Title of Invention

AN IMPROVED PHARMACEUTICAL COMPOSITION AND A PROCESS FOR ITS PREPARATION

Abstract

The present invention relates to a pharmaceutical composition in the form of a soft gel capsule resistant to gastric juice and dissoluble in intestine and is suitable for incorporating a benzimidazole derivative which require protection from acidic gastric juice until it reaches the small intestine, comprises of a gelatin and an enteric polymer in the form of the free acid or its salt. The surface of the soft gel capsule may optionally be treated with a gelatin cross linking agent and / or an acid solution to partially convert the polymer salt to free acid and a method for preparing such soft gel. The pharmaceutical composition carrying a benzimidazole derivative either in suspension or solution comprises of hydrophobic oily substance, an alkaline inert reacting substance and a surface active agent. ABSTRACT AN IMPROVED PHARMACEUTICAL COMPOSITION AND A PROCESS FOR ITS PREPARATION The present invention relates to a pharmaceutical composition in the form of a soft ge! capsule resistant to gastric juice and dissoluble in intestine and is suitable for incorporating a benzimidazole derivative which require protection from acidic gastric juice until it reaches the small intestine, comprises of a gelatin and an enteric polymer in the form of the free acid or its salt. The surface of the soft gel capsule may optionally be treated with a gelatin cross linking agent and / or an acid solution to partially convert the polymer salt to free acid and a method for preparing such soft gel. The pharmaceutical composition carrying a benzimidazole derivative either in suspension or solution comprises of hydrophobic oily substance, an alkaline inert reacting substance and a surface active agent. To, The Controller of Patents, The Patent Office Branch, Chennai.

