WO2007029093A2

WO2007029093A2 - Pharmaceutical dosage forms of oxcarbazepine

Info

Publication number: WO2007029093A2
Application number: PCT/IB2006/002440
Authority: WO
Inventors: Ajay Kumar Singla; Sachin Arora; Rahul Dabre; Vibha Puri
Original assignee: Ranbaxy Laboratories Limited
Priority date: 2005-09-05
Filing date: 2006-09-05
Publication date: 2007-03-15
Also published as: WO2007029093A3

Abstract

The present invention relates to dosage forms of oxcarbazepine and processes for the preparation thereof. The dosage forms include oxcarbazepine and a water soluble polymer selected from povidone, copovidone and mixtures thereof and processes for their preparation.

Description

PHARMACEUTICAL DOSAGE FORMS OF OXCARBAZEPINE

Technical Field of the Invention

The present invention relates to dosage forms of oxcarbazepine and processes for their preparation.

Background of the Invention

Drug insolubility is one of the major challenges in the development of many pharmaceutical products. Over one third of the drugs listed in the U.S. Pharmacopoeia and about fifty percent of new chemical entities are insoluble or poorly soluble in water. The result is that many drugs are marketed in sub-optimal formulations which after administration lead to poor or erratic bioavailability or a greater risk of adverse side effects. Oxcarbazepine (10,ll-dihydro-10-oxo-5H-dibenz[b,fJazepine-5-carboxamide) is a widely used antiepileptic drug which has poor solubility in water. Oxcarbazepine is an agent of first choice in the treatment of convulsions.

One of the earlier attempts to enhance the dissolution rate and bioavailability of oxcarbazepine relied on a particle size reduction of the oxcarbazepine to an order of 2 to 12 μm. WO 98/35681 discloses an oxcarbazepine composition for oral administration wherein micronized drug particles of 2 to 12 μm ranges are employed. It should be noted that in the examples of this publication the povidone grade being used, PVP PXL, corresponds to crospovidone which functions as a disintegrant.

Oxcarbazepine tablets are also known to undergo a color change during storage.

The discoloration is caused by the formation of a minor amount of the oxidation product, diketoiminodibenzyl, 10, l l-dihydro-5H-dibenzo [b,fj azepine-10,ll-dione. This oxidation product is considered to be pharmacologically harmless. However, the color change is not generally pharmaceutically desirable or acceptable.

U.S. Patent Nos. 5,472,714 and 5,695,782 describe color stable oxcarbazepine tablets. The color stability has been achieved by providing a double coating to the tablets. Oxcarbazepine tablets described therein are provided with hydrophilic, permeable inner layer containing white pigments and further a hydrophilic, permeable outer layer containing white pigments in combination with iron (II) oxide pigments.

WO 02/094774 discloses an oxcarbazepine formulation comprising oxcarbazepine and wetting agent, the contents of which are hereby incorporated by reference. In this patent application a wetting agent was used with oxcarbazepine. The oxcarbazepine is discloses as having a median particle size of about 20 μm to about 50 μm and a maximum residue of about 10% on a 45 μm to up to 100 μm sieve. Such particle size characteristics are believed to be attainable by milling using conventional equipment.

Summary of the Invention

hi one general aspect there is provided a pharmaceutical dosage form for oral administration. The dosage form includes oxcarbazepine and one or more water soluble polymers selected from the group consisting of povidone, copovidone and mixtures thereof.

Embodiments of the dosage form may include one or more of the following features. For example, the oxcarbazepine may have a median particle size of between about 14 μm to about 25 μm. The oxcarbazepine to water soluble polymer ratio may be from between about 1 : 1 to about 20 : 1 or it may be from between about 3 : 1 to about 15:1. The dosage form may further include one or more surfactants.

The dosage form may in the form of a capsule or tablet and the tablet may be coated. The dosage form may be a liquid dosage form. For example, the liquid dosage form may be a solution or suspension.

The dosage form may include one or more additional pharmaceutically acceptable excipients. The pharmaceutically acceptable excipients may be one or more of diluents, binders, disintegrants, lubricants, glidants, coloring agents, solvents, antioxidants, suspending agent, preservatives, surfactants, sweeteners and flavoring agents.

