The invention disclosed in this application relates to an improved pharmaceutical formulation containing omeprazole. The formulation is useful for the treatment of gastro intestinal diseases. The formulation is stable against gastric juices. The formulation may be in the form of capsules. The invention also relates to a process for the preparation of above said formulation.
Omeprazole is a potent inhibitor of acid secretion on the gastro intestinal tract and is used in the treatment of gastro intestinal ulcers. Omeprazole is very sensitive to acidic media. The stability of omeprazole is also affected by moisture.
In order to make omeprazole more useful as an oral dosage form for its use as gastro intestinal agent, it is necessary to protect it against gastric juices which is acidic in nature. Such a protection will enable the formulation to release omeprazole in the intestine. To prevent contact of omeprazole with gastric juices, the formulation comprising omeprazole is normally enteric coated. The materials used for such coating such as cellulose acetate phthalate, hydroxy propyl methyl cellulose phthalate, are themselves acidic in nature which also affects the stability of omeprazole. If formulation is prepared using such coatings, omeprazole rapidly degrades by direct or indirect contact with such materials.
In order to enhance the stability, the omeprazole-containing core should contain alkaline reacting compounds. As mentioned above normally over this core, an enteric coating is also provided. For further safety, a coating of an intermediary layer containing alkaline reacting compounds is also given between the active core and the enteric coating. The omeprazole containing formulation should also meet the standards defined therefore namely, dissolution of not less than 75% of omeprazole in 45 minutes. In the medium of pH 6.8 and gastric resistance of not less than 85% after 2 hours in medium of 1.2 pH.
In the US patent no. 004,786,505 a formulation containing omeprazole has been described. This patent provides a pharmaceutical formulation containing omeprazole comprising (a) a core region comprises an effective amount of material selected from the group consisting of omeprazole and an alkaline reacting compound , an alkaline reacting compound and an alkaline omeprazole salt alone , (b) an inert sub coating which is soluble or rapidly disintegrating in water disposed on said core region , said sub coating comprising one or more polymers of materials selected from among tablet excipients and polymeric film forming compounds and (c) an our layer disposed on said sub coating comprising of enteric coating
The core can be formulated as either small beads, pellets, tablets, hard gelatin capsules or soft gelatin capsules and the composition of separating layer varies depending on the type of core formulation. No specific method has been described for the preparation of the active core and separating layer.
In an another US patent no. 005,385,739, omeprazole along with mannitol as a diluent is applied on neutral grains consisting of a mixture of sugar and of starch by dry powder layering using hydroxypropyl methylcellulose solution as a binder. These micro granules are additionally coated with protective layers consisting of mannitol and a binding agent in order to isolate the core from the external enteric layer having
3

the acidic reacting groups. The dry powder layering process involves additional variables such as binder solution spray rate, powder application rate, load size, in addition to the variables that effect suspension and solution layering process which may result in irregular shapes and size variation of cores.
The omeprazole containing formulations are found to be very effective in the treatment of gastro intestinal ulcers which is very common occurrence in the modern life style. Accordingly, the formulation containing omeprazole has become the common remedy for such diseases. At the same time the characteristic of such formulation disintegrating rapidly in the gastric environment makes the formulation stands against its use. Therefore, studies are going on to develop improved formulation containing omeprazole which will be stable under the environment of gastric juices as well as will disintegrate gradually in the intestine.
Accordingly, the main objective of the present invention is to provide an improved formulation containing omeprazole useful for the treatment of gastro intestinal ulcers which will be resistant to gastric juices and will dissolve in neutral to alkaline media and has good stability.
Another objective of the present invention is to provide an improved method for the preparation of an improved formulation containing omeprazole useful for the treatment of gastro intestinal ulcers which will be resistant to gastric juices and will dissolve in neutral to alkaline media and has good stability.
The invention is based on our finding that if the core containing omeprazole is effectively protected from reacting with enteric layer its stability can be enhanced. Accordingly, if an inner core of sucrose , starch and an alkaline reacting compound is provided along with an intermediary layer comprising of two layers is provided between the active core containing omeprazole and the enteric coating, the stability of the formulation can be enhanced considerably. The inner core comprising of sucrose, starch, talc and an alkaline reacting compound improves the stability of omeprazole apart from giving uniform size pellets with good surface morphology and dissolution characteristics. The first layer of the intermediary layer comprises of a buffer in sugar syrup and the second layer comprising of hydrophilic polymer or a mixture thereof in an aqueous and / or organic medium. The polymer layer may contain sugar such as mannitol for increasing the thickness of this layer.
Accordingly, the present invention provides an improved pharmaceutical formulation containing omeprazole in the form of pellets filled into a capsules which is resistant to acid media and dissolves in neutral to alkaline media and having good stability and useful for the treatment of gastro intestinal ulcers which comprises
a) an inner core of sucrose, starch and an alkaline reacting compound,
b) the inner core having a coating of an active layer comprising omeprazole
suspended in sugar syrup along with an alkaline reacting compound and a surface-
active agent optionally containing a hydrophilic polymer or a mixture there of,

