Melogabalin besylate tablet and preparation method thereof

Abstract

The invention discloses a melogabalin besylate tablet and a preparation method thereof. The tablet core comprises melogabalin besylate, a filler, a disintegrant, a lubricant, a glidant and a stabilizer, wherein the disintegrant is sodium carboxymethyl starch and the stabilizers are tocopherol and tartaric acid. The invention selects sodium carboxymethyl starch as the disintegrant and, through investigation of the type and amount of the stabilizer, selects a specific stabilizer combination to prepare melogabalin besylate tablets having better stability (especially quality control of impurity I) than a reference preparation. The invention overcomes the technical prejudice in the prior art that the stability of calcium carboxymethyl cellulose is better than that of sodium carboxymethyl starch.

Description

Technical Field

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

[0002] Mirogabalin Besilate is a novel pain medication that binds to the α2δ subunit (CACNA2D) of the voltage-gated calcium channel (VGCC) and plays a supporting role in the function of voltage-dependent calcium channels in the nervous system, inhibiting calcium currents and exerting analgesic effects. Its marketed indication is the treatment of diabetic peripheral neuropathic pain. 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 shown below:

[0003]

[0004] Patent CN104334169A of Daiichi Sankyo, the original research pharmaceutical company, protects a solid composition containing melogabalin besylate, specifically protecting the composition of the filler mannitol, the disintegrant carboxymethylcellulose calcium, and the lubricant magnesium stearate or sodium stearyl fumarate. It also discloses that in the screening of disintegrants, carboxymethylcellulose calcium showed better stability than sodium carboxymethyl starch.

[0005] Based on the patent CN104334169A that the choice of carboxymethylcellulose calcium as a disintegrant would result in a better sodium carboxymethyl starch, the original research conducted a study on the formulation of the solid preparation of melogabalin besylate:

[0006] 1) Patent CN107405322A protects a solid preparation of minobalin besylate containing a stabilizer, which includes a disintegrant, carboxymethylcellulose calcium, and a stabilizer selected from one or a combination of two or more stabilizers selected from sodium edetate, citric acid hydrate, butylated hydroxytoluene, propyl gallate, magnesium citrate (anhydrous), soy lecithin, α-tocopherol, α-tocopheryl acetate, and β-cyclodextrin. The obtained preparation has an inhibited increase in total impurities under accelerated conditions.

[0007] 2) Patent CN111971036A also discloses a solid preparation of melogabalin besylate containing a stabilizer. Citric anhydride or citric acid hydrate and tocopherol at specific contents and / or content ratios are selected as stabilizers, which are combined with the disintegrant carboxymethylcellulose calcium to specifically inhibit the formation of specific impurity decomposition products A and decomposition products B.

[0008] It can be seen that in the development process of melogabalin besylate solid preparations, the types of disintegrants and stabilizers jointly affect the stability of the preparations: ① First, the preparation stability is better when the disintegrant is preferably carboxymethylcellulose calcium rather than carboxymethyl starch sodium; ② Second, even if carboxymethylcellulose calcium is selected as the disintegrant, when used with any single stabilizer or a combination of multiple stabilizers, the effect of inhibiting the growth of impurities is completely different; for example, carboxymethylcellulose calcium can only inhibit the formation of decomposition products A and B when used with specific stabilizers ("citric acid anhydride + tocopherol" or "citric acid hydrate + tocopherol").

[0009] The applicant further searched and found that the prior art also provided the following technical solutions in order to provide a melogabalin besylate preparation with good stability and low content of related substances.

[0010] Patent CN117618375A discloses a minobalin tablet, the core of which contains minobalin besylate, an excipient, a disintegrant, a lubricant, and a stabilizer. When malic acid, a stabilizer, is added and combined with carboxymethylcellulose calcium, a disintegrant, the tablet has better stability than other stabilizers (such as tartaric acid, tocopherol, and fumaric acid).

