Stable succinic acid trelagliptin tablet and preparation process thereof

Abstract

The invention provides a preparation process of trelagliptin succinate tablets, which comprises the following steps: pretreating trelagliptin succinate and internally added materials in a high-shear wet-process mixing granulator, and then transferring into a fluidized bed to granulate according to optimized parameters. According to the process, various process feasibility problems caused by poor physical properties of raw material medicines are solved in a wet pretreatment mode, and quality risks caused by product crystal transformation are solved in a mannitol addition mode.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a stable trelagliptin succinate tablet and a preparation process thereof. Background Art

[0002] Trelagliptin succinate tablets are the world's first oral hypoglycemic drug with ultra-long-acting DPP-IV inhibitors. They can be taken once a week for the treatment of type 2 diabetes. They control blood sugar by selectively and continuously inhibiting DPP-IV. On May 28, 2015, the original Takeda was approved for marketing in Japan with specifications of 50mg and 100mg, trade name: Zafatek; on December 3, 2019, a new specification of 25mg was approved; currently it is only available in Japan.

[0003] Patent document CN104519874A provides a prescription composition of a solid preparation of trelagliptin. In the embodiment, a fluidized bed preparation process is used to mix the main drug, mannitol, crystalline cellulose and cross-linked sodium carboxymethyl cellulose, and granulate by spraying hydroxypropyl cellulose. The invention provides a solid preparation with excellent disintegration performance and storage stability, improves the disintegration performance and solubility of the preparation in the stomach, and ensures the effective absorption of the active ingredients of the drug in the body.

[0004] Patent document CN110063942A provides a solid preparation of trelagliptin succinate and a preparation method thereof, and mentions the adverse effects of the physicochemical properties of the raw material on the tablet preparation process.

[0005] The inventors also found during the preparation process that when the bulk drug of Trelagliptin Succinate Tablets reaches more than 50%, the physical and chemical properties of the bulk drug will directly affect the feasibility of the product preparation process. The bulk drug of this product is loose (bulk density 0.15-0.20 g / cm 3 ), the stable crystal form (crystal form A) is needle-shaped crystal with extremely poor fluidity, easy aggregation, easy adhesion and static electricity generation, which leads to poor fluidization state in the fluidized bed granulation process, unreasonable process parameter design, uncontrollable production process and other problems, which need to be improved.

[0006] The physical properties of the raw material of Trelagliptin succinate also affect the compressibility of the product. The crystal form, bulk density and fluidity of the raw material easily lead to the phenomenon of uncovering during the tableting process, especially at the notch. The inventors have found that if the tablets are prepared according to the method provided in CN104519874A, sticking or astringent phenomena are very likely to occur during the tableting process, affecting the product production process. In severe cases, the tablets cannot be compressed into shape.

[0007] In addition, when preparing tablets according to the method provided in CN104519874A, there is a phenomenon of crystal transformation during the granulation process. When the spraying speed of the formulation containing mannitol is accelerated or the water content of the particles reaches a certain amount, crystal transformation is easy to occur. According to Ye Jiali, Zhou Xinbo, Wu Suxiang, Sun Mengying, et al. Study on the crystal structure and crystal stability of trelagliptin succinate [J]. Acta Pharmaceutica Sinica 2016, 15(11): 1759-1764, the reason why mannitol may induce crystal transformation is that one molecule of mannitol contains 6 -OH groups. Water molecules can act as bridge atoms to tightly connect several groups of molecules in trelagliptin succinate through intermolecular hydrogen bonds, while mannitol can provide more hydrogen bonds than water molecules, making trelagliptin succinate easier to convert into trelagliptin succinate. The more water content, the easier it is to promote this reaction.

[0008] Patent documents CN 110063942 A and CN113975241A also mentioned that the poor fluidity and poor material formability of trelagliptin raw materials have adverse effects on the formulation process. Therefore, the technical applicability of the prescription composition of CN104519874A is relatively poor.

[0009] Patent document CN113975241A discloses a preparation process of trelagliptin succinate tablets, in which a preferred carrier ratio is mixed with the raw material and granulated in a spray-dried form, thereby avoiding the influence of the poor physical properties of the raw material on the product process, making the process parameter design range wider, and achieving a more controllable process. However, trelagliptin succinate is extremely unstable under hot and humid conditions, which can easily lead to an increase in related substances and stability problems.