c) the active layer having a coating of two layers-first layer comprising of a buffer in sugar syrup optionally containing a hydrophilic polymer or a mixture there of and a second layer comprising of a hydrophilic polymer or a mixture thereof,
d) the resulting pellets having a coating of an enteric layer and
e) the pellets being encapsulated.
According to another feature of the invention, there is provided a process for the preparation of an improved pharmaceutical formulation containing omeprazole which is resistant to acid media and dissolves in neutral to alkaline media and having good stability and useful for the treatment of gastrointestinal ulcers which comprises
a) forming an inner core of sucrose, starch and an alkaline reacting compound,
b) coating the inner core with an active layer comprising omeprazole suspended in sugar syrup along with an alkaline reacting compound and a surface active agent, optionally containing a hydrophilic polymer or a mixture thereof,
c) coating the active layer with two layers - first layer comprising of a buffer in sugar syrup optionally containing a hydrophilic polymer or a mixture there of and a second layer comprising of a hydrophilic polymer or a mixture thereof,
d) coating the resulting pellets with an enteric polymer layer and
e) encapsulating the formed pellets by conventional methods.
In a preferred embodiment of the present invention the amount of sucrose, starch and the alkaline reacting agent employed in the inner core may range from 25.00 to 65.00, from 5.0 to 20.00 and form 2.00 to 8.00 mg/capsule respectively. More preferably, these may range from 35.00 to 55.00, from 10.0 to 15.0 and from 4.0 to 6.0mg/capsule respectively. The alkaline reacting compound such as disodium hydrogen phosphate, magnesium oxide, magnesium carbonate etc may be employed.
The sugars such as glucose, sucrose, mannitol etc. may be used in the active layer. The amount of sugar may range from 30.00 to 90.00 mg/capsule, more preferably from 40.00 to 80.00 mg/capsule. The amount of omeprazole employed in the active layer may range from 18.00 to 20.00 mg/capsule or its equivalent, preferably from 19.0 to 21.0 mg/capsule or its equivalent. The surface-active agent such as sodium lauryi sulphate, polysorbate- 80 and the like may be employed; the amount of which may range from 0.4 to 4.0 mg/capsule more preferably from 0.8 to 2.0 mg/capsule. A hydrophilic polymer is optionally employed as a binding agent in the active core. If the polymer is present its amount may range from 0.4 to 4.0 mg/capsule.
In yet another embodiment of the invention, the buffer such as disodium hydrogen phosphate, tris (hydroxy methyl) methylamine, magnesium carbonate, magnesium oxide etc may be employed in the active layer. The amount of buffer employed may range from 1.0 to 8.0 mg/capsule, more preferably from 2.0 to 6.0 mg/capsule.