[0011] Patent CN118806717A discloses a solid preparation of melogabalin besylate, which uses solid stabilizers such as tartaric acid, malic acid, and sodium citrate instead of the liquid stabilizer tocopherol, and uses carboxymethylcellulose calcium as the disintegrant. Compared with the original research, the production process is simplified while achieving the same stabilization effect.

[0012] Patent CN119235806A discloses a melogabalin besylate tablet. When the type of stabilizer is the same, the stability of the formulation using the filler and disintegrant combination of "mannitol 200SD + microcrystalline cellulose + carboxymethyl cellulose calcium" is significantly better than that of the formulation of "mannitol M100 + microcrystalline cellulose + sodium starch glycolate".

[0013] In summary, while existing technologies have expended extensive research to develop formulations with excellent stability, the influence of the original patented formulation has limited development strategies to the selection of calcium carboxymethylcellulose as a disintegrant, followed by the selection of a stabilizer. Furthermore, existing technologies have demonstrated that formulations using calcium carboxymethylcellulose exhibit superior stability compared to those using sodium carboxymethyl starch. This means it is unclear whether alternative disintegrants (such as sodium carboxymethyl starch) could achieve the same, or even superior, stability as the original patented formulation.

[0014] Therefore, how to select a suitable stabilizer (either a single stabilizer or a composite stabilizer) based on sodium carboxymethyl starch as a disintegrant and optimize the formulation process to obtain a new melogabalin besylate tablet with better stability and fewer impurities is a technical problem that has not yet been solved by those skilled in the art. Summary of the Invention

[0015] The technical problem to be solved by the present invention is to prepare a melogabalin besylate tablet with better stability and fewer impurities by selecting a suitable stabilizer and optimizing the formulation process on the basis of using sodium carboxymethyl starch as a disintegrant.

[0016] In order to solve the above technical problems, the present invention is implemented through the following technical solutions:

[0017] The invention provides a melogabalin besylate tablet, comprising a main drug melogabalin besylate, a filler, a disintegrant, a lubricant, a glidant, a stabilizer and other auxiliary materials, wherein the disintegrant is sodium carboxymethyl starch, and the stabilizer is a combination of tartaric acid and tocopherol.

[0018] Preferably, the mass ratio of tartaric acid to tocopherol in the stabilizer must be greater than 20:1.

[0019] More preferably, the mass ratio of tartaric acid to tocopherol in the stabilizer is (21.7-35.1):1.

[0020] In the present invention, the tocopherol may more preferably be DL-α-tocopherol.

[0021] In the present invention, as long as sodium carboxymethyl starch is used as a disintegrant and the mass ratio of tartaric acid to tocopherol in the stabilizer is greater than 20:1, melogabalin besylate tablets with excellent stability can be produced. Therefore, when considering the selection of fillers, lubricants, and glidants, the inventors are not limited to the components listed in Example 1 of the present invention; any conventional pharmaceutically acceptable excipients can be used.

[0022] Specifically, the filler in the present invention can be selected from one or more of mannitol, lactose, corn starch, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, and sorbitol; more preferably, it can be one or two of mannitol and microcrystalline cellulose.

[0023] Similarly, the lubricant in the present invention can be selected from one or more of magnesium stearate, sodium stearyl fumarate, and talc; more preferably, magnesium stearate.

[0024] Similarly, the flow aid in the present invention can be selected from one or more of magnesium aluminum metasilicate, magnesium aluminum silicate, and silicon dioxide, and is more preferably magnesium aluminum metasilicate.

[0025] Similarly, based on the plain tablets provided by the present invention, the plain tablets can be coated, and the coating materials are all pharmaceutically acceptable conventional coating materials, including but not limited to gastric soluble film coatings.