In another general aspect there is provided a process for the preparation of a pharmaceutical dosage form of oxcarbazepine. The process includes the steps of: dispersing a part of the oxcarbazepine in a water soluble polymer dispersion; granulating the rest of the oxcarbazepine with the dispersion of the first step to form granules; drying and sieving the granules; optionally blending one or more pharmaceutically acceptable excipients with the oxcarbazepine granules; and compressing or filling the granules into a suitably sized solid dosage form.

Embodiments of the present process may include one or more of the following features. For example, the granulation may be carried out in a fluidized bed processor or by a conventional wet granulation method.

The oxcarbazepine may have a median particle size of about between about 14 μm to about 25 μm. The water soluble polymer may be a mixture of povidone and copovidone.

The pharmaceutically acceptable excipients may be one or more of diluents, binders, disintegrants, lubricants, glidants, coloring agents, solvents, antioxidants, suspending agents, preservatives, surfactants, sweeteners and flavoring agents.

In another general aspect there is provided a method for treating partial seizures in adults with epilepsy and as an adjunctive therapy in the treatment of partial seizures in children ages 4-16 with epilepsy. The method includes administering a dosage form comprising oxcarbazepine and one or more water soluble polymers selected from the group consisting of povidone, copovidone or mixture thereof.

Embodiments of the present method may include one or more of the following features. For example, the oxcarbazepine may have a median particle size of about 14 μm to about 25 μm.

The oxcarbazepine to water soluble polymer ratio may be between about 1 : 1 to about 20:1 or, more particularly, the oxcarbazepine to water soluble polymer ratio may be from about 3:1 to about 15:1.

Detailed Description of the Invention

The inventors have now discovered that the presence of a water soluble polymer is advantageous for obtaining a bioequivalent dosage form containing oxcarbazepine. In particular, water soluble polymers such a povidone and copovidone provided dosage forms which were bioequivalent to commercially available solid and liquid dosage forms, respectively. Thus, the present invention relates to a pharmaceutical dosage form for oral administration that includes oxcarbazepine and one or more water-soluble polymers selected from the group consisting of povidone, copovidone and mixtures thereof. The oxcarbazepine may have median particle size greater than about 14 μm or the particle size may be between 14 μm and about 30 μm. For example, the dosage form may have a median particle size of between about 14 μm to 25 μm, and in particular may be approximately 17 μm.

The particle size of oxcarbazepine may be determined by commonly used methods for determining the median particle size For example, a particle size measurement may be made by using light, for example light-scattering methods, or by turbidimetric methods, sedimentation methods, for example, pipette analysis using an andreassen pipette. Particle size measurement also may be accomplished by sedimentation scales, use of photosedimentometers, or by sedimentation in a centrifugal force field, pulse methods, for example, using a Coulter counter, or sorting by means of gravitational or centrifugal force.

hi order to produce oxacarbazepine particles, e.g. crystals having the desired particle size, conventional comminution and de-agglomeration techniques may be used. For example, grinding may be accomplished in an air-jet mill or impact mill, a ball mill, vibration mill, mortar mill or pin mill.

Povidone polymers, also known as polyvidon, povidonum, PVP, and polyvinylpyrrolidone, are sold under the trade names Kollidon™ (BASF Corp.) and Plasdone™ (ISP Technologies). They are polydisperse macromolecular molecules, with a chemical name of l-ethenyl-2-pyrrolidinone polymers and l-vinyl-2-pyrrolidinone polymers. Povidone polymers are produced commercially as a series of products having mean molecular weights ranging from about 10,000 daltons to about 700,000 daltons.

The manufacturing process for povidone polymers produces polymers containing molecules of unequal chain length, and thus different molecular weights. The molecular weights of the molecules vary about a mean or average for each particular commercially available grade. Because it is difficult to determine the polymer's molecular weight directly, the most widely used method of classifying various molecular weight grades is by K-values, based on viscosity measurements. The K-values of various grades of povidone polymers represent a function of the average molecular weight, and are derived from viscosity measurements and calculated according to Fikentscher's formula.

Povidone plays diverse roles in pharmaceutical dosage forms. It is used as a dispersing and suspending agent, and has been used as a tablet binder, coating agent, and viscosity-increasing agent in pharmaceutical preparations. It also acts as a surface modifier, if the povidone polymer has a molecular weight of less than about 40,000 daltons. However, with a molecular weight of greater than 40,000 daltons, the povidone may have difficulty clearing the body. Povidone is known to improve solubility and enhance bioavailability of poorly soluble drugs by the formation of a solid dispersion.

