An orodispersible tablet of Famotidine and its process of preparation

Abstract

The present invention relates to an orodispersible tablet manufactured by a wet granulation method comprising Famotidine or pharmaceutically acceptable salts thereof, one or more diluents, at least on

Description

The present invention relates to the pharmaceutical compositions of Famotidine. More particularly, the present invention provides orodispersible tablets of Famotidine or pharmaceutically acceptable salts thereof for oral administration. The present invention provides orodispersible tablets of Famotidine comprising Famotidine, diluents, disintegrants, lubricants, binders, sweeteners, flavoring agents, and vehicles. The present invention also provides an orodispersible tablet of Famotidine for the treatment of duodenal ulcers, benign gastric ulcers, Zollinger-Ellison syndrome, reflux oesophagitis, and the process for preparing the same. Background of the Invention Peptic ulcer disease is characterized by discontinuation m the inner lining of the gastrointestinal (GI) tract because of gastric acid secretion or pepsin. It extends into the muscularis propria layer of the gastric epithelium. It usually occurs in the stomach and proximal duodenum. Famotidine is used to treat and prevent ulcers in the stomach and intestines. It also treats conditions in which the stomach produces too much acid, such as Zollinger-Ellison syndrome. Famotidine also treats gastroesophageal reflux disease (GERD) and other conditions in which acid backs up from the stomach into the esophagus, causing heartbum. Famotidine was first approved for prescription use on May 28, 1998. Famotidine was first disclosed in the U.S. Pat. No. US4283408A with the process of preparing the same. Famotidine has the ability to inhibit gastric acid secretion through a histamine H2 -receptor. Histamine H2 -receptor blocking agents have the ability to inhibit the basic secretion of gastric acid and the gastric acid secretion induced by gastrin histamine, methacholine or food. Therefore, these compounds are usefill in the treatment of gastric ulcers, Zollinger-Ellison syndrome, GERD, and duodenal ulcers caused by the hypersecretion of gastric acid. Famotidine undergoes minimal first-pass metabolism. About 25-30% of the drug is eliminated through hepatic metabolism. About 65-70% of the total administered dose of famotidine undergoes renal elimination, and 30-35% of the dose is cleared by metabolism. Famotidine belongs to BCS class II having low solubility and high permeability. The IUPAC name of Famotidine is 3-[[2-(diaminomethylideneamino)-l,3-thiazol-4-yl]methylsulfanyl]-N'-sulfamoylpropanimidamide and the chemical structure is as follows: r \ j 1¾¾ The oral route of administration is the most widely used method for delivering medications due to its numerous advantages, including ease of administration, patient convenience, and cost-effectiveness. Additionally, it does not require specialized equipment or professional assistance, enabling patients to selfadminister their medications effortlessly. There are various formulations of famotidine available on the market, including oral suspensions, tablets, and injectable solutions, each with its own set of drawbacks. Suspensions, for instance, can face issues like sedimentation, where dispersed particles gradually settle due to gravity. This settling can lead to non-uniform dosing if the suspension isn't properly shaken before use. Over time, the settled particles may form a compact mass (caking) that is difficult to re-disperse, making it challenging to restore the suspension's original uniformity. Moreover, formulating a stable suspension is complex, requiring carefill control of factors such as particle size, viscosity, and the selection of appropriate suspending agents and preservatives. Injectable formulations also come with their disadvantages. They can cause pain, discomfort, or irritation at the injection site, particularly intramuscular or subcutaneous routes. Additionally, if proper sterile techniques are not strictly adhered to, there is a risk of infection at the injection site, potentially leading to abscesses or more serious systemic infections. Furthermore, injectable formulations tend to be more expensive than oral medications due to the need for sterile production environments, specialized packaging, and administration by healthcare professionals. Therefore, there is a need to develop oral disintegrating tablets (ODTs) to overcome these challenges. ODTs offer a pain-free, convenient alternative, avoiding the discomfort and anxiety associated with injections, thereby improving patient compliance, especially in those who are needle-phobic. Orally disintegrating tablets offer several benefits, including ease of administration for those who have difficulty swallowing, such as the elderly, young children, and patients with certain medical conditions. They also enhance convenience for patients who may not have access to water or prefer not to use it. Furthermore, the rapid dissolution of these tablets in the mouth facilitates quicker onset of action and allows for drug absorption through the oral mucosa and gastrointestinal tract. There are some documents that disclose the formulations for Famotidine for the treatment of stomach ulcers and gastroesophageal reflux disease. US5650421A discloses an aqueous-based, premix formulation of famotidine. The process of this invention comprises dissolving an effective amount of famotidine into a suitable liquid to form a solution and adjusting the pH of the solution to a range of about 4.5 to about 8.0. the solution is filled into suitable containers. CN1634045A discloses the famotidine chewing tablet preparation method. The chewable tablet comprises famotidine coated granule, calcium carbonate, magnesium hydroxide, correctives, diluent, binding agent, and lubricant. Hie process of this invention comprises the mixing of coated granules of famotidine with calcium carbonate, magnesium hydroxide, and other pharmaceutic adjuvants with the equivalent incremental method then, the back tableting of granulating. CM 04095875A discloses famotidine calcium magnesium chewable tablet for treating or preventing acid regurgitation, gastric acid, heartbum (stomach burning), stomachache, stomach distension, belching, and other stomach discomfort. The famotidine calcium magnesium chewable tablet contains famotidine, calcium carbonate, and magnesium hydroxide. WO2023218480A1 discloses oral liquid formulation of famotidine or pharmaceutically acceptable salt thereof. The liquid formulation is in the form of ready to use solution, ready to use suspension, powder for suspension or powder for solution. The liquid formulation comprising Famotidine, avicel, sodium MHB, sodium PHB, aerosil 200, mannitol, citric acid anhydrous, sucralose, and natural mint flavor. US20090137645A1 discloses a