[0026] The present invention also provides the appropriate mass proportions of the components in the aforementioned melogabalin besylate tablets (taking the component types described in Example 1 of the present invention as an example), specifically:

[0027] A melogabalin besylate tablet. Based on the total weight of the tablet being 100%, the weight percentages of the components in the tablet are as follows: 1-10% melogabalin besylate, 70-78% mannitol, 0.1-10% microcrystalline cellulose, 5-20% sodium carboxymethyl starch, 0.1-0.5% tocopherol, 3-5% tartaric acid, 0.1-3% magnesium stearate, and 0.1-0.5% magnesium aluminum metasilicate; and the mass ratio of tartaric acid to tocopherol must be greater than 20:1.

[0028] Furthermore, the weight percentage of each component in the melogabalin besylate tablets can also be preferably: melogabalin besylate 2-8%, mannitol 75-78%, microcrystalline cellulose 0.1-1%, sodium carboxymethyl starch 7.5-12.5%, tocopherol 0.1-0.2%, tartaric acid 3-5%, magnesium stearate 0.5-2.5%, magnesium aluminum metasilicate 0.1-0.3%; and the mass ratio of tartaric acid to tocopherol must be greater than 20:1.

[0029] More preferably, the weight percentage of each component in the melogabalin besylate tablets in the tablets is: melogabalin besylate 5.86%, mannitol 76.47~77.95%, microcrystalline cellulose 0.9%, sodium carboxymethyl starch 10%, tocopherol 0.1~0.17%, tartaric acid 2.67~4%, magnesium stearate 2%, magnesium aluminum metasilicate 0.2%; and the mass ratio of tartaric acid to tocopherol must be greater than 20:1.

[0030] In addition, the present invention also provides some specific prescriptions of melogabalin besylate tablets, including:

[0031] Disclosed are melogabalin besylate tablets. Each 150 parts by mass of the tablets contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 116.34 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.23 parts by mass of tocopherol, 5 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

[0032] Disclosed are melogabalin besylate tablets. Each 150 parts by mass of the tablets contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 116.92 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.15 parts by mass of tocopherol, 4.5 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

[0033] Disclosed are melogabalin besylate tablets. Each 150 parts by mass of the tablets contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 116.88 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.19 parts by mass of tocopherol, 4.5 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

[0034] Disclosed are melogabalin besylate tablets. Each 150 parts by mass of the tablets contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 114.71 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.19 parts by mass of tocopherol, 6.67 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

[0035] Disclosed are melogabalin besylate tablets. Each 150 parts by mass of the tablets contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 115.06 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.21 parts by mass of tocopherol, 6.3 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

[0036] Disclosed are melogabalin besylate tablets. Each 150 parts by mass of the tablets contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 115.32 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.25 parts by mass of tocopherol, 6 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

[0037] In addition, the present invention also provides a melogabalin besylate tablet, comprising the above-mentioned plain tablet and a pharmaceutically acceptable coating carrier. The coating carrier can further be a gastric soluble film coating.

[0038] In the present invention, the coating weight gain of the melogabalin besylate tablet is 1% to 10%, preferably 2% to 8%, and more preferably 2% to 5%.

[0039] In addition, the present invention also provides a method for preparing melogabalin besylate tablets, comprising the following steps:

[0040] 1) Premixing: Add the weighed amount of melogabalin besylate, disintegrant, filler, and glidant to the wet granulation and stir to mix;

[0041] 2) Wet granulation: Prepare a tocopherol solution and a tartaric acid solution using anhydrous ethanol, water, or a combination of the two. Use a high-efficiency wet granulator to granulate the tocopherol solution and tartaric acid solution in sequence by atomization under stirring and shearing conditions.

[0042] 3) Drying; set the drying temperature and dry the multifunctional granulating and pilling coating machine;

[0043] 4) Dry granulation: the dried material is passed through a pulverizer for granulation;

[0044] 5) Total mixing: Add the remaining filler and lubricant according to the yield of dry granules, and add them into the hopper mixer together with the dry granules;

[0045] 6) Tableting;

[0046] 7) Coating: Use high-efficiency coating machine for coating.

