WO2004087113A1

WO2004087113A1 - Pharmaceutical compositions for colon specific delivery

Info

Publication number: WO2004087113A1
Application number: PCT/IB2004/001041
Authority: WO
Inventors: Praveen Raheja; Shashikanth Isloor; Sanjeev Sethi; Rajiv Malik
Original assignee: Ranbaxy Laboratories Limited
Priority date: 2003-04-04
Filing date: 2004-04-05
Publication date: 2004-10-14

Abstract

The present invention relates to pharmaceutical compositions, and processes for their preparation, for oral administration that provides a colon specific delivery. The pharmaceutical has a coating having thickness less than 60 µm. The pharmaceutical composition is in the form of single dosage unit for selectively administering to the colon an active agent or its pharmaceutically acceptable salt or ester thereof. The pharmaceutical composition includes a core and a coating. The core includes an active agent or its pharmaceutically acceptable salt or ester thereof. The coating includes a layer of an anionic copolymer of methacrylic acid and methacrylic methyl ester in which the ratio of free carboxyl to ester group is about 1:2. The active agents that can be used include prednisolone, indomethacin, ibuprofen, mesalamine and the like.

Description

PHARMACEUTICAL COMPOSITIONS FOR COLON SPECIFIC DELIVERY

Field of the Invention

The present invention relates to pharmaceutical compositions, and processes for their preparation, for oral administration that provides a colon specific delivery. The pharmaceutical has a coating having thickness less than 60 μm.

Background of the Invention

There are number of active ingredients that are efficacious in the treatment of ailments of the colon or rectum, however, many of these are inactivated prior to reaching the intestine. In addition, some substances, such as mesalamine (5-Aminosalicylic acid), cause gastric irritation and ulceration during their transit through the stomach.

Consequently, it is desirable that such active ingredients be administered in a dosage form that provides a high local concentration in the colon, but with minimal systemic side effects. Such active ingredients are conventionally administered through a rectal route, by use of either suppositories or enemas. However, this is a less acceptable route and further does not deliver the active ingredient to the right side of colon, which is the desired site. Mesalamine has been used for years as an oral dosage form for the treatment of Crohn's disease or irritable bowel syndrome. This dosage form is administered in the form of sulphasalazine, which splits into mesalamine and sulphapyridine by bacteria in the colon. However, the sulphapyridine produced leads to various undesirable side effects.

To overcome these problems, several delayed release formulations have been suggested. A delayed release dosage formulation that does not disintegrate in the stomach and releases gradually in the intestine, is one of the viable options.

Polymers, such as anionic polymers have been used for many years as coatings for tablets or other dosage forms to provide delayed or sustained release of the active ingredient. Anionic polymers, in particular, copolymers of the anionic polymer of methacrylic acid and its methyl ester provide coatings that release the drug depending on the pH of the medium and the ratio of acid to ester. Such polymers are available under the trade name of Eudragit S and Eudragit L and are supplied by Rohm Pharma, GMBH, Darmstadt, Germany. Eudragit S, in which the ratio of free carboxyl group to ester group is approximately 1 :2, is insoluble in both gastric and intestinal juice. On the other hand, Eudragit L with the above ratio of 1 : 1, is insoluble in gastric juice but dissolves readily in the intestine. Combinations of these two polymers are employed to obtain the desired release profile.

U.S. Patent No. 5,541,171 discloses a pharmaceutical composition that selectively administers mesalamine or pharmaceutical acceptable salt or ester thereof to the large intestine. The dosage form has a 60-150 μm thick coating layer of the anionic copolymer of methacrylic acid and its methyl ester. The polymers are insoluble in gastric juice and in intestinal juice at a pH that is below 7, and remains intact until it reaches the colon where it is soluble. The commercially available, delayed release, mesalamine tablets available under the brand name of Asacol® is based on this concept. However, these tablets have been reported to occasionally be eliminated from the body without any release of the active ingredient or with variable bioavailability.