granulate for oral suspension that is particularly useful for the storage and reconstitution of famotidine into a liquid form. The invention comprises famotidine, xanthan gum, confectioner's sugar, and com starch. The process of this invention includes: (a) providing a granulate for oral suspension, comprising a first granulate that contains famotidine in combination with an organic or mineral acid, where the first granulate has the morphology of a dry granulate; and (b) mixing the granulate with water at a ratio of about 40 mg of famotidine per 5 ml of water, in an amount effective to produce a pH of 6.5 to 7.5 in the resulting suspension. Therefore, the inventor of the present invention has developed an orodispersible tablet of famotidine that dissolves quickly in the mouth without the need for water, offering a more convenient method of administration. This innovative formulation provides several key advantages: it ensures accurate dosing, promotes rapid disintegration, and absorption, and improves patient compliance. It is especially beneficial for individuals who have difficulty swallowing, such as pediatric and elderly patients with dysphagia, as it eliminates the need for water and reduces the risk of choking or discomfort. Additionally, this dosage form is ideal for use in situations where immediate relief is required or water is not readily available. Summary of the Invention The main aspect of the present invention is to provide an orodispersible tablet of Famotidine for oral administration. Another main aspect of the present invention is to provide an orodispersible tablet of Famotidine for oral administration comprising Famotidine or pharmaceutically acceptable salts thereof, at least one or more diluents, at least one disintegrant, at least one binder, at least one lubricant, at least one sweetener, at least one flavoring agent and at least one vehicle. The other aspect of the present invention is to provide an orodispersible tablet of Famotidine for oral administration and a process for preparing the same. Objects of the Invention The main object of the present invention is to provide an orodispersible tablet of Famotidine or pharmaceutically acceptable salts thereof. Another object of the present invention is to provide an orodispersible tablet of Famotidine that dissolves quickly in the mouth, making it convenient for patients who may not have access to water or have difficulty swallowing. Another object of the present invention is to provide an orodispersible tablet of Famotidine which improves patient compliance especially helpful for children, elderly patients, or those with dysphagia (difficulty swallowing), as the tablet disintegrates easily on the tongue. Another object of the present invention is to provide a stable orodispersible tablet of Famotidine or pharmaceutically acceptable salts thereof. Yet another object of the present invention is to provide an orodispersible tablet of Famotidine which increases the dissolution and disintegration. Detailed description of the Invention The detailed description set forth below is intended as a description of exemplary embodiments and is not intended to represent the only forms in which the exemplary embodiments may be constructed and / or utilized. The description sets forth the functions and the sequence of steps for constructing and / or operating the exemplary embodiments. However, it is to be understood that the same or equivalent functions and sequences that may be accomplished by different exemplary methods are also intended to be encompassed within the spirit and scope of the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. As stated herein, that it follows in a transitional phrase or in the body of a claim, the terms “comprise(s)” and “comprising” are to be interpreted as having an open ended meaning. That is, the terms are to be interpreted synonymously with the phrases “having at least” or “including at least”. When used in the context of a process, the term “comprising” means that the process includes at least the recited steps, but may include additional steps. When used in the context of a composition, the term “comprising” means that the composition includes at least the recited features or components, but may also include additional features or components. The term “Orodispersible tablet” refers to a type of dosage form that rapidly dissolves and disintegrates in the mouth, releasing its active ingredients quickly without the need for chewing or swallowing with water. Tire terms 'Orodispersible tablet,' 'Orally disintegrating tablet,' and 'Fast dissolving tablet' used herein are interchangeable and convey the same meaning. As used herein, the term "formulation", “composition” or “dosage form” is unless otherwise defined as Famotidine orodispersible tablet formulation of the invention. Tire term “excipient” or “excipients” or “ingredient” means a pharmacologically inactive component that is useful in preparing a tablet formulation, which is generally safe, non-toxic, and acceptable for human pharmaceutical use. As used herein, the term “about” means an approximate or rough estimation. When used with a numerical range, it broadens the boundaries to cover values that are slightly above or below the specified range. Typically, "about" means a range extending roughly ±10% from the stated value. The term “% w / w” refers to the weight percentage of an ingredient relative to the total weight of the composition, which is considered to be 100%. This calculation of % w / w is based on the complete weight of the composition. In other words, the percentage by weight is determined by comparing the weight of the individual ingredient to the total weight of all components in the formulation. The term “therapeutically effective amount” is defined to mean the amount or quantity of the active drug (e.g., famotidine or a pharmaceutically acceptable salt 7 thereof), which is sufficient to elicit an appreciable biological response when administered to a patient. The main embodiment of the present invention is to provide an orodispersible tablet of Famotidine. Another main embodiment of the present invention is to provide an orodispersible tablet formulation of Famotidine comprising Famotidine or pharmaceutically acceptable salts thereof, one or more diluents, at least one disintegrant, at least one lubricant, at least one binder, at least one sweetener, and at least one flavoring agent. The Famotidine may be present in the form of a pharmaceutically acceptable salt. Pharmaceutically acceptable salts include, without being restricted thereto, hydrochloric acid, sulfuric acid, phosphoric acid, oxalic acid, acetic acid, citric acid, malic acid, benzoic acid, maleic acid, fumaric acid, tartaric acid, succinic acid, glutamic acid, methanesulfonic acid, and p-toluenesulfonic acid. Preferably Famotidine as used herein is in the form of the