Full Text

The present invention relates to an improved phannaceutical composition. The present invention particularly relates to an improved pharmaceutical composition, in the form of a soft gel capsule resistant to digestive juice. The composition of the present invention is made up of gelatin and an enteric polymer in the form of free acid or its salt, containing a benzimidazole derivative used in the treatment of duodenal ulcers, solubilised and/or suspended in a liquid or semisolid medium, comprising of a hydrophobic carrier, an alkaline inert reacting material and a surface active agent and/or a solubilising agent. The present invention also relation to a method for preparing the above said pharmaceutical composition. Benzimidazole derivatives such as Omeprazole, Lansoprazole Timoprazole and Pantoprazole etc., are known potent proton pump inhibitors with powerful inhibitory action against the secretion of gastric juice (Lancet, Nov. 27, 1982 pages 1223-1224). They are used in the treatment of Zollinzer - Elision syndrome and stress related esophagitis ulceration. The derivatives are well [mown and are described, for example in EP-A 0005129. [t has been found that these benzimidazole derivatives, and in particular comeprazole, are susceptible to degradation in acid and neutral media. It is known o protect oral dosage forms of such benzimidazole derivatives by providing an enteric coating. In this way, the active material is protected from acidic gastric uices until it reaches the desired site of release, e.g. the small intestine. Because certain enteric coatings can themselves be, or contain, acidic material, it is also often required to protect the benzimidazole derivatives from the acidity of the enteric coating. For example, it is known to formulate the benzimidazole ierivatives with an alkaline material before applying the enteric coating. It is also mown to provide an intermediate coating between the benzimidazole derivative and the enteric coating. Generally the intermediate coating is selected so as to be substantially water-soluble or water-dispersible. EP-A-024 7983- US 4,786,505; US 4,853,230 and US 5,385,739 describe oral phannaceutical preparations containing benzimidazole derivatives that are potent inhibitors of gastric acid secretion, which are composed of a core material in the form of small beads or tablets contaming one of the benzimidazole derivatives, particularly omeprazole, together with an alkaline reacting compound. The core material contains one or more inert reacting sub-coating layers thereon thereby providing a final outer enteric coating. Although the above-described compositions are reasonably stable over an extended period of storage, discoloration of the pellets and / or tablets with reduced gastric resistance and reduction of dissolution rate in alkaline buffers was observed. More over the processes disclosed above are time consuming and laborious, involving many stages in manufacturing of the composition, consequently increasing the cost of the final composition. In a Gennan patent DE 32 22 476 a pharmaceutical composition has been described in which a soft gelatin capsule that is resistant to digestive juice, whose wall consists of a usual gelatin mass which contain polyvinyl acetate phthalate, hydroxypropyl methyl cellulose phthalate or a vinyl acetate / crotonic acid copolymer and/or an alkah metal salt, ammonia salt or amino salt of the same in their wall, which released their contents readily in the intestines within the prescribed time. The capsules are further treated on the surface with an aldehyde-coating agent. The capsule shell composition described in DE 32 22 476 above, if used as such for manufacturing capsules containing one of the benzimidazole derivatives in a conventional manner, the free acidic groups of the polymer in the shell composition reacts with the benzimidazole derivatives and reduces the efficacy of the product during its storage / shelf hfe period. The present invention takes as basis, the production of soft gelatin capsules in the conventional manner using gelatin mass in the known composition and to additionally incorporate substances into the gelatin shell which are insoluble up to a pH value of 5.5 in aqueous media, but quickly dissolve above pH value of 6.0 Considering the importance gained for the composition containing benzimidazole derivatives, particularly for the treatment of duodenal ulcers, there is a need for the development of pharmaceutical composition containing said derivatives