FORM 2
THE PATENTS ACT 1970 (39 of 1970)
&
THE PATENTS RULE 2003
COMPLETE SPECIFICATION
(Section 10 and rule 13)
"CONTROLLED RELEASE COMPOSITION COMPRISING OXCARBAZEPINE"
Glenmark Generics Limited
an Indian Company, registered under the Indian company's Act 1957
having office at
Glenmark House,
HDO - Corporate BIdg,
Wing -A, B. D. Sawant Marg, Chakala,
Andheri (East), Mumbai - 400 099, INDIA
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED

BACKGROUND OF THE INVENTION
1. Technical Field
The present invention relates to controlled-release preparations of oxcarbazepine or a pharmaceutically acceptable salt thereof, for once-a-day administration and a process for preparing the same.
2. Description of the Related Art
Oxcarbazepine, i.e. 10, 1 l-dihydro-10-oxo-5H-dibenzo [b, f] azepine-5-carboxamide, is widely used for the treatment of epileptic diseases, for the control of neuralgic or cerebrovascular pains or for alcohol disintoxication. The preparation of oxcarbazepine and its pharmaceutically acceptable salts is described, e.g., in German patent 2,011,087 which is incorporated herein by reference. Oxcarbazepine is converted in the body into monohydroxydihydrocarbamazepine (MHD) which is the actual active component. An immediate-release (IR) oxcarbazepine tablet is currently on the market under the trade name Trileptal.(R) and are administered twice a day to control epileptic seizures, however il is noticed that multiple doses of oxcarbazepine in a day fails to maintain the constant plasma concentration of oxcarbazepine that is required for adequate therapeutic effect and less side effects.
As known in the art that patient compliance is greatly improved with control led-release (CR) dosage forms that are taken, for example, once-a-day. Moreover the need for a once a day dosage form, for chronicafly administered drug like oxcarbazepine is self-evident.
Sustained-release dosage composition of carbamazepine, oxcarbazepine and related compounds has been described by Katzhendler et al. in U.S. Pat. No. 6,296,873 wherein zero-order release profile is achieved through the use of hydrophilic and hydrophobic polymers. Franke et al. (US Patent Application 20040142033) discloses sustained-release formulations , of oxcarbazepine that releases 55%-85% of the oxcarbazepine in 15 minutes, and up to 95% in 30 minutes. In another approach taught by Wolf et al. in US Patent Application 20060057203 the control release tablet of oxcarbazepine consists of a core and a coating

wherein the core comprises oxcarbazepine, optionally, filler, and at least one further excipient selected from cellulose ethers, carboxyvinyl polymer of acrylic acid cross linked with alkyl ethers of sucrose or pentaerythritol and polymethacrylates. Bhatt et al (US Patent Application 20090005360) describes Controlled-release preparations of oxcarbazepine.The sigmoid release profile achieved for oxcarbazepine with the use of surface active agents and release promoting agents comprise pH-dependent polymers.
SUMMARY OF THE INVENTION
The present invention relates to controlled release composition comprising oxcarbazepine or a
pharmaceutically acceptable salt thereof, is formulated within polymeric matrix.
In an embodiment, the invention includes controlled release pharmaceutical composition comprising oxcarbazepine or pharmaceutically acceptable salts thereof, wherein said oxcarbazepine or a pharmaceutically acceptable salt thereof is embedded in a matrix comprising one or more polymers.
In another embodiment, the invention includes controlled release tablets, comprising oxcarbazepine or pharmaceutically acceptable salts thereof, wherein said oxcarbazepine or a pharmaceutically acceptable salt thereof is embedded in a matrix comprising one or more hydrophilic polymeric substances which swell, gel, and/or erode upon contact with aqueous liquids, and/or one or more lipophilic polymeric substances, wherein oxcarbazepine or a pharmaceutically acceptable salt thereof releases over the period of more than 12 hours.
In an embodiment, controlled release tablets of the invention comprises oxcarbazepine or a pharmaceutically acceptable salt thereof is embedded in a matrix comprising hydroxypropyl methyl cellulose (Methocel K15M), Hydroxypropyl Methyl Cellulose (Methocel E 3LV) and Microcrystalline Cellulose (Avicel PH 101), wherein the tablet is in monolithic form.

