Pristinamycin salts and their use as antibacterial agents

Abstract

The present application relates to the technical field of pharmaceutical preparation, and specifically discloses a pexidartinib hydrobromide tablet and a preparation method thereof. The pexidartinib hydrobromide tablet provided by the present application effectively inhibits the generation and growth of related substances, and significantly improves the long-term stability of the pexidartinib hydrobromide tablet by adopting an alkaline amino acid as a stabilizer, cooperating with a specific filler, and through a preparation process of fluidized bed mixing, spray granulation synchronous drying, whole granule mixing and tabletting. The tablet prepared by the present application not only has stable quality and consistent dissolution behavior, but also has good process reproducibility, easy industrial production and quality control, and has important industrial application value and clinical significance. The tablet can provide a safe and effective pharmaceutical preparation for the clinical treatment of rheumatoid arthritis, and has a broad industrialization application prospect.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, and in particular to a piracetam hydrobromide tablet and its preparation method. Background Technology

[0002] Rheumatoid arthritis (RA) is a chronic, systemic inflammatory autoimmune disease characterized primarily by the destruction of the synovial membrane in the joints, leading to irreversible bone damage. This disease not only causes persistent pain but is also frequently accompanied by joint dysfunction, severely impacting patients' quality of life. In the clinical treatment of RA, traditional regimens primarily rely on nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids to control pain and inflammation, often in combination with disease-modifying antirheumatic drugs (DMARDs). With the widespread use of methotrexate (MTX) and the advent of biologics such as tumor necrosis factor (TNF) inhibitors, the treatment efficacy of RA has significantly improved, particularly in inhibiting joint structural destruction.

[0003] Pixitinib hydrobromide is an oral YANUS kinase (JAK) inhibitor developed by Astellas Pharma Inc., which exerts its therapeutic effect by modulating immune signaling pathways. However, this compound exhibits certain chemical instability in both solid and formulation states, and is prone to degradation under high temperature, high humidity, or light conditions, potentially producing various related substances, including isomers, oxidation products, and hydrolysis products, which may affect the efficacy and safety of the drug.

[0004] Currently, commercially available or reported piracetamib hydrobromide tablets often exhibit a gradual increase in the content of related substances (especially single and total impurities) during long-term storage, sometimes exceeding the limits stipulated in the pharmacopoeia. This leads to a shortened shelf life and increases the quality risk and storage costs of the drug. Conventional tablet manufacturing processes (such as wet granulation or dry compression) have certain limitations in the application of this product: wet granulation requires the introduction of water or organic solvents (such as ethanol), which may promote the hydrolysis of the active pharmaceutical ingredient or solvent-mediated degradation reactions; although dry processes can avoid the introduction of solvents, they often involve more process steps and longer production times, causing the drug and excipients to be in contact for extended periods and exposed to the influence of environmental temperature and humidity, further exacerbating the formation of related substances.

[0005] Therefore, developing a tablet that can significantly inhibit the degradation of piracetamib hydrobromide, delay the growth of related substances, and exhibit excellent long-term stability, as well as its preparation method, is of great significance for improving the clinical applicability of this product, reducing quality control risks, and minimizing storage costs. Summary of the Invention

[0006] To address the problems of excessive levels of related substances, insufficient chemical stability, and short shelf life of existing piracetam hydrobromide tablets during long-term storage, this invention provides piracetam hydrobromide tablets and their preparation method.

[0007] To solve the above-mentioned technical problems, the technical solution provided by the present invention is as follows: In a first aspect, the present invention provides a pixitinib hydrobromide tablet comprising the following components in weight percentage: pixitinib hydrobromide 36%~42%, filler 45%~53%, binder 1%~2%, disintegrant 3%~7%, stabilizer 4%~8%, and lubricant 0.5%~2%; The stabilizer is a basic amino acid.

[0008] Compared to existing technologies, the piracetamib hydrobromide tablets provided by this invention innovatively use basic amino acids as stabilizers. These amino acids, through their basic groups, regulate the pH of the formulation's internal microenvironment, creating an alkaline environment conducive to the stable existence of piracetamib hydrobromide and inhibiting its hydrolysis, oxidation, and isomerization reactions. Simultaneously, their molecular structure can protect easily degradable sites of the drug molecule through interactions (such as intermolecular forces or weak complexation), blocking free radical reactions such as oxidation, thereby significantly slowing the growth rate of both single and total impurities. Experimental data show that the content of related substances in tablets using the above formulation is significantly lower than that in control formulations using conventional antioxidants (such as sodium bisulfite) or without this stabilizer, indicating that this formulation can effectively inhibit the formation of related substances during formulation preparation.