[0047] Finally, the present invention also provides the use of the aforementioned melogabalin besylate tablets or melogabalin besylate tablets in the preparation of a drug for treating pain, which is particularly useful for treating diabetic peripheral neuropathy pain.

[0048] Compared with the prior art, the melogabalin besylate tablets provided by the present invention have the following beneficial effects:

[0049] 1) The melogabalin besylate tablets provided by the present invention use sodium carboxymethyl starch as a disintegrant, and a specific composite stabilizer (a combination of tocopherol and tartaric acid). Compared with the combination of sodium carboxymethyl starch and other stabilizers (Formulation 4 of Example 2, Formulation 5 of Example 2) and the combination of disintegrant carboxymethyl cellulose calcium with tocopherol and tartaric acid (Comparative Example 1), the stability is better, overcoming the technical prejudice in the prior art (i.e., the reference preparation) that the stability of carboxymethyl cellulose calcium is better than that of sodium carboxymethyl starch.

[0050] 2) Based on the selection of sodium carboxymethyl starch as a disintegrant, the present invention further examined the dosage of the composite stabilizer (tartaric acid + tocopherol) and the mass ratio between the two stabilizer components. Surprisingly, it was found that when the composite stabilizer was added to the formulation in an appropriate mass ratio (i.e., the mass ratio of tartaric acid to tocopherol was greater than 20:1, more preferably (21.7-35.1):1), its impurity I, other single impurities, and total impurities all met the quality control requirements for impurity limits, indicating that the stability of the melogabalin besylate tablets provided by the present invention is superior to that of the reference preparation.

[0051] The impurity I described in the present invention has a CAS number of 3042853-06-2, a molecular weight of 191.27, a chemical name of (1R, 5S)-3-ethylspiro[bicyclo[3.2.0]hept-6,3'-pyrrolidine]-3-ene-5'-one, and a structural formula of:

[0052] . DETAILED DESCRIPTION

[0053] The technical solution of the present invention will be further described below with reference to the embodiments. However, the protection scope of the present invention includes but is not limited to these embodiments, and 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.

[0054] Stability test method:

[0055] 1) Experimental conditions and indicators

[0056]

[0057] 2) Test conditions

[0058] Determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 edition, Part IV, General Chapter 0512):

[0059] Instrument: High performance liquid chromatography;

[0060] Chromatographic column: Use octadecylsilane bonded silica gel as filler (C18 chromatographic column) or a chromatographic column with equivalent performance;

[0061] Mobile phase and gradient: 0.01 mol / L diammonium phosphate buffer (pH = 6.2) as mobile phase A, methanol-acetonitrile-0.01 mol / L diammonium phosphate buffer (pH = 6.2) (9:3:4) as mobile phase B; linear elution;

[0062] Flow rate: 1.0 mL / min; column temperature 40°C; detection wavelength 210 nm; injection volume 10 μL.

[0063] Example 1: The melogabalin besylate tablets provided by the present invention have a prescription as shown in Table 1.

[0064] Table 1. Example 1 Melogabalin Besylate Tablets Prescription

[0065]

[0066] Among them, the mass ratio of tartaric acid to tocopherol (taking DL-α-tocopherol as an example) is 21.7:1.

[0067] The preparation process of the melogabalin besylate tablets provided by the present invention is as follows:

[0068] 1) Premixing: Add the weighed melogabalin besylate, mannitol, sodium starch glycolate, and magnesium aluminum metasilicate to the wet granulation according to the ratio shown in Table 1. Set the stirring speed to 5 rpm and the cutting speed to 20 rpm, and mix for 300 s.