Commercially available grades include Plasdone K-17, Plasdone K-25, Plasdone K-30, Plasdone K-29/32, Plasdone K-90, Plasdone K-90D, Plasdone C-15, Plasdone C-30, Kollidon 12 PF, Kollidon 17 PF, Kollidon 25.

Copovidone is a synthetic, 60:40, linear, random copolymer of N-vinyl-2- pyrrolidone and vinyl acetate. The addition of vinyl acetate to the vinylpyrrolidone polymer chain reduces hydrophilicity and glass transition temperature (Tg) of the polymer relative to polyvinyl pyrrolidone (PVP) homopolymer. As a result, copovidone copolymer is an excellent adhesive material and a tougher, more flexible film former than PVP homopolymer. With these unique properties, this copolymer is well suited for use in pharmaceutical formulations as a tablet binder aid for direct compression and dry granulation, as a wet granulation binder, and as an additive to improve the properties of cellulosic-based tablet coatings. The most commonly used grade of copovidone is Plasdone^® S-630.

In the formulations, the drug to water soluble polymer ratio may vary from 1 : 1 to 20: 1. For example, the ratio of drug to water soluble polymer in the formulation may vary from 3:1 to 15:1 and the water soluble polymer may be povidone, copovidone or a mixture thereof.

The other excipients used as components in this invention may include surfactants, diluents, binders, disintegrants, lubricants, glidants, suspending agent, solvents, antioxidants, preservatives, colouring agents, flavouring agents and sweeteners. The excipients must, of course, be chemically and physically compatible with oxcarbazepine.

Suitable surfactants include one or more anionic, cationic or non-ionic surface- active agents or surfactants. Suitable anionic surfactants include those containing carboxylate, sulfonate, and sulfate ions such as sodium lauryl sulfate (SLS), sodium laurate, dialkyl sodium sulfosuccinates particularly bis-(2-ethylhexyl) sodium sulfosuccinate, sodium stearate, potassium stearate, and sodium oleate. Suitable cationic surfactants include those containing long chain cations, such as benzalkonium chloride, and bis-2-hydroxyethyl oleyl amine. Suitable non-ionic surfactants include polyoxyethylene sorbitan fatty acid esters, fatty alcohols, such as lauryl, cetyl and stearyl alcohols; glyceryl esters, such as the naturally occurring mono-, di-, and tri-glycerides; fatty acid esters of fatty alcohols; polyglycolized glycerides, such as Gelucire; polyoxyethylene-polyoxypropylene block co-polymer, such as poloxamer and other alcohols, such as propylene glycol, polyethylene glycol, sorbitan, sucrose, and cholesterol.

Suitable diluents include any pharmaceutically acceptable excipients that provides bulk to the oxcarbazepine composition. Suitable diluents may include one or more of calcium carbonate, calcium phosphate-dibasic, calcium phosphate-tribasic, calcium sulfate, cellulose-microcrystalline, cellulose powdered, dextrates, dextrins, dextrose excipients, fructose, kaolin, lactitol, lactose, mannitol, sorbitol, starch, starch pregelatinized, sucrose, sugar compressible, and sugar confectioners.

Suitable binders include any pharmaceutically acceptable excipients that have cohesive properties to act as binders. Suitable binders include one or more of methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, pregelatinized starch, agar, tragacanth, sodium alginate, and propylene glycol.

Suitable disintegrants include starches or modified starches, such as starch, modified starch, croscarmellose sodium, crospovidone and sodium starch glycolate.

Suitable lubricants include one or more of colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated vegetable oil, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax, white beeswax, glyceryl monostearate, and PEG 4000.

Suitable glidants include colloidal silicon dioxide and talc.

Suitable suspending agents may include one or more of polysaccharides, (tragacanth; xanthan gum; bentonite; acacia and lower alkyl ethers of cellulose (including the hydroxy and carboxy derivatives of the cellulose ethers)), a mixture of cellulose and of xanthan gum, a mixture of polyethylene glycol and of sodium carboxymethyl cellulose, a mixture of xanthan gum and of pregelatinized starch, a mixture of microcrystalline cellulose and of sodium carboxymethyl cellulose (Avicel RC 591), and dispersed silicon dioxide (Aerosil 200).

The dosage form may further include one or more antioxidants to protect oxcarbazepine from oxidative degradation. Suitable antioxidants may include one or more of ascorbic acid, sodium pyrosulphite, glutathion or sorbic acid.