[0009] In addition, basic amino acids themselves have no toxic side effects, good biocompatibility with the human body, and will not introduce additional safety risks. Compared with the chemical stabilizers used in existing technologies, they are more in line with the safety requirements for long-term clinical use, thus improving both the effectiveness and safety of clinical medication.

[0010] As a specific embodiment of the present invention, the pyroxitinib hydrobromide tablets comprise the following components in weight percentage: pyroxitinib hydrobromide 36%~39%, filler 45%~46%, binder 1.5%~2%, disintegrant 4%~6%, stabilizer 7%~8%, and lubricant 0.8%~1.5%.

[0011] Preferably, the piracetamib hydrobromide tablets comprise the following components in weight percentage: piracetamib hydrobromide 38.2%, filler 45.5%, binder 1.8%, disintegrant 6%, stabilizer 7.5%, and lubricant 1%.

[0012] Furthermore, the basic amino acid includes at least one of L-arginine, L-lysine, or L-histidine.

[0013] Preferably, the basic amino acid is L-arginine.

[0014] The L-arginine molecule contains a strongly basic guanidine group, which can establish and maintain a more stable and suitable weakly basic buffer system in the tablet microenvironment, thereby effectively inhibiting the hydrolysis reaction that easily occurs in piracetamib hydrobromide under acidic or neutral conditions. In addition, the molecular structure of L-arginine (including guanidine, α-amino and carboxyl groups) provides it with the ability to interact with drug molecules in multiple ways (such as hydrogen bonding and ion-dipole interactions), effectively protecting the easily oxidized groups of drug molecules and inhibiting the generation of oxidative degradation pathways.

[0015] Furthermore, the filler includes a first filler and a second filler, wherein the first filler is selected from microcrystalline cellulose, and the second filler is selected from at least one of mannitol, lactose, or pregelatinized starch.

[0016] Furthermore, the mass ratio of the first filler to the second filler is (1.0~1.5):(0.5~1.0).

[0017] Furthermore, the filler is a mixture of microcrystalline cellulose and mannitol.

[0018] Preferably, the mass ratio of microcrystalline cellulose to mannitol is 1.5:1.

[0019] The selected filler not only ensures the formulation is well-formed and has moderate hardness, but also improves its dissolution properties and promotes rapid disintegration in vivo. Simultaneously, both fillers work together to provide a dry and stable microenvironment for the drug, synergistically inhibiting the degradation pathway of piracetamib hydrobromide and effectively controlling the growth of related substances.

[0020] Furthermore, the adhesive is selected from at least one of corn starch, hydroxypropyl methylcellulose, povidone K30, or polyvinyl alcohol.

[0021] Preferably, the adhesive is polyvinylpyrrolidone K30.

[0022] The preferred binder facilitates the formation of granules with a concentrated particle size distribution and good flowability during granulation, which in turn benefits the formation of tablets with suitable hardness and acceptable friability during subsequent tableting. Simultaneously, povidone K30 itself has low hygroscopicity, helping to maintain the low moisture content of the granules and reducing the risk of moisture sensitivity introduced by the binder.

[0023] Furthermore, the disintegrant is selected from one or both of sodium carboxymethyl starch or croscarmellose.

[0024] Preferably, the disintegrant is cross-linked polyvinylpyrrolidone.

[0025] Cross-linked polyvinylpyrrolidone can rapidly absorb water and swell to form capillary channels, thereby improving dissolution efficiency.

[0026] Furthermore, the lubricant is selected from at least one of magnesium stearate, zinc stearate, talc, or micronized silica gel.

[0027] Preferably, the lubricant is magnesium stearate.

[0028] Furthermore, the pyrazinib hydrobromide tablets also include a coating agent, with a coating weight gain of 2% to 5%. Specifically, the coating agent is selected from, but not limited to, one or more of "Opadry®" provided by Calcare Company.

