A powder composition for oral suspension of proton pump inhibitors and the method of preparing the same

Abstract

Powder composition for oral suspension comprising a two phase powder mixture, where the first phase is in powder form comprising a Proton Pump Inhibitor (e.g. omeprazole) or pharmaceutically acceptable salts thereof in an amount of 0.01-7.5 % by weight, at least one diluent (e.g. mannitol), a first buffering agent (e.g. sodium hydrogen carbonate), a binding agent (e.g. xanthan gum), and the second phase is in powder form comprising a second buffering agent, a viscosity enhancer (e.g. sodium alginate) in the range 0.0010 %w / w to 2.0 wt.%, at least one diluent; at least one preservative (e.g. sodium benzoate, sodium methyl para hydroxy benzoate), a diluent, and an excipient (e.g. a flavour). Preferably, the second buffering agent is a carbonate or hydrogen carbonate. Preferably, the D50 of the omeprazole, if present, is 1.5-5.5 microns. The composition may be used in the treatment of erosive oesophagitis, gastroesophageal reflux, gastric ulcers etc.

Description

Field of the Invention The present invention relates to a powder composition for oral suspension comprising a proton pump inhibitor for oral administration. The present invention more particularly relates to methods for preparing the same. Background of the Invention The Proton Pump Inhibitor pharmacophore is 2-pyridylmethyl sulfinyl benzimidazole, corresponding in structure to Formula (I) below. The proton pump inhibitor drugs disclosed in the present invention are Omeprazole, Esomeprazole, and Lansoprazole, all contain this basic structural framework and differ only in the nature of substituents placed on the pyridine and benzimidazole rings. sulfinyl 2-pyri dyl methyl benzimidazole Proton Pump Inhibitors are a class of drugs that reduce gastric acid development significantly and for a long time. Proton pump inhibitors act by irreversibly inhibiting the gastric parietal cells’ hydrogen / potassium adenosine tri-phosphatase enzyme mechanism (the H+ / K+ ATPase, or more colloquially, the gastric proton pump). As the proton pump is directly responsible for secreting H+ ions into the gastric lumen at the end of acid secretion, it is an ideal target for acid secretion inhibition. The Proton pump inhibitors are used to treat a variety of disorders, including the healing of erosive esophagitis, maintenance of healed erosive esophagitis, treatment of gastroesophageal reflux disease, for gastric ulcers associated with nonsteroidal anti-inflammatory drugs, in reduction of the risk of duodenal ulcer recurrence by eradication of helicobacter pylori, in pathological hypersecretory conditions including Zollinger-Ellison (ZE) syndrome, and in short-term treatment and maintenance of duodenal ulcers. The present invention discloses the proton pump inhibitors drugs with a plasma half-life of about 1-1.5 hours. Proton Pump Inhibitors disclosed herein are Omeprazole, Esomeprazole, and Lansoprazole. Currently marketed solid dosage forms of Proton Pump inhibitors disclosed in the present invention for oral administration include delayed-release tablets, delayed-release capsules, gastro-resistant tablets, delayed-release oral suspension, enteric-coated capsules, enteric-coated tablets, multiple-unit pellet system and suspensions with micro particulates. Delayed-release capsules of Omeprazole are available in three strengths as follows: lOmg, 20mg and 40mg and delayed-release capsules of Esomeprazole is available in two strengths as follows: 20 mg and 40 mg. The delayed-release granule of Esomeprazole and Omeprazole is available in 5 Strengths as follows: 2.5mg, 5mg, lOmg, 20mg, and 40mg in the form of unit dose packets. The delayed-release capsule and delayed-release disintegrating tablets of Lansoprazole is available in 2 strengths as follows: 15mg and 30mg. Delayed-release oral suspension of omeprazole is available in two strengths: 2.5mg and lOmg and delayed-release suspension of Esomeprazole is available in five strengths: 2.5mg, 5mg, lOmg, 20mg, and 40mg. Additionally, the injectable form of Esomeprazole is available in two strengths: 20mg / ml and 40mg / ml. US11207307B2 discloses a suspension of Proton Pump Inhibitors, the proton pump inhibitor described is Omeprazole and other inactive ingredients like Benzyl alcohol, a copolymer of ethylene oxide and propylene oxide, simethicone emulsion, sodium bicarbonate, sodium citrate, a sweetener that comprises ammonium glycyrrhizate and sucralose, a thickening agent that is xanthan gum or hydroxyethyl cellulose and water. The pH of the suspension is at least pH 8.0. The batch was transferred to containers using a bottle and cap. EP3999066A1 discloses kits for preparing a reconstituted suspension of a proton pump inhibitor and other inactive ingredients are poloxamer, sodium carboxymethylcellulose, sodium bicarbonate, simethicone emulsion, a preservative, a sweetener, water, and optionally a flavoring agent and a coloring agent. These kits containing the omeprazole are stable under refrigerated conditions at 2-8°C. US20050031700A1 discloses a powder suspension comprising a proton pump inhibitor in micronized form, an antacid, and suspending agent wherein upon admixture of the powder with water, a substantially uniform suspension is obtained. EP3200768B1 discloses a suspension containing micro granules of Omeprazole and other inactive ingredients which are potassium sorbate, saccharin, silicon dioxide, peppermint oil, titanium dioxide, and fractionated coconut oil. The manufacturing process involves mixing of saccharin into heated myglyol. The mixture is then allowed to cool. Then potassium sorbate, titanium dioxide, and mint are added and mixed. To this solution, silicon dioxide is then added and mixed. The final mixture was formed by mixing of Omeprazole beads. The Proton Pump Inhibitors disclosed in the present invention belong to Class II of the Biopharmaceutical Classification System due to their poor solubility in water and high permeability through cell membranes. Suspensions are prepared for drugs that are poorly soluble in water, to mask the bitter taste of unpleasant drugs, for paediatric patients who are unable to swallow solid oral dosage forms and also need a dose adjustment, older patients with dysphagia, ICU patients, and for patients on enteral nutrition. Solid dosage forms of proton pump inhibitors require 2-3 times daily dosing which results in poor patient compliance. In order to successfully manage acid-related disorders, gastric acid production must be suppressed with the use of a Proton Pump inhibitor. Therefore, formulating a pharmaceutical composition in the form of powder composition for oral suspension of proton pump inhibitors would offer advantages over the aforementioned problems. Summary of the Invention In accordance with the present invention, a powder composition for oral Suspension of Proton Pump Inhibitors is prepared. The powder composition for oral suspension comprising a two phase powder mixture, where the first phase is in powder form comprising a Proton Pump Inhibitor or pharmaceutically acceptable salts thereof, at least one diluent, a first buffering agent, a binding agent, and the second phase are in powder form comprising a second buffering agent, a viscosity enhancer, at least one diluent, at least one preservative and one or more pharmaceutically acceptable salt thereof. The first phase powder mixture contains a moisture content of not more than 5.0%. Another embodiment of the present invention is to provide a powder for reconstitution as oral suspension for oral administration comprising a Proton Pump inhibitor, which achieves to mask the bitter taste of the active ingredient and provides acceptable palatability. Another embodiment of the present invention is effectively treat a variety of disorders, including the healing of erosive esophagitis, maintenance of healed erosive esophagitis, treatment of gastroesophageal reflux disease, for gastric ulcers associated with nonsteroidal anti-inflammatory drugs, to reduce the risk of duodenal ulcer recurrence by eradication of helicobacter pylori, in pathological hyper secretory conditions including Zollinger-Ellison (ZE) syndrome, and in short-term treatment