European Patent Application No. EP 1,004,297 discloses a pharmaceutical composition for oral administration in tablet form. The tablet contains mesalamine and a film coating comprising terpolymer, wliich contains methylacrylate, methyl methacrylate and methacrylic acid monomer units in the chain. The weight build up of film coating is between 5-7.5% by weight of the total weight of the core. However this dosage form does not give colon specific delivery.

WO 01/66094 discloses a controlled release oral solid dosage form for the administration of mesalamine into the colon. The dosage form is a capsule filled with mesalamine-containing multiparticulates coated with a layer of polymer that is soluble at a pH greater than 6.5.

Summary of the Invention

In one general aspect there is provided an oral pharmaceutical composition in the form of single dosage unit for selectively administering to the colon an active agent or its pharmaceutically acceptable salt or ester thereof. The pharmaceutical composition includes a core and a coating. The core includes an active agent or its pharmaceutically acceptable salt or ester thereof. The coating includes a layer of an anionic copolymer of methacrylic acid and methacrylic methyl ester in which the ratio of free carboxyl to ester group is about 1 :2 and the coating has a thickness that is less than 60 μm. Embodiments of the pharmaceutical composition may include one or more of the following features. For example, the core may be a tablet or a capsule. The active agent may be one or more of prednisolone, indomethacin, ibuprofen, and mesalamine and, in particular, may be mesalamine.

The anionic copolymer of methacrylic acid and methacrylic methyl ester may be

Eudragit S. The coating layer may have a thickness that is less than about 55 μm. In particular, the coating layer may have a thickness that is between about 25 μm and about 45 μm. The anionic copolymer of methacrylic acid and methacrylic methyl ester may be soluble at a pH of about 7.

The pharmaceutical composition may further include a second coating layer. The second coating layer may be an anionic copolymer of methacrylic acid with a ratio of 1 : 1 of free carboxylic acid to ester group. The anionic copolymer of methacrylic acid may be Eudragit L. The Eudragit L may be Eudragit L 100.

The core may further include one or more pharmaceutically acceptable excipients. The pharmaceutically acceptable excipients may be one ore more of fillers, binders, lubricants, and disintegrants. hi particular, the coating may further include one or more coating additives. The coating additives may be one or more of plasticizers, coloring agents, gloss producers, and lubricants/glidants. The plasticizer in the coating layer may be one or more of triethyl citrate, diethyl phthalate, dibutyl phthalate and polyethylene glycol. In particular, the plasticizer may be triethyl citrate. The triethyl citrate may be used in the coating layer at a concentration of between about 15% to about 40% w/w.

hi another general aspect there is provided an orally administered pharmaceutical composition in the form of single dosage unit for selectively administering to the colon mesalamine or its pharmaceutically acceptable salt or ester thereof. The pharmaceutical composition includes a core, a first coating layer, and a second coating layer. The core includes mesalamine or its pharmaceutically acceptable salt or ester thereof. The first coating layer includes a less than 60 μm thick layer of an anionic copolymer of methacrylic acid and methacrylic methyl ester in which ratio of free carboxyl to ester group is about 1:2 and the coating has a thickness that is less than 60 μm. The second coating layer includes an anionic copolymer of methacrylic acid and methacrylic methyl ester in which ratio of free carboxyl to ester group is about 1:1. hi another general aspect there is provided a process for preparing an orally administered pharmaceutical composition in the form of single dosage unit for selective administration to the colon of an active agent or its pharmaceutically acceptable salt or ester thereof. The process includes a granulating step, a compressing step, and a coating step. The granulating step includes granulating an active agent and one or more pharmaceutically acceptable excipients. The compressing step includes compressing the granules to form a core. The coating step includes coating the core with a coating composition. The coating composition includes an anionic copolymer of methacrylic acid and methacrylic methyl ester in which a ratio of free carboxyl to ester group is about 1 :2 and the coating has a thickness that is less than 55 μm.

