Melogabalin besylate tablet and preparation method thereof

Abstract

The invention discloses melogabalin besylate tablets and a preparation method thereof, a tablet core comprises melogabalin besylate, a filler, a disintegrating agent, a lubricant, a flow aid and a stabilizer, the disintegrating agent is sodium carboxymethyl starch, and the stabilizer is tocopherol and tartaric acid; on the basis of selecting sodium carboxymethyl starch as a disintegrating agent, the melogabalin besylate tablet of which the stability (especially the quality control of impurities I) is superior to that of a reference preparation is prepared by investigating the variety and the dosage of a stabilizing agent and selecting a specific stabilizing agent combination; the technical prejudice that the stability of calcium carboxymethyl cellulose is superior to that of sodium carboxymethyl starch in the prior art is overcome.

Description

Technical Field

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

[0002] Mirogabalin Besilate is a novel pain treatment drug. Its binding to the α2δ subunit (CACNA2D) of the voltage-gated calcium channel (VGCC) plays an auxiliary role in the function of voltage-dependent calcium channels in the nervous system, inhibits calcium current, and can exert an analgesic effect. 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 monophenylsulfonate, and its structural formula is shown as follows:

[0003] The original research pharmaceutical company, Daiichi Sankyo, in patent CN104334169A protects a solid composition containing mirogabalin besilate, specifically protects the composition of the filler mannitol, the disintegrant calcium carboxymethylcellulose, and the lubricants magnesium stearate or sodium stearyl fumarate, and discloses that in the screening of disintegrants, calcium carboxymethylcellulose shows more excellent stability than sodium carboxymethyl starch.

[0004] Based on the fact that in patent CN104334169A, the selection of calcium carboxymethylcellulose as the disintegrant brings better performance than sodium carboxymethyl starch, the original research conducted research on the formulation of mirogabalin besilate solid preparations: 1) Patent CN107405322A protects a mirogabalin besilate solid preparation containing a stabilizer, including the disintegrant calcium carboxymethylcellulose. The stabilizer is selected from a combination of one or two or more stabilizers such as sodium edetate, citric acid hydrate, dibutylhydroxytoluene, propyl gallate, magnesium citrate (anhydrous), soy lecithin, α-tocopherol, α-tocopherol acetate, and β-cyclodextrin. The total impurity increase amount of the prepared preparation is inhibited under accelerated conditions.

[0005] 2) Patent CN111971036A also discloses a mirogabalin besilate solid preparation containing a stabilizer. Specific contents and / or content ratios of citric anhydride or citric acid hydrate and tocopherol are selected as stabilizers and combined with the disintegrant calcium carboxymethylcellulose to specifically inhibit the generation of specific impurity decomposition products A and decomposition products B.

[0006] It can be seen that during the development of melegabalin besylate solid preparations, the types of disintegrants and stabilizers jointly affect the stability of the preparations: ① First, when the disintegrant is preferably calcium carboxymethylcellulose, the stability of the preparation is better, rather than sodium carboxymethyl starch; ② Second, even when the disintegrant is calcium carboxymethylcellulose, when used in combination with any single stabilizer or a combination of multiple stabilizers, the effect of inhibiting the growth of impurities is completely different; for example, calcium carboxymethylcellulose can only inhibit the formation of decomposition products A and B when combined with specific stabilizers ("citric anhydride + tocopherol" or "citric acid hydrate + tocopherol").

[0007] The applicant further searched and found that in order to provide a melegabalin besylate preparation with good stability and low related substance content, the prior art also provided the following technical solutions.

[0008] Patent CN117618375A discloses a milobagrine tablet, the tablet core contains minobagrine besylate, excipients, disintegrants, lubricants and stabilizers. When the stabilizer malic acid is used in combination with the disintegrant calcium carboxymethylcellulose, the stability is better than that of other stabilizers (tartaric acid, tocopherol, fumaric acid, etc.).

[0009] Patent CN118806717A discloses a melegabalin besylate solid preparation, which selects solid stabilizers such as tartaric acid, malic acid, and sodium citrate instead of the liquid stabilizer tocopherol, and the disintegrant is calcium carboxymethylcellulose, which simplifies the production process compared with the original research and achieves the same stable effect at the same time.

