Basic bismuth salicylate chewable tablet for dogs and preparation method thereof

Abstract

The invention discloses basic bismuth salicylate chewable tablets for dogs and a preparation method of the basic bismuth salicylate chewable tablets, and belongs to the technical field of veterinary pharmaceutical preparations. The basic bismuth salicylate chewable tablet for dogs is prepared from the following raw and auxiliary materials in percentage by mass: 45-60% of basic bismuth salicylate, 15-25% of a filler, 5-15% of an adhesive, 5-15% of a disintegrating agent, 0.5-3% of a lubricant and 8-20% of a flavoring agent, the preparation method comprises the following steps: uniformly mixing the basic bismuth salicylate and the filling agent; adding a disintegrating agent accounting for 40-60% of the total amount, uniformly mixing, and then adding an adhesive to enable the material to present a proper humidity that the material is clustered when held and is dispersed when touched; after granulating, drying until the water content is 1-3%; and adding the rest disintegrating agent, lubricant and flavoring agent, uniformly mixing, and tabletting to obtain the basic bismuth salicylate chewable tablet for dogs. The basic bismuth salicylate chewable tablet for dogs has the characteristic of rapid disintegration and excellent palatability.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of veterinary pharmaceutical preparations, and particularly relates to a chewable bismuth subsalicylate tablet for dogs and a preparation method thereof. BACKGROUND

[0002] Bismuth subsalicylate (chemical formula C7H5BiO4, also known as bismuth oxy-2-hydroxybenzoate or bismuth subsalicylate) is prepared by neutralization reaction of salicylic acid and bismuth hydroxide, and is an alkaline salt. It is a white to off-white powder, and the structural formula is Bismuth subsalicylate is soluble in acid and alkali solution, but not soluble in water, ethanol and diethyl ether. It is an odorless and tasteless substance, has light instability, and decomposes in high-temperature water.

[0003] The multi-effect pharmacological action of bismuth subsalicylate includes forming a mucous membrane protective layer, inhibiting gastric acid secretion, adsorbing pathogens and their toxins, and direct bacteriostatic activity, which jointly play a gastrointestinal protective role.

[0004] In view of the indications of bismuth subsalicylate, it is particularly necessary to develop a preparation which is convenient to administer, easy to carry, has rapid effect (can quickly relieve adverse symptoms) and is suitable for all dog breeds. Although conventional oral solid preparations and liquid preparations are convenient to take, they have limitations in stability, packaging, storage and transportation.

[0005] Bismuth subsalicylate has been used as a core component in the field of human gastrointestinal treatment (such as American Pepto-Bismol oral solution), and was officially included in the United States Pharmacopoeia USP 24 in 1990. However, in the field of veterinary drugs, the existing dog dosage forms (tablets / suspensions) generally have poor palatability, pH-sensitive release fluctuation of bismuth ions, and poor drug administration operability, which seriously affect the clinical medication compliance. SUMMARY

[0006] The present application aims to provide a chewable bismuth subsalicylate tablet for dogs and a preparation method thereof. The chewable bismuth subsalicylate tablet provided by the present application is convenient and flexible to take, has excellent taste, and can be directly chewed. By optimizing the compounding process of bismuth preparations and palatable excipients, the problems of poor palatability, refusal of dogs to take and poor dissolution of traditional dosage forms (such as suspensions and ordinary tablets) are solved.

[0007] The purpose of the present application is achieved by the following technical solutions:

[0008] The application provides a chewable bismuth subsalicylate tablet for dogs, which is mainly prepared from the following raw and auxiliary materials in mass percentage: 45-60% of bismuth subsalicylate, 15-30% of a filling agent, 5-15% of a binding agent, 5-15% of a disintegrating agent, 0.5-3% of a lubricant and 8-20% of a flavoring agent. The bismuth subsalicylate is an insoluble salt composed of trivalent bismuth and salicylate, and needs to be dried and ground to control the particle size range to 50-150 μm in order to reduce the grit feeling and discomfort in the oral cavity.