having stability for an extended period during which period the composition does not get discoloured. Accordingly, the main objective of the present invention is to provide an i improved pharmaceutical composition containing Benzimidazole derivatives having enhanced stability during storage. _ According to another objective of the present invention there is provided intestine dissoluble soft gel capsules composition consisting of gelatin and an enteric polymer in the form of a free acid or its salt characterised by the fact that the pharmaceutical composition consisting of benzimidazole derivatives, m particular omeprazole, mcorporated in an oily base which is stable during shelf storage.. Still another objective of the invention is to provide a pharmaceutical composition for carrying the benzimidazole derivatives, to be filled into the soft gel capsules, that reduces degradation of the benzimidazole derivatives during storage / shelf life. According to another feature of the invention there is provided a process for preparation of soft gel capsules containing benzimidazole derivatives that are resistant to the digestive / gastric juice comprising of a usual gelatin mass and an enteric polymer in the form of a free acid or as its salt. Accordingly, the present invention provides an improved pharmaceutical composition in the form of a soft gel capsule resistant to gastric juice and soluble in intestine useful for the treatment of duodenal ulcers and related ailments which comprises of a gelatin shell resistant to gastric juice and soluble in intestine having an enteric polymer in the form of free acid or its salt, the capsule incorporating a composition comprising of a benzunidazole derivative, a hydrophobic oily substance or a mixture of such substances, an alkaline inert reacting material, a surface active agent and / or a solublising agent. The capsules are insoluble in aqueous medium up to a pH of 5.5 but quickly dissolve above pHof6.0. According to another feature of the present invention, there is provided a process for the preparation of a pharmaceutical composition in the form of a soft gel capsule resistant to gastric juice and soluble in intestine usefiil for the treatment of duodenal ulcers and related ailments which comprises forming a gelatin shell resistant to gastric juice and soluble in intestine having an enteric polymer in the form of free acid or its salt by conventional methods, incorporating into the resultant capsule a composition comprising of a Benzimidazole derivative, a hydrophobic oily substance or a mixture of such substances, an alkaline inert reacting material, a surface active agent and / or a solublising agent. The capsules are insoluble in aqueous medium up to a pH of 5.5 but quickly dissolve above pHof6.0. In a preferred embodiment of the invention, the enteric polymer used in the soft gel capsule composition may be selected from among the polymers but not limited to free acid forms of hydroxypropyl methyl cellulose phthalate, alkyhnethacrylale and methacrylic acid ester copolymers, polyvinylacetate phftialate and the like or their ammonia or alkali metal salts. The amount of such enteric polymer employed may range from 5.0-40.0 percent, preferably 5.0 -25.0 percent by weight with reference to the dried shell. The gelatin mass into which the enteric polymer is incorporated is made up of a composition known in the art and contains gelatin, a plasticizer, preservatives, colourants, opacifiers, flavours etc., as required. In order to canyout fester dissolution of the enteric polymer for preparing the capsule shell composition, the polymer is first dispersed in water, then aqueous solution of ammonia or alkali metal salt is mixed while stirring. When alkali metal salt is used it may be selected from substances such as sodium hydroxide, potassium hydroxide, carbonate of hydrogen sodium, carbonate of hydrogen potassium, sodium carbonate, potassium carbonate etc. The quantity of the base materials used is such that it is sufficient to neutralise 60 to 100 percent of the free acid groups present in the selected enteric polymer. The excess ammonia or alkali has to be removed from the capsule shell composition to avoid decomposition of the ester couphngs in enteric polymers. When aqueous ammonia solution is used to prepare polymer solution, the excess ammonia has to be removed before preparing the capsule after mixing with the gelatin mass, by mixing the mass under reduced pressure in warm condition. When alkali metal salts are