The inner-separating layer consists of sugars such as sucrose, mannitol, glucose etc. The amount of sugar may range from 5.0 to 25.0 mg/ capsule more preferably from 10.0 to 20.0 mg/capsule. Sugar layer contains buffering agents such as disodium
hydrogen phosphate, tris (hydroxy methyl) methylamine, magnesium carbonate, magnesium oxide etc in an amount ranging from 0.1 to 2.0 mg/capsule more preferably from 0.5 to 1.5 mg/capsule. The inner-separating layer may optionally contain hydrophilic polymer such as polyvinylpyrrolidone, hydroxypropyl methly cellulose, hydroxypropyl cellulose, and the like as binding agents. If the polymer is present its amount may range from O.lto 1.0 mg/capsule. The final pH of the syrup is not less than 7.0, more preferably not less than 8.0.
In the second separating layer, hydrophilic polymer such as polyvinylpyrrolidone, hydroxypropyl methly cellulose, hydroxypropyl cellulose, and the like may be used. The amount of the polymer may range from 2.0 to 20 mg/capsule more preferably from 5.0 to 15.0 mg/capsule. The final pH of the suspension is not less than 6.0, more preferably not less than 7.0. The polymer layer may contain sugars such as mannitol, sucrose, and glucose to increase the thickness of the layer. If such sugar is present, the amount may range from 10.0 to 25.0 mg/capsule. This layer may also contain other materials such as binder, buffer, which our usually employed in such formulations suspended in a suitable organic solvent. Solvents such as isopropyl alcohol, ethyl alcohol, acetone and the like may be employed.
The coating may be effected employing conventional or other suitable coating equipment.
Polymers such as hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, methacrylic copolymers or their aqueous latex dispersions may be used for enteric coating. The amount of such polymers may range from 15.0 to 85.0 mg/capsule. The coating solution optionally contains plasticizers such as propylene glycol, diethyl phthalate, polyethylene glycol etc., and coloring agents such as titanium dioxide, erythrocin and anti sticking agents such as talc, magnesium stearate, colloidal silicon dioxide etc. The amount of such optional agents may range from 2.0 to 15.0mg, 0.1 to 2.0mg, 2.0 to 14.0 mg/capsule respectively. The enteric coating is applied on to protective coated pellets in mechanised perforated coating pan, or using suitable coating equipment. Enteric coated pellets are filled into hard gelatin capsules and are packed into a moisture resistant primary pack. For the long term stability of formulation, water content of the pellets in formulation is kept below 2.0%, preferably below 1.5%.
The invention is described in detail in the examples given below which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention.

EXAMPLE 1
a) Composition of the inner core mg/capsule
Sucrose 45.00
Starch 12.00
Disodium hydrogen phosphate 2.00
Syrup is made by dissolving sucrose in sufficient quantity of purified water by the aid of heat. Disodium hydrogen phosphate is dissolved in the syrup.
Sucrose is coated with starch by dry powder layering method using buffered sucrose syrup as binding agent. The pellets thus obtained are dried to reduce the moisture content to less than 2%.
b) Composition of active layer mg/capsule
Omeprazole 20.00
Sucrose 60.00
Sodium lauryl sulphate 1.10
Polyvinylpyrrolidone 0.80
Tris (hydroxymethyl) aminomethane 2.20
Syrup is made by dissolving sucrose in sufficient quantity of water by the aid of heat, followed by dissolving polyvinylpyrrolidone, sodium lauryl sulphate and tris (hydroxymethyl) aminomethane. The syrup is cooled to room temperature and omeprazole is suspended with the aid of a mechanical stirrer. This suspension is coated onto core pellets in suitable coating equipment.

c) Composition of separating layers (Inner) mg/capsule
Sucrose 14.00
Tris (hydroxymethyl) aminomethane 0.40
Polyvinylpyrrolidone 0.30
Sucrose is dissolved in sufficient purified water with the aid of heat, followed by polyvinylpyrrolidone and tris (hydroxymethyl) aminomethane. Syrup is cooled room temperature. This syrup is coated on to drug pellets in a conventional coating pan or suitable coating equipment.
d) Composition of Separating layer (Outer) mg/capsule
Mannitol 17.60
Polyvinylpyrrolidone 7.70
Tris (hydroxymethyl) aminomethane 0.20
Talc 3.50
The second separating layer, prepared by dissolving polyvinylpyrrolidone in isopropyl alcohol followed by suspending talc, mannitol and Tris (hydroxymethyl) aminomethane with the aid of mechanical stirrer, is applied on to pellets in a mechanized perforated coating pan or a suitable coating equipment.
e) Composition of Enteric layer mg/capsule
HPMC phthalate 29.00
Diethyl phthalate 4.40
Titanium dioxide 1 -00
Talc 9.70
Hydroxypropyl methylcellulose phthalate is dissolved in a blend of isopropyl alcohol, methylene chloride with the aid of mechanical stirrer followed by diethyl phthalate.
Titanium dioxide and talc are sifted through a fine mesh and suspended in the above solution.