and maintenance of duodenal ulcers. Objects of the Invention The primary object of the present invention is to provide a powder composition of Proton pump inhibitor or pharmaceutically acceptable salts thereof for oral administration to be reconstituted to form a suspension. It is an object of the present invention to provide a powder composition for oral suspension of Proton pump inhibitor, which is particularly convenient for administration for paediatric and geriatric patients. It is further another object of the present invention is to provide a process of preparation of a powder composition for oral suspension of proton pump inhibitor or its pharmaceutically acceptable salts thereof. It is yet another object of the present invention to provide a powder composition for oral suspension of Proton Pump Inhibitors with improved palatability of bitter drugs for oral administration. It is an object of the present invention is to provide a powder composition to be reconstituted to form suspension to improve the solubility of Proton pump inhibitor drugs or pharmaceutically acceptable salts which belongs to BCS Class-II drugs with poor solubility. It is an object of the present invention to provide a powder composition for oral suspension of Proton pump inhibitor drugs for oral administration comprising one or more pharmaceutically acceptable excipients or additives selected from the group consisting of diluents, buffering agents, binding agents, viscosity enhancers, preservatives, sweeteners, and flavours or any combinations thereof. Detailed description of the Invention The present invention discloses a powder formulation for oral administration suitable for reconstitution with a pharmaceutically acceptable carrier to form a suspension oral dosage form of Proton pump inhibitors. The term “proton-pump inhibitors” is defined as a class of anti-secretory compounds that suppress gastric acid secretion and are generally considered the most potent acid suppressants available. The term “suspension” refers to a disperse system in which one substance (the dispersed phase) is distributed in particulate form throughout another (the continuous phase). The term "about", as and when used in this specification, means ±10 % of the mentioned value. As used herein and in the appended claims, the singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise. The term "pharmaceutically acceptable salt" refers to salts prepared from pharmaceutically acceptable inorganic and organic acids. The term “powder” as used herein refers to any composition or formulation which is dry and flowable. The term “wet granulation” refers to a process of using a liquid binder to lightly agglomerate the powder mixture. As per one embodiment of the present invention, a Proton pump inhibitor is selected from the group consisting of Omeprazole, Pantoprazole, Lansoprazole, Rabeprazole, Dexlansoprazole, Esomeprazole, Ilaprazole, Tenetoprazole, Azeloprazole, Anaprazole or pharmaceutically acceptable salts thereof. As per one embodiment of the present invention, a Powder composition for oral suspension comprising a Proton Pump Inhibitor or its pharmaceutically acceptable salts thereof is Omeprazole, Esomeprazole, and Lansoprazole in non-micronized form. As per one embodiment of the present invention, the Proton Pump inhibitors or pharmaceutically acceptable salts thereof are present in the range from about 0.01% w / w to about 7.5% w / w, preferably in the range from about 0.05% w / w to about 6.5% w / w. In the present invention, a Proton Pump Inhibitor or its pharmaceutically acceptable salts thereof is Omeprazole present in the range from about 0.01% w / w to about 2.5% w / w, preferably in the range from about 0.05% w / w to about 1.5% w / w, Esomeprazole or its pharmaceutically acceptable salts thereof present in the range from about 0.05% w / w to about 5% w / w, preferably in the range from about 0.1% w / w to about 3.5% w / w, Lansoprazole or its pharmaceutically acceptable salts thereof present in the range from about 0.01% w / w to about 5% w / w, preferably in the range from about 0.05% w / w to about 3.5% w / w. As per one embodiment of the present invention, a Proton Pump Inhibitor drug or its pharmaceutically acceptable salts thereof is Omeprazole present in the powder composition, has D50 particle size distribution from about 1.5 pm to 5.5 pm, preferably in the range from about 2.5 pm to 4.5 pm, Esomeprazole in the powder composition has D50 particle size distribution from about 0.5 pm to 4.5 pm, preferably in the range from about 1.5 pm to 3.5 pm, Lansoprazole in the powder composition has D50 particle size distribution from about 4 pm to 16 pm, preferably in the range from about 9 pm to 11 pm. The term D50 is the diameter at which 50% of a sample's mass is comprised of smaller particles. In another embodiment of the present invention, a Proton Pump Inhibitor or its pharmaceutically acceptable salts thereof is Omeprazole in the powder composition has a D90 particle size distribution from about 5 pm to 15 pm, preferably in the range from about 8 pm to 10 pm, Esomeprazole in the powder composition has D90 particle size distribution from about 1 pm to 15 pm, preferably in the range from about 4 pm to 8 pm, Lansoprazole in the powder composition has D90 particle size distribution from about 15 pm to 45 pm, preferably in the range from about 20 pm to 30 pm. The term D90 is the diameter at which 90% of a sample mass is comprised of smaller particles in that sample size. As per one embodiment of the present invention, the diluents are selected from the group consisting of lactitol, mannitol, maltitol, xylitol, sorbitol, erythritol, isomalt, or any combinations thereof. In the present invention, the diluents are sugar alcohols selected from mannitol, maltitol, and xylitol or combination thereof present in the range from about 20% w / w to about 80% w / w, preferably in the range from about 30% w / w to about 70% w / w. As per one embodiment of the present invention, a suitable binding agent is selected from the group consisting of povidone, starch, pre-gelatinized starch, tragacanth, dextrin, sucrose, glucose, dextrose, molasses, mannitol, sorbitol, xylitol, lactose, acacia, ghatti gum, xanthan gum, polyvinylpyrrolidone, carboxymethylcellulose, methylcellulose, microcrystalline dextrose, amylose, magnesium aluminum silicate, polysaccharide acids, bentonites, gelatin or any combinations thereof. Xanthan gum is preferred as a binding agent present in the range from about 0.0010% w / w to about 2% w / w, preferably in the range from about 0.0015% w / w to about 1.5% w / w. As per one embodiment of the present invention, the buffering agents are selected from the group consisting of acetic acid, sodium acetate, citric acid, sodium citrate, sodium phosphate disodium phosphate, sodium hydrogen carbonate, potassium hydrogen carbonate, gluconate, tartrates, 1-methionine, potassium citrate, sodium carbonate anhydrous, potassium bicarbonate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium hydroxide, potassium dihydrogen phosphate, fumaric acid, tartaric acid or any combinations thereof. In the present invention, the first buffering agent is sodium hydrogen carbonate present in the range from about 0.45% w / w to about 2% w / w, preferably in the range from about 0.5% w / w to about 1.5% w / w, and the second buffering agent is selected from the group consisting of sodium hydrogen carbonate, potassium hydrogen carbonate and sodium carbonate anhydrous or combinations thereof present in the range from about 15% w / w to about 65% w / w, preferably in the range from about 25% w / w to about 55% w / w. In the present invention, the pH of the reconstituted suspension is in the range from 7.0 to 11.0, preferably it is in the range from 7.5 to 10.5. As per one embodiment of the present invention, a viscosity enhancer is selected from the group consisting of sodium alginate, carrageenan, gum acacia, gum tragacanth, sodium carboxymethyl cellulose, methylcellulose, bentonite, veegum, carbomers, colloidal silicon dioxide, glucose, fructose, acacia, bentonite, carboxymethyl cellulose sodium, gelatin, guar gum, hydroxyl ethyl cellulose, hydroxyl propyl methylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, and