FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
AND
THE PATENTS RULES, 2003
Complete Specification
[See section 10; rule 13]
1. TITLE OF THE INVENTION
"Controlled release composition of oxcarbazepine"
2. APPLICANT
(a) NAME: VerGo Pharma Research Laboratories Pvt. Ltd.
(b) NATIONALITY: An Indian Company
(c) ADDRESS: Plot No. B5, B22, B23, B23A, phase-1A, Verna Industrial Estate, Salcette, Goa- 403722, India
3. PREAMBLE TO THE DESCRIPTION
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, in general, to the field of controlled release formulations and, in particular, to ora\ solid once-a-day pharmaceutical formulations for controlled release delivery of oxcarbazepine and pharmaceutically acceptable salts thereof.
Background of the Invention
Oxcarbazepine, chemically described as 10, 11-dihydro-10-oxo-5H-dibenzo (Z) [b, f] azepine-5-carboxamide, belongs to the benzodiazepine class of drugs and is an anticonvulsant agent of the following chemical structure.

Worldwide, oxcarbazepine is prescribed as antiepileptic drug and used as monotherapy or adjunctive therapy in the treatment of partial seizures with or without secondarily generalized tonic-clonic seizures in adults and children. However, oxcarbazepine is poorly soluble in water and been widely reported in the art in micronized form to increase solubility and bioavailability. For example, the US Pat. No. 7,037,525 teaches method of treating seizures by administering oxcarbazepine formulation with improved bioavailability and having a maximum residue on a 40 micron sieve of less than or equal to 5% and a median particle size of approximately 2 microns to 12 microns. Oxcarbazepine having a median particle size of 14 to 30 microns in further disclosed in the WO Pub. No, 2006046105. Also, the US Patent Pub. No. 20060111343 teaches an oral dosage form of oxcarbazepine having a median particle size of not less than about 50 microns.
Immediate release formulation of oxcarbazepine is available in 150 mg, 300 mg and 600 mg strengths and is administered twice a day to control epileptic seizures. If clinically indicated, the dose may be increase at approximately weekly intervals. Side effects, such as allergic reactions, double vision, and increase seizure activity limit the maximum tolerable daily dosage to 2400 mg/day. The need for a controlled release formulation of oxcarbazepine is much desired, resulting into improved patient compliance and reduced side effects.

Various other controlled-release formulations for oxcarbazepine have been described in the art. For example, the US Pat. No. 6,534,090 teaches oral osmotic controlled release delivery system of carbamazepine. However, preparation of these osmotic systems is complicated requiring advanced and expensive laser drilling technology. WO Pub. No. 95/29665 teaches solid pharmaceutical tablet form for the treatment of epilepsy where the drug is released in controlled manner on the basis of laws of osmosis, diffusion, bioerosion and ion exchange, with specific bioavailability. Another approach describing controlled release tablet formulation of micronized oxcarbazepine is taught in the WO Pub. No. 98/3568.
Further, the US Pat. No. 6,296,873 describes sustained release delivery systems of carbamazepine and its derivatives using high molecular weight hydroxypropyl methyl cellulose to achieve zero-order release profile. Sustained release formulations of oxcarbazepine are also described in US Pub Nos. 20020169145 and 20040142033 where 55-85% of oxcarbazepine is characterized to release in 15 min and up to 95% in 30 minutes. Alternate approaches are also described in the WO Pub. No. 2004/026314 and US Pat. No. 7,910,131 such as using pH dependant release promoting agent.
Despite these advances in the art, there remains a need for reasonably simpler and more practical oral solid controlled release formulations of oxcarbazepine and pharmaceutically acceptable salts thereof.
Summary of the Invention
The present invention provides oral solid pharmaceutical formulations for controlled release delivery of oxcarbazepine for once-a-day administration. The invention designed to meet therapeutic need of a patient. In a preferred embodiment, the formulation comprises hydrophobic matrix system, solubility enhancing agents and release-promoting agents for controlled-release once-a-day administration of oxcarbazepine.
In another preferred embodiment, the formulation comprises pH dependent polymer and combination of solublisers for controlled release delivery of oxcarbazepine at pH above 4 of the gastrointestinal tract.

