Melogabalin besylate tablet containing excellent stabilizer and preparation method of melogabalin besylate tablet

Abstract

The invention discloses an oral solid preparation melogabalin besylate tablet containing an excellent stabilizer and a preparation method thereof. A tablet core contains but is not limited to melogabalin besylate, one or two or more filling agents, one or two or more disintegrating agents, one or two or more flow aids and various stabilizer compositions. According to the invention, the optimal stabilizer composition is selected through investigation, so that the growth of main degradation impurities and oxidation impurities is effectively controlled, the product stability is improved, and the tablets with stable quality are obtained. The product is rapidly dissolved out, the dissolution uniformity is good, the intermediate tabletting is smooth, the compressibility is good, and the prepared finished product is good in appearance, free of small holes and stable and controllable in quality.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations, and particularly relates to a melogabalin besylate tablet containing a stabilizer and a preparation method thereof. Background Art

[0002] Mirogabalin Besilate is a new type of chronic pain treatment drug. It binds to the voltage-gated calcium channel (VGCC) subunit α2δ (CACNA2D), plays an auxiliary role in the function of voltage-dependent calcium channels in the nervous system, inhibits calcium currents, and can exert analgesic effects.

[0003] Melegabalin besylate is a white to slightly yellowish white powder, and its chemical name is [(1R, 5S, 6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid monobenzenesulfonate, and its structural formula is as follows:

[0004]

[0005] Japanese pharmaceutical company Daiichi Sankyo's Tarlige (Melogabalin besylate) 2.5mg, 5mg, 10mg, 15mg tablets have been approved in Japan for the treatment of peripheral neuropathic pain (PNP). Patent CN107405322B protects a solid preparation containing melogabalin besylate, and protects a composition including a filler, a disintegrant and an antioxidant. Patent CN104334169 protects a solid composition containing melogabalin besylate, specifically protecting the filler mannitol, the disintegrant calcium carboxymethylcellulose and the lubricant magnesium stearate or sodium stearyl fumarate. CN117618375 claims protection for a melogabalin tablet, the core of which includes a core containing minobaline besylate, an excipient, a disintegrant, a lubricant and an antioxidant, and the antioxidant includes malic acid, tartaric acid, fumaric acid, ascorbyl palmitate, etc.

[0006] Existing technologies have been extensively studied to obtain preparations with good stability. However, during the storage process, drugs will still undergo oxidative degradation and increase impurities. If a drug degrades and deteriorates, not only will the efficacy be reduced, but it may even produce toxic side effects, thus affecting the effectiveness and safety of the drug in clinical applications. Therefore, ensuring the stability of drug preparations is crucial to ensuring the quality, safety and effectiveness of preparation products. In order to obtain drugs with better stability and fewer impurities and meet the requirements of different storage conditions, it is still necessary to study new stable preparations. Summary of the invention

[0007] The object of the present invention is to provide a melogabalin besylate preparation with better stability and lower content of related substances, which can effectively control the generation of oxidative impurities and degradation impurities, and effectively improve the bioavailability and safety of melogabalin.

[0008] On one hand, the present invention provides a melogabalin besylate tablet, wherein the tablet core comprises melogabalin besylate, a filler, a disintegrant, a lubricant, a glidant and a stabilizer, wherein the stabilizer is selected from propyl gallate, ascorbyl palmitate, disodium edetate, anhydrous or monohydrate citric acid, tocopherol, malic acid, tartaric acid, fumaric acid, maleic acid, butylated hydroxytoluene, preferably one or more selected from tocopherol, anhydrous citric acid, monohydrate citric acid, tartaric acid, ascorbyl palmitate and propyl gallate, and the melogabalin besylate is [(1R, 5S, 6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6yl]acetic acid monobenzenesulfonate, and the structural formula is:

[0009]

[0010] As a preferred technical solution, the filler is selected from one or more of mannitol, lactose, corn starch, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, and sorbitol; as a more preferred technical solution, the filler is selected from one or both of mannitol and microcrystalline cellulose.

