Description:FIELD OF THE INVENTION
The present invention relates to starch based enteric capsules. The capsules of this invention act as gastric acid resistant and are made up of combination of starches along with Polyvinyl alcohol (PVA) and pectin.
The present invention further relates to the process of preparing the starch based enteric capsules using single dip technology and thereby produces the enteric property by delaying the release of the drug.

BACKGROUND OF THE INVENTION
Oral delivery is routinely cited as the universally preferred route of administration for drug products and amongst the several oral dosages forms available, capsules are a widely used oral dosage form due to their simplicity and ease of manufacture. The capsule shell is an egg-shaped hollow shell which provides ease of swallowability, excellent taste masking, good bioavailability, and can be dissolved rapidly, reliably and safely. Capsule dosage forms are used to enclose one or more than one drug substance in a small shell. Encapsulation of drugs in capsules further provides the potential to improve the bioavailability wherein the active ingredients are rapidly released as soon as the shell ruptures. This is mainly due to much lower pressure used in compacting dosage as compared to manufacturing process involved in manufacturing tablets. Unlike the tablet dosage form, the complete disintegration hence is not necessary for the active ingredients encapsulated in the capsule shell to become available for absorption.
A drug which is inactivated or deteriorated in efficacy by gastric juices, a drug that stimulates the gastric mucosa, and a drug that inhibits process of digestion in the stomach are encapsulated in an enteric capsule to prescribe.
In case of the drugs which are inactivated or deteriorated in efficacy by gastric juices or a drug that stimulates the gastric mucosa or a drug that inhibits process of digestion, the shell, exhibiting enteric behaviour plays a vital role due to its acid resistant property. The dosage forms wherein the delayed release of an active is required or wherein the first-pass metabolism is expected, the enteric coating prolongs the release of the drug. Conventionally, the coating materials are polymers which are acidic in nature and containing carboxylic groups, such as phthalate (CAP) cellulose acetate, hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMC-AS), acrylic copolymers, pectin or alginates. Usually, enteric properties of pharmaceutical compositions are achieved by a coating process with enteric materials on e.g. granules, pellets, tablets or hard or soft capsules.
Enteric coating is a useful strategy for the oral delivery of drugs to prevent the drug being released in the acidic conditions of the stomach before reaching the intestine. Enteric capsule drug delivery was developed to provide oral delivery of drugs that need to be protected from release in the acid conditions of the stomach and allowing them to be released and absorbed in the small intestine instead.
During the enteric capsule shell preparation process, the dipping imparts an important role for providing the enteric characteristic to the capsule. In most cases, capsule shell manufacturing starts with the preparation of enteric dipping solution. In the next step, plurality of moulding pins made of special grade of stainless steel are dipped into the said dipping solution for a certain amount of time and certain depth, separately for capsule cap and body part. This process is called dipping and thereafter the pins get removed from the enteric solution and are transferred towards the drying area while spinning around their axis in order the enteric coat gets distributed evenly. In the drying area, pins pass several drying stages so the coating of enteric solution gets converted in thin rigid film and achieves desired prolonged release effect.
The enteric capsule made up of using the said process have a pH-dependent solubility wherein drugs may be soluble only upto less than 10% under gastric conditions at pH of 1.2 and readily soluble under intestinal conditions at a pH of 6.8.
The existing enteric capsules has been known to be prepared from a composition comprising an enteric substance and agar. Another conventional process for preparing acid resistant capsule is double dipping method. In this method, a pin is dipped into a gelatin solution and an enteric coating solution subsequently, and then dried to form a general acid resistant capsule shell.