Suspensions for oral administration are usually aqueous-based. "Aqueous-based" means a suspension that includes water, or water and a water-miscible organic solvent or solvents. Suitable solvents include water miscible solvents commonly used in the art such as propylene glycol, polyethylene glycol and ethanol. These solvents also act as solvents for preservatives.

Suitable preservatives include propylparaben, methylparaben, and sorbic acid, sodium benzoate, or sodium bisulphate.

Suitable coloring agents include any colorant used in pharmaceuticals that is approved and certified by the FDA. It may include iron oxide, lake of tartrazine, lake of quinoline yellow, lake of sunset yellow and lake of erythrosine, lake of carmosine ponceau, and allura red.

Suitable sweeteners include one or more of sucrose, lactose, glucose, aspartame, saccharine, or sorbitol solution. Suitable flavouring agents include yellow plum lemon, peppermint oil, oil of wintergreen, cherry, orange or raspberry flavouring. The desired dosage form of the present invention may be a tablet, capsule suspension or solution. Tablet dosage form of the present invention may be produced by using conventional tabletting processes including dry or wet granulation.

Also provided in the present invention is a process for the preparation of the oxcarbazepine solid dosage form. The oxcarbazepine granules are prepared by dispersing a part of drug in water soluble polymer dispersion; granulating the rest of the drug with the dispersion of the first step; and then drying and sieving the granules obtained. The oxcarbazepine granules may be blended with one or more additional excipients. The granules then may be compressed or filled into a suitable size solid dosage form.

Granulation may be carried out by a conventional wet granulation method or by using a fluidized bed processor. In the case of a fluidized bed processor, there are three options available with respect to the spraying pattern of the fluid. These options are top, bottom and tangential spray processes.

In top spray granulation, particles are fluidized in the flow of heated air, which is introduced into the product container via a base plate. The coating liquid is sprayed into the fluid bed from above against the air flow (countercurrent) by means of a nozzle.

Drying takes place as the particles continue to move upwards in the air flow. Small droplets and the low viscosity of the spray medium ensure that the distribution is uniform.

Since a maximum product surface area is exposed to the spray mist, this is a fast process and feasible for batches up to 1500 kg. This technique is usually used for coating small particles and granulation of powders.

In bottom spray granulation, the beads are kept in the product chamber and are coated with the solution with the help of a Wurster design product chamber with bottom spray nozzle and partition in the middle. The principle of operation in tangential spray is that tangential nozzles are fixed above the rotating plate so as to do different operation using the same insert. The rotating plate is a specially designed perforated plate so that the powder does not fall down and at the same time air can come through the plate and create a fluidized effect in the processor. The tablet dosage form may optionally be coated with functional and/or nonfunctional layers that include film-forming polymers. The coating composition includes polymer and other coating additives.

Suitable film-forming polymers include one or more of ethylcellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, carboxymethyl cellulose, hydroxymethylcellulose, hydroxyethylcellulose, cellulose acetate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate; waxes such as polyethylene glycol; methacrylic acid polymers such as Eudragit ® RL and RS; and mixtures thereof. Alternatively, commercially available coating compositions that include film-forming polymers marketed under various trade names, such as Opadry® may also be used for coating.

Suitable coating additives may include one or more of plasticizers, coloring agents, gloss producer, and lubricants/glidants.

A polymer solution or dispersion may be prepared in various solvents, including water, ethanol, methanol, isopropyl alcohol, chloroform, acetone, ether or mixtures thereof. The coating composition may be coated onto the solid dosage form using techniques such as spray coating in conventional coating pan or fluidized bed processor, or dip coating.

The invention is further illustrated by the following examples, which are provided for illustrative purposes and should not be construed as limiting the scope of the invention.

] EXAMPLE 1

Ingredient Quantity (mg/tablet)

Oxcarbazepine Granules

Oxcarbazepine

150.00 300.00 600.00 (Median particle size 17 μ)

Pregelatanized starch 37.00 74.00 148.00

Sodium Lauryl sulphate 3.00 6.00 12.00

Povidone 9.25 18.50 37.00

Copovidone 15.75 31.50 63.00

Purified Water q.s. q.s. q.s.