[0011] As a preferred technical solution, the disintegrant is selected from one or more of sodium carboxymethylcellulose, calcium carboxymethylcellulose, carboxymethylcellulose, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose; as a more preferred technical solution, the disintegrant is selected from one or two of sodium carboxymethyl starch and calcium carboxymethylcellulose; as the most preferred technical solution, the disintegrant is selected from calcium carboxymethylcellulose.

[0012] As a preferred technical solution, the filler and disintegrant combination is a combination of mannitol and calcium carboxymethylcellulose or a combination of mannitol and sodium starch glycolate; as a more preferred technical solution, the filler and disintegrant combination is a combination of mannitol and calcium carboxymethylcellulose; as the most preferred technical solution, the filler and disintegrant combination is a combination of mannitol 200SD and calcium carboxymethylcellulose.

[0013] As a preferred technical solution, the lubricant is selected from one or more of magnesium stearate, sodium stearyl fumarate, and talc; as a more preferred technical solution, the lubricant is selected from magnesium stearate.

[0014] As a preferred technical solution, the flow aid is selected from one or more of magnesium aluminum metasilicate, magnesium aluminum silicate, and silicon dioxide; as a more preferred technical solution, the flow aid is selected from magnesium aluminum metasilicate and magnesium aluminum silicate; as the most preferred technical solution, the flow aid is selected from magnesium aluminum metasilicate.

[0015] As a preferred technical solution, the stabilizer is selected from propyl gallate, ascorbyl palmitate, disodium edetate, anhydrous or monohydrate citric acid, tocopherol, malic acid, tartaric acid, fumaric acid, maleic acid, and butylated hydroxytoluene; as a more preferred technical solution, the stabilizer is selected from one or more of tocopherol, anhydrous citric acid, monohydrate citric acid, tartaric acid, ascorbyl palmitate, and propyl gallate; as the most preferred technical solution, the stabilizer is selected from a combination of ascorbyl palmitate and tartaric acid, propyl gallate and tartaric acid, ascorbyl palmitate and anhydrous citric acid and / or monohydrate citric acid, propyl gallate or DL-α-tocopherol and anhydrous citric acid, citric acid monohydrate and / or anhydrous citric acid and DL-α-tocopherol.

[0016] As a preferred technical solution, the stabilizer combination 1 is tartaric acid and ascorbyl palmitate, and the weight of the tablet core is 0.1% to 5% and 0 to 1%, preferably 0.5% to 3.5% and 0.05% to 0.5%, more preferably 1% to 3% and 0.1% to 0.35%, and further preferably 1.5% to 2.5% and 0.1% to 0.3%; the stabilizer combination 2 is tartaric acid and propyl gallate, and the weight of the tablet core is 0.1% to 5% and 0 ~1%, preferably 0.5%~3.5% and 0.01%~0.5%, more preferably 1%~3% and 0.02%~0.35%, further preferably 1.5%~2.5% and 0.02%~0.3%; the stabilizer combination 3-4 is anhydrous citric acid and / or citric acid monohydrate and ascorbyl palmitate, accounting for 0.5%~15% and 0~1% of the tablet weight, preferably 0.7%~10% and 0.05%~0.5%, more preferably 1%~6% and 0.1% to 0.35%, more preferably 1.2% to 4% and 0.1% to 0.3%; the stabilizer combination 5 is anhydrous citric acid and propyl gallate, accounting for 1% to 10% and 0 to 1% of the tablet weight, preferably 1.5% to 10% and 0.01% to 0.45%, more preferably 1.7% to 5% and 0.02% to 0.35%, further preferably 2% to 4% and 0.02% to 0.3%; the stabilizer combination 6 is anhydrous citric acid and citric acid monohydrate and DL-α-tocopherol, accounting for 0.1% to 15% and 0 to 1% of the tablet weight, respectively, preferably 0.2% to 10% and 0.05% to 0.5%, more preferably 0.5% to 7% and 0.1% to 0.35%, further preferably 0.7% to 6% and 0.1% to 0.3%; the stabilizer combination 7 is anhydrous citric acid and DL-α-tocopherol, accounting for 1% to 10% and 0 to 1% of the tablet weight, respectively, preferably 1.5% to 10% and

