Pharmaceutical composition containing melogabalin besylate and preparation method thereof

Abstract

The invention discloses a melogabalin besylate-containing pharmaceutical composition and a preparation method thereof, the preparation prescription adopts vitamin E polyethylene glycol succinate, gallic acid or tocopheryl succinate as antioxidants, and the specific antioxidants are screened out, so that the prepared melogabalin besylate pharmaceutical composition is better in stability and better in curative effect. Oxidative degradation impurities are effectively controlled, and the effectiveness and safety of melogabalin besylate are improved. In addition, the preparation method is stable, controllable and easy to amplify.

Description

Technical Field

[0001] This invention relates to a pharmaceutical composition containing melogabalin besylate and a method for preparing the same, and more particularly to a stable pharmaceutical composition containing melogabalin besylate and a method for preparing the same. Background Technology

[0002] Mirogabalin besilate ([(1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid monobenzenesulfonate) is a drug used to treat diabetic peripheral neuropathic pain (DPNP). This drug exerts its analgesic effect by inhibiting the increased release of neurotransmitters in nerve endings involved in pain.

[0003]

[0004] Merogabalin besylate has poor stability and is prone to oxidative degradation during storage. Furthermore, degradation can generate impurities during formulation preparation, leading to a decline in product quality and significantly impacting its efficacy and safety. CN117618375 discloses a melogabalin besylate tablet and its preparation method. The formulation uses malic acid as an antioxidant, and the preparation method involves first mixing malic acid with microcrystalline cellulose, then mixing it with the active pharmaceutical ingredient (API) and other excipients, followed by tableting. However, the prepared drug still degrades during storage, and the formulation process offers limited protection for the API, making quality control difficult. Summary of the Invention

[0005] Purpose of the invention: The present invention aims to provide a pharmaceutical composition containing melogabalin benzyl sulfonate with a controllable preparation method and stable quality, and the preparation method thereof.

[0006] Technical solution: The pharmaceutical composition containing melogabalin benzyl sulfonate of the present invention includes excipients such as fillers, disintegrants, lubricants, antioxidants, adsorbents and coating agents, wherein the antioxidant comprises a first component selected from vitamin E polyethylene glycol succinate, gallic acid or tocopherol succinate.

[0007] This invention has found that TPGS, gallic acid, and tocopherol succinate all possess certain antioxidant protective effects. In formulations, vitamin E polyethylene glycol succinate, gallic acid, or tocopherol succinate can improve the stability of melogabalin besylate formulations. Regarding the preparation process, the antioxidant vitamin E polyethylene glycol succinate, gallic acid, or tocopherol succinate is premixed with melogabalin besylate via spraying. This method of addition effectively increases the contact area between the antioxidant and melogabalin besylate, allowing the antioxidant to better exert its protective effect.

[0008] Preferably, the antioxidant comprises a first component selected from gallic acid.

[0009] Preferably, the antioxidant further includes a second component selected from one or more of tartaric acid, maleic acid, and succinic acid.

[0010] More preferably, the antioxidant further includes a second component selected from tartaric acid.

[0011] Preferably, the antioxidant is selected from vitamin E polyethylene glycol succinate-tartaric acid, gallic acid-tartaric acid, or tocopherol succinate-tartaric acid.

[0012] Further preferably, the antioxidant is selected from gallic acid-tartaric acid.

[0013] Preferably, the filler is selected from one or more of mannitol, lactose, microcrystalline cellulose, corn starch, and compressible starch.

[0014] More preferably, the filler is selected from one or two of mannitol and microcrystalline cellulose.

[0015] More preferably, the filler is mannitol and microcrystalline cellulose.

[0016] Preferably, the disintegrant is selected from one or more of calcium carboxymethyl cellulose, dry starch, sodium carboxymethyl starch, crospovidone, and sodium crospovidone carboxymethyl cellulose.

[0017] Further preferably, the disintegrant is selected from calcium carboxymethyl cellulose.

[0018] Preferably, the lubricant is selected from one or more of stearic acid, magnesium stearate, calcium stearate, sodium stearate fumarate, talc, and micronized silica gel.

[0019] Further preferably, the lubricant is selected from magnesium stearate.

[0020] Preferably, the adsorbent is selected from one or more of silica, colloidal silica, magnesium silicate, magnesium aluminum silicate, and calcium silicate.

[0021] Further preferably, the adsorbent is selected from magnesium aluminum silicate.

[0022] Preferably, the coating agent is selected from gastric-soluble coating agents.