poloxamer or any combinations thereof. Sodium alginate is preferred as a viscosity enhancer for the present invention present in the range from about 0.05% w / w to about 12.5% w / w, preferably in the range from about 0.075% w / w to about 8.5% w / w. Additionally, it contains a percentage of moisture from about 6% to about 12%, preferably in the range from about 8% to about 10%. As per one embodiment of the present invention, the preservatives are selected from the group consisting of ethanol, propylene glycol, benzyl alcohol, quaternary amines, benzalkonium chloride, sorbic acid, benzoic acid, methyl paraben, propyl paraben, glycerin, propylene glycol, sodium propionate, cetrimide, chlorobutanol phenyl mercuric acetate, potassium sorbate, sodium benzoate, disodium edetate, butylparaben, phenyl ethyl alcohol, phenoxetol or any combinations thereof. In the present invention, the combination of sodium benzoate and sodium methyl para hydroxy benzoate is preferred as a preservative in the range from about 0.05% w / w to about 4% w / w, preferably in the range from about 0.075% w / w to about 3% w / w. As per one embodiment of the present invention, a suitable sweetener is selected from the group consisting of sugars such as xylose, ribose, glucose, mannose, galactose, fructose, dextrose, sucrose, maltose, hydrogenated glucose syrup, sugar alcohols such as sorbitol, xylitol, mannitol and glycerin, partially hydrolyzed starch, corn syrup solids, artificial sweetening agents such as sodium cyclamate, saccharin, aspartame, ammonium glycyrrhizinate or any combinations thereof. In the present invention, the sweeteners are selected from sucralose and sodium saccharine dihydrate or combinations thereof and are present in the range from about 0.05% w / w to about 8.5% w / w, preferably in the range from about 0.1% w / w to about 7% w / w. As per one embodiment of the present invention, a flavour is selected from the group consisting of acacia, lavender oil, orange flower water, ginger, vanilla tincture, coriander oil, sarsaparilla syrup, cinnamon (oil, water), anise oil, mint spray dried flavour, lemon oil, dextrose, glucose, tolu balsam syrup, raspberry, spearmint oil, natural mint, citric acid syrup, ethyl acetate, glycerine, wild cherry syrup, ethyl vanillin, thyme oil, rosemary oil, caraway oil, nutmeg oil, fennel oil, clove oil, saccharin sodium, tolu balsam, cocoa syrup, honey cocoa, cherry syrup, vanilla, orange oil or any combinations thereof. In the present invention, Mint spray dried flavour and natural mint are preferred as flavours and are present in the range from about 0.01%w / w to about 2.5%w / w, preferably in the range from about 0.025%w / w to about 1.5%w / w. As per preferred embodiment of the present invention, a powder composition for oral suspension comprising Proton Pump Inhibitor or pharmaceutically acceptable salts thereof, present in an amount from about 0.01% w / w to about 7.5% w / w, preferably in the range from about 0.05% w / w to about 6.5% w / w, the sugar alcohol diluent or combination thereof is present in the range from about 20% w / wto about 80% w / w, preferably in the range from about 30% w / w to about 70% w / w, binding agent is present in the range from about 0.0010% w / w to about 2% w / w, preferably in the range from about 0.0015% w / w to about 1.5% w / w, the first buffering agent is present in the range from about 0.45% w / w to about 2% w / w, preferably in the range from about 0.5% w / w to about 1.5% w / w and the second buffering agent or combination thereof is present in the range from about 15% w / w to about 65% w / w, preferably in the range from about 25% w / w to about 55% w / w and the pH of the reconstituted suspension is in range from 7.0 to 11.0, preferably it is in the range from 7.5 to 10.5, viscosity enhancer is present in the range from about 0.05% w / w to about 12.5% w / w, preferably in the range from about 0.075% w / w to about 8.5% w / w and it contains a percentage of moisture from about 6 to about 12%, preferably in the range from about 8% to about 10%, preservatives or combination thereof are present in the range from about 0.05% w / w to about 4.0% w / w, preferably in the range from about 0.075% w / w to about 3% w / w, sweeteners or combination thereof are present in the range from about 0.05% w / w to about 8.5% w / w, preferably in the range from about 0.1% w / w to about 7% w / w and flavours present in the range from about 0.01% w / w to about 2.5% w / w, preferably in the range from about 0.025% w / w to about 1.5% w / w. As per one preferred embodiment of the present invention, a powder composition for oral suspension comprising Omeprazole, Esomeprazole, and Lansoprazole or pharmaceutically acceptable salts thereof in non-micronized form is present in an amount from about 0.01% w / w to about 7.5% w / w, preferably in the range from about 0.05% w / w to about 6.5% w / w, the mannitol, maltitol, and xylitol or combination thereof is present in the range from about 20% w / w to about 80% w / w, preferably in the range from about 30% w / w to about 70% w / w, xanthan gum is present in the range from about 0.0010% w / w to about 2% w / w, preferably in the range from about 0.0015% w / w to about 1.5% w / w, sodium hydrogen carbonate is present in the range from about 0.45% w / w to about 2% w / w, preferably in the range from about 0.5% w / w to about 1.5% w / w, the sodium hydrogen carbonate, potassium hydrogen carbonate and sodium carbonate anhydrous or combinations thereof are present in the range from about 15%w / w to about 65%w / w, preferably in the range from about 25%w / w to about 55%w / w, the pH of the reconstituted suspension is in range from 7.0 to 11.0, preferably it is in the range from 7.5 to 10.5, sodium alginate is present in the range from about 0.05% w / w to about 12.5%w / w, preferably in the range from about 0.075%w / w to about 8.5%w / w and it contains a percentage of moisture from about 6% to about 12%, preferably in the range from about 8% to about 10%, the combination of sodium benzoate and sodium methyl para hydroxy benzoate is present in the range from about 0.05% w / w to about 4.0% w / w, preferably in the range from about 0.075% w / w to about 3% w / w, sucralose and sodium saccharine dihydrate or combinations thereof and are present in the range from about 0.05% w / w to about 8.5% w / w, preferably in the range from about 0.1% w / w to about 7% w / w, mint spray dried flavour and natural mint are preferred as flavours present in the range from about 0.01%w / w to about 2.5%w / w, preferably in the range from about 0.025%w / w to about 1.5%w / w. As per one embodiment of the present invention, the ratio of a Proton Pump Inhibitor to Viscosity enhancer is in the range from about 1:1 to about 1:12 and preferably it is in the range from about 1:2 to about 1:10. As per one embodiment of the present invention, the process for the preparation of a powder composition for oral suspension comprising a Proton Pump Inhibitor drug or pharmaceutically acceptable salts thereof is by wet granulation. Wet granulation is widely used in pharmaceutical manufacturing of different dosage forms as it aids in improving the flowability, compressibility, and cohesiveness of the powder. As per one embodiment of the present invention, more than 90% of a Proton Pump Inhibitor drug from said composition is released in 60 minutes, preferably more than 90% of a Proton Pump Inhibitor drug from said composition is released within 45 minutes. As per the preferred embodiment of the present invention, a powder composition for oral Suspension of Proton Pump Inhibitors is effective in the treatment of a variety of disorders including the healing of erosive esophagitis, maintenance of healed erosive esophagitis, treatment of gastroesophageal reflux disease, for gastric ulcer associated with nonsteroidal antiinflammatory drugs, for reduction of the risk of duodenal ulcer recurrence by eradication of Helicobacter pylori, in pathological hypersecretory conditions including Zollinger-Ellison (ZE) syndrome, and short-term treatment and maintenance of duodenal ulcers. As per one embodiment of the present invention, there is provided a process for preparation for a powder