Melogabalin besylate raw material capable of controlling particle size distribution, preparation of melogabalin besylate raw material, and preparation process and application of preparation

Abstract

The invention discloses a melogabalin besylate raw material capable of controlling particle size distribution, a preparation of the melogabalin besylate raw material, and a preparation process and application of the preparation, and belongs to the technical field of pharmaceutical preparations. The technical problem to be solved is to improve the stability, mixing uniformity and dissolution rate of the melogabalin besylate preparation. According to the technical scheme, the melogabalin besylate raw material capable of controlling particle size distribution is characterized in that the particle size ranges of the melogabalin besylate raw material are as follows: D90 is 130-210 [mu] m, and D50 is 44-71 [mu] m. According to the melogabalin besylate preparation, through the synergistic effect of the specific stabilizer, the characteristics of uniformity and quick release of the product are ensured, the generation of degraded impurities is effectively controlled, and the product quality is stable and controllable.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, specifically to a melogabalin benzyl sulfonate raw material with controlled particle size distribution, its formulation, the preparation process of the formulation, and its application. Background Technology

[0002] Merogabalin besylate, chemically known as [(1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid monobenzenesulfonate, plays an important role as a calcium channel modulator in the treatment of neuropathic pain, such as diabetic peripheral neuropathy and postherpetic neuralgia. Merogabalin besylate primarily relieves pain symptoms by regulating calcium ion channels, reducing calcium ion influx, and inhibiting excessive neuronal excitation and neurotransmitter release.

[0003] Merogabalin besylate is commonly available in oral tablet form.

[0004] Relevant patents found: This document, published in China (CN104334169A) on February 4, 2015, discloses a solid composition comprising a stabilized salt of an aminocarboxylic acid. The solid composition contains the compound [(1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid monobenzenesulfonate in combination with suitable additives. The composition showed an increase in impurities of approximately 0.17-0.29% after storage at 40°C and 75% RH for 3 months, and an increase in related substances of 4.5% after storage at 60°C for 4 weeks.

[0005] This document, published in China (CN120324356A) on July 18, 2025, discloses a merogabarine besylate tablet. The tablet core comprises merogabarine besylate, a filler, a disintegrant, a lubricant, a flow aid, and a stabilizer. The disintegrant is sodium carboxymethyl starch, and the stabilizers are tocopherol and tartaric acid. The stability of the prepared merogabarine besylate tablet (especially the quality control of impurity I) is superior to that of the reference formulation. The amount of related substances generated after the tablet is stored at 40°C and 75% RH for 60 days is approximately 0.33%.

[0006] This document, published in China (CN119235806A) on January 3, 2025, discloses a merogabarine besylate tablet. The tablet core comprises merogabarine besylate, a filler, a disintegrant, a lubricant, a flow aid, and a stabilizer. The stabilizer is selected from propyl gallate, ascorbate palmitate, disodium edetate, anhydrous or monohydrate citric acid, tocopherol, malic acid, tartaric acid, fumaric acid, maleic acid, and butylated hydroxytoluene, preferably one or more of tocopherol, anhydrous citric acid, monohydrate citric acid, tartaric acid, ascorbate palmitate, and propyl gallate. Taking formulation 10 as an example, after being stored at 40°C and 75% RH for 30 days, the amount of related substances produced is approximately 0.36%, and the dissolution rate in a dissolution medium at pH 1.2 is 89.6-92.1% within 10-45 minutes.

[0007] The prior art represented by the aforementioned documents has at least the following unresolved technical problems or defects: (1) Poor stability. Relevant evidence is as follows: Under conditions of 40℃ and 75% RH, the composition of CN104334169A showed an increase of approximately 0.17-0.29% in impurities after storage at 40℃ and 75% RH for 3 months, and an increase of 4.5% in related substances after storage at 60℃ for 4 weeks. The tablet of CN120324356A showed an amount of approximately 0.33% in related substances after storage at 40℃ and 75% RH for 60 days. The tablet of CN119235806A showed an amount of approximately 0.36% in related substances after storage at 40℃ and 75% RH for 30 days.

[0008] (2) Poor dissolution performance: CN119235806A The dissolution rate of this tablet is 89.6-92.1% within 10-45 min in a dissolution medium of pH 1.2.

