F0RM2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. Title of the invention - A DELAYED RELEASE FORMULATION OF CHOLINE FENOF1BRATE
2. Applicants)

(a) NAME: ALEMBIC LIMITED
(b) NATIONALITY : An Indian Company
(C) ADDRESS: Alembic Campus, Alembic Road,
Vadodara-390 003, Gujarat, India
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed

A DELAYED RELEASE FORMULATION OF CHOLINE FENOFIBRATE
FIELD OF THE INVENTION
This invention generally relates to a delayed release formulation of choline fenofibrate and more particularly to a formulation for controlling the release of choline fenofibrate by applying at least one release rate controlling coating fayer and" at feast one enteric coating fayer.
BACKGROUND OF THE INVENTION
Choline fenofibrate is a lipid-lowering agent. The active moiety choline fenofibric acid that acts by the activation of perixisome proliferated activated receptor a (PPARa). Choline fenofibrate has a chemical name ethanaminium, 2-hydroxy-N,N,N trimethyl, 2-{4-(4-chlorobenzoyl)phenoxy] -2-methylpropanoate (1:1) and has structural formula I.

Formula I Choline fenofibrate is a white to yellow powder, which is stable under ordinary conditions. Choline fenofibrate is freely soluble in water. Choline fenofibrate in present invention is an ester salt of fenofibric acid. Fenofibric acid is well absorbed throughout the gastrointestinal tract.
Choline renotibrate is used in treatment of hypercholesterolaemia and hypertrigfyceridaemia
alone or in combination. As monotherapy, choline fenofibrate is used to reduce TG in patients
with severe hypertriglyceridaemia and to reduce elevated LDL-C, Total-C. TG. Apo B, and to
increase HDL-C in patients with primary hyperlipidemia or mixed dyslipidemia. In
combination, choline fenofibrate is used with a statin to reduce TG and increase HDL-C in
patients with mixed dyslipidemia and CHD or a CHD risk equivalent who are on optimal statin
therapy to achieve their LDL-C goal. A commercially available product containing choline
fenofibrate is Trilipix and is marketed by Abbott laboratories as 45 mg and35 mx delayed
release capsule. /

Fenofibrate is a well-known lipid regulating agent and products currently available in the market involve a formulation comprising micronized drug substance in capsule and/or tablets. However, the insolubility of fenofibrate in water may still negatively impact the in vivo performance of the product. One approach to mitigate the bioavailability issue is to render the crystalline drug amorphous, leading to accelerated drug release. However, recrystallization of amorphous materials could occur, especially for insoluble molecules such as fenofibrate. Another approach to enhance the solubility is to develop the formulation that contains salt form of fenofibrate.
US Patent No. 4,800,079 discloses a granular medicine based on controlled release of fenofibrate, each granule comprising an inert core, a layer based on fenofibrate, and a protective layer. The layer based on the fenofibrate containing the fenofibrate in the form of crystalline microparticles of dimensions not greater than 30 microns, and preferably less than 10 microns.
US Patent No. 4,895,726 discloses a novel dosage form of fenofibrate containing mixture of fenofibrate and a solid surfactant which have been co-micronized. It also relates to the method for the preparation of this dosage form and its use for improving the bioavailabity in vivo.
US application No. 20080051411 relates to a formulation in the form of molecular dispersion comprising i) fenofibric acid, a physiologically acceptable salt or derivative thereof and optionally, other active substances ii) a binder component comprising at least one enteric binder, and optionally iii) other physiologically acceptable excipients. The salt of fenofibric acid selected from the group consisting of choline, ethanolamine, diethanolamine, piperazine, calcium and tromethamine.
US Patent No. 7,259,186 discloses different salts of fenofibric acid and pharmaceutical formulations that comprises salts of fenofibric acid, which makes sufficient bioavailability of fenofibric acid. The invention also relates with the formulations that comprise fenofibric acid, a physiologically acceptable salt or a physiologically acceptable derivative thereof that is

