FIELD OF THE INVENTION:

The present invention relates to a greater than or equal tp 70% drug loaded formulation of Fenofibrate and its combinations thereof, which shows greater dissolution properties. The present invention relates to high drug load Fenofibrate formulations, processes for preparing these formulations and method of using high drug load formulations in the treatment of Hyperlipidemia.

BACKGROUND OF THE INVENTION:

Fenofibrate is a lipid regulating agent, chemically known as 2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl-propanoic acid,l-methylethyl ester having a structural formula

Fenofibrate was approved by the USFDA in 2004 for the treatment of hypercholesterolemia and marketed as TRICOR®, TRIGLIDE®, LIPOFEN®, FENOGLIDE® and ANTARA®. Fenofibrate is indicated as adjunctive therapy to diet to reduce elevated LDL-C, Total-C, Triglycerides and Apo B and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipisemia (Fredrickson Types IIa and IIb). Lipid altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and non-pharmacological interventions alone has been inadequate.
US 4,058,552, assigned to Orchimed SA first discloses Fenofibrate and a process for the preparation thereof.

US 4,961,890, assigned to Ethypharm, discloses a process for preparing a controlled release formulation containing Fenofibrate in an intermediate layer in the form of crystalline microparticles included within pores of an inert matrix. The formulation is prepared by a process involving the sequential steps of dampening said inert core with a solution based on said binder, then projecting said Fenofibrate microparticles in a single layer onto said dampened core, and thereafter drying, before said solution based on said binder dissolves said Fenofibrate microparticles, and repeating said three steps in sequence until said intermediate layer is formed.

US 5,545,628 assigned to Galephar P.R. Inc, discloses a pharmaceutical composition for treating hyperlipidemia or hypercholesterolemia or both in a mammal, which comprises an effective amount of each of Fenofibrate and an excipient comprising one or more polyglycolyzed glycerides. Further this patent also discloses that the composition o contains from about 5% to 95% by weight of Fenofibrate and fiom about 95% to 5% by weight of excipient including one or more polyglycolized glycerides.

US 6,277,405 assigned to Labaratoires Foumier, S.A., discloses a composition comprising a hydrosoluble carrier and micronized Fenofibrate having a dissolution of at least 10% in 5 minutes, 20% in 10 minutes, 50% in 20 minutes and 75% in 30 minutes, as measured using the rotating blade method at 75 rpm according to the European Pharmacopoeia, in a dissolution medium constituted by water with 2% by weight polysorbate 80 or with 0.025M sodium lauryl sulfate

US 6,652,881 assigned to Labaratoires Fournier, SA., discloses a composition comprising micronized Fenofibrate, wherein the composition has a dissolution of at least 10% in 5 minutes, 20% in 10 minutes, 50% in 20 minutes and 75% in 30 minutes, as , measured using the rotating blade method at 75 rpm according to the European Pharmacopoeia, in a dissolution medium constituted by water with 2% by weight polysorbate 80 or 0.025 M sodium lauryl sulfate.
US 7,041,319 B2 assigned to Labaratoires Foumier, S.A., discloses a composition comprising micronized Fenofibrate, wherein the composition has a dissolution of at least 95.9% in 30 minutes, as measured using the rotating blade method at 75 rpm according to the European Pharmacopoeia, in a dissolution medium constituted by water with 2% by weight polysorbate 80 or a dissolution medium which is 0.025 M sodium lauryl sulfate.

US 7,101,574 Bl, assigned to Laboratories des Products Ethiques Ethypharm discloses a composition in the form of granules, wherein each granule comprises a neutral microgranule on which is a composition comprising: micronized Fenofibrate, a surfactant, and a binding cellulose derivative as a solubilization adjuvant, and wherein said Fenofibrate is present in an amount greater than or equal to 60% by weight, relative to the weight of said pharmaceutical composition, and further wherein said binding cellulose derivative represents between 2 to 15% by weight, relative to the weight of said pharmaceutical composition.
Various dosages forms of Fenofibrate has poor bioavailability of the active ingredient. Indeed, due to it poor hydrosolubility, Fenofibrate is pooriy absorbed in the digestive tract and consequently its bioavailability is incomplete, irregular and often varies from one person to another.