[0029] Secondly, the present invention also provides a method for preparing pyrazinib hydrobromide tablets, comprising the following steps: S1, the prescribed amount of piracetamide hydrobromide, filler, partial disintegrant and stabilizer are placed in a fluidized bed and mixed to obtain fluidized material; S2, the adhesive solution is sprayed onto the fluidized material for granulation, and drying is performed simultaneously during the granulation process to obtain dry granules; S3. After granulating the dry granules, add the remaining disintegrant and lubricant, mix evenly, and compress into tablets to obtain piracetam hydrobromide tablets.

[0030] Compared to existing technologies, the preparation method of pixitinib hydrobromide tablets provided by this invention employs fluidized bed mixing in step S1, enabling rapid and uniform mixing of pixitinib hydrobromide, filler, partial disintegrant, and stabilizer in a fluidized state. This ensures uniform dispersion of L-arginine in the material, establishing a stable microenvironment in advance and preventing degradation due to uneven distribution of stabilizer in certain areas. Simultaneously, fluidized bed mixing is a dry mixing process, reducing the chance of material contact with moisture and inhibiting the hydrolytic degradation of pixitinib hydrobromide at its source. Step S2 achieves simultaneous particle formation and moisture control through spray granulation and simultaneous drying of the binder solution, effectively inhibiting the growth of related substances during granulation. The preparation method provided by this invention features a concise and controllable process flow, significantly reducing the degradation risk introduced during production and significantly improving the long-term stability of the formulation, demonstrating significant industrial value.

[0031] Furthermore, in S1, the partially disintegrant is 40% to 60% of the prescribed amount of disintegrant.

[0032] This ratio of disintegrant, when granulated together with the main and excipients, can moderately increase the internal porosity of the granules without compromising their formability, and also lays the foundation for subsequent tablet disintegration.

[0033] Furthermore, in S2, the adhesive solution is sprayed into the fluidized material in an atomized form through a spray gun, with a spraying speed of 30 rpm to 300 rpm and an atomization pressure of 0.2 MPa to 0.4 MPa.

[0034] Furthermore, in S2, the concentration of the adhesive solution is 8% to 12%.

[0035] Furthermore, in S2, the material temperature is maintained at 30℃~50℃ during the granulation process.

[0036] Furthermore, in S2, the inlet air temperature of the fluidized bed is controlled at 50℃~80℃, and when the material temperature reaches above 35℃, the adhesive solution is sprayed in.

[0037] Specifically, in S2, a sieve with an aperture of Ф1.5mm is used for granulation, and the rotation speed is 500rpm.

[0038] Specifically, in S3, a shallow concave circular punch with a diameter of 8.5mm is used for tablet pressing, the tablet weight is controlled within the range of ±5.0%, and the brittleness is ≤1.0%.

[0039] Furthermore, after tableting, the process also includes coating the piracetam hydrobromide tablets to obtain piracetam hydrobromide coated tablets.

[0040] Specifically, the temperature of the coated tablet bed is controlled at 40℃~60℃. The concentration of the coating solution is controlled at 14%~16%.

[0041] In summary, the piracetamib hydrobromide tablets provided by this invention, through the use of basic amino acids as stabilizers, synergistic use of specific fillers, and a preparation process involving fluidized bed mixing, spray granulation and simultaneous drying, granulation mixing, and tableting, effectively inhibit the formation and growth of related substances, significantly improving the long-term stability of piracetamib hydrobromide tablets. The tablets prepared by this invention not only exhibit stable quality and consistent dissolution behavior, but also demonstrate good process reproducibility, facilitating industrial production and quality control. They possess significant industrial application value and clinical significance, providing a safe and effective pharmaceutical formulation for the clinical treatment of rheumatoid arthritis, and have broad prospects for industrial application. Detailed Implementation

[0042] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0043] To better illustrate the present invention, further examples are provided below.

[0044] Example 1 This embodiment provides a pyroxitinib hydrobromide tablet, in batches of 1000 tablets, with the following prescription dosage:

[0045] The preparation method of the above-mentioned pyrazinib hydrobromide tablets is as follows: S1, the prescribed amounts of piracetam hydrobromide, microcrystalline cellulose, mannitol, partially cross-linked polyvinylpyrrolidone and L-arginine are placed in a fluidized bed granulator and mixed evenly in a fluidized state; S2, set the inlet air temperature to 70℃, record the inlet air temperature, material temperature and outlet air temperature every ten minutes. When the material temperature reaches above 35℃, start spraying. Spray the aqueous solution of povidone K30 (concentration 10wt%) into the fluidized material in the form of atomization through the spray gun. Control the spraying speed to 100rpm and the atomization pressure to 0.3MPa, maintain the material temperature in the range of 30~50℃, and complete granulation and drying at the same time. S3, the obtained granules are taken out and granulated using a sieve with a pore size of Ф1.5mm at a rotation speed of 500rpm; S4, add an additional portion of cross-linked polyvinylpyrrolidone and magnesium stearate, and mix well; S5, tablets are compressed using a Ф8.5mm round shallow concave punch, with tablet weight controlled within ±5.0% and friability ≤1.0%, to obtain piracetam hydrobromide tablets; S6. Prepare a 15% coating solution from the coating powder and coat the piracetam hydrobromide tablets. Control the tablet bed temperature at 50°C to obtain piracetam hydrobromide film-coated tablets.

[0046] The prepared pyrcitrinib hydrobromide film-coated tablets were used as the dissolution medium in water at 37°C, with a volume of 900 mL and a rotation speed of 50 rpm. The dissolution was measured after 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min. The results are shown in Table 1.

[0047] Table 1

[0048] Example 2 This embodiment provides a pyroxitinib hydrobromide tablet, in batches of 1000 tablets, with the following prescription dosage:

[0049] The preparation method of the above-mentioned pyrazinib hydrobromide tablets is as follows: S1, the prescribed amounts of piracetam hydrobromide, microcrystalline cellulose, lactose, added sodium carboxymethyl starch and L-arginine are placed in a fluidized bed granulator and mixed evenly under fluidized conditions; S2, set the inlet air temperature to 50℃, record the inlet air temperature, material temperature and outlet air temperature every ten minutes. When the material temperature reaches above 35℃, start spraying. Spray an aqueous solution of polyvinyl alcohol (concentration 10wt%) into the fluidized material in an atomized form through a spray gun. Control the spraying speed to 30rpm and the atomization pressure to 0.2MPa to maintain the material temperature in the range of 30~50℃, and complete granulation and drying at the same time. S3, the obtained granules are taken out and granulated using a sieve with a pore size of Ф1.5mm at a rotation speed of 500rpm; S4, add an additional portion of sodium carboxymethyl starch and micronized silica gel, and mix well; S5, tablets are compressed using a Ф8.5mm round shallow concave punch, with tablet weight controlled within ±5.0% and friability ≤1.0%, to obtain piracetam hydrobromide tablets; S6. Prepare a 15% coating solution from the coating powder and coat the piracetam hydrobromide tablets. Control the tablet bed temperature at 45°C to obtain piracetam hydrobromide film-coated tablets.

[0050] The prepared pyrazinib hydrobromide film-coated tablets were used as the dissolution medium in water at 37°C, with a volume of 900 mL and a rotation speed of 50 rpm. The dissolution was measured after 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min. The results are shown in Table 2.

[0051] Table 2

[0052] Example 3 This embodiment provides a pyroxitinib hydrobromide tablet, in batches of 1000 tablets, with the following prescription dosage:

[0053] The preparation method of the above-mentioned pyrazinib hydrobromide tablets is as follows: S1, the prescribed amounts of piracetam hydrobromide, microcrystalline cellulose, pregelatinized starch, partially cross-linked polyvinylpyrrolidone and L-lysine are placed in a fluidized bed granulator and mixed evenly in a fluidized state; S2, set the inlet air temperature to 80℃, record the inlet air temperature, material temperature and outlet air temperature every ten minutes. When the material temperature reaches above 35℃, start spraying. Spray the ethanol solution of hydroxypropyl methylcellulose (concentration 10wt%) into the fluidized material in the form of an atomization through a spray gun. Control the spraying speed to 300rpm and the atomization pressure to 0.4MPa, maintain the material temperature in the range of 30~50℃, and complete granulation and drying at the same time. S3, the obtained granules are taken out and granulated using a sieve with a pore size of Ф1.5mm at a rotation speed of 500rpm; S4, add an additional portion of cross-linked polyvinylpyrrolidone and talc, and mix well; S5, tablets are compressed using a Ф8.5mm round shallow concave punch, with tablet weight controlled within ±5.0% and friability ≤1.0%, to obtain piracetam hydrobromide tablets; S6. Prepare a 15% coating solution from the coating powder and coat the piracetam hydrobromide tablets. Control the tablet bed temperature at 40°C to obtain piracetam hydrobromide film-coated tablets.