Embodiments of the process include one or more of the following features. For example, the coating composition may be coated over the core in the form of a solution or dispersion. The solution or dispersion may be prepared in a solvent. The solvent may be one or more of water, ethanol, methanol, isopropyl alcohol, chloroform, acetone, ether or mixtures thereof. In particular, the solvent may be isopropyl alcohol. Coating the core may include one or more of spray coating, fiuidized bed processing, and dip coating, hi particular, the core tablet may be coated using spray coating. The core may be a tablet or a capsule.

The anionic copolymer of methacrylic acid and methacrylic methyl ester may include Eudragit S. The coating layer may have a thickness that is less than about 55 μm. i particular, the coating layer may have a thickness that is between about 25 μm and about 45 μm. The anionic copolymer of methacrylic acid and methacrylic methyl ester may be soluble at a pH of about 7.

The active agent may be one or more of prednisolone, indomethacin, ibuprofen, and mesalamine. In particular, the active agent may be mesalamine.

The process may further include a second coating layer. The second coating layer may be an anionic copolymer of methacrylic acid with a ratio of 1 : 1 of free carboxylic acid to ester group. The anionic copolymer of methacrylic acid may be Eudragit L. The Eudragit L may be Eudragit L 100.

The pharmaceutically acceptable excipients may be one or more of fillers, binders, lubricants, and disintegrants. The coating may further include one or more coating additives. The coating additives maybe one or more of plasticizers, coloring agents, gloss producers, and lubricants/glidants .

h another general aspect there is provided a method of treating ailments of the colon and/or rectum in a patient in need thereof. The method includes administering an oral pharmaceutical composition in the form of single dosage unit that provides selective administration to the colon or rectum of an active agent or its pharmaceutically acceptable salt or ester thereof. The pharmaceutical composition includes a core and a coating. The core includes an active agent or its pharmaceutically acceptable salt or ester thereof. The coating includes a layer of an anionic copolymer of methacrylic acid and methacrylic methyl ester in which the ratio of free carboxyl to ester group is about 1 :2 and the coating has a thickness that is less than 60 μm.

Embodiments of the method of treating may include one or more of the following features. For example, the coating layer may have a thickness that is less than about 55 μm. In particular, the coating layer may have a thickness that is between about 25 μm and about 45 μm.

Detailed Description of the Invention

The inventors have developed pharmaceutical compositions for oral administration, and processes for the preparation of the pharmaceutical compositions, in the form of single dosage unit that specifically releases the drug in the colon. The dosage form is coated with an anionic copolymer of methacrylic acid and methacrylic methyl ester, in which the ratio of free carboxyl to ester group is about 1 :2 and the thickness of coating layer is less than about 60 μm. The thickness of the present invention is drastically lower than the dosage forms described in prior art. hi fact, the prior art states that the coating thickness should be at least 60 μm so that the formulation can reach the target area, i.e., the colon, in its whole state. Therefore, contrary to the teachings of the prior art, it has been found that tablets coated with a layer having a thickness less than 60 μm provides satisfactory protection of the core until it reaches the colon.

This invention provides a colonic delivery dosage form with a lesser thickness of the coating layer, which leads to a weight build up of less than 5% w/w. Further, the process of preparing the dosage form involves coating the solid dosage form itself and not coating the individual particles contained therein. This provides a process that results in a relatively inexpensive and easy to manufacture dosage form. Additionally, it provides for less processing time and polymer being used, but maintains the same release profile as the oral dosage forms described in the prior art. Further, the maximum plasma concentration (T_max) and lag time in release (Tι_a ), as evaluated by in vivo bioavailability studies, were comparable to Asacol DR tablets.

The phrase "Administering an active agent or its pharmaceutically acceptable salt or ester thereof selectively to the colon" as used herein means the active agent or its pharmaceutically acceptable salt or ester thereof is released from a single dosage unit at a pH of about 7, i.e., at the pH of the colonic environment.

The term core as used herein includes tablets, capsules and the like used as single dosage units in the field of dispensing art.