To improve the dissolution profile of Fenofibrate and its bioavailability, thereby reducing the dose requiring to be administered, it would be useful.to increase its dissolution so that it could attain a level close to 100%.

And particularly difficult problem facing the pharmaceutical and medical communities is patient compliance with dosing regimens. Lack of adherence to a dosing regimen can be disastrous. Generally speaking, depending on the pharmacokinetic and pharmacodynamic behavior of a specific therapeutic, and the nature of the disease, a drug concentration profile in a target tissue must be achieved to produce a therapeutic effect. Efficacious drug concentration profiles are achieved through patient compliance with dosing regimens that were shown to produce a clinically relevant effect during controlled clinical trials.
Non-compliance (non-adherence) with a prescribed dosing regimen has negative clinical consequences. Lack of compliance can result in lower levels of drug in the target tissue and the disease may "escape" the effects of the drug since it is not present at inhibitory concentrations.

The pharmaceutical/medical community has focused drug development clinical trials on simple dosing regimens to promote compliance. Drugs that require complex dosing regimens are now routinely abandoned because patients will not or can not comply with the required dosing regimen.
One particular problem for creating acceptable dosing regimens is when large amounts of a drug need to be delivered to a patient: there is a limit to the size of a tablet a patient is able to swallow and the more tablets a patient has to take the more likely they will make a mistake, resulting in non-compliance. There is a need for formulations useful for the delivery of large amounts of drug, with manageable tablet (pill) burden and acceptable tablet size.

Formulation of pharmaceutical tablets typically involves mixing the active pharmaceutical ingredient (API) with one or more inactive ingredients (excipients). Formulations that contain low doses are often formulated with more excipient on a weight basis than the API to facilitate the manufacturing process like compaction, yet it results in small tablets that are easy for the patient to swallow. Since the excipient comprises a substantial portion of the total tablet weight, the processing and manufacturability of the tablets are readily adjusted regardless of the properties of the drug agent.

Conversely, with high dose drugs, the characteristics of the tablet are strongly influenced by the properties of the API. If these properties are not compatible with commercial manufacturing requirements, the formulator is faced with producing tablets that are larger in size (adding excipients to solve the manufacbiring problems), or requiring the administration of multiple tablets, each containing a lowered percentage of API, both of which negatively impact patient compliance.
There is a need for Fenofibrate containing dosage forms that contain a high drug load where the drug comprises a high percentage of the total dosage form weight to provide dosage forms of a size that facilitates patient compliance with common dosing regimens. Further the present invention provides advantages like ease in the preparation, usage of lesser amounts of excipients, which ultimately results in industrially applicable cost effective manufacture of the dosage forms.

OBJECTIVE OF THE INVENTION:

The main object of the present invention is to provide a composition comprising high drug load Fenofibrate, which shows greater dissolution properties and a process for preparation thereof.
Another object of the present invention is to provide composition comprising high drug load Fenofibrate in combination with lipid lowering agents and a process for preparation thereof.
Another object of the present invention is to provide composition comprising high drug load Fenofibrate in combination with anti-hypertensive agents and a process for preparation thereof.

SUMMARY OF THE INVENTION;

The first aspect of the present invention is to provide a composition comprising high (bug , load Fenofibrate, which shows greater dissolution properties and a process for preparation thereof.

Second aspect of the present invention is to provide a composition comprising > 70% drug load of Fenofibrate and a process for preparation thereof .

Third aspect of the present invention is to provide a composition comprising > 82.5% drug load of Fenofibrate and a process for preparation thereof.

Fourth aspect of the present invention is to provide a composition comprising high drug load Fenofibrate in combination with lipid lowering agents and a process for preparation thereof.
Fifth aspect of the present invention is to provide a composition high drug load Fenofibrate in combination with class of lipid lowering agents such as HMG-CoA reductase and fibrates.
Sixth aspect of the present invention is to provide a pharmaceutical composition comprising high drug load Fenofibrate in combination with anti-hypertensive agents and a process for preparation thereof.