Owing to high consumer acceptance, various methods and techniques are developed over the years to prepare enteric coated capsule shells. Enteric coated capsule shells are already present in market however the materials used for the enteric solution such as phthalate (CAP) cellulose acetate, hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMC-AS), methacrylate copolymers, pectin or alginates are required to be dissolved in organic solvents in the preparation and thus existing acid resistant capsule usually has undesired the organic solvent residues.
United States Patent Publication No. 4,138,013 discloses an enteric coated hard-shell capsules wherein capsule body and cap portions are formed by dip-molding using a homogeneous film-forming mixture of hydroxypropyl methylcellulose and an ammonium salt of cellulose acetate phthalate polymer, or mixture of gelatin and an ammonium salt of a copolymer of methacrylic acid and methacrylic acid alkyl ester. However, the capsules so made according to the mentioned techniques encountered challenges such as poor solubility in intestinal juice, high organic solvent content, inadequate stability and diffusion problems.
European Patent Application No. EP 0056825 A1 discloses method for producing enteric coated capsules wherein film forming polymers are dispersed in an aqueous solution of a plasticizer, viscosity-increasing auxiliary substances and anti-foaming agents. The said publication discloses cellulose esters (e.g., cellulose acetate phthalate), other natural semi-synthetic or synthetic film-forming substances, cellulose ether esters (e.g. hydroxypropylmethyl-cellulose phthalate), or acrylic resins (e.g. Eudragit®) as film forming polymers. This application emphasizes the importance of the viscosity of the dispersion required for the thickness of the capsule wall and for this purpose the process have used all known viscosity-increasing auxiliary substances like gelatin. Thus, this process is based on the setting ability of hot gelatin solution by cooling. Otherwise, the solution would flow down to form capsules with non-uniform wall thickness and unacceptable properties.
United States Patent Publication No. 4,365,060 discloses enterosoluble capsule prepared with mixed ester of an alkyl-, hydroxyalkyl- or hydroxyalkyl alkylcellulose esterified with succinyl anhydride and an aliphatic monocarboxylic acid anhydride. However, the solution prepared with such materials could not possess gelation ability and therefore it couldn’t be taken up for scale up.
United States Patent Publication No. 7,041,315 discloses pectin film composition for manufacturing of hard capsules for pharmaceutical and veterinary applications. The film forming composition of pectin of this invention further comprises at least one additional film-forming polymer and a setting system. The setting system referred in this patent comprises the pectin in combination with a divalent cation; or with a polysaccharide selected from carrageenan, gellan and mixtures. Pectin, as used alone, in this art encountered the problem with gelation and setting.
United States Application Publication No. US 2019/0000768 discloses seamless enteric capsule consisting of a capsule fill, a shell layer; and an enteric coating. The enteric coating layer comprises polymers selected from methacrylic acid-based polymer, polyvinyl acetate phthalate, organic acid ester of hydroxypropyl methylcellulose, carboxymethylethylcellulose, and cellulose acetate phthalate.
Japanese Patent Publication No. 58138458 discloses process for preparing enteric capsules from an aqueous solution of hydroxylepropyl methyl cellulose acetate succinate. This reference describes two-step process involving the dipping of mould pins into an aqueous solution of hydroxylepropyl methyl cellulose acetate succinate alkali metal salt and gelatin and thereafter dipping in aqueous solution. However, since the gelatin content was too low in this composition, the setting ability was too low.
Thus, as seen from above, the state-in-art currently available for the enteric coated capsule possess many disadvantages to provide highly efficient enteric coated capsule. These state-of-the-art technologies uses synthetic materials for imparting the enteric properties, increase efforts while coating of polymer over the base shells while some of the formulations show non-gelation property to provide industrially scalable capsule. The already existing state of arts are also time consuming.
However, despite the so many attempts, none have succeeded in manufacturing enteric coated capsules with sufficient uniformity in an enteric layer using single dip technology.
Therefore, in light of the aforementioned facts, there exists a need to develop new starch based enteric capsules using single dip technology.
The invention here resolves the issues faced by the various prior arts. Thus, it is an object of the present invention to provide starch based enteric capsules possessing the enteric property.

