DESC:FORM 2

THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
Complete Specification
[See Sections 10 and rule 13]

Title: Modified Release solid oral dosage form of Topiramate

Applicant: (a) FTF Pharma Private Limited
(b) Registered address: 505 “SAFAL PRELUDE”
Opp. Prahaladnagar AUDA Garden
Satelite, Ahmedabad – 380015
Gujarat , India
(c) Nationality: Indian

The following specification particularly describes the invention and the manner in which it is to be performed:
FIELD OF THE INVENTION

The present invention relates to a novel modified release oral pharmaceutical formulation of topiramate or its pharmaceutically acceptable salts or derivatives. This dosage form is a solid oral dosage form which maintains an effective plasma drug concentration over an extended period of time and thereby maintain uniform and release rate of the active pharmaceutical ingredient over an extended period of time.
BACKGROUND

Topiramate,2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate, is anticonvulsant (antiepileptic) sulfamate substituted monosaccharide discovered in 1979 by McNeil Pharmaceutical. It is approved for the prevention of migraine. Topiramate is also approved for an adjuvant therapy for patients with partial onset seizures or primary generalized tonic-clonic seizures.

Modified release formulation avoids frequent administration of the medicament while maintaining release rate of the active pharmaceutical ingredient over an extended period of time.

Modified release composition provides an effective dissolution profile to maintain effective plasma concentration of drug at expected release rate of medicament after a solid oral drug administration.

This aim has been attained in the present invention by preparing modified release dosage form of topiramate to maintain the desired blood plasma concentration of the drug over a prolonged period of time.

PRIOR ART

US5998380 discloses method of reducing the frequency or severity of migrainous episodes in a non-epileptic human patient. US6503884 discloses method of treating migraine in a non-epileptic human patient.
US7056890 and US7674776 discloses combination of topiramate and phentemine where topiramate is delayed release. Based on the description compositions include a tablet core consisting essentially topiramate, said core being in association with a layer of phentermine where the core has a delayed or sustained dissolution rate. In this composition core of delayed release topiramate is covered by layer of phentemine. Further topiramate core composition is very general which do not specify novelty of delayed release. Whereas present invention is not for combination but for specific novel formulation of topiramate or its pharmaceutical salts or derivatives.
US8329215 and US20130164377 discloses controlled release dosage form of API where core is matrix form and shell covering core is again matrix form. Both this matrix forms are containing active ingredient separately. Whereas in present invention there is no such formula that comprises two matrix and both containing active ingredient separately.
US6923988, US6569463, WO2004002447, EP1517671, WO2004010970 and EP1534238disclosescomposition comprises API and surfactant. Whereas present in composition no useof surfactant.

US8298580 and US8298576 discloses composition and release system is two extended release and one immediate release whereas in present composition release is not dual extended release.

US7390505 discloses composition comprising API and surface stabilizer. Whereas in present composition no use of surface stabilizer.
US8268352 discloses no use of HPMC in either matrix formulation or coating. Further in composition claimed in this patent coating consists of API and hydrophobic release controlling agent which is not used in present formulation.

US20130004575 claims two intelligent polymers are used in which both are having opposite wettability characteristic. This characteristic is not in the polymer used in present invention composition.

US20070196396 claims composition in which swelling agent is used which is not used in present invention composition.
US20080085306, WO2006063078 and US20060121112 claims enteric coated composition which is not in composition of the present invention.

OBJECT OF THE INVENTION

It is an object of the present invention is to provide a novel modified release oral pharmaceutical formulation of topiramate or its pharmaceutically acceptable salts or derivatives.
It is yet another object of the present invention is to provide modified release solid oral dosage form of topiramate or its pharmaceutically acceptable salts or derivatives which maintains an effective plasma drug concentration over an extended period of time and thereby maintain uniform and release rate of the active pharmaceutical ingredient over an extended period of time.
Still a further object of the invention is to develop a modified release solid oral dosage form of topiramate or its pharmaceutically acceptable salts or derivatives thereof which can be used by a patient once a day or twice a day, more preferably once a day.

It is a further object of this invention to provide a process for the preparation of orally administrable modified release solid oral dosage form of topiramate or its pharmaceutically acceptable salts or derivatives thereof.
The formulation of the present invention may be incorporated in any solid oral dosage form such as represented by, but not limited to, a tablet, a pill, and capsule.

DETAILED DESCRIPTION OF THE INVENTION

Topiramate is a sulfamate-substituted monosaccharide having the chemical name 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranosesulfamate,molecular formula is C12H21NO8S, and chemical structure is