embedded in an enteric binder as a molecular dispersion by using specialized melt granulation technique. Therefore, it is the objective of present invention to provide robust delayed release choline fenofibrate formulation, however are simple to manufacture.
SUMMARY OF THE INVENTION
In one aspect, the present invention relates to a delayed release formulation comprising: a core comprising choline fenofibrate: a release rate controlling layer coated over core; an enteric coating layer coated over release rate controlling layer.
In another aspect of invention, there is provided a delayed release formulation comprising a core which comprises choline fenofibrate and microcrystalline cellulose with one or more auxiliary pharmaceutical excipients; a release rate controlling layer coated over said core; which comprises a rate controlling hydrophobic polymer and a hydrophilic pore forming agent; an enteric coating layer coated over said release rate controlling layer; which comprises atleast one pH dependent enteric coating polymer.
In another aspect of invention, there is provided a process for preparing a delayed release formulation comprising the steps of; (a) blending choline fenofibrate with at least one diluent and at least one binder; (b) optionally, granulating the product of step (a) with a suitable solvent: (c) optionally, lubricating the product of step (a) or step (b) with a suitable lubricant; (d) compressing the product of step (c) to form a core; (e) coating the core using a hydrophobic polymer and a hydrophilic pore forming agent; (f) coating the product of step (e) using a pH dependent enteric coating polymer to form a delayed release formulation.
In another aspect, the present invention relates to delayed release pellets comprising a core comprising choline fenofibrate, a release rate controlling layer surrounding said core: an enteric coating layer surrounding said release rate controlling layer core. The said delayed release pellets are optionally compressed into tablet or filled into hard gelatin capsule.

DETAIL DESCRIPTION OF THE INVENTION
The present invention relates to delayed release formulation of choline fenofibrate. More particularly, the present invention relates to a formulation for controlling the release of choline fenofibrate by applying at least one release rate controlling coating layer and at least one enteric coating layer.
The term "delayed release" in present invention refers to release of an active ingredient from the formulation in which there is a time delay provided between oral administration of a formulation and the release of the active ingredient therefrom. Preferred "delayed release" formulations are enterically coated compositions. The delayed release pharmaceutical formulation of the present invention may release drug over a period of at least about 8 hours, or at least about 12 hours, or at least about 16 hours, or at least about 20 hours, or at least about 24 hours.
The term "dosage forms" in the present invention refers to any dosage form that is suitable for administration of active substance to an organism, particularly to mammals, preferably humans.
In an embodiment, the formulation may present in the dosage forms such as tablet, capsule, granule, powders, pellet, pellets filled in capsule, and pellets compressed into tablet.
In a preferred embodiment, the delayed release formulation comprises: a core comprising choline fenofibrate; a release rate controlling layer coated over core; an enteric coating layer coated over release rate controlling layer.
The core may comprise any inert material or mixture of materials known to one of skill in the art of drug formulation for use as cores that does not interact adversely with choline fenofibrate. Preferably, the core comprises microcrystalline cellulose. The core may preferably present in an amount of not more than about 75 percent by total weight of the formulation. More preferably, the core may present in an amount of not more than about 65 percent by

weight of the formulation. Preferably, the core may present in a weight ratio of about 3:1 to about 2.5:1 relative to the drug layer.
The choline fenofibrate in present invention may present in amount from about 20 to 50%, preferably about 30 to 40%, more preferably about 25 to 35 % by total weight of the formulation.
The term "release rate controlling layer" in present invention refers to a layer, which controls the release of the active ingredient from the formulation for a prolonged period of time.
The release rate controlling layer may contain hydrophobic polymer and hydrophilic pore forming agent and optionally plasticizer. The hydrophilic pore forming agent forms a channel through which drug is released and release rate controlling hydrophobic polymer controls the release of drug from the core. The release rate controlling layer may present in amount from about 5-25%, more preferably from 10-20% by total weight of the formulation.
The release rate controlling hydrophobic polymer can be selected from ethyl cellulose, cellulose acetate and polyvinyl acetate or any combination thereof. The release rate controlling hydrophobic polymer may present in an amount from about 10-98%. preferably from about 20-80% by total weight of the release rate controlling layer. The release rate controlling hydrophobic polymers may control the release of drug over a period of 6 to 24 hours, preferably 6-12 hours.
The term "hydrophilic pore forming agent" in present invention refers to an agent which, when used in the formulation, forms pore in contact with fluids and control the release of an active ingredient from the pores. The hydrophilic pore forming agent includes polyvinylpyrollidone, lactose, polyethylene glycol, lower grades of hydroxyl propyl methyl cellulose, hydroxyl propyl cellulose, hydroxyl ethyl cellulose or any combination thereof or other water soluble derivatives. The hydrophilic pore forming agent may present in an amount from 10-90%, preferably from about 20-80% by total weight of the release rate controlling layer.