Seventh aspect of the present invention is to provide pharmaceutical composition comprising high drug load Fenofibrate in combination with class of anti-hypertensive agents such as diuretics, adrenergic receptor antagonist, ACE inhibitors. Angiotensin II receptor antagonists, aldosterone antagonists, calcium channel blockers and vasodilators.

BRIEF DESCRIPTION OF THE DRAWINGS;

Further objects of the present invention together with additional features contributing thereto and advantages accruing there from will be apparent from the following description of preferred embodiments of the invention which are shown in the accompanying drawing figures, wherein:

Figure 1 illustrates the drug dissolution profile of Fenofibrate.
Figure 2 illustrates the drug dissolution profile, of Fenofibrate

DETAILED DESCRIPTION OF THE INVENTION;

The present invention relates to high drug load formulation of Fenofibrate comprising as the active pharmaceutical ingredient The current inventors have found the formulation of Fenofibrate having excellent dissolution profiles and therapeutically desirable pharmacokinetic profiles. The inventive high drug load formulation allow for the preparation of compositions comprising more than 70% or more (by weight) Fenofibrate.

The invention also relates to composition and process for making pharmaceutical compositions that exhibit one or more superior properties relative to other compositions comprising Fenofibrate.

According to the present invention, the granule or pellets or beadlets of Fenofibrate are prepared using Extrusion spheronization technique, comprising the following steps:

a) blending fenofibrate with desired excipients
b) preparing the binder solution,
c) mixing the blend with the binder solution to prepare a wet mass which is subjected to extrusion and optionally,
d) converting the extrudes to related dosage forms such as tablets, mups, capsules, sachets.

Extrusion spheronization is a well-known technique for forming beadlets of medicament. The process, in essence, comprises forming a mixture of an art-recognized spheronizing agent and other suitable dry excipients with the medicament, wet granulating the mixture with a limited amount of water to form a wetted mass of powder that is extruded through a conventional extruder equipped with a suitable screen to form discrete extrudates. The extrudates are then transferred to a spheronizer wherein they are cut and shaped into discrete spherical beadlets, which are thereafter dried. Spheronizers are commercial equipment well known to those of ordinary skill in the art.

In the one preferred embodiment dosage forms suited for oral administration like tablets, capsules, mups and sachets. The first embodiment of the invention further provides a Fenofibrate formulation having from 70% to 98% by weight Fenofibrate and from 2% to 30% by weight inactive pharmaceutical ingredients. In one aspect, the formulation has from 75% to 85% by weight Fenofibrate and 15%-25% by weight inactive pharmaceutical ingredients.

Another aspect of the present invention is to provide a composition comprising high drug load Fenofibrate in combination with other lipid lowering agents or with anti¬hypertensive agents.
According to the embodiment of the present invention the other lipid lowering agent are selected from the group of HMG-CoA reductases such as Atorvastatin, Simivastatin, Rosuvastatin, Fluvastatin, Lovastatin, Pravastatin, Fitavastatin, Cerivastatin and Mevastatin; Fibrates such as Benzafibrate, Ciprofibrate, Clofibrate and Gemfibrozil; Ezetimibe, Orlistat, Niacin, β-Sitosterol.
According to one aspect of the present invention is to provide pharmaceutical composition comprising high drug load Fenofibrate in combination with class of anti¬hypertensive agents such as Diuretics, Adrenergic Receptor Antagonist, ACE inhibitors,Angiotensin II Receptor Antagonists, Aldosterone Antagonists, Calcium Channel Blockers and Vasodilators.
In one embodiment of the present invention diuretics are selected from the group Bumetanide, Ethacrynic Acid, Furosemide, Torsemidet, Epitizide, Hydrochlorothiazide, Bendroflumiethiazide, Indapamide, Chlorthalidone, Metolazone, Amiloride, Triamterene, Spironolactone.