Suitable active agents include compounds that are used conventionally in the treatment of colitis, ulcerative colitis, Crohn's disease and other disorders of the colon and/or rectum, including nonsteroidal anti-inflammatory compounds, such as salicylates, indomethacin and ibuprofen; steroids, such as prednisolone, hydrocortisone, prednisolone phosphate, beclomethasone propionate and valerate; compounds active in the relief of constipation or diarrhea; compounds active in the relief of spasms and improvement of motility, such as peppermint oil and other carminative essential oils; compounds for removal of excessive bile acids, such as cholestyramine; and antibacterial or antiparasitic compounds, such as erythromycin, chloroquine, iodochlorhydroxyquin, disodohydroxyquin, neomycin and tetracyclines. This invention has particular application to dosage forms of prednisolone, indomethacin, ibuprofen and mesalamine and their salts or esters thereof.

In addition to containing the active agent, the core may include one or more fillers, binders, lubricants and/or disintegrants. The core may be prepared by conventional procedures, such as dry granulation, wet granulation, direct compression, in case of tablets, or by filing, in case of capsules. The core may be coated with a solution or dispersion of the coating composition. The coating composition may include methylesterified methacrylic acid polymers and other coating additives. Methylesterified methacrylic acid polymers are available under the trade name of Eudragit S and Eudragit L and are supplied by Rohm Pharma. Eudragit S is used for coating tablets, or other solid dosage forms, to make them impervious to water and gastric juices although it is soluble in neutral or slightly alkaline media, thus releasing the drug at a pH that is greater than 7.0. Eudragit S is insoluble in gastric juices, but is readily soluble in intestinal juices. Eudragit L dissolves at pH values greater than 6, whereas Eudragit S is soluble at pH values greater than 7, thus achieving local delivery in the colon. Optionally, the Eudragit S layer can be further coated with Eudragit L, such as Eudragit L 100 and/or Eudragit L 30D-55 to obtain the desired release profile.

Coating additives may include one or more of plasticizers, coloring agents, gloss producer and lubricants/glidants. Suitable plasticizer may include one or more of diethyl phthalate, dibutyl phthalate, triethyl citrate and polyethylene glycol. The plasticizers may present in an amount between about 15% to about 40%, and in particular, about 25% to about 30% by weight with respect to the acrylic acid copolymer.

A polymer solution or dispersion may be prepared in various solvents, such as 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 a conventional coating pan, fluidized bed processing or dip coating. The coating process provides a coating thickness of about 25 μm to about 55 μm, in particular, about 25 μm to about 45 μm, with the resulting weight build up being less than about 5% w/w.

The following examples further exemplify the invention and are not intended to limit the scope of the invention.

EXAMPLE 1

A. Composition of Core Tablets (composition A)

A core was prepared containing mesalamine as the active ingredient and the following other ingredients:

Ingredients: mg/tablet

Mesalamine 400.0 Polyvinyl pyrrolidone 25.0 Microcrystalline Cellulose 51.0

Colloidal Silicon Dioxide 5.0

Sodium Starch Glycolate 10.0

Magnesium Stearate 5.0 Purified Water q.s.

Process:

Mesalamine was granulated in a rapid mix granulator using polyvinyl pyrrolidone dissolved in water. The resulting granules were then dried in a fluidized bed drier at 60°C. The granules then were blended with microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate, and magnesium stearate and compressed using a 12 mm circular, standard concave tooling on a 16 station, single rotary compression machine at 20 rpm.

B. Coating Composition

A coating composition was prepared in the form of a dispersion containing the following ingredients:

Ingredients:

Eudragit S-100 60.0 g

Triethyl citrate 18.0 g

Talc 12.0 g

Iron oxide red 1.20 g Iron oxide yellow 0.30 g

Purified water 50.0 ml

Isopropyl alcohol 600.0 ml

C. Coating Process

Eudragit S-100 was dissolved in isopropyl alcohol. Triethyl citrate, talc and colors were dispersed in purified water, and then the two were mixed to obtain the coating composition. Tablets of composition A were pre- warmed to about 40°C and spray coated in a pan coater (Freund Hi Coater) at an atomization pressure of 1-2 kg/cm², to a weight build up of about 3% w/w (about 35 μm thick). The coated tablets were then dried in the coating pan at about 45°C to about 55°C.

