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 the technical field of H2 receptor antagonist pharmaceutical preparations, and particularly relates to a stable calcium magnesium famotidine chewable tablet and its preparation. Background Art

[0002] Disclosing the information of this background art section is only intended to increase the understanding of the overall background of the present invention, and is not necessarily regarded as an admission or an implication in any form that this information constitutes the prior art already known to those of ordinary skill in the art.

[0003] Gastric acid is a main component in gastric juice, secreted by gastric parietal cells, and has functions such as helping to digest food and killing bacteria. However, when gastric acid secretion is excessive, it will cause adverse effects on the stomach, esophagus and other parts. Excessive gastric acid may be caused by various factors, such as improper diet (overeating spicy, greasy, acidic foods, etc.), excessive mental stress, bad living habits (smoking, alcoholism, staying up late, etc.) and certain gastric diseases (such as gastric ulcer, duodenal ulcer, gastroesophageal reflux disease, etc.).

[0004] Calcium magnesium famotidine is a drug for treating gastrointestinal-related diseases by adjusting gastric acid secretion. Calcium magnesium famotidine 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 antacid effect of famotidine and the electrolyte effects of calcium and magnesium, can effectively relieve the symptoms caused by excessive gastric acid, and has good therapeutic effects and tolerability. Calcium magnesium famotidine is mainly used to treat diseases related to excessive gastric acid, especially suitable for the following diseases: (1) Gastroesophageal reflux disease (GERD): Calcium magnesium famotidine 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, promoting ulcer healing. (3) Functional dyspepsia: In some patients, excessive gastric acid secretion may cause symptoms of dyspepsia, such as abdominal distension, stomachache, belching, etc., and calcium magnesium famotidine helps relieve these symptoms. (4) Gastritis: Gastric mucosal inflammation caused by gastric acid, and calcium magnesium famotidine can reduce the irritation of the acidic environment to the gastric mucosa, thereby relieving the inflammatory reaction.

[0005] Calcium magnesium famotidine chewable tablet is a dosage form of this drug, which is particularly suitable for patients who need to quickly relieve symptoms of excessive gastric acid. Different from traditional tablets or capsules, chewable tablets can dissolve faster in the mouth, quickly release the drug, and provide faster curative effects. However, there are problems with the chemical stability of famotidine and the compatibility with magnesium hydroxide.

[0006] The Chinese patent with the publication number CN1768744A discloses a method for preparing compound famotidine chewable tablets. Famotidine is uniformly mixed with excipients and pressed into tablets. The famotidine tablets are wrapped with β-cyclodextrin as an isolating agent. Calcium carbonate and magnesium hydroxide are uniformly mixed with excipients to form granules, which are coated on the surface of the famotidine tablets and then pressed into tablets. The Chinese patent with the publication number CN104971073A discloses a method for preparing famotidine calcium magnesium chewable tablets and its products. Famotidine and part of calcium carbonate are made into granules containing famotidine and calcium carbonate by wet granulation coating technology with a gastric-soluble coating material. The remaining calcium carbonate and magnesium hydroxide are made into granules containing calcium carbonate and magnesium hydroxide by wet granulation with pharmaceutically acceptable excipients. The granules containing famotidine and calcium carbonate and the granules containing calcium carbonate and magnesium hydroxide are respectively added into a feeder and then pressed into bilayer tablets, namely the famotidine calcium magnesium chewable tablets. The problems of the chemical stability of famotidine and its compatibility with magnesium hydroxide are solved by wet granulation coating technology and bilayer tablet isolation technology. Although the isolation technology isolates famotidine from magnesium hydroxide, the content of impurities is still relatively high in the accelerated experiment, posing a certain safety hazard. Summary of the Invention

[0007] To overcome the deficiencies of the prior art, the present invention provides a famotidine calcium magnesium chewable tablet with high stability and low impurity content, which specifically consists of the following components: 20 parts by weight of famotidine, 5 - 15 parts by weight of costunolide (CAS: 69809-22-9), 2 - 10 parts by weight of oleic acid (CAS: 112-80-1, ≥98.5%), 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.

[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 crospovidone, sodium carboxymethyl starch, cross-linked carboxymethyl cellulose sodium, and low-substituted hydroxypropyl cellulose; the flavoring agent is selected from one or more of sucrose, glucose, aspartame, and stevioside; the lubricant is selected from one or more of magnesium stearate, colloidal silicon dioxide, and talc powder.