[0023] Further preferably, the coating agent is selected from Opadry 02A64001-CN.

[0024] Preferably, the pharmaceutical composition of the present invention comprises, by weight, the following components: 1 to 10 parts of melogabalin besylate, 50 to 95 parts of filler, 2 to 10 parts of disintegrant, 0.5 to 3 parts of lubricant, 0.5 to 6 parts of antioxidant, 0.1 to 1 part of adsorbent and 1 to 6 parts of coating agent.

[0025] Further preferably, the pharmaceutical composition of the present invention comprises, by weight, the following components: 1 to 5 parts of melogabalin besylate, 70 to 90 parts of filler, 5 to 10 parts of disintegrant, 1 to 3 parts of lubricant, 0.5 to 5 parts of antioxidant, 0.1 to 0.5 parts of adsorbent and 2 to 5 parts of coating agent.

[0026] More preferably, the pharmaceutical composition of the present invention comprises, by weight, the following components: 3-5 parts of melogabalin besylate, 75-85 parts of filler, 7-10 parts of disintegrant, 1-2 parts of lubricant, 0.5-4 parts of antioxidant, 0.1-0.3 parts of adsorbent and 2-4 parts of coating agent.

[0027] In a further preferred embodiment, the antioxidant is selected from vitamin E polyethylene glycol succinate-tartaric acid in a mass ratio of 1:6, gallic acid-tartaric acid in a mass ratio of 1:6, or tocopherol succinate-tartaric acid in a mass ratio of 1:6.

[0028] Preferably, the pharmaceutical composition of the present invention comprises, by weight, the following components: 4.4 parts of melogabalin besylate, 79.5 parts of D-mannitol, 1 part of microcrystalline cellulose, 10 parts of calcium carboxymethyl cellulose, 0.5 parts of vitamin E polyethylene glycol succinate, gallic acid or tocopherol succinate, 3 parts of tartaric acid, 0.1 parts of magnesium aluminum silicate, 1.5 parts of magnesium stearate, and 4 parts of film coating agent.

[0029] Further preferably, the unit formulation of the pharmaceutical composition of the present invention comprises the following components: 8.78 weight units of melogabalin besylate, 159 weight units of D-mannitol, 2 weight units of microcrystalline cellulose, 20 weight units of calcium carboxymethyl cellulose, 1 weight unit of vitamin E polyethylene glycol succinate or 1 weight unit of gallic acid or 1 weight unit of tocopherol succinate, 6 weight units of tartaric acid, 0.2 weight units of magnesium aluminum silicate, 3.02 weight units of magnesium stearate, and 8 weight units of coating agent; wherein, the weight units of each component are the same.

[0030] More preferably, the unit formulation of the pharmaceutical composition of the present invention comprises the following components: 8.78 mg melogabalin besylate, 159 mg D-mannitol, 2 mg microcrystalline cellulose, 20 mg calcium carboxymethyl cellulose, 1 mg vitamin E polyethylene glycol succinate or 1 mg gallic acid or 1 mg tocopherol succinate, 6 mg tartaric acid, 0.2 mg magnesium aluminum silicate, 3.02 mg magnesium stearate, and 8 mg coating agent.

[0031] The method for preparing the pharmaceutical composition of the present invention includes the following steps:

[0032] (1) Preparation of a mixture containing melogabalin benzyl sulfonate and antioxidant component one: Prepare antioxidant component one into a solution, premix melogabalin benzyl sulfonate, a portion of the filler and antioxidant component one solution, sieve and dry;

[0033] (2) Mixing: The mixture containing melogabalin benzyl sulfonate obtained in step (1) is mixed with the remaining filler, disintegrant, second antioxidant component and adsorbent, and then sieved.

[0034] (3) Mixing: Mix the lubricant with the material obtained in step (2);

[0035] (4) Tableting: The material obtained in step (3) is compressed into tablets to obtain melogabalin benzyl sulfonate tablets;

[0036] (5) Coating: Prepare a coating solution from the coating powder and coat the uncoated tablets obtained in step (4) to obtain the pharmaceutical composition.

