Stable famotidine calcium magnesium chewable tablet and preparation thereof

Abstract

The invention belongs to the technical field of H2 receptor antagonistic drug preparations, and particularly relates to a stable famotidine calcium magnesium chewable tablet and preparation thereof. The famotidine calcium magnesium chewable tablet is prepared from famotidine, agilawood tetrol, oleic acid, calcium carbonate, magnesium hydroxide, a filling agent, a disintegrating agent, a flavoring agent, a lubricating agent and ethyl alcohol. According to the famotidine calcium-magnesium chewable tablet, the surface of famotidine particles is coated with the agilawood tetrol-oleic acid blend to serve as a protective barrier, the influence of external environmental factors on famotidine is blocked, hydrolysis and oxidation reactions are reduced, and therefore the stability of the famotidine calcium-magnesium chewable tablet is improved.

Description

Technical Field

[0001] The present invention belongs to H 2 The technical field of receptor antagonist drug preparations, specifically relates to a stable famotidine calcium magnesium chewable tablet and its preparation. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Gastric acid is a major component of gastric juice, secreted by gastric parietal cells, and helps digest food and kill bacteria. However, when gastric acid is secreted excessively, it can have adverse effects on the stomach and esophagus. Excessive gastric acid may be caused by a variety of factors, such as improper diet (excessive consumption of spicy, greasy, acidic foods, etc.), excessive mental stress, bad living habits (smoking, alcoholism, staying up late, etc.), and certain stomach diseases (such as gastric ulcers, duodenal ulcers, gastroesophageal reflux disease, etc.).

[0004] Famotidine calcium magnesium is a drug that treats gastrointestinal diseases by adjusting gastric acid secretion. Famotidine calcium magnesium is a calcium and magnesium salt complex of famotidine. Famotidine is an H2 receptor antagonist that can inhibit gastric acid secretion, while calcium and magnesium help regulate the balance of electrolytes in the body and promote gastrointestinal function. It combines the anti-acid effect of famotidine with the electrolyte effect of calcium and magnesium, can effectively relieve the symptoms caused by excessive gastric acid, and has good therapeutic effect and tolerability. Famotidine calcium magnesium is mainly used to treat diseases related to excessive gastric acid, especially for the following diseases: (1) Gastroesophageal reflux disease (GERD): Famotidine calcium magnesium can relieve esophageal reflux symptoms caused by gastric acid by reducing gastric acid secretion. (2) Peptic ulcer: including gastric ulcer and duodenal ulcer, by reducing gastric acid secretion, promote ulcer healing. (3) Functional dyspepsia: In some patients, excessive gastric acid secretion may lead to symptoms of indigestion, such as abdominal distension, stomach pain, belching, etc. Famotidine calcium magnesium helps relieve these symptoms. (4) Gastritis: Inflammation of the gastric mucosa caused by gastric acid. Famotidine calcium magnesium can reduce the irritation of the acidic environment to the gastric mucosa, thereby alleviating the inflammatory response.

[0005] Famotidine calcium magnesium chewable tablets are a dosage form of the drug, especially suitable for patients who need to quickly relieve the symptoms of excessive gastric acid. Unlike traditional tablets or capsules, chewable tablets can dissolve faster in the mouth, quickly release the drug, and provide faster efficacy. However, there are problems with the chemical stability of famotidine and compatibility with magnesium hydroxide.

[0006] The Chinese patent with publication number CN1768744A discloses a method for preparing a composite famotidine chewable tablet, wherein famotidine is mixed evenly with auxiliary materials and pressed into tablets; β-cyclodextrin is used as an isolating agent to wrap the famotidine tablets; calcium carbonate and magnesium hydroxide are mixed evenly with auxiliary materials to form granules, which are coated on the surface of the famotidine tablets and pressed into tablets. The Chinese patent with publication number CN104971073A discloses a method for preparing a famotidine calcium magnesium chewable tablet and its product, wherein famotidine and part of calcium carbonate are used with a gastric soluble coating material to form famotidine and calcium carbonate-containing granules by wet granulation and coating technology; the remaining calcium carbonate and magnesium hydroxide are used with pharmaceutically acceptable auxiliary materials to form calcium carbonate and magnesium hydroxide-containing granules by wet granulation; the famotidine and calcium carbonate-containing granules and the calcium carbonate and magnesium hydroxide-containing granules are added to a feeder respectively, and then pressed into double-layer tablets, so as to obtain famotidine calcium magnesium chewable tablets. The chemical stability of famotidine and its compatibility with magnesium hydroxide were solved by wet granulation coating technology and double-layer tablet isolation technology. Although the isolation technology isolates famotidine from magnesium hydroxide, the impurity content is still high in the accelerated experiment, which poses a considerable safety hazard. Summary of the invention