[0010] Patent document CN102548556A discloses a tablet comprising trelagliptin succinate or its salt and a glidant, wherein the content of trelagliptin succinate is 35% to 50%, and the glidant is light silicon dioxide, i.e., micro-powder silica gel. The addition of the glidant micro-powder silica gel prevents poor fluidity and poor granulation effect during the granulation process. However, the inventors found in their research that there are compatibility issues between trelagliptin succinate and micro-powder silica gel. When micro-powder silica gel is added to the product, the impurities in trelagliptin succinate increase significantly. Therefore, it is still necessary to provide a means that can solve the problem of poor fluidity of trelagliptin succinate leading to poor granulation effect without affecting the stability of the product.

[0011] Patent document CN106074422A adopts a dry direct compression method, which is relatively simple and does not require solvent mediation (especially water) during the entire granulation process, effectively avoiding the risk of crystal transformation. However, the API is needle-shaped crystallized and has poor self-adhesion. If dry granulation is used, the rolling granules of the raw materials and auxiliary materials have poor formability, resulting in unstable dry granulation process, large batch differences, large granule bulk density, and poor tablet compressibility.

[0012] A method for preparing a solid preparation of trelagliptin succinate which avoids crystal transformation during the preparation process and has good tableting properties is needed. Summary of the invention

[0013] The invention provides a preparation method of trelagliptin succinate tablets, which is first pretreated by a high shear wet mixing granulator and then transferred to a fluidized bed for granulation. During the process, the fluidized boiling state of the material is good, and the process parameters are reasonably designed. The obtained particles have good fluidity and compressibility, and there is no sticking and lid-off phenomenon during the tableting process. After mannitol is added, the self-made product is consistent with the reference preparation in crystal form, and the product quality is controllable.

[0014] The present invention provides a method for preparing trelagliptin succinate tablets, comprising the following steps:

[0015] (1) Prepare the binder solution: dissolve the binder in water and stir until it is completely dispersed;

[0016] (2) Place the active ingredient, filler, and internal disintegrant in a wet granulator and spray the binder solution into the granulator to moisten it. The amount used is 10% of the feed amount.

[0017] (3) The material obtained in step (2) is sent to a fluidized bed for granulation: the air inlet temperature and air volume are set, and after the material is completely and normally fluidized, the remaining binder solution is sprayed in for granulation; drying and granulation.

[0018] (4) adding an external disintegrant, a lubricant, and a filler, mixing, tableting, and film coating to prepare the trelagliptin succinate tablets.

[0019] In a specific embodiment of the preparation method of the present invention, the Trelagliptin succinate tablets are composed of the following components in parts by weight:

[0020]

[0021] In a specific embodiment of the preparation method of the present invention, the binder is hydroxypropyl cellulose or hydroxypropyl methyl cellulose, and the concentration of its aqueous solution is 2% to 5%, preferably 2%. In a specific embodiment of the preparation method of the present invention, the filler is one or more of lactose, mannitol, and microcrystalline cellulose, preferably mannitol; the disintegrant is one or more of low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, and cross-linked polyvinylpyrrolidone, preferably cross-linked sodium carboxymethyl cellulose; the lubricant is one or more of magnesium stearate, calcium stearate, and sodium stearyl fumarate, preferably sodium stearyl fumarate.

[0022] In a specific embodiment of the preparation method of the present invention, the added filler is mannitol.

[0023] Advantages of the present invention: In the preparation method of the trelagliptin succinate tablets of the present invention, a high shear wet mixing granulator is used to pretreat the added materials, thereby solving the influence of the poor physical properties of the raw materials on the product process, including the influence of easy aggregation, easy adhesion, poor fluidity, easy generation of static electricity, etc. on the fluidization state of the materials during the preheating of the fluidized bed.

[0024] The preparation method of the present invention can effectively solve the crystal transformation problem of the product, reduce the moisture control requirements in the production process, improve the operability and compliance of the production process, and ensure that the product quality is controllable.