[0009] Therefore, there is still a need in this field to develop a more stable melogabalin benzyl sulfonate raw material and its formulations, preparation processes, and applications with better dissolution performance. Summary of the Invention

[0010] The purpose of this invention is to provide: A benzenesulfonic acid melogabalin raw material for controlling particle size distribution, and related technologies, to solve technical problems such as improving stability, improving dissolution, improving mixing uniformity, or combinations thereof.

[0011] In a first aspect, the present invention provides: a benzenesulfonic acid melogabalin raw material with controlled particle size distribution, wherein the particle size range of the benzenesulfonic acid melogabalin raw material is: D90 of 130-210 μm and D50 of 44-71 μm; more preferably, D90 of 134-210 μm and D50 of 44-71 μm.

[0012] This specific particle size range helps improve drug stability and mixing uniformity, reduces drug changes during storage, and thus improves drug safety and efficacy.

[0013] In a second aspect, the present invention provides: a melogabalin besylate formulation comprising the melogabalin besylate raw material and pharmaceutically acceptable excipients.

[0014] Pharmaceutically acceptable excipients include at least one of stabilizers, fillers, gliding agents, and lubricants.

[0015] The stabilizer is anhydrous citric acid.

[0016] The filler includes at least one of mannitol, microcrystalline cellulose, and corn starch.

[0017] The flow aid includes at least one of magnesium aluminum metasilicate and colloidal silica.

[0018] The lubricant includes magnesium stearate.

[0019] The preparation is a tablet.

[0020] The formulation also includes a coating.

[0021] The coating is selected from: gastrointestinal film coating premix.

[0022] The gastrointestinal film coating premix consists of at least one of hydroxypropyl methylcellulose, titanium dioxide, talc, yellow iron oxide, and iron oxide.

[0023] The melogabalin besylate formulation comprises, by weight, the following components: 4-6 parts of melogabalin besylate raw material, 1-4 parts of stabilizer, 87-94 parts of filler, 0.1-0.5 parts of flow aid, and 1-2 parts of lubricant.

[0024] The filler includes mannitol, microcrystalline cellulose and corn starch; preferably, the amount of mannitol is 44-82 parts, the amount of microcrystalline cellulose is 5-29 parts, and the amount of corn starch is 7-15 parts.

[0025] Thirdly, the present invention provides a preparation process for a melogabalin besylate formulation, comprising the following steps: (1) Premixed: First, melogabalin benzyl sulfonate and the stabilizer are mixed evenly to obtain mixture A; mixture A is then mixed evenly with the filler and the flow aid to obtain mixture B. (2) Total mixture: Add the lubricant to mixture B and mix thoroughly to obtain mixture C; (3) Tableting: The mixture C is compressed into tablets, with or without coating, to obtain the final product.

[0026] In step (1), the stabilizer is passed through an 80-mesh sieve before being mixed with melogabalin benzylsulfonic acid.

[0027] In step (3), the pressure of the tablet is 7-16KN.

[0028] In step (3), the average hardness of the 2.5 mg mixture C after tableting is controlled within the range of 50-100 N.

[0029] In step (3), the average hardness of the 5mg mixture C tablets is controlled within the range of 70-120N.

[0030] In step (3), the weight gain after coating is 3-5% of the mass of mixture C.

[0031] Fourthly, the present invention provides the use of the described merogabalin besylate raw material, the described merogabalin besylate preparation, or the merogabalin besylate preparation obtained by the described preparation process in the preparation of a medicament for treating neuropathic pain.

[0032] Based on further solutions to the technical problems of the present invention, or simultaneous solutions to multiple technical problems, the preferred solution in the technical solution provided in the second aspect of the present invention includes: The first preferred embodiment is a melogabalin benzyl sulfonate formulation comprising, by weight, the following components: 4-6 parts of melogabalin benzyl sulfonate raw material, 1-4 parts of stabilizer, 87-94 parts of filler, 0.1-0.5 parts of flow aid, and 1-2 parts of lubricant. This technical solution solves the technical problems of "improving mixing uniformity and improving dissolution".

[0033] The second preferred embodiment: A melogabalin besylate formulation, by weight, comprises the following components: 4-6 parts of melogabalin besylate raw material, 1-4 parts of stabilizer, 87-94 parts of filler, 0.1-0.5 parts of flow aid, and 1-2 parts of lubricant, wherein the stabilizer is anhydrous citric acid. This technical solution solves the technical problem of "improving stability".

