Description:TECHNICAL FIELD OF THE INVENTION
The present invention relates to enteric coated colchicine compositions. The present invention further relates to a process for the preparation of the enteric coated colchicine compositions.

BACKGROUND AND PRIOR ART OF THE INVENTION
Colchicine has been in use to treat various ailments for thousands of years. The first-known description of colchicine appears in the Ebers papyrus of ancient Egypt in 1550 BC, where it was described as a treatment for pain and swelling. Colchicine is one of the few medications known from that time period whose use has survived to modernity.

Colchicine, chemically is (−)-N-[(7S,12aS)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]-acetamide, of formula (I)
(I)

Colchicine is a tricyclic alkaloid widely used for treatment of acute gout flares, prophylaxis against gout flares and treatment of other crystal diseases and familial Mediterranean fever. In addition to its commonly known uses, colchicine has potential benefits in a wide range of other conditions due to its broad anti-inflammatory effect.

Colchicine is absorbed in the jejunum and ileum and is trapped in the body tissues. It is metabolized in the liver and the intestine by cytochrome P (CYP) 450 3A4 and P-glycoprotein (PGY). Colchicine is excreted mainly by the biliary system, intestines and the kidneys. It has a narrow therapeutic range, but with normal liver and kidney functions, is relatively safe and thus can be used during pregnancy, nursing and in infants. The main mechanism of action of colchicine appears to be through interaction with microtubules affecting leukocyte chemotaxis, thereby suppressing inflammation. The blood level of colchicine may be affected by concomitant drug administration and therefore, caution should be exercised when such medications are added.

The most frequent adverse effects of oral colchicine are those involving the gastrointestinal tract and may be associated with its antimitotic action. Diarrhea, nausea, vomiting, and abdominal pain are often the first signs of toxicity and are usually an indication that colchicine therapy should be stopped or the dose should be reduced. Larger doses may cause profuse diarrhea, gastrointestinal hemorrhage, skin rashes, and renal and hepatic damage.

There is ample patented literature available on colchicine and colchicine compositions and methods of use etc.

WO2014/170755 discloses a sustained release formulation of colchicine and a pharmaceutically acceptable excipient. WO’755 recites that polymers and mixtures thereof may be used to provide the coating for the delayed or the extended release of active ingredient. WO’755 particularly discloses the sustained release tablet formulation of colchicine in gastrointestinal environment. However, WO’755 does not disclose the enteric coated composition of colchicine.

US7964647B2 describes stable ultrapure colchicine compositions comprising ultrapure colchicine and pharmaceutically acceptable excipients, methods for preparing such compositions; methods of use and methods of treating gout flares with such colchicine compositions.

WO2017156392A1 discloses liquid solution or suspension suitable for oral administration comprising colchicine and a pharmaceutically acceptable solvent system comprised of one or more agents selected from the group consisting of water, glycols, buffering agents, sweeteners, flavoring agents, preservatives, and dyes.

The prior art in its entirety fails to recognize the fact that colchicine can be provided as enteric coated compositions so that the side effects such as diarrhea, gastrointestinal hemorrhage, skin rashes, and renal and hepatic damage can be minimized or eliminated.

In order to reduce the adverse effects associated with colchicine, there is a need in the art to provide colchicine as enteric coated compositions which is stable at acidic pH so as to bypass hepatic metabolism thereby reducing the gastrointestinal adverse effects and optimizing the local absorption at the site of jejunum and ileum.

OBJECT OF THE INVENTION
In line with the above, it is an object of the present invention to provide enteric coated colchicine compositions to reduce the gastrointestinal adverse effects of colchicine and to facilitate the local absorption at the site of jejunum and ileum.

It is another object of the present invention to provide a process for preparation of the enteric coated colchicine composition.

SUMMARY OF THE INVENTION
The present invention provides enteric coated colchicine compositions to reduce the adverse gastrointestinal effects of colchicine.

