FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
COMPLETE SPECIFICATION
[See section 10]
NOVEL pH DEPENDENT ROBUST
ENTERIC POLYMERIC CONTAINER, AN
IMPROVEMENT OVER EXISTING
ENTERIC DOSAGE FORMS;


ORIGINAL
691/MUMNP/2002
02.08.02

SCITECH CENTRE, A COMPANY INCORPORATED UNDER SECTION 25 OF THE COMPANIES ACT, 1956, WHOSE ADDRESS IS 7, PRABHAT NAGAR, JOGESHWARI (WEST), MUMBAI - 400 102, MAHARASHTRA, INDIA;
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES AND ASCERTAINS THE NATURE OF THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFOMED.

GRANTED
5-5-2004

TITLE OF INVENTION
NOVEL pH DEPENDENT ROBUST ENTERIC POLYMERIC CONTAINER, AN IMPROVEMENT OVER EXISTING ENTERIC DOSAGE FORMS.
The present invention relates to enteric polymeric capsules and more particularly to two-piece hard capsules for pharmaceutical, nutraceuticals, herbal, and the like applications.
At present, capsules for pharmaceutical applications consists of capsule shell and a coating there on. Such capsules contain two parts: a capsule body and a cap.
Conventionally, made enteric hard gelatin capsules are somewhat brittle in nature, thus creating a major problem on the capsule filling machines.
It is known in the art to use plasticizer particularly triethyl citrate as a stabilizing agent with regard to gelatin capsules. Japanese Patent No. JP62016432A2 titled ENTERIC COATING COMPOSITION also teaches the use of triethyl citrate as a stabilizing agent. The enteric coating composition as disclosed by JP62016432A2 consists essentially of a water- dispersible copolymer obtained by emulsion polymerizing of ethyl acrylate with methacrylic acid and triethyl citrate. Although the above-mentioned water - dispersible copolymer is used in an enteric coating, the addition of a plasticizer is indispensable to prevent the cracking and embrittling of the coating layer. However the above mentioned Japanese
2

patent uses triethyl citrate in mixed form with the enteric coating composition.
Various plasticizers are known in the art for use in the capsules. In the case of the polyethylene glycol as plasticizer, the delay in disintegration time is sometimes recognized with time. If triacetin is used, there is a problem of acetic acid smell formation with time.
Soft Gelatin capsules known in the art are found to use Glycerol combined with Triethyl citrate as plasticizer in the shell composition. Moreover the soft gelatin capsule is prepared along with the inside content. The present invented capsule can be supplied as empty containers with enteric properties where any kind of material can be filled inside the container.
German Patent No. DE 322 22476 describes a pharmaceutical composition in which a soft gelatin capsule that is resistant to digestive juice whose wall includes gelatin mass which contain polyvinyl acetate phthalate, hydroxypropyl methylcelluiose phthalate or a vinyl acetate or crotonic acid copolymer and an alkali metal salt, ammonia salt, or amino salt of the same in their wall, and which released its contents readily in the intestines within the prescribed time. The capsules are further treated on the surface with an aldehyde-coating agent. However, this composition has a disadvantage that the free acidic groups of the polymer in the shell reacts with the active ingredient and reduces the efficacy of the product during its storage or shelf fife period.

Another object of the present invention is to provide a process for producing the capsule without conventional coating wherein desired plasticity of the capsule is maintained wherein use of glycerol or propylene glycol are done away with.
SUMMARY AND DETAILED DESCRIPTION OF THE INVENTION
The present invention essentially resides in a surprising discovery that triethyl citrate (TEC) in particular and other plasticizers in general when used with polymeric composition, especially gelatin and other compositions like HPMC, modified starch, modified polyvinyl acetate (PVA), carrageenan or any other suitable material to make the enteric hard capsules the step of providing enteric coating can be dispensed with still retaining the desired enteric property of the capsules and also undesired brittleness of the capsules can be eliminated. The other substances which can substitute triethyl citrate are dibutyl pthalate, diethyl pthalate, benzyl phenyl formate, sorbitol and others.
In commerce, coating of tablets and capsules are the general methods adapted for enteric or controlled dissolution properties. Uniform coating of the polymer and uniform release of the drug are the most common problems encountered. Some of the coated tablets when tested for the release of the drug in gastric medium shows variation from 4% to 12.8% . The present invention gives an answer to the coating problems and gives a ready to use enteric container which releases only up to 2% of the drug in the gastric medium.