[0010] Patent CN119235806A discloses a melegabalin besylate tablet. Under the same selection of stabilizer types, the stability of the preparation formula with the filler and disintegrant combination of "mannitol 200SD + microcrystalline cellulose + carboxymethylcellulose calcium" is significantly better than that of the formula of "mannitol M100 + microcrystalline cellulose + sodium carboxymethyl starch".

[0011] In summary, although the prior art has obtained preparations with good stability through a large amount of research, due to the influence of the original research patent formula, the development ideas are mostly limited to selecting calcium carboxymethylcellulose as the disintegrant and then selecting the stabilizer. And the prior art has proved that the formula using calcium carboxymethylcellulose has better stability than the formula using sodium carboxymethyl starch. That is to say, if other disintegrants (such as sodium carboxymethyl starch) are selected for the preparation development, it is impossible to know whether the same or even better stability as the original research can be achieved.

[0012] Therefore, based on using sodium carboxymethyl starch as a disintegrant, how to select a suitable stabilizer (either a single stabilizer or a compound stabilizer), and optimize the formulation process to obtain a new meloxicam and pregabalin besylate tablet with better stability and fewer impurities is a technical problem that has not been solved by those skilled in the art. Summary of the Invention

[0013] The technical problem to be solved by the present invention is: based on using sodium carboxymethyl starch as a disintegrant, by selecting a suitable stabilizer and optimizing the formulation process, to prepare a meloxicam and pregabalin besylate tablet with better stability and fewer impurities.

[0014] To solve the above technical problem, the present invention will be realized through the following technical solutions: The present invention provides a plain tablet of meloxicam and pregabalin besylate, which includes the main drug meloxicam and pregabalin besylate, and excipients such as a filler, a disintegrant, a lubricant, a glidant, and a stabilizer. Among them, the disintegrant is selected as sodium carboxymethyl starch, and the stabilizer is selected as a combination of tartaric acid and tocopherol.

[0015] Preferably, the mass ratio of tartaric acid to tocopherol in the stabilizer must be greater than 20:1.

[0016] More preferably, the mass ratio of tartaric acid to tocopherol in the stabilizer is (21.7 - 35.1):1.

[0017] In the present invention, the aforementioned tocopherol can be further preferably DL-α-tocopherol.

[0018] In the present invention, as long as the disintegrant is selected as sodium carboxymethyl starch and the mass ratio of tartaric acid to tocopherol in the stabilizer must be greater than 20:1, a plain tablet of meloxicam and pregabalin besylate with excellent stability can be prepared. Therefore, when the inventor considers the selection of the filler, the lubricant, and the glidant, it is not limited to the components listed in Example 1 of the present invention, and conventional excipients acceptable in pharmacy can be selected.

[0019] 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; further preferably, it is one or two of mannitol and microcrystalline cellulose.

[0020] Similarly, the lubricant in the present invention can be selected from one or more of magnesium stearate, sodium stearyl fumarate, and talc powder; further preferably, it is magnesium stearate.

[0021] Similarly, the glidant in the present invention can be selected from one or more of magnesium aluminum metasilicate, magnesium aluminum silicate, and silicon dioxide, and further preferably, it is magnesium aluminum metasilicate.

[0022] Similarly, based on the plain tablets provided by the present invention, the plain tablets can be coated, and the coating materials are all conventional pharmaceutically acceptable coating materials, including but not limited to gastric-soluble film coatings and the like.

[0023] The present invention also provides the suitable mass ratios of the components in the aforementioned megalol gabapentin besylate plain tablets (taking the component types described in Example 1 of the present invention as an example), specifically: For a megalol gabapentin besylate plain tablet, based on the total weight of the plain tablet being 100%, the weight percentages of the components in the plain tablet are: megalol gabapentin besylate 1-10%, mannitol 70-78%, microcrystalline cellulose 0.1-10%, sodium carboxymethyl starch 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 must be greater than 20:1.

[0024] Furthermore, the weight percentages of the components in the megalol gabapentin besylate plain tablet can also be preferably: megalol gabapentin 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.

[0025] More preferably, the weight percentages of the components in the megalol gabapentin besylate plain tablet are: megalol gabapentin 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.

[0026] In addition, the present invention also provides some specific prescriptions for the megalol gabapentin besylate plain tablet, including: For a megalol gabapentin besylate plain tablet, the components and their dosages contained in every 150 parts by mass are: megalol gabapentin besylate 8.78 parts by mass, mannitol 116.34 parts by mass, microcrystalline cellulose 1.35 parts by mass, sodium carboxymethyl starch 15 parts by mass, tocopherol 0.23 parts by mass, tartaric acid 5 parts by mass, magnesium stearate 3 parts by mass, magnesium aluminum metasilicate 0.3 parts by mass.