[0025] In the preparation method of the present invention, a fluidized bed granulation process is used to integrate granulation and drying, which is convenient to operate and simple in process. The obtained granules have good fluidity and a smooth tableting process, which is particularly beneficial to industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Comparative Example 1: Adhesion of fine powder materials

[0027] Figure 2 Crystalline form of reference preparation

[0028] Figure 3 API crystal form map

[0029] Figure 4 Example 1 Preparation Crystalline Spectrum

[0030] Figure 5 Example 2 Preparation Crystalline Spectrum

[0031] Figure 6 Example 3 Preparation Crystalline Spectrum

[0032] Figure 7 Example 4 Preparation Crystalline Spectrum

[0033] Figure 8 Example 5 Preparation Crystalline Spectrum

[0034] Fig. 9 Comparative Example 1 Preparation Crystalline Spectrum

[0035] Fig.10 Comparative Example 2 Preparation Crystalline Spectrum

[0036] Fig.11 Comparative Example 3 Preparation Crystalline Spectrum Specific implementation method:

[0037] Examples 1 to 5 all adopt the preparation process of wet granulator material pretreatment and mannitol addition. During the granulation process, the material fluidization state is good, there is no aggregation, adhesion and wall adhesion, and no crystal transformation occurs in the self-product quality inspection, and the process reproducibility is good. The dosage and type of the binder and lubricant prescription within the scope of the embodiment can prepare qualified products.

[0038] Example 1

[0039] prescription

[0040]

[0041] Technology

[0042] 1) Prepare a 2.0% hydroxypropyl cellulose solution: Disperse hydroxypropyl cellulose in purified water and continue stirring until the solution becomes clear.

[0043] 2) Wet pretreatment: Add trelagliptin succinate, cross-linked sodium carboxymethyl cellulose (internal addition) and microcrystalline cellulose into a wet granulator, and spray hydroxypropyl cellulose solution to moisten the granules, with the amount being 10% of the feed amount.

[0044] 3) Fluidized bed granulation: Set the air inlet temperature and air volume, and after the material is completely fluidized, spray the remaining hydroxypropyl cellulose solution into the granulation.

[0045] 4) Drying: Adjust the air inlet temperature for drying.

[0046] 5) Granulation: The dried granules are granulated.

[0047] 6) External mixing: add cross-linked sodium carboxymethyl cellulose (external) and mannitol and mix for 10 minutes, add sodium stearyl fumarate and mix for 5 minutes.

[0048] 7) Tablet compression: Use an oval die to compress the tablets, with a notch in the middle, tablet weight 180.36 mg, hardness 90-140N.

[0049] 8) Coating: Set the air inlet temperature to preheat the tablets and apply film coating. The solvent is water.

[0050] Example 2

[0051] prescription

[0052]

[0053] Technology

[0054] 1) Prepare a 2.0% hydroxypropyl cellulose solution: Disperse hydroxypropyl cellulose in purified water and continue stirring until the solution becomes clear.

[0055] 2) Wet pretreatment: Add trelagliptin succinate, cross-linked sodium carboxymethyl cellulose (internal addition) and microcrystalline cellulose into a wet granulator, and spray hydroxypropyl cellulose solution to moisten the granules, with the amount being 10% of the feed amount.

[0056] 3) Fluidized bed granulation: Set the air inlet temperature and air volume, and after the material is completely fluidized, spray the remaining hydroxypropyl cellulose solution into the granulation.

[0057] 4) Drying: Adjust the air inlet temperature for drying.

[0058] 5) Granulation: The dried granules are granulated.

[0059] 6) External mixing: add cross-linked sodium carboxymethyl cellulose (external) and mannitol and mix for 10 minutes, add sodium stearyl fumarate and mix for 5 minutes.

[0060] 7) Tablet compression: Use an oval die to compress the tablets, with a notch in the middle, tablet weight 180.00 mg, hardness 90-140N.

[0061] 8) Coating: Set the air inlet temperature to preheat the tablets and apply film coating. The solvent is water.

[0062] Example 3

[0063] prescription

[0064]

[0065]

[0066] Technology

[0067] 1) Prepare a 2.0% hydroxypropyl cellulose solution: Disperse hydroxypropyl cellulose in purified water and continue stirring until the solution becomes clear.

[0068] 2) Wet pretreatment: Add trelagliptin succinate and microcrystalline cellulose into a wet granulator, and spray hydroxypropyl cellulose solution to moisten the granules, with the amount being 10% of the feed amount.

[0069] 3) Fluidized bed granulation: Set the air inlet temperature and air volume, and after the material is completely fluidized, spray the remaining hydroxypropyl cellulose solution into the granulation.

[0070] 4) Drying: Adjust the air inlet temperature for drying.

[0071] 5) Granulation: The dried granules are granulated.

[0072] 6) External mixing: add cross-linked sodium carboxymethyl cellulose and mannitol and mix for 10 minutes, add sodium stearyl fumarate and mix for 5 minutes.

[0073] 7) Tablet compression: Use an oval die to compress the tablets, with a notch in the middle, tablet weight 180.36 mg, hardness 90-140N.