[0034] Based on further solutions to the technical problems of the present invention, or simultaneous solutions to multiple technical problems, the preferred solution in the technical solution provided in the third aspect of the present invention includes: The first preferred embodiment: a preparation process for a melogabalin besylate formulation, comprising the following steps: (1) Premixed: First, melogabalin benzyl sulfonate and the stabilizer are mixed evenly to obtain mixture A; mixture A is then mixed evenly with the filler and the flow aid to obtain mixture B. (2) Total mixture: Add the lubricant to mixture B and mix thoroughly to obtain mixture C; (3) Tableting: The mixture C is compressed into tablets and then coated. The weight gain of the coating is 3-5%, which yields the final product.

[0035] This technical solution addresses the technical problem of "improving stability".

[0036] The second preferred embodiment: a preparation process for a melogabalin besylate formulation, comprising the following steps: (1) Premixed: Merogabalin benzenesulfonic acid and anhydrous citric acid (after passing through an 80-mesh sieve) were weighed and placed in a mixing tank, and then thoroughly mixed to obtain the sieved material. Mannitol, microcrystalline cellulose, corn starch, and magnesium aluminum metasilicate were then added to the sieved material, and the mixture was then placed in a lifting hopper mixer and mixed thoroughly to obtain the premixed material.

[0037] (2) Total mixture: Weigh out the prescribed amount of magnesium stearate and add it to the premixed material, then mix it evenly using a lifting hopper mixer.

[0038] (3) Tableting: Control the main pressure at 7-16KN, and control the average hardness range of 2.5mg at 50-100N and the average hardness range of 5mg at 70-120N.

[0039] (4) Coating: Choose a film coating premix for coating, and the coating weight gain is 3-5%.

[0040] This technical solution addresses the technical problem of "improving stability".

[0041] The present invention has at least the following beneficial effects: Compared with existing technologies, this invention optimizes the particle size, excipient composition, and dosage of merogabarine besylate, resulting in better technical effects in terms of stability, dissolution, and improved mixing uniformity. The merogabarine besylate tablets prepared by this invention, after being stored at 60°C for 10 days, show a total impurity content of less than 0.26%. Detailed Implementation

[0042] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0043] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all instruments, devices, equipment, reagents, products, etc., used in the embodiments of the present invention are obtained through conventional commercial means.

[0044] The methods for stability testing, dissolution testing, and mixing uniformity testing in the following embodiments are as follows.

[0045] (1) Stability assessment method: Influencing factors test: high temperature 60℃; bare film (without packaging).

[0046] Accelerated testing: 40℃±2℃, 75%RH±5%RH; testing should be conducted with packaging, using aluminum-plastic pillow packaging with built-in silica gel desiccant.

[0047] (2) Dissolution test method: The test was conducted according to Method II (paddle method) in General Chapter 0931 of the 2025 edition of the Chinese Pharmacopoeia, and the specific test conditions are shown in Table 1.

[0048] Dissolution medium 1 (pH 1.2 hydrochloric acid sodium chloride solution): Take 2.0g of sodium chloride, dissolve it in degassed water and dilute it to 1000ml, mix well, and add an appropriate amount of hydrochloric acid to adjust the pH value to 1.2.

[0049] Dissolution medium 2 (pH 4.5 acetate solution): Accurately weigh approximately 2.99 g of sodium acetate trihydrate, add degassed water to dissolve and dilute to 1000 ml, mix well, and then adjust the pH to 4.5 with glacial acetic acid.

[0050] Dissolution medium 3 (pH 6.8 phosphate solution): Accurately weigh approximately 6.80 g of potassium dihydrogen phosphate and approximately 0.896 g of sodium hydroxide, dissolve and dilute with degassed water to 1000 ml, mix well, and adjust the pH to 6.8 with sodium hydroxide solution.

[0051] Dissolution medium 4 (water): Take degassed water, which is obtained.

[0052] Table 1 Dissolution test conditions

[0053] (3) Methods for assessing the uniformity of mixing: During the preparation of melogabalin besylate tablets, after the total mixing was completed, samples were taken from 11 different locations in the elevator hopper mixer to test the content of melogabalin besylate.