This suspension is applied on to protective coated pellets in a mechanized perforated coating pan or suitable coating equipment. The pellets are then dried in the coating pan or in suitable drying equipment.
The dried pellets are filled into capsules to contain 20mg of omeprazole .
EXAMPLE 2
a) Composition of the inner core mg/capsule
Sucrose 45.00
Starch 12.00
Dibasic calcium phosphate dihydrate 2.00
Syrup is made by dissolving sucrose in sufficient quantity of purified water by the aid of heat. Dibasic calcium phosphate dihydrate is suspended in the syrup.
Sucrose is coated with starch by dry powder layering method using buffered sucrose syrup as binding agent. The pellets thus obtained are dried to reduce the moisture content to less than 2%.
b) Composition of active layer mg/capsule
Omeprazole 20.00
Mannitol 60.00
Sodium lauryi sulphate 1.10
Polyvinylpyrrolidone 3.00
Tris (hydroxymethyl) aminomethane 4.40
Syrup is made by dissolving mannitol in sufficient quantity of water by the aid of heat, followed by dissolving polyvinylpyrrolidone, sodium lauryi sulphate and tris (hydroxymethyl) aminomethane. The syrup is cooled to room temperature and omeprazole is suspended with the aid of a mechanical stirrer. This suspension is coated onto core pellets in suitable coating equipment.

c) Composition of separating layers (Inner) mg/capsule
Sucrose 14.00
Tris (hydroxymethyl) aminomethane 0.80
Polyvinylpyrrolidone 0.30
Sucrose is dissolved in sufficient purified water with the aid of heat, followed by polyvinylpyrrolidone and tris (hydroxymethyl) aminomethane. Syrup is cooled room temperature. This syrup is coated on to drug pellets in a conventional coating pan or suitable coating equipment.
d) Composition of Separating layer (Outer) mg/capsule
Mannitol 17.60
Polyvinylpyrrolidone 7.70
Tris (hydroxymethyl) aminomethane 0.40
Talc 3.50
The second separating layer, prepared by dissolving polyvinylpyrrolidone in isopropyl alcohol followed by suspending talc, mannitol and tris (hydroxymethyl) aminomethane with the aid of mechanical stirrer, is applied on to pellets in a mechanized perforated coating pan or a suitable coating equipment.
e) Composition of Enteric layer mg/capsule
HPMC phthalate 29.00
Diethyl phthalate 4.40
Titanium dioxide 1.00
Talc 9.70
Hydroxypropyl methylcellulose phthalate is dissolved in a blend of isopropyl alcohol and acetone with the aid of mechanical stirrer followed by diethyl phthalate.
Titanium dioxide and talc are sifted through a fine mesh and suspended in the above solution.

This suspension is applied or* to protective coated pellets in a mechanized perforated coating pan or suitable coating equipment. The pellets are then dried in the coating pan or in suitable drying equipment.
The dried pellets are filled into capsules to contain 20mg of omeprazole.
EXAMPLE 3
a) Composition of the inner core rag/capsule
Sucrose 45.00
Starch 12.00
Dibasic calcium phosphate dihydrate 2.00
Syrup is made by dissolving sucrose in sufficient quantity of purified water by the aid of heat. Dibasic calcium phosphate dihydrate is suspended in the syrup.
Sucrose is coated with starch by dry powder layering method using buffered sucrose syrup as binding agent. The pellets thus obtained are dried to reduce the moisture content to less than 2%.
b) Composition of active layer mg/capsule
Omeprazole 20.00
Sucrose 60.00
Sodium lauryl sulphate 110
Polyvinylpyrrolidone 0.80
Tris (hydroxymethyl) aminomethane 4.40

Syrup is made by dissolving sucrose in sufficient quantity of water by the aid of heat, followed by dissolving polyvinylpyrrolidone, sodium lauryl sulphate and tris (hydroxymethyl) aminomethane. The syrup is cooled to room temperature and omeprazole is suspended with the aid of a mechanical stirrer. This suspension is / coated onto core pellets in suitable coating equipment.
c) Composition or separating layers (Inner) mg/capsufe
Sucrose 14.00
Magnesium carbonate 1.20
Sucrose is dissolved in sufficient purified water with the aid of heat, followed by suspension of magnesium carbonate. Syrup is cooled room temperature. This syrup is coated on to drug pellets in a conventional coating pan or suitable coating equipment.
d) Composition of Separating layer (Outer) mg/capsule
Mannitol 15.00
Polyvinylpyrrolidone 7.70
Magnesium carbonate 3.50
Talc 3.50
The second separating layer, prepared by dissolving polyvinylpyrrolidone in isopropyl alcohol followed by suspending talc, mannitol and magnesium carbonate with the aid of mechanical stirrer, is applied on to pellets in a mechanized perforated coating pan or a suitable coating equipment.
e) Composition of Enteric layer mg/capsule
HPMC phthalate 29.00
Diethyl phthalate 4.40
Titanium dioxide 1.00