[0017] 0.05% to 0.7%, more preferably 1.7% to 6% and 0.1% to 0.5%, further preferably 2% to 4% and 0.1% to 0.3%

[0018] As a preferred technical solution, melogabalin besylate accounts for 1% to 10% of the weight of the tablet core, preferably 2.5% to 7.5%, and more preferably 3% to 5%; mannitol 200SD accounts for 70% to 90% of the weight of the tablet core, preferably 72% to 85%, and more preferably 75% to 83%; microcrystalline cellulose accounts for 0% to 20% of the weight of the tablet core, preferably 1% to 10%, and more preferably 1.3% to 3%; carboxymethylcellulose calcium accounts for 2% to 20% of the weight of the tablet core, preferably 4% to 18%, more preferably 6% to 16%, and more preferably 7.5% to 15%; magnesium stearate accounts for 0.1% to 3% of the weight of the tablet core, preferably 0.5% to 2.5%, and more preferably 1.0% to 2.0%; magnesium aluminum metasilicate accounts for 0% to 0.5% of the weight of the tablet core, preferably 0.1% to 0.3%.

[0019] As a preferred technical solution, the melogabalin besylate tablets include melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, tartaric acid, and ascorbyl palmitate, wherein the percentage of each component in the weight of the tablet core is as follows:

[0020]

[0021] Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, tartaric acid, and propyl gallate, wherein the percentage of each component in the weight of the tablet core is as follows:

[0022]

[0023] Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, anhydrous citric acid, and propyl gallate, wherein the percentage of each component in the weight of the tablet core is as follows:

[0024]

[0025] Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, anhydrous citric acid, and ascorbyl palmitate, wherein the percentage of each component in the weight of the tablet core is as follows:

[0026]

[0027]

[0028] Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, citric acid monohydrate, and ascorbyl palmitate, wherein the percentage of each component in the weight of the tablet core is as follows:

[0029]

[0030] Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, citric acid monohydrate, anhydrous citric acid, and ascorbyl palmitate, wherein the percentage of each component in the weight of the tablet core is as follows:

[0031]

[0032] Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, anhydrous citric acid, and DL-α-tocopherol, wherein the percentage of each component in the weight of the tablet core is as follows:

[0033]

[0034] Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, anhydrous citric acid, monohydrate citric acid, and DL-α-tocopherol, wherein the percentage of each component in the weight of the tablet core is as follows:

[0035]

[0036] As a preferred technical solution, the tablet is a coated tablet, the coating agent is selected from a gastric soluble film coating agent, the coating weight gain is 1% to 7%, preferably the coating weight gain is 2% to 6%, and more preferably 2% to 5%.

[0037] The present invention also provides a melogabalin besylate tablet, which comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, tartaric acid, and ascorbyl palmitate, wherein the percentage of each component in the weight of the tablet core is as follows:

[0038]

[0039]

[0040] The present invention also provides a method for preparing melogabalin besylate tablets, which is characterized by comprising the following steps:

[0041] 1) passing melogabalin benzenesulfonate through a 80-mesh sieve;

[0042] 2) Grind the stabilizer and pass it through a 120-mesh sieve or directly pass it through a 120-mesh sieve;

[0043] 3) Weigh the prescribed amount of melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium aluminum metasilicate, and stabilizer, mix them, and then sieve the mixture three times;

[0044] 4) weighing the prescribed amount of magnesium stearate and adding it to step 3) for mixing;

[0045] 5) Use a 10.7*5.7mm oval punch with notches for tableting to control tablet weight and hardness;

[0046] 6) Prepare coating solution and coat the core tablets in step 5) with a target weight gain of 2% to 5%.