[0009] The preparation method of the famotidine calcium magnesium chewable tablet includes the following steps:

[0010] A. Dissolve oleic acid in an appropriate amount of ethanol to form a uniform solution, rotary evaporate it in a water bath at 35°C ± 5°C until it reaches 1 / 2 volume, add the ethanol solution containing costunolide, and continue rotary evaporation until the mass of the remaining solution is 1.5 - 3.0 times that of famotidine to obtain a costunolide-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, granulated by wet method, sized, dried, and the blend of khellactone - oleic acid in step (1) is evenly sprayed on the surface, and then dried to obtain famotidine granules for standby; the phenolic hydroxyl group in the khellactone molecule and the carboxyl group in the oleic acid will form a hydrogen bond interaction, and the hydrophilicity of khellactone and the hydrophobicity of oleic acid can combine into a complex or a mixture.

[0012] C. Calcium carbonate and magnesium hydroxide are mixed with the remaining filler, an appropriate amount of ethanol is added, granulated by wet method, sized, and dried to obtain calcium carbonate - magnesium hydroxide granules for standby;

[0013] D. The calcium carbonate - magnesium hydroxide granules, famotidine granules are mixed evenly with a disintegrant, a lubricant, and a flavoring agent, and then compressed 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 use of ethanol is as a solvent, and the purpose is to dissolve oleic acid and khellactone. Subsequently, the solvent needs to be removed by rotary evaporation. Therefore, the amount of the solvent ethanol is appropriate, which belongs to the conventional skills of those skilled in the art. In steps B and C, the use of ethanol is as a wetting agent, that is, its functions are to improve the wettability of the granules, improve the fluidity and compressibility of the granules, control the particle size and morphology, and wet the excipients for further granulation. The amount used is also appropriate, which belongs to the basic skills of those skilled in the art.

[0015] Compared with the prior art, the technical effect of the present invention is as follows:

[0016] The famotidine molecule is prone to oxidation, hydrolysis and other reactions under certain conditions, resulting in the generation of impurities. The present invention uses khellactone and oleic acid to form a protective barrier, which is sprayed on the surface of the famotidine granules, can block the influence of external environmental factors on famotidine, prevent water and oxygen from contacting famotidine, reduce the occurrence of hydrolysis and oxidation reactions, and thus improve the stability of famotidine. The accelerated test proves that the content of the active ingredient in the famotidine calcium and magnesium chewable tablets of the present invention is stable, the content of related substances is low, and the drug safety is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 : Structural formula of impurity Ι.

[0018] Figure 2 : Structural formula of impurity ΙΙ.

[0019] Figure 3 : Change of impurity Ι content in the famotidine calcium and magnesium chewable tablets during the accelerated test.

[0020] Figure 4 : Change of impurity ΙΙ content in the famotidine calcium and magnesium chewable tablets during the accelerated test. DETAILED DESCRIPTION OF THE INVENTION

[0021] In order to make the objectives and technical solutions of the present invention more clear and understandable, the following provides further descriptions of the present invention in combination with embodiments. However, the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. Those skilled in the art should understand 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] Formulation:

[0024]

[0025] Preparation method:

[0026] A. Dissolve oleic acid in 50 ml of ethanol to form a uniform solution. Rotavapor it in a 35°C water bath until it reaches 1 / 2 of its volume. Add an ethanol solution containing asarotetraol, and continue rotavaporizing until the remaining solution mass is twice that of famotidine to obtain an asarotetraol-oleic acid blend.

[0027] B. After sieving famotidine, add 1 / 2 part by weight of a filler and an appropriate amount of ethanol. Granulate by wet method, size the granules, dry them, and uniformly spray the asarotetraol-oleic acid blend obtained in step (1) on the surface, then dry to obtain famotidine granules for standby.

[0028] C. Mix calcium carbonate, magnesium hydroxide with the remaining filler, add an appropriate amount of ethanol, granulate by wet method, size the granules, dry them to obtain calcium carbonate-magnesium hydroxide granules for standby.

[0029] D. Mix the calcium carbonate-magnesium hydroxide granules, famotidine granules with a disintegrant, a lubricant, and a flavoring agent evenly, and press tablets to obtain the product.

[0030] Example 2: Stable Famotidine Calcium Magnesium Chewable Tablets

[0031] Formulation:

[0032]

[0033] Preparation method:

[0034] A. Dissolve oleic acid in 30 ml of ethanol to form a uniform solution. Rotavapor it in a 30°C water bath until it reaches 1 / 2 of its volume. Add an ethanol solution containing asarotetraol, and continue rotavaporizing until the remaining solution mass is 1.5 times that of famotidine to obtain an asarotetraol-oleic acid blend.

