Title of Invention

IMPROVED DETERGENT COMPOSITION WITH BENEFIT AGENTS

Abstract

A water in-oil emulsion system as a storage stable carrier of high pH sensitivity benefit agents or actives comprising i) an aqueous phase including at least one water soluble and /or dispersible benefit agent; ii) a hydrophobic protenctive carrier phase for the aqueous phase containing the benefit agent; and iii) an emulsiffier or a dispersant. Also provided is a rinse off non-liquid cleaning composition comprising the water-in-oil emulsion system and a second phase which is a continuous alkaline phase.

Full Text

FORM -2 THE PATENTS ACT, 1970 (39 ot 1970) COMPLETE SPECIFICATION (See Section 10; RULE 13) IMPROVED DETERGENT COMPOSITION WITH BENEFIT AGENTS HINDUSTAN LEVER LIMITED, a company incorporated under the Indian Companies Act, 1913 and having its registered office at Hindustan Lever House, 165/166, Backbay Reclamation, Mumbai -400 020, Maharashtra, India The following specification particularly describes the nature of the invention and the manner in which it is to be performed. - 2 NOV 2004 The present invention relates to A method for the preparation of an effervescent tablet of active pharmaceutical substance Ranitidine and Domperidone. The present invention provides a process for preparation of Ranitidine effervescent tablet. It is desirable to make Ranitidine effervescent tablet by a process, particularly as an effervescent tablet since such a tablet provides many of the advantages of both tablet and liquid formulation. For oral administration of drug effervescent tablets are more suitable way than swallowing tablets. Generally pharmaceutical composition for oral administration is tablets/lozenges, capsules, granules, powders, solutions, syrups, etc. Ranitidine effervescent tablets are formulated for oral administration gives antacid effect. Ranitidine HCl is used as an active ingredient in formulation of effervescent tablets. Ranitidine N-[2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethyl]-N"-methyl-2-nitro-l,l-ethenediamine HCl, is the potent histamine H2-receptor antagonist. It acts to markedly decrease acid output by completely inhibiting histamine induced gastric acid secretion. 2 Ranitidine in the form of hydrochloride salt, is used in the treatment of Duodenal & benign gastric ulcer, Drug induced ulceration, Reflux oesophagitis, Dyspepsia & Hyperacidity Syndrome. In the present invention Domperidone used as an active ingredient along with Ranitidine HC1. Domperidone is a potent Dopamine receptor antagonist with antiemetic action. It acts markedly & gives symptomatic relief from acute nausea, vomiting, reflux oesophagitis, dyspepsia. IN 1,840,06 discloses the process for the preparation of novel pharmaceutical composition containing ranitidine or its hydrochloride in effervescent form. US 5,728,401 describes an effervescent pharmaceutical composition and process for making thereof for oral use in tablet/granule/powder form in the treatment of a condition mediated through histamine H.sub.2 receptors contains a therapeutically effective amount of ranitidine or a physiologically acceptable salt thereof, the pharmaceutical composition comprises disodium citrate, glycine, sodium bicarbonate, fumaric acid, a flavouring agent, a sweetening agent, binding agent, lubricant. The process for making effervescent composition comprising mixing of disodium citrate, 3 sodium bicarbonate and fumaric acid in a solvent system and forming granules of it, after drying the granules are mixed with ranitidine or physiologically acceptable salt thereof. The said process further comprises adding amino acid glycine, sarcosine, alanine, taurine, glutamic acid into the granules said composition is or combination thereof. US 5,102,665 describes an effervescent pharmaceutical composition for oral use in tablets, granules or powder form. The composition comprises effective amount of ranitidine or a physiologically acceptable salt thereof, monosodium citrate & sodium bicarbonate for effervescence production, other pharmaceutical excipients/carrier such as binding agent, lubricant, one or more flavourig agent and/or sweetening agents sodium saccharin, sodium cyclamate, aspartame are used. US 5,792,473 provided a granular effervescent product suitable for preparing an aqueous solution or suspension of one or more pharmaceutically active substances for oral administration, capable of being pressed into tablets, and/or said product in tablet form, comprising effervescent grains obtained form carrier crystals of atleast one solid, edible organic acid which are substantially covered 4 by at least one coating containing at least one water-soluble neutral substance, and at least one substance selected form