Tablet of methimazole, application and preparation process

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a methimazole tablet, application and a preparation process. The tablet is composed of a medicine-containing tablet core, an isolating layer and an enteric layer from inside to outside, the medicine-containing tablet core is composed of methimazole, a pH buffering agent, a stabilizer, an antioxidant, a filler, a disintegrating agent, a lubricant and an adhesive, the methimazole tablet has the advantages of being high in dissolution rate and capable of being continuously released for 24 h, and it is found through an acceleration test that the content of related substances is low, and the content of the related substances is low. The product quality is stable, and the market prospect is good.

Description

Technical Field

[0001] The present invention belongs to the technical field of specific therapeutic activities of pharmaceutical preparations, and particularly relates to a tablet of methimazole, its uses and preparation processes. Background Art

[0002] Methimazole (MMI), also known as thiamazole, is a thiourea anti-thyroid drug with a molecular weight of 114.16, a melting point between 143 and 146 °C, and a solubility in water as high as 200 mg / mL. Its structural formula is as follows:

[0003]

[0004] Methimazole has the advantages of a long half-life, a relatively low incidence of liver damage, a wide range of applications, convenient administration, and low price, and is used as a first-line drug for the treatment of hyperthyroidism in clinical practice. Until now, methimazole is still the first choice for the treatment of hyperthyroidism in clinical practice.

[0005] The half-life of ordinary tablets is relatively short (about 3 hours), with a large dosage and frequent administration, which is inconvenient for patients to take. Moreover, the blood drug concentration is not stable, and there are safety problems in long-term use. In the prior art, when methimazole is prepared into tablets, the problems are: poor taste, difficult for patients to accept; irritating to the gastric mucosa; easily destroyed by gastric acid, affecting the absorption of active ingredients. At present, the research on sustained-release methimazole enteric-coated tablets is relatively less. Summary of the Invention

[0006] Overcoming the deficiencies of the prior art, the present invention provides a tablet containing the active ingredient methimazole, especially an enteric-coated tablet, which can be released for up to 24 hours, reducing the number of drug administrations, reducing gastric irritation and the problems of multiple drug administrations. Through accelerated tests, it is found that the active substance remains at a relatively high level, and the preparation process is relatively simple, suitable for large-scale commercial production.

[0007] Specifically, the technical solution of the present invention is realized as follows:

[0008] The first object of the present invention is to provide a tablet containing methimazole, especially an enteric-coated tablet, wherein the enteric-coated tablet is composed of a drug-containing core, a separating layer and an enteric layer. The drug-containing core is composed of methimazole, a pH buffer, a stabilizer, an antioxidant, a filler, a disintegrant, a lubricant, and a binder; calculated by weight ratio, specifically as follows:

[0009]

[0010] The second object of the present invention is to provide the preparation method of the tablet as follows:

[0011] 1) Mix methimazole and an antioxidant uniformly in 70 - 90% ethanol - water, perform rotary evaporation, and carry out ultrafine pulverization with an average particle size below 45 μm to obtain mixture A for standby.

[0012] 2) Weigh a stabilizer, dissolve it in absolute ethanol to make a binder for standby.

[0013] 3) Mix mixture A uniformly with a filler, a disintegrant, add the binder to make a soft material, perform wet granulation and drying to obtain mixture B for standby.

[0014] 4) Add a lubricant to mixture B, mix uniformly, and press into tablets to obtain the tablet core.

[0015] 5) Coat the tablet core with an isolating layer coating and an enteric - coated layer to obtain enteric - coated tablets.

[0016] Furthermore, in a preferred embodiment of the present invention, the tablet is composed of a medicated tablet core, an isolating layer, and an enteric - coated layer. The medicated tablet core is composed of methimazole, a pH buffer, a stabilizer, an antioxidant, a filler, a disintegrant, a lubricant, and a binder; calculated by weight ratio, specifically as follows:

[0017]

[0018]

[0019] Furthermore, in a preferred embodiment of the present invention, the stabilizer is poloxamer and citric acid. Calculated by weight ratio, the ratio of poloxamer to citric acid is 2 - 4:1, preferably, the ratio of poloxamer to citric acid is 3:1.