D. In vitro dissolution test

An In vitro dissolution test was performed on the formulation of composition A by following the method described in the United States Pharmacopoeia for delayed release tablets (USP) using a USP apparatus type 2. The results of both the dissolution testing of the formulation prepared by Example 1 and Asacol® DR tablets are listed in Table 1.

Table 1. In vitro dissolution data of Mesalamine DR tablets vs Asacol® DR tablets

E. Method of measurement of coat thickness by means of a micrometer (Mititoyo model 395-741-30)

The coat thickness of tablets prepared according to composition A were measured using a micrometer. The tablets were bisected (n=10) and put into an aqueous acidic media and sonicated for 30 minutes so that material inside the coat was removed. The coats were then dried at about 40°C in an oven for 10 minutes. The coating thickness was measured in the center and across the edges using a micrometer with a least count of 1 μm. The results of these measurements are listed in Table 2.

Table 2. Coat thickness of mesalamine tablets measured using a micrometer

F. Dissolution study under stressed conditions

A dissolution study under stressed conditions was conducted in a USP apparatus type 2 on tablets prepared according to the composition A. The study involved dissolution of the tablets for 2 hours in a pH of 1.2 (0.1 N HCl, 500 ml) followed by 4 hours at a pH of 4.5 (Acetate buffer, 900 ml) and 2 hours at a pH of 6.5 (Phosphate buffer, 900 ml). The results of the study, as shown in Table 3, clearly indicate that even under the stressed conditions encountered during variable gastric residence times in the stomach and intestine, mesalamine DR tablets provided a more consistent and predictable release profile, releasing mesalamine only at a pH above 7.2.

Table 3. Results of dissolution study under stressed conditions

G. Bioavailability study of mesalamine DR tablets

A bioavailability study of composition A and Asacol®, which is produced by Proctor and Gamble, was carried out in healthy male volunteers (n=9), the results of which are provided below in Table 4. The objective of this study was to show that a formulation prepared by this invention releases mesalamine into the distal tract of the intestine and provides an activity and safety profile that is similar to or better then the one obtained with the equivalent commercial product.

A single dose (400 mg x 2) crossover, fully replicated and open randomized study was designed as a two treatment, four period study to compare the bioavailability of mesalamine DR 400 mg of the present invention and Asacol® DR 400 mg under fasting conditions.

Plasma levels of mesalamine were analyzed and the results indicated a higher absorption of the drag from the formulation produced according to present invention. It also indicated that no release of the drug occurred in the proximal region of the colon. The pharmacokinetics results showed no significant difference in T_maχ and Tι_ag values as shown in Table 4, while the maximum plasma concentration (C_max) and the area under the plasma concentration vs time curve (AUC) values were found to be higher in the case of the present formulation as compared to an equivalent product. The cores of entire and partially disintegrated Asacol® tablets were found to be eliminated in the stool, whereas none of the tablets manufactured according to the present invention were eliminated as entire or partially disintegrated particles in the stool.

The formulation according to invention provided plasma parameters that were drastically higher than the commercially available formulation. This is evidence that the systemic absorption of mesalamine has increased, indicating a higher concentration of drag is available in the colon.

Table 4. Results of the bioavailability study of mesalamine DR and Asacol® DR tablets

Pharmacokinetic

AUC (ng.h/ml) parameter (h) Tia_g (h) Cma (ng/ml)

Mesalamine DR tablets 1980.26 10.19 4.94 225.70

Asacol® DR tablets 575.87 10.92 5.31 69.16 EXAMPLE 2

A. Composition of Core Tablets:

A core tablet was prepared containing mesalamine as the active ingredient and the following other ingredients: Mesalamine USP 400 mg

Polyvinyl pyrrolidone 25 mg

Microcrystalline Cellulose 64.875 mg

Colloidal Silicon Dioxide 5.0 mg

Sodium Starch Glycolate 0.125 mg Magnesium Stearate 5.0 mg

Purified water qs

Core tablet weight 500 mg

Process:

Mesalamine was granulated in a rapid mix granulator using polyvinyl pyrrolidone dissolved in water. The granules were then dried in a fluidized bed drier at 60°C. The granules were blended with microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate, and magnesium stearate and then compressed using 12 mm circular standard, concave tooling on a 16 station, single rotary compression machine at 20 rpm.