In an aspect, the present invention provides an enteric coated colchicine composition comprising:
(i) An inert inner core coated with colchicine and polyvinyl pyrrolidone, wherein, the colchicine and the polyvinyl pyrrolidone are in a ratio of 1:1 to 1:25;
(ii) A seal coat over the first coat consisting of Hydroxy propyl methylcellulose E5 in an amount of 4-10% weight of the composition; and
(iii) An enteric coat over the seal coat consisting of Methacrylic acid co-polymer in an amount of 15-25wt% of the composition;
along with pharmaceutically acceptable excipients.

In an aspect, the enteric coated colchicine composition is in the form of pellets.

In an aspect, the present invention provides the pellets of different particle size to reduce the gastric time variation.

In another aspect, the present invention provides a process for preparation of enteric coated colchicine composition comprising;
a) Preparing the drug coating solution by dissolving colchicine and Polyvinyl pyrrolidone in a diluent and coating the inert inner core comprising of sugar spheres with said drug solution followed by drying to obtain the pellets until LOD (Loss-on-drying) ranges between 1 to 5%;
b) Sieving the pellets through 18-20 mesh size;
c) Coating the colchicine loaded pellets of step b) with seal coating solution comprising Hydroxypropylmethylcellulose E5 and drying the pellets until LOD (Loss- on- drying) is NMT 1.0%;
d) Coating the pellets of step c) with enteric coating solution consisting of Methacrylic acid co-polymer along with pharmaceutically acceptable excipients; and
e) Sieving the pellets of step d) through 16-20 mesh size to obtain the desired product.

Accordingly, the present process for preparing the enteric coated colchicine composition provides the initial pellets of 18-20mesh size(1000-840 micron) which on coating an increase in size is observed and the pellets of 16-20 mesh (1190-840) micron are obtained wherein 100% passes through the 16 mesh and 100%retained on 20 mesh.

In yet another aspect, the present invention provides a process for preparation of enteric coated colchicine composition comprising;
a) Preparing the drug coating solution by dissolving colchicine and Polyvinyl pyrrolidone in a diluent and coating the inert inner core comprising of sugar spheres with said drug solution followed by drying to obtain the pellets until LOD (Loss-on-drying) ranges between 1 to 5%;
b) Sieving the pellets through 25-30 mesh size;
c) Coating the colchicine loaded pellets of step b) with seal coating solution comprising Hydroxypropylmethylcellulose E5 and drying the pellets until LOD (Loss- on- drying) is NMT 1.0%;
d) Coating the pellets of step c) with enteric coating solution consisting of Methacrylic acid co-polymer along with pharmaceutically acceptable excipients; and
e) Sieving the pellets through 20-30 mesh size to obtain the desired product.

Accordingly, the present process for preparing the enteric coated colchicine composition provides the initial pellets of 25-30 mesh size(710-590 micron) which on coating an increase in size is observed and the pellets of 20-30 mesh (840-590 micron) are obtained wherein 100% passes through the 20 mesh and 100%retained on 30 mesh.

In another aspect, the enteric coated colchicine pellets are formulated into suitable dosage form selected from pill, capsule, sachet, pouch, or any other form suitable for oral administration; preferably as capsules.

In an aspect, the enteric coated colchicine pellets obtained by the process of the present invention are filled into HPMC capsule or of vegetable origin capsule by a known method.
In an aspect, the pellets of the particle size of 20-30 mesh (590-840 micron), i.e. below 1mm were used for formulation.

In another aspect, the enteric coating colchicine composition with Polyvinyl pyrrolidone in said ratio facilitates its dissolution at a higher pH thereby facilitating the absorption of colchicine at the site of jejunum and ileum of the small intestine

DETAILED DESCRIPTION OF THE INVENTION
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.

Unless specified 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. To describe the invention, certain terms are defined herein specifically as follows.

Unless stated to the contrary, any of the words, “including”, “includes”, “comprising”, and “comprises” mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items.