In an embodiment, controlled release tablets of the invention comprises oxcarbazepine or a pharmaceutically acceptable salt thereof is embedded in a matrix comprising Hydroxypropyl cellulose (Klucel MXF), hydroxypropyl methyl cellulose (Methocel K4M), Hydroxypropyl Methyl Cellulose (Methocel E 3LV) and Microcrystalline Cellulose (Avicel PH 101), wherein the tablet is in monolithic form.
In an embodiment, controlled release tablets of the invention comprises oxcarbazepine or a pharmaceutically acceptable salt thereof is embedded in a matrix comprising Sodium carboxymethylcellulose (Blanose 7H4FPH), hydroxypropyl methyl cellulose (Methocel K4M), Hydroxypropyl Methyl Cellulose (Methocel E 3LV) and Microcrystalline Cellulose (Avicel PH 101), wherein the tablet is in monolithic form.
In an embodiment, controlled release tablets of the invention comprises oxcarbazepine or a pharmaceutically acceptable salt thereof is embedded in a rrtatrix comprising methacrylic acid derivative (Eudragit RS30D / Eudragit NM30D) and Microcrystalline Cellulose (Avicel PH 101), wherein the tablet is in monolithic form.
In another embodiment, the invention includes controlled release tablets comprising oxcarbazepine or pharmaceutically acceptable salts thereof, wherein said oxcarbazepine or a pharmaceutically acceptable salt thereof is surrounded by polymeric reservoir comprising one or more hydrophilic polymeric substances which swell, gel, and/or erode upon contact with aqueous liquids, and/or one or more lipophilic polymeric substances, wherein oxcarbazepine or a pharmaceutically acceptable salt thereof releases over the period of more than 12 hours.
In an embodiment, controlled release composition of the invention comprises oxcarbazepine or a pharmaceutically acceptable salt thereof is surrounded by polymeric reservoir comprising Ethyl Cellulose (Ethocel 100 cPs) and Povidone (Kollidone 90 F), wherein the composition is in tablet, minitablet or multiparticulate reservoir form.

In an embodiment, controlled release composition of the invention comprises oxcarbazepine or a pharmaceutically acceptable salt thereof is surrounded by polymeric reservoir comprising methacrylic acid derivative (Eudragit L30D55) and talc, wherein the composition is in tablet, minitablet or multiparticulate reservoir form.
In another embodiment, the invention includes a controlled release multi- layer tablet, comprising: (a) at least one active layer comprising oxcarbazepine or a pharmaceutically acceptable salt thereof and one or more polymers comprising any of: (i) hydrophilic polymeric substances which swell, gel, and/or erode upon contact with aqueous liquids; and/or (ii) lipophilic substances, wherein oxcarbazepine or a pharmaceutically acceptable salt thereof releases over the period of more than 12 hours.
In another embodiment, the invention includes methods of preparing pharmaceutical compositions of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention relates to controlled-release formulations comprising the active pharmaceutical ingredient oxcarbazepine or a pharmaceutically acceptable salt thereof, and one or more hydrophilic polymeric substances which swell, gel, and/or erode upon contact with aqueous liquids, and/or one or more lipophilic polymeric substances. In one embodiment, the formulations of the present invention employ oxcarbazepine or a pharmaceutically acceptable salt thereof having a particle size D90 of not less than about 50 p.m. In another embodiment of the present invention, the formulations of the present invention employ oxcarbazepine or a pharmaceutically acceptable salt thereof having a particle size D90 of about 50 to about 200 u.m, which can be achieved using conventional techniques.