[0074] 8) Coating: Set the air inlet temperature to preheat the tablets and apply film coating. The solvent is water.

[0075] Example 4

[0076] prescription

[0077]

[0078] Technology

[0079] 1) Prepare a 2.0% hydroxypropyl cellulose solution: Disperse hydroxypropyl cellulose in purified water and continue stirring until the solution becomes clear.

[0080] 2) Wet pretreatment: Add trelagliptin succinate, cross-linked polyvinylpyrrolidone (internal addition) and microcrystalline cellulose into a wet granulator, and spray hydroxypropyl cellulose solution to moisten the granules, with the amount being 10% of the feed amount.

[0081] 3) Fluidized bed granulation: Set the air inlet temperature and air volume, and after the material is completely fluidized, spray the remaining hydroxypropyl cellulose solution into the granulation.

[0082] 4) Drying: Adjust the air inlet temperature for drying.

[0083] 5) Granulation: The dried granules are granulated.

[0084] 6) External mixing: add cross-linked polyvinylpyrrolidone (external) and mannitol and mix for 10 minutes, add sodium stearyl fumarate and mix for 5 minutes.

[0085] 7) Tablet compression: Use an oval die to compress the tablets, with a notch in the middle, tablet weight 180.36 mg, hardness 90-140N.

[0086] 8) Coating: Set the air inlet temperature to preheat the tablets and apply film coating. The solvent is water.

[0087] Example 5

[0088] prescription

[0089]

[0090] Technology

[0091] 1) Prepare a 2.0% solution of HPMC: Disperse HPMC in purified water and continue stirring until the solution becomes clear.

[0092] 2) Wet pretreatment: Add trelagliptin succinate, cross-linked sodium carboxymethyl cellulose (internal addition) and microcrystalline cellulose into a wet granulator, and spray with hypromellose solution for wetting, with the amount being 10% of the feed amount.

[0093] 3) Fluidized bed granulation: Set the air inlet temperature and air volume, and after the material is completely fluidized, spray the remaining HPMC solution into the granulation.

[0094] 4) Drying: Adjust the air inlet temperature for drying.

[0095] 5) Granulation: The dried granules are granulated.

[0096] 6) External mixing: add cross-linked sodium carboxymethyl cellulose (external) and mannitol and mix for 10 minutes, add sodium stearyl fumarate and mix for 5 minutes.

[0097] 7) Tablet compression: Use an oval die to compress the tablets, with a notch in the middle, tablet weight 180.36 mg, hardness 90-140N.

[0098] 8) Coating: Set the air inlet temperature to preheat the tablets and apply film coating. The solvent is water.

[0099] Comparative Example 1

[0100] prescription

[0101]

[0102]

[0103] Technology

[0104] 1) Prepare a 2.0% hydroxypropyl cellulose solution: Disperse hydroxypropyl cellulose in purified water and continue stirring until the solution becomes clear.

[0105] 2) Fluidized bed granulation: Add trelagliptin succinate, mannitol, cross-linked sodium carboxymethyl cellulose (4.0% added internally), and microcrystalline cellulose into a fluidized bed, set the air inlet temperature and air volume, and after the materials are completely fluidized normally, spray the hydroxypropyl cellulose solution into the granulation.

[0106] 3) Drying: Adjust the air inlet temperature for drying.

[0107] 4) Granulation: The dried granules are granulated.

[0108] 5) External mixing: Add crosslinked sodium carboxymethyl cellulose (external 6.0%) and mix for 10 minutes, add sodium stearyl fumarate and mix for 5 minutes.

[0109] 6) Tabletting: Use an oval punch die for tableting with a notch in the middle. The tablet weight is 180.36 mg and the hardness is 90-140N.

[0110] 7) Coating: Set the air inlet temperature to preheat the tablets and apply film coating. The solvent is water.

[0111] Example 1 uses a wet mixing granulator to pre-treat the raw material, ensuring the fluidization state of the material in the fluidized bed preheating stage. Comparative Example 1 is prepared using the prescription process of patent document CN104519874A, which is a fluidized bed direct granulation, and no raw material pretreatment step is performed. The comparison results show that in the fluidized bed preheating stage, the boiling state of the material in Comparative Example 1 is not good. After inspection, more than 50% of the fine powder material adheres to the pot wall, and about 10% to 20% of the material agglomerates (see attached Figure 1 ), the granulation test could not be completed.