[0020] Furthermore, in a preferred embodiment of the present invention, the antioxidant is selected from sodium thiosulfate, sodium metabisulfite, sodium sulfite, and preferably, the antioxidant is selected from sodium thiosulfate.

[0021] Furthermore, in a preferred embodiment of the present invention, the filler is selected from one or more combinations of microcrystalline cellulose and sorbitol, mannitol, xylitol; the disintegrant is selected from one of dry starch, sodium carboxymethyl starch, pre - gelatinized starch, low - substituted hydroxypropyl cellulose, cross - linked carboxymethyl cellulose sodium, polyvinylpyrrolidone; the lubricant is selected from one of magnesium stearate, sodium lauryl sulfate, talc, colloidal silica, and colloidal silicon dioxide.

[0022] Furthermore, in a preferred embodiment of the present invention, the filler is selected from microcrystalline cellulose and xylitol. Calculated by weight ratio, the ratio of microcrystalline cellulose to xylitol is 2 - 5:1; further, the ratio of microcrystalline cellulose to xylitol is 4:1.

[0023] The disintegrant is selected from sodium carboxymethyl starch; the lubricant is selected from magnesium stearate.

[0024] Further, in a preferred embodiment of the present invention, the process of coating the isolation layer is as follows: Weigh the prescription amount of sodium carboxymethylcellulose, polyethylene glycol - 2000, and talc powder, add them to the citric acid - sodium citrate buffer solution, stir to dissolve, stir evenly, add purified water to the full volume, and adjust the pH value to 5.0 - 6.0 with citric acid, stir until the solids are completely dissolved, and perform coating according to the coating process parameters. After the coating solution is sprayed out, dry to obtain the methimazole tablets containing the isolation layer.

[0025] Further, in a preferred embodiment of the present invention, the process of coating the enteric - soluble layer is as follows: Weigh the prescription amount of Opadry enteric - coating material, polysorbate - 80, and sodium lauryl sulfate, add them to the citric acid - sodium citrate buffer solution, stir to dissolve, stir evenly, add water to the full volume, and adjust the pH value to 6.5 - 7.5 with sodium bicarbonate, stir until completely dissolved. Place the methimazole tablets containing the isolation layer in a coating pan, coat with enteric - soluble coating, and dry after coating to obtain the enteric - coated methimazole tablets.

[0026] Further, in a preferred embodiment of the present invention, the pH buffer is selected from the citric acid - sodium citrate buffer solution, and the pH value of the buffer is 5.0 - 6.0.

[0027] Further, in a preferred embodiment of the present invention, the tablets are composed of a drug - containing core, an isolation layer, and an enteric - soluble layer. The drug - containing core is composed of methimazole, a pH buffer, a stabilizer, an antioxidant, a filler, a disintegrant, a lubricant, and a binder; calculated by weight ratio, specifically as follows:

[0028]

[0029] Further, the preparation method of the tablets is as follows:

[0030] 1) Mix methimazole and sodium thiosulfate evenly in 70 - 90% ethanol - water, perform rotary evaporation, and carry out ultrafine pulverization with an average particle size below 45μm to obtain mixture A for standby;

[0031] 2) Weigh poloxamer and citric acid, dissolve them in absolute ethanol to prepare a binder for standby; wherein, the weight - volume ratio of ethanol to the stabilizer is 1:10;

[0032] 3) Mix mixture A evenly with microcrystalline cellulose, xylitol, and sodium carboxymethyl starch, add the binder to make soft materials, perform wet granulation and drying to obtain mixture B for standby;

[0033] 4) Add magnesium stearate to mixture B, mix evenly, and press into tablets to obtain the tablet core;

[0034] 5) Weigh the prescribed amounts of sodium carboxymethylcellulose, polyethylene glycol - 2000, and talc powder, add them to the citric acid - sodium citrate buffer solution, stir to dissolve, mix evenly, add purified water to the full volume, and adjust the pH value to 5.0 - 6.0 with citric acid. Stir until the solids are completely dissolved, and coat the tablet cores according to the coating process parameters. After the coating solution is completely sprayed, dry to obtain methimazole tablets with a separating layer, and the weight of the tablet cores increases by about 3 - 5%;

[0035] 6) Weigh the prescribed amounts of Opadry enteric - coating material, polysorbate - 80, and sodium lauryl sulfate, add them to the citric acid - sodium citrate buffer solution, stir to dissolve, mix evenly, add water to the full volume, and adjust the pH value to 6.5 - 7.5 with sodium bicarbonate. Stir until completely dissolved, coat the methimazole tablets with a separating layer obtained in step 5), and dry. The weight of the enteric - coating layer increases by about 7 - 10% to obtain enteric - coated methimazole tablets.