The present invention provides enteric coated pellets which are advantageous over the solid tablet enteric coated colchicine compositions. The enteric coated pellet composition of the present invention ensures NMT 10% of the colchicine in the gastric environment thus overcoming hepatic metabolism thereby reducing the gastrointestinal adverse effects and optimizing the local absorption at the site of jejunum and ileum which the prior arts have failed to disclose.

In an embodiment, the present invention relates to an enteric coated colchicine composition comprising:
(i) An inert inner core coated with colchicine and polyvinyl pyrrolidone, wherein, the colchicine and the polyvinyl pyrrolidone are in a ratio of 1:1 to 1:25;
(ii) A seal coat on top of the first coat consisting of Hydroxy propyl methyl cellulose E5 in an amount of 4-10% weight of the composition; and
(iii) An enteric coat over the seal coat consisting of methacrylic acid co-polymer in an amount of 15-25wt% of the composition ;
Along with pharmaceutically acceptable excipients.

The enteric coated colchicine compositions comprises 0.1wt % to 1.0wt %, or more specifically, 0.2 wt % to 0.75 wt %, of colchicine, based on the total weight of the colchicine composition.

The polyvinylpyrrolidone is used as a binder in the drug solution to be coated onto inert inner core is present in an amount ranging between 0.2 wt % to 5.0 wt % of the composition, or more specifically, in the range of 0.2wt % to 2.5wt % of the composition. Preferably, the polyvinylpyrrolidone is PVPK-30.

The methacrylic acid co-polymers for enteric coating are selected from the group consisting of Methacrylic acid methylmethacrylate copolymers, and/or methacrylic acid ethyl acrylate copolymer.

In an embodiment, the Methacrylic acid co-polymer contains free carboxylic acid groups which ionize in the pH range of 5.5 to 7.0, thereby releasing the colchicine in the lower gastrointestinal tract.

In an embodiment, the composition of the present invention is in the form of pellets having the size 16-20 mesh or 20-30 mesh; preferably 20-30 mesh.

In an embodiment, the pharmaceutically acceptable excipient(s) is selected from the group consisting of pH adjusting agent(s), plasticiser(s), emulsifier(s), glidant(s), pharmaceutically acceptable solvents as diluent(s), flavorant(s), colorant(s) and the like in suitable amounts.

The solvents which act as diluents are selected from methylene chloride, ethanol, isopropyl alcohol, hydro alcohols and purified water which is removed during the preparation of the composition.

The glidant is employed to improve flow properties and to reduce caking while coating the pellets. Suitable glidants are selected from colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, purified talc, tribasic calcium phosphate and the like, alone or combination thereof in an amount ranging between 0.2 wt % to 1.0 wt % of the composition, specifically 0.2 wt % to 0.75 wt % of the composition. Preferably, the glidant is purified talc.

The plasticizer is selected from diethylphthalate or triethylcitrate in an amount ranging between 1.5 wt % to 10 wt % of the composition, preferably in an amount of 1.5 wt % to 7.5 wt % of the composition. More specifically, the plasticizer is triethylcitrate.

The emulsifier is selected from polysorbate 80 in an amount ranging between 0.1 to 3.0 wt% of the composition, specifically 1wt% to 2wt% of the composition.

The pH adjusting agent is selected from alkali metal hydroxides such as sodium hydroxide in an amount ranging between 0.1 to 0.3 wt% of the composition, more specifically 0.1wt% to 0.2 wt% of the composition.

In an embodiment, the enteric coated colchicine composition is in the form of pellets.