[0027] A Meloxicam Gabapentin Sulfonate tablet, the components and their dosages per 150 parts by mass are as follows: Meloxicam Gabapentin Sulfonate 8.78 parts by mass, mannitol 116.92 parts by mass, microcrystalline cellulose 1.35 parts by mass, sodium carboxymethyl starch 15 parts by mass, tocopherol 0.15 parts by mass, tartaric acid 4.5 parts by mass, magnesium stearate 3 parts by mass, magnesium aluminum metasilicate 0.3 parts by mass.

[0028] A Meloxicam Gabapentin Sulfonate tablet, the components and their dosages per 150 parts by mass are as follows: Meloxicam Gabapentin Sulfonate 8.78 parts by mass, mannitol 116.88 parts by mass, microcrystalline cellulose 1.35 parts by mass, sodium carboxymethyl starch 15 parts by mass, tocopherol 0.19 parts by mass, tartaric acid 4.5 parts by mass, magnesium stearate 3 parts by mass, magnesium aluminum metasilicate 0.3 parts by mass.

[0029] A Meloxicam Gabapentin Sulfonate tablet, the components and their dosages per 150 parts by mass are as follows: Meloxicam Gabapentin Sulfonate 8.78 parts by mass, mannitol 114.71 parts by mass, microcrystalline cellulose 1.35 parts by mass, sodium carboxymethyl starch 15 parts by mass, tocopherol 0.19 parts by mass, tartaric acid 6.67 parts by mass, magnesium stearate 3 parts by mass, magnesium aluminum metasilicate 0.3 parts by mass.

[0030] A Meloxicam Gabapentin Sulfonate tablet, the components and their dosages per 150 parts by mass are as follows: Meloxicam Gabapentin Sulfonate 8.78 parts by mass, mannitol 115.06 parts by mass, microcrystalline cellulose 1.35 parts by mass, sodium carboxymethyl starch 15 parts by mass, tocopherol 0.21 parts by mass, tartaric acid 6.3 parts by mass, magnesium stearate 3 parts by mass, magnesium aluminum metasilicate 0.3 parts by mass.

[0031] A Meloxicam Gabapentin Sulfonate tablet, the components and their dosages per 150 parts by mass are as follows: Meloxicam Gabapentin Sulfonate 8.78 parts by mass, mannitol 115.32 parts by mass, microcrystalline cellulose 1.35 parts by mass, sodium carboxymethyl starch 15 parts by mass, tocopherol 0.25 parts by mass, tartaric acid 6 parts by mass, magnesium stearate 3 parts by mass, magnesium aluminum metasilicate 0.3 parts by mass.

[0032] In addition, the present invention also provides a Meloxicam Gabapentin Sulfonate tablet, which includes the above-mentioned tablet and a pharmaceutically acceptable coating carrier. The coating carrier can further be selected as a gastric-soluble film coating.

[0033] In the present invention, the weight gain of the coating layer of the Meloxicam Gabapentin Sulfonate tablet is 1% - 10%, preferably 2% - 8%, and more preferably 2% - 5%.

[0034] In addition, the present invention also provides a preparation method of a Meloxicam Gabapentin Sulfonate tablet, which includes the following steps: 1) Premixing: Add the weighed megalopregabalin besylate, disintegrant, filler, and glidant to the wet granulation process and stir for mixing; 2) Wet granulation: Prepare the tocopherol solution and tartaric acid solution with anhydrous ethanol, water, or a combination of both for standby; Granulate using a high-efficiency wet granulator. Under stirring and shearing conditions, atomize and sequentially add the tocopherol solution and tartaric acid solution for granulation; 3) Drying; Set the drying temperature and dry using a multi-functional granulating, pelleting, and coating machine; 4) Dry screening: Screen the dried material through a pulverizer for sizing; 5) Total mixing: Based on the yield of the dry granules, add the remaining filler and lubricant, and mix them with the dry granules in a hopper mixer; 6) Tabletting; 7) Coating: Perform coating using a high-efficiency coating machine.