In second embodiment of the present invention adrenergic receptor antagonist are selected from the group of Atenolol, Metoprolol, Nadolol, Propanolol, Pindolol, Oxqprenolol, Timolol, Doxazosin, Phentolamine, Indoramin, Phenoxybenzanine, Prazosin, Terazosin, Tolazoline, Carvedilol, Labetalol, Bucindolol.
In third embodiment of the present invention calcium channel blockers are selected from the group of Amlodipine, Felodipine, Isradipine, Lercanidipine, Nicardipine, Nifedipine, Nimodipine, Nitrendipine, Diltiazem, Verapamil.
In fourth embodiment of the present invention ACE inhibitors are selected from the group of Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Perindopril, Quinapril, Ramipril and Trandolapril.

In fifth embodiment of the present invention Angiotensin II receptors are selected from the group of Candesartan, Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan and Valsartan.
In sixth embodiment of the present invention Aldosterone antagonists are selected from the group of Eplerenone and $pironolactone; vasodilators are selected from Sodium Nitroprusside.

In another embodiment, the invention provides compositions and methods usefiil for preparing unit dosage forms having Fenofibrate, or a pharmaceutically acceptable salt
thereof, as the active phannaceutical ingredient. According to one aspect of this embodiment of the invention, the composition is a pre-blend composition having Fenofibrate, one or more binders, diluents, disintegrants, and solubilizers as inactive ingredients.
One embodiment of the present invention is to provide Fenofibrate in the pre-blend composition in amounts from 70-98%, 80-98% or 85-98% of the total weight of the pre-blend composition.
The inactive ingredients (excipients) present in an amount sufficient to allow for adequate mixing with the other formulation ingredients and/or allow for adequate flowability during manufacturing. In some aspects of this embodiment, the pre-blend composition has one or more diluents present in amounts from 2-30%, 2-20% or 2-15% of the total weight of the pre-blend composition.

The preferred embodiment of the present invention is to provide compositions of Fenofibrate having 80-85% drug load of Fenofibrate.

The formulations and unit dosage forms of the invention can have a number of different ingredients. Depending on the dosage strength, a unit dosage form has an amount of active pharmaceutical ingredient (API) suffcient for achieving a therapeutic effect in a target population. Additionally "inactive pharmaceutical ingredients(excipients) need to be present to achieve a therapeutically effective release of the API. Thus the amount and type of inactive ingredients help achieve a terapeutically effective release of the therapeutic agent.

According to the embodiment of the prissent invention, the inactive pharmaceutical ingredients (excipients) include binders, diluents, disintegrants, surfactants and solubilizers.

In one aspect of the invention, a unit dosage form is provided having the following inactive ingredients: one or more disintegrants in an amount sufficient to facilitate break¬up (disintegration) of the tablet after administration (e.g., provide an, immediate release dissolution profile), one or more binders in an amount sufficient to impart adequate cohesiveness to the tablet and/or provide adequate free flowing qualities by formulation of granules of desired size/hardness, one or more diluents in an amount sufficient to impart satisfactory compression characteristics, one or more lubricants in an amoimt sufficient to provide an adequate flow rate of the granulation and/or prevent adhesion of the material to the die/punch, reduce interparticle friction, and/or facilitate ejection from the die, and if desired, optional ingredients.

When a dosage form such as a tablet is nude by the compaction of a powdered formulation, the formulation is subjected to pressure from a punch and dye. Some excipients and active pharmaceutical ingredients have a tendency to adhere to the surfaces of the punch and dye, which can cause the product to have pitting and other surface irregularities. A lubricant can be added to the formulation to reduce adhesion and ease the release of the product from the dye.
The disintegration rate and often the dissolution rate of a compacted solid pharmaceutical formulation in an aqueous environment (e.g., the patient's stomach) may be increased by the addition of a disintegrant to the formulation.

According to one embodiment of the present invention disintegrants include, but are not limited to alginic acid, crosslinked polyvinyl pyrrolidone, com starch, carboxymethylcellulose calcium, carboxymethylcellulose sodium (e.g., Ac-Di-Sol® Primellose®.), colloidal silicon dioxide, croscarmellose sodium, crospovidone (e.g., Kollidon®, Polyplasdone®), guar gum, magnesium aluminum silicate, maize starch and modified starches, methyl cellulose, microcrystalline cellulose, polyacrilin potassium, potato starch, powderpd cellulose, pregelatinized starch, sodium alginate, sodium Starch glycolate (e.g., Explotab), pregelatinized starch, starch and mixtures thereof.