used, the excess alkah is to be neutralized by treating the capsules with an acid selected from any of the following ones, hydrochloric acid, sulphric acid, nitric acid, phosphoric acid, mono carboxylic acids such as acetic acid, propionic acid, benzoic acid etc., dicarboxylic acids such as oxalic acid, maleic acid, fumiaric acid etc. The acids are used in the form of cold aqueous solutions in the concentration range of 3 to 30% depending on the type of acid used. The acid treatment may be carried out after manufecturing and partial drying of the capsules to avoid deformation and / or leakage of the capsule contents. According to another feature of the invention the soft gel capsules are optionally treated with a cross-linking agent that reacts with gelatin and makes it insoluble in gastric juice. The cross-linking agent may be selected from among the aldehydes such as formaldehyde, glutaraldehyde, crotonaldehyde 1,2-phthalic acid aldehyde, 1,3-phthahc acid aldehyde, 1,4-phthahc acid aldehyde or carbodiimides like 1 -ethyI-3-[2-morphohnyl-(4)-ethyl]-carbodiiniide-metho-p-toluene-sulfonate. The freatment may be done by either coating 0.05 to 1.0% w/v of the substance in an alcohol containing aqueous solution on to the soft gel capsule surface or mixing these substances in the gelatin mass before capsule manufecturing. According to another feature of the invention the phannaceutical composition containing benzimidazole derivative, known for its potent proton pump inhibition with powerful inhibitory action against the secretion of gastric juice, is prepared by suspending and/or solubilising the benzimidazole derivative in a carrier mixture composed of a hydrophobic oily carrier material, an alkaline inert reacting material and a surface active agent. The amount of such benzimidazole derivative used is equivalent to one unit dose recommended depending on the benzimidazole derivative incorporated i.e. for omeprazole the amount incorporated into enteric soft gel capsule may range fi-om 10.0 to 60.0mg per capsule preferably 20.0 to 40.0 mg per capsule. The hydrophobic oily material may be selected fi-om among the following fats and oils: Fats and oils of vegetable origin such as sesame oil, com, maize oil, soybean oil, sunflower oil, arachis oil, gingly oil etc.; animal oils such as fish oil, pig oil beef oil etc.; esters of straight chained aliphatic oils contained in glycerol such as SunSoft 700 P-2 (a monoester substance manufactured by Taiho Chemicals Company) Panasete 810 ( a triester substance, manufactured by Nippon Oils and Fats); hydrogenated vegetable oils or a mixture thereof The amount of such hydrophobic oily material may range from 50.0 to 80.0 percent by weigh with reference to the contents filled in capsule. The alkaline buffering material present in the phannaceutical composition may be selected from among but are not restricted to substances such as the sodium, potassium, calcium, magnesium and aluminumi salts of phosphoric acid, carbonic acid, citric acid, other suitable organic or inorganic acids; substances used in antacid preparations; meglumine; triethanolamine etc. The amount of such alkaline buffering material present in the composition may range from 5.0 to 40.0 percent, preferably 10.0 to 25.0 percent by weight with reference to the contents filled in capsule. The surfece active agent used a& solubiUsing and / or dispersing ^ents is selected from among but are not restricted to substances such as glyceryl monostearate, polyoxyethylene castor oil derivatives such as Cremophor RH 40, Cremophor EL (Make : BASF Corporation), lecithin, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulphate, doccusate sodium etc. The amount of such surface active agent present in the composition may range from 2.0 to 20.0 percent preferably 5.0 to 15.0 percent by weight with reference to contents filled in capsule. The seamless soft gel capsules can be manufactured on a rotary die machine filling with the liquid and / or semi solid composition containing benzimidazole derivatives. 