[0036] The present invention also provides the use of the above - mentioned enteric - coated methimazole tablets in the preparation of drugs for treating hyperthyroidism.

[0037] Compared with the prior art, the technical effects of the present invention are as follows:

[0038] (1) The enteric - coated methimazole tablets of the present invention select citric acid and poloxamer as stabilizers, and when combined with an antioxidant, can significantly improve the stability of methimazole. Through accelerated tests, it is found that the impurity content of methimazole is low, and the activity remains consistent during long - term storage.

[0039] (2) The enteric - coated methimazole tablets of the present invention have a high dissolution rate. The preferred excipients and weights can make the product quality stable, and they can dissolve stably within 24 hours, having good market prospects. Description of the Drawings

[0040] Figure 1 : The related - substance contents (%) of Examples 1 - 5 and Comparative Examples 1 - 7 at 0, 1, 2, 3, and 6 months of the accelerated test.

[0041] Figure 2 : The cumulative release degrees (%) of Examples 1 - 3, Example 5, Comparative Examples 1 - 3, and Comparative Examples 5 - 7 at the end of 1, 2, 4, 8, 12, 16, and 24 hours in phosphate buffer solution (pH 6.8). Detailed Embodiments

[0042] In order to make the objectives and technical solutions of the present invention more clear, the following further describes the present invention with reference to the 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.

[0043] Example 1

[0044] Formula:

[0045]

[0046]

[0047] Preparation method:

[0048] 1) Add methimazole and sodium thiosulfate to 70 - 90% ethanol - water, mix evenly, perform rotary evaporation, and carry out ultrafine pulverization with an average particle size below 45μm to obtain mixture A for standby;

[0049] 2) Weigh poloxamer and citric acid, dissolve them with absolute ethanol to make an adhesive for standby; among them, the weight - volume ratio of ethanol to the stabilizer is 1:10;

[0050] 3) Mix mixture A with microcrystalline cellulose, xylitol, and sodium carboxymethyl starch evenly, add the adhesive to make soft materials, perform wet granulation and drying, and obtain mixture B for standby;

[0051] 4) Add magnesium stearate to mixture B, mix evenly, and press tablets to obtain the tablet core;

[0052] 5) Take 6g of sodium carboxymethylpropyl cellulose, 3g of polyethylene glycol - 2000, and 1g of talc powder, add them to the citric acid - sodium citrate buffer solution, stir to dissolve, stir evenly, add purified water to a total volume of 200mL, adjust the pH value to 5.0 with citric acid, stir to completely dissolve the solids, and coat the tablet core according to the coating process parameters. After the coating solution is sprayed out, dry to obtain the methimazole tablets with a separating layer, and the weight of the tablet core increases by about 5%;

[0053] 6) Take 85g of Opadry enteric - coating material, 3g of polysorbate - 80, and 1.5g of sodium dodecyl sulfate, add them to the citric acid - sodium citrate buffer solution, stir to dissolve, stir evenly, add water to a total volume of 200mL, adjust the pH value to 6.5 with sodium bicarbonate, stir to completely dissolve, coat the methimazole tablets with a separating layer obtained in step 5), dry, and the weight of the enteric - coating layer increases by about 10% to obtain methimazole enteric - coated tablets.