the group consisting of alkali carbonate, alkali bicarbonate, alkaline earth carbonate, alkaline earth bicarbonate, alkali salt of at least one solid edible organic acid, alkaline earth salt of at least one solid edible organic acid is applied onto said coating. In preparation of effervescent composition using citric acid and/or monosodium citrate with the active pharmaceutical ingredient-histamine H2 receptor antagonist results in instability or lower stability of the tablet. Moreover, commercially available tablet of Ranitidine HC1 with Domperidone tablet is available as its physiologically acceptable salt as uncoated or film coated tablets for oral use, contains flavourants, which mask the unpleasant taste. Film coating on Ranitidine HC1 with Domperidone tablets is done to protect tablets from environmental condition, i.e. protect from light, humidity & temperature of environment. It is also done for masking the bitter taste of tablets. This tablet is swallowed as it is, film of the tablet breaks in stomach and tablet get dispersed/dissolved in gastric secretion and then absorption of drug will start. Which 5 takes more time to get drug dissolve/disperse in stomach and consequently take more time to start absorption and action in body. Generally film coated Ranitidine HC1 with Domperidone tablets are manufactured by simple wet & dry granulation process. Prepared granules are coated by putting in coating solution using HydroxyPropyl Methyl Cellulose (HPMC), Plasticizer, colour, Titanium Dioxide, Water, IPA, Methylene Chloride etc. as per standard methods. Tablets are loaded in coating pan & uniform films are coated on all tablets. Coated tablets are packed in aluminum strip & sealed under controlled temperature & humidity. This ensures that the product (tablet) will remain stable until utilized by the consumer. Commercially available film coated tablet of Ranitidine HC1 with Domperidone, are swallowable tablets and are not liked by Children, Senior Citizens & other patients, because of difficulty in swallowing. However, Film coating on it masks bitter taste of pharmaceutical ingredients. To overcome and control these problems a new effervescent tablet is developed. Effervescent tablets are uncoated tablets, containing acidic substances and either carbonates or bicarbonates, which react rapidly 6 in the presence of water to release carbon dioxide. For oral administration Ranitidine HCl with Domperidone effervescent tablets are prepared gives antacid effect. Ranitidine HCl & Domperidone are used as an active ingredient. The effervescent mixture provides an immediate transient increase in pH of the esophagus and stomach. This property is especially useful in dyspepsia. Present invention of preparing effervescent tablets of Ranitidine HCl with Domperidone aid the patient to get fast symptomatic relief from heart burn, dyspepsia, belching, flatulence, reflux, nausea sensation and hyperacidity, within very short time due to prior dispersion of active ingredient Ranitidine HCl & Domperidone in liquid (drinking water) form before engulf it. Effervescent tablet formulation of Ranitidine HCl with Domperidone is the most preferred & provide fixed dose for patient who find difficulty in swallowing tablets. Effervescent tablet of Ranitidine HCl with Domperidone is well absorbed after oral administration. In the present invention, each effervescent tablet of Ranitidine HCl with Domperidone, Ranitidine HCl is 167.5 mg/unit dose, where as Ranitidine H2-receptor antagonist comprises 150 mg & 7 Domperidone 10 mg/unit dose. Unit dose of tablet is preferably advisable to intake once or twice a day, depending on the age and weight of the patient. The tablet of Ranitidine HCl with Domperidone prepared by novel process gives synergistic effect against heart burn, dyspepsia, belching, flatulence, reflux, nausea sensation and hyperacidity or a mixture of thereof, within very short time. Unit dose of tablet is preferably advisable to intake once or twice a day, depending on the age and weight of the patient. Unique properties of Ranitidine HCl are: Bioavailability; 50% Plasma half-life (hours): 1.6-2.4 Approximate duration of Therapeutic effect (ulcers): 8 hours Drug for Treatment of Gastro esophageal Reflux Disease (GERD): For Nonerosive GERD where Ranitidine 150 mg twice/day. For Erosive GERD Ranitidine 150 mg every 6 hours. Current Recommendations for Treatment of Gastroduodenal Ulcers: For Active Ulcer: Ranitidine 300 mg 8 The present invention relates to A novel method for the preparation of an effervescent tablet of active pharmaceutical substance Ranitidine and Domperidone in acid media. The present invention provides a novel process for preparation of Ranitidine effervescent tablet. It is