SUMMARY OF THE INVENTION
The invention discloses the enteric capsules prepared from native starch and a modified starch in combination with pectin and polyvinyl alcohol. The enteric capsule prepared in this manner are designed to protect the formulation ingredients from being damaged or degraded by stomach acid and thereby prolonging the release of the drug.
The invention further discloses the preparation of acid-resistant or gastric-resistant capsules used to prevent the drug from inactivation which are degraded by gastric enzyme and are prepared by single-dip technology.

DETAILED DESCRIPTION OF THE INVENTION
Capsules are solid oral dosage form wherein a medicinally active ingredient is enclosed within the hard or soft polymer capsule shell.
The term “enteric coat” as used throughout the specification refers to a polymer barrier applied to oral medication that prevents its dissolution or disintegration in the gastric environment. Such enteric coat helps by either protecting drugs from the acidity of the stomach, the stomach from the detrimental effects of the drug, or to release the drug after the stomach, preferably into small intestine.
The term “modified starch” as used throughout the specification are starch derivatives that are prepared by changing the properties of native starch using physical, enzymatical, or chemical means. Starches are modified to increase their stability against excessive heat, acid, shear, time, cooling, or freezing; are also modified to change their texture; to decrease or increase their viscosity; to lengthen or shorten gelatinization time; or to increase their visco-elastic stability. The term “modified starch” may as used throughout the specification may be referred as film forming polymer.
The term “native starch” as used throughout the specification are plant-based ingredients obtained from various agricultural raw materials and are pure forms of the starch. Native starch are generally derived from sources such as maize, waxy maize, high amylose maize, wheat, tapioca and potato. The term “native starch” may as used throughout the specification may be referred as film forming polymer.
The term “hydrocolloid” as used throughout the specification is used to describe range of polysaccharides and proteins widely used to perform a number of functions including thickening and gelling aqueous solutions, stabilising foams, emulsions and dispersions etc. Hydrocolloids also possess the adhesive properties. Hydrocolloids can be selected from the group consisting of gum talha, gum ghatti, gum karaya, gum tragacanth, arabinogalactan, dextran, pectin, tapioca-dextrin, carboxymethyl cellulose (CMC), methyl cellulose (MC), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), carbopol, polyethylene oxide (PEO), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), retene, pullulan, chitosan and combination thereof.
The term “gelling agent” as used throughout the specification can be selected from the group consisting of gelatin, carrageenan, gellan gum, xanthan gum, pectin, locust bean gum, guar gum, agar or any combination thereof alone or jointly with its corresponding cations such as sodium, potassium, calcium. Primarily, gelling agents are used to achieve film forming as well as enteric properties.
The term “emulsifying agent” as used throughout the specification generally offer some oil-wetting characteristics, comprising both oil-soluble hydrophobic (nonpolar) and water-soluble hydrophilic (polar) portions that act as a stabilizer of the droplets (globules) of the internal phase of an emulsion. Emulsifying agents can be selected from the group consisting of potassium laurate, triethanolamine stearate, sodium lauryl sulfate, alkyl polyoxyethylene sulfates, sodium dodecyl sulfate, and dioctyl sodium sulfosuccinate, quaternary ammonium compounds, cetyltrimethyllammonium bromide, and lauryldimethylbenzylammonium chloride etc.nonionic: polyoxyethylene fatty acid derivatives of the sorbitan esters (for example, tween series), polyoxyethylene fatty alcohol ethers sorbitan fatty acid esters polyoxyethylene alkyl ethers (macrogols) polyoxyethylene sorbitan fatty acid esters, polyoxyethylene polyoxypropylene block copolymers (poloxamers), polyethylene glycol 400 monostearate, lanolin alcohols, ethoxylated lanolin, cetyl alcohol, glyceryl monostearate, methylcellulose, sodium carboxymethylcellulose and combinations thereof.
The term “dispersing agent” as used throughout the specification provide additional oil-wetting characteristics and also provide the stability.
In one aspect, the invention provides the capsule prepared from single dip technology method.
In another aspect, the invention provides the capsules made up from the blend of modified starch and native starch.
In one embodiment, the modified starch and native starch are used in a combination in a ratio ranging from about 95:05 to about 50:50.
Modified starch is generally used to give the mechanical strength and film formability while the native starch is primarily used to impart the characteristics of delayed release to the drug via the mechanism of absorption, swelling and thereafter releasing the drug via osmosis process.
In one aspect of the invention native starch in its original form with distinct micro particles acts like a barrier for the release and delaying osmotic dissolution of the drug via the mechanism of absorption, swelling and then releasing the drug.
In another aspect of the invention the enteric capsule comprises gelling agent and hydrocolloid in combination with modified starch and native starch.
In one embodiment, the gelling agent of the present invention is selected from the group consisting of gelatin, carrageenan, gellan gum, xanthan gum, pectin, locust bean gum, guar gum, agar and combination; preferably, the gelling agent selected for the present invention is pectin.
In another embodiment of the invention, the gelling agent present in an enteric capsule ranges from an amount of about 0.5% to about 15%, preferably from about 1% to about 12% and more preferably from about 2% to about 10%.
In one aspect of the invention, the hydrocolloid used for present invention is selected from the group consisting of gum talha, gum ghatti, gum karaya, gum tragacanth, arabinogalactan, dextran, pectin, tapioca-dextrin, carboxymethyl cellulose (CMC), methyl cellulose (MC), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), carbopol, polyethylene oxide (PEO), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), retene, pullulan, chitosan and combination; preferably, polyvinyl alcohol (PVA) acts as a hydrocolloid in the present invention.
In another aspect of the invention, the hydrocolloid present in an enteric capsule range from an amount of about 1% to about 25%, preferably from about 1.5% to about 20% and more preferably from about 2% to about 15%.
In one embodiment of the invention the enteric capsule comprises pectin and polyvinyl alcohol (PVA) in combination with modified starch and native starch.
Hydrogel-based materials such as hydrogels of polyvinyl alcohol (PVOH) and the biopolymer pectin are freely available.
PVOH is a semi-crystalline hydrophilic synthetic polymer produced by the hydrolysis of polyvinyl acetate (PVA). The PVOH structure contains several –OH groups and is, therefore, a highly hydrophilic and water-soluble polymer that exhibits excellent mechanical properties, chemical stability and the ability to form films.
Pectin is a polysaccharide extracted from plants origin mainly from fruits such as apple, pomegranate etc. It is mainly composed of a (1-4)-linked galacturonic acid (GalA) units containing varying amount of methyl ester substituents (methoxylation degree), depending on the pectin’s origin and purification method.
The presence of hydrophilic sites, such as –OH and/or –COOH in the PVOH and pectin, is expected to promote the interaction between the two polymers i.e pectin and PVOH. Hydrogel prepared only with PVOH did not allow any water permeation through the gel. As highly hydrolyzed PVOH was employed, a gel with a high degree of reticular closure was obtained, thus hindering the permeation of water through the hydrogel. The addition of pectin into the hydrogel increased the amphiphilic character of the sorbent phase, due to presence of methyl ester groups in the pectin structure. The carboxylic groups present in pectin also helps to resist acidic environment. This assured slow extraction efficiencies for all drugs in the capsules under acidic conditions.
This forms a network due to hydrogen bonding between the -COOH groups of Pectin and -OH groups of PVA as shown below enhancing the delayed release of drugs in acidic medium and imparting enteric property to the capsule.