[0054] Example 2

[0055] Formula:

[0056]

[0057]

[0058] Preparation method:

[0059] 1) Mix methimazole and sodium thiosulfate evenly in 70 - 90% ethanol - water, perform rotary evaporation, carry out ultrafine grinding, with the average particle size below 45 μm, to obtain mixture A for standby;

[0060] 2) Weigh poloxamer and citric acid, dissolve them with absolute ethanol to prepare an adhesive for standby; among them, the weight - volume ratio of ethanol to the stabilizer is 1:10;

[0061] 3) Mix mixture A evenly with microcrystalline cellulose, xylitol and sodium carboxymethyl starch, add the adhesive to make soft materials, perform wet granulation and drying, to obtain mixture B for standby;

[0062] 4) Add magnesium stearate to mixture B, mix evenly, and press tablets to obtain the tablet cores;

[0063] 5) Take 6 g of sodium carboxymethylpropyl cellulose, 3 g of polyethylene glycol - 2000 and 1 g of talc powder, add them to the citric acid - sodium citrate buffer solution, stir to dissolve, stir evenly, add purified water to a total volume of 200 mL, and adjust the pH value to 6.0 with citric acid, stir to completely dissolve the solids, coat the tablet cores according to the coating process parameters, after the coating solution is sprayed out, dry to obtain methimazole tablets with a separating layer, and the weight of the tablet cores increases by about 3%;

[0064] 6) Take 85 g of Opadry enteric - coating material, 3 g of polysorbate - 80, 1.5 g of sodium dodecyl sulfate, add them to the citric acid - sodium citrate buffer solution, stir to dissolve, stir evenly, add water to a total volume of 200 mL, and adjust the pH value to 7.5 with sodium bicarbonate, stir to completely dissolve, coat the methimazole with a separating layer obtained in step 5), dry, and the weight of the enteric - coating layer increases by about 7% to obtain methimazole enteric - coated tablets.

[0065] Example 3

[0066] Formulation:

[0067]

[0068]

[0069] Preparation method:

[0070] 1) Mix methimazole and sodium thiosulfate evenly in 70 - 90% ethanol - water, perform rotary evaporation, carry out ultrafine grinding, with the average particle size below 45 μm, to obtain mixture A for standby;

[0071] 2) Weigh poloxamer and citric acid, dissolve them with absolute ethanol to prepare an adhesive for standby; among them, the weight - volume ratio of ethanol to the stabilizer is 1:10;

[0072] 3) Mix mixture A evenly with microcrystalline cellulose, xylitol and sodium carboxymethyl starch, add a binder to make soft materials, granulate by wet method and dry. Reserve mixture B.

[0073] 4) Add magnesium stearate to mixture B and mix evenly, then press tablets to obtain tablet cores.

[0074] 5) Take 85 g of Opadry enteric coating material, 3 g of polysorbate - 80, and 1.5 g of sodium dodecyl sulfate, add them to the citric acid - sodium citrate buffer solution and stir to dissolve. Stir evenly and add water to make up the volume to 200 mL in total. Adjust the pH value to 5.5 with sodium bicarbonate, stir to completely dissolve the solids, and coat the tablet cores according to the coating process parameters. After spraying the coating solution, dry to obtain methimazole tablets with a separating layer, and the weight of the tablet cores increases by about 4%.

[0075] 6) Take the prescribed amount of Opadry enteric coating material, polysorbate - 80, and sodium dodecyl sulfate, add them to the citric acid - sodium citrate buffer solution and stir to dissolve. Stir evenly and add water to make up the volume to 200 mL in total. Adjust the pH value to 7.0 with sodium bicarbonate, stir to completely dissolve, coat the methimazole tablets with a separating layer obtained in step 5), and dry. The weight of the enteric coating layer increases by about 8.5% to obtain methimazole enteric - coated tablets.

[0076] Example 4

[0077] Formulation:

[0078]

[0079]

[0080] The preparation method is the same as that of Example 3.

[0081] Example 5 Formulation:

[0082]

[0083] The preparation method is the same as that of Example 3.

[0084] Formulation of Comparative Example 1:

[0085]

[0086] The preparation method is the same as that of Example 3.

[0087] Formulation of Comparative Example 2:

[0088]

[0089] The preparation method is the same as that of Example 3.

[0090] Formulation of Comparative Example 3:

[0091]

[0092] The preparation method is the same as that of Example 3.

[0093] Formulation of Comparative Example 4:

[0094]

[0095]

[0096] The preparation method is the same as that of Example 3.