According to one embodiment of the present invention binders include, but are not limited to, acacia, alginic acid, carbomers, caiboxymethyl cellulose sodium, carrageenan, cellulose acetate phthalate, ceratonia, chitosan, confectioners sugar, cottonseed oil, dextrates, dextrin, dextrose, ethylcellulose, gelatin, glucose, glyceryl behenate, guar gum, hydrogenated vegetable oil, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxylpropyl cellulose, hypromellose, magnesium aluminum silicate, maltodextrin, maltodextrin, maltose, methylcellulose, microcrystalline cellulose, poloxamer, polydextrose, polyethylene oxide, polymethyl acrylates, povidone, sodium alginate, starch, pregelantized starch, stearic acid, sucrose, sunflower oil, zein and mixtures thereof.
According to another embodiment of the present invention diluents include, but are not limited to, calcium carbonate, calcium phosphate, calcium sulfate, cellulose, cellulose acetate, compressible sugar, confectioner's sugar, dextrates, dextrin, dextrose, dibasic calcium prosphate dihydrate, ethyl cellulose, fructose, fumaric acid, glyceryl palmitostearate, hydrogenated vegetable oil, kaolin, lactitol, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, medium chaim glyceride, microcrystalline cellulose, polydextrose, polymethylacrylates, potassium chloride, powdered cellulose, simethicone, sodium alginate, sodium chloride, sorbitol, starch, pregelantized starch, sterilizable maize, sucrose, sugar spheres, talc, tragacanth, trehalose, tribasic calcium phosphate, xylitol and mixtures thereof.

In another embodiment of the present invention lubricants include, but are not limited to, calcium stearate, glycerin monostearate, glyceryl behenate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, light mineral oil, magnesium lauryl sulfate, magnesium stearate, medium chain triglycerides, mineral oil, poloxamer, polyethylene glycol, sodium benzoate, sodium chloride, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc, zinc stearate and mixtures thereof.

Yet another embodiment of the present invention glidants include, but are not limited to, calcium phosphate, calcium silicate, cellulose powdered, colloidal silicon dioxide,
magnesium silicate, magnesium trisilicate, silicon dioxide, starch, talc and mixtures thereof According to one more embodiment of the present invention surfactants comprises non-ionic surfactants like alkyl poly(ethylene oxide),a poly(ethyleneoxide). Copolymers of poly(ethylene oxide) and poly(propylene oxide) (commercially called Poloxamers or Poloxamines), alkyl polyglucosides like octly glucoside, decyl maltoside, fatty alcohols like Cetyl alcohol, oleyl alcohol, Cocamide MEA, Cocamide DEA, Polysorbates like , Tween 20, Tween 80; anionic surfactants , such as Perfluorooctanoate, perfluorooctanesulfonate, sodium dodecyl sulfate, ammonium lauryl sulfate, sodium lauryl sulfate, alkyl benzene sulfonate, soaps or fatty acid salts and cationic surfactants
such as Cetyl trimethylammonium bromide, cetylpyridinium chloride, polyethoxylated tallow amine, benzalkonium chloride, benzethonium chloride, and cetrimide (alkyltrimethylammonium bromide, predominantly C14 alkyl. The a-tocopherol and phospholipids are also used as the surfactants which enhance the bioavailability of the drug and also effects the better dissolution properties of Fenofibrate. The preferred surfactants are α-tocopherol and the compounds selected from the group of phospholipids.

According to furrther embodiment of the present invention solvent comprises: water, ethanol or mixtures thereof.

The compressed tablet can also be film coated. Film coat concentration can be varied up to about 10% to complement the drug amount, and preferably about 3.1% to about 3.3%.

Film coating suspensions include combinations of one, two or three of the following components: carboxymethylcellulose sodium, camauba wax, cellulose acetate phthalate, cetyl alcohol, confectioner's sugar, ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, liquid glucose, maltodextrin, methyl cellulose, microcrystalline wax, Opadry and Opadry II, polymethacrylates, polyvinyl alcohol, shellac, sucrose, talc, titanium dioxide, and zein.