In yet another preferred embodiment, the formulation comprises oxcarbazepine with a particle size having d90 less than 20 microns, more specifically less than 10 microns.
Detailed Description of the Invention
The invention relates to oral solid pharmaceutical formulations for one-a-day controlled release administration of oxcarbazepine and pharmaceutically acceptable salts thereof.
The following disclosure describes the oral solid pharmaceutical formulations which constitutes the invention. The invention is not limited to the specific formulation or composition described herein, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention.
It must be noted that as used herein and in the appended claims, the singular forms "a", "and", and "the" include plural references unless the context clearly dictates otherwise.
Unless defined otherwise, all technical and scientific terms as used herein have the ordinary meaning as understood by those skilled in the art to which this invention belongs.
The term "active agent", "active ingredient" and "drug" are used interchangeably and include oxcarbazepine and pharmaceutically acceptable salts thereof.
The present inventors meticulously studied and found that oxcarbazepine close contact with both pH dependent polymer and solublisers gives required dissolution with ascending type release profile using more bio-relevant dissolution methods such as multimedia dissolution study in 0.1 N HCI, 4.5 Acetate buffer, and 6.8 Phosphate buffer.
The present invention relates.to oral controlled-release formulations of oxcarbazepine providing maximum uniformity of dispersion of oxcarbazepine in suitable hydrophobic wax matrices and constant bioavailability and therapeutic efficacy. The oral controlled-reiease formulations of the present invention further comprises solublisers, hydrophobic non-swellable matrix wax, pH dependent polymer and sucrose as binder.

The formulation of the present invention comprises oxcarbazepine with or without pharmaceutically acceptable excipients may in the form of tablets, mini-tablets, tablet in tablet, inlay tablets, MUPS (multi unit particulate system), pellets (extruded or fluidized) or beads or spheres or cores that are either encapsulated or compressed into tablets or minitablets or inlay tablets or capsules encapsulating minitablets or pellets or both, powders or lyophilized powders. The most preferred formulation is tablet.
Suitable pH dependent polymer include cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, ethylhydroxycellulose phthalate, polyvinylacetate phthalate, polyvinylbutyrate acetate, vinyl acetate-maleic anhydride copolymer, styrene-maleic monoester copolymer, methyl acrylate-methacrylic acid copolymer, methacrylate-methacrylic acid-octyl acrylate copolymer,etc. These copolymers are anionic polymers based on methacrylic acid and methyl methacrylate and, preferably, have a mean molecular weight of about 135000. A ratio of free carboxyl group to methyl-esterified carboxyl group in these copolymers may range, for example, from 1:1 to 1:, e.g. around 1:1 or 1:2. Such polymers are sold under the trade name Eudragit™ such as the Eudragit L series e.g. Eudragit L 12.5, Eudragit L 12.5P, Eudragit L 100, Eudragit L 100-55, Eudragit L 30D, Eudragit L-30 D-55,the Eudragit S series e.g. Eudragit S 12.5, Eudragit S 12.5P, Eudragit S 100 are the release promoting agent.
The release-promoting agent as pH dependent polymer can be incorporated in an amount from 10% to 90%, by weight of the dosage unit. The agent can be incorporated into the formulation either prior to or after granulation. The release-promoting agent can be added into the formulation either as a dry material, or it can be dispersed or dissolved in an appropriate solvent, and dispersed during granulation.
Further pharmaceutically acceptable excipients may include anionic, cationic and nonionic surfactants. These include but are not limited to anionic surfactants such as chenodeoxycholic acid, 1-octanesulfonic acid sodium salt, sodium deoxycholate, glycodeoxycholic acid sodium salt, N-lauroylsarcosine sodium salt, lithium dodecyl sulfate, sodium cholate hydrate, sodium lauryl sulfate (SLS) and sodium dodecyl sulfate (SDS); cationic surfactants such as cetylpyridinium chloride monohydrate and hexadecyltrimethylammonium bromide; nonionic surfactants such as N-decanoyl-N-