In one aspect of the invention, the enteric capsule comprises hydroxypropylated starch and native starch selected from potato starch, corn starch, maize starch, tapioca starch, sago starch and combination along with polyvinyl alcohol and pectin.
Polyvinyl alcohol (PVA) is known to prolong the drug release owing to its high viscosity solutions, which provide a slow diffusion of drugs and its ability of PVA functional groups to form complex compounds with drugs through hydrogen bonds. On the other side, pectin being the acid resistant material provides the enteric property to the capsule.
In one aspect of the invention, PVA-Pectin combination works synergistically to enable supramolecular interaction involving hydrogen bonding and better setting and gelation without the use of any external gelling agents.
In another aspect of the invention, enteric capsule made using single dip technology comprises
• Modified starch
• Native starch
• Hydrocolloid
• Gelling agent
• Optionally, Dispersing and emulsifying agent and/or colouring agents
In another aspect of the invention, enteric capsule comprises modified starch which is also called as film forming starch. In one aspect, the modified starch provides mechanical strength and film formability and is hydroxypropylated starch.
In one embodiment of the invention, the modified starch present in an enteric capsule range from an amount of about 70% to about 95%, preferably from about 75% to about 90% and more preferably from about 80% to about 85%.
In one aspect of the invention, enteric capsule comprises native starch which is also called as supporting starch. In one aspect, the native starch helps in delaying the release of the drug and is selected from the group consisting of potato starch, corn starch, maize starch, tapioca starch and sago starch.
In another aspect of the invention, the native starch (supporting starch) present in an enteric capsule range from an amount of about 5% to about 30%, preferably from about 10% to about 25% and more preferably from about 15% to about 20%.
In one aspect of the invention, dispersing and emulsifying agent present in an enteric capsule range from an amount of about 1% to about 1.5%, preferably from about 0.5% to about 1% and more preferably from about 0.1% to about 0.5%. In another aspect, the dispersing and emulsifying agent is selected form the group consisting of potassium laurate, triethanolamine stearate, sodium lauryl sulfate, alkyl polyoxyethylene sulfates, sodium dodecyl sulfate, and dioctyl sodium sulfosuccinate, quaternary ammonium compounds, cetyltrimethyllammonium bromide, and lauryldimethylbenzylammonium chloride etc.nonionic: polyoxyethylene fatty acid derivatives of the sorbitan esters (for example, tween series), polyoxyethylene fatty alcohol ethers sorbitan fatty acid esters polyoxyethylene alkyl ethers (macrogols) polyoxyethylene sorbitan fatty acid esters, polyoxyethylene polyoxypropylene block copolymers (poloxamers), polyethylene glycol 400 monostearate, lanolin alcohols, ethoxylated lanolin, cetyl alcohol, glyceryl monostearate, methylcellulose, sodium carboxymethylcellulose and combinations thereof. More preferably, the dispersing and emulsifying agent used for the present invention is sodium lauryl sulfate.
In one embodiment of the invention, enteric capsule prepared using single dip technology comprises
• Film forming starch i.e., hydroxypropylated starch
• Supporting starch selected from potato starch, corn starch, maize starch, tapioca starch and sago starch
• Polyvinyl alcohol
• Pectin
• Optionally, Sodium lauryl sulfate
• Colouring and opacifying agents.
In another embodiment of the invention, the present invention comprises process to prepare the dipping solution.
In another embodiment, the present invention provides the process to prepare the dipping solution comprising mixing the film forming starch, native starch, hydrocolloid, gelling agent and emulsifying and dispersing agent in specific ratio.
In one aspect of the invention, the process to prepare the dipping solution comprises mixing the film forming starch in an amount ranges from about 70% to about 95%, native starch in an amount ranges from about 5% to about 30%, hydrocolloid in an amount ranges from about 1% to about 25%, gelling agent in an amount ranges from about 0.5% to about 15% and emulsifying and dispersing agent in an amount ranges from about 1% to about 1.5%.