In an embodiment, the present invention discloses the pellets of different particle size to reduce the gastric time variation.
In another embodiment, the present invention relates to a process for the preparation of enteric coated colchicine composition comprising;
a) Preparing the drug coating solution by dissolving colchicine and Polyvinyl pyrrolidone in a diluent and coating the inert inner core comprising of sugar spheres with said drug solution followed by drying to obtain the pellets until LOD (Loss-on-drying) ranges between 1 to 5%;
b) Sieving the pellets through 18-20 mesh;
c) Coating the colchicine loaded pellets of step b) with seal coating solution comprising Hydroxypropylmethylcellulose E5 and drying the pellets until LOD (Loss- on- drying) is NMT 1.0%;
d) Coating the pellets of step c) with enteric coating solution consisting of Methacrylic acid co-polymer along with pharmaceutically acceptable excipients; and
e) Sieving the pellets through 16-20 mesh to obtain the desired product.

Accordingly, the present process for preparing the enteric coated colchicine composition provides the initial pellets of 18-20mesh size(1000-840 micron) which on coating an increase in size is observed and the pellets of 16-20 mesh (1190-840) micron are obtained wherein 100% passes through the 16 mesh and 100%retained on 20 mesh.

In yet another embodiment, the present invention discloses a process for preparation of enteric coated colchicine composition comprising;
a) Preparing the drug coating solution by dissolving colchicine and Polyvinyl pyrrolidone in a diluent and coating the inert inner core comprising of sugar spheres with said drug solution followed by drying to obtain the pellets until LOD (Loss-on-drying) ranges between 1 to 5%;
b) Sieving the pellets through sieve size of 25-30 mesh;
c) Coating the colchicine loaded pellets of step b) with seal coating solution comprising Hydroxypropylmethylcellulose E5 and drying the pellets until LOD (Loss- on- drying) is NMT 1.0%;
d) Coating the pellets of step c) with enteric coating solution consisting of Methacrylic acid co-polymer along with pharmaceutically acceptable excipients; and
e) Sieving the pellets through sieve size of 20-30 mesh to obtain the desired product.

Accordingly, the present process for preparing the enteric coated colchicine composition provides the initial pellets of 25-30 mesh size(710-590 micron) which on coating an increase in size is observed and the pellets of 20-30 mesh (840-590 micron) are obtained wherein 100% passes through the 20 mesh and 100%retained on 30 mesh.

In an embodiment, the present invention relates to a process for preparation of enteric coated colchicine composition comprising preparing the drug coating solution by dissolving colchicine and polyvinyl pyrrolidone (PVPK-30) in isopropyl alcohol, wherein, the colchicine and polyvinyl pyrrolidone are present in a ratio of 1:1 to 1:25. Coating the sugar spheres which are loaded into conventional coating pan or perforated or partially perforated coating pan or into a fluid bed processor with said drug coating solution until the complete solution has been coated onto the sugar pellets. After the completion of the coating, the coated pellets are dried until a limit of LOD ranges between 1 to 5%. The pellets are then sieved through sieve size 18-20 mesh or through the sieve size of 25-30mesh.

The drug loaded pellets are then coated with a sealing coat with HPMC dissolved in IPA and methylene chloride. HPMC used is in the range of 4-10% weight of the total coating composition. The pellets thus obtained are then dried, so as to provide LOD NMT 1.0%.

The pellets thus obtained are further enteric coated with methacrylic acid co-polymer in an amount of 15wt% to 20wt% of the composition along with suitable pharmaceutically acceptable excipients. These pellets are then sieved through 16-20 mesh size (wherein 100% passes through 16 mesh, 100% retained on 20 mesh) or the pellets are sieved through 20-30 mesh (wherein 100% passes through 20 mesh, 100% retained on 30 mesh).

In an embodiment, the process of the present invention provides the final pellet size of around 1mm when passed through 16-20mesh (1190-840 micron) as well as below 1mm when passed through 20-30 mesh (840-590 micron).

In an embodiment, the pharmaceutically acceptable excipient(s) selected from the group consisting of pH adjusting agent(s), plasticiser(s), emulsifier(s), glidant(s), pharmaceutically acceptable solvents as diluent(s), flavorant(s), colorant(s) and the like in suitable amounts.