As used herein the term "oxcarbazepine" includes the compound oxcarbazepine, and pharmaceutically acceptable salts of oxcarbazepine, including polymorphs, solvates and hydrates thereof.
The prophylactic or therapeutic dose of oxcarbazepine or pharmaceutically acceptable salt thereof can vary widely depending upon a variety of factors including, for example, the body weight, general health, sex, diet, time and route of administration, rates of absorption and excretion, combination with other drugs, the severity of the particular condition being treated, etc. Generally, the amount of oxcarbazepine or a pharmaceutically acceptable salt thereof may range from about 20 w/w % to about 90.0 w/w % of the dosage form.
In the controlled-release formulations of the invention, the drug is present in amount from about 100 mg to about 1,200 mg per tablet, preferably from about 200 mg to about 800 mg per tablet.
As described here the controlled-release pharmaceutical composition wherein the active pharmaceutical ingredient oxcarbazepine or a pharmaceutically acceptable salt thereof, distributed throughout the polymer matrix (monolithic system) or surrounded by rate controlling polymer membrane (reservoir system).
The pharmaceutical composition of the invention is formulated in the form of matrix and/or reservoir systems are to affect the controlled release of the active pharmaceutical ingredient oxcarbazepine or a pharmaceutically acceptable salt thereof within the gastrointestinal tract.
A pharmaceutical composition according to the present invention can be presented in forms such as tablets, multilayered tablets, capsules, granules, pellets or minitablets.
One or more polymers that can be used in the present invention include hydrophilic, hydrophobic and lipophilic substances, and combinations thereof.

Polymers which swell, and/or gel, and/or erode upon contact with aqueous liquids, that can be used in present invention include, without limitation thereto, cellulose ethers, e.g., hydroxypropyl methylcelluloses or hypromelloses (HPMC), hydroxypropyl eelluloses (HPC), hydroxyethylcelluloses, ethylcelluloses and carboxymethylcellulose sodium, polymers of vinylpyrrolidone, including homopolymers (povidones) and cross-linked polyvinylpyrrolidones, carboxymethyl starches, polyethylene glycols, polyoxyethylenes, poloxamers (polyoxyethylene-polyoxypropylene copolymers), polyvinylalcohols, glucanes (glucans), carrageenans, scleroglucanes (scleroglucans), mannans, galactomannans, gellans, alginic acid and derivatives (e.g., sodium or calcium alginate, propylene glycol alginate). polyaminoacids (e.g. gelatin), methyl vinyl ether/maleic anhydride copolymers, polysaccharides (e.g. carageenan, guar gum, xanthan gum, tragacanth and ceratonia). alpha, beta or gamma cyclodextrins, and dextrin derivatives (e.g. dextrin), polymethacrylates (e.g. copolymers of acrylic and methacrylic acid esters containing quaternary ammonium groups-marketed under the brand Eudragit.TM (Eudrgif RS 30D / Eudragit NM 30 D, Eudragit L30D55); acrylic acid polymers (e.g., carbomers); shellac, and derivatives thereof, etc.
HPMC is particularly preferred for use with oxcarbazepine or a pharmaceutically acceptable salt thereof, because of very low water solubility of oxcarbazepine or a pharmaceutically acceptable salt thereof. HPMC is available in a low, normal or high viscosity grades. The viscosity of the polymer controls the release rate of the drug from the formulation and affects its zero-order release kinetics. Specific HPMCs which are most suitable for the current formulation are Methocel K100M, K15M, F4M, E4M, K4M, K100LV, K3, E15LV, E15LN, E15CLV, E50, E5 and E3, commercially available from Colorcon, Orpington, England.
Polymers, which do not swell and do not gel and do not erode upon contact with aqueous liquids, that can be used in the present invention include, without limitation thereto, cellulose acetate, cellulose butyrate, cellulose diacetate, cellulose triacetate, cellulose propionate, cellulose acetate butyrate, and other acetylated cellulose derivatives, etc.