In another embodiment, the rate controlling hydrophobic polymer and hydrophilic pore forming agent in release rate controlling layer may present in ratio from about 5:95 to 95:5, preferably from 30:70 to 70:30, more preferably from about 40:60 to 60:40. The coating may be applied by dispersing or suspending the rate controlling polymer in a suitable medium such as, water or ethanol or mixtures thereof. The resultant solution or suspension may be sprayed directly on the core followed by drying the coat.
The compositions of the present invention may be prepared using methods including wet granulation, dry granulation such as slugging or compaction, direct compression, spray coating, extrusion-spheronization and film coating.
fn another embodiment, a pH dependent enteric coating polymer layer is coated over the release rate controlling layer to protect the drug from an acid stage environment. The enteric coating polymer may be applied by dispersing or suspending the enteric polymer in a suitable medium, such as water or organic solvent or mixtures thereof, and the resultant solution or suspension may be sprayed directly over the release rate controlling layer, followed by drying to obtain delayed release formulation.
The term "pH dependant enteric coating polymer" in present invention refers to a polymer which is preferentially soluble in the less acid environment of the intestine relative to the more acid environment of the stomach. Enteric coating polymers are pH sensitive. Typically the polymers are carboxylated and interact (swell) very little with water at low pH. whilst at high pH the polymers ionise causing swelling, or dissolving of the polymer. The pH dependant enteric coating polymer can therefore be designed to remain intact in the acidic environment of the stomach (protecting either the drug from this environment or the stomach from the drug), but to dissolve in the more alkaline environment of the intestine. Preferred "enteric coating polymer" includes, but not limited to poly(methacrylic acid-co-methyl methacrylate) 1:2, poly(methacrylic acid-co-ethyl acrylate) 1:1. poly(methacrylic acid-co-methyl methacrylate) 1:1, poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) 7:3:1, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate and shellac. The enteric coating polymer

may present in amount from about 20-90%, preferably from about 30-80% by total weight of the enteric coating layer.
In one embodiment, core comprising choline fenofibrate is uncoated. In another embodiment. formulation of the present invention comprising a release rate controlling layer comprises hydrophobic polymers and hydrophilic pore forming agent. In still other embodiment. formulation comprising choline fenofibrate comprises an enteric coating layer comprises pH dependent enteric coating poJymers.
In another embodiment, the delayed release formulation exhibits less than 10% release of active ingredient after 2 hours in phosphate buffer (pH 3.5 + 0.05). The delayed release formulation exhibits about 5 to 40% release of drug after 2.5 hours, or about 40 to 60% release of drug after 3 to 4 hours, or about 95% release of drug after 6 to 8 hours in phosphate buffer (pH greater than 5).
In another embodiment, the process for producing a delayed release choline fenofibrate formulation comprises the steps of: (a) blending choline fenofibrate with at least one diluent and at least one binder; (b) optionally, granulating the product of step (a) with a suitable solvent; (c) optionally, lubricating the product of step (a) or step (b) with a suitable lubricant; (d) compressing the product of step (c) to form a core; (e) coating the core using a hydrophobic polymer and a hydrophilic pore forming agent; (f) coating the product of step (e) using a pH dependent enteric coating polymer to form a delayed release formulation.
In another embodiment, the dosage form may present in pellets form comprising an inert core, an active layer of choline fenofibrate, a release rate controlling layer surrounding said core and an enteric coating layer surrounding said release rate controlling layer.
In another embodiment, pellets formulation may present in the particle size ranging from about 0.1 to 2.0 mm in diameter. Pellets having a narrow particle size distribution from about 0.2 to 0.8 mm and with an essential round shape are preferred.