B. Coating Composition

Primary coat:

Ingredients: mg/tablet

Eudragit S 100 6.47

Triethyl citrate 1.94

Talc 1.29 Iron oxide red 0.258

Iron oxide yellow 0.032

Isopropyl alcohol qs

Water qs

Eudragit S was dissolved in isopropyl alcohol and triethyl citrate, talc and colors were dispersed in purified water. The two were mixed to obtain the coating composition. Tablets of composition A were pre- warmed to about 40°C and spray coated in a pan coater (Freund Hi Coater) at an atomization pressure of 1-2 kg/cm², to a weight build up of about 3% w/w (about 35 μm thick) and the coated tablets were then dried in the coating pan at about 45°C to about 55°C. Top coat:

Ingredients: mg/tablet

Eudragit L 100 16.8

Dibutyl phthalate 5.04 Talc 3.36

Iron oxide red 0.67

Iron oxide yellow 0.084

Isopropyl alcohol q.s

Water qs Eudragit L was dissolved in isopropyl alcohol. Dibutyl phthalate, talc and colors were dispersed in purified water, and then the two were mixed to obtain the coating composition. Tablets coated with the primary coat were further spray coated in a pan coater (Freund Hi Coater) at an atomization pressure of 1-2 kg/cm² until obtaining a weight gain of 5% w/w of the primary coated tablet and then the coated tablets were dried in the coating pan at about 45°C to about 55°C.

EXAMPLE 3

A. Composition of Core Tablets

Polyvinyl pyrrolidone 25 mg

Microcrystalline Cellulose 64.875 mg

Colloidal Silicon Dioxide 5.0 mg

Sodium Starch Glycolate 0.125 mg Magnesium Stearate 5.0 mg

Purified water qs

Core tablet weight 500 mg

Process:

Mesalamine was granulated in a rapid mix granulator using polyvinyl pyrrolidone dissolved in water. The granules were then dried in a fluidized bed drier at 60°C. The granules were blended with microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate, and magnesium stearate and then compressed using 12 mm circular standard, concave tooling on a 16 station single, rotary compression machine at 20 rpm, Tablets were coated with a subcoat of Opadry to a weight build up of 2% w/w of the core tablet.

B. Coating Composition

Primary coat:

Ingredients: Eudragit S 100 60 g

Triethyl citrate 18 g

Talc 12 g

Iron oxide red 2.4 g

Iron oxide yellow 0.3 g Isopropyl alcohol qs

Water qs

Eudragit S was dissolved in isopropyl alcohol. Triethyl citrate, talc and colors were dispersed in purified water, and then the two were mixed to obtain the coating composition. Tablets of composition A were pre- warmed to about 40°C and spray coated in a pan coater (Freund Hi Coater) at an atomization pressure of 1-2 kg/cm², to a weight build up of about 3% w/w (about 40-50 μm thick). The coated tablets were then dried in the coating pan at about 45°C to about 55°C.

Top coat:

Ingredients: Eudragit L 100 60 g

Dibutyl phthalate 18 g

Talc 12 g

Iron oxide red 2.4 g

Iron oxide yellow 0.3 g Isopropyl alcohol q.s

Water qs

Eudragit L was dissolved in isopropyl alcohol. Dibutyl phthalate, talc and colors were dispersed in purified water, and then the two were mixed to obtain the coating composition. Tablets were coated with the primary coat and were further spray coated in a pan coater (Freund Hi Coater) at an atomization pressure of 1-2 kg/cm² until obtaining a weight gain of 5% w/w of the primary coated tablet. The coated tablets were then dried in the coating pan at about 45°C to about 55°C. C. In vitro dissolution test

An In vitro dissolution test was performed on composition A by following the method described in the United States Pharmacopoeia (USP) for delayed release tablets using a USP apparatus type 2. The results of the dissolution testing of the tablet prepared by Example 3 are shown in Table 5.