The containers may or may not be sealed either by applying an enteric polymeric band around the container or by sealing the cap and body by any other suitable process.
The above said containers can be printed both axially and radially in one or more colours.
The present invention also teaches an improved process for reducing the brittleness in enteric hard gelatin capsule by the following examples and illustrations.
A series of experiments were designed with varying concentrations of Triethyl citrate to optimize the correct desired concentration. Triethyl citrate was used in 0.5, 1.0, 1.5, 2, 3, 4, 5, 6 and 7% addition level. The brittleness was checked by standard brittleness checking equipment at 0 hr. 17 hrs., 24 hrs., 65 hrs. and 240 hrs. The capsules prepared with 1 to 2.5 % TEC did not become brittle and was having good mechanical strength to run on the machines.
Triethyl citrate (TEC) finds use in this invention as mentioned herein:
Methacrylic acid polymer was added in ammoniated water and stirred for complete dissolution. Triethyl citrate was added in the solution. The entire mixture was homogenized, which was an important step, otherwise the TEC floats on top and does not give uniform solution.
The containers of the present invention are made by the conventional dip molding process. Other modified processes can also be used to make the containers such as injection- moulding and the like.

In general the present invention suggests the use of 0.5% - 5% of triethyl citrate for achievement of better stability in the hard gelatin capsules.
Accelerated stability study shows that the capsules are stable at storage conditions of 40°C and 75% relative humidity and room temperature for three months.
The following table explains the dissolution data of three months accelerated stability, performed with diclofenac sodium drug formulation filled in the enteric hard gelatin capsule.

SAMPLES % Drug release in Gastric medium for 2 hrs. % Drug release in intestinal medium for 2 hrs.
INITIAL 0.90 89.80
1 month room temperature 2.05 82.87
2 month room temperature 1.98 85.20
3 month room temperature 2.05 84.27
1 month 40 deg./ 75% RH 1.98 83.80
2 month 40 deg./ 75% RH 2.05 83.33
3 month 40 deg./75% RH 2.05 83.80

Composition
7.86 g. 53.70 g. q.s
1.96 g 40.00 g
The following examples enable a better understanding of the invention. Example-1
Ingredients
Methacrylic acid copolymer
Water
Ammonia solution ( 10 % v/v )
Propylene Glycol
Gelatin Solution ( 33.33% )

US Patent No. 4, 138, 013 describes a hard-shell pharmaceutical capsule being characterized by relative freedom from brittleness and by substantial absence of degradation on exposure to artificial gastric juice for 120 minutes, and the body and cap portions being formed by the dip-molding technique from a homogeneous film-forming composition comprising hydroxypropyl methylcellulose and an ammonium salt of cellulose acetate phthalate polymer or gelatin and an ammonium salt of a copolymer of methacrylic acid and methacrylic acid ester, optionally with the inclusion of plasticizer and/or coloring agents. The patent claims glycerin and propylene glycol as plasticizers. Further, the patent claims that use of plasicizers is optional. The present invention shows that the use of plasticizer is not just optional, but it is mandatory requirement in view of avoiding brittleness. Moreover, the present invention describes the use of triethyl citrate as plasticizer in a particular proportion to overcome the brittleness of the capsule since the use of propylene glycol and glycerin as plasticizers renders the capsule soft and pliable, and the capsules become non-sturdy
OBJECTS OF THE INVENTION
The primary object of the present invention is to overcome the above problems and particularly the problem of brittleness and also to make the capsule commercially feasible.
Still most important object of the present invention is to eliminate the step of coating the capsules as practiced at present thus saving in cost of manufacture and simultaneously reducing its undesirable brittleness to the desired extent.

The present invention comprises the use of enteric polymers such as methacrylic acid copolymer, cellulose acetate phthalate, hydroxy propyl methylcellulose and hydroxypropyl methylcellulose phthalate, Polyvinyl acetate phthalate and other gastro resistant polymers and combinations thereof.
The present invention provides a novel pH dependent robust enteric polymeric container consisting of a body and a cap such as hard capsules and the like and a process of manufacturing the same comprising the steps of:
(a) neutralizing enteric polymer slowly in alkaline solution under stirring,
(b) de-aeration of the solution on the water bath,
(c) adding plasticizer to the polymer solution under stirring and homogenized,
(d) adding gelatin solution to the polymer solution under stirring at desired temperature,
(e) de-aeration of the final solution at desired temperature,
(f) dipping and molding the capsule, by conventional process known in the art.
The alkaline solution used for neutralizing enteric polymer is prepared by adding water to a base like ammonia, sodium carbonate, sodium bicarbonate and like under stirring.