methylglucamine, octyl a-D-glucopyranoside, n-Dodecyl b-D-maltoside (DDM), polyoxyethylene sorbitan esters like polysorbates and the like.
Suitable solublisers used in the present invention include without any limitations surface active agents such as sodium docusate, sodium lauryl sulfate, sodium stearyl fumarate, Tweens® and Spans (PEO modified sorbitan monoesters and fatty acid sorbitan esters), poly(ethylene oxide)-polypropylene oxide-poly(ethy!ene oxide) block copolymers (aka Pluronics™); complexing agents such as low molecular weight polyvinyl pyrrolidone and low molecular weight hydroxypropyl methyl cellulose; molecules that aid solubility by molecular entrapment such as cyclodextrins, and pH modifying agents, including acidifying agents such as citric acid, fumaric acid, tartaric acid, and hydrochloric acid; and alkalizing agents such as Meglumine and sodium hydroxide.
Solublisers typically constitute from 1% to 80% by weight of the dosage form and can be incorporated in a variety of ways. They can be incorporated in the formulation prior to granulation in dry or wet form. They can also be added to the formulation after the rest of the materials are granulated or otherwise processed. During granulation, solublisers can be sprayed as solutions with or without a binder.
Common diluents that can be used so as to add bulk to the core tablet or resinates of the invention include: lactose, starch, pregelatinized starch, calcium carbonate, calcium sulfate, sugar, mannitol, sorbitol, dextrates, dextrin, maltodextrin, dextrose, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, magnesium carbonate, magnesium oxide, and the like.
Various hydrophobic excipients can be used to modify the hydration rate of the dosage unit when exposed to water or aqueous media. These excipients retard the wetting of the dosage unit and hence modify the release of the active agent. Hydrophobic excipients suitable for this invention are represented by, but not limited to, glyceryl behenate, glyceryl monstearate, mixtures of glyceryl monostearate and glyceryl monopalmitate (Myvaplex, Eastman Fine Chemical Company), glycerylmonooleate, a mixture of mono, di and tri-glycerides (ATMUL 84S), glycerylmonolaurate, glyceryl behenate, paraffin, white wax, hydrogenated castor oil, hydrogenated vegetable oil, long chain carboxylic acids, long chain carboxylic acid esters and long chain carboxylic acid alcohols.

Binders can be included in the present invention to help hold tablets together after compression various saccharides (ike monosaccharide, disaccharide, oligosaccharide and polysaccharide can be used as a binder, especially starch and sucrose used as a binder but not cellulose derivative are present in the amount from 10% to 80% by weight of the dosage form. Starches like potato starch, wheat starch, corn starch, e.g. having a molecular weight of from 30000 to 120000.
The US Pat. No. 7,910,131 discloses use of pH dependent polymers and surfactant but fails to explain , how the advancement in dissolution can be achieved , all data which appears to cover in dissolution method using water with 1% SLS doesn't show any advancement in dissolution and thus fails to explain importance of SLS and L100 polymer. It is apparently possible to achieve a very good dissolution in this methodology (water with 1%SLS) even after without use of any pH dependent polymers, this is essentially due to good solubility of a drug in presence of surfactant hence this patent has limitations to explain how the advancement in solubility or dissolution can be achieved.
The present inventors have identified the critical aspect of formulation such as drug need close contact of pH dependent polymers such as by granulation, co-grinding, co-mixing or by any alternate method; similarly it is a part of the present invention to use sugar as a binding agent, which provides good density and compressibility to granules. Also, it is part of the present invention to achieve dissolution such as NMT 80 % in 6 hrs and NMT 95 % in 10 hrs and NLT 95% in 12 hrs using multimedia dissolution methodology using USP II method, 900 ml.
The present invention may further include wet granulation of oxcarbazepine using sugar as a binder and granulation of oxcarbazepine with pH dependant polymer, and a surfactant using water as granulating fluid and sucrose as a binder.
The compositions for tabletting may further include additional pharmaceutically acceptable excipients, including one or more of glidants, lubricants, surfactants and other commonly used excipients. Formulation of the present invention may include antioxidants including, but not limited to, ascorbic acid and its esters, butylated hydroxy