free base. In one embodiment, the composition contains Famotidine, or a pharmaceutically acceptable salt thereof, in an amount ranging from about 10 %w / w to about 30 % w / w, with a preferred range of 15 %w / w to about 25 %w / w. As per one embodiment of the present invention, the D90 particle size of Famotidine, or pharmaceutically acceptable salts thereof, is less than 50 microns, more preferably less than 20 microns. In one embodiment of the present invention, a suitable diluent is selected from the group consisting of calcium carbonate, cellulose derivatives, microcrystalline cellulose, microfine cellulose, sugar alcohols such as maltitol, spray dried mannitol, sorbitol, com starch, potato starch, hydroxypropyl methylcellulose (HPMC), dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, lactose, starch, pregelatinized starch, dicalcium phosphate dihydrate, dicalcium phosphate anhydrous or any combination thereof. In the preferred embodiment of the present invention, the combination of spray-dried mannitol and microcrystalline cellulose is used as diluents. Mannitol is preferred for its high flowability, non-hygroscopicity, chemical inertness, and excellent compressibility, which enhance mechanical properties and ensure uniform compression. Spray-dried mannitol also promotes rapid disintegration upon contact with saliva, leading to quick dissolution and a faster onset of action. Microcrystalline Cellulose facilitates efficient dry blending and tablet compression, and its water-imbibing action promotes quick wetting and drying. Therefore, the combination of microcrystalline cellulose and spray-dried mannitol ensures the production of stable, uniform tablets with consistent quality and rapid disintegration, making it the preferred choice of diluents in the present invention. In another preferred embodiment of the present invention, the combination of diluents is included in an amount ranging from about 50 % w / w to about 90 % w / w, preferably from about 60 % w / w to about 80 % w / w. In one another preferred of the present invention, spray-dried mannitol is present in an amount ranging from about 45 %w / w to about 70 %w / w, preferably from about 50 %w / w to about 65 %w / w. Microcrystalline Cellulose is present in an amount ranging from about 5 %w / w to about 20 %w / w, more preferably from about 10 %w / w to about 15 %w / w. In one embodiment of the present invention, a suitable dismtegrant is selected from the group consisting of alginic acid, guar gum, croscarmellose sodium, cross-linked polyvinylpyrrolidone, carmellose calcium, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, sodium carboxymethylcellulose (CMC), carboxy methyl cellulose, cross-linked sodium carboxy methylcellulose (Ac-di-sol), poloxamer, magnesium aluminum silicate, pregelatinized starch, sodium starch glycolate, microcrystalline cellulose, or any combination thereof. In the preferred embodiment of the present invention, cross-linked Polyvinylpyrrolidone is used as the disintegrant. In one embodiment of the present invention, disintegrant is included in an amount ranging from about 0.5% w / w to about 10% w / w, preferably from about 1% w / w to about 5% w / w. In one embodiment of the present invention, a suitable lubricant is selected from the group consisting of magnesium stearate, sodium stearyl fumarate, micronized polyoxyethylene glycol, colloidal silicon dioxide, glyceryl behenate, hydrogenated vegetable oils, sodium benzoate, beeswax, polyethylene glycol (peg), sodium lauryl sulfate, stearic acid, talc, sodium stearate, sodium starch glycolate, calcium stearate, or combinations thereof. In the preferred embodiment of the present invention, magnesium stearate is used as the lubricant. In one embodiment of the present invention, the lubricant is included in an amount ranging from about 0.1% w / w to about 5 % w / w, preferably from about 1 % w / w to about 3 % w / w. In one embodiment of the present invention, a suitable binder is selected from the group consisting of starch, pregelatinized starch, sodium alginate, gelatin, acacia polyvinyl pyrrolidone (pvp), polyvinylpyrrolidone, methylcellulose, hydroxy propyl methyl cellulose (hpmc), polymethacrylates, sodium carboxy methyl cellulose, polyethylene glycol (peg) and methylcellulose, hydroxyethylmethyl cellulose, hydroxyethyl cellulose, guar gum or combinations thereof. In the preferred embodiment of the present invention, polyvinylpyrrolidone is used as the binder. In one embodiment of the present invention, the binder is included in an amount ranging from about 0.1 %w / w to about 10 % w / w, preferably from about 1 % w / w to about 5 % w / w. In one embodiment of the present invention, a suitable flavoring agent is selected from the group consisting of raspberry flavor, strawberry flavor, blueberry flavor, caramel flavor, butterscotch flavor, floral fennel flavor, mint powder, vanillin, mint flavor, orange flavor, peppermint oil, spearmint oil or combinations thereof. In the preferred embodiment of the present invention, raspberry’ flavor is used as a flavoring agent. In one embodiment of the present invention, the flavoring agent is included in an amount ranging from about 0.1 %w / w to about 5 %w / w, preferably in the range from about 1 %w / w to about 3 %w / w. In one embodiment of the present invention, a suitable sweetener is selected from the group consisting of saccharin, aspartame, sucralose, stevioside, acesulfame, xylitol, sucrose, liquid glucose, glycerol, sorbitol, acesulfame potassium, fructose or combinations thereof. In the preferred embodiment of the present invention, sucralose is used as a sweetener. In one embodiment of the present invention, the sweetener is included in an amount ranging from about 0.1 %w / w to about 10 % w / w, preferably in the range from about 1 %w / w to about 5 % w / w. In one embodiment of the present invention, the orodispersible tablet comprising Famotidine or pharmaceutically acceptable salts thereof is present in an amount ranging from about 10 %w / w to about 30 %w / w, preferably in the range from about 15 %w / w to about 25 %w / w, diluent combinations are present in the range from about 50 % w / w to about 90% w / w, preferably from about 60 % w / w to about 80 % w / w, disintegrant is present in the range from about 0.5 % w / w to about 10 % w / w, preferably from about 1 % w / w to about 5 % w / w, lubricant is present in the range from about 0.1 %w / w to about 5 %w / w, preferably in tire range from about 1 %w / w to about 3 %w / w, binder is present in the range from about 0.1 %w / w to about 10 %w / w, preferably in the range from about 1 %w / w to about 5 %w / w, flavoring agent is present in the range from about 0.1 %w / w to about 5 %w / w, preferably in the range from about 1 %w / w to about 3 %w / w and sweetener is present in the range from about 0.1 %w / w to about 10 %w / w, preferably