The dissolution of the Fenofibrate pellets may be determined by the following method.
Table-I
Instniment Apparatus H, USP (Paddle)
Revolution 75/min.
Temperature 37±0.5°C
Dissolution 1000 ml 0.05 M Sodium lauryl sulfate. Fenofibrate was determined
medium using a UV Spectrophotometer.
In the appended table, the above described dissolution test was used to determine the release rates of the particular dosage forms.
Table II-Dissolution Profile:
Time (minutes) % Release
10 49.70%
20 67.80%
30 77.40%
45 86.70%
60 90.50%
The dissolution of the Fenofibrate pellets is enhanced when the surfactant used is either
a-tocopherol or phospholipids, which is determined by the following method.
Table-III
Instrument Apparatus H, USP (Paddle)
Revolution 75/min.
Temperature 37±0.5°C
Dissolution 1000 ml 0.05 M Sodium lauryl sulfate. Fenofibrate was determined
medium using a UV Spectrophotometer.

In the appended table, the above described dissolution test was used to detemine the release rates of the particular dosage fonns.
Table IV-Dissolution Profile:
Time (minutes) % Release
0 0%

5 57.9% 10 81.6%
15 88.6%
30 94.1%
45 97.0%
60 97.5%
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

The present invenition can be illustrated in one of its embodiment by the following non-
limiting examples.

EXAMPLES:

Example 1: Preparation of Fenofibrate pellets containg 82.50% drug load

a) Preparation of binder solution:
2.12 gm of PVP K30 and 4.24 gm of Sodium lauryl sulfate were and dissolved in SO mi of purified water with constant stirring.

b) Preparation of pellets:
165 gm of Fenofibrate and 3.4 gm of sodium lauryl sulfate were passed through # 40 and blended for 2 minutes. 10.28 gm of sodium starch glycolate, 9.82 gm of microcrystalline cellulose and 5.14 gm of PVP K30 were mixed and passed through # 40 and blended with the above prepared blend for 2 minutes. The binder solution was mixed with the above prepared dry mixture to produce a wet mass. The wet mass was transferred to an extruder (0.05mm) to result extrudes of Fenofibrate composition. After the extrusion process was completed the extrudes were air dried for about 20 minutes at room temperature and the temperature was raised to 45°C and maintained for 1 hr. The resulting extrudes were sieved using # 24 and # 40 mesh and packed in a suitable HDPE containers.

Example 2: Preparation of capsules containing 84.84% drug load of Fenofibrate pellets

a) Preparation of binder solution:
12.5 gm of PVP K30 and 25 gm of Sodium lauryl sulfate were sieved and dissolved in 500 ml of purified water with constant stirring.
b) Preparation of Capsules:
1 kg of Fenofibrate, 60.6 gm of sodium starch glycolate and 3.4 gm of sodium lauryl sulfate were passed through # 40 and blended for 2 minutes. 30.3 gm of microcrystalline cellulose and 30.3 gm of PVP K30 were mixed and passed through # 40 and blended with the above prepared blend for 2 minutes. The binder solution was mixed with the above prepared dry mixture to produce a wet mass. The wet mass was transferred to an extruder (0.05mm) to produce extrudes of Fenofibrate composition. After the extrusion process was completed the extrudes were air dried for about 20 minutes at room temperature and the temperature was raised to 45°C and maintained for I hr. The resulting extrudes were sieved using # 24 and # 40 mesh. The final coated pellets are filled into suitable capsules.

Example 3: Preparation of capsules containing 82.5% drug load of Fenofibrate pellets

a) Preparation of binder solution:
2 gm of PVP K30 and 6 gm of Sodium lauryl sulfate were sieved and dissolved in 100 ml of purified water with constant stirring.

b) Prqparation of Capsules:
165 gm of Fenofibrate, 5.2 gm of microcrystalline cellulose and 6.2 gm of sodium lauryl sulfate were passed through # 40 and blended for 2 minutes. 30.3 gm of sodium starch glycolate and 30.3 gm of PVP K30 were mixed and passed through # 40 and blended with the above prepared blend for 2 minutes. The binder solution was mixed with the above prepared dry mixture to produce a wet mass. The wet mass was transferred to an extruder (0.05mm) to produce extrudes of Fenofibrate composition. After the extrusion process was completed the extrudes were air dried for about 20 minutes at room temperature and the temperature was raised to 45°C and maintained for 1 hr. The resulting extrudes were sieved using # 24 and # 40 mesh. The final coated pellets are filled into suitable capsules.