[0069] 2) Wet granulation

[0070] Preparation of stabilizer solution: ① Dissolve the prescribed amount of DL-α-tocopherol in anhydrous ethanol to obtain a DL-α-tocopherol solution, set aside; ② Dissolve tartaric acid in purified water to obtain a tartaric acid solution, set aside; Set the stirring speed of the high-efficiency wet granulator to 5 r / s and the shear speed to 20 r / s, and add the DL-α-tocopherol solution and tartaric acid solution in atomization in the stirring and shearing state. After the slurry is added, set the stirring speed to 5 r / s and the shear speed to 25 r / s, and continue granulation for 60 seconds.

[0071] 3) Drying: Set the drying temperature to 40~60℃ and use a multifunctional granulating and pilling coating machine for drying. The drying loss is required to be less than 1.5%.

[0072] 4) Dry granulation: The dried material is passed through a grinder for granulation.

[0073] 5) Total mixing: According to the yield of dry granules, microcrystalline cellulose and magnesium stearate are added and mixed together with the dry granules in a hopper mixer.

[0074] 6) Tablet coating: Tablets are compressed according to the dosage, and high-efficiency coating machines are used for coating, with appropriate air volume and product temperature controlled.

[0075] Example 2: Investigation of stabilizer types

[0076] Based on Example 1, only the effect of the type of stabilizer on the stability of Formulations 1 to 5 (see Table 2) was examined.

[0077] The type of stabilizer can be selected from: any one or more combinations of tocopherol (taking DL-α-tocopherol as an example), tartaric acid, ascorbyl palmitate, and sodium metabisulfite.

[0078] Table 2. Prescriptions 1 to 5

[0079]

[0080] According to the prescription shown in Table 2, melogabalin besylate tablets of prescriptions 1 to 5 were prepared, and the preparation process was carried out with reference to Example 1.

[0081] The prepared plain tablets of formulations 1 to 5 of Example 2 were subjected to stability testing. The test item was the content of impurity I. The results are shown in Table 3.

[0082] Table 3. Stability study of formulations 1 to 5

[0083]

[0084] The test results show that:

[0085] ① In the melogabalin besylate tablets whose disintegrant is sodium carboxymethyl starch, the plain tablets of Formulations 1-2 using a single stabilizer were placed under accelerated conditions for 30 days. The growth of impurity I was much greater than that of Formulations 3-5 using a combination of stabilizers. In addition, the impurity content of Formulations 1-2 was greater than the prescribed limit, and the stability did not meet the requirements.

[0086] ② In the melogabalin besylate tablets in which the disintegrant is sodium carboxymethyl starch, the content of impurity I in prescription 3, which uses tocopherol and tartaric acid as a combination stabilizer, was within the prescribed limit (<0.5%) after being placed under accelerated conditions for 30 days. However, in prescriptions 4 (tartaric acid + ascorbyl palmitate) and 5 (ascorbyl palmitate + sodium metabisulfite) using other stabilizer combinations, the content of impurity I exceeded 0.5%, and the stability did not meet the requirements.

[0087] In summary, it is determined that in the melogabalin besylate tablets of the present invention, when the disintegrant is sodium carboxymethyl starch, tocopherol and tartaric acid need to be added simultaneously as stabilizers.

[0088] Example 3: Investigation of the dosage of stabilizers tocopherol and tartaric acid

[0089] Based on the formulation 3 of Example 2, the effect of the amount of the composite stabilizer tocopherol and tartaric acid on the stability was further investigated.

[0090] Table 4. Prescriptions of Examples 3 to 7 Melogabalin Besylate Tablets

[0091]

[0092] Melogabalin besylate tablets were prepared according to the prescription shown in Table 4. The preparation process was referred to Example 1.

[0093] Comparative Example 1

[0094] The difference between Comparative Example 1 and Example 1 is that the only difference is the type of disintegrant. Comparative Example 1 uses 10% carboxymethyl cellulose calcium as a disintegrant, while Example 1 uses 10% carboxymethyl starch sodium as a disintegrant.

[0095] Preparation process: Replace the corresponding components and prepare melogabalin besylate tablets according to Example 1.