composition for oral suspension comprising Proton Pump Inhibitor or its pharmaceutically acceptable salts thereof, wherein a manufacturing process comprises the following steps: Part-I (i) Sift a proton pump Inhibitor, a first buffering agent, and at least one diluent together through a 40# sieve. (ii) Dry mixing of the sifted ingredients of Step-(i) for 10 minutes in the rapid mixer granulator with the impeller at slow speed and chopper off. (iii) Adding binding agent in 70% of total purified water and stirring for about 45 minutes and dissolving to prepare the clear viscous solution. (iv) Continuous mixing of the binder solution of Step (iii) in the dry mix of step (ii) in a rapid mixer granulator at slow impeller speed for 1-2 minutes. (v) Continuous mixing of ingredients of Step-(iv) and water for a minute at slow impeller speed and continuous kneading of wet mass for a minute with a chopper off during all process, further check the dough mass for proper granulation characteristics. (vi) Scarp the side of the rapid mixer granulator and impeller blades for raking the mass obtained in Step-(v). Then, discharge the wet mass into the fluid bed drier blow by opening the discharge port and operating the sampling and chopper at a slow speed. (vii) Dry and sift the wet mass of Step- (vi) in FBD, these dried granules passed through a 40# sieve, and the retained granules are milled through the multi mill by 1.0 mm screen, transfer the remaining milled granules through 40# sieve, the final blending of the granules in a blender for 10 minutes. The obtained first powder mixture contains a moisture content of not more than 5.0%. Part-II (viii) Milling of the second buffering agent through the multi mill with 3 mm screen, adding this milled second buffering agent with previously sifted viscosity enhancer agent, sweetener, flavor, preservative, and passed through 30 #sieve. (ix) Mixing of diluent and preservatives in the blender for 10 minutes and pass through 30# sieve. This final sifted material is mixed with the above-sifted material in the blender for 20 min. Part-Ill (x) Fill separately the API part in Plunger (Powder Holding Cap) and the dry mix blend in a 150 ml PET amber bottle, closed by a white outer cap. As per one embodiment of the present invention, the stability study of a powder composition for oral Suspension of Proton Pump Inhibitors was carried out by placing a dry mix blend in a 150 ml PET amber bottle and API part in Plunger (Powder Holding Cap), said packing material was closed with white outer cap and this powder containing packaging was stored at 25°C / 60% RH and at 40°C / 75% RH for 3 months and 6 months. The powder composition for oral suspension of proton pump Inhibitors provided good physicochemical parameters in stability studies with said packaging and storage conditions. The invention is further defined by reference to the following examples describing in detail the method for the preparation and testing parameters of Proton Pump Inhibitor drugs in Powder composition to be reconstituted to form an oral suspension, which is by no means intended to limit the scope of the invention but are given by way of illustration. Example 1: The manufacturing of a Powder composition for oral Suspension of Omeprazole was conducted according to the method defined below having the ingredients shown in Table-I: Table-I Omeprazole Powder for oral Suspension 20mg / ml Sr. No Name of Ingredient(s) llllllll^ Part-I 1. Omeprazole 0.82 2. Mannitol 5.16 3. Xanthan Gum 0.01 4. Sodium Hydrogen carbonate 0.87 5. Purified Water QS Part-II 6. Sodium Hydrogen carbonate 7.35 7. Potassium Hydrogen carbonate 28.58 8. Maltitol 55.5 9. Mint Spray dried Flavour 0.20 10. Sodium benzoate 1.02 11. Sodium methyl para hydroxy benzoate 0.47 Total weight 100.00 Manufacturing process: Part -1 (i) Sift the omeprazole, sodium hydrogen carbonate, and mannitol together through a 40# sieve, (ii) Dry mixing of the sifted ingredients of Step-(i) for 10 minutes in the rapid mixer granulator with the impeller at slow speed and chopper off. (iii) Adding xanthan gum in 70% of the total purified water and stirring for about 45 minutes and dissolve to prepare the clear viscous solution. (iv) Continuous mixing of the binder solution of Step (iii) in a dry mix of step (ii) in a rapid mixer granulator at slow impeller speed. (v) Discharge the wet mass into the fluid bed drier blow by opening the discharge port and operating the sampling and chopper at a slow speed. (vi) Dry and sift the wet mass of Step- (v) in FBD, these dried granules are passed through a 40# sieve and the retained granules are milled through the multi mill by 1.0 mm screen, transfer the remaining milled granules through 40# sieve, the final blending of the granules in a blender for 10 minutes. The obtained first powder mixture contains a moisture content of not more than 4.0%. Part-II (viii) Milling potassium hydrogen carbonate through the multi mill with a 3mm screen, adding this milled potassium hydrogen carbonate with previously sifted sodium hydrogen carbonate, sodium alginate, mint spray dried flavor, sodium methyl para hydroxy benzoate and passing through 30# sieve. (ix) Mixing of maltitol and sodium benzoate in the blender for 10 minutes and pass through a 30# sieve. This final sifted mixture is mixed with the above-sifted material in the blender for 20 min. Part-Ill (ix) Fill separately the API part in Plunger (Powder Holding Cap) and the dry mix blend in a 150 ml PET amber bottle, closed by a white outer cap. Suspension after reconstitution was not properly pourable due to lower viscosity. Hence, a viscosity enhancer was added in subsequent trials. Example 2: The manufacturing of a Powder composition for oral suspension of Omeprazole was conducted according to the method defined below having the ingredients shown in table-II: Table-II Omeprazole Powder for oral Suspension 20mg / mI Sr, No Name of Ingredient(s) |||||® Part-I 1. Omeprazole 0.78 2. Mannitol 4.88 3. Xanthan Gum 0.01 4. Sodium Hydrogen carbonate 0.82 5. Purified Water QS Part-II 6. Sodium Hydrogen carbonate 6.96 7. Potassium Hydrogen carbonate 27.04 8. Sodium Alginate 5.40 9. Maltitol 52.50 10. Mint Spray dried Flavour 0.19 11. Sodium benzoate 0.97 12. Sodium methyl parahydroxy benzoate 0.45 Total weight 100.00 Manufacturing process: Part -1 (i) Sift the omeprazole, sodium hydrogen carbonate, and mannitol together through a 40# sieve. (ii) Dry mix the sifted ingredients of Step-(i) for 10 minutes in the rapid mixer granulator with the impeller at slow speed and chopper off. (iii) Adding xanthan gum in 70% of the total purified water and stirring for about 45 minutes and dissolve to prepare the clear viscous solution. (iv) Continuous mixing of the binder solution of Step (iii) in the dry mix of step (ii) in a rapid mixer granulator at slow impeller speed. (v) Discharge the wet mass into the fluid bed drier blow by opening the discharge port and operating the sampling and chopper at a slow speed. (vi) Dry and sift the wet mass of Step- (v) in FBD, these dried granules are passed through a 40# sieve and the retained granules are milled through the multi mill by 1.0 mm screen, transfer the remaining milled granules through 40# sieve, the final blending of the granules in the blender for 10 minutes. The obtained first powder mixture contains a moisture content of not more than 4.0%. Part-II (viii) Milling Potassium hydrogen carbonate through the multi mill with a 3mm screen, adding this milled potassium hydrogen carbonate with previously sifted sodium hydrogen carbonate, sodium alginate, mint spray dried flavor, sodium methyl para hydroxy benzoate passed through 30 # sieve. (ix) Mixing of maltitol and sodium benzoate in the blender for 10 minutes and pass through 30# sieve. This final sifted mixture is mixed with the above-sifted material in the blender for 20 min. Part-Ill (ix) Fill separately the API part in Plunger (Powder Holding Cap) and the Dry Mix Blend in a 150 ml PET amber bottle, closed by a white outer cap. Suspension after reconstitution has satisfactory pourability. It was further evaluated for palatability as suspension after reconstitution had a bitter taste. Hence, there was a need to improve palatability by adding sweetener. Example -3 