desirable to make Ranitidine effervescent tablet by a novel process, particularly as an effervescent tablet since such a tablet provides many of the advantages of both tablet and liquid formulation. For oral administration of drug effervescent tablets are more suitable way than swallowing tablets. Generally pharmaceutical composition for oral administration is tablets/lozenges, capsules, granules, powders, solutions, syrups, etc. Ranitidine effervescent tablets are formulated for oral administration gives antacid effect. Ranitidine HC1 is used as an. active ingredient in formulation of effervescent tablets. Ranitidine N-[2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethyl]-N,-methyl-2-nitro-l,l-ethenediamine HC1, is the potent histamine H2-receptor antagonist. It acts to markedly decrease acid output by completely inhibiting histamine induced gastric acid secretion. 2 Ranitidine in the form of hydrochloride salt, is used in the treatment of Duodenal & benign gastric ulcer, Drug induced ulceration, Reflux oesophagitis, Dyspepsia & Hyperacidity Syndrome. In the present invention Domperidone used as an active ingredient along with Ranitidine HCI. Domperidone is a potent Dopamine receptor antagonist with antiemetic action. It acts markedly & gives symptomatic relief from acute nausea, vomiting, reflux oesophagitis, dyspepsia. Commercially available tablet of Ranitidine HCI with Domperidone tablet is available as its physiologically acceptable salt as uncoated or film coated tablets for oral use, contains flavourants, which mask the unpleasant taste. Film coating on Ranitidine HCI with Domperidone tablets is done to protect tablets from environmental condition, i.e. protect from light, humidity & temperature of environment. It is also done for masking the bitter taste of tablets. This tablet is swallowed as it is, film of the tablet breaks in stomach and tablet get dispersed/dissolved in gastric secretion and then absorption of drug 3 will start. Which takes more time to get drug dissolve/disperse in stomach and consequently take more time to start absorption and action in body. Generally film coated Ranitidine HC1 with Domperidone tablets are manufactured by simple wet & dry granulation process. Prepared granules are coated by putting in coating solution using HydroxyPropyl Methyl Cellulose (HPMC), Plasticizer, colour, Titanium Dioxide, Water, IPA, Methylene Chloride etc. as per standard methods. Tablets are loaded in coating pan & uniform films are coated on all tablets. Coated tablets are packed in aluminum strip & sealed under controlled temperature & humidity. This ensures that the product (tablet) will remain stable until utilized by the consumer. Commercially available film coated tablet of Ranitidine HCF with Domperidone, are swallowable tablets and are not liked by Children, Senior Citizens & other patients, because of difficulty in swallowing. However, Film coating on it masks bitter taste of pharmaceutical ingredients. 4 To overcome and control these problems a new effervescent tablet is developed. Effervescent tablets are uncoated tablets, containing acidic substances and either carbonates or bicarbonates, which react rapidly in the presence of water to release carbon dioxide. For oral administration Ranitidine HCl with Domperidone effervescent tablets are prepared gives antacid effect. Ranitidine HCl & Domperidone are used as an active ingredient. The effervescent mixture provides an immediate transient increase in pH of the esophagus and stomach. This property is especially useful in dyspeosia. Present invention of preparing effervescent tablets of Ranitidine HCl with Domperidone aid the patient to get fast symptomatic relief from heart burn, dyspepsia, belching/ flatulence, reflux, nausea sensation and hyperacidity, within very shoit time due to prior dispersion of active ingredient Ranitidine HCl & Domperidone in liquid (drinking water) form before engulf it. 5 Effervescent tablet formulation of Ranitidine HC1 with Domperidone is the most preferred & provide fixed dose for patient who find difficulty in swallowing tablets. Effervescent tablet of Ranitidine HC1 with Domperidone is well absorbed after oral administration. In the present invention, each effervescent tablet of Ranitidine HC1 with Domperidone, Ranitidine HC1 is 167.5 mg/unit dose, where as Ranitidine H2-receptor antagonist comprises 150 mg & Domperidone 10 mg/unit dose. Unit dose of tablet is preferably advisable to intake once or twice a day, depending on the age and weight of the patient. The tablet of Ranitidine HC1 with Domperidone prepared by novel process gives synergistic effect against heart burn, dyspepsia, belching, flatulence, reflux, nausea sensation and hyperacidity or a mixture" of