[0009] Preferably, the filling agent comprises one or more of microcrystalline cellulose, lactose, calcium carbonate and mannitol. Further preferably, the filling agent is a combination of calcium carbonate and mannitol, and the mass ratio of calcium carbonate to mannitol is preferably 3:5. The calcium carbonate is both a filling agent and an active ingredient (calcium supplement / acid inhibitor), which reduces the complexity of the formula, simultaneously meets the nutritional requirements and pathological relief of the dogs, has high performance and low cost, and is suitable for large-scale production; and the mannitol has good water solubility, a cool and slightly sweet taste, and can improve the compliance of the sick animals to the medicine.

[0010] Preferably, the binding agent comprises one or more of starch paste, polyvinylpyrrolidone (PVP) K90 or K30 anhydrous ethanol solution and cellulose derivative solution. Further preferably, the binding agent is polyvinylpyrrolidone K30 anhydrous ethanol solution, and the concentration is preferably 15% (w / v). The polyvinylpyrrolidone can not only improve the compressibility of the powder particles, but also has the function of a wetting agent due to its own hygroscopicity, and promotes disintegration.

[0011] Preferably, the disintegrating agent comprises one or more of cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch. Further preferably, the disintegrating agent is cross-linked polyvinylpyrrolidone. The tablet prepared by using the cross-linked polyvinylpyrrolidone has large hardness, a clean and beautiful appearance, short disintegration time and high dissolution rate. The disintegrating agent can be added by internal addition, external addition or a combination of internal and external addition.

[0012] Preferably, the lubricant comprises one or more of magnesium stearate, talc and sodium dodecyl sulfate. Further preferably, the lubricant is a combination of magnesium stearate and sodium dodecyl sulfate, and the mass ratio of magnesium stearate to sodium dodecyl sulfate is preferably 5:3. The combination of magnesium stearate and sodium dodecyl sulfate can not only improve the fluidity, reduce the friction and prevent sticking and ejection, but also has outstanding performance in optimizing the dissolution performance and improving the quality of the tablet.

[0013] Preferably, the flavoring agent comprises one or more of aspartame, chicken powder, chicken liver powder and beef powder.

[0014] The application further provides a preparation method of the bismuth subsalicylate chewable tablet for dogs, which comprises the following steps: uniformly mixing bismuth subsalicylate and a filler; uniformly mixing the half of the total amount of disintegrants, and then adding a binder to make the material have a suitable humidity of "holding together and scattering immediately"; drying the granules to have a water content of 1%-3% after granulation; uniformly mixing the remaining disintegrants, lubricants and flavoring agents, and then tabletting to obtain the bismuth subsalicylate chewable tablet for dogs.

[0015] Preferably, the preparation method of the bismuth subsalicylate chewable tablet for dogs comprises the following steps:

[0016] S1, preparation of the binder: uniformly suspending PVP-K30 ground through a 100-mesh sieve in anhydrous ethanol solution in proportion, and magnetically stirring (300-500 rpm, 10 min) until a colloidal solution is obtained, to obtain a 15% PVP-K30 anhydrous ethanol solution binder.

[0017] S2, granulation: grinding bismuth subsalicylate through an 80-mesh sieve, and grinding the remaining excipients through a 100-mesh sieve; uniformly mixing bismuth subsalicylate and the filler; uniformly mixing the half of the total amount of disintegrants, and then adding a binder to make the material have a suitable humidity of "holding together and scattering immediately", and then granulating through a 24-mesh sieve to obtain soft material; and drying at 60°C until the water content is 1%-3%. The disintegrant is preferably cross-linked polyvinylpyrrolidone; and the filler is preferably a combination of calcium carbonate and mannitol. In this step, the disintegrant is added by an internal-external composite process, and the raw and auxiliary materials are homogenized by a step-by-step mixing strategy.

[0018] S3, tabletting: after the dried granules are sized through a 20-mesh sieve, the remaining disintegrants, lubricants and flavoring agents are uniformly mixed, and then tabletted to obtain the bismuth subsalicylate chewable tablet for dogs. The disintegrant is preferably cross-linked polyvinylpyrrolidone; and the lubricant is preferably a combination of magnesium stearate and sodium dodecyl sulfate.