The manufacturing of a Powder composition for oral suspension of Omeprazole was conducted according to the method defined below having the ingredients shown in table-Ill: Table-Ill Omeprazole Powder for oral Suspension 20mg / ml Sr. No Name of Ingredients) lllll® Part-I 1. Omeprazole 0.78 2. Mannitol 4.87 3. Xanthan Gum 0.01 4. Sodium Hydrogen carbonate 0.82 5. Purified Water QS Part-II 6. Sodium Hydrogen carbonate 6.94 7. Potassium Hydrogen carbonate 26.98 8. Sodium Alginate 5.39 9. Maltitol 52.39 10. Sucralose 0.22 11. Mint Spray dried Flavour 0.19 12. Sodium benzoate 0.97 13. Sodium methyl para hydroxy benzoate 0.45 Total weight 100.00 Manufacturing process: Part -1 (i) Sift the omeprazole, sodium hydrogen carbonate, and mannitol together through a 40# sieve, (ii) Dry mixing the previously sifted ingredients of Step-(i) for 10 minutes in the rapid mixer granulator with the impeller at slow speed and chopper off. (iii) Adding xanthan gum in 70% of the total purified water and stirring for about 45 minutes and dissolve to prepare the clear viscous solution. (iv) Continuous mixing of the binder solution of Step (iii) in the dry mix of step (ii) in a rapid mixer granulator at slow impeller speed. (v) Discharge the wet mass into the fluid bed drier blow by opening the discharge port and operating the sampling and chopper at a slow speed. (vi) Dry and sift the wet mass of Step- (v) in FBD, these dried granules passed through a 40# sieve, and the retained granules are milled through the multi mill by 1.0 mm screen, transfer the remaining milled granules through 40# sieve, the final blending of the granules in the blender for 10 minutes. The obtained first powder mixture contains a moisture content of not more than 4.0%. Part-II (viii) Milling the Potassium hydrogen carbonate through the multi mill with a 3mm screen, adding this milled potassium hydrogen carbonate with previously sifted sodium hydrogen carbonate, sodium alginate, sucralose, mint spray dried flavor, sodium methyl para hydroxy benzoate passed through 30 #sieve. (ix) Mixing of maltitol and sodium benzoate in the blender for 10 minutes and pass through 30# sieve. This final sifted mixture is mixed with the above-sifted material in the blender for 20 min. Part-Ill (ix) Fill separately the API part in Plunger (Powder Holding Cap) and the dry mix blend in a 150 ml PET amber bottle, closed by a white outer cap. Suspension after reconstitution has satisfactory pourability. It was evaluated further for palatability as suspension after reconstitution had a bitter taste. Hence, there was a need to improve palatability by adding sweetener. Therefore, the next trial was performed by increasing sucralose by 0.39% to mask the taste. Example -4 The manufacturing of a Powder composition for oral suspension of Omeprazole was conducted according to the method defined below having the ingredients shown in Table IV: Table-IV Omeprazole Powder for oral Suspension 20mg / ml Sr. No Name of Ingredient(s) llllll® Part-I 1. Omeprazole 0.78 2. Mannitol 4.86 3. Xanthan Gum 0.01 4. Sodium Hydrogen carbonate 0.82 5. Purified Water QS Part-II 6. Sodium Hydrogen carbonate 6.93 7. Potassium Hydrogen carbonate 26.93 8. Sodium Alginate 5.38 9. Maltitol 52.30 10. Sucralose 0.39 11. Mint Spray dried Flavour 0.19 12. Sodium benzoate 0.97 13. Sodium methyl parahydroxy benzoate 0.45 Total weight 100.0 Manufacturing process: Part-I (i) Sift the omeprazole, sodium hydrogen carbonate, and mannitol together through a 40# sieve. (ii) Dry mixing of the sifted ingredients of Step-(i) for 10 minutes in the rapid mixer granulator with the impeller at slow speed and chopper off. (iii) Adding xanthan gum in 70% of the total purified water and stirring for about 45 minutes and dissolve to prepare the clear viscous solution. (iv) Continuous mixing of the binder solution of Step (iii) in the dry mix of step (ii) in a rapid mixer granulator at slow impeller speed for 2-5 minutes. (v) Continuous mixing of ingredients of Step-(iv) and water for a minute at slow impeller speed and continuous kneading of wet mass for a minute with a chopper off during all process, further checking the dough mass for proper granulation characteristics. (vi) Scarp the sides of the rapid mixer granulator and impeller blades for raking the mass obtained in Step-(v). Then, the wet mass is discharged into the fluid bed drier blow by opening the discharge port and operating the sampling and chopper at a slow speed. (vii) Dry and sift the wet mass of Step- (vi) in FBD, these dried granules are passed through a 40# sieve and the retained granules are milled through the multi mill by 1.0 mm screen, transfer the remaining milled granules through 40# sieve, the final blending of the granules in the blender for 10 minutes. The obtained first powder mixture contains a moisture content of not more than 4.0%. Part-II (viii) Milling of the Potassium hydrogen carbonate through the multi mill with a 3 mm screen, adding this milled potassium hydrogen carbonate with previously sifted sodium hydrogen carbonate, sodium alginate, sucralose, mint spray dried flavor, sodium methyl para hydroxy benzoate and passed through 30 #sieve. (ix) Mixing of maltitol and sodium benzoate in the blender for 10 minutes and pass through 30# sieve. This final sifted mixture is mixed with the above-sifted material in the blender for 20 min. Part -III (x) Fill separately the API part in Plunger (Powder Holding Cap) and the dry mix blend in a 150 ml PET amber bottle, closed by a white outer cap. Example -5 The manufacturing of a Powder composition for oral suspension of Esomeprazole was conducted according to the method defined below having the ingredients shown in Table-V for dose Strengths 40mg / 5ml and 20mg / 5ml: Table-VA Esomeprazole Powder for oral Suspension 40mg / 5ml Sr. No Name of Ingredient(s) iiiiio Part-I 1 Esomeprazole 1.32 2 Mannitol 3.10 3 Xanthan Gum 0.01 4 Sodium Hydrogen carbonate 0.64 5 Purified Water QS Part-II 6 Sodium carbonate anhydrous 21.51 7 Mannitol 5.69 8 Potassium Hydrogen carbonate 21.11 9 Sodium Alginate 3.38 10 Maltitol 38.82 11 Sucralose 2.70 12 Natural Mint Flavouring 0.68 13 Sodium benzoate 0.49 14 Sodium methyl para hydroxy benzoate 0.22 15 Sodium saccharine dihydrate 0.34 16 Purified water Upto 90 ml Total weight 100.00 Table-VB Esomeprazole Powder for oral Suspension 20mg / 5ml Sr. No Name of Ingredient(s) Part-I 1 Esomeprazole 0.66 2 Mannitol 3.75 3 Xanthan Gum 0.01 4 Sodium Hydrogen carbonate 0.64 5 Purified Water QS Part-II 6 Sodium carbonate anhydrous 21.51 7 Mannitol 5.69 8 Potassium Hydrogen carbonate 21.11 9 Sodium Alginate 3.38 10 Maltitol 38.82 11 Sucralose 2.70 12 Natural Mint Flavouring 0.68 13 Sodium benzoate 0.49 14 Sodium methyl para hydroxy benzoate 0.22 15 Sodium saccharine dihydrate 0.34 16 Purified water Upto 90 ml Total weight 100.00 Manufacturing process: Part-I (i) Sift the Esomeprazole, mannitol, and sodium carbonate anhydrous together through a 40# sieve. (ii) Dry mixing of sifted ingredients of Step-(i) for 10 minutes in the rapid mixer granulator with the impeller at slow speed and chopper off. (iii) Adding xanthan gum in 70% of the total purified water and stirring for about 45 minutes and dissolved to prepare the clear viscous solution. (iv) Continuous mixing of the binder solution of Step (iii) in the dry mix of step (ii) in a rapid mixer granulator at slow impeller speed for 1-2 minutes. (v) Continuous mixing of ingredients of Step-(iv) and water for a minute at slow impeller speed and continuous kneading of wet mass for a minute with a chopper off during all process, further checking the dough mass for proper granulation characteristics. (vi) Scarp the side of the rapid mixer granulator and impeller blades for raking the mass obtained in Step-(v). Then, discharge the wet mass into the fluid bed drier blow by opening the discharge port and operating the sampling and chopper at a slow speed. (vii) Dry and sift the wet mass of Step- (vi) in FBD, these dried granules are passed through a 40# sieve and the retained granules are milled through the multi mill by 1.0 mm screen, transfer the remaining milled granules through 40# sieve, the final blending of the granules in the blender for 10 minutes. The obtained first powder mixture contains a