[0007] In order to overcome the shortcomings of the prior art, the present invention provides a famotidine calcium magnesium chewable tablet with high stability and low impurity content, which is specifically composed of the following ingredients: 20 parts by weight of famotidine, 5 to 15 parts by weight of agarwood tetraol (CAS: 69809-22-9), 2 to 10 parts by weight of oleic acid (CAS: 112-80-1, ≥98.5%), 200 to 500 parts by weight of calcium carbonate, 50 to 150 parts by weight of magnesium hydroxide, 50 to 200 parts by weight of a filler, 5 to 15 parts by weight of a disintegrant, 20 to 120 parts by weight of a flavoring agent, 2 to 6 parts by weight of a lubricant, and an appropriate amount of ethanol.

[0008] Furthermore, the filler is selected from one or more of starch, microcrystalline cellulose, dextrin, mannitol, and lactose; the disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose; the flavoring agent is selected from one or more of sucrose, glucose, aspartame, and steviol glycosides; the lubricant is selected from one or more of magnesium stearate, micro-powdered silica gel, and talc.

[0009] The preparation method of famotidine calcium magnesium chewable tablets comprises the following steps:

[0010] A. Dissolve oleic acid in an appropriate amount of ethanol to form a uniform solution, and evaporate the solution to 1 / 2 volume in a water bath at 35°C±5°C, add an ethanol solution containing agarwood tetraol, and continue to evaporate the solution until the mass of the remaining solution is 1.5 to 3.0 times that of famotidine, thereby obtaining an agarwood tetraol-oleic acid blend;

[0011] B. Famotidine is mixed with 1 / 3 to 2 / 3 parts by weight of a filler and an appropriate amount of ethanol, wet granulated, granulated, dried, and evenly coated on the surface with the agarwood tetraol-oleic acid blend of step (1), dried, and famotidine particles are obtained for later use; the phenolic hydroxyl groups in the agarwood tetraol molecules and the carboxyl groups in the oleic acid can form hydrogen bonds to interact with each other, and the hydrophilicity of the agarwood tetraol and the hydrophobicity of the oleic acid can be combined into a complex or a mixture.

[0012] C. Mixing calcium carbonate, magnesium hydroxide and the remaining filler, adding an appropriate amount of ethanol, wet granulating, granulating, drying, and obtaining calcium carbonate-magnesium hydroxide particles for later use;

[0013] D. Evenly mix the calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant and lubricant, and press into tablets to obtain the product.

[0014] It should be noted that the ethanol mentioned in the present invention is anhydrous ethanol. In step A, the purpose of ethanol is a solvent, the purpose is to dissolve oleic acid and agarwood tetraol, and the solvent needs to be removed by rotary evaporation later. Therefore, the amount of solvent ethanol is appropriate, which belongs to the routine skills of those skilled in the art. The purpose of ethanol in steps B and C is a wetting agent, that is, it acts to improve the wettability of the particles, improve the fluidity and compressibility of the particles, control the particle size and morphology, and wet the auxiliary materials for further granulation. The amount is also appropriate, which belongs to the basic skills of those skilled in the art.

[0015] Compared with the prior art, the technical effects of the present invention are:

[0016] Famotidine molecules are prone to oxidation, hydrolysis and other reactions under certain conditions, resulting in the generation of impurities. The present invention uses agarwood tetraol and oleic acid to make a protective barrier, which is sprayed on the surface of famotidine particles to block the influence of external environmental factors on famotidine, prevent moisture and oxygen from contacting famotidine, reduce the occurrence of hydrolysis and oxidation reactions, and thus improve the stability of famotidine. Accelerated tests have shown that the active ingredient content of the famotidine calcium magnesium chewable tablets of the present invention is stable, the content of related substances is low, and the medication safety is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 : Impurity Ι structural formula.