in the range from about 1 %w / w to about 5 %w / w. In the preferred embodiment of the present invention, the orodispersible tablet comprising Famotidine or pharmaceutically acceptable salts thereof, is present in an amount ranging from about 10 %w / w to about 30 %w / w, preferably in the range from about 15 %w / w to about 25 %w / w, a combination of spray-dried mannitol and microcrystalline cellulose present in the range from about 50 % w / w to about 90% w / w, preferably from about 60 % w / w to about 80 % w / w, spray-dried mannitol is present in the range from about 45 %w / w to about 70 %w / w, preferably in the range from about 50 %w / w to about 65 %w / w, microcrystalline cellulose is present in the range from about 5 %w / w to about 20 %w / w, more preferably in the range from about 10 %w / w to about 15 %w / w, cross-linked Polyvinylpyrrolidone is present in the range from about 0.5 %w / w to about 10 %w / w, preferably in the range from about 1 %w / w to about 5 %w / w, magnesium stearate is present in the range from about 0.1 %w / w to about 5 %w / w, preferably in the range from about 1 %w / w to about 3 %w / w, polyvinylpyrrolidone is present in the range from about 0.1 %w / w to about 10 %w / w, preferably in the range from about 1 %w / w to about 5 %w / w, raspberry flavor is present in the range from about 0.1 %w / w to about 5 %w / w, 12 preferably in the range from about 1 %w / w to about 3 %w / w, sucralose is present in the range from about 0.1 %w / w to about 10 %w / w, preferably in the range from about 1 %w / w to about 5 %w / w. In another preferred embodiment of the present invention, the orodispersible tablet comprising 20.00 % w / w of Famotidine or pharmaceutical acceptable salts thereof, 56.50 % w / w of spray-dried mannitol, and 12.50 % w / w of microcrystalline cellulose as a combination of diluents, 3 % w / w of cross-linked polyvinylpyrrolidone as a disintegrant, 2.50 % w / w of polyvinylpyrrolidone as a binder, 1.50 % w / w of raspberry flavor as a flavoring agent, 2.50 % w / w of sucralose as sweetner and 1.50 % w / w of magnesium stearate as a lubricant. In one embodiment of the present invention, an orodispersible tablet of Famotidine is manufactured by using the wet granulation method. In one embodiment of the present invention, the disintegrating time of the Famotidine orodispersible tablet is less than 3 minutes, preferably less than 60 seconds. In one embodiment of the present invention, more than 80% of Famotidine is released within 15 minutes, preferably 85 % is released within 15 minutes. In one embodiment of the present invention, the packaging material for an orodispersible tablet of Famotidine is selected from the group consisting of an aluminum foil blister, PVC / aluminum combinations blister, polypropylene bottle with a silica canister, PP bottle with an oxygen scavenger, HDPE bottle, an HDPE bottle with SAF, an HDPE container with a CR cap, HDPE bottle with silica canister, HDPE bottle with an oxygen scavenger, Alu-Alu blister, PVC / PVDC-alu film, aluminum foil strip, polyethylene (pe) strip and polypropylene (pp) strip. In the preferred embodiment of the present invention, an HDPE container with a CR cap and Alu- Alu blister is used as packaging material. In one embodiment of the present invention, the orodispersible tablet of Famotidine is effective in the treatment of duodenal ulcers, benign gastric ulcers, Zollinger-Ellison syndrome, and reflux oesophagitis. In one embodiment of the present invention, the process for preparing the orodispersible tablet of Famotidine by the wet granulation method comprises the following steps: (a) Weighing all raw materials individually; (b) Sieving famotidine or pharmaceutically acceptable salts thereof, spray-dried mannitol, and microcrystalline cellulose through a 40# sieve. Separately sieve cross-linked polyvinylpyrrolidone, sucralose, and raspberry flavor through a 40# sieve, and sieve magnesium stearate separately through a 60# sieve; (c) Dissolving polyvinylpyrrolidone in 50% of the total purified water in a stainless steel container with continuous stirring until a clear viscous solution is obtained; (d) Transferring the previously sifted famotidine, spray-dried mannitol, and microcrystalline cellulose from step (b) into a rapid mixer granulator (RMG); (e) Mixing of step (d) for 15 minutes in the RMG with the impeller at slow speed and the chopper off; (Q Adding binder solution in rapid mixer granulator (RMG) while operating the impeller at slow speed and keeping the chopper off for 5 minutes; continuing to mix the contents for an additional 2 minutes with the impeller at slow speed and the chopper at slow speed, while intermittently adding the remaining quantity of purified water; switching off the impeller and opening the RMG lid, followed by scraping the sides of the RMG and the impeller blades to rake the granulated mass; and discharging the wet mass into a fluid bed dryer bowl by opening the discharge port and operating both the impeller and the chopper at slow speed; (g) Drying the granules from step (f) in a fluidized bed dryer with an inlet temperature of 50°C ±5°C and continuing the drying till LOD is achieved up to 3.0%w / w; (h) Sieving the dried granules from step (g) through a 24# sieve, milling tire retained granules through a 1.5 mm mill screen, and passing the entire blend through a 24# sieve; (i) Transferring previously sifted cross-linked polyvinylpyrrolidone, sucralose, and raspberry flavor adding in a blender with the above blend mix at 12 rpm for 10 minutes; (j) Transferring previously sifted magnesium stearate in a blender and blend for 5 minutes at 12 RPM; and (k) Compressing the resulting mixture into a tablet dosage form. The invention is exemplified by the following examples, which are provided to illustrate the invention and are not intended to restrict its scope. While specific embodiments of the present invention have been described, modifications and equivalents that would be apparent to those skilled in the art are considered to fall within the scope of the present invention. EXAMPLES Example 1: The orodispersible tablet was prepared by dry granulation according to the method described below, using the composition having the ingredients shown in Table I, for a dose strength of 40 mg. Ingredients Quantity (mg / tablet) %w / w Famotidine 40.00 20.00 Spray Dried Mannitol (Particle size-50 to 200 microns) 119.00 59.50 Microcrystalline cellulose (Particle size 15 to 170 pm) 25.00 12.50 Polyvinylpyrrolidone 5.00 2.50 (MW - 40,000 and 60,000 g / mol) Cross-linked Polyvinylpyrrolidone (Particle size: 5-100 microns) 2.00 1.00 Sucralose 5.00 2.50 Raspberry flavor 3.00 1.50 Magnesium Stearate 1.00 0.50 Total 200.00 100.00 Table 1: Composition of Famotidine tablet Manufacturing process: (a) All raw materials were weighed individually. 