[0112] Comparative Example 2

[0113] prescription

[0114]

[0115]

[0116] Technology

[0117] 1) Prepare a 2.0% hydroxypropyl cellulose solution: Disperse hydroxypropyl cellulose in purified water and continue stirring until the solution becomes clear.

[0118] 2) Wet pretreatment: Add trelagliptin succinate, mannitol, cross-linked carboxymethyl cellulose sodium (4.0% added internally), and microcrystalline cellulose into a wet granulator, and spray hydroxypropyl cellulose solution for wetting, with the amount being 10% of the feed amount.

[0119] 3) Fluidized bed granulation: Set the air inlet temperature and air volume, and after the material is completely fluidized, spray the remaining hydroxypropyl cellulose solution into the granulation.

[0120] 4) Drying: Adjust the air inlet temperature for drying.

[0121] 5) Granulation: The dried granules are granulated.

[0122] 6) External mixing: add cross-linked sodium carboxymethyl cellulose (external 6.0%) and mix for 10 minutes, add sodium stearyl fumarate and mix for 5 minutes.

[0123] 7) Tablet compression: Use an oval punch die for tablet compression with a notch in the middle. The tablet weight is 180.36 mg and the hardness is 90-140N.

[0124] 8) Coating: Set the air inlet temperature to preheat the tablets and apply film coating. The solvent is water.

[0125] Comparative Example 3

[0126] prescription

[0127]

[0128] Technology

[0129] 1) Prepare a 2.0% hydroxypropyl cellulose solution: Disperse hydroxypropyl cellulose in purified water and continue stirring until the solution becomes clear.

[0130] 2) Dry direct compression pretreatment of API: Dry granulate the API and pass the roller-compacted API through a 20-mesh sieve.

[0131] 3) Fluidized bed granulation: Set the air inlet temperature and air volume, add the dry-processed trelagliptin succinate into the fluidized bed equipment, then add mannitol, cross-linked sodium carboxymethyl cellulose (internal addition), and microcrystalline cellulose, preheat, and after the materials are completely fluidized, spray the hydroxypropyl cellulose solution for granulation.

[0132] 4) Drying: Adjust the air inlet temperature for drying.

[0133] 5) Granulation: The dried granules are granulated.

[0134] 6) External mixing: add cross-linked sodium carboxymethyl cellulose (external) and mix for 10 minutes, add sodium stearyl fumarate and mix for 5 minutes.

[0135] 7) Tabletting: Use an oval punch die for tableting with a notch in the middle. The target tablet weight is 180.00 mg and the target hardness is 90 N (60 to 130 N).

[0136] 8) Coating: Set the air inlet temperature to preheat the tablets and apply film coating. The solvent is water.

[0137] Comparison of powder properties before and after dry pretreatment of API:

[0138]

[0139] Comparative Example 3 uses dry granulation to increase bulk density of the API and improve fluidity of the granulated material. API samples 1 to 3 are prepared with different dry granulation parameters, and API sample 4 is untreated raw material coarse powder.

[0140] The comparison results show that the bulk density of the API samples obtained by different roller speeds (rpm) and roller pressures (mpa) is significantly different, but the angle of repose (°) is basically the same, indicating that the fluidity of the API has not been improved. When the API pretreated by dry method is granulated in a fluidized bed, the problem of poor fluidization state cannot be solved. The granulation results show that the amount of fine powder below 80 mesh is still relatively large, as shown in the table below. At the same time, simply pressing the API into particles with a higher hardness affects the disintegration and dissolution of the variety, which is not conducive to drug release.

[0141] Comparative Example 3 Particle Fine Powder Statistics Table

[0142] project Sample 1 Sample 2 Sample 3 Sample 4 80 mesh or less percentage % 55.199 52.220 34.845 34.573

[0143] Note: Use the pharmacopoeia sieve sieving method to measure the particle size. When the amount of fine powder below 80 mesh is greater than 15%, the tablets are prone to sticking.

[0144] Example 6

[0145] Crystal form detection method:

[0146] Take an appropriate amount of this product, grind it into powder, take an appropriate amount of sample powder, put it in the groove of the sample slide, use the glass slide to roll the powder with appropriate force, so that there is a sample in every corner of the groove of the sample slide, put one side of the glass slide against the surface of the sample slide, and tilt the other side by less than 10°, and use the edge of the glass slide to scrape the surface of the powder sample to make the sample surface flat. According to the X-ray diffraction method (General Rule 0451 X-ray Diffraction Method), CuKα is used as the light source, the light tube voltage and light tube current are 40kV and 40mA respectively, the divergence slit is 1 / 8°, the anti-scattering slit is 1 / 4°, the scanning axis is Gonio, the step length is 0.0167°2θ, the counting time for each step is 19.7s, scan in the range of diffraction angle (2θ) 2°~60°, and record the diffraction spectrum. The X-ray powder diffraction spectrum of the test sample shall not show a diffraction peak at a diffraction angle (2θ) of about 9.6°±0.2°.