In another embodiment, pellets can be prepared by drug layering, extrusion and spheronization, and by melt-pelletization process. Drug layering layer is applied to the inert core by means of spraying the solution to the inert core in fluid bed coating equipment.
In another embodiment, inert core may be present in amount from about 10 to 50 %, preferably from about 20 to 30 %, more preferably from about 25 to 35 % by total weight of the formulation.
In an embodiment, the process for preparing pellets formulation comprising the steps of: a) dissolving the choline fenofibrate and copovidone in a mixture of ethanol and water; b) spraying the solution of step (a) on to the inert sugar core; c) optionally, coating the drug loaded pellets with polymer solution; d) coating the pellets of step b) or step c) with hydrophobic polymer and hydrophilic pore forming agent to control the release of active ingredient; d) enteric coating the coated pellets using pH dependent enteric coating polymer.
The term "diluent" in present invention refers to an inactive substance, which is used for ordinary pharmaceutical function, increase the bulk of the dosage form and give the strength to the solid dosage forms. Preferred "diluent" includes, but not limited to microcrystalline cellulose, lactose, mannitol, sorbitol, calcium phosphate, calcium carbonate, calcium sulfate and starch. The diluent may present in an amount from about 10-70%, preferably from about 15-40% by total weight of the formulation.
The term "binder" in present invention refers to an inactive substance, which is added to help hold the tablet together and give it strength. Preferred "binder" includes, but not limited to starch, gum acacia, tragacanth, sodium carboxymethylcellulose, gelatin, hydroxypropyl cellulose (e.g. Klucel®), hydroxypropyl methyl cellulose (e.g. Mefhocel®), povidone (e.g. Kollidon®, Plasdone®), sodium alginate and co-povidone. The binder may present in an amount from about 1-15%, more preferably from about 5-10% by total weight of the formulation.

The term "lubricant" in present invention refers to an excipients that reduce friction, heat and wear when applied as a surface coating to moving parts within the equipment used to make the matrices, such as dies and punches. Suitable lubricants include, either individually or in combination, stearic acid and salts thereof, including magnesium, calcium, aluminium, zinc and sodium stearates. hydrogenated vegetable oils, colloidal silica, talc, boric acid, sodium benzoate, sodium fumarate, sodium acetate, sodium stearyl fumarate and mixtures thereof. The lubricant may present in an amount from about 1-10% by total weight of the formulation.
The term "plasticizer" in present invention refers to an excipients that increase the flexibility and strength of the coating layer. Suitable plasticizers include, but not limited to propylene glycol, polyethylene glycol, triethyl citrate, acetyl triethyl citrate, diethyl phthalate, dibutyl phthalate, dibutyl sebacate, or mixtures thereof. The plasticizer may be present in an amount ranging from about 1-30% of release rate controlling layer or enteric coating layer.
The invention can be further illustrated by the non-limiting examples. Example 1
Table-1

Excipients % w/w
Choline fenofibrate 47.48
Microcrystalline cellulose 23.72
Povidone K-90 2.20
Purified talc 0.38
Magnesium stearate 0.38
Colloidal silica 0.76
Ethyl cellulose 6.76
Co-povidone 4.50
Ethanol q.s
Enteric coating 13.81
Purified water q.S

Procedure: Choline fenofibrate. microcrystalline cellulose was passed through suitable sieve and mixed properly. The powder mixture was granulated using povidone solution used as a binder. The resulting granules were dried in fluid bed dryer or tray drier and milled through suitable sieve. The extragranular materials were sieved and mixed with the sifted granules. The pre-lubricated granules were mixed with colloidal silica, magnesium stearate and talc and compressed into minitablets of desired weight. The minitablets were coated with coating dispersion and finally, enteric coated with enteric coating polymers to form a delayed release formulation.
Example 2
Table-2

Excipients % w/w
Choline fenofibrate 47.48
Microcrystalline cellulose 23.72
Povidone K-90 2.20
Purified talc 0.38
Magnesium stearate 0.38
Colloidal silica 0.76
Ethyl cellulose 6.19
Co-povidone 4.50
Triethyl citrate 0.57
Ethanol q.s
Enteric coating 13.81
Purified water q.s
Procedure: Choline fenofibrate, microcrystalline cellulose was passed through suitable sieve and mixed properly. The powder mixture was granulated using povidone solution used as a binder. The resulting granules were dried in fluid bed dryer or tray drier and milled through suitable sieve. The extragranular materials were sieved and mixed with the sifted granules. The pre-lubricated granules were mixed with colloidal silica, magnesium stearate and talc and compressed into minitablets of desired weight. The minitablets were coated with coating

dispersion and finally, enteric coated with enteric coating polymers to form a delayed release formulation.
Example 3
Table-3