[0018] Figure 2 : Impurity II structural formula.

[0019] Figure 3 : Changes of impurity Ι content in famotidine calcium magnesium chewable tablets in accelerated test.

[0020] Figure 4 : Changes of impurity II content in famotidine calcium magnesium chewable tablets in accelerated test. DETAILED DESCRIPTION

[0021] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0022] Example 1 Stable Famotidine Calcium Magnesium Chewable Tablets

[0023] formula:

[0024]

[0025] Preparation method:

[0026] A. Dissolve oleic acid in an appropriate amount of ethanol to form a uniform solution, and evaporate the solution to 1 / 2 volume in a 35°C water bath, add an ethanol solution containing agarwood tetraol, and continue to evaporate the solution until the mass of the remaining solution is twice that of famotidine, thereby obtaining an agarwood tetraol-oleic acid blend;

[0027] B. After sieving famotidine, add 1 / 2 weight portion of filler and appropriate amount of ethanol, wet granulate, shape the granules, dry, and evenly spray the agarwood tetraol-oleic acid blend in step (1) on the surface, dry, and obtain famotidine granules for later use;

[0028] C. Mixing calcium carbonate, magnesium hydroxide and the remaining filler, adding an appropriate amount of ethanol, wet granulating, granulating, drying, and obtaining calcium carbonate-magnesium hydroxide particles for later use;

[0029] D. Evenly mix the calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant and lubricant, and press into tablets to obtain the product.

[0030] Example 2 Stable Famotidine Calcium Magnesium Chewable Tablets

[0031] formula:

[0032]

[0033] Preparation method:

[0034] A. Dissolve oleic acid in an appropriate amount of ethanol to form a uniform solution, and evaporate it in a 30°C water bath to 1 / 2 volume, add an ethanol solution containing agarwood tetraol, and continue to evaporate until the mass of the remaining solution is 1.5 times that of famotidine, to obtain an agarwood tetraol-oleic acid blend;

[0035] B. After sieving famotidine, add 1 / 3 weight portion of filler and appropriate amount of ethanol, wet granulate, shape the granules, dry, and evenly spray the agarwood tetraol-oleic acid blend in step (1) on the surface, dry, and obtain famotidine granules for later use;

[0036] C. Mixing calcium carbonate, magnesium hydroxide and the remaining filler, adding an appropriate amount of ethanol, wet granulating, granulating, drying, and obtaining calcium carbonate-magnesium hydroxide particles for later use;

[0037] D. Evenly mix the calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant and lubricant, and press into tablets to obtain the product.

[0038] Example 3 Stable Famotidine Calcium Magnesium Chewable Tablets

[0039] formula:

[0040]

[0041] Preparation method:

[0042] A. Dissolve oleic acid in an appropriate amount of ethanol to form a uniform solution, and evaporate the solution to 1 / 2 volume in a 40°C water bath, add an ethanol solution containing agarwood tetraol, and continue to evaporate the solution until the mass of the remaining solution is 3.0 times that of famotidine, thereby obtaining an agarwood tetraol-oleic acid blend;

[0043] B. After sieving famotidine, add 2 / 3 weight parts of filler and appropriate amount of ethanol, wet granulate, shape the granules, dry, and evenly spray the agarwood tetraol-oleic acid blend in step (1) on the surface, dry, and obtain famotidine granules for later use;

[0044] C. Mixing calcium carbonate, magnesium hydroxide and the remaining filler, adding an appropriate amount of ethanol, wet granulating, granulating, drying, and obtaining calcium carbonate-magnesium hydroxide particles for later use;

[0045] D. Evenly mix the calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant and lubricant, and press into tablets to obtain the product.