Blend

Oxcarbazepine Granules 215.00 430.00 860.00

Microcrystalline cellulose 20.00 40.00 80.00

Crospovidone 12.50 25.00 50.00

Magnesium stearate 2.50 5.00 10.00

Core tablet weight 250.00 500.00 1000.00

Coating Composition

Opadry Yellow 7.50 15.00 30.00

Purified Water q.s. q.s. q.s.

Total tablet Weight 257.50 515.00 1030.00

Drug Containing Granules

1. Povidone and Copovidone were dissolved in purified water.

2. An amount of Oxcarbazepine was sifted and dispersed in the solution of step 1.

3. Sodium lauryl sulfate was dissolved in purified water and transferred to the dispersion of step 1 under stirring.

4. Pregelatinized starch and the remaining quantity of Oxcarbazepine were sifted together.

5. The blend of step 4 was granulated with the dispersion of step 3 using a top spray granulation process in a fluidized bed processor. 6. The granules were dried and passed through a sieve.

Blend

7. Microcrystalline cellulose and crospovidone were sifted together and blended with the granules of step 6.

8. Magnesium stearate was passed through a sieve and blended with the blend of step 7.

9. The blend of step 8 was compressed into suitable size tablets.

10. Tablets were film coated with the coating composition given in the table above.

The oxcarbazepine tablets were tested in 1% sodium lauryl sulphate in water according to the procedure described in the United States Pharmacopoeia XXIII, Apparatus USPII (Paddle) at 60 rpm. A comparative dissolution profile with Trileptal® 600 mg (commercially available tablets of Novartis) is given in Table 1.

TABLE 1: Dissolution profile of oxcarbazepine tablets (prepared according to Example 1) in comparison with Trileptal® in 1% aqueous sodium lauryl sulphate solution at 37⁰C /60 rpm using apparatus USP II (Paddle)/900ml.

Further, a bioavailability study of the Oxcarbazepine tablets (600 mg) of Example 1 was carried out on healthy male volunteers (n =15) taking Trileptal® Tablets (600 mg) produced by Novartis as the reference, the results of which are presented in Table 2.

Open randomized, 2 treatment, 2 period, 2 sequence, and single dose crossover, was used for comparative bioavailability study of oxcarbazepine 600 mg tablets against Trileptal® tablets 600 mg of Novartis under fast and fed conditions: The results of the study are provided in Table 2, below. Table 2: Pharmacokinetic parameters obtained through the bioavailability studies of Oxcarbazepine tablets and Trileptal® tablets.

As illustrated in Table 2, the AUC_O-K for Oxcarbazepine tablets was within 80- 125% as per FDA guidelines on bioequivalence. The above results show that Oxcarbazepine tablets 600 mg prepared as per Example 1 have a bioavailability that is comparable to the reference product, Trileptal® tablet 600 mg of Novartis.

The tablets of the present invention thus provide an effective delivery system for the administration of oxcarbazepine to patients in need of such treatment.

EXAMPLE 2

1. Methyl paraben, propyl paraben and sorbic acid were dissolved in propylene glycol.

2. Polyoxyl 8 stearate was dispersed in warm water.

3. Povidone and copovidone was dispersed in the dispersion of step 2.

4. Microcrystalline cellulose and carboxymethyl cellulose were dispersed in water.

5. Colloidal silicon dioxide was dispersed in the dispersion of step 4.

6. The dispersion of step 3 was added to dispersion of step 5.

7. Oxcarbazepine was dispersed in the dispersion of step 6 under continuous homogenization.

8. Hydroxyethylcellulose was dispersed in the oxcarbazepine dispersion.

9. A noncrystallizing sorbitol solution was added to the oxcarbazepine dispersion of step 8.

10. A solution of sodium saccharin and ascorbic acid was prepared in water and added to dispersion of step 9.

11. Preservative solution of step 1 was added to dispersion of step 10.

12. The dispersion of step 11 was homogenized until a uniform suspension was obtained and the volume was made up with purified water.

The oxcarbazepine suspension was tested in 1% sodium lauryl sulphate in water according to the procedure described in the United States Pharmacopoeia XXIII, Apparatus USPII (Paddle) at 50 rpm. A comparative dissolution profile with Trileptal® suspension 300 mg/5 ml (commercially available suspension of Novartis) is provided below in Table 3.

TABLE 3: Dissolution profile of oxcarbazepine suspension (prepared according to Example 2) in comparison with Trileptal®, in 0.6% aqueous sodium lauryl sulphate solution at 37°C/50 rpm using apparatus USP II (Paddle) / 900ml.