moisture content of not more than 2%. Part-II (viii) Milling potassium hydrogen carbonate through the multi mill with a 3mm screen, adding this milled potassium hydrogen carbonate with previously sifted sodium carbonate anhydrous, mannitol, sodium alginate, sodium saccharin dihydrate, sucralose, mint spray dried flavor, sodium methyl para hydroxy benzoate and these milled ingredients are passed through 30#sieve. Also, maltitol and sodium benzoate are sifted through a 30# sieve. (ix) Mixing the previously sifted maltitol and sodium benzoate in the blender for 10 min. The final sifted mixture is mixed with the above-sifted material in the blender for 20 min. Part-Ill (x) Fill separately the API part in Plunger (Powder Holding Cap) and the Dry Mix Blend in a 150 ml PET amber bottle, closed by a white outer cap. Example -6 The manufacturing of a Powder composition for oral Suspension of Lansoprazole was conducted according to the method defined below having the ingredients shown in Table VI for dose strengths 30mg / ml and 15mg / 5ml: Table-VIA Lansoprazole powder for oral suspension 30mg / 5ml Sr. No Name of Ingredientfs) Part-I 1. Lansoprazole 1.16 2. Mannitol 4.47 3. Xanthan Gum 0.01 4. Sodium Hydrogen carbonate 0.82 5. Purified Water QS Part-II 6. Sodium carbonate anhydrous 6.93 7. Potassium Hydrogen carbonate 26.93 8. Sodium Alginate 5.38 9. Xylitol 53.13 10. Sucralose 0.39 11. Natural Mint Flavour 0.19 12. Sodium benzoate 0.35 13. Sodium methyl para hydroxy benzoate 0.23 14. Purified water Up to 90 ml Total weight 100.00 Table-VIB Lansoprazole powder for oral suspension 15mg / 5ml Sr. No Name of Ingredient(s) If® Part-I 1. Lansoprazole 0.58 2. Mannitol 5.05 3. Xanthan Gum 0.01 4. Sodium Hydrogen carbonate 0.82 5. Purified Water QS Part-II 6. Sodium carbonate anhydrous 6.93 7. Potassium Hydrogen carbonate 26.93 8. Sodium Alginate 5.38 9. Xylitol 53.13 10. Sucralose 0.39 11. Natural Mint Flavouring 0.19 12. Sodium benzoate 0.35 13. Sodium methyl para hydroxy benzoate 0.23 14. Purified water Up to 90 ml Total weight 100.00 Manufacturing process: Part-I (i) Sift the Lansoprazole, mannitol, and sodium carbonate anhydrous together through a 40# sieve. (ii) Dry mix the sifted ingredients of Step-(i) for 10 minutes in the rapid mixer granulator with the impeller at slow speed and chopper off. (iii) Adding xanthan gum in 70% of the total purified water and stirring for about 45 minutes and dissolve to prepare the clear viscous solution. (iv) Continuous mixing of the binder solution of Step (iii) in a dry mix of step (ii) in a rapid mixer granulator at slow impeller speed for 1-2 minutes. (v) Continuous mixing of ingredients of Step-(iv) and water for a minute at slow impeller speed and continuous kneading of wet mass for a minute with a chopper off during all process, further checking the dough mass for proper granulation characteristics. (vi) Scarp the side of the rapid mixer granulator and impeller blades for raking the mass obtained in Step-(v). Then, discharge the wet mass into the fluid bed drier blow by opening the discharge port and operating the sampling and chopper at a slow speed. (vii) Dry and sift the wet mass of Step- (vi) in FBD, these dried granules passed through a 40# sieve, and the retained granules are milled through the multi mill by 1.0 mm screen, transfer the remaining milled granules through 40# sieve, final blending the granules in the blender for 10 minutes. The obtained first powder mixture contains a moisture content of not more than 2%. Part-II (viii) Milling the potassium hydrogen carbonate through the multi mill with a 3mm screen, adding this milled potassium hydrogen carbonate with previously sifted sodium carbonate anhydrous, mannitol, sodium alginate, sucralose, mint spray dried flavor, sodium methyl para hydroxyl benzoate, and this milled ingredient are passed through 30# sieve. In addition to this xylitol and sodium benzoate are sieved through a 30# sieve. (ix) Mixing the previously sifted maltitol and sodium benzoate in the blender for 10 minutes and the final sifted mixture is mixed with the above-sifted material in the blender for 20min. Part-Ill (x) Fill separately the API part in Plunger (Powder Holding Cap) and the dry mix blend in a 150 ml PET amber bottle, closed by a white outer cap. Example 7 The Dissolution condition of Powder composition for oral Suspension of a Proton Pump Inhibitor was prepared for Example 4. The conditions of the dissolution system are as follows: Product Name: Omeprazole Powder Composition Strengths: 20mg / ml Media: pH 6.8 phosphate buffer Apparatus: Paddle Rate of rotation: 100 RPM Volume: 900 ml Example 8 A powder composition of Omeprazole for its dissolution profile was analyzed in 900 ml of pH 6.8 phosphate buffer at 100 RPM in USPII (Paddle) apparatus and subjected to a stability study of 25°C / 60%RH and 40°C / 75%RH for 3 months. Results are tabulated below: A Powder composition for oral suspension of Omeprazole Parameters Specification Initial Assay (%) Omeprazole 95.0% - 105.0% 103.2 101.0 100.0 Sodium Benzoate 90.0% - 110.0% 105.6 102.0 96.5 Sodium methyl parahydroxybenzoate 90.0% - 110.0% 102.4 106.0 101.1 pH 8.0 to 9.5 8.25 8.17 8.27 Dissolution NLT 75% (Q) labelled amount of Omeprazole should be dissolved in 45 minutes. 91.1 89.7 89.9 Impurities (%) Impurity D Not more than 0.2% 0.0636 0.0702 0.0789 Impurity E Not more than 0.2% ND ND ND Single maximum unknown impurity Not more than 0.2% 0.0436 0.0481 0.0489 Total Impurity Not more than 1.0% 0.2676 0.2877 0.2916 Example 9 The Dissolution condition of Powder composition for oral suspension of a Proton Pump Inhibitor was prepared for Example 5-A. The conditions of the dissolution system are as follows: Product Name: Esomeprazole powder composition Strengths: 40mg / 5ml Media: pH 6.8 phosphate buffer Apparatus: Paddle Rate of rotation: 100 RPM Volume: 900 ml Example 10 A powder composition of Esomeprazole for its dissolution profile was analyzed in 900 ml of pH 6.8 phosphate buffer at 100 RPM in USP II (Paddle) apparatus and subjected to a stability study of 25°C / 60%RH and 40°C / 75% RH for 3 months. Results are tabulated below: A Powder composition for oral suspension of Esomeprazole Parameters Specification Initial 25°C / 60%RH 40°C / 75%RH Assay (%) Esomeprazole 95.0% - 105.0% 98.5 99.7 92.2 Sodium Benzoate 90.0% - 110.0% 97.9 96.3 93.5 Sodium methyl para hydroxy benzoate 90.0% - 110.0% 97.0 97.9 99.6 pH To be established 9.70 10.16 10.29 Dissolution NLT 75% (Q) labelled amount of Esomeprazole should be dissolved in 45 minutes. 96.4 103.7 97.9 Impurities (%) Impurity D Not more than 0.5% 0.020 0.0193 0.0411 Impurity E Not more than 0.2% 0.0013 0.0089 0.0113 Parameters Specification Initial 25°C / 60%RH 40°C / 75%RH Single maximum unknown impurity Not more than 0.2% Not Detected Not Detected Not Detected Total Impurity To be established 0.083 0.0891 0.1095 Example 11 The Dissolution condition of Powder composition for oral suspension of a Proton Pump Inhibitor was prepared for Example 6-A. The conditions of the dissolution system are as follows: Product Name: Lansoprazole powder composition Strengths: 30mg / 5ml Media: pH 6.8 phosphate buffer Apparatus: Paddle Rate of rotation: 150 RPM Volume: 900 ml Example 12 A powder composition of Lansoprazole for its dissolution profile was analyzed in 900ml of pH 6.8 phosphate buffer at 150 RPM in USPII (Paddle) apparatus and subjected to a stability study of 25°C / 60%RH and 40°C / 75%RH for 6 months. Results are tabulated below: A Powder composition for oral suspension of Lansoprazole Parameters Specification Initial 25°C / 60%RH Assay (%) Lansoprazole 95.0% - 105.0% 98.0 98.4 97.1 Sodium Benzoate 90.0% - 110.0% 101.3 100.9 98.2 Sodium Methyl Parahydroxy Benzoate 90.0% - 110.0% 106.0 94.4 34.4 pH 8.5 to 10.0 8.95 9.19 9.75 Parameters Specification Initial 25°C / 60%RH 40°C / 75%RH Dissolution NLT 75% (Q) labelled amount of Lansoprazole should be dissolved in 45 minutes. 99.0 98.0 98.9 Impurities (%) Impurity A Not more than 0.3% ND ND ND Impurity B Not more than 0.5% 0.0175 0.0461 0.0545 Impurity D Not more than 0.2% ND ND ND Impurity E Not more than 0.4% ND ND ND Single maximum unknown impurity Not more than 0.2% ND ND ND Total impurities Not more than 2.0% 0.0302 0.782 0.0829