[0047] As a preferred technical solution, the stabilizer is selected from DL-α-tocopherol.

[0048] As a preferred technical solution, the DL-α-tocopherol needs to be mixed with microcrystalline cellulose before mixing.

[0049] The beneficial effects of the present invention are as follows: through a lot of labor, a specific preparation prescription is screened out, the stability of melogabalin besylate is improved, the content of related impurities thereof is controlled, rapid dissolution is ensured, and the quality is stable and controllable.

[0050] The degradation impurities described in the present invention are mainly J, and the impurity is named a.

[0051] The structural formula of impurity a is:

[0052] DETAILED DESCRIPTION

[0053] The present invention is further described below in conjunction with Examples and Comparative Examples. The following description is only for explaining the present invention and is not intended to limit its content in any way. In the embodiments, if specific conditions are not specified, the conditions are carried out according to normal conditions or manufacturer recommendations. If the manufacturer is not specified for reagents or instruments used, they are all conventional products that can be purchased commercially.

[0054] The following is a detailed description of the melogabalin besylate tablet preparations and preparation methods thereof according to the embodiments and comparative examples of the present invention.

[0055] In Examples 1 to 20, the stability of the combination of one or more stabilizers was investigated by fixing the filler as a combination of mannitol 200SD and microcrystalline cellulose and the disintegrant as carboxymethylcellulose calcium in Formulas 1 to 20.

[0056] Table 1 Single stabilizer and stabilizer dosage of prescriptions 1 to 5

[0057]

[0058]

[0059] Table 2 Two stabilizers and their dosages in prescriptions 6 to 12

[0060]

[0061] Table 3 Three stabilizers and their dosage in prescriptions 13 to 16

[0062]

[0063]

[0064] Table 4 Two stabilizers and their dosages in prescriptions 17 to 20

[0065]

[0066] Comparative Examples 1 to 3: In the comparative example prescriptions, the fixed fillers were mannitol M100 and microcrystalline cellulose, and the disintegrant was sodium starch glycolate. The stability of the formulations in which the filler + disintegrant combinations were mannitol 200SD, microcrystalline cellulose + calcium starch glycolate, mannitol 100M, and microcrystalline cellulose + sodium starch glycolate was investigated.

[0067] Table 5 Comparative Example Prescriptions 1 to 3 (5 mg)

[0068]

[0069] Comparative Example 4: Zhengda Tianqing patent CN117618375 A discloses a low impurity level formula for coated tablets placed at 40℃ / 75%RH for 1M, see Table 6

[0070] Table 6 Comparative Example Prescription 4 (5 mg)

[0071] prescription Comparative Example 4 (Zhengda Tianqing) - 5mg specification Name of raw materials Single dose (mg / tablet) Melogabalin Besylate 8.78 Mannitol M100 166.8 Microcrystalline Cellulose 8 Carboxymethylcellulose calcium 10 Malic Acid 3 Magnesium aluminum silicate 0.4 Magnesium Stearate 3 Total (in plain film) 200 OPADRY(R) 2～5％

[0072] According to the prescription in the above table, tablet cores were prepared based on the following preparation method of melogabalin besylate tablets:

[0073] The raw material of melogabalin besylate is passed through an 80-mesh sieve, and the raw material is weighed according to the prescription amount; mannitol, disintegrant, magnesium aluminum metasilicate, and microcrystalline cellulose are weighed according to the prescription amount; the stabilizer is crushed and passed through a 120-mesh sieve or directly passed through a 120-mesh sieve, and the stabilizer is weighed according to the prescription amount; the sieved melogabalin besylate, mannitol, disintegrant, stabilizer, magnesium aluminum metasilicate, and microcrystalline cellulose (if the stabilizer is DL-α-tocopherol, it needs to be mixed with microcrystalline cellulose before mixing) are mixed evenly; magnesium stearate is added for total mixing. A 10.7×5.7mm oval punch is used, and the theoretical tablet weight is 200mg (the weight difference is controlled to be ±5%, i.e. 190-210mg) for tableting; the tablet core is coated, and the target weight gain is 2%-5%.