In another aspect of the invention, the process to prepare the dipping solution comprises mixing the hydroxypropylated starch in an amount range from about 80% to about 85%, native starch in an amount ranges from about 15% to about 20%, polyvinyl alcohol in an amount ranges from about 2% to about 15%, pectin in an amount ranges from about 2% to about 10% and optionally, sodium lauryl sulfate in an amount ranges from about 0.1% to about 0.5%.
In one embodiment of the invention, the process comprises the single dip technology wherein the capsules are prepared by cold pin process at temperature of about 10ºC to about 35ºC, preferably at a temperature of about 15ºC to about 30ºC and more preferably at a temperature of about 20ºC to about 25ºC.
In one embodiment, the invention provides the process to prepare enteric capsule comprising-
a. Preparing dipping solution of the film forming starch, native starch, hydrocolloid, gelling agent and optionally, emulsifying and dispersing agent
b. Dipping the capsule shells in the solution as prepared in step (a)
c. Drying of the capsules
d. Stripping of the capsule
In one embodiment, the invention provides the process to prepare enteric capsule comprising-
a. Preparing dipping solution by mixing the hydroxypropylated starch in an amount ranges from about 80% to about 85%, native starch in an amount range from about 15% to about 20%, polyvinyl alcohol in an amount ranges from about 2% to about 15%, pectin in an amount ranges from about 2% to about 10% and optionally, sodium lauryl sulfate in an amount ranges from about 0.1% to about 0.5%.
b. Dipping the capsule shells in the solution as prepared in step (a)
c. Drying of the capsules
d. Stripping of the capsule
In one embodiment, the invention provides the process to prepare dipping solution comprising-
a. Setting the water bath at a temperature of about 98±1° C and adding required quantity of demineralised water (DM) in vessel.
b. Adding the potassium chloride in solution of step (a) and stirring at 150-200 RPM of for 10 min
c. Optionally, adding sodium lauryl sulfate
d. Adding polyvinyl alcohol in above solution and stirring for 10 min.
e. Adding mixture of measured quantity of modified starch & native starch slowly to avoid lumps formation at 150-200 RPM
f. Increasing the stirring speed to 350-400 RPM and maintaining for the next 3 hrs at 80°C
g. Preparing the pectin solution separately in cold water at 15°C to 16°C by mixing known quantity of powder manually for 15 min to get uniform dispersion. Then increasing the temperature of this dispersion to 80°C to get clear solution.
h. Transferring the pectin solution of step (g) to solution prepared in step (f) kept at 80°C and maintaining the stirring speed at 200-300 RPM for 30 min
i. Decreasing the temperature of solution prepared in step (h) to 70°C and reducing the stirring to 100-150 RPM.
j. Maintaining the condition of step (i) for next 30 min to 45 min to clear the bubbles generated during mixing process, promote gel formation and homogenization of the solution.
k. Recording the viscosity, solid content, and gel flow of the solution after the temperature of solution decreased to 65°C to 70°C.
In one aspect of the invention, the process comprises two-stage dissolution method as prescribed in pharmacopeia for evaluating enteric property for oral dosage form, consists of a two-hour acid stage dissolution in 0.1 N HCl with five sampling points and subsequently one-hour buffer- stage dissolution at pH 6.8 phosphate buffer with five sampling points.
The present invention is further explained in detail by referring to the following, which are not to be construed as limitative.
Examples / Experiments
1- Evaluation of base polymer and altering drug release profile.
Various starches were dissolved in hot water. They were then casted on glass plate to make thin films of about 100 micron thickness. The film casting machine was in house developed in ACG Associated capsules. The solution was measured for viscosity on Brookfield viscometer DV-II+Pro. It was also measured for concentration and gelling ability. The films were visually observed for its formability and solubility in 0.1N HCl solution. The trials were conducted as per plan given as nos T1-1 to T1-8