Excipients % w/w
Choline fenofibrate 47.48
Microcrystalline cellulose 23.72
Povidone K-90 2.20
Purified talc 0.38
Magnesium stearate 0.38
Colloidal silica 0.76
Ethyl cellulose 6.56
Co-povidone 6.56
Ethanol q.s
Enteric coating 13.80
Purified water q.s
Procedure: Choline fenofibrate, microcrystalline cellulose was passed through suitable sieve and mixed properly. The powder mixture was granulated using povidone solution used as a binder. The resulting granules were dried in fluid bed dryer or tray drier and milled through suitable sieve. The extragranular materials were sieved and mixed with the sifted granules. The pre-lubricated granules were mixed with colloidal silica, magnesium stearate and talc and compressed into minitablets of desired weight. The minitablets were coated with coating dispersion and finally, enteric coated with enteric coating polymers to form a delayed release formulation.
Example 4
Table-4

Excipients % w/w
Sugar sphere 30.49

Choline fenofibrate 43.58
Povidone K-90 1.31
Purified water q.S
Ethanol q.s
Povidone K-90 2.18
Ethanol q.s
Ethyl cellulose 20 cps 6.20
Co-povidone 1.60
Dibutyl sebacate 0.78
Ethanol q.s
Purified water q.s
Enteric coating 13.61
Purified water q.s
Procedure: Choline fenofibrate and povidone K-90 were dissolved in a mixture of a water and ethanol. The inert sugar core was loaded in fluid bed coating equipment and coated with the above drug solution. The drug loaded pellets were sub-coated with the co-povidone solution. The sub-coated pellets were coated with the ethyl cellulose and co-povidone solution and further coated using enteric coating polymer. The pellets were optionally compressed into tablet or filled in a hard gelatin capsules.
Example 5
Table-5

Excipients % w/w
Choline fenofibrate 49.63
Microcrystalline cellulose 19.80
Povidone 1.83
Talc 0.80
Magnesium Stearate 0.80
Colloidal Silica 0.47
Ethyl cellulose 7.00

Co-povidone 7.00
Enteric coating 12.67
(Eudragit + TEC + Talc)
Procedure: Choline fenofibrate, microcrystalline cellulose was passed through suitable sieve and mixed properly. The powder mixture was granulated usjng povidone solution used as a binder. The resulting granules were dried in fluid bed dryer or tray drier and milled through suitable sieve. The extragranular materials were sieved and mixed with the sifted granules. The pre-lubricated granules were mixed with colloidal silica, magnesium stearate and talc and compressed into minitablets of desired weight. The miriitablets were coated with coating dispersion and finally, enteric coated with enteric coating polymers to form a delayed release formulation.
Example 6

Excipients % w/w
Choline fenofibrate 49.63
Microcrystalline cellulose 25.47
Povidone 1.83
Talc 0.80
Magnesium stearate 0.80
Colloidal Silica 0.47
Ethyl cellulose 7.00
Co-povidone 7.00
Enteric coating 7.00 (Eudragit + PEG + Tween 80 + Talc)
Procedure: Choline fenofibrate, microcrystalline cellulose was passed through suitable sieve and mixed properly. The powder mixture was granulated using povidone solution used as a binder. The resulting granules were dried in fluid bed dryer or tray drier and milled through suitable sieve. The extragranular materials were sieved and mixed with the sifted granules. The pre-lubricated granules were mixed with colloidal silica, magnesium stearate and talc and

compressed into minitablets of desired weight. The minitablets were coated with coating dispersion and finally, enteric coated with enteric coating polymers to form a delayed release formulation.
The delayed released properties of the formulation of present invention may be demonstrated by monitoring the dissolution of the active ingredient. The dissolution of the active ingredient may be monitored using standard procedures well known to those skilled in the art (e.g. the dissolution test procedures such as the Rotating Basket Method (Apparatus I) or Paddle Method (Apparatus II), disclosed in the U.S. Pharmacopoeia (USP). Such procedure includes those, in which the formulation is initially immersed in 500 ml phosphate buffer (pH 3.5 + 0.05) at acid stage for 2 hours. After that, pH is adjusted using sodium phosphate buffer and aliquots of the medium are withdrawn at various time points using USP type II apparatus at 50 rpm and 37 C over a period of 8 hours.
Dissolution Studies Data: Table 1

Time (hrs) Innovator (Trilipix) Example 1

% Drug dissolved
Acid stage
2 0 0
Buffer stage
2.5 32 21
3 51 53
4 76 81
5 89 90
6 98 93
8 100 95
Table 2