[0074] Stability study of experimental example

[0075] Stability test plan

[0076] Place the above prescription core tablets or bare coated tablets / aluminum-plastic blister + 1 bag of desiccant + composite film bag under accelerated conditions (40°C 75% RH) for 0, 10, and 30 days respectively, examine the properties of the core tablets / coated tablets and related substances, and screen the best prescription.

[0077] Table 7 Stability test conditions

[0078] Related substance detection method: weigh 3.0g sodium hydroxide and place it in 2000ml purified water, add 8.7ml perchloric acid after dissolving, and adjust the pH value to 2.0 with diluted sodium hydroxide solution (0.1mol / L). The chromatographic column is Agilent Zorbax, Eclipse XDB-phenyl (250x 4.6) mm, 5um; detection method: high performance liquid chromatography; flow rate 1.0ml / min, column temperature 30℃, injection volume 10μL, wavelength 210nm, mobile phase B: acetonitrile.

[0079]

[0080]

[0081] Stability test results

[0082] Table 9 Stabilizer screening prescription tablet core stability test results

[0083]

[0084]

[0085]

[0086]

[0087] In summary, the stability of the formulations in which the filler + disintegrant combination is mannitol 200SD, microcrystalline cellulose + carboxymethylcellulose calcium is significantly better than the combination of mannitol M100 and microcrystalline cellulose + carboxymethyl starch sodium; the stabilizer combination is tartaric acid or citric acid monohydrate and ascorbyl palmitate, tartaric acid and propyl gallate, citric acid monohydrate and anhydrous citric acid and DL-α-tocopherol, all of which have obvious advantages, low total impurity growth rate, and good product appearance, meeting the drug quality requirements. When the stabilizer is selected as a combination of tartaric acid (2.5%) and ascorbyl palmitate (0.2%), its stability is unexpectedly good.

[0088] Comparison of stability between homemade prescription preparation and reference preparation

[0089] The coating and placement stability of the homemade optimal formulation were tested, and the stability was compared with that of the reference formulation (specification: 5 mg; manufacturer: Daiichi Sankyo Co., Ltd.) and comparative example 4, and the dissolution curve was simultaneously examined; the stability test plan and detection method are shown in Tables 6 to 7.

[0090] Table 10 Stability comparison results between the best prescription preparation and the reference preparation (properties, related substances)

[0091]

[0092] The dissolution test was carried out in accordance with the second method (paddle method) of Part IV of the 2020 edition of the Chinese Pharmacopoeia, 0931, to measure the cumulative dissolution of prescription 10, prescription 12 and the reference preparation in pH 1.2 and pH 6.8 media. The chromatographic analysis method was the same as the chromatographic analysis method in the stability test. The dissolution test results are shown in Table 11.

[0093] Table 11 Stability comparison results of the best prescription preparation and the reference preparation (dissolution curve)

[0094]

[0095] It can be seen from Tables 10-11 that the properties and related substances of the homemade preparation prescription provided by the present invention and the reference preparation all meet the requirements of medicines, and the quality level of the homemade preparation samples is equivalent to that of the reference preparation, and basically complete release is achieved in 10 minutes, which meets the requirements of medicines.