[0035] Finally, the present invention also provides the use of the megalopregabalin besylate plain tablets or megalopregabalin besylate tablets as described above in the preparation of drugs for treating pain. This drug is especially used for treating diabetic peripheral neuropathic pain.

[0036] Compared with the prior art, the beneficial effects of the megalopregabalin besylate tablets provided by the present invention are as follows: 1) For the megalopregabalin besylate tablets provided by the present invention, sodium carboxymethyl starch is selected as the disintegrant, and in combination with a specific composite stabilizer (a combination of tocopherol and tartaric acid), it has better stability compared to using sodium carboxymethyl starch in combination with other stabilizers (Prescription 4 and Prescription 5 in Example 2), and the combination of disintegrant calcium carboxymethyl cellulose with tocopherol and tartaric acid (Comparative Example 1). It overcomes the technical prejudice in the prior art (i.e., the reference preparation) that the stability of calcium carboxymethyl cellulose is better than that of sodium carboxymethyl starch.

[0037] 2) On the basis of selecting sodium carboxymethyl starch as the disintegrant, the present invention further examines the dosage of the composite stabilizer (tartaric acid + tocopherol) and the mass ratio between the two stabilizer components, and surprisingly finds that: when adding a composite stabilizer with an appropriate mass ratio (i.e., the mass ratio of tartaric acid to tocopherol is greater than 20:1, more preferably (21.7 - 35.1):1) to the prescription, the impurity I, other single impurities, and total impurities all meet the quality control requirements of the impurity limits, indicating that the megalopregabalin besylate tablets provided by the present invention have better stability than the reference preparation.

[0038] The CAS number of the impurity I described in the present invention is 3042853 - 06 - 2, the molecular weight is 191.27, the chemical name is (1R,5S)-3-ethylspiro[bicyclo[3.2.0]hept-6,3'-pyrrolidine]-3-ene-5'-one, and the structural formula is: 。 Specific implementation mode

[0039] The technical solution of the present invention will be further described below in conjunction with 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.

[0040] Stability experiment method: 1) Experimental conditions and indicators

[0041] 2) Test conditions Determined according to the high performance liquid chromatography method (General Principles 0512, Volume IV, Chinese Pharmacopoeia 2020 Edition): Instrument: High performance liquid chromatograph; Chromatographic column: Octadecylsilane-bonded silica gel as the packing material (C18 chromatographic column) or a chromatographic column with equivalent efficiency; Mobile phase and gradient: 0.01 mol / L diammonium hydrogen phosphate buffer solution (pH = 6.2) is mobile phase A, and methanol-acetonitrile-0.01 mol / L diammonium hydrogen phosphate buffer solution (pH = 6.2) (9:3:4) is mobile phase B; linear elution; Flow rate: 1.0 mL / min; column temperature 40 °C; detection wavelength 210 nm; injection volume 10 μL.

[0042] Example 1. The melogabalin besylate tablets provided by the present invention have the prescription shown in Table 1.

[0043] Table 1. Prescription of melogabalin besylate tablets in Example 1

[0044] Among them, the mass ratio of tartaric acid to tocopherol (taking DL-α-tocopherol as an example) is 21.7:1.

[0045] The preparation process of the melogabalin besylate tablets provided by the present invention is as follows: 1) Premixing: Weigh the melogabalin besylate, mannitol, sodium carboxymethyl starch, and magnesium metasilicate aluminate according to the ratio shown in Table 1 and add them to the wet granulation. Set the stirring speed to 5 r / s, the cutter speed to 20 r / s, and mix for 300 s.

[0046] 2) Wet granulation Preparation of the stabilizer solution: ① Dissolve the prescribed amount of DL-α-tocopherol in absolute ethanol to obtain a DL-α-tocopherol solution for standby; ② Dissolve tartaric acid in purified water to obtain a tartaric acid solution for standby. Set the stirring speed of the high-efficiency wet granulator at 5 r / s and the shearing speed at 20 r / s. Under the stirring and shearing states, atomize and add the DL-α-tocopherol solution and tartaric acid solution successively. After the addition of the slurry is completed, set the stirring speed at 5 r / s and the shearing speed at 25 r / s, and continue granulation for 60 s.

[0047] 3) Drying: Set the drying temperature at 40 - 60 °C, and dry using a multi-functional granulating, pill-making, and coating machine. The requirement is that the loss on drying is < 1.5%.

[0048] 4) Dry screening: Screen the dried material through a pulverizer for screening.