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 he scope of the invention. EXAMPLE -1 1) Composition of the Soft gelatin shell: Name of the ingredient Percent by wt. Gelatin 35.0 Glycerin 17.5 Water 20.0 Hydroxypropyl methyl cellulose phthalate 7.5 Ammonia solution (25%wA') 20.0 Gelatin mass is prepared by dispersing gelatin in a mixture of water and glycerin maintained at 70oC. Hydroxypropyl methylcellulose phthalate is dissolved by stirring in to armnonia solution at room temperature. The polymer solution is added to gelatin mass while stirring the mass maintained at 45 - 50°C. Vacuum is applied to the mixing vessel to remove the ammonia evolved and to obtain bubble free transparent mixture of polymer solution and gelatin mass. b) Composition of the medicament: Name of the ingredient mg / Capsule Soybean oil 280.0 Omeprazole 20.0 Meglumine 20.0 Lecithin 30.0 Lecithin is dispersed into soybean oil using a mechanical stirrer. Omeprazole and meglumine are added to the dispersion whUe stirring to obtain a smooth dispersion. c) Manufacturing of capsule; This gelatin mixture is transferred to the holding tank of rotary die c^sulation machine for manufacture of capsule shell. The dispersion containing medicament is transferred to the hopper of the capsulation machine for filling into the soft gel capsules. The soft gel capsules are manufactured by rotary die process. EXAMPLE - 2 a) Composition of the Soft gelatin shell: Name of the ingredient Percent by wt. Gelatin 30.0 Glycerin 15.0 Water 20.0 Hydroxypropyl methyl cellulose phthalate 10.0 Ammonia solution (25%w/v) 25.0 Gelatin mass is prepared by dispersing gelatin in a mixture of water and glycerin maintained at 70°C. Hydroxypropyl methyl cellulose phthalate is dissolved by stirring in to ammonia solution at room temperature. The polymer solution is added to gelatin mass while stirring the mass maintained at 45 - 50°C. Vacuum is applied to the mixing vessel to remove the ammonia evolved and to obtain bubble free transparent mixture of polymer solution and gelatin mass. b) Composition of the medicament: Name of the ingredient mg / Capsule Soybean oil 280.0mg Omeprazole 20.0mg Meglumine 20.0mg Lecithin 30.0mg Lecithin is dispersed into soybean oil using a mechanical stirrer. Omeprazole and meglumine are added to the dispersion while stirring to obtain a smooth dispersion. c) Manufacturing of capsule: This gelatin mixture is transferred to the holding tank of rotary die capsulation machine for manufacture of capsule shell. The dispersion containing medicament is transferred to the hopper of the capsulation machine for filling into the soft gel capsules. The soft gel capsules are manufactured by rotary die process. EXAMPLE - 3 a) Composition of the Soft gelatin shell: Name of the ingredient Percent by wt Gelatin 40.0 Glycerin 17.5 Water 20.0 Hydroxypropyl methyl cellulose phthalate 5.0 Ammonia solution (25%w/v) 17.5 Gelatin mass is prepared by dispersing gelatin in a mixture of water and glycerin maintained at 70°C. Hydroxypropyl methyl cellulose phthalate is dissolved by stirring in to ammonia solution at room temperature. The polymer solution is added to gelatin mass while stirring the mass maintained at 45 - 50°C. Vacuum is applied to the mixing vessel to remove the ammonia evolved and to obtain bubble free transparent mixture of polymer solution and gelatin mass. b) Compositioa of the medicament: Name of the ingredient mg / Capsule Soybean oil 280.0mg Omeprazole 20.0mg Meglumine 20.0mg Lecithin 30.0mg Lecithin is dispersed into soybean oil using a mechanical stirrer. Omeprazole and meglumine are added to the dispersion while stirring to obtain a smooth dispersion. c) Manufacturing of capsule: This gelatin mixture is transferred to the holding tank of rotary die capsulation machine for manufature of capsule shell. The dispersion containing medicament is transferred to the hopper of the capsulation machine for tilling into the soft gel capsules. The soft gel capsules are manufactured by rotary die process. EXAMPLE - 4 a) Composition of the Soft gelatin shell: Name of the ingredient Percent by wt. Gelatin 35.0 Glycerin 17.5 Water 25.0 Hydroxypropyl methyl cellulose phthalate 7.5 Ammonia solution (25%w/v) 15.0 Gelatin mass containing Hydroxypropyl methyl cellulose is prepared by dispersing Hydroxypropyl methyl cellulose phthalate in the form of a fine powder in a mixture of glycerin and water maintained at 70°C in which gelatin is dispersed to dissolve forming the gelatin mass. After cooling the mass to 45°C, ammonia solution is added slowly along the stirrer rod while stirring into the gelatin preparation tank. Stirring is continued till Hydroxypropyl methyl cellulose phthalate is completely dissolved. The mass is made bubble free by applying vacuum while maintaining the mass at 45 - 50°C under continuous mixing. b) Composition of the medicament: Name of the ingredient mg / capsule Soybean oil 200.0mg CremohorRH40 - 40.0mg Lansoprazole 30. Omg Disodium hydrogen orthophosphate 30.Omg