[0037] Specifically, the preparation method of the pharmaceutical composition containing melogabalin besylate according to the present invention includes premixing, mixing, total mixing, tableting, and coating. The specific operations are as follows:

[0038] (1) Preparation of a mixture containing melogabalin benzyl sulfonate and antioxidant component 1: Prepare a solution of vitamin E polyethylene glycol succinate or gallic acid or tocopherol succinate in a pharmaceutically acceptable solvent, add melogabalin benzyl sulfonate and microcrystalline cellulose to a granulator, then spray in the vitamin E polyethylene glycol succinate solution or gallic acid solution or tocopherol succinate solution for premixing until uniform, and pass the premixed material through a 60-mesh sieve, and then dry the sieved material at 40°C;

[0039] (2) Mixing: Weigh the amount of melogabalin benzenesulfonic acid premix obtained in step (1), and add the amount of mannitol filler, calcium carboxymethyl cellulose disintegrant, calcium tartaric acid antioxidant and magnesium aluminum silicate adsorbent in the prescription amount. Mix thoroughly until uniform, and pass the mixed material through a 40-mesh sieve.

[0040] (3) Mixing: Weigh the prescribed amount of magnesium stearate and add it to the above materials for mixing until uniform;

[0041] (4) Tableting: The total powder mixture is compressed into tablets to obtain melogabalin benzyl sulfonate tablets. The tablet weight and hardness are controlled during the tableting process.

[0042] (5) Coating: The coating powder is added to water and dispersed evenly to obtain a coating solution. The prepared uncoated tablets are coated with the coating solution, and the weight gain of the coating is in the range of 2% to 4%, thus obtaining melogabalin besylate coated tablets. The pharmaceutically acceptable solvent is selected from water or ethanol, and the solid content of the coating solution is 12% (w / w).

[0043] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:

[0044] The formulation designed in this invention uses vitamin E polyethylene glycol succinate, gallic acid, or tocopheryl succinate as antioxidants. After being prepared into a solution, it is evenly sprayed onto the active pharmaceutical ingredient, increasing the contact area between the two and resulting in better stability of the prepared merogabalin besylate drug composition. This effectively controls oxidative degradation impurities and improves the efficacy and safety of merogabalin besylate. Furthermore, the preparation method is stable, controllable, and easily scaled up. Detailed Implementation

[0045] The technical solution of the present invention will be further described below with reference to the embodiments.

[0046] Example 1: Screening of preparation process

[0047] 1. Pharmaceutical formulation

[0048] The prescription composition of melogabalin besylate tablets is as follows:

[0049]

[0050] 2. Formulation process

[0051] (1) Process 1

[0052] Weighing and preparing ingredients: Weigh each raw and auxiliary material according to the prescription amount and set aside;

[0053] Premix: Gallic acid was prepared into an aqueous solution. The prescribed amounts of melogabalin benzyl sulfonate and microcrystalline cellulose were added to the Mini-CG wet granulation pot. Then, the antioxidant gallic acid solution was sprayed in for premixing. The stirring speed was set to 100 rpm, the shearing speed to 1000 rpm, and the mixing time to 5 min.

[0054] Sieving 1: The mixed material is sieved through a 60-mesh sieve, and then the sieved material is dried at 40℃ for 30 min to 60 min.

[0055] Mixing: Add the prescribed amounts of melogabalin benzyl sulfonate premix, mannitol, calcium carboxymethyl cellulose, tartaric acid, and magnesium aluminum silicate to the HBD 20 square cone hopper mixer, set the mixing speed to 15 rpm, and the mixing time to 30 min;

[0056] Sieving 2: The mixed material is sieved through a 40-mesh sieve;

[0057] Sieving 3: Pass magnesium stearate (added) through a 40-mesh sieve, weigh the prescribed amount of magnesium stearate, and set aside;

[0058] Total mixing: The mixture after sieving 2 and the magnesium stearate after sieving 3 are added to the square cone hopper mixer for mixing. The mixing speed is set to 15 rpm and the mixing time is 4 min.

[0059] Tableting: The total mixture is compressed into tablets to obtain melogabalin besylate tablets. During the tableting process, the tablet weight is controlled within the range of 200mg±3% (194~206mg), and the hardness is controlled within the range of 8~12kg.

[0060] Coating: A coating solution (solid content: 12%) is prepared using a film coating agent. The prepared uncoated tablets are coated using the coating solution. The weight gain of the coating is in the range of 2% to 4%, thus completing the preparation of melogabalin besylate tablets.