[0046] Comparative Example 1 Stable Famotidine Calcium Magnesium Chewable Tablets

[0047] formula:

[0048]

[0049]

[0050] Preparation method:

[0051] A. Dissolve oleic acid in an appropriate amount of ethanol to form a uniform solution, and evaporate in a water bath at 35°C until the mass of the remaining solution is twice that of famotidine to obtain an agarwood tetraol-ethanol blend;

[0052] B. After sieving famotidine, add 1 / 2 weight portion of filler and appropriate amount of ethanol, wet granulate, shape the granules, dry, and evenly spray the agarwood tetraol-ethanol blend in step (1) on the surface, dry, and obtain famotidine granules for later use;

[0053] C. Mixing calcium carbonate, magnesium hydroxide and the remaining filler, adding an appropriate amount of ethanol, wet granulating, granulating, drying, and obtaining calcium carbonate-magnesium hydroxide particles for later use;

[0054] D. Evenly mix the calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant and lubricant, and press into tablets to obtain the product.

[0055] Comparative Example 2 Stable Famotidine Calcium Magnesium Chewable Tablets

[0056] formula:

[0057]

[0058]

[0059] Preparation method:

[0060] A. Dissolve agarwood tetraol in an appropriate amount of ethanol to form a uniform solution, and evaporate in a water bath at 35°C until the mass of the remaining solution is twice that of famotidine to obtain an oleic acid-ethanol blend;

[0061] B. After sieving famotidine, add 1 / 2 weight portion of filler and appropriate amount of ethanol, wet granulate, shape the granules, dry, and evenly spray the surface with the oleic acid-ethanol blend of step (1), dry, and obtain famotidine granules for later use;

[0062] C. Mixing calcium carbonate, magnesium hydroxide and the remaining filler, adding an appropriate amount of ethanol, wet granulating, granulating, drying, and obtaining calcium carbonate-magnesium hydroxide particles for later use;

[0063] D. Evenly mix the calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant and lubricant, and press into tablets to obtain the product.

[0064] Comparative Example 3: Stable Famotidine Calcium Magnesium Chewable Tablets

[0065] formula:

[0066]

[0067]

[0068] Preparation method:

[0069] A. Dissolve oleic acid in an appropriate amount of ethanol to form a uniform solution, and evaporate the solution to 1 / 2 volume in a 35°C water bath, add an ethanol solution containing agarwood tetraol, and continue to evaporate the solution until the mass of the remaining solution is twice that of famotidine, thereby obtaining an agarwood tetraol-oleic acid blend;

[0070] B. After sieving famotidine, add 1 / 2 weight portion of filler and appropriate amount of ethanol, wet granulate, shape the granules, dry, and evenly spray the agarwood tetraol-oleic acid blend in step (1) on the surface, dry, and obtain famotidine granules for later use;

[0071] C. Mixing calcium carbonate, magnesium hydroxide and the remaining filler, adding an appropriate amount of ethanol, wet granulating, granulating, drying, and obtaining calcium carbonate-magnesium hydroxide particles for later use;

[0072] D. Evenly mix the calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant and lubricant, and press into tablets to obtain the product.

[0073] Comparative Example 4: Stable Famotidine Calcium Magnesium Chewable Tablets

[0074] formula:

[0075]

[0076] Preparation method:

[0077] A. Dissolve palmitoleic acid in an appropriate amount of ethanol to form a uniform solution, and evaporate it in a water bath at 35°C to 1 / 2 volume. Add an ethanol solution containing agarwood tetraol, and continue to evaporate until the mass of the remaining solution is twice that of famotidine, thereby obtaining an agarwood tetraol-palmitoleic acid blend;

[0078] B. After sieving famotidine, add 1 / 2 weight portion of filler and appropriate amount of ethanol, wet granulate, shape the granules, dry, and evenly spray the agarwood tetraol-palmitoleic acid blend in step (1) on the surface, dry, and obtain famotidine granules for later use;

[0079] C. Mixing calcium carbonate, magnesium hydroxide and the remaining filler, adding an appropriate amount of ethanol, wet granulating, granulating, drying, and obtaining calcium carbonate-magnesium hydroxide particles for later use;

[0080] D. Evenly mix the calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant and lubricant, and press into tablets to obtain the product.