Lipophilic substances that can be used in the present invention include, without limitation thereto, waxes (e.g., carnauba wax , microcrystalline wax, beeswax, polyethoxylated beeswax); natural fats (coconut, soya, cocoa) including modified forms such as totally or partially hydrogenated, hydrogenated castor oil, hydrogenated vegetable oil, and fatty acid derivatives such as mono-, bi- and th-substituted glycerides, phospholipids, glycerophospholipids, glyceryl palmitostearate, glyceryl behenate, glyceryl monostearate, diethyleneglycol palmitostearate, polyethyleneglycol stearate, polyethyleneglycol palmitostearate, polyoxyethylene-glycol palmitostearate, glyceryl monopalmitostearate, cetyl palmitate, fatty alcohols associated with polyethoxylate fatty alcohols, cetyl alcohol, stearic acid, saturated or unsaturated fatty acids and their hydrogenated derivatives, lecithin, cephalins, chitosan and derivatives thereof, sphingolipids, sterols such as cholesterol and its substituted derivatives, etc.
A controlled release oral drug delivery system of present invention comprising oxcarbazepine or pharmaceutically acceptable salts thereof is formulated within a polymeric matrix, said matrix optionally further containing additional pharmaceutically acceptable constituents and additives. The polymer in the polymeric matrix or reservoir permits oxcarbazepine or pharmaceutically acceptable salts thereof to be released from the matrix at a predictable, controllable, continuous mariner.
Other ingredients which may be incorporated into the compositions to facilitate processing and/or provide enhanced properties of the composition include well-known tableting binders (e.g., gelatin, sugars, natural and synthetic gums, polyvinylpyrrolidone), disintegrants (e.g., croscarmelose, crospovidone, sodium starch glycolate), lubricants (e.g., magnesium stearate, hydrogenated vegetable oil, carnauba wax); flow agents (e.g., silicon dioxide), anti-adherents or glidants (e.g., talc) as well as sweeteners, coloring mediums (e.g., iron oxide, aluminum flakes), filler materials (e.g., lactose and other carbohydrates, pregelitinized starch, potassium bicarbonate, microcrystalline cellulose (Avicel)), flavoring mediums, and antioxidants.

Selection of a particular ingredient or combinations of ingredients and the amounts used will be readily determinable by one skilled in the art by reference to standard procedures and practices for preparing tableted or encapsulated or other dosage forms.
Other useful additives for coating include but are not limited to plasticizers (e.g. castor oil, diacetylated monoglycerides, dibutyl sebacate, diethyl phthalate, glycerin, polyethylene glycol, propylene glycol, triacetin, and triethyl citrate), antiadherents (e.g. talc), opacifiers (e.g. titianium dioxide), solvents (e.g. methylene chloride, isopropyl alcohol, water, methanol, ethanol), and optionally colorants (e.g. iron oxides), lubricants, pigments, antifoam agents, and polishing agents (e.g. glycerol monostearate, fatty alcohols, waxes and poloxamers).
Additionally, the delivery system of the invention optionally contains release accelerating agents, an example of which are polyethylene glycol, salts and surfactants (sorbitan esters (SPAN™), polyhydroxyethylenically treated sorbitan esters (TWEEN™) and sodium lauryl sulphate). Other pharmaceutically acceptable accelerating agents may also be added, as known in the art of pharmaceutical sciences.
If desired, pH modifier (meglumine) may be included in the formulations of the present invention.
A process for preparing pharmaceutical composition of the invention comprises: i) mixing the Oxcarbazepine , polymer, diluent and optionally other additives and followed by blending with lubricant and then ii) compressing into tablets; and iii) optionally, coating tablets of step ii) with a suitable polymer.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any method and material similar or equivalent to those described herein

can be used in the practice or testing of the present invention, the preferred methods and materials are described.
The following examples are provided to enable one skilled in the art to practice the invention and are merely illustrative of the invention. The examples should not be read as limiting the scope of the invention as defined in the claims. EXAMPLE 1: Monolithic Controlled Release Tablet with single hydrophilic polymer

TABLE I
Sr.
No. Ingredient Qry/ tablet (nig)
GRANULA TION STAGE
1 Oxcarbazepine 600.0
2 Microcrystalline Cellulose (Avicel PH 101) 66.0
3 Hydroxy propyl methyl cellulose (15M) 102.0
4 Hydroxy Propyl Methyl Cellulose (Methocel E 3LV) 16.0
5 Purified Water q.s
BLENDING & LUBRICATION
7 Colloidal Silicon Dioxide (Aerosil 200) 8.0
8 Magnesium Stearate 8.0
Wt of Core Tablets / Total 800.0
The manufacturing process consists of the preparation of a granulate obtained by mixing the stated amounts of hydroxypropylmethylcellulose K15M, Microcrystalline cellulose and Oxcarbazepine in Rapid Mixer granulator for 10 min; the uniform powder mixture is moistened with an aqueous solution of HPMC (Methocel E3 LV) and the uniformly moistened mass is dried in a fluidized-air bed at 40-450C. The dried granulate, milled through 1.5 mm screen and mixed with magnesium stearate and colloidal silica passed through a 60 mesh screen. The granulation blend is then compressed into tablets.