[0054] The prepared pyrcitrinib hydrobromide film-coated tablets were used as the dissolution medium in water at 37°C, with a volume of 900 mL and a rotation speed of 50 rpm. The dissolution was measured after 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min. The results are shown in Table 3.

[0055] Table 3

[0056] Example 4 This embodiment provides a pyroxitinib hydrobromide tablet, in batches of 1000 tablets, with the following prescription dosage:

[0057] The preparation method of the above-mentioned pyrazinib hydrobromide tablets is as follows: S1, the prescribed amounts of piracetam hydrobromide, microcrystalline cellulose, mannitol, partially cross-linked polyvinylpyrrolidone and L-histidine are placed in a fluidized bed granulator and mixed evenly in a fluidized state; S2, set the inlet air temperature to 65℃, record the inlet air temperature, material temperature and outlet air temperature every ten minutes. When the material temperature reaches above 35℃, start spraying. Spray the corn starch aqueous solution (concentration 10wt%) into the fluidized material in the form of atomization through the spray gun. Control the spraying speed to 200rpm and the atomization pressure to 0.3MPa, maintain the material temperature in the range of 30~50℃, and complete granulation and drying at the same time. S3, the obtained granules are taken out and granulated using a sieve with a pore size of Ф1.5mm at a rotation speed of 500rpm; S4, add an additional portion of cross-linked polyvinylpyrrolidone and zinc stearate, and mix well; S5, tablets are compressed using a Ф8.5mm round shallow concave punch, with tablet weight controlled within ±5.0% and friability ≤1.0%, to obtain piracetam hydrobromide tablets; S6. Prepare a 15% coating solution from the coating powder and coat the piracetam hydrobromide tablets. Control the tablet bed temperature at 60°C to obtain piracetam hydrobromide film-coated tablets.

[0058] The prepared pyrcitrinib hydrobromide film-coated tablets were used as the dissolution medium in water at 37°C, with a volume of 900 mL and a rotation speed of 50 rpm. The dissolution amount was measured after 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min. The results are shown in Table 4.

[0059] Table 4

[0060] Comparative Example 1 This comparative example provides a piracetamib hydrobromide tablet, which differs from Example 1 only in that it does not contain L-arginine. The batch size is 1000 tablets, and the prescribed dosage is as follows:

[0061] The preparation method of the above-mentioned pyridine hydrobromide tablets is the same as that in Example 1, and will not be repeated here.

[0062] The prepared pyrcitrinib hydrobromide film-coated tablets were used as the dissolution medium in water at 37°C, with a volume of 900 mL and a rotation speed of 50 rpm. The dissolution was measured after 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min. The results are shown in Table 5.

[0063] Table 5

[0064] Comparative Example 2 This comparative example provides a piracetamib hydrobromide tablet, which differs from Example 1 only in that L-arginine is replaced with an equal amount of sodium bisulfite. The batch size is 1000 tablets, and the prescribed dosage is as follows:

[0065] The preparation method of the above-mentioned pyridine hydrobromide tablets is the same as that in Example 1, and will not be repeated here.

[0066] The prepared pyrcitrinib hydrobromide film-coated tablets were used as the dissolution medium in water at 37°C, with a volume of 900 mL and a rotation speed of 50 rpm. The dissolution amount was measured after 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min. The results are shown in Table 6.

[0067] Table 6

[0068] Comparative Example 3 This comparative example provides a piracetamib hydrobromide tablet with the same formulation as Example 1, except that it uses a wet granulation process, the specific steps of which are as follows: S1, Weigh the prescribed amount of povidone K30 and add it to purified water, stir to dissolve, and prepare a 10% povidone K30 solution; S2, the prescribed amounts of piracetam hydrobromide, microcrystalline cellulose, mannitol, added polyvinylpyrrolidone and L-arginine are placed in a wet granulator and mixed for 10 min. Then, the povidone K30 solution is added to the wet granulator under high-speed shearing to make soft material. Wet granulation is carried out using a rapid granulator. The drying temperature is set at 60℃ and the material is dried in a fluidized bed dryer. The dry granules are granulated through a Ф2.0mm sieve. S3, add the remaining added polyvinylpyrrolidone and magnesium stearate, and mix well in the mixing tank; S4, tablets are compressed using a Ф8.5mm round shallow concave punch, with tablet weight controlled within ±5.0% and friability ≤1.0%, to obtain piracetam hydrobromide tablets; S5, prepare a 15% coating solution from the coating powder, and coat the piracetam hydrobromide tablets with the tablet bed temperature controlled at 50℃ to obtain piracetam hydrobromide film-coated tablets.