[0019] The application has the following advantages and effects relative to the prior art:

[0020] The bismuth subsalicylate chewable tablet developed by the application has the characteristics of rapid disintegration and excellent palatability. The active ingredient is eliminated by grinding and sieving in a mortar to improve the swallowing compliance of dogs. In vitro disintegration experiments prove that the chewable tablet is completely disintegrated and uniformly dispersed in water within 2 minutes.

[0021] The chewable tablet is produced by using conventional tabletting equipment, without additional equipment investment, and the production process is simple and efficient. The unique prescription design (containing a composite disintegration system and flavoring agents) ensures the full release of drug efficacy while achieving convenient administration. The dosage form meets the needs of all dog breeds and has significant clinical value and market potential. DETAILED DESCRIPTION

[0022] The following examples further illustrate the details of the implementation of the technical solutions of the present application. If the experimental conditions are not specified, refer to the conventional standards or the recommended parameters of the equipment manufacturers, but the protection scope of the present application is not limited thereto.

[0023] Example 1

[0024] A basic bismuth salicylate chewable tablet is prepared according to the prescription shown in Table 1 below, and 500 tablets are prepared. The 0.5 g tablet weight specification (main drug content 262 mg) is used to press the tablets into shape.

[0025] Table 1

[0026] Name of raw and auxiliary materials Prescription one (g) Bismuth subsalicylate 262 Microcrystalline cellulose + lactose (5:3, mass ratio) 96 15% PVP-K30 anhydrous ethanol solution 30 Cross-linked polyvinylpyrrolidone 50 Magnesium stearate 5 Sodium dodecyl sulfate 3 Beef powder 54

[0027] The specific preparation method is as follows: first, dry the main drug basic bismuth salicylate and grind it through an 80-mesh sieve for use, with the particle size range controlled at 50-150 μm; the rest of the excipients are sieved through a 100-mesh sieve for use. First, prepare a 15% (w / v) polyvinylpyrrolidone K30 anhydrous ethanol solution as a binder; weigh the prescription amount of basic bismuth salicylate, microcrystalline cellulose, and lactose (5:3) and mix them uniformly according to the principle of equal increments; add the prescription amount of 50% internal added disintegrant cross-linked polyvinylpyrrolidone and mix it uniformly; add the binder to the material until it has the appropriate moisture, which is "held together and scattered immediately"; granulate through a 24-mesh sieve to prepare the soft material; dry at a temperature of 60°C until the water content is 1%-3%. After drying the granules through a 20-mesh sieve, add the remaining 50% of the external added disintegrant cross-linked polyvinylpyrrolidone, the lubricant magnesium stearate + sodium dodecyl sulfate, and the flavoring agent beef powder for final mixing. Measure the angle of repose α of the mixed powder to be <30°, and press the tablets to obtain the basic bismuth salicylate chewable tablets, whose appearance characteristics, hardness parameters, and disintegration time limit indicators are shown in Table 4.

[0028] The angle of repose of the mixed powder is measured by the fixed conical bottom method. This parameter is negatively correlated with the flowability of the powder, and the smaller the value, the better the flowability. According to the industry standard, α < 30° is excellent flowability, α > 45° is substandard flowability, and 30°-40° meets the needs of industrial production. In this test, the angle of repose α is <30°.

[0029] The hardness of the chewable tablets is measured by a hardness tester. The hardness of the chewable tablets is controlled in the range of 5-120 N, which is lower than that of ordinary tablets.

[0030] Disintegration time limit determination: accurately calibrate the orientation of the basket to ensure that the distance between the bottom of the sieve and the base of the beaker is 25 mm. Control the temperature of the water bath system to be 37±1°C, and adjust the liquid level so that the immersion depth of the sieve is 15 mm when the basket is at the highest point, and the top of the basket is above the liquid surface. Take 6 pieces of the test product and put them into the basket glass tube, and start the disintegration time limit determination program.