[0096] Stability study: The plain tablets of Example 1, Formulation 3 of Example 2, Examples 3 to 7, and Comparative Example 1 were placed under accelerated conditions (40°C, 75% RH) for 0, 14, and 30 days, respectively, to examine the properties of the tablet core and related substances.

[0097] Stability test results:

[0098] Table 5. Stability test results of Example 1, Example 2, Formula 3, Examples 3 to 7, and Comparative Example 1 bare chips after accelerated storage for 0, 14, and 30 days.

[0099]

[0100] Table 6: Stability test results of Example 1 coated tablets, compared to the reference formulation packaging (PVC / PVDC + pharmaceutical aluminum foil + molecular sieve desiccant + composite film) under accelerated conditions (40°C, 75% RH) for 60 days

[0101]

[0102] The test results show that:

[0103] ① According to the stability data of Example 1 and Comparative Example 1:

[0104] When using the same mass ratio of tartaric acid and tocopherol, Example 1 (disintegrant: sodium carboxymethyl starch) exhibited superior stability compared to Comparative Example 1 (disintegrant: sodium carboxymethyl cellulose). After 30 days of storage under accelerated conditions, the contents of Impurity I, other single impurities, and total impurities in Example 1 were all within the prescribed limits, while the total impurities in Comparative Example 1 exceeded the prescribed limits.

[0105] ② According to the stability test data of Example 1, Prescription 3 of Example 2, and Examples 3 to 7:

[0106] When sodium carboxymethyl starch was selected as the disintegrant and tartaric acid and tocopherol were the stabilizers, the greater the amount of tartaric acid used, the less impurity I was produced during accelerated storage.

[0107] When the mass ratio of tartaric acid to tocopherol is greater than 20:1, the stability of the preparation is good: Example 1 and Examples 3 to 7 are placed under accelerated conditions for 30 days, and the impurity I, other single impurities, and total impurities meet the requirements and are within the specified limits;

[0108] When the mass ratio of tartaric acid to tocopherol was 20:1 (Formulation 3 in Example 2), although the limit of impurity I met the requirement after 30 days under accelerated conditions, the other single impurities and total impurities exceeded the limit.

[0109] In summary, by adopting the formulation and process of the aforementioned melogabalin besylate tablets of the present invention (Examples 1 and 3 to 7), selecting sodium carboxymethyl starch as a disintegrant, and a mass ratio of tartaric acid to tocopherol greater than 20:1, melogabalin besylate tablets with stability meeting the requirements can be prepared, and the stability is better than that of the reference preparation.

Claims

1. A melogabalin besylate tablet comprising melogabalin besylate, a disintegrant, a stabilizer and other pharmaceutically acceptable excipients, characterized in that: The disintegrant is sodium carboxymethyl starch, and the stabilizer is a combination of tartaric acid and tocopherol, wherein the mass ratio of tartaric acid to tocopherol is (21.7-35.1):

1.

2. The melogabalin besylate tablet according to claim 1, wherein The other pharmaceutically acceptable excipients include fillers, lubricants, and glidants; wherein, The filler is selected from one or more of mannitol, lactose, corn starch, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, and sorbitol; The lubricant is selected from one or more of magnesium stearate, sodium stearyl fumarate, and talc; The flow aid is selected from one or more of magnesium aluminum metasilicate, magnesium aluminum silicate, and silicon dioxide.

3. The melogabalin besylate tablet according to claim 2, wherein The filler is selected from one or both of mannitol and microcrystalline cellulose; or The lubricant is selected from magnesium stearate; or The flow aid is selected from magnesium aluminum metasilicate.

4. The melogabalin besylate tablet according to claim 1, wherein The tocopherol is selected from DL-α-tocopherol.

5. The melogabalin besylate tablet according to any one of claims 1 to 4, characterized in that Taking the total weight of the tablet as 100%, the weight percentage of each component in the tablet is: Meloxaline besylate 1-10%, mannitol 70-78%, microcrystalline cellulose 0.1-10%, sodium starch glycolate 5-20%, tocopherol 0.1-0.5%, tartaric acid 3-5%, magnesium stearate 0.1-3%, magnesium aluminum metasilicate 0.1-0.5%; and the mass ratio of tartaric acid to tocopherol is (21.7-35.1):

1.