In another embodiment, the process for preparation of enteric coated composition comprises the ingredients;
a) 0.1wt% to 0.75wt% of colchicine;
b) 0.2wt% to 5wt% of polyvinylpyrrolidone as a binder ;
c) 4 to 10% weight of hydroxyl propylmethyl cellulose E5 in the seal coat;
d) 15wt% to 20wt% of Methacrylic acid co-polymer in the enteric coat;
e) 1.5 wt % to 10 wt % of Triethyl citrate as plasticizer;
f) 0.1 wt % to 3 wt % of Polysorbate 80 as emulsifier;
g) 0.2 wt % to 1 wt % of purified talc as glidant; and
h) 0.1 wt % to 0.3 wt % of sodium hydroxide as a pH adjusting agent.

In an embodiment, the enteric coated colchicine composition of the present invention may be suitably formulated into a dosage form selected from pill, capsule, sachet, pouch or any other form suitable for oral administration.

In a preferred embodiment, the enteric coated colchicine composition of the present invention is formulated as capsules.
In another embodiment, the enteric coated colchicine pellets prepared by the present process are filled into of HPMC capsules or of vegetable origin capsules by a known method.

In an embodiment, the pellets of smaller particle size passed through the stomach more quickly as compared to the pellets of large particle size which resulted in a more consistent gastric emptying time.

In an embodiment, the enteric coated colchicine composition of the present invention is stable at acidic pH as shown in the dissolution studies in the tables below.

In yet another embodiment, the dissolution profile of the enteric coated colchicine composition of the present invention was determined at various time points and was found to be NLT 70-75% in buffer medium at 30ᵒC and 75% relative humidity and at 40ᵒC and 75% relative humidity as shown in the tables below.

The enteric coated Colchicine composition of the present invention thus results in reduced gastrointestinal adverse effects, as it gets dissolved at a higher pH in the intestine and further facilitates the absorption of Colchicine at jejunum and ileum site of the lower gastrointestinal tract.

In another embodiment, the present invention discloses the use of enteric coated colchicine composition for treatment of inflammatory diseases such as acute gout flares, prophylaxis against gout flares, familial Mediterranean fever, age-related macular degeneration and Alzheimer's disease and v for treatment and prevention of cardiovascular diseases.

In another embodiment, the present invention relates to a method for treating inflammatory diseases such as acute gout flares, prophylaxis against gout flares, familial Mediterranean fever, age-related macular degeneration and Alzheimer's disease and for treatment and prevention of cardiovascular diseases comprising administering to a subject in need thereof a therapeutically effective amount of the enteric coated colchicine composition of the present invention.

Examples:
Following examples are given by way of illustration therefore should not be construed to limit the scope of the invention.

Example 1:
Composition of Enteric coated Colchicine Capsule (0.5 mg)
Name of the ingredient Function Amount of the ingredient by wt%
Cochicine API 0.2
IPA Diluent Q.S
PVPK-30 Binder 0.2 to 0.5
Sugar Spheres (18-20 mesh) Inner core Q.S
HPMC E5 Seal coat 4 to 10
IPA Diluent Q.S
Methacrylic acid co-polymer Retarding agent in acidic pH. 15 to 20
Sodium hydroxide pH adjuster 0.1 to 0.3
Triethyl citrate Plasticizer 1.5 to 10
Polysorbate 80 Emulsifier 0.1to 3
Purified talc Glidant 0.2 to 1
Purified water Diluent Q.S
Methylene chloride Diluent/solvent Q.S

Manufacturing process:
The drug coating solution was prepared by dissolving the colchicine (API) and Polyvinyl pyrrolidone in IPA. The sugar spheres were loaded into conventional coating pan or perforated or partially perforated coating pan or into a fluid bed processor and coating was carried out until the complete solution has been coated onto the sugar pellets.