Further, a bioavailability study of the Oxcarbazepine suspension (300 mg/5 ml) of Example 2 was carried out on healthy male volunteers (n=16) taking Trileptal® suspension (300 mg/5ml) produced by Novartis as the reference product. The results of this study are presented below in Table 4.

An open randomized, 2 treatment, 2 period, 2 sequence, and a single dose crossover study was used for comparative bioavailability study of oxcarbazepine 300 mg/5 ml suspension against Trileptal® suspension 300 mg/5 ml of Novartis under fast and fed conditions. The results of that study are presented below in Table 4.

Table 4: Pharmacokinetic parameters obtained through the bioavailability studies of Oxcarbazepine suspension and Trileptal® suspension.

The AUC_0-X for the oxcarbazepine suspension was within 80-125% as per FDA guidelines on bioequivalence (Table 4). The above results show that the oxcarbazepine suspension 300 mg/5 ml prepared as per Example 2 has a bioavailability comparable to the reference product, Trileptal® suspension 300 mg/5 ml of Novartis.

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 included within the scope of the present invention. The examples are provided mdrely to illustrate particular aspects of the disclosure and should not be construed as limiting the scope of the present invention as defined by the claims.

Claims

We claim:

1. A pharmaceutical dosage form for oral administration comprising oxcarbazepine and one or more water soluble polymers selected from the group consisting of povidone, copovidone or mixture thereof.

2. The dosage form according to claim 1, wherein the oxcarbazepine has a median particle size of between about 14 μm to about 25 μm.

3. The dosage form according to claim 1, wherein the oxcarbazepine to water soluble polymer ratio comprises from between about 1 : 1 to about 20:1.

4. The dosage form according to claim 3, wherein the oxcarbazepine to water soluble polymer ratio comprises from between about 3 : 1 to about 15:1.

5. The dosage form according to claim 1 , wherein the dosage form further comprises one or more surfactants.

6. The dosage form according to claim 1, wherein the dosage form comprises a capsule or tablet.

7. The dosage form according to claim 6, wherein the tablet is coated.

8. The dosage form according to claim 1, wherein the dosage form comprises a liquid dosage form.

9. The dosage form according to claim 8, wherein the dosage form comprises a solution or suspension.

10. The dosage form according to claim 1, further comprising one or more additional pharmaceutically acceptable excipients.

11. The dosage form according to claim 10, wherein the pharmaceutically acceptable excipients comprise one or more of diluents, binders, disintegrants, lubricants, glidants, coloring agents, solvents, antioxidants, suspending agents, preservatives, surfactants, sweeteners and flavoring agents.

12. A process for the preparation of a pharmaceutical dosage form of oxcarbazepine, the process comprising the steps of:

a) dispersing a part of the oxcarbazepine in a water soluble polymer dispersion;

b) granulating the rest of the oxcarbazepine with dispersion of step a) to form granules;

c) drying and sieving the granules;

d) optionally blending one or more pharmaceutically acceptable excipients with the oxcarbazepine granules; and

e) compressing or filling the granules into a suitable sized solid dosage form.

13. The process according to claim 12, wherein the granulation is carried out in a fluidized bed processor or by conventional wet granulation method.

14. The process according to claim 12, wherein the oxcarbazepine comprises a median particle size of between about 14 μm to about 25 μm.

15. The process according to claim 12, wherein the water soluble polymer comprises a mixture of povidone and copovidone.

16. The process according to claim 12, wherein the pharmaceutically acceptable excipients comprise one or more of diluents, binders, disintegrants, lubricants, glidants, coloring agents, solvents, antioxidants, suspending agent, preservatives, surfactants, sweeteners and flavoring agents.

17. A method for treating partial seizures in adults with epilepsy and as adjunctive therapy in the treatment of partial seizures in children ages 4-16 with epilepsy, the method comprising administering a dosage form comprising oxcarbazepine and one or more water soluble polymers selected from the group consisting of povidone, copovidone and mixtures thereof.

18. The method according to claim 17, wherein the oxcarbazepine comprises a median particle size of about 14 μm to about 25 μm.

19. The method according to claim 17, wherein the oxcarbazepine to water soluble polymer ratio comprises from between about 1 : 1 to about 20: 1.

20. The method according to claim 17, wherein the oxcarbazepine to water soluble polymer ratio comprises from between about 3 : 1 to about 15:1.