[0031] Example 2

[0032] A bismuth subsalicylate chewable tablet is prepared according to the prescription shown in Table 2 below, and 500 tablets are prepared. The tablets are formed by compression molding using a 0.5 g tablet weight specification (262 mg of main drug content).

[0033] Table 2

[0034] Name of raw and auxiliary materials Prescription two (g) Bismuth subsalicylate 262 Calcium carbonate + mannitol (3:5, mass ratio) 96 15% PVP-K30 anhydrous ethanol solution 30 Cross-linked polyvinylpyrrolidone 50 Magnesium stearate 5 Sodium dodecyl sulfate 3 Beef powder 54

[0035] The specific preparation method is as follows: first, dry the main drug bismuth subsalicylate and grind it through an 80 mesh sieve for use, with a particle size range of 50-150 μm. The remaining excipients are sieved through a 100 mesh sieve for use. First, prepare a 15% polyvinylpyrrolidone K30 ethanol solution as a binder; weigh the prescription amount of bismuth subsalicylate, mannitol, and calcium carbonate (5:3) and mix them evenly according to the principle of equal increments; add the prescription amount of 50% internal disintegrant, cross-linked polyvinylpyrrolidone, and mix evenly; add the binder to the material until it has the appropriate moisture, which is "held together and scattered immediately when touched"; granulate through a 24 mesh sieve to make the soft material; dry at 60°C until the water content is 1-3%. After drying the granules through a 20 mesh sieve, add the remaining 50% of the external disintegrant, cross-linked polyvinylpyrrolidone, the lubricant magnesium stearate + sodium dodecyl sulfate, and the flavoring agent beef powder for final mixing. Measure the angle of repose of the mixed powder, which is <30°, and compress the tablets to obtain the bismuth subsalicylate chewable tablets. The appearance characteristics, hardness parameters, and disintegration time indicators are shown in Table 4.

[0036] Example 3

[0037] A bismuth subsalicylate chewable tablet is prepared according to the prescription shown in Table 3 below, and 500 tablets are prepared. The tablets are formed by compression molding using a 0.5 g tablet weight specification (262 mg of main drug content).

[0038] Table 3

[0039] Name of raw and auxiliary materials Prescription three (g) Bismuth subsalicylate 262 Mannitol 96 15% PVP-K30 anhydrous ethanol solution 30 Cross-linked polyvinylpyrrolidone 50 Magnesium stearate 5 Sodium dodecyl sulfate 3 Beef powder 54

[0040] The specific preparation method is as follows: first, dry the main drug bismuth subsalicylate, grind it, and pass it through an 80-mesh sieve for use, with the particle size range controlled at 50-150 μm; pass the rest of the excipients through a 100-mesh sieve for use. First, prepare a 15% polyvinylpyrrolidone K30 ethanol solution as a binder; weigh the prescribed amount of bismuth subsalicylate and mannitol, and mix them evenly according to the principle of equal increments; add the prescribed amount of 50% internal disintegrant, cross-linked polyvinylpyrrolidone, and mix it evenly; add the binder to the material until it reaches the appropriate humidity, which is characterized by the property of "holding together when pressed, and scattering immediately when touched"; granulate it through a 24-mesh sieve to make a soft material; dry it at a temperature of 60°C until the water content is 1%-3%. Granulate the dried particles through a 20-mesh sieve, and add the remaining 50% of the external disintegrant, cross-linked polyvinylpyrrolidone, the lubricant magnesium stearate + sodium dodecyl sulfate, and the flavoring agent beef powder to the mixture for final mixing. Measure the angle of repose of the mixed powder, which is less than 30°, and press the tablet. The bismuth subsalicylate chewable tablet is obtained, and its appearance characteristics, hardness parameters, and disintegration time limit indicators are shown in Table 4.

[0041] Table 4

[0042]

[0043] As can be seen from the data in Table 4, when using microcrystalline cellulose and lactose combination, calcium carbonate combined with mannitol, and single mannitol as the filler, the appearance characteristics, hardness parameters, and disintegration time limit indicators of the tablets are basically the same. However, the tablets prepared from the microcrystalline cellulose / lactose combination and single mannitol formulation have a slight surface powder shedding phenomenon. The flow characteristics of the prescription two (calcium carbonate + mannitol) mixed powder are the best. Based on the comprehensive evaluation results, the calcium carbonate and mannitol complex system is determined to be the optimal filler combination.