The pellets were dried in a coating pan for 30 minutes at 45℃ or until LOD (Loss-on-drying) NMT 1.0% is obtained. The pellets were then sieved through sieve size 25-30 mesh.

The drug loaded pellets were then coated with a sealing coat using HPMC E5, IPA and methylene chloride. Drug pellets loaded in to autocoater / fluid bed coater and coating was carried out until the complete solution has been coated on to drug coated pellets. The pellets were then dried, so as to provide an LOD (Loss-on-drying) NMT 1.0%.

The pellets were then analyzed and final enteric coating was carried out with the enteric coating solution comprising Methacrylic acid co-polymer along with suitable pharmaceutical excipients such as glidant, plasticizer, emulsifier and a pH adjusting agent using suitable diluents selected from purified water, methylene dichloride and IPA. The enteric coated pellets thus obtained were then sieved through a mesh size of 20-30 mesh size (wherein 100% passed through 20 mesh and 100% retained on 30mesh) to obtain the desired product.

The enteric coated pellets of 16-20mesh are prepared from 18-20mesh by the process described above.

Example 2:
Analysis of Colchicine enteric coated Pellets/Capsule specifications
Test Specification
Description Off white spherical pellets, filled in pink cap and blue body hard gelatin capsule shells, size “2”.

Identification By HPLC: In the assay, the principal peak in the chromatogram obtained with the test solution has the same retention time as that of the principal peak in the chromatogram obtained with standard solution.
Uniformity of weight of content Between 92.5% and 107.5% of the average net content found.

Average net content 0.2790 – 0.3410 gm
90-110% of 0.31 gm

Uniformity of content
(COLCHICINE) Between 85% and 115% of the average value found (By HPLC).

Dissolution (COLCHICINE) 0.5mg /cap Not less than 0.375mg, NLT 75% (By HPLC)
Assay (COLCHICINE) 0.450 – 0.550 mg/cap
90 – 110% (By HPLC)

Example 3: Stability data and dissolution profile
Table 1:

Table 2:

Table 3:

Table 4:

 
Table 5:

Table 6:

Although the invention has been described in detail in the foregoing for the purpose of illustration, it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention except as it may be limited by the claims.
, Claims:1. An enteric coated colchicine composition comprising:
a) An inert inner core coated with colchicine and polyvinyl pyrrolidone, wherein, the colchicine and polyvinyl pyrrolidone is in a ratio of 1:1 to 1:25;
b) A seal coat over the first coat consisting of Hydroxy propyl methyl cellulose E5 in an amount of 4-10% weight of the composition; and
c) An enteric coat over the seal coat consisting of Methacrylic acid co-polymer in an amount of 15wt% to 20wt % of the composition;
along with pharmaceutically acceptable excipients.

2. The colchicine composition as claimed in claim 1, wherein the enteric coated colchicine composition is in the form of pellets.

3. The colchicine composition as claimed in claim 1, wherein colchicine is in an amount of 0.1wt% to 1.0 wt % of the composition.

4. The colchicine composition as claimed in claim 1, wherein the polyvinylpyrrolidone is present in an amount of 0.2wt % to 5.0 wt% of the composition.

5. The colchicine composition as claimed in claim 1, wherein the Methacrylic acid co-polymer selected from the group consisting of Methacrylic acid methylmethacrylate copolymers, and/or methacrylic acid ethyl acrylate copolymer.

6. The colchicine composition as claimed in claim 1, wherein the pharmaceutically acceptable excipient(s) selected from the group consisting of pH adjusting agent(s), plasticiser(s), emulsifier(s), glidant(s), pharmaceutically acceptable solvents as diluent(s), flavorant(s), colorant(s) and the like in suitable amounts.

7. The colchicine composition as claimed in claim 1, wherein the diluent is selected from methylene chloride, ethanol, isopropyl alcohol, hydro alcohols, purified water alone or combination thereof.

