DESC:FIELD OF THE INVENTION

The invention relates to orally administrable pharmaceutical composition in the form of tablet and process of preparation thereof. Disclosed invention comprises pantoprazole or pharmaceutically acceptable salts thereof in inner core tablet and middle drug coat wherein the inner core is further acrylic coated and the middle drug coat is enteric coated to provide dual time-dependent release of pantoprazole in gastrointestinal tract.

BACKGROUND OF THE INVENTION

Many active pharmaceutical agents, including drugs and prodrugs, have been formulated as orally deliverable dosage forms providing sustained release (otherwise known as slow release or extended release) of such agents over a period of time effective to permit once daily administration. In particular, number of drug delivery and release systems have been developed that influence the control of drug release.

Pantoprazole, 5-(difluoromethoxy)-2-[(3,4-dimethoxy-2-pyridyl)methylsulphinyl]-1H-benzimidazole, is a H+/K+-adenosine triphosphate (ATP) inhibitor (also known as acid pump or proton pump inhibitor (PPI), an enzyme present in the gastric parietal cells. It is believed that these drugs are metabolized in the parietal cells to active sulfenamide metabolites that inactivate the sulfhydryl group of the proton pump, thus reducing the hydrogen ion secretion. PPIs are generally lipophilic weak bases with poor aqueous solubility at low pH. Many PPIs are unstable in low pH solutions and undergo rapid acid-catalyzed degradation, and they are relatively stable at neutral or high pH.

U.S. Patent No. 5,997,903 discloses oral –administration forms of pantoprazole that consist of a core, an intermediate layer surrounding the core and an outer gastric acid resistant layer surrounding intermediate layer.
U.S. Patent Application No. 2006/165797 discloses oral forms of PPI wherein PPI (omeprazole) is present in outer coat and inner delayed release coat. The outer coat is not enteric coated and quickly dissolves in the stomach of a patient immediately after ingestion (60 min).

PCT Application No. WO1999/032093 (A1) discloses enteric coated dosage forms of proton pump inhibitor (omeprazole) with pulsed delayed release and instant release fraction wherein the portions are released in time by from 0.5 up to 4 or 8 or 12 hours interval.

PCT Application No. WO 2006/049565 (A1) discloses solid forms of PPI (esomeprazole) comprising delayed and immediate release tablets with lag time of 1-10 hrs.

The average half life of pantoprazole is only 1 hour. Diseases like H. pylori infection and gastroesophageal reflux diseases need twice daily administration of the pantoprazole. The two times daily dosing regimen for pantoprazole tablets is well tolerated, but patient compliance would be much improved if a once-daily regimen were possible. In this regard, it will be noted that once-daily regimen would be especially useful in enhancing compliance among elderly patients.

Thus, there is a need to develop a drug delivery system for the release of drug in the gastrointestinal tract that provides, for example: (1) long-lasting drug efficacy (2) site-specific delivery to multiple release sites and (3) reduced dosing frequency.

It has been found by the inventors that formulation of pantoprazole tablet in a dual release system is generally helpful in providing once-daily dosing. Release characteristics can be further modified by coating the tablet with an acrylic acid copolymer and enteric coating polymer.

OBJECT OF THE INVENTION

The main object of the invention is to provide a dual time-dependent release of oral tablet composition of pantoprazole or pharmaceutically acceptable salts thereof.
It is an object of the invention to provide a novel compositions and methods for the multiple releases of pantoprazole or pharmaceutically acceptable salts thereof in the gastrointestinal tract of a subject through the use of dual drug release system. The dual drug release system provides, for example, site-specific release of the drug in the form of multiple controlled doses for long-lasting efficacy, thereby reducing the drug dosing frequency.

Yet another object of the invention is to provide an improved and simple process for preparing the dual release oral tablet composition of pantoprazole or pharmaceutically acceptable salts thereof.

It is an object of the invention to provide a dual release oral tablet composition comprising:
a) an acrylic coated core tablet comprising a therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients;
b) a middle drug coat comprising a therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients;
c) an outer enteric coating surrounding the said middle drug coat, wherein;
the first dose of pantoprazole is released from the middle drug coat immediately after administration and second dose of pantoprazole or pharmaceutically acceptable salts thereof is released from tablet core after a lag of 6 to 12 hours from the first dose.