[0044] Example 4

[0045] A bismuth subsalicylate chewable tablet is prepared according to the prescription shown in Table 5 below, and 500 tablets are prepared. The 0.5 g tablet weight specification (main drug content 262 mg) is used to press the tablet into shape.

[0046] Table 5

[0047] Name of raw and auxiliary materials Prescription four (g) Bismuth subsalicylate 262 Calcium carbonate + mannitol (3:5, mass ratio) 96 15% PVP-K30 anhydrous ethanol solution 30 Sodium carboxymethyl starch 50 Magnesium stearate 5 Sodium dodecyl sulfate 3 Beef powder 54

[0048] The specific preparation method is as follows: first, dry the main drug bismuth subsalicylate, grind and pass through an 80-mesh sieve for use, with the particle size range controlled at 50-150 μm; the rest of the excipients are passed through a 100-mesh sieve for use. First, prepare a 15% polyvinylpyrrolidone K30 ethanol solution as a binder; weigh the prescribed amount of bismuth subsalicylate, mannitol and calcium carbonate (5:3) and mix uniformly according to the principle of equal increments; add the prescribed amount of 50% internal disintegrant sodium carboxymethyl starch, mix uniformly, add the binder to the material to a suitable humidity of "hold it together, touch it and it will scatter", granulate through a 24-mesh sieve, and prepare the soft material; dry at 60°C to a water content of 1%-3%. After drying the granules, pass them through a 20-mesh sieve, add the remaining 50% external disintegrant sodium carboxymethyl starch, lubricant magnesium stearate + sodium dodecyl sulfate and flavoring agent beef powder to the final mixture. Measure the angle of repose of the mixed powder, which is <30°, and press the tablets. The bismuth subsalicylate chewable tablets are obtained, with the appearance characteristics, hardness parameters and disintegration time limit indicators shown in Table 7.

[0049] Example 5

[0050] A bismuth subsalicylate chewable tablet is prepared according to the prescription shown in Table 6, with 500 tablets prepared. The tablets are formed by pressing with a 0.5 g tablet weight specification (main drug content 262 mg).

[0051] Table 6

[0052] Name of raw and auxiliary materials Prescription five (g) Bismuth subsalicylate 262 Calcium carbonate + mannitol (3:5, mass ratio) 96 15% PVP-K30 anhydrous ethanol solution 30 Low-substituted hydroxypropyl cellulose 50 Magnesium stearate 5 Sodium dodecyl sulfate 3 Beef powder 54

[0053] The specific preparation method is as follows: first, dry the main drug bismuth subsalicylate, grind and pass through an 80-mesh sieve for use, with the particle size range controlled at 50-150 μm; the rest of the excipients are passed through a 100-mesh sieve for use. First, prepare a 15% polyvinylpyrrolidone K30 ethanol solution as a binder; weigh the prescribed amount of bismuth subsalicylate, mannitol and calcium carbonate (5:3) and mix uniformly according to the principle of equal increments; add the prescribed amount of 50% internal disintegrant sodium carboxymethyl starch, mix uniformly, add the binder to the material to a suitable humidity of "hold it together, touch it and it will scatter", granulate through a 24-mesh sieve, and prepare the soft material; dry at 60°C to a water content of 1%-3%. After drying the granules, pass them through a 20-mesh sieve, add the remaining 50% external disintegrant sodium carboxymethyl starch, lubricant magnesium stearate + sodium dodecyl sulfate and flavoring agent beef powder to the final mixture. Measure the angle of repose of the mixed powder, which is <30°, and press the tablets. The bismuth subsalicylate chewable tablets are obtained, with the appearance characteristics, hardness parameters and disintegration time limit indicators shown in Table 7.