[0061] (2) Process 2

[0062] Weighing and preparing ingredients: Weigh each raw and auxiliary material according to the prescription amount and set aside;

[0063] Mixing: Add the prescribed amounts of melogabalin benzyl sulfonate, mannitol, microcrystalline cellulose, calcium carboxymethyl cellulose, gallic acid, tartaric acid, and magnesium aluminum silicate to the HBD 20 square cone hopper mixer, set the mixing speed to 15 rpm, and the mixing time to 30 min;

[0064] Sieving 1: Pass the mixed material through a 40-mesh sieve;

[0065] Sieving 2: Pass magnesium stearate (added) through a 40-mesh sieve, weigh the prescribed amount of magnesium stearate, and set aside;

[0066] Total mixing: The mixture after sieving 1 and the magnesium stearate after sieving 2 are added to the square cone hopper mixer for mixing. The mixing speed is set to 15 rpm and the mixing time is 4 min.

[0067] Tableting: The total mixture is compressed into tablets to obtain melogabalin besylate tablets. During the tableting process, the tablet weight is controlled within the range of 200mg±3% (194~206mg), and the hardness is controlled within the range of 8~12kg.

[0068] Coating: A coating solution (solid content: 12%) is prepared using a film coating agent. The prepared uncoated tablets are coated using the coating solution, and the weight gain of the coating ranges from 2% to 4%.

[0069] 3. Stability Evaluation

[0070] Stability storage conditions: 40±2℃, 75%±5%RH, storage time: 5d, 10d, 30d.

[0071] The tablet samples prepared by processes 1 to 2 and the corresponding active pharmaceutical ingredients (process 1: premixed active pharmaceutical ingredients, process 2: unmixed active pharmaceutical ingredients) were placed in a petri dish and placed under the above-mentioned stability conditions to detect appearance and related substances.

[0072] Table 1. Results of API testing in the process screening experiment.

[0073]

[0074] Table 2. Tablet test results in the process screening experiment.

[0075]

[0076]

[0077] As shown in Tables 1 and 2, the stability of the active pharmaceutical ingredient (API) was significantly improved after treatment with process 1. By comparing the stability results of the formulations prepared using process 1 and process 2, it was found that the formulation prepared using process 1 had better stability than that prepared using process 2. This indicates that increasing the contact area between the antioxidant and the API in the formulation preparation process can effectively improve the stability of the formulation during storage and improve product quality.

[0078] In summary, through stability evaluation, the formulation prepared by process 1 has significantly better stability than that prepared by process 2. Therefore, process 1 is the preferred preparation process for subsequent formulation evaluation.

[0079] Example 2: Screening of Antioxidant Types

[0080] 1. Pharmaceutical formulation

[0081] The prescription composition of melogabalin besylate tablets is as follows:

[0082]

[0083] 2. Formulation process

[0084] Using process 1 in Example 1, the specific operation is as follows:

[0085] Weighing and preparing ingredients: Weigh each raw and auxiliary material according to the prescription amount and set aside;

[0086] Premix: Prepare the first group of antioxidants into a solution, add the prescribed amount of melogabalin benzyl sulfonate and microcrystalline cellulose to the Mini-CG wet granulation pot, and then spray in the antioxidant solution for premixing. Set the stirring speed to 100 rpm, the shearing speed to 1000 rpm, and the mixing time to 5 min.

[0087] Sieving 1: The mixed material is sieved through a 60-mesh sieve, and then the sieved material is dried at 40℃ for 30 min to 60 min.

[0088] Mixing: Add the prescribed amounts of melogabalin benzyl sulfonate premix, mannitol, calcium carboxymethyl cellulose, and tartaric acid to an HBD 20 square cone hopper mixer, set the mixing speed to 15 rpm, and the mixing time to 30 min;

[0089] Sieving 2: The mixed material is sieved through a 40-mesh sieve;

[0090] Sieving 3: Pass magnesium stearate (added) through a 40-mesh sieve, weigh the prescribed amount of magnesium stearate, and set aside;

[0091] Total mixing: The mixture after sieving 2 and the magnesium stearate after sieving 3 are added to the square cone hopper mixer for mixing. The mixing speed is set to 15 rpm and the mixing time is 4 min.

[0092] Tableting: The total mixture is compressed into tablets to obtain melogabalin besylate tablets. During the tableting process, the tablet weight is controlled within the range of 200mg±3% (194~206mg), and the hardness is controlled within the range of 8~12kg.

[0093] Coating: A coating solution (solid content: 12%) is prepared using a film coating agent. The prepared uncoated tablets are coated using the coating solution. The weight gain of the coating is in the range of 2% to 4%, thus completing the preparation of melogabalin besylate tablets.