Table 5. In vitro dissolution data of Mesalamine DR tablets

While several particular forms of the invention have been illustrated and described, it will be apparent that various modifications and combinations of the invention detailed in the text can be made without departing from the spirit and scope of the invention.

Accordingly, it is not intended that the invention be limited, except as by the appended claims.

Claims

WE CLAIM:

1. An orally administered pharmaceutical composition in the form of single dosage unit for selectively administering to the colon an active agent or its pharmaceutically acceptable salt or ester thereof, the pharmaceutical composition comprising:

a) a core, wherein the core comprises an active agent or its pharmaceutically acceptable salt or ester thereof; and

b) a coating, wherein the coating comprises a layer of an anionic copolymer of methacrylic acid and methacrylic methyl ester in which the ratio of free carboxyl to ester group is about 1 :2 and the layer has a thickness of less than 60 μm.

2. The pharmaceutical composition according to claim 1, wherein the core comprises a tablet or capsule.

3. The pharmaceutical composition according to claim 2, wherein the core comprises a tablet.

4. The pharmaceutical composition according to claim 1, wherein the active agent comprises one or more of prednisolone, indomethacin, ibuprofen, and mesalamine.

5. The pharmaceutical composition according to claim 4, wherein the active agent comprises mesalamine.

6. The pharmaceutical composition according to claim 1, further comprising a second coating layer.

7. The pharmaceutical composition according to claim 6, wherein the second coating layer comprises an anionic copolymer of methacrylic acid with a ratio of 1 : 1 of free carboxylic acid to ester group.

8. The pharmaceutical composition according to claim 6, wherem the anionic copolymer of methacrylic acid comprise Eudragit L.

9. The pharmaceutical composition according to claim 8, wherein the Eudragit L comprises Eudragit L 100.

10. The pharmaceutical composition according to claim 1, wherein the anionic copolymer of methacrylic acid and methacrylic methyl ester comprises Eudragit S.

11. The pharmaceutical composition according to claim 1, wherein the coating layer has a thickness that is between about less than about 55 μm.

12. The pharmaceutical composition according to claim 1, wherein the coating layer has a thickness that is between about 25 μm and about 45 μm.

13. The pharmaceutical composition according to claim 1, wherein the anionic copolymer of methacrylic acid and methacrylic methyl ester is soluble at a pH of about 7.

14. The pharmaceutical composition according to claim 1, wherein the core further comprises one or more pharmaceutically acceptable excipients.

15. The pharmaceutical composition according to claim 14, wherein the pharmaceutically acceptable excipients comprise one ore more of fillers, binders, lubricants, and disintegrants.

16. The pharmaceutical composition according to claim 1, wherein the coating further comprises one or more coating additives.

17. The pharmaceutical composition according to claim 16, wherein the coating additives comprise one or more of plasticizers, coloring agents, gloss producers, and lubricants/glidants.

18. The pharmaceutical composition according to claim 17, wherein the plasticizer in the coating layer comprises one or more of triethyl citrate, diethyl phthalate, dibutyl phthalate and polyethylene glycol.

19. The pharmaceutical composition according to claim 18, wherein the plasticizer comprises triethyl citrate.

20. The pharmaceutical composition according to claim 19, wherein the triethyl citrate is used in the coating layer at a concentration of between about 15% to about 40% w/w.