5 (b) Hie ingredients were sieved separately from step (a), including famotidine. Spray Dried Mannitol, and microcrystalline cellulose through a 40# sieve, sieved cross-linked polyvinylpyrrolidone, sucralose and raspberry flavor separately through a 40# sieve and sieved separately magnesium stearate through 60# sieve, (c) Famotidine, spray dried mannitol, microcrystalline cellulose were transferred 10 into a blender and blend it for 15 minute at 12 RPM. (d) Hie previously sifted Cross-linked Polyvinylpyrrolidone, sucralose and raspberry flavor from step (b) were transferred into the blender and mixed at 12 rpm for 10 minutes. (e) The previously sifted magnesium stearate from step (b) was transferred into the 15 blender and blended for about 5 minutes at 12 RPM. (f) The lubricated blend was compressed into a tablet dosage form. Result Test Parameters of blend Result Bulk Density (gm / ml) 0.296 Tap Density (gm / ml) 0.367 Carr's Index (%) 19.34 Hausner’s Ratio 1.24 Table 2: Result of example 1 tablet formulation As shown in the above table, it was concluded that the physical parameters of the blend were unsatisfactory, and poor blend flow was observed. To optimize blend flow, the manufacturing process changed from dry mixing to wet granulation in 5 Example 2. Example 2: The 40 mg orodispersible tablet w as prepared using the wet granulation method to improve the physical parameters of the blend. Ingredients Quantity (mg / tablet> ■■■ Famotidine 40.00 20.00 Spray Dried Mannitol (Particle size-50 to 200 microns) 119.00 59.50 Microcrystalline cellulose (Particle size 15 to 170 pm) 25.00 12.50 Polyvinylpyrrolidone (MW - 40,000 and 60,000 g / mol) 5.00 2.50 Water Q.s. Q.s. Cross-linked Polyvinylpyrrolidone (Particle size: 5-100 microns) 2.00 1.00 Sucralose 5.00 2.50 Raspberry flavor 3.00 1.50 Magnesium Stearate 1.00 0.50 Total 200.00 100.00 10 Table 3: Composition of Famotidine tab et Manufacturing process: (a) All raw materials were weighed individually. (b) The ingredients were sieved separately from step (a), including famotidine, spray dried mannitol, and microcrystalline cellulose through a 40# sieve, sieved separately Cross-linked Polyvinylpyrrolidone, sucralose and raspberry flavor through 40# sieve and sieved separately magnesium stearate through 60# sieve. (c) Dissolved Polyvinylpyrrolidone in 50 % of total purified water in a stainless steel container with continuous stirring until it gets a clear viscous solution. (d) Transferred previously sifted Famotidine, spray-dried mannitol, and microcrystalline cellulose from step (b) in a rapid mixer granulator. (e) The mixture from step (d) was mixed for 15 minutes in the RMG with the impeller at slow speed and the chopper off. (f) The binder solution was added to the rapid mixer granulator (RMG) while operating the impeller at a slow speed and keeping the chopper off for 5 minutes. The contents were then mixed for an additional 2 minutes with the impeller at a slow speed and the chopper at a slow speed, while intermittently adding the remaining quantity of purified water. Ilie impeller was switched off, the RMG lid was opened, and the sides of the RMG and the impeller blades were scraped to rake the granulated mass. The wet mass was discharged into a fluid bed dryer bowl by opening the discharge port and operating both the impeller and the chopper at a slow speed. (g) The granules from step (f) were dried in a fluidized bed dryer at an inlet temperature of 50°C ±5°C, continuing the drying until the LOD was achieved up to 3.0% w / w. (h) The dried granules from step (g) were sieved through a 24# sieve, and the retained granules were milled through a 1.5 mm mill screen, after which the entire blend was passed through a 24# sieve. (i) The previously sifted Cross-linked Polyvinylpyrrolidone, sucralose, and raspberry flavor were transferred to a blender and mixed with the above blend at 12 RPM for 10 minutes. (j) The previously sifted magnesium stearate was transferred to a blender and blended for 5 minutes at 12 RPM. (k) The resulting mixture was compressed into a tablet dosage form. Conclusion: After performing Example 2, the physical parameters were found to be unsatisfactory, and minor sticking was observed during compression. To resolve the sticking issue, the concentration of the lubricant was increased in 5 further trials. Example 3: The 40 mg orodispersible tablet was prepared using the wet granulation method to achieve acceptable physical properties. Ingredients Quantity (mg / tablet) 111111»» Famotidine 40.00 20.00 Spray Dried Mannitol (Particle size-50 to 200 microns) 117.00 58.50 Microcrystalline cellulose (Particle size 15 to 170 pm) 25.00 12.50 Polyvinylpyrrolidone (MW - 40,000 and 60,000 g / mol) 5.00 2.50 Purified water Q.s. Q.s. Cross-linked Polyvinylpyrrolidone (Particle size: 5-100 microns) 2.00 1.00 Sucralose 5.00 2.50 Raspberiy flavour 3.00 1.50 Magnesium Stearate 3.00 1.50 Total 200.00 100.00 10 Table 5: Composition of Famotidine tablet Manufacturing process: (a) Weighing all raw materials individually; (b) Sieving famotidine or pharmaceutically acceptable salts thereof, spray-dried mannitol, and microcrystalline cellulose through a 40# sieve. Separately sieve Cross-linked Polyvinylpyrrolidone, sucralose, and raspberry flavor through a 40# sieve, and sieve magnesium stearate separately through a 60# sieve; (c) Dissolving Polyvinylpyrrolidone in 50% of the total purified water in a stainless steel container with continuous stirring until a clear viscous solution is obtained; (d) Transferring the previously sifted famotidine, spray-dried mannitol, and microcrystalline cellulose from step (b) into a rapid mixer granulator (RMG); (e) Mixing of step (d) for 15 minutes in the RMG with the impeller at slow speed and the chopper off; (f) Adding binder solution in rapid mixer granulator (RMG) while operating the impeller at slow speed and keeping the chopper off for 5 minutes; continuing to mix the contents for an additional 2 minutes with the impeller at slow speed and the chopper at slow speed, while intermittently adding the remaining quantity of purified water; switching off the impeller and opening the RMG lid, followed by scraping the sides of the RMG and the impeller blades to rake the granulated mass; and discharging the wet mass into a fluid bed dryer bowl by opening the discharge port and operating both the impeller and the chopper at slow speed; (g) Drying the granules from step (f) in a fluidized bed diy er with an inlet temperature of 50°C ±5°C and continuing the drying till LOD is achieved up to 3.0%w / w; (h) Sieving the dried granules from step (g) through a 24# sieve, milling the retained granules through a 1.5 mm mill screen, and passing the entire blend through a 24# sieve; (i) Transferring previously sifted Cross-linked Polyvinylpyrrolidone, sucralose, and raspberry flavor adding in a blender with the above blend mix at 12 rpm for 10 minutes; (j) Transferring