Talc

9.70

Hydroxypropyl methylcellulose phthalate is dissolved in a blend of isopropyl alcoho! and methylene chloride with the aid of mechanical stirrer followed by diethyl phthalate.
Titanium dioxide and talc are sifted through a fine mesh and suspended in the above solution.
This suspension is applied on to protective coated pellets in a mechanized perforated coating pan or suitable coating equipment. The pellets are then dried in the coating pan or in suitable drying equipment.
The dried pellets are filled into capsules to contain 20mg of omeprazole.

EXAMPLE 4
a) Composition of the inner core mg/capsule
Sucrose 45.00
Starch 12.00
Magnesium carbonate 2.00
Syrup is made by dissolving sucrose in sufficient quantity of purified water by the aid of heat. Magnesium carbonate is suspended in the syrup.
Sucrose is coated with starch by dry powder layering method using buffered sucrose syrup as binding agent. The pellets thus obtained are dried to reduce the moisture content to less than 2%.
b) Composition of active layer mg/capsule
Omeprazole 20.00
Sucrose 60.00
Sodium lauryl sulphate 1 10
Polyvinylpyrrolidone 0.80
Magnesium carbonate 4.00

Syrup is made by dissolving sucrose in sufficient quantity of water by the aid of heat followed by dissolving polyvinylpyrrolidone, sodium lauryl sulphate and magnesiuir carbonate. The syrup is cooled to room temperature and omeprazole is suspended with the aid of a mechanical stiirer. This suspension is coated onto core pellets ir suitable coating equipment.
c) Composition of separating layers (Inner) mg/capsule
Sucrose 14.00
Magnesium carbonate 1.20
Sucrose is dissolved in sufficient purified water with the aid of heat, followed by suspension of magnesium carbonate. Syrup is cooled room temperature. This syrup is coated on to drug pellets in a conventional coating pan or suitable coating equipment.
d) Composition of Separating layer (Outer) mg/capsule
Mannitol 15.00
Polyvinylpyrrolidone 7.70
Magnesium carbonate 5.00
Talc 3.50
The second separating layer, prepared by dissolving polyvinylpyrrolidone in ethyl alcohol followed by suspending talc, mannitol and magnesium carbonate with the aid of mechanical stirrer, is applied on to pellets in a mechanized perforated coating pan or a suitable coating equipment.
e) Composition of Enteric layer mg/capsule
HPMC phthalate 40.00
Diethyl phthalate 6.00
Titanium dioxide 1 00
Talc '0

Hydroxypropyl methylcellulose phthalate is dissolved in a blend of ethyl alcohol and acetone with the aid of mechanical stirrer followed by diethyl phthalate.
Titanium dioxide and talc are sifted through a fine mesh and suspended in the above solution.
This suspension is applied on to protective coated pellets in a mechanized perforated coating pan or suitable coating equipment. The pellets are then dried in the coating pan or in a suitable drying equipment.
The dried pellets are filled into capsules to contain 20mg of omeprazole.

The drug loaded pellets obtained at different stages of coating (b-e) shown in the Examples lto 4 are kept openly at accelerated condition i.e., 40 deg. C/75%RH and observed for changes in colour for 7 days. The results are summarized in Table 1. Remarkable stabilizing effect has been achieved when increased quantities of buffers are present.


STABILITY OF CAPSULES:
The results of stability studies carried out on capsule formulations, filled with enteric-coated pellets, prepared according to the process described in examples 1 to 4 and packed in aluminium strips (Thickness 0.04mm) are summarised below.

Capsules are found to have good stability at 25 deg. C/ 60%RH. Total impurities are less than 0.5%. Increase in total impurities has been observed in samples stored at higher temperature and humidity i.e. 40 deg. C /75% RH. Capsule formulation made according to the process described in example 4 are relatively more stable at 25°C/60%RH.
Advantages of the invention:
1. The formulation is more stable than the hither to known formulation of
omeprazole.
2. The formulation meets requirements with respect to gastric resistance of not less than 85% after 2 hours in medium of 1.2 pH and dissolution of not less than 75% of omeprazole in 45 minutes in the medium of pH 6.8.
3. The formulation is more effective in the treatment of gastro intestinal ulcers.