Time (hrs) Innovator (Trilipix) Example 2

% Drug dissolved
Acid stage
2 0 0
Buffer stage
2.5 32 27
3 51 60
4 76 85 J

5
89 94
6 98 96
8 100 98
Table 3
Time (hrs) Innovator (Trilipix) Example 3
% Drug dissolved
Acid stage
2 0 0
Buffer stage
2.5 32 29
51 54
4 76 76
5 89 84
6 98 90
8 100 96
Table 4
Time (hrs) Innovator (Trilipix) Example 4

% Drug dissolved
Acid stage
2 0 0
Buffer stage
2.5 32 26
3 51 57
4 76 78
5 89 93
6 98 100
Table 5: (Stability & dissolution data)

40°C/75°/oRH-HDPE
Example 5
Initial IM 2M 3M 6M
Assay 101 99.6 101.7 100.7 101.3
Av.Fill wt. 387.9 388.7 387.67 391.62 388.61
LOD 2.56 2.617 4.25 2.93
Water 3.814 3.017 4.78 3.948
II. Dissolution
Acid
2hrs 0.4 0.4 0.2 0.7 0

Buffer
0.5 22 15 35 15 33
1 57 52 60 53 64

2 82 80 86 83 85
3 91 89 94 91 93
4 95 94 100 98 98
6 102 99 100 101 100
III. RS
Total Impurity 0.012 0.011 0.015 0.035 0.023
Dissolution: 2 hrs in pH 3.5 phosphate buffer followed by pH 6.8 phosphate buffer, 50 rpm, Paddle
Table 6
(900ml, pH4.5 phosphate buffer, 50 rpm, paddle)

Time (hrs) Innovator (Trilipix) Example 6
% Drug dissolved
0.5 2 0
1 10 0
2 40 15
3 60 61
4 75 78
5 80 84
6 82 88
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 intended to be included within the scope of the invention.

We claim,
1) A delayed release formulation comprising: a) a core comprising choline fenofibrate; b) a release rate controlling layer coated over core; c) an enteric coating layer coated over release rate controlling layer.
2) The delayed release formulation according to claim 1. \vherein said core further comprises microcrystalline cellulose with one or more auxiliary pharmaceutical excipients.
3) The delayed release formulation according to claim 1, wherein said release rate controlling layer coated over core comprises rate controlling hydrophobic polymer and hydrophilic pore forming agent.
4) The delayed release formulation according to claim 3, wherein said rate controlling hydrophobic polymer is at least one selected from ethylcellulose, cellulose acetate. polyvinyl acetate and any combination thereof or with one or more other rate controlling polymer.
5) The delayed release formulation according to claim 3, wherein said hydrophilic pore forming agent is at least one selected from polyvinylpyrollidone, lactose, polyethylene glycol and any combination thereof or with one or more other pore forming agent.
6) The delayed release formulation according to claims 3, wherein said rate controlling hydrophobic polymer and hydrophilic pore forming agent is present in a ratio from about 5:95 to 95-.5.
7) The delayed release formulation according to claim 1, wherein said enteric coating layer comprises pH dependent enteric coating polymer at least one selected from poly(methacrylic acid-co-methyl methacrylate) 1:2. poly(methacrylic acid-co-ethyl acrylate) 1:1, poly(methacrylic acid-co-methyl methacrylate) 1:1, poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) 7:3:1, hydroxypropyl methylcellulose phthalate,

cellulose acetate phthalate, shellac and any combination thereof or with one or more other enteric polymers.
8) A delayed release formulation comprising: a) a core which comprises choline fenofibrate and microcrystalline cellulose with one or more auxiliary pharmaceutical excipients; b) a release rate controlling layer coated over said core; which comprises a rate controlling hydrophobic polymer and a hydrophilic pore forming agent; c) an enteric coating layer coated over said release rate controlling layer; which comprises at least one pH dependent enteric coating polymer.
9) A delayed release formulation comprising choline fenofibrate prepared by a process comprising me steps of;

(a) blending choline fenofibrate with at least one diluent and at least one binder;
(b) optionally, granulating the product of step (a) with a suitable solvent;
(c) optionally, lubricating the product of step (a) or step (b) with a suitable lubricant;
(d) compressing the product of step (c) to form a core;
(e) coating the core using a hydrophobic polymer and a hydrophilic pore forming agent;
(f) coating the product of step (e) using a pH dependent enteric coating polymer.