[0054] Sampling method: Sampling was performed from top to bottom at 11 locations: the top of the mixer (sampling points 1, 2, 3, 4, 5), the corner edges (sampling points 6, 7, 8, 9, 10), and the discharge port (sampling point 11). One sample was tested at each sampling point, and the RSD of all samples was calculated. All individual values ​​were within ±10.0% (absolute) of the mean. If the RSD ≤ 5.0%, the requirement was met. If the RSD > 5.0%, the mixing uniformity of two additional parallel samples from each sampling point was measured.

[0055] 1.1 Study on particle size of active pharmaceutical ingredient In the stage of studying the particle size of the active pharmaceutical ingredient (API), this invention first collected samples of melogabalin besylate API with different particle size ranges. The manufacturers and batch numbers of the APIs were as follows: Hubei Tianshu Pharmaceutical Co., Ltd., batch numbers 405-1-240101 (Example 1), 405-1-240702 (Example 2), and 405-1-240703 (Example 3); and Shanghai Yaotan Pharmaceutical Research and Development Co., Ltd., batch number NEU2055-L-2405001T (Example 5).

[0056] Example 4: Preparation process of active pharmaceutical ingredient (API): The API with batch number NEU2055-L-2405001T was pulverized. The specific process was as follows: Merogabalin besylate API was pulverized using a dust-collecting pulverizer (20BVT type). The pulverizer had a built-in sieve with a mesh size of 30 mesh.

[0057] The particle size distribution of these samples was precisely measured using equipment such as a laser particle size analyzer, covering a range from fine to large particle sizes, to comprehensively evaluate the impact of particle size on drug performance. Subsequently, a series of dissolution experiments were conducted. Dissolution of active pharmaceutical ingredients with different particle sizes was investigated in a dissolution medium simulating the human gastrointestinal environment. 10 mg of merogalaline besylate from Examples 1-5 was added to 900 ml of pH 1.2 sodium chloride hydrochloride solution (equivalent to 5.69 mg of merogalaline) for dissolution testing, with six samples taken from each example. The dissolution results are shown in Table 2.

[0058] Table 2 Dissolution results of active pharmaceutical ingredients with different particle sizes (mg / ml) (n=6)

[0059] Experimental results showed that when the particle size of the active pharmaceutical ingredient was in the range of D90 (34.5-398 μm) and D50 (13-132 μm), the active pharmaceutical ingredient exhibited rapid solubility.

[0060] Further investigation will be conducted on the stability of formulations prepared from active pharmaceutical ingredients with different particle sizes.

[0061] Table 3 shows the experimental factor levels, and Table 4 shows the specific prescriptions for Merogabalin Besylate Tablets in Examples 6-9.

[0062] Table 3. Levels of Experimental Factors

[0063] Table 4. Prescriptions for Merogabalin Besylate Tablets (Examples 6-9)

[0064] Examples 6-9: Preparation process of merogabarine besylate tablets (800g / batch, 4000 tablets): (1) Premixed: Merogabalin benzenesulfonic acid and anhydrous citric acid (after passing through an 80-mesh sieve) were weighed and placed in a mixing tank, and then thoroughly mixed to obtain the sieved material. Mannitol, microcrystalline cellulose, corn starch, and magnesium aluminum metasilicate were then added to the sieved material, and the mixture was then placed in a lifting hopper mixer and mixed thoroughly to obtain the premixed material.

[0065] (2) Total mixture: Weigh out the prescribed amount of magnesium stearate and add it to the premixed material, then mix it evenly using a lifting hopper mixer.

[0066] (3) Tableting: Control the main pressure at 11-13KN and keep the average hardness of 5mg within the range of 90N-110N.

[0067] (4) Coating: A film coating premix was selected for coating, and the coating weight gain was 4.0%.

[0068] The stability of the melogabalin besylate tablets prepared in Examples 6-9 was investigated by the influencing factor test, and the stability results are shown in Table 5.

[0069] Table 5. Stability results of Examples 6-9

[0070] Impurity A has the molecular formula C 12 H 19 NO2, with a molecular weight of 191.27, has the chemical name (1R,5S,6S)-3-ethylspirocyclic [bicyclo[3.2.0]hept-3-en-6,3'-pyrrolidine]-5'-one, and its structural formula is:

[0071] The mixing uniformity of the materials obtained after total mixing during the preparation of melogabalin benzyl sulfonate tablets in Examples 6-9 was investigated, and the results of the mixing uniformity are shown in Table 6.