[0049] 5) Total mixing: Based on the yield of the dry granules, proportionally add microcrystalline cellulose and magnesium stearate, and add them together with the dry granules to a hopper mixer for mixing.

[0050] 6) Tabletting and coating: Based on the content proportion, conduct tabletting, and use a high-efficiency coating machine for coating, controlling the appropriate air volume and product temperature.

[0051] Example 2. Investigation of the type of stabilizer On the basis of Example 1, only investigate the influence of the selection of the type of stabilizer on the stability of Formulations 1 - 5 (see Table 2).

[0052] The type of stabilizer can be selected from any one or a combination of multiple of the following: tocopherol (taking DL-α-tocopherol as an example), tartaric acid, ascorbyl palmitate, sodium metabisulfite.

[0053] Table 2. Formulations 1 - 5

[0054] Prepare the meloxicam and pregabalin tablets of Formulations 1 - 5 according to the prescriptions shown in Table 2, and the preparation process refers to Example 1.

[0055] Conduct stability tests on the plain tablets of Formulations 1 - 5 prepared in Example 2. The test item is the content of Impurity I, and the results are shown in Table 3.

[0056] Table 3. Stability investigation of Formulations 1 - 5

[0057] The test results show that: ①In the meloxicam gabapentin tablets with sodium carboxymethyl starch as the disintegrant, the growth of impurity I in the plain tablets of Formulations 1 - 2 with a single stabilizer was much greater than that of Formulations 3 - 5 with a combined stabilizer after being placed under accelerated conditions for 30 days. Moreover, the impurity content of Formulations 1 - 2 exceeded the specified limit, and the stability did not meet the requirements.

[0058] ②In the meloxicam gabapentin tablets with sodium carboxymethyl starch as the disintegrant, for Formulation 3 with tocopherol and tartaric acid as the combined stabilizer, the content of impurity I was within the specified limit (<0.5%) after being placed under accelerated conditions for 30 days; while for Formulation 4 (tartaric acid + ascorbyl palmitate) and Formulation 5 (ascorbyl palmitate + sodium metabisulfite) with other stabilizer combinations, the content of impurity I exceeded 0.5%, and the stability did not meet the requirements.

[0059] In summary, it is determined that for the meloxicam gabapentin tablets of the present invention, when the disintegrant is sodium carboxymethyl starch, tocopherol and tartaric acid need to be added simultaneously as stabilizers.

[0060] Example 3. Investigation on the Dosages of Stabilizers Tocopherol and Tartaric Acid On the basis of Formulation 3 in Example 2, the influence of the dosages of the composite stabilizers tocopherol and tartaric acid on the stability was further investigated.

[0061] Table 4. Formulations of Meloxicam Gabapentin Tablets in Examples 3 - 7

[0062] Prepare meloxicam gabapentin tablets according to the formulations shown in Table 4, and the preparation process refers to Example 1.

[0063] Comparative Example 1 The difference between Comparative Example 1 and Example 1 is that only the type of disintegrant is different. In Comparative Example 1, 10% calcium carboxymethylcellulose is used as the disintegrant, while in Example 1, 10% sodium carboxymethyl starch is used as the disintegrant.

[0064] Preparation process: Replace the corresponding components and refer to Example 1 to prepare meloxicam gabapentin tablets.

[0065] Stability investigation: Place the plain tablets of Example 1, Formulation 3 of Example 2, Examples 3 - 7, and Comparative Example 1 under accelerated conditions (40°C, 75% RH) for 0, 14, and 30 days respectively, and investigate the tablet core properties and related substances.

[0066] Stability test results: Table 5. Stability Investigation Results of the Plain Tablets of Example 1, Formulation 3 of Example 2, Examples 3 - 7, and Comparative Example 1 Placed under Accelerated Conditions for 0, 14, and 30 days

[0067] Table 6: Stability study results of the coated tablets of Example 1 packed in the same way as the reference preparation (PVC / PVDC + pharmaceutical aluminum foil + molecular sieve desiccant + composite film) under accelerated conditions (40°C, 75% RH) for 60 days

[0068] The test results show that: ① According to the stability data of Example 1 and Comparative Example 1: When using the same mass ratio of tartaric acid and tocopherol, Example 1 (with sodium carboxymethyl starch as the disintegrant) showed better stability than Comparative Example 1 (with sodium carboxymethyl cellulose as the disintegrant). After storing under accelerated conditions for 30 days, the contents of impurity I, other single impurities, and total impurities in Example 1 were all within the specified limits, while the total impurities in Comparative Example 1 exceeded the specified limits.