previously sifted magnesium stearate in a blender and blend for 5 minutes at 12 RPM; and (k) Compressing the resulting mixture into a tablet dosage form. Conclusion: The physical parameters of the tablets from Example 3 were found to be unsatisfactory, as the disintegration time was more than 3 minutes. To optimize the disintegration time, it was necessary to increase the concentration of the disintegrant. Example 4: The 40 mg orodispersible tablet was prepared using the wet granulation method to achieve acceptable physical parameters. Ingredients Quantity (mg / tablel) %w / w Famotidine 40.00 20.00 Spray Dried Mannitol (Particle size-50 to 200 microns) 113.00 56.50 Microcrystalline cellulose (Particle size 15 to 170 pm) 25.00 12.50 Polyvinylpyrrolidone (MW - 40,000 and 60,000 g / mol) 5.00 2.50 Purified water* Q.s. Q.s. Cross-linked Polyvinylpyrrolidone (Particle size: 5-100 microns) 6.00 3.00 Sucralose 5.00 2.50 Raspberry flavour 3.00 1.50 Magnesium Stearate 3.00 1.50 Total 200.00 100.00 Table 6: Composition of Famotidine tablet 10 Manufacturing process: (a) Weighing all raw materials individually; (b) Sieving famotidine or pharmaceutically acceptable salts thereof, spray-dried mannitol, and microcrystalline cellulose through a 40# sieve. Separately sieve Cross-linked Polyvinylpyrrolidone, sucralose, and raspberry flavor through a 40# sieve, and sieve magnesium stearate separately through a 60# sieve; (c) Dissolving Polyvinylpyrrolidone in 50% of the total purified water in a stainless steel container with continuous stirring until a clear viscous solution is obtained; (d) Transferring the previously sifted famotidine, spray-dried mannitol, and microcrystalline cellulose from step (b) into a rapid mixer granulator (RMG); (e) Mixing of step (d) for 15 minutes in the RMG with the impeller at slow speed and the chopper off; (f) Adding binder solution in rapid mixer granulator (RMG) while operating the impeller at slow speed and keeping the chopper off for 5 minutes; continuing to mix the contents for an additional 2 minutes with the impeller at slow speed and the chopper at slow speed, while intermittently adding the remaining quantity of purified water; switching off the impeller and opening the RMG lid, followed by scraping the sides of the RMG and the impeller blades to rake the granulated mass; and discharging the wet mass into a fluid bed dryer bowl by opening the discharge port and operating both the impeller and the chopper at slow speed; (g) Drying the granules from step (f) in a fluidized bed diy er with an inlet temperature of 50°C ±5°C and continuing the drying till LOD is achieved up to 3.0%w / w; (h) Sieving the dried granules from step (g) through a 24# sieve, milling the retained granules through a 1.5 mm mill screen, and passing the entire blend through a 24# sieve; (i) Transferring previously sifted Cross-linked Polyvinylpyrrolidone, sucralose, and raspberry flavour adding in the blender with the above blend mix at 12 rpm for 10 minutes; (j) Transferring previously sifted magnesium stearate in a blender and blend for 5 minutes at 12 RPM; and (k) Compressing the resulting mixture into a tablet dosage form. Result Test Parameters Result Bulk Density (gm / ml) 0.409 Tap Density (gm / ml) 0.566 Carr’s Index (%) 27.74 Hausner Ratio 1.38 Table 6: Results of the tablet formulation from Example 4 Test Specification Exp.4 (Initial) (After 1 month at io Average weight 200.00 mg ± 7.5% (185.00 - 215.00 mg) 201.5 200.9 Hardness 20Nto70N 46N 44N Thickness 3.09 ± 0.3 mm (2.79 mm - 3.39 mm) 3.10mm 3.08mm Friability NMT 1.0% 0.25% 0.27% Disintegration time NMT 3 Minute 25sec 30sec Assay 95.0% - 105.0% of the labelled amount of Famotidine 101.2 102.4 Dissolution NLT 75% (Q) labelled amount of Famotidine should be dissolve in 45 minutes. 98.0 97.4 Related Substances Impurity C Not more than 0.5% ND ND Impurity D Not more than 0.5% ND ND Impurity F Not more than 0.5% ND ND Impurity 3 Not more than 1.0% ND ND Unspecified impurity Not more than 0.2% 0.1224 0.2121 Total impurities Not more than 2.5% 0.1224 0.2121 ND: Not detected Table 7: Results of the tablet formulation from Example 4 As shown in the above results, it was found that all parameters such as hardness, average weight, thickness, friability, and disintegration meet the specified ranges and provide satisfactory results. Therefore, Example 4 was considered an optimized batch. Further studies, such as stability studies, and dissolution studies were 5 performed on the optimized batch. Example 5: Dissolution data of optimized batch (Example 4) The dissolution study of an orally disintegrating tablet of 40 mg was conducted with the following dissolution condition. Product Name: Famotidine 40 mg orally disintegrating tablet 10 Dissolution Media: 0.1 N HC1, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer Apparatus: Apparatus II (Paddle) Rate of rotation: 50 RPM Volume: 900 ml 15 Temperature: 37±5°C Detection: 275 run Dissolution Famotidine ODT 40 mg Batch no: ORB / S / FAM / 04 Media: 900ml, 50 RPM, paddle Time point 0.1 N HCL pH 4.5 Acetate buffer pH 6.8 Phosphate buffer (min) % Drug Release % RSD % Drug Release % RSD % Drug Release % RSD 10 87.9 1.3 97.4 3.9 91.7 2.7 15 86.3 1.2 97.6 3.8 93.4 2.8 20 74.4 1.1 97.3 3.7 94.3 2.7 30 73.3 0.8 97.6 4.0 94.6 2.5 45 70.1 1.3 97.8 3.8 95.4 2.2 60 67.3 1.4 96.7 1.8 95.3 2.1 Table 8: Dissolution data of reference and test product As shown in the dissolution data, the test product provided more than 85% drug release within 15 minutes in 0.1 N HC1 and more than 90% drug release in both pH 4.5 acetate buffer and pH 6.8 phosphate buffer. The final dissolution medium is the pH 4.5 acetate buffer. Example 5: Stability study The orally disintegrating tablets prepared according to example 4 were subjected to 5 a stability study of 25°C / 60%RH and 40°C / 75%RH for 1, 3, and 6 months. The stability study was performed for the 40 mg dose strength of Famotidine. Results are tabulated below. Parameters Specification Initial iiiim |f|^ iiillll 25°C / 60 |f|^ bibb® |f||^ Hardness 20-70N 46N 47N 44N 46N 45N Dissolution NLT 75% (Q) labelled amount of Famotidine should be dissolve in 45 minutes. 98.0 98.9 99.0 98.8 98.5 Assay (%) 95.0-105.0 % 101.1 98.7 98.8 98.4 99.9 Impurities (%) Impurity C Not more than 0.5% ND ND ND ND ND Impurity D Not more than 0.5% ND ND ND ND ND Impurity' F Not more than 0.5% ND ND ND ND ND Impurity 3 Not more than 1.0% ND ND ND ND ND Unspecified impurity Not more than 0.2% 0.1224 0.1319 0.1540 0.1431 0.1444 Total impurity Not more than 2.5% 0.1224 0.1319 0.1540 0.1431 0.1444 ND* - Not detect Table 9: Stability study of Famotidine ODT 10 As shown in the above stability data, there was not much difference observed in hardness, assay, and dissolution results before, after one month, and after three months and six months of the study, indicating that the famotidine ODT formulation is stable.