21. An orally administered pharmaceutical composition in the form of single dosage unit for selectively administering to the colon mesalamine or its pharmaceutically acceptable salt or ester thereof, the pharmaceutical composition comprising:

a) a core comprising mesalamine or its pharmaceutically acceptable salt or ester thereof; b) a first coating layer comprising a less than 60 μm thick layer of an anionic copolymer of methacrylic acid and methacrylic methyl ester in which ratio of free carboxyl to ester group is about 1 :2 and the coating has a thickness that is less than 60 μm; and c) a second coating layer comprising an anionic copolymer of methacrylic acid and methacrylic methyl ester in which ratio of free carboxyl to ester group is about 1:1.

22. A process for the preparation of an orally administered pharmaceutical composition in the form of single dosage unit for selective administration to the colon of an active agent or its pharmaceutically acceptable salt or ester thereof, the process comprising a) granulating an active agent and one or more pharmaceutically acceptable excipients; b) compressing the granules to form a core; and c) coating the core with a coating composition, the coating composition comprising an anionic copolymer of methacrylic acid and methacrylic methyl ester in which a ratio of free carboxyl to ester group is about 1:2 and having a thickness that is less than 60 μm.

23. The process according to claim 22, wherein the coating composition is coated over the core in the form of a solution or dispersion.

24. The process according to claim 23, wherein the solution or dispersion is prepared in a solvent.

25. The process according to claim 24, wherein the solvent comprises one or more of water, ethanol, methanol, isopropyl alcohol, chloroform, acetone, ether or mixtures thereof.

26. The process according to claim 25, wherein the solvent comprises isopropyl alcohol.

27. The process according to claim 22, wherein the coating the core comprises one or more of spray coating, fluidized bed processing, and dip coating.

28. The process according to claim 27, wherein the core tablet is coated using spray coating.

29. The process according to claim 22, wherein the core comprises a tablet or a capsule.

30. The process according to claim 22, wherein the core comprises a tablet.

31. The process according to claim 22, wherein the active agent comprises one or more of prednisolone, indomethacin, ibuprofen, and mesalamine.

32. The process according to claim 31 , wherein the active agent comprises mesalamine.

33. The process according to claim 22, further comprising a second coating layer.

34. The process according to claim 33, wherein the second coating layer comprises an anionic copolymer of methacrylic acid with a ratio of 1 : 1 of free carboxylic acid to ester group.

35. The process according to claim 34, wherein the anionic copolymer of methacrylic acid comprise Eudragit L.

36. The process according to claim 35, wherein the Eudragit L comprises Eudragit L 100.

37. The process according to claim 22, wherein the anionic copolymer of methacrylic acid and methacrylic methyl ester comprises Eudragit S.

38. The process according to claim 22, wherein the coating layer has a thickness that is less than about 55 μm.

39. The process according to claim 22, wherein the coating layer has a thickness that is between about 25 μm and about 45 μm.

40. The process according to claim 22, wherein the anionic copolymer of methacrylic acid and methacrylic methyl ester is soluble at a pH of about 7.

41. The process according to claim 22, wherein the pharmaceutically acceptable excipients comprise one ore more of fillers, binders, lubricants, and disintegrants.

42. The process according to claim 22, wherein the coating further comprises one or more coating additives.

43. The process according to claim 42, wherein the coating additives comprise one or more of plasticizers, coloring agents, gloss producers, and lubricants/glidants.

44. A method of treating ailments of the colon and/or rectum in a patient in need thereof, the method comprising orally administering a pharmaceutical composition in the form of single dosage unit that provides selective administration to the colon or rectum of an active agent or its pharmaceutically acceptable salt or ester thereof, the pharmaceutical composition comprising: a) a core, wherein the core comprises an active agent or its pharmaceutically acceptable salt or ester thereof; and b) a coating, wherein the coating comprises a layer of an anionic copolymer of methacrylic acid and methacrylic methyl ester in which the ratio of free carboxyl to ester group is about 1 :2 and the coating has a thickness of less than 60 μm.

45. The method according to claim 44, wherem the coating layer has a thickness that is less than about 55 μm.

46. The method according to claim 44, wherein the coating layer has a thickness that is between about 25 μm and about 45 μm.