Example 2: Monolithic Controlled Release Tablet with combination of hydrophilic polymer

Table 2
Sr. No. Ingredient Qty/ tablet (nig)
GRANULA TION STA GE
1 Oxcarbazepine@ 600
2 Microcrystalline Cellulose (Avicel PH 101) 50.0
3 Hydroxy propyl cellulose (Klucel MXF) 50.0
4 Hydroxy propyl methyl cellulose (HPMC K4M) 76.0
5 Hydroxy Propyl Methyl Cellulose (Methocel E 3LV) 8.0
6 Purified Water q.s
BLENDING & LUBRICATION
7 Collidal Silicon Dioxide (Aerosil 200) 8.0
8 Magnesium Stearate 8.0
Wt. of Core Tablets / Total 800.0

The manufacturing process consists of the preparation of a granulate obtained by mixing the required amounts of Hydroxypropyl cellulose (Klucel MXF), hydroxypropylmethylcellulose K4M, Microcrystalline cellulose and Oxcarbazepine in Rapid Mixer granulator for 10 min; the uniform powder mixture is moistened with an aqueous solution of HPMC (Methocel E3 LV) and the uniformly moistened mass is dried in a fluidized-air bed at 40-45°C. The dried granulate, milled through 1.5 mm screen and mixed with magnesium stearate and colloidal silica passed through a 60 mesh screen. The granulation blend is then compressed into tablets.
Example 3: Monolithic Controlled Release Tablet with two hydrophilic polymers

Table 3
Sr.No. Ingredient Qty/ tablet (mg)

GRANULA TION STA GE
1 Oxcarbazepine 600
2 Microcrystalline Cellulose (Avicel PH 101) 50.0
3 Sodium carboxy methyl cellulose (Blanose 7H4FPH) 50.0
4 Hydroxypropyl methyl cellulose (HPMC K4M) 76.0
5 Hydroxypropyl Methyl Cellulose (Methocel E 3LV) 8.0


6 Purified Water q.s
BLENDING & L UBRICA TION
7 Colloidal Silicon Dioxide (Aerosil 200) 8.0
8 Magnesium Stearate 8.0
Wi. of Core Tablets / Total 800.0
The manufacturing process consists of the preparation of a granulate obtained by mixing the
required amounts of Sodium carboxy methyl cellulose (Blanose 7H4FPH), hydroxypropyl
methyl cellulose K4M, Microcrystalline cellulose (Avicel PH 101) and Oxcarbazepine in
Rapid Mixer granulator for 10 min; the uniform powder mixture is moistened with an aqueous
solution of HPMC (Methocel E3 LV) and the uniformly moistened mass is dried in a
fluidized-air bed at 40-45°C.The dried granulate, milled through 1.5 mm screen and mixed
with magnesium stearate and colloidal silica passed through a 60 mesh screen. The
granulation blend is then compressed into tablets.
Example 4: Reservoir Controlled Release system, wherein immediate release core coated with combination of hydrophobic and hydrophilic polymers.
Table 4

Sr. No. Ingredient Qty/ tablet
(mg)
GRANULA TIONSTAGE
1 Oxcarbazepine 600
2 Microcrystalline Cellulose (Avicel PH 101) 73.0
5 Hydroxy Propyl Methyl Cellulose (Methocel E 3LV) 16.0
6 Purified Water q.s
BLENDING & LUBRICATION
7 Colloidal Silicon Dioxide (Aerosil 200) 8.0
8 Magnesium Stearate 8.0
WL of Core Tablets / Total 705.0
Ethyl Cellulose Coating
' 7 Ethyl Cellulose (Ethocel Standard 100 cPs Premium) 52.5

8 Povidone (Kollidone 90 F) 26
9 Polyethylene Glycol 4000 8.25
10 Dibuty] Sebacate 8.25
11 Ethanol (99 %) QS
Total (Coated tablet) 800.0
The manufacturing process consists of the preparation of a granulate obtained by mixing the required amounts of Microcrystalline cellulose (Avicel PH 101) and Oxcarbazepine in Rapid Mixer granulator for 10 min; the uniform powder mixture is moistened with an aqueous solution of HPMC (Methocel E3 LV) and the uniformly moistened mass is dried in a fluidized-air bed at 40-45°C. The dried granulate, milled through 1.5 mm screen and mixed with magnesium stearate and colloidal silica passed through a 60 mesh screen. The. granulation blend is then compressed into tablets.
To coat the tablets, the Ethyl cellulose, Povidone (Kollidone 90 F), Polyethylene Glycol 4000, Dibutyl Sebacate are mixed in Ethanol (99 %) to obtain coating suspension. The tablets are then spray coated with coating suspension until a 2-4 percent solid weight gain per tablet is achieved.
Example 5: Reservoir Controlled Release system, wherein immediate release core coated with enteric polymer polymers.