[0081] Comparative Example 5: Stable Famotidine Calcium Magnesium Chewable Tablets

[0082] formula:

[0083]

[0084] Preparation method:

[0085] A. dissolving oleic acid and agarwood tetraol in an appropriate amount of ethanol to form an agarwood tetraol-oleic acid blend with a mass twice that of famotidine;

[0086] B. After sieving famotidine, add 1 / 2 weight portion of filler and appropriate amount of ethanol, wet granulate, shape the granules, dry, and evenly spray the agarwood tetraol-oleic acid blend in step (1) on the surface, dry, and obtain famotidine granules for later use;

[0087] C. Mixing calcium carbonate, magnesium hydroxide and the remaining filler, adding an appropriate amount of ethanol, wet granulating, granulating, drying, and obtaining calcium carbonate-magnesium hydroxide particles for later use;

[0088] D. Evenly mix the calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant and lubricant, and press into tablets to obtain the product.

[0089] Comparative Example 6 Famotidine calcium magnesium chewable tablets

[0090] Famotidine calcium magnesium chewable tablets available on the market: National Medicine Approval No. H20052502

[0091] Accelerated test to verify the stability of famotidine calcium magnesium chewable tablets

[0092] Accelerated test: Famotidine calcium magnesium chewable tablets of Examples 1 to 3 and famotidine calcium magnesium chewable tablets of Comparative Examples 1 to 6 were packaged as commercially available and placed at a temperature of 40±2°C and a relative humidity of 75%±5% for 6 months. Samples were taken during the test to detect the contents of related substances, famotidine, calcium carbonate and magnesium hydroxide.

[0093] The related substances of famotidine are determined according to the HPLC method (General Rule 0512) of the 2020 edition of the Chinese Pharmacopoeia. Solvent: Take 13.6g of sodium dihydrogen phosphate, place it in 900ml of water, adjust the pH to 7.0±0.1 with 1mol / L sodium hydroxide solution, add water to 1000ml, mix well, take 930ml and mix with 70ml of acetonitrile. Test solution: Take this product, add an appropriate amount of methanol to dissolve, and dilute with solvent to make a solution containing about 0.5mg of famotidine per 1ml. Control solution: Accurately measure an appropriate amount of the test solution and quantitatively dilute with solvent to make a solution containing about 5μg per 1ml. System suitability solution: Take about 25 mg of famotidine, add 2 ml of acetonitrile and 2 ml of solvent to dissolve, add 3 ml of 0.5 mol / L hydrochloric acid solution, heat in a water bath at 40°C for 5 minutes, add 3 ml of 0.5 mol / L sodium hydroxide solution, add 5 ml of 1 mol / L sodium hydroxide solution, heat in a water bath at 60°C for 5 minutes, add 5 ml of 1 mol / L hydrochloric acid solution, and dilute with solvent to make a solution containing about 0.5 mg per 1 ml. Chromatographic conditions: octadecylsilane bonded silica gel is used as filler (Kromasil C18, 4.6 mm × 250 mm, 5 μm or a chromatographic column with equivalent performance); acetate buffer (13.6 g of sodium acetate is placed in 900 ml of water, the pH value is adjusted to 6.0 ± 1.0 with glacial acetic acid, and water is added to 1000 ml)-acetonitrile (93:7) is used as mobile phase A, acetonitrile is used as mobile phase B, and gradient elution is performed according to the table below, with a flow rate of 1.5 ml per minute; the detection wavelength is 270 nm; the column temperature is 35°C; the injection volume is 20 μl.

[0094] Table 1 Elution program

[0095]

[0096]

[0097] System suitability requirements: Adjust the proportion of mobile phase so that the retention time of the famotidine peak in the system suitability solution chromatogram is about 10 minutes, and the retention time of the impurity I peak and the impurity II peak relative to the famotidine peak is about 0.7 and 1.2. The number of theoretical plates calculated based on the famotidine peak is not less than 5000. The separation between the famotidine peak and the adjacent impurity peak should meet the requirements. Determination method: Accurately measure the test solution and the control solution, inject them into the liquid chromatograph respectively, and record the chromatogram. Limit: If there are impurity peaks in the chromatogram of the test solution, the area of ​​a single impurity peak shall not be greater than 0.3 times (0.3%) the area of ​​the main peak of the control solution, and the sum of the areas of each impurity peak shall not be greater than the main peak area of ​​the control solution (1.0%).