[0035] B. After screening famotidine, add 1 / 3 part by weight of filler and an appropriate amount of ethanol, granulate by wet method, size the granules, dry, uniformly spray the mixture of 10 - hydroxyagarotetrol - oleic acid obtained in step (1) on the surface, and dry to obtain famotidine granules for standby;

[0036] C. Mix calcium carbonate, magnesium hydroxide with the remaining filler, add an appropriate amount of ethanol, granulate by wet method, size the granules, dry to obtain calcium carbonate - magnesium hydroxide granules for standby;

[0037] D. Mix the calcium carbonate - magnesium hydroxide granules, famotidine granules with a disintegrant, a lubricant, and a flavoring agent uniformly, and press into tablets to obtain the product.

[0038] Example 3 Stable Calcium Magnesium Famotidine Chewable Tablets

[0039] Formulation:

[0040]

[0041] Preparation method:

[0042] A. Dissolve oleic acid in 70 ml of ethanol to form a uniform solution, rotary evaporate in a 40 °C water bath until the volume is reduced to 1 / 2, add the ethanol solution containing 10 - hydroxyagarotetrol, and continue rotary evaporation until the mass of the remaining solution is 3.0 times that of famotidine to obtain the 10 - hydroxyagarotetrol - oleic acid mixture;

[0043] B. After screening famotidine, add 2 / 3 part by weight of filler and an appropriate amount of ethanol, granulate by wet method, size the granules, dry, uniformly spray the mixture of 10 - hydroxyagarotetrol - oleic acid obtained in step (1) on the surface, and dry to obtain famotidine granules for standby;

[0044] C. Mix calcium carbonate, magnesium hydroxide with the remaining filler, add an appropriate amount of ethanol, granulate by wet method, size the granules, dry to obtain calcium carbonate - magnesium hydroxide granules for standby;

[0045] D. Mix the calcium carbonate - magnesium hydroxide granules, famotidine granules with a disintegrant, a lubricant, and a flavoring agent uniformly, and press into tablets to obtain the product.

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

[0047] Formulation:

[0048]

[0049]

[0050] Preparation method:

[0051] A. Dissolve oleic acid in 50 ml of ethanol to form a uniform solution, rotary evaporate in a 35 °C water bath until the mass of the remaining solution is 2 times that of famotidine to obtain the mixture;

[0052] B. After screening famotidine, add 1 / 2 part by weight of filler and an appropriate amount of ethanol, granulate by wet method, size the granules, dry, uniformly spray the blend in step (1) on the surface, and dry to obtain famotidine granules for standby;

[0053] C. Mix calcium carbonate and magnesium hydroxide with the remaining filler, add an appropriate amount of ethanol, granulate by wet method, size the granules, dry to obtain calcium carbonate - magnesium hydroxide granules for standby;

[0054] D. Mix the calcium carbonate - magnesium hydroxide granules, famotidine granules with the disintegrant, lubricant, and flavoring agent evenly, and press tablets to obtain the tablets.

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

[0056] Formulation:

[0057]

[0058]

[0059] Preparation method:

[0060] A. Dissolve sesaminol in 50 ml of ethanol to form a uniform solution, and rotary evaporate in a 35°C water bath until the mass of the remaining solution is twice that of famotidine to obtain a blend;

[0061] B. After screening famotidine, add 1 / 2 part by weight of filler and an appropriate amount of ethanol, granulate by wet method, size the granules, dry, uniformly spray the blend in step (1) on the surface, and dry to obtain famotidine granules for standby;

[0062] C. Mix calcium carbonate and magnesium hydroxide with the remaining filler, add an appropriate amount of ethanol, granulate by wet method, size the granules, dry to obtain calcium carbonate - magnesium hydroxide granules for standby;

[0063] D. Mix the calcium carbonate - magnesium hydroxide granules, famotidine granules with the disintegrant, lubricant, and flavoring agent evenly, and press tablets to obtain the tablets.