Anhydrous Cremophor RH 40 is dispersed in soybean oil at 30°C. After cooling to room temperature Lansoprazole and disodium hydrogen orthophosphate are dispersed in to the mixture in the form of fine particles with the help of a mechanical stirrer and / or a homogeniser. c) Manufacturing of capsule: This gelatin mixture is transferred to the holding tank of rotary die capsulation machine for manufacture of capsule shell. The dispersion containing medicament is transferred to the hopper of the capsulation machine for filling into the soft gel capsules. The soft ge1 capsules are manuiactired by rotary die process. EXAMPLE - 5 a) Composition oftbe Soft gelatin shell: Name of the ingredient Percent by wt. Gelatin 35.0 Glycerin 15.0 Water 20.0 Hydroxypropyl methyl cellulose phthalate 10.0 Sodium hydroxide solution I % w/v 20.0 Gelatin mass is prepared by dispersing gelatin in a mixture of water and glycerin maintained at 70°C. Hydroxypropyl methyl cellulose phthalate is dissolved by stirring in to Sodium hydroxide solution at room temperature. Hydroxypropyl methyl cellulose phthalate solution in ammonia is added to gelatin mass while stirring the mass maintained at 45 - 50°C. Vacuum is apphed to the mixing vessel to remove the ammonia evolved and to obtain bubble free transparent mixture of polymer solution and gelatin mass. b) Composition of the medicament: Name of the ingredient mg / capsule Soybean oil ^- 200.0mg Hydrogenated vegetable oil 85 Omg Lecithin 20.0mg Pantoprazole sodium 45.0mg Meglumine 20.Omg Hydrogenated vegetable oil is melted and dispersed into soybean oil at 30 -40°C followed by lecithin, meglumine and pantoprazole sodium and cooled to room temperature. The mixture is kneaded into a smooth paste using a triple roller mill. c) Manufacturing of capsule: This gelatin mixture is transferred to the holding tank of rotary die capsulation machine for manufacture of capsule shell. The dispersion containing medicament is transferred to the hopper of the c^sulation machine for filling mto the soft gel capsules. The soft gel c^sules are manufactured by rotary die process. EXAMPLE-6 a) Composition of the Soft gelatin shell: Name of the ingredient Percent by wt. Gelatin 30.0 Propylene glycol 15.0 Water 20.0 Hydroxypropyl methyl cellulose phthalate 10.0 Gelatin mass is prepared by dispersing in water at 70°C. Hydroxypropyl methyl cellulose phthalate is dissolved in propylene glycol at 60 - 70°C. and mixed with the gelatin mass to obtain uniform mixture. b) Composition of the medicament: Name of the ingredient mg / Capsule Soybean oil 280.0mg Omeprazole ^ 20.0mg Meglumine 20.0mg Lecithin 30.0mg Lecithin is dispersed into soybean oil using a mechanical stirrer. Omeprazole and meglumine are added to the dispersion while stirring to obtain a smooth dispersion. c) Mannfacturing of capsule: This gelatin mixture is transferred to the holding tank of rotary die capsulation machine for manufacture of capsule shell. The dispersion containing medicament is transferred to the hopper of the capsulation machine for filling into the soft gel capsules. The soft gel capsules are manufactured by rotary die process. EXAMPLE - 7 a) Composition of the Soft gelatin shell: Name of the ingredient Percent by wt Gelatin 35.0 Glycerin 17.5 Water 20.0 Polyvinylacetate phthalate (P VAP) 7.5 Ammonia solution (25%w/v) 20.0 Gelatin mass is prepared by dispersing gelatin in a mixture of water and glycerin maintained at 70°C. Polyvinylacetate phthalate is dissolved by stirring in to ammonia solution at room temperature. Polyvinylacetate phthalate solution in ammonia is added to gelatin mass while stirring the mass maintained at 45 - 50°C. Vacuum is applied to the mixing vessel to remove the ammonia evolved and to obtain bubble free transparent mixture of polymer solution and gelatin mass. b) Composition of the medicament: Name of the ingredient mg / capsule Sunflower oil f 200.Omg CremohorRH40 - 40.0mg Lansoprazole 30 .Omg Disodium hydrogen orthophosphate 30.0mg Anhydrous Cremophor RH 40 is dispersed in sunflower oil at 30°C. After cooling to room temperature Lansoprazole and disodium hydrogen orthophosphate are dispersed into the mixture in the form of fine particles with the help of a mechanical stirrer and / or a homogeniser. C) Manufacturing of capsule: This gelatin mixture is transferred to the holding tank of rotary die capsulation machine for manufacture of capsule sheU. The dispersion containing medicament is transferred to the hopper of the c^sulation machine for filling into the soft