Table -1 Trial combinations for parameter studies

As can be seen from the observations that the drug release profile can be altered by combination of different starches.
2- Selection of starch combination to facilitate capsules manufacturing.
Experiment 1 above showed possibility of making film which can be modified for drug release profile. For these various combinations of starches along with polyvinyl alcohol and pectin and /or other gums were studied. The details of composition combination is as given in table-2 below.
Here again Various compositions were dissolved in hot water as prescribed in table-2. They were then casted on glass plate to make thin films of about 100 micron thickness. The film casting machine was in house developed in ACG Associated capsules. The solution was measured for viscosity on Brookfield viscometer DV-II+Pro at different temperatures such as 65ºC, 60ºC and 55ºC. It was also measured for concentration and gelling ability at these temperatures. The films were visually observed for its formability and compositions were judged for its usability in capsule dip molding process. The observations for each composition were summarised in Table-3 below.

Table- 2 Trial compositions for evaluation


Table- 3 Evaluation summary for Table 2 experiments.

As can be seen from the data there were various combinations which can be explored for capsule manufacturing step.

3- Evaluation of alternate to Modified starch (DCG starch )
It was also explored use of clear gum in place of DCG starch to assess the effect on drug release and film formability. The composition trials as given in Table -4 below.

Table-4 Composition trials for replacement of modified starch.

Clear gum can be used as replacement to DCG starch.
4- Manufacturing of capsules.
Based on learning from earlier 3 studies, certain combinations were selected for capsule manufacturing trials. Following method was followed for preparing dipping solution and manufacturing capsules.
Solution Preparation:
1. The water bath temperature was set at 98±1°C. The water temperature was maintained at 95±1°C throughout. DM water of known quantity was weighed in suitable vessel and the temperature was achieved.
2. KCl of known quantity was added and stirred for 10 min. The 150-200 RPM was maintained.
3. Optionally, sodium lauryl sulfate was added and stirred for 10 min.
4. Polyvinyl alcohol was added and stirred for 10 min.
5. Mixture of measured quantity of modified starch and potato starch was added slowly and carefully to avoid lumps formation during addition of material. The 150-200 RPM was maintained until the addition of powder was finished.
6. After adding the powder, the stirring speed was increased to 350-400 RPM and maintained it for the next 3 hrs, until complete dispersion of starch material was achieved. The vessel was covered adequately to ensure minimum evaporation loss and maintained at 80°C.
7. Pectin solution was prepared separately in cold water at 15°C to 16°C by mixing known quantity of powder manually for 15 min until uniform dispersion was achieved. Thereafter, the temperature of dispersion is increased to 80°C and the stirring speed was maintained at 200-300 RPM for 30 min to completely dissolve pectin in water.
8. The pectin solution so prepared is then transferred to solution prepared in step (6) above.
9. The set temperature of above solution was decreased to temperature to 70°C and the stirring was reduced to 100-150 RPM. The condition was maintained for next 30 min to 45 min to clear the bubbles generated during mixing process, promote gel formation and homogenization of the solution.
10. After the temperature of solution decreased to 65°C to 70°C, viscosity, solid content, and gel flow of the solution was recorded.
Dipping Condition:
11. On achieving and recording the viscosity, solid and gel flow under acceptable limit, the solution was transferred to dip bath.
12. The Dip bath temp and RPM was maintained at 65±5°C and 20 to 60 RPM respectively.
13. The pin bar temp was set at 23°C to 25°C.
14. The machine speed was set at 4 BPM
15. The dipping was carried out by setting a suitable pin dipping and withdrawal profile.
16. The pin bars with wet shells were rotated to have uniform distribution on pin and then subjected to stream of dry air.
17. The air was maintained at adequate velocity and temperatures between 20 to 35°C. The absolute humidity was maintained between 6 to 8 g/kg of dry air.
18. The dried shells were then stripped, cut to appropriate size for joined to form empty capsules.
19. The parameters such as pick up weight, solution viscosity, solid content and gel flow were monitored in regular interval to ensure formation of capsule shell of appropriate weight and dimension.
Evaluation of capsules.
20. The capsules so formed were evaluated for dimensional uniformity.
21. The capsules were filled with model formulation namely Acetaminophen. The filled capsules were subjected to dissolution test as prescribed in USP and Indian Pharmacopoeia . (2 hrs in 0.1 N HCL and the 6.8 mixed phosphate buffer solution)
22. The results are summarised in table 5 below.
Table- 5 Dissolution test results.
Sample code Composition (Percentage) Avg Acidic pH Release
(120 min) Avg Buffer pH6.8 Release (60 min)
A1-1 Modified Starch – Potato starch-PVA-Pectin (80-20-10-5) 2.9% 88.3%
A2-2 Modified starch-Corn Starch-PVA-Pectin (80-20-10-5) 13% 99%
A3-3 Modified starch-Maize Starch -PVA-Pectin (80-20-10-5) 7% 84%
A4-4 Modified starch-Tapioca-PVA-Pectin (80-20-10-5) 3% 79%
A5-5 Modified starch-sago starch-PVA-Pectin (80-20-10-5.0) 1% 70%
A6-6 Modified Starch-Potato starch-PVA-Pectin-LBG-XG (80-20-10-5.0-1.0-0.5) 2% 65%
A7-7 Clear Gum-Potato-PVA-Pectin (50-50-10-5) 1% 12%