[0069] ② According to the prescription 3 of Example 2, and the stability test data of Examples 3 - 7: When the disintegrant is selected as sodium carboxymethyl starch and the stabilizers are tartaric acid and tocopherol, the greater the amount of tartaric acid used, the less impurity I is generated during storage under accelerated conditions; When the mass ratio of tartaric acid to tocopherol is greater than 20:1, the stability of the preparation is good: for Examples 1, 3 - 7, after being placed under accelerated conditions for 30 days, the impurity I, other single impurities, and total impurities all meet the requirements and are within the specified limits; When the mass ratio of tartaric acid to tocopherol is 20:1 (prescription 3 of Example 2), although the limit of impurity I meets the requirements after 30 days under accelerated conditions, the other single impurities and total impurities exceed the limits.

[0070] In summary, by using the prescription and process of the megalol gabapentin benzenesulfonate tablets of the present invention as described above (Examples 1, 3 - 7), selecting sodium carboxymethyl starch as the disintegrant, and when the mass ratio of tartaric acid to tocopherol is greater than 20:1, megalol gabapentin benzenesulfonate tablets with qualified stability can be prepared, and the stability is better than that of the reference preparation.

Claims

1. A megalicinium besylate tablet, comprising megalicinium besylate, a disintegrant, a stabilizer and other pharmaceutically acceptable excipients, characterized in that, The disintegrant selected is sodium carboxymethyl starch, and the stabilizer selected is a combination of tartaric acid and tocopherol, wherein the mass ratio of tartaric acid to tocopherol must be greater than 20:

1.

2. The melegabalin besylate tablet according to claim 1, wherein In the stabilizer, the mass ratio of tartaric acid to tocopherol is (21.7~35.1):

1.

3. The melegabalin besylate tablets according to claim 1, characterized in that, The other pharmaceutically acceptable excipients include fillers, lubricants, and glidants; among them, 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 powder; the glidant is selected from one or more of magnesium aluminum metasilicate, aluminum magnesium silicate, and silicon dioxide.

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

5. The melegabalin besylate tablet according to any one of claims 1 to 4, wherein Based on the total weight of the plain tablets being 100%, the weight percentages of each component in the plain tablets are: Meloxicam gabapin benzenesulfonate 1~10%, mannitol 70~78%, microcrystalline cellulose 0.1~10%, sodium carboxymethyl starch 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 must be greater than 20:

1.

6. The melegabalin besylate tablets according to claim 5, characterized in that, Based on the total weight of the plain tablets being 100%, the weight percentages of each component in the plain tablets are: Meloxicam gabapin benzenesulfonate 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.

7. The melegabalin besylate tablets according to claim 6, wherein Based on the total weight of the plain tablets being 100%, the weight percentages of each component in the plain tablets are: Meloxicam gabapin benzenesulfonate 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.

8. A meloxicam gabapin benzenesulfonate tablet, comprising the plain tablet as described in any one of claims 1~7 and a pharmaceutically acceptable coating carrier.

9. A method for preparing the meloxicam gabapin benzenesulfonate tablet as described in claim 8, comprising the following steps: 1) Premixing: Add the prescribed amounts of meloxicam gabapin benzenesulfonate, disintegrant, filler, and glidant to wet granulation, and stir and mix. 2) Wet granulation: Prepare a tocopherol solution and a tartaric acid solution with absolute ethanol, water, or a combination of both for standby; Use a high-efficiency wet granulator to granulate, and atomize and add the tocopherol solution and the tartaric acid solution in sequence under stirring and shearing conditions for granulation. 3) Drying; Set the drying temperature and dry with a multi-functional granulating, pelleting, and coating machine. 4) Dry screening: Screen the dried material through a pulverizer for screening. 5) Total mixing: Input the remaining filler and lubricant according to the yield of the dry granules, and add them to a hopper mixer together with the dry granules for mixing. 6) Tableting; 7) Coating: Perform coating with a high-efficiency coating machine.

10. Use of the melegabalin besylate tablets according to any one of claims 1 to 7 or the melegabalin besylate tablets according to claim 8 in the preparation of a medicament for treating pain.

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