gQ\ capsules. The soft gel capsules are manufactured by rotary die process. Advantages of the invention: The advantages of the present invention are: 1) Simple method of manufacturing, when compared to the methods disclosed in the prior art. 2) improved bioavailability when compared to the solid enteric coated pellets as the medicament is solublised or suspended in the form of very fine particles in the liquid / semisolid pharmaceutical composition filled into the soft gel capsule. We claim: 1. A pharmaceutical composition in form of a soft gel capsule resistant to gastric juice and soluble in intestine useful for the treatment of duodenal ulcers and related ailments which comprises of a gelatin shell resistant to gastric juice and soluble in intestine having an enteric polymer in the form of free acid or its salt, the capsule incorporating a composition comprising of benzimidazole derivative, a hydrophobic oily substance or a mixture of such substances, an alkaline inert reacting material, a surface active agent and / or a solublising agent; where the capsules are insoluble in aqueous medium up to a pH of 5.5 but quickly dissolve above pH of 6.0. 2. A pharmaceutical composition as claimed in claim 1 wherein the benzimidazole derivative, is selected from medicaments such as omeprazole, lansoprazole, pantoprazole, timoprazole and the like. 3. A pharmaceutical composition as claimed in claims 1 & 2 wherein the amount of benzimidazole derivative in the formulation is equivalent to one unit dose of selected benzimidazole derivative. 4. A pharmaceutical composition as claimed in claims I to 3 wherein the enteric polymer employed in the gelatin shell is selected from polymers such as hydroxypropyl methyl cellulose phthalate, alkyl methacrylate and methacrylic acid copolymers, polyvinyl acetate phthalate and the like in the form of free acid or their ammonia or alkali metal salts. 5. A pharmaceutical composition as claimed in claims 1 and 4 where in the amount of enteric polymer employed in the gelatin shell ranges from 5.0 to 40.0 percent, preferably 5.0 lo 25.0 percent by weight, with reference to the dried shell. 6. A pharmaceutical composition as claimed in claims 1 to 5 wherein the benzimidazole derivative in the formulation is suspended / solubilised in a hydrophobic oily substance selected from fats and oils of vegetable origin such as sesame oil, com oil, maize oil, soybean oil, sunflower oil, arachis oil, gingly oil and the like; animal origin such as fish oil, pig oil, beef oil and the like; esters of straight chain aliphatic oils such as Sunsoft 700 P-2 (Taiho chemical company) Panasete 810 (Nippon oils and Fats); hydrogenated vegetable oils or a mixture thereof. 7. A pharmaceutical composition as claimed in claims 1 to 6 wherein the amount of hydrophobic oily substance used in the formulation ranges from 50.0 to 80.0 percent by weight, with reference to the contents filled in capsules. 8. A pharmaceutical composition as claimed in claims 1 to 7 wherein materials such as glyceryl monostearate, lecithin, polyoxyethyiene castor oil derivative such as Cremophor RH 40, Cremophor EL (BASF) polyoxyethyiene sorbitan fatty acid esters, sodium lauryl sulphate, docusate sodium and the like are used as surface active agents. 9. A pharmaceutical composition as claimed in claims 1 to 8 wherein the amount of surface active agent and/or solublising agent incorporated into the formulation ranges from 2.0 to 20.0 percent, preferably 5.0 to 15.0 percent by weight, with reference to the contents filled in capsule. 10. A pharmaceutical composition as claimed in claims 1 to 9 wherein materials such as the sodium, potassium, calcium, magnesium and aluminium sahs of phosphoric acid, carbonic acid, citric acid, other suitable organic or inorganic acids; substances used in antacid preparations; meglumine; triethanolamine and the like is used as alkaline inert reacting materials. 11. A pharmaceutical composition as claimed in claims 1 to 10 wherein the amount of alkaline inert reacting substance incorporated in the formulation ranges from 5.0 to 40.0 percent, preferably 10.0 to 25.0 percent by weight, with reference to the contents filled in capsule. 