Claims

1. A melogabalin besylate tablet, characterized in that: The tablet core comprises melogabalin besylate, a filler, a disintegrant, a lubricant, a glidant and a stabilizer, wherein the stabilizer is selected from propyl gallate, ascorbyl palmitate, disodium edetate, anhydrous or monohydrate citric acid, tocopherol, malic acid, tartaric acid, fumaric acid, maleic acid, butylated hydroxytoluene, preferably one or more selected from tocopherol, anhydrous citric acid, monohydrate citric acid, tartaric acid, ascorbyl palmitate, and propyl gallate, and melogabalin besylate is [(1R, 5S, 6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6yl]acetic acid monobenzenesulfonate.

2. The melogabalin besylate tablet according to claim 1, characterized in that: The filler is selected from one or more of mannitol, lactose, corn starch, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, and sorbitol, preferably one or two of mannitol and microcrystalline cellulose.

3. The melogabalin besylate tablet according to claim 1, characterized in that The disintegrant is selected from one or more of sodium carboxymethylcellulose, calcium carboxymethylcellulose, carboxymethylcellulose, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose, preferably one or two of sodium carboxymethyl starch and calcium carboxymethylcellulose, and more preferably calcium carboxymethylcellulose.

4. The melogabalin besylate tablet according to claim 2-3, characterized in that: The filler and disintegrant combination is a combination of mannitol and carboxymethylcellulose calcium or a combination of mannitol and sodium starch glycolate, preferably a combination of mannitol and carboxymethylcellulose calcium, more preferably a combination of mannitol 200SD and carboxymethylcellulose calcium.

5. The melogabalin besylate tablet according to claim 1, characterized in that: The lubricant is selected from one or more of magnesium stearate, sodium stearyl fumarate, and talc, preferably magnesium stearate.

6. The melogabalin besylate tablet according to claim 1, characterized in that: The glidant is selected from one or more of magnesium aluminum metasilicate, magnesium aluminum silicate, and silicon dioxide, preferably magnesium aluminum metasilicate and magnesium aluminum silicate, and more preferably magnesium aluminum metasilicate.

7. The melogabalin besylate tablet according to claim 1, wherein the stabilizer is selected from the group consisting of ascorbyl palmitate and tartaric acid, propyl gallate and tartaric acid, ascorbyl palmitate and anhydrous citric acid and / or citric acid monohydrate, propyl gallate or DL-α-tocopherol and anhydrous citric acid, citric acid monohydrate and / or a combination of anhydrous citric acid and DL-α-tocopherol.

8. The melogabalin besylate tablet according to claim 1, characterized in that: The stabilizer combination 1 is tartaric acid and ascorbyl palmitate, accounting for 0.1% to 5% and 0 to 1% of the tablet weight, preferably 0.5% to 3.5% and 0.05% to 0.5%, more preferably 1% to 3% and 0.1% to 0.35%, and further preferably 1.5% to 2.5% and 0.1% to 0.3%; the stabilizer combination 2 is tartaric acid and propyl gallate, accounting for 0.1% to 5% and 0 to 1% of the tablet weight, preferably 0.5% to 3.5% and 0.01% The stabilizer combination 3-4 is citric acid anhydrous and / or citric acid monohydrate and ascorbyl palmitate, accounting for 0.5%-15% and 0-1% of the tablet weight, preferably 0.7%-10% and 0.05%-0.5%, more preferably 1%-6% and 0.1%-0.35%, further preferably 1.2%-4% and 0.1%-0. .3%; the stabilizer combination 5 is anhydrous citric acid and propyl gallate, accounting for 1% to 10% and 0 to 1% of the tablet weight, preferably 1.5% to 10% and 0.01% to 0.45%, more preferably 1.7% to 5% and 0.02% to 0.35%, and further preferably 2% to 4% and 0.02% to 0.3%; the stabilizer combination 6 is anhydrous citric acid, citric acid monohydrate and DL-α-tocopherol, accounting for 0.1% to 15% and 0 to 1% of the tablet weight, preferably 0 .2%~10% and 0.05%~0.5%, more preferably 0.5%~7% and 0.1%~0.35%, further preferably 0.7%~6% and 0.1%~0.3%; the stabilizer combination 7 is anhydrous citric acid and DL-α-tocopherol, which account for 1%~10% and 0~1% of the tablet weight respectively, preferably 1.5%~10% and 0.05%~0.7%, more preferably 1.7%~6% and 0.1%~0.5%, further preferably 2%~4% and 0.1%~0.3%.