[0094] 3. Stability Evaluation

[0095] Stability storage conditions: 40±2℃, 75%±5%RH accelerated test and 60℃ high temperature test, storage time: 5d, 10d, 30d. The tablets prepared by formulations 1 to 10 were placed in a petri dish and placed under the above stability conditions to test the product appearance and related substances.

[0096] Table 3-1 Results of Prescription Screening Experiment

[0097]

[0098]

[0099] Table 3-2 Results of Prescription Screening Experiment

[0100]

[0101]

[0102] The protective effects of different antioxidants on the product during the stability storage process were investigated, as shown in Tables 3-1 and 3-2. Some antioxidants (such as vitamin E polyethylene glycol succinate, gallic acid, tocopherol succinate, and tocopherol) had a positive protective effect compared to Formulation 10 (formulation without antioxidants). However, some antioxidants (such as tert-butylhydroquinone, ascorbic acid, and thioglycerol) accelerated the degradation of impurities compared to Formulation 10 (formulation without antioxidants), thus affecting product quality.

[0103] Meanwhile, it was found that under accelerated storage conditions for 30 days, the formulations with added vitamin E polyethylene glycol succinate, gallic acid, or tocopherol succinate showed better stability. The formulation with added gallic acid was preferred, and its antioxidant effect was significantly better than that of formulation 10 (without added antioxidants) and also better than that of the formulation with added tocopherol. Moreover, the three formulations had comparable protective effects on the main component melogabalin benzyl sulfonate. The appearance of the product met the requirements, and the degradation rate of oxidative impurities was slower. Under high temperature conditions (60°C) for 30 days, it was significantly better than the formulations without added antioxidants or tocopherol.

[0104] Tocopherol, also known as vitamin E, is an oily substance that is difficult to mix evenly with the active pharmaceutical ingredient during the formulation process. Therefore, in this invention, the preferred antioxidants are vitamin E polyethylene glycol succinate, gallic acid, or tocopherol succinate, with gallic acid being a more preferred antioxidant.

[0105] Example 3: Screening of Antioxidant Dosage

[0106] 1. Pharmaceutical formulation

[0107] The prescription composition of melogabalin besylate tablets is as follows (based on unpackaged tablet weight):

[0108]

[0109]

[0110] The prescription composition of melogabalin besylate tablets is as follows:

[0111]

[0112] 2. Formulation process

[0113] The preparation process is the same as process 1 in Example 1, and the specific operation is as follows:

[0114] Weighing and preparing ingredients: Weigh each raw and auxiliary material according to the prescription amount and set aside;

[0115] Premix: Gallic acid was prepared into an aqueous solution. The prescribed amounts of melogabalin benzyl sulfonate and microcrystalline cellulose were added to the Mini-CG wet granulation pot. Then, the antioxidant gallic acid solution was sprayed in for premixing. The stirring speed was set to 100 rpm, the shearing speed to 1000 rpm, and the mixing time to 5 min.

[0116] Sieving 1: The mixed material is sieved through a 60-mesh sieve, and then the sieved material is dried at 40℃ for 30 min to 60 min.

[0117] Mixing: Add the prescribed amounts of melogabalin benzyl sulfonate premix, mannitol, calcium carboxymethyl cellulose, tartaric acid, and magnesium aluminum silicate to the HBD 20 square cone hopper mixer, set the mixing speed to 15 rpm, and the mixing time to 10 min;

[0118] Sieving 2: The mixed material is sieved through a 40-mesh sieve;

[0119] Sieving 3: Pass magnesium stearate (added) through a 40-mesh sieve, weigh the prescribed amount of magnesium stearate, and set aside;

[0120] Total mixing: The mixture after sieving 2 and the magnesium stearate after sieving 3 are added to the square cone hopper mixer for mixing. The mixing speed is set to 15 rpm and the mixing time is 4 min.

[0121] The total mixture was compressed into tablets to obtain melogabalin benzyl ...

[0122] Coating: A coating solution (solid content: 12%) is prepared using a film coating agent. The prepared uncoated tablets are coated using the coating solution. The weight gain of the coating is in the range of 2% to 4%, thus completing the preparation of melogabalin besylate tablets.

[0123] 3. Stability Evaluation

[0124] Stability testing conditions: 40±2℃, accelerated test at 75%±5%RH, and high-temperature test at 60℃; storage times: 5d, 10d, and 30d. Tablets prepared according to formulations 1–3 were placed in petri dishes and subjected to the above stability conditions. Appearance and related substances were then tested.