thereof, within very short time. Unit dose of tablet is preferably advisable to intake once or twice a day, depending on the age and weight of the patient. Unique properties of Ranitidine HC1 are: Bioavailability: 50% 6 Plasma half-life (hours): 1.6-2.4 Approximate duration of Therapeutic effect (ulcers): 8 hours Drug for Treatment of Gastro esophageal Reflux Disease (GERD): For Nonerosive GERD where Ranitidine 150 mg twice/day. For Erosive GERD Ranitidine 150 mg every 6 hours. Current Recommendations for Treatment of Gastroduodenal Ulcers: For Active Ulcer: Ranitidine 300 mg For Maintenance therapy: Ranitidine 150 mg The above properties of Ranitidine give prominent effect when it is formulated as effervescent tablet containing Domperidone and in physiologically acceptable acid media. The process for the preparation of effervescent tablets Ranitidine HC1 with Domperidone is given below. Step 1: Preparation of effervescent granules: Disodium Hydrogen citrate 2148 gm/unit dose, Sodium Bicarbonate 1100 gm/unit dose and Sodium Saccharine 30 gm/unit 7 dose are altogether passed through 40# mesh and mixed in the mixer. Finally effervescent granules are prepared. Step 2:Preparing a binder solution: - Preparing a binder solution of Polyvinylpyrrolidone. 5% Polyvinyipyrrolidoie (PVP K-30) 50 gm/unit dose is taken and made a solution in Isopropyl alcohol 1200 ml/unit dose solvent. Step-3: Preparing wet effervescent granules:- Effervescent granules obtained from the above step-1 are mixed with the binder solution obtained from step-2. These wet granules are passed through 16# mesh. These wet granules are dried in tray dryer. Finally dry effervescent granules are prepared. Step-4: Mixing of other excepients with effervescent granules: - Dry flavour 10 gm/unit dose and Sodium Benzoate 42 gm/unit dose are passed through 100# mesh. These flavoured granules are mixed with Simethicon 4.5 gm/unit dose. Flavoured granules containing Sodium Benzoate and Simethicon are admixed with granules obtained from step-3. 8 Step-5: Preparing granules of active ingredients: - Mixing the active ingredients Ranitidine HCI 167.5 mg/unit dose and Domperidone 10 mg/unit dose. This mixture is passed through 4G# mesh. The granules prepared are mixed with the flavour, to mask its bitter taste. The granules prepared, are admixed with granules obtained from step-4. Mix well the granules. Pack these granules in double layer polyethylene bag and putted in plastic drum with airtight seal. Ranitidine Hydrochloride is an active ingredient & H2-receptor antagonist, was mixed with an active ingredient Domperidone. Step-5: Preparing granules of active ingredients: - Granules obtained from step-4 are compressed into tablet form. These effervescent tablets of Ranitidine HCl with Domperidone are packed in Aluminium strip & sealed under controlled temperature & humidity. This ensures that the product (tablet) will remain stable until utilized by the consumer. For the preparation of effervescent tablets according to the present invention requires active and inactive ingredients; and other 9 excipients, conventional to the art such as fillers, binders, diluent, lubricants, sweetening agents and/or flavourant. In the process of preparation of effervescent tablets comprising Ranitidine Hydrochloride with Domperidone, Ranitidine is active ingredient and H2-receptor antagonist have antacid effect, pharmaceutically accepted compound of alkaline nature and being able as for example as Sodium Bicarbonate to neutralize gastric acidity. Domperidone is a potent Dopamine Receptor antagonist with antiemetic action. Sweetening agent as Sodium Saccharine is used in the present invention to impart its delicious taste into tablet and mask bitter taste of it. Most suitably Sodium Bicarbonate, Disodium hydrogen citrate are used as the effervescent base components. Mixing of Sodium Bicarbonate (NaHC03), in tablet formulation, produce C02 gas at the time of dispersion of tablet in drinking water and also in the presence of Disodium hydrogen citrate. When Disodium hydrogen citrate present in tablet formulation, the tablet gets easily engulfed by bubbles of carbon dioxide (C02) produced, 10 thus lowering the effective density of the tablet and easily gets dissolved in dispersion medium. The binder Polyvinylpyrrolidone (PVP) in iso-propyl alcohol, to bind the whole mass of active and inactive ingredients during granulation process in tablet formulation. It also forms a protective layer on granules and protects it from the environmental condition and also imparts the stability to the product. Simethicon is used as lubricant, to give smoothness to tablets. Dry flavourant added in the granulation process imparts its colour and taste. All these ingredients