It is an object of invention to provide a pharmaceutical composition in the form of a tablet comprising:
a) an acrylic coated core tablet comprising a therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof, sodium carbonate anhydrous and a pharmaceutically acceptable excipient;
b) a middle drug coat comprising a therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable excipient;
c) an outer enteric coating surrounding the said middle drug coat,
wherein; the weight ratio of pantoprazole or pharmaceutically acceptable salts thereof to sodium carbonate anhydrous is from 7:1 to 1:1 and the first dose of pantoprazole is released from the middle drug coat and second dose of pantoprazole is released from tablet core after a lag of about 6 to about 12 hours from the first dose.

SUMMARY OF THE INVENTION

One embodiment describes a novel composition comprising pantoprazole or pharmaceutically acceptable salts thereof having dual release system. Particularly the preferred embodiment describes stable dual release oral tablet composition of pantoprazole wherein the pantoprazole is present in inner core tablet and in middle drug coat wherein the inner core tablet is further acrylic coated and the middle drug coat is further enteric coated. The said composition provides dual time-dependent release of the pantoprazole to achieve better bioavailability and therapeutic efficacy. One embodiment also provides process for preparation of such composition.

DETAILED DESCRIPTION OF THE INVENTION

It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the invention will be limited only by the appended claims.

Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the invention, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited.

Unless otherwise indicated, this disclosure uses the following definitions.

"Pharmaceutical composition" refers to the combination of one or more drug substances and one or more excipients.

The term ‘pantoprazole’ refers to 5-(difluoromethoxy)-2-[(3,4-dimethoxy-2-pyridyl)methylsulphinyl]-1H-benzimidazole and enantiomers and salts and hydrates thereof.

"Pharmaceutically acceptable" substances refer to those substances which are within the scope of sound medical judgment suitable for use in contact with the tissues of subjects without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit-to-risk ratio, and effective for their intended use.

The term "extended release" as used in the invention refers to a composition that makes the drug available over an extended period after ingestion, and preferably, although not necessarily, results in substantially constant blood levels of the drug over an extended time period. The term extended release used in context of the invention includes, but not limited to, zero order release of the drug.

The term “dose” herein means a portion of a pharmaceutical composition that contains an amount of a therapeutic agent.

The term “immediately after administration” refer to release of drug at least after 1 hour of administration.

In this invention, we had a desired dual release profile of the oral tablet compositions of pantoprazole or pharmaceutically acceptable salts thereof comprising pantoprazole in inner core tablet which is coated with acrylic acid copolymer and in middle drug coat which is coated with enteric coating. The composition also contains pharmaceutically acceptable excipients such talc, colloidal silicon dioxide, magnesium stearate, hydrophobic agents, an alkali compound, fillers, binders, disintegrants or their mixtures.

According to the main embodiment there is provided a pharmaceutical composition in the form of a tablet comprising:
a) an acrylic coated core tablet comprising a therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients;
b) a middle drug coat comprising a therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients;
c) an outer enteric coating surrounding the said middle drug coat, wherein;
the first dose of pantoprazole is released from the middle drug coat immediately after administration and second dose of pantoprazole or pharmaceutically acceptable salts thereof is released from tablet core after a lag of 6 to 12 hours from the first dose.

In one embodiment the first dose of pantoprazole or pharmaceutically acceptable salts thereof is released from the middle drug coat immediately after administration that is at least after 1 hour of administration.

In one embodiment of the invention, the pharmaceutical composition comprises pantoprazole or salt thereof. Pantoprazole can be present in the form of pantoprazole sodium sesquihydrate. Alternatively pantoprazole can be present in any salt known to person skilled in the art.

A novel pharmaceutical composition according to the embodiment comprises one or more orally deliverable dose units of pantoprazole or pharmaceutically acceptable salts thereof. Each dose unit comprises the drug in a therapeutically effective amount of about 1% to about 20% of the total weight of the tablet, preferably about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% or 20%. More preferred is about 5% or 10% or 15% or 20% of the total weight of the tablet.