Example 4: Preparation of capsules containing 87% drug load of Fenofibrate pellets comprising a-Tocopherol as surfactant

a) Preparation of binder solution:
1.5 gm of PVP K30, 2 gm of sodium lauryl sulphate, 32 gm of Fenofibrate and 1 gm of PEG 6000 were dissolved in methylene chloride and isopropyl alcohol (IP A) to prepare a binder solution.

b) Preparation of pellets:
55 gm of Fenofibrate was blpnded with 2 gm of HPMC E5, 2.5 gm of microcrystalline cellulose, 1.5 gm of polyplasdone XL-10 and 2.5 gm of a-Tocopherol in a blender for 2 minutes and sieved imder # 40 mesh. The blended powder was mixed with the binder solution to prepare wet mass. Prepared wet mass was extruded with 0.5mm screen at 60 rpm. The elongated pellets obtained were dried at 45°C to a moisture content of between 1.5 to 2%.The final pellets were filled into suitable capsules.

Example 5: Preparation of capsules containing 66% drug load of Fenofibrate pellets

a) Preparation of binder solution:
1 gm of PVP K30, 2 gm of sodium lauryl sulphate, 26 gm of Fenofibrate and 4 gm of PEG 6000 were dissolved in methylene chloride and IPA to prepare a binder solution.

b) Preparation of pellets:
40 gm of Fenofibrate was blended with 2 gm of HPMC E5, 3 gm of sodium lauryl sulfate, 17gm of microcrystalline cellulose, 2 gm of polyplasdone XL-10, 2.5 gm of a-tocopherol and 1.5 gm of phospholipon 80H in a blender for 2 minutes and sieved under # 40 mesh. The blended powder was mixed with the binder solution to prepare wet mass. Prepared wet mass was extruded with 0.5mm screen at 60rpm. The elongated pellets obtained were dried at 45°C to a moisture content of between 1.5 to 2%. The final pellets are filled into suitable capsules.

We claim:

1) A pharmaceutical composition comprising a high drag load of Fenofibrate, wherein the Fenofibrate is present in more than 70% by weight of total composition.

2) The pharmaceutical composition according to claim 1, dissolution properties such as greater than 60% drug release in 5 minutes in presence of an absorption enhancer.

3) The pharmaceutical composition according to claim 1, comprising not more than 30% by weight of excipients, selected from the group of gUdants, lubricants, fillers, binders, disintegrants, diluents, surfactants, and solutions.

4) The pharmaceutical composition according to claim 3, the surfactants is selected preferably from phospholipids or alpha tocopherol or mixtures thereof,

5) A process for the preparation of pharmaceutical composition of Fenofibrate
comprising the steps of:

a. blending Fenofibrate with excipients
b. preparing the binder solution,
c. mixing the blend with the binder solution to prepare a wet mass which is
subjected to extrusion and optionally,
d. converting the extrades to related dosage forms.

6) A process for the preparation of pharmaceutical composition of Fenofibrate
comprising the steps of:

a. blending a Fenofibrate, α-tocopherol and other excipients,
b. preparing the binder solution,
c. mixing the blend with the binder solution to prepare a wet mass which is
subjected to extrusion and optionally,
d. converting the extrudes to related dosage forms.

7) A process for the preparation of pharmaceutical composition of Fenofibrate
comprising the steps of:
a. blending a Fenofibrate, a surfactant selected from the group of phospholipids and
other excipients,
b. preparing the binder solution,
c. mixing the blend with the binder solution to prepare a wet mass which is
subjected to extrusion and optionally,
d. converting the extrudes to related dosage forms.

8) The process of preparation Fenofibrate according to claim 5, 6 and 7, wherein flie
related dosage forms are selected from the group of capsules, tablets, mups and sachets.