[0147] Crystal form test results comparison table

[0148] project Crystallization characteristic peak (2θ) Crystallization Trelagliptin raw materials none Untransformed Example 1 none Untransformed Example 2 none Untransformed Example 3 none Untransformed Example 4 none Untransformed Example 5 none Untransformed Comparative Example 1 9.7673° diffraction peak Crystal Transformation Comparative Example 2 9.7154° diffraction peak Crystal Transformation Comparative Example 3 9.7267° diffraction peak Crystal Transformation

[0149] The comparison results show that Examples 1 to 5 all adopt the preparation process of adding mannitol, and the crystal form of the prepared tablets is consistent with the raw material drug and the reference preparation. No crystal transformation phenomenon occurs after preparation (i.e., there is no 9.6°±0.2° diffraction peak). The crystal form detection spectrum is shown in the attached Figure 2 , Attachment Figure 3 , Attachment Figure 4 , Attachment Figure 5 , Attachment Figure 6 , Attachment Figure 7 and attached Figure 8 Comparative Examples 1 to 3 selected the preparation process of adding mannitol, and the tablets obtained were crystallized. The crystal form detection spectrum is shown in the attached Fig. 9 , Attachment Fig.10 and attached Fig.11 .

[0150] Example 7

[0151] Reference preparation information: Trade name: Zafatek

[0152] Manufacturer: Takeda Pharmaceutical Co., Ltd.

[0153] 1) Comparison of dissolution results between the reference preparation and the preparation of the present invention:

[0154] time Reference preparation Example 1 Example 2 Example 3 Example 4 Example 5 5min 44.6 48.0 55.6 46.0 47.4 45.6 10min 80.7 82.0 86.9 88.4 77.6 78.6 15min 91.4 91.4 95.4 97.7 89.6 90.5 20min 94.6 95.6 98.2 100.0 94.3 94.9 30min 96.5 97.7 99.5 100.03 96.7 97.6 45min 97.0 99.0 100.1 100.03 97.6 98.6 60min 97.2 99.6 99.7 100.02 97.9 98.9

[0155] 2) Comparison of dissolution results of stability samples of the reference preparation and the preparation of the present invention:

[0156]

[0157]

[0158] From the comparison results, it can be seen that the dissolution results of the reference preparation and Example 1, Example 2 and Example 3 are greater than 85% in 15 minutes, which meets the requirements of rapid dissolution, and the stability data show that the dissolution stability of this process is good.

[0159] The above describes the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing trelagliptin succinate tablets, comprising the following steps: (1) Prepare the binder solution: dissolve the binder in water and stir until it is completely dispersed; (2) Place the active ingredient, filler, and internal disintegrant in a wet granulator and spray the binder solution into the granulator to moisten it. The amount used is 10% of the feed amount. (3) feeding the material obtained in step (2) into a fluidized bed for granulation: setting the air inlet temperature and air volume, and after the material is completely and normally fluidized, spraying the remaining binder solution into the fluidized bed for granulation; Drying and whole grain; (4) adding an external disintegrant, a lubricant, and a filler, mixing, tableting, and film coating to prepare the trelagliptin succinate tablets.

2. The preparation method according to claim 1, wherein the trelagliptin succinate tablets are composed of the following components in parts by weight:

3. The preparation method according to claim 1 or 2, wherein the binder is hydroxypropyl cellulose or hydroxypropyl methyl cellulose, and the concentration of its aqueous solution is 2% to 5%, preferably 2%.

4. The preparation method according to claim 1 or 2, wherein the filler is one or more of lactose, mannitol, and microcrystalline cellulose, preferably mannitol; wherein the disintegrant is one or more of low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, and cross-linked polyvinylpyrrolidone, preferably cross-linked sodium carboxymethyl cellulose; wherein the lubricant is one or more of magnesium stearate, calcium stearate, and sodium stearyl fumarate, preferably sodium stearyl fumarate.

5. The preparation method according to claim 1 or 2, wherein the external filler is mannitol.

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