In an embodiment, the first dose of the pantoprazole or pharmaceutically acceptable salts thereof in a composition of the invention, which is the fraction providing immediate release, is present in a middle coat, wherein the amount of pantoprazole or pharmaceutically acceptable salts thereof present in said middle coat is from about 1% to about 20% of the total weight of the tablet; preferably about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% or 20%. More preferred is about 5% or 10% or 15% or 20% of the total weight of the tablet. The second dose of the pantoprazole or pharmaceutically acceptable salts thereof in a composition of the invention, which is the fraction providing release after a lag time of about 6 to 12 hours, is present in a inner core tablet, wherein the amount of pantoprazole or pharmaceutically acceptable salts thereof present in said inner core tablet is from about 1% to about 20% of the total weight of the tablet; preferably about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% or 20%. More preferred is about 5% or 10% or 15% or 20% of the total weight of the tablet.

In another embodiment, the core tablet comprises therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients including but not limited to mannitol, pregelatinised starch, colloidal silicon dioxide, sodium starch glycolate, talc, calcium sterate and sodium carbonate anhydrous.

The said core tablet is prepared by conventional method known to the person skilled in the art. Pantoprazole or pharmaceutically acceptable salts thereof and sodium carbonate anhydrous in inner core tablet are present in a weight ratio of about 7:1 to about 1:1; preferably about 7:1, about 6.5:1, about 6:1, about 5.5:1, about 5:1, about 4.5:1, about 4:1, about 3.5:1, about 3:1, about 2.5:1, about 2:1, about 1.5:1 or about 1:1. More preferred ratio is about 3.5:1.

Alternatively, the sodium carbonate anhydrous is present in the invention composition in about 1% to about15% by weight of total composition, preferably about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14% or 15% by weight of total composition.

Further seal coating of about 1% to about 5% or about 2% of the total weight of the composition is applied to the core tablet. Seal coating solution is prepared by the addition of PEG400 followed by hypromellose to purified water under stirring. Then it is applied using conventional method such as autocoater.

In another embodiment, acrylic acid co-polymer coating is applied over the core tablet which is seal coated. Various acrylic acid co-polymers used in the invention comprise polyacrylic acid, polymethacrylic acid, acrylic acid/methacrylic acid copolymers (such as Eudragit S100), polyvinyl alcohols, high molecular weight polyethylene glycols, polyoxyethylene/polyoxypropylene block copolymers, high molecular weight polyvinylpyrrolidones or mixtures thereof. This polymer may present in an amount of about 3% to about 9% by weight of the total weight of the composition, preferably about 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5% or 9% by weight of the total weight of the composition. More preferred is about 4.5% or 6.5 % or 8.5% by weight of the total weight of the composition.

The acrylic acid co-polymer (Eudragit® S100) coating solution is prepared by the addition of triethyl citrate and talc to IPA:water (95:5) mixture followed Eudragit S100, under continuous stirring for 45 minutes. A 6% coating is applied on seal coated tablets. Further seal coating is again applied on the acrylic acid coating. Approximately 2.0% seal coating is given using an autocoater.

In another embodiment, pantoprazole or pharmaceutically acceptable salts or thereof is present in a middle drug coat along with one or more pharmaceutically acceptable excipients comprising triethyl citrate and sodium carbonate anhydrous. This drug coating solution is prepared by the addition of triethyl citrate and sodium carbonate to purified water under stirring followed by Pantoprazole and stirring for 30 minutes. Pantoprazole and sodium carbonate anhydrous in middle coat is present in a weight ratio of about 30:1 to about 10:1, preferably about 30:1 or about 25:1 or about 20:1 or about 15:1 or about 10:1. More preferred is about 20:1. Further seal coating is again applied on the middle drug coating. Approximately 2.0% seal coating is given using an autocoater.