Table 5
Sr. No. Ingredient Qty/ tablet (mg)
GRANULATION STAGE
1 Oxcarbazepine 600.0
2 Microcrystalline Cellulose (Avicel PH 101) 88.0
3 Hydroxypropyl Methyl Cellulose (Methocel E 3LV) 16.0
4 Purified Water q.s.
BLENDING & LUBRICATION
7 Colloidal Silicon Dioxide (Aerosil 200) 8.0
8 Magnesium Stearate 8.0
Wt. of Core Tablets /Total 720,0
Eudragit coating


9 Eudragit L30D55 50.0
10 Talc 22.32
11 Propylene glycol 7.68
12 Water q.s.
The manufacturing process consists of the preparation of a granulate obtained by mixing the required amounts of Microcrystalline cellulose (Avicel PH 101) and Oxcarbazepine in Rapid Mixer granulator for 10 min; the uniform powder mixture is moistened with an aqueous solution of HPMC (Methocel E3 LV) and the uniformly moistened mass is dried in a fluidized-air bed at 40-45°C. The dried granulate, milled through 1.5 mm screen and mixed with magnesium stearate and colloidal silica passed through a 60 mesh screen. The granulation blend is then compressed into tablets.
To coat the tablets, the Eudragit L30D55, Propylene glycol, Talc are mixed in water to obtain coating suspension. The tablets are then spray coated with coating suspension until a 2-4 percent solid weight gain per tablet is achieved.
Example 6: Monolithic controlled release tablets using Eudragit Polymers

Table 6
Sr. No. Ingredient Qty/ tablet (mg)

GRANULA TION ST A GE
1 Oxcarbazepine 600
2 Microcrystalline Cellulose (Avicel PH 101) 124.0
6 Eudragit RS30D 60.0
BLENDING & LUBRICATION
7 Colloidal Silicon Dioxide (Aerosil 200) 8.0
8 Magnesium Stearate 8.0
Wt. of Core Tablets / Total 800.0
The manufacturing process consists of the preparation of a granulate obtained by mixing the required amounts of Microcrystalline cellulose (Avicel PH 101) and Oxcarbazepine in Rapid Mixer granulator for 10 min; the uniform powder mixture is moistened with solution of

Eudragit RS30D and the uniformly moistened mass is dried in a fluidized-air bed at 40-45°C. The dried granulate, milled through 1.5 mm screen and mixed with magnesium stearate and colloidal silica, passed through a 60 mesh screen. The granulation blend is then compressed into tablets.
Example 7: Trilayer Controlled release Composition
Table 7

Sr. Ingredient Qty/tablet (mg)
Composition of Supportive Layer I
GRANULA TION STA GE
1 Microcrystalline Cellulose (Avicel PH 101) 75.0
2 Hydroxy Propyl Methyl Cellulose (Methocel E 6LV) 3.0
3 Hydroxy propyl methyl cellulose (HPMC K4M) 30.0
4 Sodium carboxy methyl cellulose (Blanose 7H4FPH) 30.0
5 Purified Water q.s
BLENDING & LUBRICATION
6 Colloidal Silicon Dioxide (Aerosil 200) 1.0
7 Magnesium Stearate 1.0
Wt. of Core Tablets / Total J 40.0
Composition for Active layer
GRANULA TION STA GE
1 Oxcarbazepine@ 600.0
2 Microcrystalline Cellulose (Avicel PH 101) 25.0
3 Hydroxy propyl methyl cellulose (HPMC K15M) 58.0
4 Hydroxy Propyl Methyl Cellulose (Methocel E 6LV) 10.0
5 Purified Water q.s
BLENDING & LUBRICATION
6 Magnesium Stearate 7.0
Composition of Supportive Layer 2
GRANULA TION STA GE
1 Microcrystalline Cellulose (Avicel PH 101) 75.0
2 Hydroxy Propyl Methyl Cellulose (Methocel E 6LV) 3.0
3 Hydroxy propyl methyl cellulose (HPMC K4M) 30.0
4 Sodium carboxy methyl cellulose (Blanose 7H4FPH) 30.0
5 Purified Water q.s
BLENDING & LUBRICATION
6 Colloidal Silicon Dioxide (Aerosil 200) 1.0
7 Magnesium Stearate 1.0