Claims

1. A Powder composition for oral suspension comprising a two phase powder mixture, where the first phase is in powder form comprising:(a) a Proton Pump Inhibitor or pharmaceutically acceptable salts thereof, present in the range from about 0.01% w / w to about 7.5% w / w, preferably in the range from about 0.05% w / w to about 6.5% w / w;(b) at least one diluent;(c) a first buffering agent;(d) at least binding agent present in the range from about 0.0010% w / w to about 2.0% w / w, preferably in the range from about 0.0015% w / w to about 1.5% w / w;(e) the second phase is in powder form comprising a second buffering agent;(f) at least a viscosity enhancer present in the range from about 0.05% w / w to about 12.5% w / w, preferably in the range from about 0.075% w / w to about 8.5% w / w;(g) at least one diluent;(h) at least one preservative; and(i) at least one or more pharmaceutically acceptable excipients;wherein the first phase powder mixture contains a moisture content of not more than 5.0%.

2. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, wherein the diluents are selected from the group consisting of lactitol, mannitol, maltitol, xylitol, sorbitol, erythritol, isomalt, or any combinations thereof.

3. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 2, wherein the diluents are sugar alcohols or a combination thereof present in the range from about 20 % w / w to about 80 % w / w, preferably in the range from about 30 % w / w to about 70 % w / w.

4. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 3, wherein the sugar alcohols diluent is selected from mannitol, maltitol, and xylitol or combinations thereof.

5. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, wherein the first and second buffering agents are selected from the group consisting of acetic acid, sodium acetate, citric acid, sodium citrate, sodium phosphate, sodium hydrogen carbonate, potassium hydrogen carbonate, gluconates, tartrates, L-methionine, potassium citrate, sodium carbonate anhydrous, potassium bicarbonate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium hydroxide, potassium dihydrogen phosphate, fumaric acid, tartaric acid or any combinations thereof.

6. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 5, wherein the first buffering agent is sodium hydrogen carbonate present in the range from about 0.45% w / w to about 2% w / w, preferably in the range from about 0.5% w / w to about 1.5% w / w.

7. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 5, wherein the second buffering agent is selected from the group consisting of sodium hydrogen carbonate, potassium hydrogen carbonate, and sodium carbonate anhydrous or any combinations thereof present in the range from about 15% w / w to about 65% w / w, preferably in the range from about 25% w / w to about 55% w / w.

8. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 5, wherein the pH of the reconstituted suspension is in the range from 7.0 to 11.0, preferably it is in the range from 7.5 to 10.5.

9. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, wherein the binding agent is selected from the group consisting of povidone, starch, pregelatinized starch, tragacanth, dextrin, sucrose, glucose, dextrose, molasses, mannitol, sorbitol, xylitol, lactose, acacia, tragacanth, ghatti gum, xanthan gum, polyvinylpyrrolidone, carboxymethylcellulose, methylcellulose, microcrystalline dextrose, amylose, magnesium aluminum silicate, polysaccharide acids, bentonites, gelatin or any combinations thereof.

10. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 9, wherein the binding agent is xanthan gum.

11. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, wherein the viscosity enhancer is selected from the group consisting of sodium alginate, carrageenan, gum acacia, gum tragacanth, sodium carboxymethyl cellulose, methyl cellulose, bentonite, veegum, carbomers, colloidal silicon dioxide, glucose, fructose, acacia, bentonite, carboxy methyl cellulose sodium, gelatin, guar gum, hydroxyl ethyl cellulose, hydroxyl propyl methylcellulose, polyvinyl pyrrolidone, polyvinyl alcohol, and poloxamer or any combinations thereof.

12. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 11, wherein the viscosity enhancer is sodium alginate that contains a percentage of moisture from about 6% to about 12%, preferably in the range from about 8% to about 10%.

13. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, wherein the preservatives are selected from the group consisting of ethanol, propylene glycol, benzyl alcohol, quaternary amines, benzalkonium chloride, sorbic acid, benzoic acid, methyl paraben, propyl paraben, glycerin, propylene glycol, sodium propionate, cetrimide, chlorobutanol, phenylmercuric acetate, potassium sorbate, sodium benzoate, disodium edetate, butylparaben, phenyl ethyl alcohol, phenoxetol or any combinations thereof in the range from about 0.05% w / w to about 4% w / w, preferably in the range from about 0.075% w / w to about 3% w / w.

14. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 13, wherein the preservative is the combination of sodium benzoate and sodium methyl para hydroxy benzoate.

15. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, wherein the pharmaceutical composition further comprises at least one or more pharmaceutically acceptable excipients selected from the group consisting of sweeteners and flavours.

16. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, wherein the ratio of a Proton Pump Inhibitor to Viscosity enhancer is in the range from about 1:1 to about 1:12 and preferably it is in the range from about 1:2 to about 1:10.

17. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, is for the treatment or prevention of a variety of disorders including the healing of erosive esophagitis, maintenance of healed erosive esophagitis, treatment of gastroesophageal reflux disease, for gastric ulcers associated with nonsteroidal anti-inflammatory drugs, to reduce the risk of duodenal ulcer recurrence by eradication of helicobacter pylori, in pathological hypersecretory conditions including Zollinger-Ellison (ZE) syndrome, and in short-term treatment and maintenance of duodenal ulcers.

18. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, wherein a Proton Pump Inhibitor is selected from the group consisting of Omeprazole, Pantoprazole, Lansoprazole, Rabeprazole, Dexlansoprazole, Esomeprazole, Ilaprazole, Tenetoprazole, Azeloprazole, Anaprazole or pharmaceutically acceptable salts thereof.

19. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 18, wherein a Proton Pump Inhibitor or pharmaceutically acceptable salts thereof is Omeprazole, Esomeprazole, and Lansoprazole in non-micronized form.

20. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 19, wherein the D50 particle size of Omeprazole or a pharmaceutically acceptable salt thereof is in the range from about 1.5 pm to 5.5 pm, preferably in the range from about 2.5 pm to 4.5 pm, the D50 particle size of Esomeprazole or a pharmaceutically acceptable salt thereof is in the range from about 0.5 pm to 4.5 pm, preferably in the range from about 1.5 pm to 3.5 pm, the D50 particle size of Lansoprazole or a pharmaceutically acceptable salt thereof is in the range from about 4 pm to 16 pm, preferably in the range from about 9 pm to 11 pm.

21. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 19, wherein the D90 particle size of Omeprazole or a pharmaceutically acceptable salt thereof is in the range from about 5 pm to 15 pm, preferably in the range from about 8 pm to 10 pm, the D90 particle size of Esomeprazole or a pharmaceutically acceptable salt thereof is in the range from about 1 pm to 15pm, preferably in the range from about 4 pm to 8 pm, the D90 particle size of Lansoprazole or a pharmaceutically acceptable salt thereof is in the range from about 15 pm to 45 pm, preferably in the range from about 20 pm to 30 pm.

22. The powder composition for oral Suspension of Proton Pump Inhibitors according to claim 1, wherein the powder composition comprising:a) 0.01% w / wto about 2.5% w / w, preferably in the range from about 0.05% w / wto about 1.5% w / w of omeprazole or pharmaceutically acceptable salts thereof;b) a combination of mannitol and maltitol present in the range from about 20% w / w to about 80% w / w, preferably in the range from about 30% w / w to about 70% w / w;c) 0.0010% w / w to about 2% w / w, preferably in the range from about 0.0015% w / w to about 1.5% w / w of xanthan gum;d) a first buffering agent is sodium hydrogen carbonate present in the range from about 0.45% w / w to about 2% w / w, preferably in the range from about 0.5% w / w to about 1.5% w / w, a second buffering agent is a combination of sodium hydrogen carbonate and potassium hydrogen carbonate present in the range from about 15% w / w to about 65% w / w, preferably in the range from about 25% w / w to about 55% w / w;e) 0.05% w / w to about 12.5% w / w, preferably in the range from about 0.075% w / w to about 8.5% w / w of sodium alginate;f) a combination of sodium benzoate and sodium methyl parahydroxy benzoate present in the range from about 0.05% w / w to about 4% w / w, preferably from about 0.075% w / w to about 3% w / w;g) 0.05% w / w to about 8.5% w / w, preferably in the range from about 0.10% w / w to about 7% w / w of sucralose; andh) 0.010% w / w to about 2.5% w / w, preferably in the range from about 0.025% w / w to about 1.5% w / w of mint spray dried flavour.

23. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, wherein the powder composition comprising:a) 0.05% w / w to about 5% w / w, preferably in the range from about 0.1% w / w to about 3.5% w / w of Esomeprazole or pharmaceutically acceptable salts thereof;b) a combination of mannitol and maltitol present in the range from about 20%w / w to about 80% w / w, preferably in the range from about 30% w / w to about 70% w / w;c) 0.0010% w / w to about 2.0% w / w, preferably in the range from about 0.0015% w / w to about 1.5% w / w of xanthan gum;d) a first buffering agent is sodium carbonate anhydrous present in the range from about 0.45% w / w to about 2% w / w, preferably in the range from about 0.5% w / w to about 1.5% w / w, a second buffering agent is a combination of sodium carbonate anhydrous and potassiumhydrogen carbonate present in the range from about 15% w / w to about 65% w / w, preferably in the range from about 25% w / w to about 55% w / w;e) 0.05% w / w to about 12.5% w / w, preferably in the range from about 0.075% w / w to about 8.5% w / w of sodium alginate;f) a combination of sodium benzoate and sodium methyl para hydroxy benzoate present in the range from about 0.05% w / w to about 4% w / w, preferably in the range from about 0.075% w / w to 3% w / w;g) a combination of sucralose and sodium saccharin dihydrate present in the range from about 0.05% w / w to about 8.5% w / w, preferably in the range from about 0.1% w / w to about 7% w / w; andh) 0.01% w / w to about 2.5% w / w, preferably in the range from about 0.025% w / w to about 1.5% w / w of natural mint flavour.

24. The powder composition for oral suspension of Proton Pump Inhibitors according to claim 1, wherein the powder composition comprising:a) 0.01% w / w to about 5% w / w, preferably in the range from about 0.05% w / w to about 3.5% w / w of Lansoprazole or pharmaceutically acceptable salts thereof;b) a combination of mannitol and xylitol present in the range from about 20% w / w to about 80% w / w, preferably in the range from about 30% w / w to about 70% w / w;c) 0.0010% w / w to about 2.0% w / w, preferably in the range from about 0.0015% w / w to about 1.5% w / w of xanthan gum;d) a first buffering agent is sodium carbonate anhydrous present in the range from about 0.45% w / w to about 2% w / w, preferably in the range from about 0.5% w / w to about 1.5% w / w, a second buffering agent is a combination of sodium carbonate anhydrous and potassium hydrogen carbonate present in the range from about 15% w / w to about 65% w / w, preferably in the range from about 25% w / w to about 55% w / w;e) 0.05% w / w to about 12.5% w / w, preferably in the range from about 0.075% w / w to about 8.5% w / w of sodium alginate;f) a combination of sodium benzoate and sodium methyl para hydroxy benzoate present in the range from about 0.05% w / w to about 4% w / w, preferably in the range from about 0.075% w / w to about 3% w / w;g) 0.05% w / w to about 8.5% w / w, preferably in the range from about 0.1% w / w to about 7% w / w of sucralose; andh) 0.01% w / w to about 2.5% w / w, preferably in the range from about 0.025% w / w to about 1.5% w / w of natural mint flavour.