[0054] Table 7

[0055]

[0056] By screening disintegrants in Example 3, Example 4, and Example 5, cross-linked polyvinylpyrrolidone is selected as the disintegrant, which shows the shortest disintegration time and good tabletting quality, and the tablet has a complete appearance and a smooth surface. Cross-linked polyvinylpyrrolidone is a white powder with good flowability, and as a disintegrant, it has excellent dispersion properties and dissolution promotion effect. It swells rapidly after coming into contact with water and avoids forming a high-viscosity gel blocking layer.

[0057] Example 6

[0058] A chewable tablet of bismuth subsalicylate is prepared according to the prescription shown in Table 8 below, and 500 tablets are prepared. Tablets are formed by tabletting with a 0.5 g tablet weight specification (main drug content of 262 mg).

[0059] Table 8

[0060] Name of raw and auxiliary materials Prescription six (g) Bismuth subsalicylate 262 Calcium carbonate + mannitol (3:5, mass ratio) 96 15% PVP-K30 anhydrous ethanol solution 30 Cross-linked polyvinylpyrrolidone 50 Magnesium stearate 8 Beef powder 54

[0061] The specific preparation method is as follows: first, dry and grind the main drug bismuth subsalicylate, and pass it through an 80-mesh sieve for use, with a particle size range of 50-150 μm. The rest of the excipients are passed through a 100-mesh sieve for use. First, prepare a 15% polyvinylpyrrolidone K30 ethanol solution as a binder; weigh the prescription amount of bismuth subsalicylate, mannitol, and calcium carbonate (5:3) and mix them evenly according to the principle of equal increments; add the prescription amount of 50% internal disintegrant cross-linked polyvinylpyrrolidone, mix evenly, add the binder to the material to achieve a suitable moisture level, i.e., “hold it together and it will scatter when touched”, granulate through a 24-mesh sieve, and prepare the soft material; dry at a temperature of 60°C until the water content is 1%-3%. After drying the granules through a 20-mesh sieve, add the remaining 50% of the external disintegrant cross-linked polyvinylpyrrolidone, magnesium stearate, and flavoring agent beef powder for final mixing. Measure the rest angle α of the mixed powder to be <30°, and press the tablets to obtain the bismuth subsalicylate chewable tablets. The appearance characteristics, hardness parameters, and disintegration time indicators of the tablets are shown in Table 9.

[0062] Table 9

[0063]

[0064] By comparing Example 2 and Example 6, it can be seen that magnesium stearate is not easy to stick, but has a slight powdering phenomenon. It can be seen that the flowability of magnesium stearate is poor, but through a series of pre-tests, it is found that the combination of magnesium stearate and sodium lauryl sulfate can significantly improve the lubricating effect, and finally magnesium stearate and sodium lauryl sulfate are selected as the lubricant.

[0065] Example 8

[0066] Three batches of small test samples are prepared to verify the prescription two:

[0067] Three batches of samples were homogeneous light brown tablets, no texture abnormalities and color spot defects. The surface of each batch of samples was smooth and the color was uniform, which met the tablet appearance standard of the General Rules of the People's Republic of China Veterinary Drug (2020 edition).

[0068] 10 samples were randomly selected from each batch, and the average tablet weight was calculated after precise weighing. The out-of-limit sample of single weight and mean deviation should not exceed 2 tablets, and the single weight deviation should not be >100%. The test data showed that the measured average tablet weight 0.4963g met the quality specification.

[0069] Three production batch samples were tested for disintegration performance. The test data showed that the average disintegration time of each sample was 85.00s, 56.66s and 63.83s, respectively, all ≤15min, fully meeting the requirements of the relevant detection specifications of the People's Republic of China Veterinary Drug (2020 edition);

[0070] The powder loss rates of 3 batches of basic bismuth salicylate chewable tablets were 0.9317%, 0.8000% and 0.8566%, respectively, and the powder loss rate of the friability test was less than 1%, all meeting the requirements of the second part of the People's Republic of China Veterinary Drug (2020 edition) Appendix.

[0071] The average hardness of three different batches of basic bismuth salicylate chewable tablets was 45.43N, 45.15N and 43.95N, respectively, which met the relevant provisions of chewable tablets.