[0097] Comparative Example 5

[0098] Formulation:

[0099]

[0100] Preparation method:

[0101] 1) Add methimazole and sodium thiosulfate to 70 - 90% ethanol - water, mix evenly, perform rotary evaporation, conduct ultrafine grinding, with an average particle size below 45 μm, to obtain mixture A for standby;

[0102] 2) Weigh poloxamer and citric acid, dissolve them with absolute ethanol to make an adhesive for standby; among them, the weight - volume ratio of ethanol to the stabilizer is 1:10;

[0103] 3) Mix mixture A evenly with microcrystalline cellulose, xylitol, and sodium carboxymethyl starch, add the adhesive to make soft materials, perform wet granulation and drying, and obtain mixture B for standby;

[0104] 4) Add magnesium stearate to mixture B, mix evenly, and press tablets to obtain tablet cores;

[0105] 5) Take 85 g of Opadry enteric - coating material, 3 g of polysorbate - 80, and 1.5 g of sodium dodecyl sulfate, add them to water and stir. After stirring evenly, add water to a total volume of 200 mL. Coat the tablet cores according to the coating process parameters. After the coating solution is sprayed out, dry to obtain methimazole tablets with a barrier layer, and the weight of the tablet cores increases by about 4%;

[0106] 6) Take the prescribed amount of Opadry enteric - coating material, polysorbate - 80, and sodium dodecyl sulfate, add them to water and stir. After stirring evenly, add water to a total volume of 200 mL, adjust the pH value to 7.0 with sodium bicarbonate, stir, coat the methimazole tablets with a barrier layer obtained in step 5), dry, and the weight of the enteric - coating layer increases by about 8.5% to obtain methimazole enteric - coated tablets.

[0107] Comparative Example 6

[0108] Formulation:

[0109]

[0110] The preparation method is the same as that of Example 3. The weight gain of the isolation coating is 1%, and the enteric coating is 15%.

[0111] Comparative Example 7

[0112] Formulation:

[0113]

[0114]

[0115] The preparation method is the same as that of Example 3.

[0116] Quality Evaluation of Methimazole Enteric-coated Tablets

[0117] Acidity: Take 1 tablet of this product, grind it finely, transfer it to a 100 ml volumetric flask with water in portions, and determine it according to the law (General Rule 0631).

[0118] Related Substances: Take 1 tablet of this product, grind it finely, transfer it to a 100 ml volumetric flask with water in portions, dissolve it with ethyl acetate and dilute it to make a solution containing 10 mg per 1 ml as the test solution; accurately measure an appropriate amount and dilute it with ethyl acetate to make solutions containing 200 μg, 100 μg, 50 μg, and 10 μg per 1 ml, respectively, as control solutions (1), (2), (3), and (4). According to the thin-layer chromatography method (General Rule 0502), take 20 μl of each of the above five solutions and spot them on the same silica gel G thin-layer plate. Use toluene-isopropanol-concentrated ammonia solution (70:29:1) as the developing agent, develop, air dry, and spray with potassium iodoplatinate solution (take 0.30 g of chloroplatinic acid, dissolve it in 97 ml of water, and add 3.5 ml of potassium iodide test solution immediately before use) to make it develop color. If impurity spots appear in the test solution, compare them with the main spots shown in control solutions (1), (2), (3), and (4).

[0119] Dissolution: Take 1 tablet of this product, grind it finely, transfer it to a 100 ml volumetric flask with water in portions, and determine it according to the dissolution and release determination method (General Rule 0931, Method 2). Use 1000 ml of 0.1 mol / L hydrochloric acid solution as the dissolution medium, rotate at a speed of 100 revolutions per minute, and operate according to the law. After 2 hours, immediately lift the rotating basket out of the liquid surface, and none of the test tablets shall have cracks or disintegration phenomena; immediately immerse the rotating basket in phosphate buffer solution (pH 6.8)

[0120] In 1000 ml of dissolution medium, with the rotation speed unchanged, continue the operation according to the law. At 45 minutes, filter the solution, accurately measure 5 ml of the subsequent filtrate, place it in a 10-ml volumetric flask, dilute it to the mark with water, shake well, and determine the absorbance at a wavelength of 252 nm according to the ultraviolet-visible spectrophotometry (General Principles 0401); take an appropriate amount of methimazole reference substance, accurately weigh it, dissolve it in water and quantitatively dilute it to make a solution containing about 5 μg per 1 ml, and determine it in the same method. Calculate the dissolution of each tablet.

