon dioxide
10. The composition of claim 3 wherein the first pellet population comprises a core and a coating comprising controlled release polymer wherein the coating provides a weight gain of about 6-10% over the core.
11. The composition of claim 3 wherein the second pellet population comprises a core and a coating comprising controlled release polymer wherein the coating provides a weight gain of about 10-14% over the core.
12. The composition according to claim 1 wherein said composition comprises the two populations of pellets filled into a capsule.
13. The composition according to claim 1 wherein said composition comprises the two populations of pellets compressed into a tablet.
14. A process of preparing an extended release composition of topiramate comprising two populations of coated pellets; the process comprising the following steps:
a. Preparation of first coated pellet population
(i) Preparing the core pellets of topiramate along with other excipients
(ii) Coating the core pellets with a controlled release coating solution that comprises 1-10% w/w of controlled release polymer and other excipient
b. Preparation of second coated pellet population
(i) Preparing the core pellets of topiramate along with other excipients
(ii) Coating the core pellets with a controlled release coating solution that comprises 5-15% w/w of controlled release polymer and other excipient
c. Lubricating the two population of coated pellets with a suitable lubricant
d. Mixing the two populations of coated pellets and filling into the capsule.

Dated: 25th day of October, 2016
--------------------------------------- Taranpreet Singh Lamba
Vice President
IPM and Global Product Portfolio Management
Glenmark Pharmaceuticals Limited

ABSTRACT
The present invention relates to extended release pharmaceutical compositions of Topiramate or a salt thereof. The invention also relates to processes for the preparation of such compositions and use thereof for treatment of seizures.

,CLAIMS:1. An extended release composition comprising two populations of coated pellets of topiramate in a ratio of about 10: 90 to about 90:10; wherein said two population of coated pellets comprises a core and an extended release coating and wherein the two population of coated pellets differ in their composition and process of making.
2. The composition of claim 2 wherein the ratio of the two populations of extended release pellets of topiramate is about 50:50
3. An extended release composition of claim 1 wherein the two populations of coated pellets comprises the first pellet population and a second pellet population wherein:
(a) the first coated pellet population comprises
(i) a core comprising about 25%-75% w/w topiramate, about 15%-50%
w/w of a filler, about 1%-10% w/w of a binder, about 1%-10% w/w of a
disintegrant.
(ii) an extended release coating comprising about 1%-10% w/w of a
controlled release polymer, about 0.1%-5% w/w of a plasticizer.
(b) the second coated pellet population comprises
(i) a core comprising about 25%-75% w/w topiramate, about 15%-50%
w/w of a filler, about 1%-10% w/w of a binder, about 1%-10% w/w of a
disintegrant.
(ii) an extended release coating comprising about 5%-15% w/w of a
controlled release polymer, about 0.1%-5% w/w of a plasticizer, about
0.01%-1% w/w of a glidant, and about 0.01-1% w/w of a colorant.
4. The composition according to claim 3 wherein the filler comprises microcrystalline cellulose, di- or tri-basic calcium phosphate, crystalline cellulose, powdered cellulose, calcium carbonate, calcium sulphate, magnesium silicate, magnesium trisilicate, magnesium aluminium metasilicate, kaolin, starch, starch derivatives, magnesium carbonate, magnesium oxide and co-processed insoluble excipients
5. The composition according to claim 3 wherein the binder comprises polyvinylpyrrolidone, lactose, starches, modified starches, sugars, gum acacia, gum tragacanth, guar gum, pectin, wax binders, microcrystalline cellulose, methylcellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, copolyvidone, gelatin and sodium alginate, preferably polyvinylpyrrolidone.
6. The composition according to claim 3 wherein the disintegrant comprises highly refined isomorphous silicate, crospovidone, cellulose, kaolin, crosslinked carboxy methyl cellulose, microcrystalline cellulose, crosslinked polyvinyl pyrrolidone, and mixtures thereof.
7. The composition according to claim 3 wherein the plasticizer comprises castor oil, diacetylated monoglycerides, dibutyl sebacate, diethyl phthalate, glycerin, polyethylene glycol, propylene glycol, triacetin, and triethyl citrate
8. The composition according to claim 3 wherein the controlled release polymer comprises one or more of cellulose derivatives, one or more of methylcellulose, ethyl cellulose, hydroxymethyl cellulose, different viscosity grades of hydroxypropyl methylcellulose, hydroxy propyl cellulose, hydroxyethylcellulose, carboxymethyl cellulose, polysaccharides, gums both natural and semi-synthetic like alginates, Karaya, Guar, Locust bean, xanthan gum, gellan gum, welan gum, rhamsan gum and dextran, a polyacrylate, polyvinyl alcohol or polyvinyl pyrrolidone, carbopols, polyethylene oxides, magnesium aluminum silicate, modified starch derivatives or a derivative of such hydrophilic polymers, one or more of waxes, ethylcellulose, copolymer of acrylic acid and methacrylic acid esters, polyethylene, polyamide, polyvinyl acetate, glycerol monostearate, stearylalcohol, glyceryl behenate or combinations thereof
9. The composition according to claim 3 wherein the glidant comprises stearic acid and its derivatives or esters like sodium stearate, magnesium stearate and calcium stearate and the corresponding esters such as sodium stearyl fumarate; talc and colloidal silicon dioxide
10. The composition of claim 3 wherein the first pellet population comprises a core and a coating comprising controlled release polymer wherein the coating provides a weight gain of about 6-10% over the core.
11. The composition of claim 3 wherein the second pellet population comprises a core and a coating comprising controlled release polymer wherein the coating provides a weight gain of about 10-14% over the core.
12. The composition according to claim 1 wherein said composition comprises the two populations of pellets filled into a capsule.
13. The composition according to claim 1 wherein said composition comprises the two populations of pellets compressed into a tablet.
14. A process of preparing an extended release composition of topiramate comprising two populations of coated pellets; the process comprising the following steps:
a. Preparation of first coated pellet population
(i) Preparing the core pellets of topiramate along with other excipients
(ii) Coating the core pellets with a controlled release coating solution that comprises 1-10% w/w of controlled release polymer and other excipient
b. Preparation of second coated pellet population
(i) Preparing the core pellets of topiramate along with other excipients
(ii) Coating the core pellets with a controlled release coating solution that comprises 5-15% w/w of controlled release polymer and other excipient
c. Lubricating the two population of coated pellets with a suitable lubricant
d. Mixing the two populations of coated pellets and filling into the capsule.