toluene (BHT), butylated hydroxy anisole (BHA), α-tocopherol, cystein, citric acid, propyl gallate, and sodium bisulfate.
A lubricant can be added to the present invention to reduce adhesion and/or ease the release of the product from e.g. the dye. Lubricants include magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc and zinc stearate. In the present invention a suitable solvent system comprises solvents such as purified water or alkaline water, ethanol, isopropyl alcohol, acetone, methylene chloride and the like.
Oxcarbazepine, polymers, and other excipients are typically combined and wet granulated using a granulating fluid, however, other methods of forming granules such as slugging, and roller compaction can also be used to manufacture non matrix granules. Non matrix tablets can also be made by direct compression. In wet granulation, typical granulating fluids are: water, a mixture of water and alcohol, anhydrous alcohol.
Wet granules can be made in any granulating device such as mixers, high shear granulators, and fluid bed granulators. Granules can be dried in appropriate drying equipment such as fluid bed dryers, ovens, microwave dryers etc. Granules can also be air-dried. Dried granules can be milled using appropriate milling device to achieve a particular particle size distribution. Granules can be filled in to capsules, or blended with other excipients and tableted on a tablet press, Granules can also be packaged into sachets for sprinkle application. Other excipients used to aid tableting are well known to those skilled in the art and include magnesium stearate, talc, cabosil etc. Granules and tablets can, optionally, be coated to further modify release rates. Furthermore, formulations can also optionally contain dyes.
The oral solid pharmaceutical formulation of the present invention can be in the form of inlay tablet. An inlay tablet is a compressed solid oral dosage form which has a small tablet placed within a large tablet, such that three sides of a small tablet are within a large tablet and only one surface of the small tablet is exposed. The invention provides in further aspect a compressed tablet of an ovaloid shape. The tablet may be in

dimension e.g. 12 to 22 mm in length, preferably 16 to 20 mm; 6 to 12 mm in width, preferably 8 to 10 mm.
The compositions for tabletting may further include additional pharmaceutically

acceptable excipients, including one or more of glidants, lubricants, surfactants and other commonly used excipients. Basic organic substances that can be used as stabilizers in this invention are but not limited to amines such as TRIS (tromethamine), ethanolamine, diethanolamine, triethanolamine, N-methyl-glucamine (meglumine), glucosamine, ethylenediamine, diethyl amine, triethylamine, isopropylamine, diisopropylamine, urea and the like; amino acids such as L-arginine, cysteine, tyrosine, histidine, lysine and the like.
The process for manufacturing the formulation of present invention is not limited to the processes described in the application and the formulation can be prepared by using any of the processes known to one skilled in the art. The active ingredient can be granulated by wet granulation or dry granulation with or without excipients. The granules of active(s) are prepared by sifting the actives and excipients through the desired mesh size sieve and then are mixed using a rapid mixer granulator or planetary mixer or mass mixer or ribbon mixer or fluid bed processor or any other suitable device. The blend can be granulated, such as by adding a solution of a binder whether aqueous or alcoholic or hydro-alcoholic in a low or high shear mixer, fluidized bed granulator and the like. The granulate can be dried using a tray drier or fluid bed drier or rotary cone vacuum drier and the like. The sizing of the granules can be done using an oscillating granulator or comminuting mill or any other conventional equipment equipped with a suitable screen. Alternatively, granules can be prepared by extrusion and spheronization, or roller compaction. The dried granulate particles are sieved, and then mixed with lubricants and disintegrants. In one of the embodiments of the present invention, a suitable solvent system such as aqueous or alcoholic or hydro-alcoholic or organic may be used in the granulation or coating. In another embodiment of the present invention a suitable solvent system comprises solvents such as purified water, ethanol, isopropyl alcohol, acetone, methylene chloride and the like.
The present inventors have meticulously identified that as concentration of surfactant increases in dissolution media the percentage of drug release is also increased, hence

concentration of surfactant is regulated in dissolution media to control or to get adequate discrimination. The concentration of surfactant can range from 0.1 % to 5% more preferably 0.5% to 1% or more preferably 0.3% to 1%.
The present invention relates to controlled release tablet of oxcarbazepine containing a tablet core containing hydrophobic non swellable matrix forming wax as hydrogenated vegetable oil, hydrogenated castor oil or oils of such categories and pH dependent polymer. The ascending type of release of oxcarbazepine is modulated by using hydrophobic non swellable matrix forming wax and pH dependent polymer along with surfactant in tablet core which is compressed using punches. The desired ascending profile is achieved by adjusting the concentration of hydrophobic wax and pH dependent polymer in the present invention.
The following examples illustrate various aspects of the present, but should not be understood to limit the scope of the invention.
Example 1
Oxcarbazepine formulation
Oxcarbazepine with microcrystailine cellulose, povidone, sodium iauryl sulfate, polymethacrylic acid and ethyl acrylate were sifted in suitable mesh and granulated with purified water. The granulated mass is dried. HPMC 2208, aerosil, magnesium stearate were added to the dried granules and compressed with a suitable punch.
Table 1