[0098] Figure 3 To accelerate the change of impurity Ⅰ content in famotidine calcium magnesium chewable tablets. Figure 4The change of the impurity II content of the famotidine calcium magnesium chewable tablets in the accelerated test shows that the famotidine calcium magnesium chewable tablets of Examples 1 to 3 of the present invention have high stability, and the content of impurities I and impurities II increases at a low rate under high temperature and high humidity conditions.

[0099] Table 2 Stability study of famotidine calcium magnesium chewable tablets

[0100]

[0101]

[0102] Table 2 shows that the content of active ingredients in the famotidine calcium magnesium chewable tablets of the present invention is stable, the content of related substances is low, and the agarwood tetraol-oleic acid blend forms a protective barrier around famotidine, blocking the influence of external environmental factors on famotidine, reducing the occurrence of hydrolysis and oxidation reactions, thereby improving the stability of famotidine.

Claims

1. A stable famotidine calcium magnesium chewable tablet, characterized in that: The stable famotidine calcium magnesium chewable tablet is composed of the following ingredients: 20 parts by weight of famotidine, 5-15 parts by weight of agarwood tetraol, 2-10 parts by weight of oleic acid, 200-500 parts by weight of calcium carbonate, 50-150 parts by weight of magnesium hydroxide, 50-200 parts by weight of filler, 5-15 parts by weight of disintegrant, 20-120 parts by weight of flavoring agent, 2-6 parts by weight of lubricant, and an appropriate amount of ethanol; The preparation method of the stable famotidine calcium magnesium chewable tablets comprises the following steps: A. Dissolve oleic acid in an appropriate amount of ethanol to form a uniform solution, and evaporate the solution to 1 / 2 volume in a water bath at 35°C±5°C, add an ethanol solution containing agarwood tetraol, and continue to evaporate the solution until the mass of the remaining solution is 1.5 to 3.0 times that of famotidine, thereby obtaining an agarwood tetraol-oleic acid blend; B. Famotidine is mixed with 1 / 3 to 2 / 3 parts by weight of a filler and an appropriate amount of ethanol, wet granulated, granulated, dried, and evenly coated on the surface with the agarwood tetraol-oleic acid blend of step (1), dried, to obtain famotidine granules for later use; C. Mixing calcium carbonate, magnesium hydroxide and the remaining filler, adding an appropriate amount of ethanol, wet granulating, granulating, drying, and obtaining calcium carbonate-magnesium hydroxide particles for later use; D. Evenly mix the calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant and lubricant, and press into tablets to obtain the product.

2. The stable famotidine calcium magnesium chewable tablet according to claim 1, characterized in that The filler is selected from one or more of starch, microcrystalline cellulose, dextrin, mannitol and lactose.

3. The stable famotidine calcium magnesium chewable tablet according to claim 1, characterized in that The disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose.

4. The stable famotidine calcium magnesium chewable tablet according to claim 1, characterized in that The flavoring agent is selected from one or more of sucrose, glucose, aspartame and steviol glycoside.

5. The stable famotidine calcium magnesium chewable tablet according to claim 1, characterized in that The lubricant is selected from one or more of magnesium stearate, micro powder silica gel and talc.

6. The stable famotidine calcium magnesium chewable tablet according to claim 2, characterized in that: The filler is starch or dextrin.

7. The stable famotidine calcium magnesium chewable tablet according to claim 3, characterized in that: The disintegrant is low-substituted hydroxypropyl cellulose.

8. The stable famotidine calcium magnesium chewable tablet according to claim 4, characterized in that: The flavor correctives are sucrose and aspartame.

9. The stable famotidine calcium magnesium chewable tablet according to claim 5, characterized in that: The lubricant is magnesium stearate.

10. The stable famotidine calcium magnesium chewable tablet according to claim 1, characterized in that: The stable famotidine calcium magnesium chewable tablets are composed of the following ingredients: 20 parts by weight of famotidine, 10 parts by weight of agarwood tetraol, 5 parts by weight of oleic acid, 400 parts by weight of calcium carbonate, 100 parts by weight of magnesium hydroxide, 100 parts by weight of starch, 20 parts by weight of dextrin, 8 parts by weight of low-substituted hydroxypropyl cellulose, 45 parts by weight of sucrose, 5 parts by weight of aspartame, 4 parts by weight of magnesium stearate, and an appropriate amount of ethanol.

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