In another embodiment, enteric coating is applied over the middle drug coat which is seal coated. Enteric coating may comprises cellulose acetate phthalate, cellulose acetate succinate, hydroxpropyl cellulose phthalate, hydroxpropyl ethylcellulose phthalate, hydroxylpropyl methyl cellulose phthalate, hydroxylpropyl methyl cellulose acetate succinate, hydroxyethyl cellulose phthalate, methylcellulose phthalate, polyvinyl acetate phthalate, polyvinylacetate hydrogen phthalate, amylase acetate phthalate, cellulose ester phthalates, cellulose ether phthalates, sodium cellulose acetate phthalate, starch acid phthalate, cellulose acetate butyrate, cellulose acetate maleate, cellulose acetate trimellitate, cellulose acetate propionate, styrene maleic acid dibutyl phthalate copolymer, styrene maleic acid polyvinyl acetate phthalate copolymer propionate, shellac or mixtures thereof.

Enteric coating solution is prepared by the addition of Instacoat super to purified water, and then homogenizing the solution for 20 mins. Enteric coating is applied between 2% to 10% of the total weight of the tablet or about 6% of the total weight of the tablet.

The dual release oral tablet composition of this invention comprise one or more pharmaceutically acceptable excipients selected from the group comprising binders, diluents, fillers, lubricants, glidants, disintegrants, alkalizers, basic stabilizers, coloring agents and flavoring agents.

Suitable binders may comprise but are not limited to pregelatinised starch, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol, polymethacrylates, starch, gelatin, alginic acid, sucrose and the like or mixtures thereof.

Suitable diluents and fillers may comprise but are not limited to microcrystalline cellulose, cellulose, lactose, starch, calcium phosphates, calcium sulphates, mannitol, glucose, sucrose, sorbitol and the like or mixtures thereof.

Suitable lubricants may comprise but are not limited to stearic acid, magnesium, calcium or sodium stearate, sodium stearyl fumarate, talc, waxes, liquid paraffin, and the like or mixtures thereof.

Suitable glidants may comprise but are not limited to talc, aluminium silicate, colloidal silica, starch and the like or mixtures thereof.

Suitable disintegrants may comprise but are not limited to alginic acid and salts, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, starch, sodium starch glycolate, crosslinked polyvinyl pyrrolidone and the like or mixtures thereof.

Suitable alkalizer may comprise but are not limited to sodium carbonate anhydrous, sodium bicarbonate, potassium citrate and the like or mixtures thereof.

In one embodiment, first dose of pantoprazole or pharmaceutically acceptable salts thereof from middle coat is released immediately after the administration of tablet, preferably after 1 hour. Second dose of pantoprazole from core tablet is released after lag time of about 6 to about 12 hours or about 8 hours from the first dose.

In another embodiment there is provided a pharmaceutical composition in the form of a tablet comprising:
a) an acrylic coated core tablet comprising a therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof, sodium carbonate anhydrous and a pharmaceutically acceptable excipient;
b) a middle drug coat comprising a therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable excipient;
c) an outer enteric coating surrounding the said middle drug coat,
wherein; the weight ratio of pantoprazole or pharmaceutically acceptable salts thereof to sodium carbonate anhydrous is from 7:1 to 1:1 and the first dose of pantoprazole is released from the middle drug coat and second dose of pantoprazole is released from tablet core after a lag of about 6 to about 12 hours from the first dose.

In another embodiment there is provided a pharmaceutical composition in the form of a tablet comprising:
a) an acrylic coated core tablet comprising pantoprazole or pharmaceutically acceptable salts thereof in about 10% of total weight of the tablet, sodium carbonate anhydrous and a pharmaceutically acceptable excipient;
b) a middle drug coat comprising pantoprazole or pharmaceutically acceptable salts thereof in about 10% of total weight of the tablet and a pharmaceutically acceptable excipient;
c) an outer enteric coating surrounding the said middle drug coat,
wherein; the weight ratio of pantoprazole or pharmaceutically acceptable salts thereof to sodium carbonate anhydrous is from 3.5:1 and the first dose of pantoprazole is released from the middle drug coat and second dose of pantoprazole is released from tablet core after a lag of about 6 to about 12 hours from the first dose.

Tablets can be made using standard technology well known in the art. Drugs used in the core or the middle coating may be granulated by methods such as slugging, low-shear or high-shear granulation, wet granulation, or fluidized bed granulation. Coatings may be formed by preparing a mixture containing appropriate polymers and a sufficient amount of drug to produce a therapeutically effective dose.