Ingredient %w/w
Oxcarbazepine 60
Povidone 5
Sodium Iauryl sulfate 5
Polymethacrylic acid; ethyl acrylate 10
Microcrystailine cellulose 9.25
HPMC 2280 10
Aerosil 2.5
Magnesium stearate 5

Purified water
q.s.
Example 2 Release Profile
Table 2

Time point (hr) With 0.3% SLS With 0.6% SLS With 1% SLS
Media
Multimedia-HCJ, Acetate, Phosphate Water
B.No. Table 1
% release % release
2 6 12 26
4 20 41 59
6 29 75 89
8 41 93 98
10 61 96 100
12 97 —
14 67 97 100
18 67 98 —
The release profile indicate that 0.6% SLS in multimedia is good discriminatory method to establish effect of methacrylic acid polymer and surfactant. It is part of the present invention to use multimedia dissolution methodology to develop oral controlled release oxcarbazepine formulations.
Example 3
Oxcarbazepine with povidone, sodium lauryl sulfate and poly (methacrylic acid; ethyl acrylate) were sifted in suitable mesh and granulated with purified water. The granulated mass is dried. Sterotex k NF, compritol 888, aerosil and magnesium stearate were added to the dried granules at lubrication stage and compressed with a suitable punch.
Table 3

Ingredient %w/w
Oxcarbazepine 70
Povidone 6
Sodium lauryl sulfate 6
Polymethacrylic acid; ethyl acrylate 12
Glyceryl behenate 5
Aerosil 4

Magnesium stearate 0.6
Table 4

Ingredient %w/w
Oxcarbazepine 66
Povidone 5.5
Sodium lauryl sulfate 5.5 10
Polymethacrylic acid; ethyl acrylate

Hydrogenated vegetable oil Type 1 10
Aerosil 4
Magnesium stearate 0.6
Example 4 Release profile
Table 5

The release profile indicates hydrogenated vegetable oil as a rate controlling agent. Example 5

Media Time point (hr) With 0.6% SLS Without SLS With 0.6% SLS Without SLS
BNo. Table-3 Tab Ie4
% release % release
0.1 N HCL 2 3 4 7 2
4.5 Acetate 4 47 17 18 3
6.8 Phosphate 6 76 22 78 13
8 77 29 89 21
10 77 33 93 29
12 77 36 93 35
14 16 18 77 38 96 40

_ 40 43 — 43

96 47

Oxcarbazepine with povidone, eudragit RLPO/hypromellose P55 were sifted in suitable sieve and granulated with purified water. The granulated mass is dried. HPMC 2280, microcrystalline cellulose, aerosil and magnesium stearate were blended with the dried granules and compressed with a suitable punch.
Table 6

Ingredient %w/w
Oxcarbazepine 60
Povidone 5
Sodium lauryl sulfate 5
Hypromellose phthalate 10
HPMC 2280 10
Microcrystalline cellulose 9.25
Aerosil 0.25
Magnesium stearate 0.5
Table 7

Ingredient %w/w
Oxcarbazepine 60
Povidone 5
Sodium lauryl sulfate 5
Eudragit RLPO 10
HPMC 2280 10
Microcrystalline cellulose 9.25
Aerosil 0.25
Magnesium stearate 0.5
Example 6 Release profile

Table 8

Media Time point (hr) Multimedia 0.6% SLS Water 1% SLS Multimedia 0.6% SLS Water 1% SLS
B.No. Table 6 Table 7
% release % release
2 8 26 8 18
4 17 54 14 35
6 32 77 25 50
10 69 97 40 74
14 81 99 53 93
18 , 81 99 65 97
The release profile indicates that pH dependent polymers can also be used to achieve required dissolution but appears to have limited dissolution.
Example 7
Oxcarbazepine with poly methacrylic acid-ethyl acrylate was sifted in suitable sieve and granulated with binder solution obtained by dissolving sucrose and sodium lauryl sulfate in purified water. The granulated mass is dried. Dicalcium phosphate, hydrogenated vegetable oil/castor oil, Aerosil and Magnesium stearate were blended with the dried granules and compressed with suitable punch.
Table 9