From the above results, it can be confirmed that several compositions can be developed to meet enteric criteria as prescribed in USP and IP.
The present invention is further construed in detail by referring to the following, which are not to be construed as limitative in any way.
Solution Preparation:
1. The water bath temperature was set at 98±1°C. The solution temperature was maintained at 95±1°C throughout. DM water of known quantity was weighed and added in suitable vessel. Then hold till the temperature was achieved.
2. KCl of known quantity was added and stirred for 10 min. The RPM was maintained at 150-200 RPM
3. Optionally, sodium lauryl sulfate was added and stirred for 10 min.
4. Polyvinyl alcohol was added and stirred for 10 min.
5. Mixture of measured quantity of modified starch and Potato starch was added slowly and carefully to avoid lumps formation during addition of material. The RPM was maintained at 150-200 RPM until the addition of powder was finished.
6. After adding the powder, the stirring speed was increased to 350-400 RPM and maintained it for the next 3 hrs at 80°C, until complete dispersion of starch material was achieved. The vessel was covered adequately to ensure minimum evaporation loss.
7. Pectin solution was prepared separately in cold water at 15°C to 16°C by mixing known quantity of powder manually for 15 min until uniform dispersion was achieved. Thereafter, the temperature of dispersion is increased to 80°C and the stirring speed was maintained at 150-200 RPM for 30 min to completely dissolve pectin in water.
8. The pectin solution so prepared is then transferred to solution prepared in step (6) above.
9. The set temperature of solution was decreased to temperature to 70°C and the stirring was reduced to 100- 150 RPM. The condition was maintained for next 30 min to 45 min to clear the bubbles generated during mixing process, promote gel formation and homogenization of the solution.
10. After the temperature of solution decreased to 65°C to 70°C, viscosity, solid content, and gel flow of the solution was recorded.
Dipping Condition:
11. On achieving and recording the viscosity, solid and gel flow under acceptable limit, the solution was transferred to dip bath.
12. The Dip bath temp and RPM was maintained at 65±5°C and 20 to 60 RPM respectively.
13. The pin bar temp was set at 23°C to 25°C.
14. The machine speed was fixed at 4 bars per min.
15. The dipping was carried out by setting a suitable dipping and withdrawal profile.
16. The parameters such as pick up weight, solution viscosity, solid content and gel flow were monitored in regular interval to ensure formation of capsule shell of appropriate weight and dimension.

, Claims:1. The enteric capsule comprising modified starch and native starch in combination with hydrocolloid and gelling agent.

2. The modified starch and Native starch as claimed in claim 1 are the main film forming polymer.

3. The modified starch and Native starch as claimed in claim 1 are used in a combination in a ratio ranging from about 95:05 to about 50:50.

4. The modified starch as claimed in claim 2, is hydroxypropylated starch.

5. The native starch as claimed in claim 2 is selected from the group consisting of potato starch, corn starch, maize starch, tapioca starch, sago starch and combination thereof.

6. The native starch as claimed in claim 5 is Potato Starch.

7. The hydrocolloid as claimed in claim 1 is selected from the group consisting of gum talha, gum ghatti, gum karaya, gum tragacanth, arabinogalactan, dextran, pectin, tapioca-dextrin, carboxymethyl cellulose (CMC), methyl cellulose (MC), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), carbopol, polyethylene oxide (PEO), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), retene, pullulan, chitosan and combination.

8. The hydrocolloid as claimed in claim 7, is polyvinyl alcohol.

9. The hydrocolloid as claimed in claim 7, is present in an amount ranging from about 1% to about 25%, preferably from about 1.5% to about 20% and more preferably from about 2% to about 15% over film forming polymer on dry basis.