The enteric polymer is selected in the range 1% to 60%.
The plasticizer is selected in the range of 0.5% to 7% preferably 1 to 5%.
The aqueous gelatin solution is in the range of 3 to 35% preferably in the range 5 to 25%.
The gelatin solution was added at a temperature in the range 45°C to 55° C, preferably in the range 46°C to 52°C.
The enteric polymer is selected from a group consisting methacrylic acid copolymer in the range 5% to 60% W/W, Cellulose acetate phthalate in the range of 2 to 12% preferably 3 to 8%, hydroxypropyl methylcellulose phthalate in the range of 1 to 20%.
Methacrylic acid copolymer comprises 5% W/W to 60% W/W preferably it within the range 8% to 20%, more preferably within the range 12% to 18%.
Cellulose acetate phthalate (CAP) is to be used in the range of 2 to 12%, more preferably within the range 3% to 8%.
Hydroxypropyl methylcellulose pthalate is to be used within the range of 1 to 20%.
Gelatin is used in the range of 3 to 35% in the composition, preferably should be in range of 5 to 25%.
Colourants, surfactants, opacifiers, silicon dioxide, preservatives like parabens, acetic acid, sweeteners, flavours can be incorporated in the capsule body shell and cap shell like any other regular capsule.

To water add propylene glycol and ammonia solution under stirring. Add Eudragit slowly to above solution under stirring, de-aerate the solution on the water bath. Gelatin solution is added to the polymer solution under stirring at temp 52°C and deareate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Propylene glycol is a plasticizer and gives capsules that are not sturdy. The capsules were soft and pliable.
Example-2
Ingredients Composition
Methacrylic acid copolymer 13.79 g.
Water 60.00 g.
Ammonia solution ( 25 % w/v ) q.s g.
Propylene Glycol 1.00 g.
Gelatin Solution ( 33.33% ) 24.21 g.
To water add propylene glycol and ammonia solution under stirring. Add Methacrylic acid copolymer C slowly to above solution under stirring de-aerate the solution on the water bath. Gelatin solution is added to the polymer solution under stirring at temp 52°C and deareate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Propylene glycol is a plasticizer and gives capsules that are not sturdy. The capsules were soft and pliable.

Example-3
Ingredients Composition in g
Methacrylic acid copolymer 13.79
Water 57.47
Ammonia solution ( 25 % w/v ) q.s
Propylene Glycol 3.45
Gelatin Solution ( 33.33% w/v ) 21.83
To water add propylene glycol and ammonia solution under stirring. Add Methacrylic acid copolymer C slowly to above solution under stirring deareate the solution on the water bath. Gelatin solution is added to the

polymer solution under stirring at temp 52°C and deareate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Propylene glycol is a plasticizer and gives capsules that are not sturdy. The capsules were soft and pliable.
Example-4
Ingredients Composition in g.
Methacrylic acid copolymer 10.06
Water 56.54
Ammonia solution ( 25 % w/v ) q.s
Propylene Glycol 0.7
Triethyl citrate 5.10
Gelatin Solution ( 33.33% w/v ) 26.81
To water add ammonia solution under stirring. Add Methacrylic acid copolymer C slowly to above solution under stirring deareate the solution on the water bath. Add propylene glycol and triethyl citrate to the polymer solution under stirring. Gelatin solution is added to the polymer solution under stirring at temp 52°C and de-aerate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Propylene glycol is a plasticizer and gives capsules that are not sturdy. The capsules were soft and pliable.
Example-5
Ingredients Composition in g.
Methacrylic acid copolymer 14.00
Water 45.00
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 0.5
Gelatin Solution ( 33.33% w/v ) 40.00
To water add ammonia solution under stirring. Add Methacrylic acid copolymer C slowly to above solution under stirring de-aerate the solution