[0072] The dissolution limit of basic bismuth salicylate was 91.5% by conversion, which was greater than 80% and met the requirements.

[0073] The above examples are only for illustrating the present application, and are not used to limit the protection scope of the present application. Any modification, change, combination or simplification within the spirit and principles of the present application should be considered as equivalent replacement and belongs to the protection scope of the present application.

Claims

1. A chewable tablet of basic bismuth salicylate for dogs, characterized in that, It is made of the following raw and auxiliary materials with the mass percentage content: Alkaline bismuth salicylate 45%~60% Filling agent 15%~30% Binder 5%~15% Disintegrant 5%~15% Lubricant 0.5%~3% Flavoring agent 8%~20%.

2. The chewable tablet of basic bismuth salicylate for dogs according to claim 1, characterized in that, The filling agent includes one or several of microcrystalline cellulose, lactose, calcium carbonate, mannitol.

3. The chewable tablet of basic bismuth salicylate for dogs according to claim 1, wherein The binder includes one or several of starch paste, polyvinylpyrrolidone K90 or K30 anhydrous ethanol solution, cellulose derivative solution.

4. The chewable tablet of basic bismuth salicylate for dogs according to claim 1, characterized in that, The disintegrant includes one or several of cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch.

5. The chewable tablet of basic bismuth salicylate for dogs according to claim 1, characterized in that, The lubricant includes one or several of magnesium stearate, talc, sodium dodecyl sulfate.

6. The chewable tablet of basic bismuth salicylate for dogs according to claim 1, characterized in that, The flavoring agent includes one or several of aspartame, chicken powder, chicken liver powder, beef powder.

7. The alkaline bismuth salicylate chewable tablet for dogs according to claim 1, wherein the filling agent is a combination of calcium carbonate and mannitol; the binder is polyvinylpyrrolidone K30 anhydrous ethanol solution; the disintegrant is cross-linked polyvinylpyrrolidone; and the lubricant is a combination of magnesium stearate and sodium dodecyl sulfate.

8. The alkaline bismuth salicylate chewable tablet for dogs according to claim 7, wherein the mass ratio of calcium carbonate to mannitol in the filling agent is 3:5; the concentration of the polyvinylpyrrolidone K30 anhydrous ethanol solution is 15%; and the mass ratio of magnesium stearate to sodium dodecyl sulfate in the lubricant is 5:

3. It includes the following steps: Mix alkaline bismuth salicylate and filling agent uniformly; add half of the total amount of disintegrant and mix uniformly, then add binder to make the material have a humidity of "holding together and scattering immediately when touched"; dry the granules to a water content of 1%~3% after granulation; then add the remaining disintegrant, lubricant and flavoring agent and mix uniformly, and press into tablets to obtain the alkaline bismuth salicylate chewable tablet for dogs. It includes the following steps: S1. Preparation of binder: grind polyvinylpyrrolidone K30 through a 100-mesh sieve, suspend in anhydrous ethanol solution, and stir until a colloidal solution is formed to obtain 15% polyvinylpyrrolidone K30 anhydrous ethanol solution; S2. Granulation: grind alkaline bismuth salicylate through an 80-mesh sieve and the rest of the auxiliary materials through a 100-mesh sieve; mix alkaline bismuth salicylate and filling agent uniformly; add half of the total amount of disintegrant and mix uniformly, then add binder to make the material have a humidity of "holding together and scattering immediately when touched"; granulate through a 24-mesh sieve to obtain soft material; dry at a temperature of 60℃ until the water content is 1%~3%; S3. Tablet pressing: after the dried granules are sieved through a 20-mesh sieve, add the remaining disintegrant, lubricant and flavoring agent and mix uniformly, and press into tablets to obtain the alkaline bismuth salicylate chewable tablet for dogs. ​ 9. Process for the preparation of chewable tablets of basic bismuth salicylate for dogs according to any one of claims 1 to 8, characterized in that, ​ ​ 10. A process for the preparation of chewable tablets of basic bismuth salicylate for dogs according to claim 9, characterized in that, ​ ​ ​ ​

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