8. The colchicine composition as claimed in claim 1, wherein the glidants are selected from colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, purified talc, tribasic calcium phosphate and the like, alone or combination thereof in an amount ranging between 0. 2 wt % to 1.0 wt % of the composition.

9. The colchicine composition as claimed in claim 1, wherein the plasticizer is selected from diethylphthalate or triethylcitrate in an amount ranging between 1.5 wt % to 10 wt % of the composition.

10. The colchicine composition as claimed in claim 1, wherein the emulsifier is selected from polysorbate 80 in an amount ranging between 0.1 to 3.0 wt% of the composition.

11. The colchicine composition as claimed in claim 1, wherein the pH adjusting agent is sodium hydroxide in an amount ranging between 0.1 to 0.3 wt% of the composition.

12. The colchicine composition as claimed in claim 1, wherein said composition is formulated in a dosage form selected from pills, capsules, sachets or pouch or any other form suitable for oral administration.

13. The colchicine composition as claimed in claim 1, wherein the dosage form is a capsule.

14. A process for preparing the enteric coated colchicine composition comprising;
a) Preparing the drug coating solution by dissolving colchicine and Polyvinyl pyrrolidone in a diluent and coating the inert inner core comprising of sugar spheres with said drug solution followed by drying to obtain the pellets until LOD (Loss-on-drying) ranges between 1 to 5%;
b) Sieving the pellets of step a) through sieve size of 18-20 mesh;
c) Coating the colchicine loaded pellets of step b) with seal coating solution comprising Hydroxypropylmethylcellulose E5 and drying the pellets until LOD (Loss- on- drying) is NMT 1.0%;
d) Coating the pellets of step c) with enteric coating solution consisting of Methacrylic acid co-polymer along with pharmaceutically acceptable excipients; and
e) Sieving the pellets of step d) through sieve size of 16-20 mesh to obtain the desired product.

15. The process as claimed in claim 14, wherein the pellets formed in step a) may be sieved through 25-30 mesh to obtain the pellets of 20-30 mesh in step e).

16. The process as claimed in claim 14, wherein the diluent is selected from methylene chloride, ethanol, isopropyl alcohol, hydro alcohols, purified water alone or combination thereof.

17. The process as claimed in claim 14, wherein the pharmaceutically acceptable excipient(s) selected from the group consisting of pH adjusting agent(s), plasticiser(s), emulsifier(s), glidant(s), pharmaceutically acceptable solvents as diluent(s), flavorant(s), colorant(s) and the like in suitable amounts.

18. The process as claimed in claim 14, wherein the enteric coated pellets are further filled into transparent HPMC capsules or capsules of vegetable origin by known method.
19. The process as claimed in any one of the claims 14 to 18, wherein the ingredients used in the process comprises;
a) 0.1wt% to 0.75wt% of colchicine;
b) 0.2wt% to 5wt% of polyvinylpyrrolidone;
c) 4wt% to 10wt% of hydroxyl propylmethyl cellulose E5 ;
d) 15wt% to 20wt% of Methacrylic acid co-polymer;
e) 1.5 wt % to 10 wt % of Triethyl citrate;
f) 0.1 wt % to 3 wt % of Polysorbate 80;
g) 0.2 wt % to 1 wt % of purified talc; and
h) 0.1 wt % to 0.3 wt % of sodium hydroxide as a pH adjusting agent.

20. Use of enteric coated colchicine composition as claimed in any one of the preceding claims 1-19 for treatment of inflammatory diseases such as acute gout flares, prophylaxis against gout flares, familial Mediterranean fever, age-related macular degeneration and Alzheimer's disease and for treatment and prevention of cardiovascular diseases.

21. A method for treating inflammatory diseases such as acute gout flares, prophylaxis against gout flares, familial Mediterranean fever, age-related macular degeneration and Alzheimer's disease and for treatment and prevention of cardiovascular diseases comprising administering in therapeutic effective amount the enteric coated colchicine composition as claimed in any one of the preceding claims 1-20.