[0125] Table 4 Results of the Antioxidant Dosage Screening Experiment

[0126]

[0127] As shown in Table 4, gallic acid (0.5%) in Formula 1 has better stability than that in Formula 2 (0.1%) and Formula 3 (1.0%). This indicates that adding an appropriate amount of antioxidant to the formula is beneficial to the stability of the formulation and effectively reduces the growth of oxidative impurities during storage. Therefore, in this invention, the preferred amount of antioxidant gallic acid in the formula is 0.5% of the weight of the tablets.

[0128] In summary, the merogabalin besylate tablet composition designed in this invention exhibits good stability and fewer degradation impurities compared to the original tablet (antioxidant: tocopherol, formulation 5 in Example 2). Furthermore, this invention involves mixing the antioxidant vitamin E polyethylene glycol succinate, gallic acid, or tocopherol succinate with the active pharmaceutical ingredient merogabalin besylate before preparing the formulation, further enhancing the antioxidant effect. Overall, this significantly improves the product quality, efficacy, and controllable safety, while also significantly reducing the difficulty of controlling the storage and transportation conditions of the active pharmaceutical ingredient.

Claims

1. A pharmaceutical composition containing merogabarine besylate, characterized in that, The excipients include fillers, disintegrants, lubricants, antioxidants, adsorbents, and coating agents. The antioxidants include a first component selected from vitamin E polyethylene glycol succinate, gallic acid, or tocopherol succinate.

2. The pharmaceutical composition according to claim 1, characterized in that, The antioxidants include a first component selected from gallic acid.

3. The pharmaceutical composition according to claim 1, characterized in that, The antioxidant also includes a second component selected from one or more of tartaric acid, maleic acid, and succinic acid.

4. The pharmaceutical composition according to claim 3, characterized in that, The antioxidants mentioned are selected from vitamin E polyethylene glycol succinate-tartaric acid, gallic acid-tartaric acid, and tocopheryl succinate-tartaric acid.

5. The pharmaceutical composition according to claim 1, characterized in that, The filler is selected from one or more of mannitol, lactose, microcrystalline cellulose, corn starch, and compressible starch.

6. The pharmaceutical composition according to claim 1, characterized in that, The disintegrant is selected from one or more of calcium carboxymethyl cellulose, dry starch, sodium carboxymethyl starch, crospovidone, and sodium crospovidone carboxymethyl cellulose.

7. The pharmaceutical composition according to claim 1, characterized in that, The lubricant is selected from one or more of stearic acid, magnesium stearate, calcium stearate, sodium stearate fumarate, talc, and micronized silica gel.

8. The pharmaceutical composition according to claim 1, characterized in that, The adsorbent is selected from one or more of silica, colloidal silica, magnesium silicate, magnesium aluminum silicate, and calcium silicate.

9. The pharmaceutical composition according to claim 1, characterized in that, By weight, it comprises the following components: 1 to 10 parts of melogabalin benzyl sulfonate, 50 to 95 parts of filler, 2 to 10 parts of disintegrant, 0.5 to 3 parts of lubricant, 0.5 to 6 parts of antioxidant, 0.1 to 1 part of adsorbent and 1 to 6 parts of coating agent.

10. The pharmaceutical composition according to claim 1, characterized in that, By weight, it comprises the following components: 4.4 parts melogabalone benzenesulfonate, 79.5 parts D-mannitol, 1 part microcrystalline cellulose, 10 parts calcium carboxymethyl cellulose, 0.5 parts vitamin E polyethylene glycol succinate, gallic acid or tocopherol succinate, 3 parts tartaric acid, 0.1 parts magnesium aluminum silicate, 1.5 parts magnesium stearate, and 4 parts film coating agent.

11. A method for preparing the pharmaceutical composition according to claim 1, characterized in that, Includes the following steps: (1) Preparation of a mixture containing melogabalin benzyl sulfonate and antioxidant component one: Prepare antioxidant component one into a solution, premix melogabalin benzyl sulfonate, a portion of the filler and antioxidant component one solution, sieve and dry; (2) Mixing: The mixture containing melogabalin benzyl sulfonate obtained in step (1) is mixed with the remaining filler, disintegrant, second antioxidant component and adsorbent, and then sieved. (3) Mixing: Mix the lubricant with the material obtained in step (2); (4) Tableting: The material obtained in step (3) is compressed into tablets to obtain melogabalin benzyl sulfonate tablets; (5) Coating: Prepare a coating solution from the coating powder and coat the uncoated tablets obtained in step (4) to obtain the pharmaceutical composition.

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