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

[0065] Formulation:

[0066]

[0067] Preparation method:

[0068] A. Dissolve oleic acid in 50 ml of ethanol to form a uniform solution, rotary evaporate in a 35°C water bath to 1 / 2 volume, add the ethanol solution containing sesaminol, and continue rotary evaporation until the mass of the remaining solution is twice that of famotidine to obtain a sesaminol - oleic acid blend;

[0069] After famotidine is sieved, 1 / 2 part by weight of filler and an appropriate amount of ethanol are added, granulated by wet method, sized, dried, and the mixture of asiaticoside - oleic acid in step (1) is evenly sprayed on the surface, then dried to obtain famotidine granules for standby;

[0070] Calcium carbonate, magnesium hydroxide and the remaining filler are mixed, an appropriate amount of ethanol is added, granulated by wet method, sized, dried to obtain calcium carbonate - magnesium hydroxide granules for standby;

[0071] The calcium carbonate - magnesium hydroxide granules, famotidine granules, disintegrant, lubricant and flavoring agent are mixed evenly and then pressed into tablets to obtain the product.

[0072] Comparative Example 4 Stable Calcium Magnesium Famotidine Chewable Tablets

[0073] Formula:

[0074]

[0075] Preparation method:

[0076] Palmitoleic acid is dissolved in 50 ml of ethanol to form a homogeneous solution, which is rotary evaporated in a 35 °C water bath to 1 / 2 volume, then the ethanol solution containing asiaticoside is added, and rotary evaporation is continued until the mass of the remaining solution is twice that of famotidine to obtain asiaticoside - palmitoleic acid blend;

[0077] After famotidine is sieved, 1 / 2 part by weight of filler and an appropriate amount of ethanol are added, granulated by wet method, sized, dried, and the asiaticoside - palmitoleic acid blend in step (1) is evenly sprayed on the surface, then dried to obtain famotidine granules for standby;

[0078] Calcium carbonate, magnesium hydroxide and the remaining filler are mixed, an appropriate amount of ethanol is added, granulated by wet method, sized, dried to obtain calcium carbonate - magnesium hydroxide granules for standby;

[0079] The calcium carbonate - magnesium hydroxide granules, famotidine granules, disintegrant, lubricant and flavoring agent are mixed evenly and then pressed into tablets to obtain the product.

[0080] Comparative Example 5 Stable Calcium Magnesium Famotidine Chewable Tablets

[0081] Formula:

[0082]

[0083] Preparation method:

[0084] Oleic acid and asiaticoside are dissolved in 50 ml of ethanol to form an asiaticoside - oleic acid blend with a mass twice that of famotidine;

[0085] After famotidine is sieved, 1 / 2 part by weight of a filler and an appropriate amount of ethanol are added, and wet granulation is carried out, followed by sizing, drying, and uniformly spraying the mixture of kinsenoside-oleic acid in step (1) on the surface, and then drying to obtain famotidine granules for standby.

[0086] Calcium carbonate, magnesium hydroxide and the remaining filler are mixed, and an appropriate amount of ethanol is added, followed by wet granulation, sizing, and drying to obtain calcium carbonate-magnesium hydroxide granules for standby.

[0087] The calcium carbonate-magnesium hydroxide granules, famotidine granules, disintegrant, lubricant, and flavoring agent are mixed evenly and then compressed into tablets to obtain the product.

[0088] Comparative Example 6 Famotidine Calcium Magnesium Chewable Tablets

[0089] Commercially available famotidine calcium magnesium chewable tablets: Approval number for drugs in China: H20052502

[0090] Accelerated test to verify the stability of famotidine calcium magnesium chewable tablets

[0091] Accelerated test: The famotidine calcium magnesium chewable tablets of Examples 1 to 3 and the famotidine calcium magnesium chewable tablets of Comparative Examples 1 to 6 are packaged as commercially available products and placed at a temperature of 40 ± 2 °C and a relative humidity of 75% ± 5% for 6 months. Samples are taken during the test period to detect the contents of related substances, famotidine, calcium carbonate, and magnesium hydroxide.

[0092] The related substances of famotidine are determined by the high performance liquid chromatography method (General Rule 0512) in Chinese Pharmacopoeia (2020 Edition). Solvent: Dissolve 13.6 g of sodium dihydrogen phosphate in 900 ml of water, adjust the pH value to 7.0 ± 0.1 with 1 mol / L sodium hydroxide solution, add water to 1000 ml, mix well, take 930 ml and mix with 70 ml of acetonitrile. Test solution: Take this product, dissolve it with an appropriate amount of methanol, and dilute it with the solvent to make a solution containing about 0.5 mg of famotidine per 1 ml. Control solution: Accurately measure an appropriate amount of the test solution, and quantitatively dilute it with the solvent to make a solution containing about 5 μg per 1 ml. System suitability solution: Take about 25 mg of famotidine, dissolve it with 2 ml of acetonitrile and 2 ml of the solvent, add 3 ml of 0.5 mol / L hydrochloric acid solution, heat it in a water bath at 40°C for 5 minutes, add 3 ml of 0.5 mol / L sodium hydroxide solution, then add 5 ml of 1 mol / L sodium hydroxide solution, heat it in a water bath at 60°C for 5 minutes, add 5 ml of 1 mol / L hydrochloric acid solution, and dilute it with the solvent to make a solution containing about 0.5 mg per 1 ml. Chromatographic conditions: Use octadecylsilane chemically bonded silica gel as the filler (Kromasil C18, 4.6 mm × 250 mm, 5 μm or a chromatographic column with equivalent efficiency); use acetate buffer solution (dissolve 13.6 g of sodium acetate in 900 ml of water, adjust the pH value to 6.0 ± 1.0 with glacial acetic acid, add water to 1000 ml)-acetonitrile (93:7) as mobile phase A, and acetonitrile as mobile phase B, perform gradient elution according to the following table, 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.