Present invention is to provide a novel modified release solid oral pharmaceutical formulation of topiramate or its pharmaceutically acceptable salts or derivatives which maintains an effective plasma drug concentration over an extended period of time and thereby and maintain uniform and release rate of the active pharmaceutical ingredient over an extended period of time.
Present solid modified release oral dosage form of topiramate or its pharmaceutically acceptable salts or derivatives thereof is prepared for patient to administer once a day or twice a day, more preferably once a day preferably in the form of a tablet, a pill, or a capsule. In the present invention if capsule is prepared it can be filled directly by granules, pills, tablet, pellets or capsule.
In the present invention formulations topiramateis between 15% - 85% and other pharmaceutically acceptable excepientsare between 0.2% to 85% which in total between 15 to 85%.These excepients includes but not limited to controlled release polymer, binder, diluent, disintegrant, lubricant or glidant.
Controlled release polymer selected from but not limited to, cellulose polymers such as Hypromellose, ethylcellulose, methyl cellulose, hydroxyporpyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, cellulose acetate and cellulose acetate pthalate etc., polyvinyl alcohol, acrylic polymers such as polyacrylates, polymethacrylates and copolymers theresof and other water based or solvent based coating materials, other polymers are carbopol, povidone chitosan, carragenan.
Binder selected from but not limited to, starch, povidone, hypromellose, hydroxypropyl cellulose, hydroxyethyl cellulose, microcrystalline cellulose, candelilla wax and the like.
Diluent selected from but not limited to, lacotse, microcrystalline cellulose, starch, mannitol, sucrose, sorbitol, calcium phosphate such as dicalcium phosphate, tribasic calcium phosphate, polyalkylene glycols, polyethylene glycols, magesium oxide, sodium chloride and the like.
Disintegrant selected from but not limited to, crospovidone, croscarmellose sodium, sodium starch glycolate, starch, povidone, citric acid and the like.
Lubricant selected from but not limited to, Magnesium stearate, stearic acid, calcium stearate, sodium lauryl sulphate, sodium stearyl fumarate and the like.
Glidant selected from but not limited to, colloidal silicon dioxide, talc, starch and the like.

Examples
The present invention has been described by way of example only, and it is to be recognized that modifications thereto falling within the scope and spirit of the appended claims, and which would be obvious to a person skilled in the art based upon the disclosure herein, are also considered to be included within the scope of this invention.
Total filled wt – 425 mg / capsules
Sr.No. Ingredients Functional activity % w/w
1 Topiramate Active 47.05 %
2 HPMC Controlled release polymer 28.23%
3 Di-calcium Phosphate Diluents 16.47 %
4 Povidone Binder 4.7 %
5 Ethyl cellulose Controlled release polymer 2.35 %
6 Mg-Stearate VG Lubricant 1.18 %
7 Isopropyl alcohol Solvent

Process
1) Mix Topiramate with HPMC, Dicalcium phosphate and povidone.
2) Add Ethyl cellulose in IPA and granulate the above blend.
3) Dry the granules till the LOD achieved.
4) Lubricate the above granules with Mg Stearate VG.
5) Fill the granules in appropriate sized capsules.

,CLAIMS:We Claim,

1. Modified release solid oral pharmaceutical formulation of topiramate or its pharmaceutically acceptable salts or derivatives.
2. Modified release solid oral pharmaceutical formulation as claimed in claim 1, wherein topiramateor or its pharmaceutically acceptable salts is between 15% - 85% and other pharmaceutically acceptable excepients are between 0.2% to 85% which in total between 15 to 85%.
3. Modified release solid oral pharmaceutical formulation as claimed in claim 1 and 2, wherein the excepients includes controlled release polymer, binder, diluent, disintegrant, lubricant or glidant.
4. Modified release solid oral pharmaceutical formulation as claimed in claim 1, 2 and 3, wherein the Controlled release polymer selected from cellulose polymers such as Hypromellose, ethylcellulose, methyl cellulose, hydroxyporpyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, cellulose acetate and cellulose acetate pthalate, polyvinyl alcohol, acrylic polymers such as polyacrylates, polymethacrylates and copolymers theresof and other water based or solvent based coating materials, other polymers are carbopol, povidone chitosan, carrageenan,
Binder selected from starch, povidone, hypromellose, hydroxypropyl cellulose, hydroxyethyl cellulose, microcrystalline cellulose, candelilla wax and the like.
Diluent selected from lacotse, microcrystalline cellulose, starch, mannitol, sucrose, sorbitol, calcium phosphate such as dicalcium phosphate, tribasic calcium phosphate, polyalkylene glycols, polyethylene glycols, magesium oxide, sodium chloride and the like.
Disintegrant selected from crospovidone, croscarmellose sodium, sodium starch glycolate, starch, povidone, citric acid and the like.
Lubricant selected from magnesium stearate, stearic acid, calcium stearate, sodium lauryl sulphate, sodium stearyl fumarate and the like.
Glidant selected from colloidal silicon dioxide, talc, starch and the like.
5. Modified release solid oral pharmaceutical formulation as claimed in claim 1, wherein solid oral formulation is in the form of tablet, pill, or capsule.
6. Modified release solid oral pharmaceutical formulation as claimed in claim 1 and 4, wherein capsule is filled directly by granules, pills, tablet, pellets or another capsule.
7. Modified release solid oral pharmaceutical formulation as claimed in claim 1, wherein the dose is given to patient once a day or twice a day.
8. Process for preparation of modified release solid oral pharmaceutical formulation of topiramate or its pharmaceutically acceptable salts or derivatives comprises
a) Mix Topiramate with HPMC, Dicalcium phosphate and povidone.
b) Add Ethyl cellulose in IPA and granulate the above blend.
c) Dry the granules till the LOD achieved.
d) Lubricate the above granules with Mg Stearate VG.
e) Fill the granules in appropriate sized capsules.