Claims

1. An orodispersible tablet of famotidine for oral administration, comprising:a) Famotidine or pharmaceutically acceptable salts thereof, present in an amount ranging from about 10 %w / w to about 30 %w / w, preferably in the range from about 15 %w / w to about 25 %w / w;b) one or more diluents present in the range from about 50 % w / w to about 90 % w / w, preferably from about 60 % w / w to about 80 % w / w;c) at least one disintegrate present in the range from about 0.5 % w / w to about 10 % w / w, preferably from about 1 % w / w to about 5 % w / w;d) at least one lubricant present in the range from about 0.1 %w / w to about 5 %w / w, preferably in the range from about 1 %w / w to about 3 %w / w;e) at least one binder presents in the range from about 0.1 %w / w to about 10 %w / w, preferably in the range from about 1 %w / w to about 5 %w / w; andf) at least one flavoring agent present in the range from about 0.1 %w / w to about 5 %w / w, preferably in the range from about 1 %w / w to about 3 %w / w;g) at least one sweetener presents in the range from about 0.1 %w / w to about 10 %w / w, preferably in the range from about 1 %w / w to about 5 %w / w;h) one or more pharmaceutically acceptable excipients.

2. The orodispersible tablet according to claim 1, wherein the diluent is selected from the group consisting of a calcium carbonate, cellulose derivatives, microcrystalline cellulose, microfine cellulose, sugar alcohols such as maltitol, spray-dried mannitol, sorbitol, com starch, potato starch, hydroxypropyl methylcellulose (HPMC), dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, lactose, starch, dicalcium phosphate dihydrate, dicalcium phosphate anhydrous or any combination thereof.

3. The orodispersible tablet according to claim 2, wherein the diluents comprise a combination of spray-dried mannitol and microcrystalline cellulose.

4. The orodispersible tablet according to claim 3, wherein diluent spray-dried mannitol presents in the range from about 45 %w / w to about 70 %w / w, preferably in the range from about 50 %w / w to about 65 %w / w.

5. The orodispersible tablet according to claim 3, wherein diluent microcrystalline cellulose presents in the range from about 5 %w / w to about 20 %w / w, more preferably in the range from about 10 %w / w to about 15 %w / w.

6. The orodispersible tablet according to claim 1, wherein the disintegrant is selected from the group consisting of alginic acid, guar gum, croscarmellose sodium, carmellose calcium, cross-linked Polyvinylpyrrolidone, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, sodium carboxymethylcellulose (CMC), carboxy methyl cellulose, cross-linked sodium carboxy methylcellulose (Ac-Di-Sol), poloxamer, magnesium aluminum silicate, pregelatinized starch, sodium starch glycolate, microcrystalline cellulose, or any combination thereof.

7. The orodispersible tablet according to claim 6, wherein the disintegrant is crosslinked Polyvinylpyrrolidone.

8. The orodispersible tablet according to claim 1, wherein the lubricant is selected from the group consisting of magnesium stearate, sodium stearyl fumarate, micronized polyoxyethylene glycol, colloidal silicon dioxide, glyceryl behenate, hydrogenated vegetable oils, sodium benzoate, beeswax, polyethylene glycol (PEG), sodium lauryl sulfate, stearic acid, talc, sodium stearate, sodium starch glycolate, calcium stearate, or combinations thereof.

9. The orodispersible tablet according to claim 8, wherein the lubricant is magnesium stearate.

10. The orodispersible tablet according to claim 1, wherein the flavoring agent is selected from the group consisting of raspberry flavor, strawberry flavour, blueberry flavour, caramel flavor, butterscotch flavor, floral fennel flavor, mint powder, vanillin, mint flavor, orange flavor, peppermint oil, spearmint oil or combinations thereof.

11. The orodispersible tablet according to claim 10, wherein the flavoring agent is raspberry flavor.

12. The orodispersible tablet according to claim 1, wherein the binder is selected from the group consisting of starch, pregelatinized starch, sodium alginate, gelatin, acacia polyvinyl pyrrolidone (pvp), polyvinylpyrrolidone, methylcellulose, hydroxy propyl methyl cellulose (hpmc), polymethacrylates, sodium carboxy methyl cellulose, polyethylene glycol (peg) and methylcellulose, hydroxyethylmethyl cellulose, hydroxyethyl cellulose, guar gum or combinations thereof.