In another embodiment, the composition is prepared by mixing pantoprazole with one or more pharmaceutically acceptable excipients to produce a homogeneous mixture that forms the drug core of the tablet. A seal coating solution is applied onto the drug core. The acrylic acid co-polymer coat is prepared, e.g., by dissolving Eudragit S100, triethyl citrate and talc to IPA:water (95:5) mixture. This acrylic coating is applied on core tablet which is seal coated. Again seal coating is applied onto acrylic acid coating. Middle coat containing pantoprazole and triethyl citrate and sodium carbonate is prepared and applied onto the seal coat. Again seal coating is applied onto middle coat. Finally outer enteric coating is prepared and applied using autocoater.

In another embodiment there is provided a process for preparation of pharmaceutical composition disclosed in any embodiment, wherein the said process comprises:
i) preparation of core tablet containing pantoprazole or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable excipient, seal coating the said core tablet;
ii) applying acrylic acid copolymer coating over seal coated core tablet and seal coating over the acrylic coating;
iii) forming middle drug coat containing pantoprazole or pharmaceutically acceptable salts thereof over seal coat, applying seal coating to the drug coat;
iv) applying enteric coating over seal coating using an autocoater.

The embodiments of the specification are further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the invention.

Example 1: Pharmaceutical composition containing Pantoprazole
Table 1
Sr. No. Ingredients % W/W Unit qty. (mg)
Core Tablet
Dry mixing
1 Pantoprazole sodium Sesqui hydrate 9.90 22.76
2 Mannitol (Pearlitol 25C) 31.10 71.52
3 Pregelatinised starch 1500 6.52 15
4 Aerosil 200 0.87 2
Granulation
5 Sodium carbonate anhydrous 2.83 6.5
6 Purified water q.s
Lubrication
7 Pregelatinised starch 1500 5.65 13
8 Sodium Starch Glycollate 6.52 15
9 Talc 0.28 0.65
10 Calcium stearate 1.52 3.5
Seal Coating
11 Hypromellose 6CPS 1.74 4
12 PEG 400 0.22 0.5
13 Purified Water q.s
Release Retarding coating
14 Methacrylic acid Copolymer (Eudragit S100) 6.52 15
15 Triethyl Citrate 0.61 1.5
16 Talc 0.61 1.5
17 Isopropyl alcohol (95%) q.s
18 Purified Water (5%) q.s
Seal Coating
19 Hypromellose 6CPS 1.96 4.5
20 PEG 400 0.28 0.65
21 Purified Water q.s
Active Coating
22 Pantoprazole sodium Sesqui hydrate 9.90 22.76
23 Triethyl citrate 1.39 3.2
24 Sodium Carbonate Anhydrous 0.52 1.2
25 Purified Water q.s
Seal Coating
26 Hypromellose 6CPS 2.30 5.3
27 PEG 400 0.33 0.76
28 Purified Water q.s
Delayed Release Coating
29 Instacoat EN Super II 7.39 17
30 Purified Water q.s
Total 100.00 230

Process of preparation:
Step 1 (Core Tablets):
1. Pantoprazole Sodium was mixed with mannitol, pregelatinised starch and aerosil and resultant mixture was sifted through sieve ASTM 40.
2. Binder solution was prepared by the addition of sodium carbonate to purified water.
3. Step 1 material was granulated using Step 2 material till suitable consistency obtained.
4. Above material was dried using FBD till LOD found between 2-3%
5. Dried material then passed through sieve no: ASTM 25.
6. Extragranular material compensated as per the practical yield.
7. Except calcium stearate all extragranular ingredients passed through sieve ASTM 40 and blended for 10mins with step 5 material in double cone blender.
8. Above material was lubricated for 3 mins with sieve ASTM 60 and compressed using 6.50 mm punches for desired thickness and weight.
Step 2 (Seal Coating I):
9. Preparation of seal coating solution: Seal coating solution was prepared by the addition of PEG 400 followed by hypromellose 6cps to purified water under stirring
10. A 2.0% seal coating was applied using an autocoater.