[0121] Content uniformity: Take 1 tablet of this product, grind it finely, transfer it to a 100-ml volumetric flask in portions with water, ultrasonically dissolve methimazole, dilute it to the mark with water, shake well, filter, accurately measure 5 ml of the subsequent filtrate, place it in a 100-ml volumetric flask, dilute it to the mark with water, shake well, and use it as the test solution; take an appropriate amount of methimazole reference substance, accurately weigh it, dissolve it in water and quantitatively dilute it to make a solution containing about 5 μg per 1 ml, and use it as the reference solution. Take the above two solutions, determine the absorbance at a wavelength of 252 nm according to the ultraviolet-visible spectrophotometry (General Principles 0401), and calculate the content of each tablet.

[0122] The physical properties of methimazole enteric-coated tablets are specifically shown in Table 1.

[0123] Table 1 Quality inspection of methimazole enteric-coated tablets

[0124]

[0125] It can be seen from Table 1 that in the accelerated test, Examples 1-5 can maintain good stability in appearance and pH value, and all meet the requirements of the Chinese Pharmacopoeia (2020 Edition), while Comparative Examples 1-7 show different disadvantages in appearance, hardness and pH value, which illustrates the superiority of the tablets of the present invention from the side.

[0126] Regarding the particle size selection of methimazole, the inventors of this application found that when the average particle size is below 45 μm, the angle of repose and fluidity of the particle size are better, and the tablet uniformity meets the requirements; when it is higher than 60 μm, the fluidity of the particles is poor, and colloidal silica needs to be added to meet the requirements, and the fluidity requirements cannot be achieved.

[0127] Figure 1 : The related substance contents (%) of Examples 1 to 5 and Comparative Examples 1-7 at 0, 1, 2, 3, and 6 months of the accelerated test.

[0128] Figure 2 : The cumulative release degrees (%) of Examples 1-3, Example 5, Comparative Examples 1-5, and Comparative Examples 6-7 at the end of 1, 2, 4, 8, 12, 16, and 24 hours in phosphate buffer (pH 6.8).

Claims

1. A tablet containing methimazole, characterized in that, The described tablet is composed of a drug-containing core, a separating layer, and an enteric-coated layer. The drug-containing core is composed of methimazole, a pH buffer, a stabilizer, an antioxidant, a filler, a disintegrant, a lubricant, and a binder; calculated by weight ratio, specifically as follows: The preparation method of the described tablet is as follows: 1) Add methimazole and an antioxidant to 70-90% ethanol water, mix evenly, perform rotary evaporation, and conduct ultrafine grinding with an average particle size below 45 μm to obtain mixture A for standby; 2) Weigh a stabilizer, dissolve it with absolute ethanol to make a binder for standby; 3) Mix mixture A evenly with a filler and a disintegrant, add the binder to make a soft material, perform wet granulation and drying to obtain mixture B for standby; 4) Add a lubricant to mixture B, mix evenly, and press tablets to obtain the tablet core; 5) Coat the tablet core with a separating layer coating and an enteric-coated layer coating to obtain the enteric-coated tablet.

2. The tablet according to claim 1, characterized in that, The described tablet is composed of a drug-containing core, a separating layer, and an enteric-coated layer. The drug-containing core is composed of methimazole, a pH buffer, a stabilizer, an antioxidant, a filler, a disintegrant, a lubricant, and a binder; calculated by weight ratio, specifically as follows:

3. The tablet according to claim 1, characterized in that, The stabilizer is poloxamer and citric acid. Calculated by weight ratio, the ratio of poloxamer to citric acid is 2-4:

1. Preferably, the ratio of poloxamer to citric acid is 3:

1.

4. The tablet according to claim 1, characterized in that, The antioxidant is selected from sodium thiosulfate, sodium metabisulfite, and sodium sulfite. Preferably, the antioxidant is selected from sodium thiosulfate.