are added as per the stability of the tablet & taste requirement. It is important that the final product should have a high degree of stability; Ranitidine and its HC1 salt are unstable in the presence of moisture and elevated temperature. When Ranitidine is granulated along with the other excipients, and then subjected to drying, it is likely to give stability problems. Therefore, effervescent granules comprising Disodium hydrogen citrate, sodium bicarbonate, a binding agent and one or more of the other 11 excipients, such as sweeteners, are first formed into effervescent granules and then dried. In invented process for preparation of effervescent tablet: two form of granules are prepared, one which is by using effervescent base Disodium hydrogen citrate, Sodium bicarbonate and the other is of using active ingredients Ranitidine HCl and Domperidone. This is to prevent instability of the tablet and to prevent inter reaction the chemicals during the granulation process. 12 For Maintenance therapy: Ranitidine 150 mg The above properties of Ranitidine give prominent effect when it is formulated as effervescent tablet containing Domperidone and in physiologically acceptable acid media. The process for the preparation of effervescent tablets Ranitidine HC1 with Domperidone is given below. Step 1: Preparation of effervescent granules: Disodium Hydrogen citrate 2148 gm/unit dose, Sodium Bicarbonate 1100 gm/unit dose and Sodium Saccharine 30 gm/unit dose are altogether passed through 40# mesh and mixed in the mixer. Finally effervescent granules are prepared. Step 2:Preparing a binder solution: - Preparing a binder solution of Polyvinylpyrrolidone. 5% Polyvinylpyrrolidone (PVP K-30) 50 gm/unit dose is taken and made a solution in Isopropyl alcohol 1200 ml/unit dose solvent. Step-3: Preparing wet effervescent granules:- Effervescent granules obtained from the above step-1 are mixed with the binder solution obtained from step-2. These wet granules are passed through 16# mesh. These wet granules are dried in tray dryer. Finally dry effervescent granules are prepared. 9 Step-4: Mixing of other excepients with effervescent granules: - Dry flavour 10 gm/unit dose and Sodium Benzoate 42 gm/unit dose are passed through 100# mesh. These flavoured granules are mixed with Simethicon 4.5 gm/unit dose. Flavoured granules containing Sodium Benzoate and Simethicon are admixed with granules obtained from step-3. Step-5: Preparing granules of active ingredients: - Mixing the active ingredients Ranitidine HCl 167.5 mg/unit dose and Domperidone 10 mg/unit dose. This mixture is passed through 40# mesh. The granules prepared are mixed with the flavour, to mask its bitter taste. The granules prepared, are admixed with granules obtained from step-4. Mix well the granules. Pack these granules in double layer polyethylene bag and putted in plastic drum with airtight seal. Ranitidine Hydrochloride is an active ingredient & H2-receptor antagonist, was mixed with an active ingredient Domperidone. Step-6: Preparing tablet form active ingredients granules: - Granules obtained from step-4 are compressed into tablet form. These effervescent tablets of Ranitidine HCl with Domperidone are packed in Aluminium strip & sealed under controlled temperature & 10 humidity control at pH level 5.0 to 6.5. This ensures that the product (tablet) will remain stable until utilized by the consumer. For the preparation of effervescent tablets according to the present invention requires active and inactive ingredients; and other excipients, conventional to the art such as fillers, binders, diluent, lubricants, sweetening agents and/or flavourant. In the process of preparation of effervescent tablets comprising Ranitidine Hydrochloride with Domperidone, Ranitidine is active ingredient and H2-receptor antagonist have antacid effect, pharmaceutically accepted compound of alkaline nature and being able as for example as Sodium Bicarbonate to neutralize gastric acidity. Domperidone is a potent Dopamine receptor antagonist with antiemetic action. Sweetening agent as Sodium Saccharine is used in the present invention to impart its delicious taste into tablet and mask bitter taste of it. Most suitably Sodium Bicarbonate, Disodium hydrogen citrate are used as the effervescent base components. Mixing of Sodium Bicarbonate (NaHCO3), in tablet formulation, produce CO2 gas at the time of dispersion of tablet in drinking water and also in the presence of Disodium hydrogen citrate. When Disodium hydrogen citrate 11 present in tablet formulation, the tablet gets easily engulfed by bubbles of carbon dioxide (C02) produced, thus lowering the effective density of the tablet and easily gets dissolved in dispersion medium. The binder Polyvinylpyrrolidone (PVP) in iso-propyl alcohol, to bind the whole mass of active and inactive ingredients during granulation process in tablet formulation. It also forms a protective layer on granules and protects it from the environmental condition and also imparts the stability to the product. Simethicon is used as lubricant, to give smoothness to tablets. Dry flavourant added in the granulation process imparts its colour and taste. All these ingredients are added as per the stability of the tablet & taste requirement. It is important that the final product should have a high degree of stability; Ranitidine and its HCl salt are unstable in the presence of moisture and elevated temperature. When Ranitidine is granulated along with the other excipients, and then subjected to drying, it is likely to give stability problems. Therefore, effervescent granules comprising Disodium hydrogen citrate, sodium bicarbonate, a binding agent and one or more of the other 12 excipients, such as sweeteners, are first formed into effervescent granules and then dried. In invented process for preparation of effervescent tablet: two form of granules are prepared, one which is by using effervescent base Disodium hydrogen citrate, Sodium bicarbonate and the other is of using active ingredients Ranitidine HC1 and Domperidone. This is to prevent instability of the tablet and to prevent inter reaction the chemicals during the granulation process. 13 For Maintenance therapy: Ranitidine 150 mg The above properties of Ranitidine give prominent effect when it is formulated as effervescent tablet containing Domperidone and in physiologically acceptable acid media. The process for the preparation of effervescent tablets Ranitidine HC1 with Domperidone is given below. Step 1: Preparation of effervescent granules: Disodium Hydrogen citrate 2148 gm/unit dose, Sodium Bicarbonate 1100 gm/unit dose and Sodium Saccharine 30 gm/unit dose are altogether passed through 40# mesh and mixed in the mixer. Finally effervescent granules are prepared. Step 2:Preparing a binder solution: - Preparing a binder solution of Polyvinylpyrrolidone. 5% Polyvinylpyrrolidone (PVP K-30) 50 gm/unit dose is taken and made a solution in Isopropyl alcohol 1200 ml/unit dose solvent. Step-3: Preparing wet effervescent granules:- Effervescent granules obtained from the above step-1 are mixed with the binder solution obtained from step-2. These wet granules are passed through 16# mesh. These wet granules are dried in tray dryer. Finally dry effervescent granules are prepared. 9 Step-4: Mixing of other excepients with effervescent granules: - Dry flavour 10 gm/unit dose and Sodium Benzoate 42 gm/unit dose are passed through 100# mesh. These flavoured granules are mixed with Simethicon 4.5 gm/unit dose. Flavoured granules containing Sodium Benzoate and Simethicon are admixed with granules obtained from step-3. Step-5: Preparing granules of active ingredients: - Mixing the active ingredients Ranitidine HCl 167.5 mg/unit dose and Domperidone 10 mg/unit dose. This mixture is passed through 40# mesh. The granules prepared are mixed with the flavour, to mask its bitter taste. The granules prepared, are admixed with granules obtained from step-4. Mix well the granules. Pack these granules in double layer polyethylene bag and putted in plastic drum with airtight seal. Ranitidine Hydrochloride is an active ingredient & H2-receptor antagonist, was mixed with an active ingredient Domperidone. Step-6: Preparing tablet form active ingredients granules: - Granules obtained from step-4 are compressed into tablet form. These effervescent tablets of Ranitidine HCl with Domperidone are packed in Aluminium strip & sealed under controlled temperature & 10 humidity control at pH level 5.0 to 6.5. This ensures that the product (tablet) will remain stable until utilized by the consumer. For the preparation of effervescent tablets according to the present invention requires active and inactive ingredients; and other excipients, conventional to the art such as fillers, binders, diluent, lubricants, sweetening agents and/or flavourant. In the process of preparation of effervescent tablets comprising Ranitidine Hydrochloride with Domperidone, Ranitidine is active ingredient and H2-receptor antagonist have antacid effect, pharmaceutically accepted compound of alkaline nature and being able as for example as Sodium Bicarbonate to neutralize gastric acidity. Domperidone is a potent Dopamine receptor antagonist with antiemetic action. Sweetening agent as Sodium Saccharine is used in the present invention to impart its delicious taste into tablet and mask bitter taste of it. Most suitably Sodium Bicarbonate, Disodium hydrogen citrate are used as the effervescent base components. Mixing