Example 8 Release profile

Ingredient %w/w
Oxcarbazepine 60
Poly methacrylic acid; ethyl acrylate 10
Sodium lauryl sulfate 5
Sucrose 5
Dicalcium phosphate anhydrous 9.25
Hydrogenated veg/castor oil 10
Aerosil 0.25
Magnesium stearate 0.5

Table 10

Media Time point (hr) Table 9
B. No. 2 6
2 hr in 0.1N HCI, 2 hr in 4.5 acetate buffer, up to 18hrs in pH6.8 phosphate buffer 6 46

10 71

12 84

14 90

16 96

18 99
Example 9
Oxcarbazepine and polymethacrylic acid-ethyl acrylate were sifted in suitable sieve and transferred in high shear mixer granulator, granulated with binder solution obtained by dissolving sucrose and sodium lauryl sulfate in purified water. The granulated mass is dried. Di calcium phosphate anhydrous, Poly (Methacrylic Acid; ethyl acrylate), and Aerosil and Magnesium stearate were blended with dried granules and roller compacted to get slugs. These slugs are milled through 0.5mm multimill to obtain #30 mesh granules and lubricated with hydrogenated vegetable oil Type I, aerosil and magnesium stearate and compressed with suitable punch. The dissolution was carried out in multimedia dissolution in USP II, 900ml and 60rpm.
Table 11

Ingredient %w/w
Oxcarbazepine 60
Poly methacrylic acid; ethyl acrylate 10
Sodium lauryl sulfate 5
Sucrose 5
Dicalcium phosphate anhydrous 9.25
Hydrogenated veg/castor oil 10
Aerosil 0.25
Magnesium stearate 0.5
Table 12

Media 2 hr in 0.1N HCI, 2hr in 4.5
acetate buffer, upto 18 hrs in
pH 6.8 phosphate buffer
a wo. Time point (hr) I Table 11

2 1
6 24
10 44
12 54
On comparing Table 10 and Table 12, it can be concluded that polymer polymethacrylic acid; ethyl acrylate and surfactant should be granulated in close contact with oxcarbazepine.
Example 10 Comparative study
Table 13

Time (hr) Multimedia dissolution Roller compacted , granules
where Poly (Methacrylic Acid ;
ethyl acrylate) is outside in
Lubrication Wet Granulation, where Poly
(Methacrylic Acid ; ethyl
acrylate) is in granulation in
intimate contact of
Oxcarbazepine
0 0 0
2 1 6
6 24 46
10 44 71
14 54 84
Dissolution studies of the present invention shows a distinctive, innovative dissolution profile as below in water + 1% SLS, 900 ml, USP II, 60 rpm as a dissolution method.
It indicates that dissolution with 0.6% SLS and 1% SLS in water has almost similar dissolution profile but in multimedia or in water without SLS appears to show very slow or incomplete dissolution profile, in 0.6% SLS with multimedia in the pH region of 6.8 shows a jump of almost 20-30%.
The present inventors found that the process of making Oxcarbazepine controlled release compositions by using sucrose as a binder, sodium lauryl sulfate as surfactant and Poly Methacrylic Acid; ethyl acrylate as solubility enhancer by formulating composition in such a way that Oxcarbazepine is close contact of Poly Methacrylic Acid; ethyl acrylate & sodium lauryl sulfate and is being achieved by granulation, co-milling, co-processing and analyzing dissolution of said formulation in 0.6% SLS with multimedia in 0.1N HCI for 2 hrs followed by pH 4.5 acetate buffer for 2 hrs followed by pH 6.8 phosphate buffer for up to 18 hrs.

Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

Claims
1. An oral solid once-a-day controlled release pharmaceutical formulation comprising oxcarbazepine, a hydrophobic matrix system, a pH dependent polymer, one or more solubilizer, and a binder.
2. The pharmaceutical formulation as claimed in claim 1, wherein the hydrophobic matrix system is hydrophobic non-swellable matrix forming wax selected from the group consisting of hydrogenated vegetable oil, hydrogenated castor oil and the like.
3. The pharmaceutical formulation as claimed in claim 1 further comprises a surfactant.
4. The pharmaceutical formulation as claimed in claim 1, wherein the binder is sucrose.
5. The pharmaceutical formulation as claimed in claim 1, wherein the formulation is tablet.
6. The pharmaceutical formulation as claimed in claim 1, wherein the formulation is capsule.