We claim;
1. An improved pharmaceutical formulation containing omeprazole in the form of
pellets filled into capsules which is resistant to acid media and dissolves in neutral
to alkaline media and having stability and useful for the treatment of gastro
intestinal ulcers which comprises
a. an inner core of sucrose, starch and an alkaline reacting compound,
b. the inner core having a coating of an active layer comprising omeprazole
suspended in sugar syrup along with an alkaline reacting compound and a
surface active agent, optionally containing the hydrophilic polymer or a
mixer thereof,
c. the active layer having a coating of two layers - first layer comprising of a
buffer in sugar syrup optionally containing the hydrophilic polymer or a
mixer thereof and a second layer comprising of a hydrophilic polymer or a
mixture thereof,
d. the resulting pellets having a coating of an enteric layer and
e. the pellets being encapsulated.
2. A formulation as claimed in claim 1 wherein the alkaline reacting compound such as disodium hydrogen phosphate, magnesium oxide, magnesium carbonate and the like is employed in the inner core.
3. A formulation as claimed in claims 1 & 2 wherein the amount of sucrose, starch and the alkaline reacting compound used in the inner core range from 25.0 to 65.0, from 5.0 to 20.0, from 2.0 to 8.0 mg/capsule respectively, more preferably from 35.0 to 55.0, from 10.0 to 15.0, and from 4.0 to 6.0 mg/capsule respectively.
4. A formulation as claimed in claims 1 to 3 wherein the amount of omeprazole employed in the active core ranges from 18.0 to 22. Omg/capsule, more preferably from 19.0 to 21 -Omg/capsule,
5. A formulation as claimed in claims 1 to 4 wherein the surface-active agent employed in the active core is selected from sodium lauryl sulphate, polysorbate-80 and the like.
6. A formulation as claimed in claims 1 to 5 wherein the amount of surface-active agent in the active core used ranges from 0.4 to 4.Omg/capsule, more preferably from 0.8 to 2.0 mg/capsule.
7. A formulation as claimed in claims I to 6 wherein the buffer employed in the active layer is selected from disodium hydrogen phosphate, tris (hydroxymethy) aminomethane, magnesium carbonate, magnesium oxide and the like.
8. A formulation as claimed in claims 1 to 7 wherein the amount of buffer used in the active layer range from 1.0 to 8.Omg/capsule, more preferably from 4.0 to 6. Omg/capsule.

9. A formulation as claimed in claims 1 to 8 wherein the sugar emplyed in the inner separating layer is selected from sucrose, mannitol, glucose and the like.
10. A formulation as claimed in claims 1 to 9 wherein the amount of sugar used in the inner separating layer range from 5.0 to 25.0mg/capsule, more preferably from 10.0 to 20.0mg/capsule.
11. A formulation as claimed in claims 1 to 10 wherein the buffer employed in the first separating layer is selected from disodium hydrogen phosphate, tris (hydroxy methy) aminomethane, magnesium carbonate, magnesium oxide and the like.
12. A formulation as claimed in claims 1 to II wherein the amount of buffer used in the first separating layer range from 0.1 to 2.0 mg/capsule, more preferably from 0.50 to 1.50 mg/capsule.
13. A formulation as claimed in claims 1 to 12 wherein the polymer employed in the second separating layer is selected from polyvinylpyrrolidone, hydrosypropyl methyl cellulose and the like or a mixture thereof.
14. A formulation as claimed in claims 1 to 13 wherein the amount of polymer or the mixture used in the second separating layer range from 2.0 to 20.0mg/capsule, more preferably from 5.0 to 15.0mg/capsule.
15. A formulation as claimed in claims 1 to 14 wherein the sugar used in the second layer is selected from mannitol, sucrose, glucose and the like and the amount of sugar used range from 10.0 to 25.0mg/capsule.
16. A formulation as claimed in claims 1 to 15 wherein the organic solvent such as isopropyl alcohol, ethyl alcohol, acetone, methylene chloride and the like or mixture thereof is used to form the suspension of second separating layer and enteric coating layer.
17. An improved process for the preparation of an enteric coated omeprazole formulation in the form of capsules which is resistant to acid media and dissolves in neutral to alkaline media and having good stability and useful as gastrointestinal agent which comprises,
a. forming an inner core of sucrose, starch and an alkaline reacting compound,
b. coating the inner core with an active layer comprising omeprazole suspended
in sugar syrup along with an alkaline reacting compound and a surface-active
agent, optionally containing a hydrophilic polymer or a mixture thereof,
c. coating the active layer with two layers - first layer comprising of a buffer
dissolved in sugar syrup optionally containing a hydrophilic polymer or a
mixture thereof and a second layer comprising of a hydrophilic polymer or a
mixture thereof,
d. coating the resulting pellets with an enteric layer and
e. encapsulating the pellets by conventional methods.