Step 3 (Acrylic acid co-polymer coating):
11. Acrylic acid co-polymer (Eudragit® S100) coating solution was prepared by the addition of Tri-ethyl citrate and talc to IPA:Water (95:5) mixture followed by Eudragit S100, and stirred continuously for 45 mins.
12. A 6% coating was applied on seal coated tablets.

Step 4 (Seal Coating II):
13. Preparation of seal coating solution: Seal coating solution was prepared by the addition of PEG 400 followed by hypromellose 6cps to purified water under stirring
14. A 2.0% seal coating was applied using an autocoater.

Step 5 (Drug Coating):
15. Drug coating solution was prepared by the addition of triethyl citrate and sodium carbonate to purified water under stirring followed by pantoprazole and stirred for 30 mins.
16. A 27.16 mg/tablet coating was applied on step 15 tablets using an autocoater.

Step 6 (Seal Coating III):
17. Preparation of seal coating solution: Seal coating solution was prepared by the addition of PEG 400 followed by hypromellose 6cps to purified water under stirring
18. A 2.0% seal coating was applied using an autocoater.

Step 7 (Enteric Coating):
19. Enteric coating solution was prepared by the addition of Instacoat super to purified water. The resultant solution was homogenized for 20 mins.
20. A 6% coating autocoater using an autocoater.
,CLAIMS:1. A pharmaceutical composition in the form of a tablet comprising:
a) an acrylic coated core tablet comprising a therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof, sodium carbonate anhydrous and a pharmaceutically acceptable excipient;
b) a middle drug coat comprising a therapeutically effective amount of a pantoprazole or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable excipient;
c) an outer enteric coating surrounding the said middle drug coat,
wherein; the weight ratio of pantoprazole or pharmaceutically acceptable salts thereof to sodium carbonate anhydrous is from about 7:1 to 1:1 and the first dose of pantoprazole is released from the middle drug coat and second dose of pantoprazole is released from tablet core after a lag of about 6 to 12 hours from the first dose.

2. The pharmaceutical composition of claim 1, wherein the acrylic coating comprises acrylic acid co-polymers present in an amount of about 3 % to about 9% of the total weight of the tablet.

3. The pharmaceutical composition of claim 1, wherein the tablet core or middle drug coat comprises pantoprazole or pharmaceutically acceptable salts thereof in an amount of about 1% to about 20% of the total weight of the tablet.

4. The pharmaceutical composition of claim 3, wherein the tablet core or middle drug coat comprises pantoprazole or pharmaceutically acceptable salts thereof in an amount of about 10% of the total weight of the tablet.

5. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable excipient of the tablet core comprises mannitol, pregelatinised starch, colloidal silicon dioxide, sodium starch glycolate, talc, calcium stearate and sodium carbonate anhydrous or mixtures thereof.
6. The pharmaceutical composition of claim 1, wherein the tablet core comprises pantoprazole or pharmaceutically acceptable salts thereof and sodium carbonate anhydrous in a weight ratio of about 3.5:1.

7. A process for preparation of pharmaceutical composition of claim 1, wherein the said process comprise:
i) preparation of core tablet containing pantoprazole or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable excipient, seal coating the core tablet;
ii) applying acrylic acid copolymer coating over seal coated core tablet and seal coating over the acrylic coating;
iii) forming middle drug coat containing pantoprazole or pharmaceutically acceptable salts thereof over seal coat, applying seal coating to the drug coat;
iv) applying enteric coating over seal coating using an autocoater.

8. A pharmaceutical composition in the form of a tablet comprising:
a) an acrylic coated core tablet comprising pantoprazole or pharmaceutically acceptable salts thereof in about 10% of total weight of the tablet, sodium carbonate anhydrous and a pharmaceutically acceptable excipient;
b) a middle drug coat comprising pantoprazole or pharmaceutically acceptable salts thereof in about 10% of total weight of the tablet and a pharmaceutically acceptable excipient;
c) an outer enteric coating surrounding the said middle drug coat,
wherein; the weight ratio of pantoprazole or pharmaceutically acceptable salts thereof to sodium carbonate anhydrous is from about 3.5:1 and the first dose of pantoprazole is released from the middle drug coat and second dose of pantoprazole is released from tablet core after a lag of about 6 to about 12 hours from the first dose.