of Sodium Bicarbonate (NaHCO3), in tablet formulation, produce CO2 gas at the time of dispersion of tablet in drinking water and also in the presence of Disodium hydrogen citrate. When Disodium hydrogen citrate 11 present in tablet formulation, the tablet gets easily engulfed by bubbles of carbon dioxide (C02) produced, thus lowering the effective density of the tablet and easily gets dissolved in dispersion medium. The binder Polyvinylpyrrolidone (PVP) in iso-propyl alcohol, to bind the whole mass of active and inactive ingredients during granulation process in tablet formulation. It also forms a protective layer on granules and protects it from the environmental condition and also imparts the stability to the product. Simethicon is used as lubricant, to give smoothness to tablets. Dry flavourant added in the granulation process imparts its colour and taste. All these ingredients are added as per the stability of the tablet & taste requirement. It is important that the final product should have a high degree of stability; Ranitidine and its HCl salt are unstable in the presence of moisture and elevated temperature. When Ranitidine is granulated along with the other excipients, and then subjected to drying, it is likely to give stability problems. Therefore, effervescent granules comprising Disodium hydrogen citrate, sodium bicarbonate, a binding agent and one or more of the other 12 excipients, such as sweeteners, are first formed into effervescent granules and then dried. In invented process for preparation of effervescent tablet: two form of granules are prepared, one which is by using effervescent base Disodium hydrogen citrate, Sodium bicarbonate and the other is of using active ingredients Ranitidine HC1 and Domperidone. This is to prevent instability of the tablet and to prevent inter reaction the chemicals during the granulation process. 13 We Claim, 1. A method for the preparation of an effervescent tablet of active pharmaceutical substance Ranitidine HC1 with Domperidone comprising the steps of: (a) preparing effervescent granules containing 2148 gm/unit dose of Disodium hydrogen citrate & 1100 gm/unit dose of Sodium Bicarbonate as effervescence base and sweetening agent Sodium Saccharine 30 gm/unit dose; (b) preparing binder solution using 5 % Polyvinylpyrrolidone as 50 gm/unit dose in 1200 ml/unit dose of iso-propyl Alcohol solvent; (c) mixing the granules obtained from step-a with the binder Polyvinylpyrrolidone (PVP K-30) as prepared in step-b, finally dry effervescent granules are prepared; (d) admixing 10 gm/unit dose of dry flavours, 4.5 gm/unit dose of Simethicon and 42 gm/unit dose of Sodium Benzoate with the effervescent granules obtained from step-c; (e) preparing granules containing active ingredients Ranitidine HC1 167.5 mg/unit dose with Domperidone 14 10 mg/unit dose and mixing the granules with the granules obtained from step-d. 2. A method for the preparation of an effervescent tablet of active pharmaceutical substance Ranitidine HC1 with Domperidone as claimed in claim 1 (a) wherein granules are prepared by mixing of Disodium hydrogen citrate with Sodium Bicarbonate & Sodium Saccharine and passing the said mixture through 40# mesh and mixing well. 3. A method for the preparation of an effervescent tablet of active pharmaceutical substance Ranitidine HC1 with Domperidone in acidic media as claimed in claim 1 (c) wherein mixing the granules obtained from step-1 (a) with the solution obtained from step-1 (b), passing the wet granules through 16# mesh and preparing the dry granules. 4. A method for the preparation of an effervescent tablet of active pharmaceutical substance Ranitidine HC1 with Domperidone as claimed in claim 1 (d) wherein mixing the dry flavours with Sodium benzoate & Semethicon and passing 15 the mixture through 100# mesh, admixing with the dry granules obtained from step-1 (c). 5. A method for the preparation of an effervescent tablet of active pharmaceutical substance Ranitidine HC1 with Domperidone as claimed in claim 1 (e) wherein preparing the granules containing active pharmaceutical substances Ranitidine HC1 167.50 mg/unit dose with Domperidone 10 mg/unit dose after passing through 40# mesh, mixing the granules with dry flavours and the granules obtained from step-1 (d), compressing the said flavoured granules into tablet form and packaging the said tablet at maintained temperature and humidity. 6. A method for the preparation of an effervescent tablet of active pharmaceutical substance Ranitidine HC1 with Domperidone as claimed in claim 1 to 5 substantially herein described with foregoing description. Dated this on 28th of October 2003. Dr. Rajeshkumar H. Acharya. Advocate & Patent agent For and on behalf of the applicant 16