on the water bath. Add triethyl citrate to the polymer solution under stirring. Gelatin solution is added to the polymer solution under stirring at temp 52°C and dearate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Capsules were brittle.
Example-6
Ingredients Composition in g.
Methacrylic acid copolymer 14.00
Water 45.00
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 0.75
Gelatin Solution ( 33.33% w/v ) 40.00
To water add ammonia solution under stirring. Add Methacrylic acid copolymer C slowly to above solution under stirring deareate the solution on the water bath. Add triethyl citrate to the polymer solution under stirring. Gelatin solution is added to the polymer solution under stirring at temp 52°C and dearate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Capsules were brittle.
Example-7
Ingredients Composition in g.
Methacrylic acid copolymer 17.00
Water 46.00
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 0.5
Gelatin Solution ( 33.33% w/v ) 36.5
To water add ammonia solution under stirring.Add Methacrylic acid copolymer C slowly to above solution under stirring de-aerate the solution on the water bath. Add triethyl citrate to the polymer solution under

stirring. Gelatin solution is added to the polymer solution under stirring at temp 52°C and de-aerate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Capsules were brittle.
Example-8
Ingredients Composition in g.
Methacrylic acid copolymer 17.00
Water 46.00
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 1 0
Gelatin Solution ( 33.33% w/v ) 36.00
To water add ammonia solution under stirring. Add Methacrylic acid copolymer C slowly to above solution under stirring de-aerate the solution on the water bath. Add triethyl citrate to the polymer solution under stirring. Gelatin solution* is added to the polymer solution under stirring at temp 52°C and dearate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Capsules were brittle after some time.
Example-9
Ingredients Composition in g.
Methacrylic acid copolymer 17.00
Water 46.00
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 1 5
Gelatin Solution ( 33.33% w/v ) 35.5
To water add ammonia solution under stirring. Add Methacrylic add copolymer C slowly to above solution under stirring deareate the solution on the water bath. Add triethyl citrate to the polymer solution under stirring. Gelatin solution is added to the polymer solution under stirring at

temp 52°C and de-aerate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Capsules were not brittle for 10 days.
Example-10
Ingredients Composition in g.
Methacrylic acid copolymer 17.00
Water 46.00
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 2.0
Gelatin Solution ( 33.33% w/v ) 35.0
To water add ammonia solution under stirring. Add Methacrylic acid copolymer C slowly to above solution under stirring de-aerate the solution on the water bath. Add triethyl citrate to the polymer solution under stirring. Gelatin solution is added to the polymer solution under stirring at temp 52°C and de-aerate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Capsules were not brittle for 10 days and retained the mechanical strength.
Example-11
Ingredients Composition in g.
Methacrylic acid copolymer 17.00
Water 45.00
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 3.0
Gelatin Solution ( 33.33% w/v ) 35.00
To water add ammonia solution under stirring. Add Methacrylic acid copolymer C slowly to above solution under stirring de-aerate the solution on the water bath at temp 52°C . Add triethyl citrate to the polymer solution under stirring. Gelatin solution is added to the polymer solution

under stirring at temp 52°C and de-aerate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Capsules were not brittle , but they were very soft and were not sturdy to hold the medicaments.
Example-12
Ingredients Composition in g.
Water 44.00
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 4.0
Gelatin Solution ( 33.33% w/v ) 35.00
To water add ammonia solution under stirring.Add Methacrylic acid copolymer C slowly to above solution under stirring deareate the solution on the water bath. Add triethyl citrate to the polymer solution under stirring. Gelatin solution is added to the polymer solution under stirring at temp 52°C and de-aerate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Capsules were not brittle , but they were very soft and were not sturdy to hold the medicaments.
Example-13
Ingredients Composition in g.
Methacrylic acid copolymer 17.00
Water 43.00
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 5.0
Gelatin Solution ( 33.33% w/v ) 35.00
To water add ammonia solution under stirring.Add Methacrylic acid copolymer C slowly to above solution under stirring deareate the solution on the water bath. Add triethyl citrate to the polymer solution under

stirring. Gelatin solution is added to the polymer solution under stirring at temp 52°C and de-aerate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Capsules were not brittle , but they were very soft and were not sturdy to hold the medicaments.
Example-14
Ingredients
Methacrylic acid copolymer suspension Ammonia solution ( 25 % w/v ) Triethyl citrate Gelatin Solution ( 33.33% w/v )
To Methacrylic acid copolymer C Suspension slowly add ammonia solution under stirring de-aerate the solution on the water bath. Add triethyl citrate to the polymer solution under stirring. Gelatin solution is added to the polymer solution under stirring at temp 52°C and de-aerate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process.
Example-15
Ingredients Composition in g.
Cellulose Acetate Phthalate 3.0
Water 36.0
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 1.0
Gelatin Solution ( 33.33% w/v ) 60.0
To water add ammonia solution under stirring. Add Cellulose Acetate Phthalate slowly to above solution under stirring de-aerate the solution on the water bath. Add triethyl citrate to the polymer solution under stirring. Gelatin solution is added to the polymer solution under stirring at temp 52°C and de-aerate the final solution at temp 52°C. Hard gelatin capsules