18. An improved process as claimed in claim 17 wherein the alkaline reacting compound such as disodium hydrogen phosphate, magnesium carbonate, magnesium oxide and the like is employed.
19. An improved process as claimed in claims 17 to 18 wherein the amount of < sucrose, starch and the alkaline reacting compound used in the inner core range from 25.0 to 65.0, from 5.0 to 20.0, from 2.0 to 8.0mg/capsule respectively, more preferably from 35.0 to 55.0, from 10.0 to 15.0, and from 4.0 to 6.0 mg/capsule respectively
20. An improved process as claimed in claims 17 to 19 wherein the amount of Omeprazole employed in the active core ranges from 18.00 to 22.00mg/capsule, more preferably from 19.0 to 21.0mg/capsule.
21. An improved process as claimed in claims 17 to 20 wherein the surface active agent employed in the active core is selected from sodium lauryl sulphate, Polysorbate 80 and the like.
22. An improved process as claimed in claims 17 to 21 wherein the amount of surface-active agent used in the active core ranges from 0.4 to 4.0mg/capsule, more preferably from 0.8 to 2.0 mg/capsule.
23. An improved process as claimed in claims 17 to 22 wherein the buffer employed in the active layer and first separating layer is selected from disodium hydrogen phosphate, tris (hydroxymethyl) aminomethane, magnesium carbonate, magnesium oxide and the like.
24. An improved process as claimed in claims 17 to 23 wherein the amount of buffer used in the active layer and first separating layer range from 1.00 to 8.00mg and 0.1 to 2.0mg/capsule, more preferably from 2.0 to 6.0 mg and 0.5 to 1.5 mg/capsule respectively.
25. An improved process as claimed in claims 17 to 24 wherein the polymer employed in the second separating layer is selected from polyvinylpyrrolidone, hydroxypropyl methyl cellulose, hydroxypropyl cellulose and the like or a mixture thereof.
26. An improved process as claimed in claims 17 to 25 wherein the polymer employed in the second separating layer ranges from 2.0 to 20.0mg/capsule, more preferably from 5 to 15mg/capsule.
27. An improved process as claimed in claims 17 to 26 wherein the organic solvent employed in applying second separating layer and enteric layer is selected from isopropyl alcohol, ethyl alcohol, acetone, methylene chloride and the like or a mixture there of

28. An improved process as claimed in claims 17 to 27 wherein the enteric coating in the step d optionally contains plasticizer such as propylene glycol, diethyl phthalate, polyethylene glycol, coloring agents such as titanium dioxide, erythrosine and/or anti sticking agents such as talc, magnesium stearate, colloidal silicon dioxide.
29. An improved process as claimed in claim 17 to 28 wherein the amount of plasticizer ranges from 2.0 to 15.0mg/capsule, coloring agent ranges from 0.1 to 2.0mg/capsule and the anti sticking agent from 12.0 to H.Omg/capsule.
30. An improved process as claimed in claims 17 to 29 wherein the formulation is made into pellet form using mechanized perforated coating pan or by another suitable equipment.
31. An improved formulation containing omeprazole in the form of pellets filled into capsules which is resistant to acid media and dissolves in neutral to alkaline media and having good stability and useful as gastrointestinal agent substantially as herein described with reference to the examples.
32. Process for the preparation of an improved formulation containing omeprazole in the form of pellets fdled into capsules which is resistant to acid media and dissolves in neutral to alkaline media and having good stability and useful as gastrointestinal agent substantially as herein described with reference to the examples.