6. The melogabalin besylate tablet according to claim 5, characterized in that Taking the total weight of the tablet as 100%, the weight percentage of each component in the tablet is: Meloxaline besylate 2-8%, mannitol 75-78%, microcrystalline cellulose 0.1-1%, sodium starch glycolate 7.5-12.5%, tocopherol 0.1-0.2%, tartaric acid 3-5%, magnesium stearate 0.5-2.5%, magnesium aluminum metasilicate 0.1-0.3%; and the mass ratio of tartaric acid to tocopherol is (21.7-35.1):

1.

7. The melogabalin besylate tablets according to claim 6, characterized in that Taking the total weight of the tablet as 100%, the weight percentage of each component in the tablet is: Melogabalin besylate 5.86%, mannitol 76.47~77.95%, microcrystalline cellulose 0.9%, sodium starch glycolate 10%, tocopherol 0.1~0.17%, tartaric acid 2.67~4%, magnesium stearate 2%, magnesium aluminum metasilicate 0.2%; and the mass ratio of tartaric acid to tocopherol is (21.7~35.1):

1.

8. A melogabalin besylate tablet, wherein each 150 parts by mass contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 116.34 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.23 parts by mass of tocopherol, 5 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

9. A melogabalin besylate tablet, wherein each 150 parts by mass contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 116.92 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.15 parts by mass of tocopherol, 4.5 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

10. A melogabalin besylate tablet, wherein each 150 parts by mass contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 116.88 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.19 parts by mass of tocopherol, 4.5 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

11. A melogabalin besylate tablet, wherein each 150 parts by mass contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 114.71 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.19 parts by mass of tocopherol, 6.67 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

12. A melogabalin besylate tablet, wherein each 150 parts by mass contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 115.06 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.21 parts by mass of tocopherol, 6.3 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

13. A melogabalin besylate tablet, wherein each 150 parts by mass contains the following components and their amounts: 8.78 parts by mass of melogabalin besylate, 115.32 parts by mass of mannitol, 1.35 parts by mass of microcrystalline cellulose, 15 parts by mass of sodium carboxymethyl starch, 0.25 parts by mass of tocopherol, 6 parts by mass of tartaric acid, 3 parts by mass of magnesium stearate, and 0.3 parts by mass of magnesium aluminum metasilicate.

14. A melogabalin besylate tablet comprising the plain tablet according to any one of claims 1 to 13 and a pharmaceutically acceptable coating carrier.

15. A method for preparing the melogabalin besylate tablets according to claim 14, comprising the following steps: 1) Premixing: Add the prescribed amount of melogabalin besylate, disintegrant, filler, and glidant to the wet granulation and stir to mix; 2) Wet granulation: Prepare a tocopherol solution and a tartaric acid solution using anhydrous ethanol, water, or a combination of the two. Use a high-efficiency wet granulator to granulate the tocopherol solution and tartaric acid solution in sequence by atomization under stirring and shearing conditions. 3) Drying; set the drying temperature and dry the multifunctional granulating and pilling coating machine; 4) Dry granulation: the dried material is passed through a pulverizer for granulation; 5) Total mixing: Add the remaining filler and lubricant according to the yield of dry granules, and add them into the hopper mixer together with the dry granules; 6) Tableting; 7) Coating: Use high-efficiency coating machine for coating.

16. Use of the melogabalin besylate tablets according to any one of claims 1 to 13 or the melogabalin besylate tablets according to claim 14 in the preparation of a drug for treating pain.

17. The use according to claim 16, characterized in that The medicine is used for treating diabetic peripheral neuropathic pain.

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