9. The melogabalin besylate tablet according to claims 1-8, characterized in that: The amount of melogabalin besylate in the tablet core is 1% to 10%, preferably 2.5% to 7.5%, and more preferably 3% to 5%; the amount of mannitol 200SD in the tablet core is 70% to 90%, preferably 72% to 85%, and more preferably 75% to 83%; the amount of microcrystalline cellulose in the tablet core is 0% to 20%, preferably 1% to 10%, and more preferably 1.3% to 3%; the amount of carboxymethylcellulose calcium in the tablet core is 2% to 20%, preferably 4% to 18%, more preferably 6% to 16%, and more preferably 7.5% to 15%; the amount of magnesium stearate in the tablet core is 0.1% to 3%, preferably 0.5% to 2.5%, and more preferably 1.0% to 2.0%; the amount of magnesium aluminum metasilicate in the tablet core is 0% to 0.5%, and preferably 0.1% to 0.3%.

10. The melogabalin besylate tablet according to claim 1, characterized in that: The melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, tartaric acid, and ascorbyl palmitate, wherein the percentage of each component in the weight of the tablet core is as follows: Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, tartaric acid, and propyl gallate, wherein the percentage of each component in the weight of the tablet core is as follows: Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, anhydrous citric acid, and propyl gallate, wherein the percentage of each component in the weight of the tablet core is as follows: Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, anhydrous citric acid, and ascorbyl palmitate, wherein the percentage of each component in the weight of the tablet core is as follows: Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, citric acid monohydrate, and ascorbyl palmitate, wherein the percentage of each component in the weight of the tablet core is as follows: Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, citric acid monohydrate, anhydrous citric acid, and ascorbyl palmitate, wherein the percentage of each component in the weight of the tablet core is as follows: Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, anhydrous citric acid, and DL-α-tocopherol, wherein the percentage of each component in the weight of the tablet core is as follows: Alternatively, the melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, anhydrous citric acid, monohydrate citric acid, and DL-α-tocopherol, wherein the percentage of each component in the weight of the tablet core is as follows: 。 11. The melogabalin besylate tablet according to any one of claims 1 to 10, characterized in that: The tablet is a coated tablet, the coating agent is selected from a gastric soluble film coating agent, the coating weight gain is 1% to 7%, preferably the coating weight gain is 2% to 6%, and more preferably 2% to 5%.

12. A melogabalin besylate tablet, characterized in that: The melogabalin besylate tablet comprises melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium stearate, magnesium aluminum metasilicate, tartaric acid, and ascorbyl palmitate, wherein the percentage of each component in the weight of the tablet core is as follows: 。 13. A method for preparing melogabalin besylate tablets, characterized in that: Including the following processes: Pass melogabalin benzenesulfonate through a 80-mesh sieve; After the stabilizer is crushed, it is passed through a 120-mesh sieve or directly passed through a 120-mesh sieve; Weigh the prescribed amount of melogabalin besylate, mannitol 200SD, microcrystalline cellulose, carboxymethylcellulose calcium, magnesium aluminum metasilicate, and stabilizer, mix, and then sieve the mixture three times; Weigh the prescribed amount of magnesium stearate and add it into step 3) for mixing; Use a 10.7*5.7mm oval punch with notches for tableting to control tablet weight and hardness; Prepare coating solution and coat the core tablets in step 5) with a target weight gain of 2% to 5%; The stabilizer is selected from DL-α-tocopherol.

14. The method for preparing melogabalin besylate tablets according to claim 13, characterized in that: The DL-α-tocopherol is mixed with microcrystalline cellulose and then mixed.

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