[0072] Table 6. Mixing homogeneity results for Examples 6-9 (n=11)

[0073] a This indicates the percentage of melogabalin benzyl sulfonate obtained from actual testing compared to the theoretical content.

[0074] As shown in Table 6, D50: 132 μm and D90: 398 μm are difficult to meet the uniformity requirements. The other particle size ranges do not affect the mixing uniformity results. Combined with the stability results, the preferred API particle size results are determined to be: D90 130-210 (μm); D50 44-71 (μm).

[0075] 1.2 Selection of Stabilizer The main degradation impurity A of melogabalin besylate is formed by the dehydration and cyclization of the amino carboxyl group of the active pharmaceutical ingredient (lactam, five-membered ring), and the amino group is oxidized to a nitro group in an oxidation reaction.

[0076] To screen for the most suitable stabilizer for merogabarine besylate tablets, this invention conducted a comprehensive experimental study. First, anhydrous citric acid, citric acid, and several other common stabilizers were selected as research subjects and added to the formulation of merogabarine besylate tablets, as shown in Table 7.

[0077] In the stability test, formulation samples containing different stabilizers were placed under accelerated conditions such as high temperature for evaluation. The samples were periodically tested to analyze the formation of impurities and changes in appearance. The results are shown in Table 8.

[0078] Table 7. Prescriptions for Merogabalin Besylate Tablets (Examples 10-14)

[0079] Note: The particle size of the melogabalin benzenesulfonic acid raw material used in Examples 10-14 is the same as that in Example 7.

[0080] The preparation processes of Examples 10-14 are the same as those in Example 7.

[0081] Table 8. Stability test results

[0082] Note: ND indicates not detected.

[0083] Experimental results show that formulations using anhydrous citric acid as a stabilizer exhibit excellent stability. The mechanism is believed to be primarily due to the presence of three carboxyl groups in anhydrous citric acid, classifying it as a tribasic weak organic acid (pKa1≈3.13, pKa2≈4.76, pKa3≈6.40). This acid can slow down the degradation of drugs containing γ-aminobutyric acid (GABA) structures through pH regulation, weak interactions, and physical protection. Furthermore, the use of weakly acidic excipients ensures that the pH of the formulation remains stable near the isoelectric point of GABA, thereby reducing the occurrence of amino carboxyl dehydration and cyclization reactions.

[0084] Citric acid becomes anhydrous when dried or heated to 40-50°C. The water of crystallization contained in citric acid after dehydration becomes an inducing condition for degradation. Conversely, anhydrous citric acid can more effectively inhibit the degradation reaction of drug molecules, reduce the generation of impurities, and thus extend the shelf life of the drug.

[0085] 1.3 Optimization of prescription composition and proportion In the formulation of merogabarine besylate tablets of this invention, mannitol serves as the main filler, exhibiting good flowability and compressibility, increasing tablet weight and volume, ensuring tablet formation, and its high solubility also facilitates rapid drug release in vivo. Microcrystalline cellulose and corn starch not only act as fillers but also improve tablet hardness. Magnesium aluminum metasilicate, as a flow aid, improves material flowability, ensuring uniform mixing and smooth tablet compression during preparation, and also possesses adsorbent properties, effectively adsorbing moisture from the formulation. Magnesium stearate acts as a lubricant, reducing friction between the material and the die, preventing sticking and ensuring tablet appearance quality. Anhydrous citric acid, as a stabilizer, provides a weakly acidic environment, mitigating the degradation of γ-aminobutyric acid (GABA) structured drugs, and as mentioned above, plays a crucial role in maintaining formulation stability.

[0086] The dosage range of excipients was screened below. The specific formulations for Examples 15-17 are shown in Table 9. The dissolution test results are shown in Table 10.

[0087] Table 9 Prescriptions for Examples 15-17

[0088] Note: The particle size of the melogabalin benzenesulfonic acid raw material used in Examples 15-17 is the same as that in Example 7.

[0089] The preparation processes of Examples 15-17 are the same as those in Example 7.

[0090] Table 10 Dissolution results of sodium chloride hydrochloride solution at pH 1.2

[0091] As shown in Table 10, each component can achieve rapid release under different ratios, so the formulation ratios all meet the requirements within the scope of protection of this invention.