12. A process for the preparation of a pharmaceutical composition in the form of a soft gel capsule resistant to gastric juice and soluble in intestine useful for the treatment of duodenal ulcers and related ailments which comprises forming a gelatin shell resistant to gastric juice and soluble in intestine having an enteric polymer in the form of free acid or its salt, and incorporating into the resultant capsule a composition comprising of a benzimidazole derivative, a hydrophobic oily substance or a mixture of such substances, an alkaline inert reacting material, a surface active agent and / or a solublising agent; where the resultant capsules are insoluble in aqueous medium up to a pH of 5.5 but quickly dissolve above pH of 6.0. 13. A process as claimed in claim 12 wherein the benzimidazole derivative is selected from medicaments such as omeprazole, lansoprazole, pantoprazole, timoprazole and the like. 14. A process as claimed in claims 12 and 13 wherein the amount of benzimidazole derivative used in the formulation is equivalent to one unit dose of selected benzimidazole derivative. 15. A process as claimed in claims 12 to 114 wherein the enteric polymer employed in the gelatin shell is selected from polymers such as hydroxypropyl methyl cellulose phthalate, alkyl methacrylate -methacrylic acid copolymers, polyvinyl acetate phthalate and the like in the form of free acid or their ammonia or alkali metal salts. 16. A process as claimed in claims 12 and 15 wherein the amount of enteric polymer employed in the gelatin shell ranges from 5.0 to 40.0 percent preferably 5.0 to 25.0 percent by weight with reference to the dried shell. 17. A process as claimed in claims 12 to 16 wherein the enteric polymer is incorporated into gelatin mass, in the form of a free acid or its ammonia or alkali metal salt by dispersing the free acid or its salt into the gelatin mass at 45 - 50°C using a top driven mechanical stirrer. 18. A process as claimed in claims 12 to 17 wherein the hydrophobic oily substance employed in the formulation is selected from fats and oils of vegetable origin such as sesame oil, com oil, maize oil, soybean oil, sunflower oil, arachis oil, gingly oil and the like; animal origin such as fish oil, pig oil, beef oil and the like; esters of straight chain aliphatic oils such as SunSoft 700 P-2 (Taiho chemical company) Panasete 810 (Nippon oils and Fats); hydrogenated vegetable oils or a mixture thereof. 19. A process as claimed in claims 12 to 18 wherein the amount of hydrophobic oily substance used in the formulation ranges from 50.0 to 80.0 percent by weight with reference to the contents filled in capsules, 20. A process as claimed in claims !2 to 19 wherein the materials such as glyceryl monostearate, lecithin, polyoxyethylene castor oil derivative such as Cremophor RH 40, Cremophor EL (BASF) polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulphate, docusate sodium and the like is used as surface active agent. 21. A process as claimed in claims 12 to 20 wherein the amount of surface active agent and/or solublising agent incorporated into the formulation ranges from 2.0 to 20.0 percent, preferably 5.0 to 15.0 percent by weight, with reference to the contents filled in capsule. 22. A process as claimed in claims 12 to 21 wherein materials such as the sodium, potassium, calcium, magnesium and aluminum salts of phosphoric acid, carbonic acid, citric acid, other suitable organic or inorganic acids; substances used in antacid preparations; meglumine; triethanolamine and the like is used as alkaline reacting material. 23. A process as claimed in claims 12 to 22 where in the amount of alkaline inert reacting material used in the formulation ranges from 5.0 to 40.0 percent, preferably 10 to 25.0 percent by weight, with reference to the contents fill in capsule. 24. A pharmaceutical composition in the form of a soft gel capsule resistant to gastric juice and soluble in intestine useful for the treatment of duodenal ulcer and related ailments substantially as herein described with reference to the Examples 1 to 7. 25.A process for the preparation of pharmaceutical composition in the form of a soft gel capsule resistant to gastric juice and soluble in initiated useful for the treatment of duodenal ulcer and related ailments substantially as herein described with reference to the Examples 1 to 7.

Documents:

968-mas-1999 abstract duplicate.pdf

968-mas-1999 abstract.pdf

968-mas-1999 claims duplicate.pdf

968-mas-1999 claims.pdf

968-mas-1999 correspondence others.pdf

968-mas-1999 correspondence po.pdf

968-mas-1999 description (complete) duplicate.pdf

968-mas-1999 description (complete).pdf

968-mas-1999 description (provisional).pdf

968-mas-1999 form-1.pdf

968-mas-1999 form-11.pdf

968-mas-1999 form-19.pdf

968-mas-1999 form-3.pdf

968-mas-1999 form-5.pdf

968-mas-1999 others.pdf