Wt. of Core Tablets / Total 140.0
Wt of Triple layer Tablet 980.0
1. Granulates of Support layer 1 and 2 obtained by mixing the stated amounts of
Microcrystalline cellulose (Avicel PH 101) and Hydroxypropyl methyl cellulose (HPMC
K4M) and Sodium carboxy methyl cellulose (Blanose 7H4FPH) in Rapid Mixer granulator
for 10 min; the uniform powder mixture is moistened with solution of Hydroxypropyl Methyl
Cellulose (Methocel E 6LV) and the uniformly moistened mass is dried in a fluidized-air bed
at 40-45.degree. C. The dried granulate, milled through 1.5 mm screen and mixed with
magnesium stearate and colloidal silica passed through a 60 mesh screen.
2. Granulates of active layer obtained as per the process given in example 3
3. Preparation of the Three-Layer Systems (by Compression).
The granulates, obtained as previously quoted and according to well known models to all experts in the field, are loaded in. the feedboxes of a rotary compressing machine suitable for producing multi-layer tablets (e.g. Manesty Layer-Press, Liverpool, UK). In particular, the granulates of support layer 1 and 2 are loaded in the first and third feedboxes; whereas the granulates of active layer is loaded in the second feedbox.
Example 8: Melt Granulated Controlled Release Tablet

Table 8
Sr. No. Ingredient Qty/ tablet (mg)
GRANVLA TION STA GE
1 Oxcarbazepine 600.0
2 Microcrystalline Cellulose (Avicel PH 101) 100.0
3 Hydrogenated Castor oil 60.0
BLENDING & LUBRICATION
4 Colloidal Silicon Dioxide (Aerosil 200) 8.0
5 Glyceryl Monostearate 4.0
6 Magnesium Stearate 4.0



Wt. of Core Tablets / Total 776.0
7 Optional Non-functional film Coating 24.0
Wt. of Film coated Tablets 800.0

The manufacturing process consists of the preparation of a granulate obtained by mixing the stated amounts of Microcrystalline cellulose (Avicel PH 101) and Oxcarbazepine with Hydrogenated castor oil (sifted through # 40) in Jacketed Rapid Mixer granulator for 10 min at 80-90 C; the uniformly moistened mass is solidified at room temperature. The solidified granulate, milled through 1.5 mm screen and mixed with magnesium stearate and Glyceryl monostearate, passed through a 60 mesh screen. The granulation blend is then compressed into tablets.
It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. For example, the functions described above and implemented as the best mode for operating the present invention are for illustration purposes only. Other arrangements and methods may be implemented by those skilled in the art without departing from the scope and spirit of this invention. Moreover, those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.

Claims:
1. A controlled release pharmaceutical composition comprising oxcarbazepine or a pharmaceutically acceptable salt thereof dispersed within polymeric matrix.
2. The controlled release pharmaceutical composition of claim 1, releases oxacrbazapine or a pharmaceutically acceptable salt, over the period of more than 12 hours.
3. The polymeric matrix of claim 1 comprises a) one or more hydrophilic polymeric substances which swell, gel, and/or erode upon contact with aqueous liquids (b) optionally one or more lipophilic polymeric substances.
4. The controlled release pharmaceutical composition according to claim 3 wherein hydrophilic polymer is selected from cellulose ethers, polymers of vinylpyrrolidone, copolymers of acrylic and methacrylic acid esters containing quaternary ammonium groups.
5. The controlled release pharmaceutical composition of claim 1, wherein the composition can be coated or uncoated.
6. The controlled release dosage form of claim 1, comprising

a) about 70-85% by weight of oxcarbazepine or a pharmaceutically acceptable salt thereof,
b) about 10-20% by weight of polymer.
c) about 1-10% by weight of diluent,
d) about 1-10% by weight of binder.