are molded in conventional dip molding process. Capsules were not brittle for 10 days and retained the mechanical strength. But cellulose acetate phthalate (CAP) did not give good result in stability studies.
Example-16
Ingredients Composition in g.
Cellulose Acetate Phthalate 6.0
Water 40.0
Ammonia solution ( 25 % w/v ) q.s
Triethyl citrate 1.0
Gelatin Solution ( 33.33% w/v ) 53.0
To water add ammonia solution under stirring.Add Cellulose Acetate Phthalate slowly to above solution under stirring de-aerate the solution on the water bath. Add triethyl citrate to the polymer solution under stirring. Gelatin solution is added to the polymer solution under stirring at temp 52°C and de-aerate the final solution at temp 52°C. Hard gelatin capsules are molded in conventional dip molding process. Capsules were not brittle for 10 days and retained the mechanical strength.
Example 17
Ingredients Composition in g.
Gelatin solution ( 33.33%w/v) 35 g.
Methacrylic acid copolymer 17 g.
Water 30.5 g.
Glycerin 10 g.
Ammonia solution ( 25%) q.s.
Triethyl citrate 7.5 g.
To water added glycerin and stirred until it mixes with water. Added ammonia and stirred. Added methacrylic acid copolymer to the above and de-aerated the solution for overnight at temperature 40 deg. C.

Added triethyl citrate to the above and stirred well. Added gelatin solution to the above solution. This solution was taken for hard capsule dip molding process. The viscosity was very high and the hard capsules were not formed. Very soft capsules were formed that are not sturdy. This combination was not found suitable for dip molding process of capsules.
Example 18
Ingredients Composition in g.
Sodium carbonate 10 g.
Water 100 ml.
Methacrylic acid copolymer 15 g.
Gelatin solution ( 33.33% w/v) 100 ml
Added water to sodium carbonate and mixed well. Added methacrylic acid copolymer to the above and stirred. Gelatin solution was added to above solution and mixed well. De-aerated the solution at 40 deg. C on a water bath. Films were prepared before dip molding the capsules to check the disintegration properties. The films were not stable at gastric pH and disintegrated completely at 25 mins. This composition was not found suitable to retain enteric properties.
Example 19
Ingredients Composition in g.
Sodium - Bicarbonate 19 g.
Water 190 ml.
Methacrylic acid copolymer 38 g.
Gelatin solution ( 33.33% w/v) 53 ml
Added water to sodium bicarbonate and mixed well. Added methacrylic acid copolymer to the above and stirred. Gelatin solution was added to above solution and mixed well. De-aerated the solution at 40 deg. C on a water bath. Films were prepared before dip molding the capsules to check the disintegration properties. The films did not disintegrate in

Example 22
Ingredients Composition in g.
Hydroxypropylmethyl cellulose phthalate 10 g.
Water 50 ml.
Ammonia solution ( 25 % ) 3 ml
Gelatin solution ( 33.33 % w/v) 15 ml
Carrageenan ( gelling aid ) 0.4 g.
Potassium chloride 0.04 g.
HPMCP was dispersed in water and ammonia was added to solubilise it. Carrageenan and potassium chloride was added and gelatin solution was added to the above. A film was prepared to check the disintegration properties. The film was very BRITTLE and did not dissolve in gastric pH for 2 hours.
Example 23
Ingredients Composition in g.
Hydroxypropylmethyl cellulose phthalate 10 g.
Water 60 ml.
Ammonia solution ( 25 % ) 3 ml
Gelatin solution ( 33.33 % w/v) 15 ml
Carrageenan ( gelling aid ) 0.5 g.
Potassium chloride 0.04 g.
HPMCP was dispersed in water and ammonia was added to solubilise it. Carrageenan and potassium chloride was added and gelatin solution was added to the above. A film was prepared to check the disintegration properties. The film was very BRITTLE and did not dissolve in gastric pH for 2 hours.