10. The gelling agent as claimed in claim 1 is selected from the group consisting of gelatin, carrageenan, gellan gum, xanthan gum, pectin, locust bean gum, guar gum, agar and combination thereof.

11. The gelling agent as claimed in claim 10, is pectin.

12. The gelling agent as claimed in claim 10, is present in an amount ranging from about 0.5% to about 15%, preferably from about 1% to about 12% and more preferably from about 2% to about 10% over film forming polymer on dry basis.

13. The enteric capsule comprising hydroxypropylated starch and native starch selected from potato starch, corn starch, maize starch, tapioca starch, sago starch and combination along with polyvinyl alcohol and pectin.

14. The enteric capsule as claimed in claim 12 comprises from about 70% to about 90% film forming polymer having ratio of hydroxypropylated starch and native starch selected from potato starch, corn starch, maize starch, tapioca starch, sago starch and combination thereof in combination with about 2% to about 15% polyvinyl alcohol and from about 2% to about 10% pectin.

15. The enteric capsule comprising hydroxypropylated starch and native starch in combination with polyvinyl alcohol and pectin is prepared for delaying the drug release and to resist the acid in stomach.

16. The enteric capsule comprising hydroxypropylated starch and native starch is prepared to provide barrier to the drug release.

17. The enteric capsule as claimed in Claim 1 optionally comprises emulsifying agent.

18. The emulsifying agent as claimed in claim 17 is selected from the group consisting of potassium laurate, triethanolamine stearate, sodium lauryl sulfate, alkyl polyoxyethylene sulfates, sodium dodecyl sulfate, and dioctyl sodium sulfosuccinate, quaternary ammonium compounds, cetyltrimethyllammonium bromide, and lauryldimethylbenzylammonium chloride etc.nonionic: polyoxyethylene fatty acid derivatives of the sorbitan esters (for example, tween series), polyoxyethylene fatty alcohol ethers sorbitan fatty acid esters polyoxyethylene alkyl ethers (macrogols) polyoxyethylene sorbitan fatty acid esters, polyoxyethylene polyoxypropylene block copolymers (poloxamers), polyethylene glycol 400 monostearate, lanolin alcohols, ethoxylated lanolin, cetyl alcohol, glyceryl monostearate, methylcellulose, sodium carboxymethylcellulose and combinations thereof.

19. The emulsifying agent as claimed in claims 18 is sodium lauryl sulfate.

20. The emulsifying agent as claimed in claim 19, is present in an amount ranging from about 1% to about 1.5%, preferably from about 0.5% to about 1% and more preferably from about 0.1% to about 0.5% over film forming polymer on dry basis.

21. The enteric capsule prepared using single dip technology comprises -
a. Film forming starch i.e., hydroxypropylated starch
b. Supporting starch selected from potato starch, corn starch, maize starch, tapioca starch and sago starch
c. Polyvinyl alcohol
d. Pectin
e. Optionally, Sodium lauryl sulfate
f. Colouring and opacifying agents.

22. The process to prepare enteric capsule comprises-
a. Preparing dipping solution of the film forming starch, native starch, hydrocolloid, gelling agent and optionally, emulsifying and dispersing agent
b. Dipping the capsule shells in the solution as prepared in step (a)
c. Drying of the capsules
d. Stripping of the capsule

23. The process to prepare dipping solution as claimed in claim 22 comprises
a. Setting the water bath at a temperature of about 98±1°C and adding required quantity of DM water in vessel.
b. Adding the potassium chloride in solution of step (a) and stirring at 150-200 RPM for 10 min
c. Optionally, adding sodium lauryl sulfate
d. Adding polyvinyl alcohol in above solution and stirring for 10 min.
e. Adding mixture of measured quantity of modified starch & native starch slowly to avoid lumps formation at 150-200 RPM
f. Increasing the stirring speed to 350-400 RPM and maintaining for the next 3 hrs at 80°C
g. Preparing the pectin solution separately in cold water at 15°C to 16°C by mixing known quantity of powder manually for 15 min to get uniform dispersion. Then increasing the temperature of this dispersion to 80°C to get clear solution.
h. Transferring the pectin solution of step (g) to solution prepared in step (f) kept at 80°C and maintaining the stirring speed at 200-300 RPM for 30 min.
i. Decreasing the temperature of solution prepared in step (h) to 70°C and reducing the stirring to 100-150 RPM
j. Maintaining the condition of step (i) for next 30 min to 45 min to clear the bubbles generated during mixing process, promote gel formation and homogenization of the solution.
k. Recording the viscosity, solid content, and gel flow of the solution after the temperature of solution decreased to 65°C to 70°C.