Documents:

1166-mum-2003 claims.doc

1166-mum-2003 claims.pdf

1166-mum-2003 correspondence(ipo).pdf

1166-mum-2003 correspondence.pdf

1166-mum-2003 description(granted).pdf

1166-mum-2003 discription(granted).doc

1166-mum-2003 form 1.pdf

1166-mum-2003 form 13.pdf

1166-mum-2003 form 18.pdf

1166-mum-2003 form 2(granted)..doc

1166-mum-2003 form 2(title page).pdf

1166-mum-2003 form 3.pdf

1166-mum-2003 form 5.pdf

1166-mum-2003 pct-isa-220.pdf

1166-mum-2003 pition under rule 137.pdf

1166-mum-2003 power of attorney.pdf

1166-mum-2003-cancelled pages(17-12-2007).pdf

1166-mum-2003-claim(granted)-(17-12-2007).doc

1166-mum-2003-claim(granted)-(17-12-2007).pdf

1166-MUM-2003-CORRESPONDENCE(8-2-2012).pdf

1166-mum-2003-corrospondence(ipo)-(05-12-2007).pdf

1166-mum-2003-corrospondence1(23-02-2006).pdf

1166-mum-2003-corrospondence2(17-12-2007).pdf

1166-mum-2003-drawing(17-12-2007).pdf

1166-mum-2003-form 1(06-11-2003).pdf

1166-mum-2003-form 13(03-10-2007).pdf

1166-mum-2003-form 2(granted)-(17-12-2007).doc

1166-mum-2003-form 2(granted)-(17-12-2007).pdf

1166-mum-2003-form 2(granted)-(2-11-2004).pdf

1166-mum-2003-form 3(02-11-2004).pdf

1166-mum-2003-form 5(02-11-2004).pdf

1166-mum-2003-form-pct-ipea-409(13-04-2007).pdf

1166-mum-2003-form-pct-isa-210(13-04-2007).pdf

1166-mum-2003-general power of attorney(10-05-2004).pdf

1166-mum-2003-general power of attorney(13-04-2007).pdf

1166-mum-2003-general power of attorney(14-11-2007).pdf

1166-mum-2003-petition under rule 137(17-12-2007).pdf

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