13. The orodispersible tablet according to claim 12, wherein the binder is Polyvinylpyrrolidone.

14. The orodispersible tablet according to claim 1, wherein the sweetener is selected from the group consisting of saccharin, aspartame, sucralose, stevioside, acesulfame, xylitol, sucrose, liquid glucose, glycerol, sorbitol, acesulfame potassium, fructose or combinations thereof.

15. The orodispersible tablet according to claim 14, wherein the sweetener is sucralose.

16. The process for preparing an orodispersible tablet by the wet granulation method according to claim 1, comprising the steps of(a) Weighing all raw materials individually;(b) Sieving famotidine or pharmaceutically acceptable salts thereof, spray-dried mannitol, and microcrystalline cellulose through a 40# sieve. Separately sieve Crosslinked Polyvinylpyrrolidone, Sucralose, and raspberry flavor through a 40# sieve, and sieve magnesium stearate separately through a 60# sieve;(c) Dissolving Polyvinylpyrrolidone in 50% of the total purified water in a stainless steel container with continuous stirring until a clear viscous solution is obtained;(d) Transferring the previously sifted famotidine, spray-dried mannitol, and microcrystalline cellulose form step (b) into a rapid mixer granulator (RMG);(e) Mixing of step (d) for 15 minutes in the RMG with the impeller at slow speed and the chopper off;(f) Adding binder solution in rapid mixer granulator (RMG) while operating the impeller at slow speed and keeping the chopper off for 5 minutes; continuing to mix the contents for an additional 2 minutes with the impeller at slow speed and the chopper at slow speed, while intermittently adding the remaining quantity of purified water; switching off the impeller and opening the RMG lid, followed by scraping the sides of the RMG and the impeller blades to rake the granulated mass; and discharging the wet mass into a fluid bed dryer bowl by opening the discharge port and operating both the impeller and the chopper at slow speed;(g) Drying the granules from step (f) in a fluidized bed dryer with an inlet temperature of 50°C ±5°C and continuing the drying till LOD is achieved up to 3.0%w / w;(h) Sieving the dried granules from step (g) through a 24# sieve, milling the retained granules through a 1.5 mm mill screen, and passing the entire blend through a 24# sieve;(i) Transferring previously sifted Cross-linked Polyvinylpyrrolidone, sucralose and raspberry flavour adding in blender with the above blend mix at 12 rpm for 10 minutes;(j) Transferring previously sifted magnesium stearate in a blender and blend for 5 minutes at 12 RPM; and(k) Compressing the resulting mixture into tablet dosage form.

17. The orodispersible tablet according to claim 1, wherein the orally disintegrating tablet is disintegrated in the buccal cavity upon contact with saliva in not more than 3 minutes, preferably less than 60 seconds.

18. The use of orodispersible tablets according to claim 1, for the treatment of duodenal ulcers, benign gastric ulcers, Zollinger-Ellison syndrome, and reflux oesophagitis.

19. The orodispersible tablet according to claim 1, wherein the hardness of the orally disintegrating tablet is between about 20 N to about 60 N, preferably between 40 N to 50 N.

20. The orodispersible tablet according to claim 1, wherein 90 % of the Famotidine or pharmaceutically acceptable salts thereof, is released within 60 minutes, preferably more than 95 % is released within 45 minutes under the condition of 50 RPM and 900 ml pH 4.5 acetate buffer dissolution media.

21. The orodispersible tablet according to claim 1, wherein the packaging material of the container is selected from the group consisting of an aluminum foil blister, PVC / aluminum combinations blister, polypropylene bottle with a silica canister, PP bottle with an oxygen scavenger, HDPE Bottle, an HDPE bottle with SAF, an HDPE container with a CR cap, HDPE bottle with silica canister, HDPE bottle with an oxygen scavenger, Alu-Alu blister, PVC / PVDC-alu film, aluminum foil strip, polyethylene (pe) strip and polypropylene (pp) strip.

22. The orodispersible tablet according to claim 1, wherein said tablet composition comprises:a) 10 %w / w to about 30 %w / w, preferably in the range from about 15 %w / w to about 25 %w / w of famotidine or pharmaceutically acceptable salts thereof;b) combination of spray-dried mannitol, and microcrystalline cellulose present in the range from about 50 % w / w to about 90% w / w, preferably from about 60 % w / w to about 80 % w / w;c) 45 %w / w to about 70 %w / w, preferably in the range from about 50 %w / w to about 65 %w / w of spray-dried mannitol;d) 5 %w / w to about 20 %w / w, more preferably in the range from about 10 %w / w to about 15 %w / w of microcrystalline cellulose;g) 0.5 %w / w to about 10 %w / w, preferably in the range from about 1 %w / w to about 5 %w / w of cross-linked Polyvinylpyrrolidone;h) 0.1 %w / w to about 5 %w / w, preferably in the range from about 1 %w / w to about 3 %w / w of magnesium stearate;i) 0.1 %w / w to about 10 %w / w, preferably in the range from about 1 %w / w to about 5 %w / w of Polyvinylpyrrolidone;j) 0.1 %w / w to about 5 %w / w, preferably in the range from about 1 %w / w to about 3 %w / w of raspberry flavour; andk) 0.1 %w / w to about 10 %w / w, preferably in the range from about 1 %w / w to about 5 %w / w of sucralose.

23. The orodispersible tablet according to claim 1, wherein said tablet composition comprises:a) 20.00 % w / w of famotidine or pharmaceutical-acceptable salts thereof;b) 56.50 % w / w of spray-dried mannitol, and 12.50 % w / w of microcrystalline cellulose as a combination of diluents;c) 3 % w / w of Cross-linked Polyvinylpyrrolidone;d) 2.50 % w / w of Polyvinylpyrrolidone;e) 1.50 % w / w of raspberry flavour;f) 2.50 % w / w of sucralose; andg) 1.50 % w / w of magnesium stearate.34