gastric pH for 2 hrs. This passes the enteric test. The films were soft without any brittleness.
Example 20
Ingredients Composition in g.
Methacrylic acid copolymer 6 g.
Isopropyl alcohol 85 ml
Water 5 ml
Triethyl citrate 0.6 g.
Added methacrylic acid copolymer into isopropyl alcohol and dissolved . Added water and TEC and stirred well. Films were made with this solution . Films were not brittle and were very elastic with no mechanical strength. Added gelatin solution to give mechanical strength , but there was an incompatibility and gelatin precipitated out in the solvent.
Example 21
Ingredients Composition in g.
Hydroxypropylmethyl cellulose phthalate 10 g.
Water 50 ml.
Ammonia solution ( 25 % ) 3 ml
Gelatin solution ( 33.33 % w/v) 15 ml
Carrageenan ( gelling aid ) 0.12 g.
Potassium chloride 0.04 g.
HPMCP was dispersed in water and ammonia was added to solubilise it. Carrageenan and potassium chloride was added and gelatin solution was added to the above. A film was prepared to check the disintegration properties. The film was very BRITTLE and did not dissolve in gastric pH for 2 hours.

Study of Brittleness of Enteric capsules with different concentrations of Triethyl citrate.

Brittleness is checked by Brittleness Rod
Brittleness: Take 100 capsule shells devoid of long short, broken or separated ones, place each shell on a smooth hard surface. Using a brass rod of 150mm length and 25 mm diameter and weighing approximately 0.5 kg, press the entire length of the shell until the sides meet. Repeat with another 99 shells. Not more than two shells crack, ship or break. If more than two but less than six shells fail to comply with the test, repeat the test with another 100 shells taken at random. The sample being examined if not more than six out of 200 shells fail to comply with the test.

WE CLAIM
1. A process for manufacturing a pH dependent enteric polymeric
container without coating such as a hard capsule containing a body
and a cap comprising the steps of :
(a) neutralizing enteric polymer slowly in alkaline solution under stirring,
(b) de-aerating the solution on the water bath,
(c) adding plasticizer to the polymer solution under stirring and homogenized,
(d) adding gelatin solution to the polymer solution under stirring at desired temperature,
(e) de-aerating the final solution at desired temperature,
dipping and molding the capsule by conventional process known in the art.
2. A process as claimed in claim 1 wherein the alkaline solution used for neutralizing enteric polymer is prepared by adding water to a base like ammonia, sodium carbonate, sodium bicarbonate, sodium hydroxide and the like under stirring.
3. A process as claimed in claim 1 wherein gelatin solution is added at a temperature in the range of 45 degree centigrade to 55 degree centigrade, preferably between 46 degree centigrade and 52 degree centigrade.
4. A process as claimed in claims 1 to 3wherein the polymeric container comprises methacrylic acid, triethyl citrate and gelatin.

5. A process as claimed in claims 1 to 4 wherein the container is a robust and sturdy capsule.
6. A pH dependent enteric polymeric container without coating such as a hard capsule containing a body and a cap consisting of an enteric polymer, triethyl citrate, and gelatin characterized in that it contains 1 to 5% of triethyl citrate and the container is robust and sturdy.
7. An enteric polymeric container as claimed in claim 6 wherein the enteric polymer is 5 to 60% of methacrylic acid copolymer, 1 to 2% triethyl citrate, and 3 to 35% gelatin and the container is robust.
8. An enteric polymeric container as claimed in claim 6 wherein the enteric polymer may be selected from a group consisting of methacrylic acid copolymer in the range of 5% w/w to 60% w/w, preferably 8% to 20%; a more preferably 12 to 18%. Cellulose acetate phthalate in the range of 2% to 12%, preferably 3% to 8%; hydroxypropyl methylcellulose phthalate in the range of 1% to 20%, polyvinyl acetate phthalate and other gastro resistant polymers and the like and combinations thereof, in powdered form or in suspension form.
9. An enteric polymeric container as claimed in any of the preceding claims wherein the container is a hard capsule.
10. An enteric polymeric container as claimed in any of the preceding claims wherein the container may optionally include colourants, surfactants, opacifiers, silicon dioxide, preservatives, sweeteners, flavours, and the like.

11. An enteric polymeric container as claimed in any of the preceding claims wherein the container may or may not be seaied.
12. An enteric polymeric container as claimed in any of the preceding claims wherein the container may optionally be printed axially and/or radially in or more colours.
Dated this 2nd day of August, 2002.
FOR SCITECH CENTRE By their Agent


(MANISH KRISHNA

SAURASTRI) & SAURASTRI