[0092] Example 16 was scaled up in three batches of 200,000 tablets each, designated as Example 16-1, Example 16-2, and Example 16-3, respectively. Stability and dissolution were investigated. The results of the influencing factors for Example 16-1 are shown in Table 11, the dissolution results for the three batches are shown in Table 12, and the accelerated release test results are shown in Table 13. Table 12 shows that rapid release was achieved in all media.

[0093] Table 11 Results of the investigation of influencing factors in Example 16-1

[0094] Table 12 Dissolution Results

[0095] Table 13 Results of Accelerated Tests

[0096] 1.4 Conclusion This invention, in the preparation of merogabarine besylate tablets, through in-depth research on the particle size of the active pharmaceutical ingredient, determined the optimal particle size range, effectively improving the drug's dissolution and stability, and providing patients with a more efficient treatment option. Regarding the selection of stabilizers, the application of anhydrous citric acid demonstrated excellent stability advantages, greatly improving the quality stability of the formulation during storage and use, ensuring that patients can use reliable medications.

[0097] Optimization of the formulation composition and proportions achieved optimal synergistic effects among excipients such as mannitol, microcrystalline cellulose, corn starch, magnesium aluminum metasilicate, magnesium stearate, and anhydrous citric acid, ensuring tablet formability, hardness, and drug dissolution performance, thus improving the overall quality of the formulation. Optimization of the film coating played a crucial role in improving drug appearance, moisture protection, and masking unpleasant odors, ultimately achieving the best balance between drug performance, quality, and cost, and enhancing the patient's medication experience.

Claims

1. A melogabalin benzenesulfonic acid raw material for controlling particle size distribution, characterized in that, The particle size range of the melogabalin benzenesulfonic acid raw material is: D90 is 130-210μm, and D50 is 44-71μm.

2. A melogabalin besylate formulation, characterized in that, It includes the melogabalin benzyl sulfonate raw material as described in claim 1 and pharmaceutically acceptable excipients.

3. The melogabalin besylate formulation according to claim 2, characterized in that, The product comprises the following components by weight: 4-6 parts of melogabalin benzenesulfonic acid raw material, 1-4 parts of stabilizer, 87-94 parts of filler, 0.1-0.5 parts of flow aid and 1-2 parts of lubricant.

4. The melogabalin benzyl sulfonate formulation according to claim 3, characterized in that, The stabilizer is anhydrous citric acid.

5. The melogabalin benzylsulfonate formulation according to claim 4, characterized in that, The filler includes at least one of mannitol, microcrystalline cellulose, and corn starch; and / or the flow aid includes at least one of magnesium aluminum metasilicate and colloidal silica; and / or the lubricant includes magnesium stearate. Preferably, the filler includes mannitol, microcrystalline cellulose and corn starch; more preferably, by weight, mannitol is 44-82 parts, microcrystalline cellulose is 5-29 parts and corn starch is 7-15 parts.

6. The melogabalin besylate formulation according to any one of claims 2-5, characterized in that, The preparation is a tablet.

7. The melogabalin besylate formulation according to any one of claims 2-5, characterized in that, The formulation also includes coating.

8. A preparation process for a melogabalin benzylsulfonic acid formulation according to any one of claims 3-7, characterized in that, Includes the following steps: (1) Premixed: First, melogabalin benzyl sulfonate and the stabilizer are mixed evenly to obtain mixture A; mixture A is then mixed evenly with the filler and the flow aid to obtain mixture B. (2) Total mixture: Add the lubricant to mixture B and mix thoroughly to obtain mixture C; (3) Tableting: The mixture C is compressed into tablets, with or without coating, to obtain the final product.

9. The preparation process according to claim 8, characterized in that, The pressure for pressing the tablet in step (3) is 7-16 kN; Preferably, the average hardness of the 2.5 mg mixture C tablet is controlled within the range of 50-100 N; Preferably, the average hardness of the 5mg mixture C tablets is controlled within the range of 70-120N; Preferably, the weight gain after coating is 3-5% of the mass of mixture C.

10. The use of the merogabalin besylate raw material according to claim 1, or the merogabalin besylate preparation according to any one of claims 2-7, or the merogabalin besylate preparation prepared by the preparation process according to any one of claims 8-9, in the preparation of a medicament for treating neuropathic pain.

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