5. The tablet according to claim 1, wherein The filler is selected from one or more combinations of microcrystalline cellulose and sorbitol, mannitol, and xylitol; the disintegrant is selected from one or more combinations of dry starch, sodium carboxymethyl starch, pregelatinized starch, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium, and polyvinylpyrrolidone; the lubricant is selected from one or more combinations of magnesium stearate, sodium lauryl sulfate, talc, microcrystalline silica, and colloidal silica.

6. The tablet according to claim 1, characterized in that, The filler is selected from microcrystalline cellulose and xylitol. Calculated by weight ratio, the ratio of microcrystalline cellulose to xylitol is 2-5:

1. Preferably, the ratio of microcrystalline cellulose to xylitol is 4:1; the disintegrant is selected from sodium carboxymethyl starch; the lubricant is selected from magnesium stearate.

7. The tablet according to claim 1, characterized in that, The process of the separating layer coating is as follows: Take the prescribed amount of sodium carboxymethylcellulose, polyethylene glycol-2000, and talc, add them to a citric acid-sodium citrate buffer solution, stir and dissolve, stir evenly, add purified water to the full volume, and adjust the pH value to 5.0-6.0 with citric acid, stir and dissolve, perform coating according to the coating process parameters, and after the coating solution is sprayed out, dry to obtain the methimazole tablet containing the separating layer.

8. The tablet according to claim 1, characterized in that, The process of the enteric-coated layer coating is as follows: Take the prescribed amount of Opadry enteric material, polysorbate-80, and sodium dodecyl sulfate, add them to a citric acid-sodium citrate buffer solution, stir and dissolve, stir evenly and add water to the full volume, and adjust the pH value to 6.5-7.5 with sodium bicarbonate, stir to completely dissolve, place the methimazole tablet containing the separating layer in a coating pan, perform enteric coating, and dry after coating to obtain the methimazole enteric-coated tablet.

9. The tablet according to claim 7 or 8, characterized in that, The pH buffer is selected from a citric acid-sodium citrate buffer solution, and the pH value of the buffer is 5.0-6.

0.

10. The tablet according to claim 1, characterized in that, The described tablet consists of a drug-containing core, a separating layer, and an enteric-coated layer. The drug-containing core is composed of methimazole, a pH buffer, a stabilizer, an antioxidant, a filler, a disintegrant, a lubricant, and a binder. Calculated by weight ratio, specifically as follows: The preparation method of the tablet is as follows: 1) Add methimazole and sodium thiosulfate to 70 - 90% ethanol water, mix evenly, perform rotary evaporation, and conduct ultrafine grinding with an average particle size below 45 μm to obtain mixture A for standby; 2) Weigh poloxamer and citric acid, dissolve them with absolute ethanol to prepare a binder for standby. Among them, the weight - volume ratio of ethanol to the stabilizer is 1:10; 3) Mix mixture A with microcrystalline cellulose, xylitol, and sodium carboxymethyl starch evenly, add the binder to make a soft material, perform wet granulation and drying to obtain mixture B for standby; 4) Add magnesium stearate to mixture B, mix evenly, and press tablets to obtain the tablet core; 5) Take the prescribed amount of sodium carboxymethylpropylcellulose, polyethylene glycol - 2000, and talcum powder, add them to the citric acid - sodium citrate buffer solution, stir and dissolve, stir evenly, add purified water to the full volume, adjust the pH value to 5.0 - 6.0 with citric acid, stir until the solids are completely dissolved, and coat the tablet core according to the coating process parameters. After the coating solution is sprayed out, dry to obtain the methimazole tablet with a separating layer, and the tablet core weight gain is about 3 - 5%; 6) Take the prescribed amount of Opadry enteric material, polysorbate - 80, and sodium dodecyl sulfate, add them to the citric acid - sodium citrate buffer solution, stir and dissolve, stir evenly, add water to the full volume, adjust the pH value to 6.5 - 7.5 with sodium bicarbonate, stir until completely dissolved, coat the methimazole tablet with a separating layer in step 5), dry, and the enteric-coated layer weight gain is about 7 - 10% to obtain the enteric-coated methimazole tablet.

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