[0093] Table 1 Elution Program

[0094]

[0095]

[0096] System suitability requirements: Adjust the proportion of the mobile phase to make the retention time of the famotidine chromatographic peak in the chromatogram of the system suitability solution about 10 minutes, and the retention times of impurity I peak and impurity II peak relative to the famotidine peak are about 0.7 and 1.2. The number of theoretical plates calculated by the famotidine peak is not less than 5000. The resolution between the famotidine peak and the adjacent impurity peaks should meet the requirements. Determination method: Accurately measure the test solution and the control solution, and 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%) of the main peak area 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%).

[0097] Figure 3 To accelerate the change of the content of impurity Ι in calcium and magnesium chewable tablets of famotidine. Figure 4To accelerate the change in the content of impurity II in famotidine calcium and magnesium chewable tablets during the accelerated test. Overall, it shows that the famotidine calcium and magnesium chewable tablets in Examples 1 to 3 of the present invention have high stability, and the growth rates of the contents of impurity I and impurity II are relatively low in high-temperature and high-humidity environments.

[0098] Table 2 Stability investigation of famotidine calcium and magnesium chewable tablets

[0099]

[0100]

[0101] Table 2 shows that the content of the active ingredient in the famotidine calcium and magnesium chewable tablets of the present invention is stable, the content of related substances is low, and the aloesol-oleic acid blend forms a protective barrier around famotidine, blocking the influence of external environmental factors on famotidine and reducing the occurrence of hydrolysis and oxidation reactions, thereby improving the stability of famotidine.

Claims

1. A stable famotidine calcium and magnesium chewable tablet, characterized in that, The stable famotidine calcium magnesium chewable tablets are composed of the following components: 20 parts by weight of famotidine, 5-15 parts by weight of agarotetrol, 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, rotary evaporate it in a water bath at 35°C ± 5°C until it reaches 1 / 2 volume, add the ethanol solution containing agarotetrol, and continue rotary evaporation until the mass of the remaining solution is 1.5-3.0 times that of famotidine to obtain an agarotetrol-oleic acid blend; B. Mix famotidine with 1 / 3-2 / 3 parts by weight of filler and an appropriate amount of ethanol, granulate by wet method, size the granules, dry them, uniformly spray the agarotetrol-oleic acid blend obtained in step (1) on the surface, and dry to obtain famotidine granules for standby; C. Mix calcium carbonate and magnesium hydroxide with the remaining filler, add an appropriate amount of ethanol, granulate by wet method, size the granules, and dry to obtain calcium carbonate-magnesium hydroxide granules for standby; D. Mix the calcium carbonate-magnesium hydroxide granules, famotidine granules with the disintegrant, lubricant, and flavoring agent evenly, and press tablets to obtain the tablets.

2. The stable famotidine calcium and magnesium chewable tablets 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 and magnesium chewable tablets according to claim 1, wherein The disintegrant is selected from one or more of crospovidone, sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose.

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

5. The stable famotidine calcium and magnesium chewable tablets according to claim 1, wherein The lubricant is selected from one or more of magnesium stearate, colloidal silica, and talc powder.

6. The stable famotidine calcium and magnesium chewable tablets according to claim 2, wherein, The filler is starch and dextrin.

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

8. The stable famotidine calcium and magnesium chewable tablets according to claim 4, wherein The flavoring agent is sucrose and aspartame.

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

10. The stable famotidine calcium and magnesium chewable tablets according to claim 1, characterized in that, The stable famotidine calcium magnesium chewable tablets are composed of the following components: 20 parts by weight of famotidine, 10 parts by weight of agarotetrol, 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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