[0069] The prepared pyrcitrinib hydrobromide film-coated tablets were used as the dissolution medium in water at 37°C, with a volume of 900 mL and a rotation speed of 50 rpm. The dissolution amount was measured after 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min. The results are shown in Table 7.

[0070] Table 7

[0071] Comparative Example 4 This comparative example provides a piracetamib hydrobromide tablet with the same formulation as Example 1, except that it uses a dry-mix direct compression process. The specific steps are as follows: S1, mix the prescribed amounts of piracetam hydrobromide, microcrystalline cellulose, mannitol, polyvinylpyrrolidone, L-arginine, povidone K30 and magnesium stearate evenly in a mixing tank; S2, tablets are compressed using a Ф8.5mm round shallow concave punch, with tablet weight controlled within ±5.0% and friability ≤1.0%, to obtain piracetam hydrobromide tablets; S3, prepare a 15% coating solution from the coating powder, and coat the piracetam hydrobromide tablets with the tablet bed temperature controlled at 50℃ to obtain piracetam hydrobromide film-coated tablets.

[0072] The prepared pyrcitrinib hydrobromide film-coated tablets were used as the dissolution medium in water at 37°C, with a volume of 900 mL and a rotation speed of 50 rpm. The dissolution was measured after 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min. The results are shown in Table 8.

[0073] Table 8

[0074] The pyrcini hydrobromide tablets prepared in Examples 1-4 and Comparative Examples 1-4 of this invention were tested for appearance, content, and related substances (total and single impurities) in accordance with ICH guidelines. The results are shown in Table 9.

[0075] Table 9

[0076] This demonstrates that the piracetam hydrobromide tablets prepared according to the embodiments of the present invention have good stability, which can effectively ensure the consistency and reliability of efficacy during clinical use.

[0077] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A piracetamib hydrobromide tablet, characterized in that, It includes the following components by weight percentage: pyrsitinib hydrobromide 36%~42%, filler 45%~53%, binder 1%~2%, disintegrant 3%~7%, stabilizer 4%~8%, and lubricant 0.5%~2%; The stabilizer is a basic amino acid.

2. The pyrazinib hydrobromide tablets as described in claim 1, characterized in that, The basic amino acid includes at least one of L-arginine, L-lysine, or L-histidine.

3. The pyrazinib hydrobromide tablets as described in claim 1, characterized in that, The filler includes a first filler and a second filler, wherein the first filler is selected from microcrystalline cellulose and the second filler is selected from at least one of mannitol, lactose or pregelatinized starch.

4. The pyrazinib hydrobromide tablets as described in claim 3, characterized in that, The mass ratio of the first filler to the second filler is (1.0~1.5):(0.5~1.0).

5. The pirazitinib hydrobromide tablets as described in claim 4, characterized in that, The filler is a mixture of microcrystalline cellulose and mannitol.

6. The pyrazinib hydrobromide tablets as described in claim 1, characterized in that, The adhesive is selected from at least one of corn starch, hydroxypropyl methylcellulose, polyvinyl chloride K30, or polyvinyl alcohol.

7. The pyrazinib hydrobromide tablets as described in claim 1, characterized in that, The disintegrant is selected from one or both of sodium carboxymethyl starch or cross-linked polyvinylpyrrolidone.

8. The pyrazinib hydrobromide tablets as described in claim 1, characterized in that, The lubricant is selected from at least one of magnesium stearate, zinc stearate, talc, or micronized silica gel.

9. The method for preparing pyrazinib hydrobromide tablets according to any one of claims 1 to 8, characterized in that, Includes the following steps: S1, the prescribed amount of piracetamide hydrobromide, filler, partial disintegrant and stabilizer are placed in a fluidized bed and mixed to obtain fluidized material; S2, the adhesive solution is sprayed onto the fluidized material for granulation, and drying is performed simultaneously during the granulation process to obtain dry granules; S3. After granulating the dry granules, add the remaining disintegrant and lubricant, mix evenly, and compress into tablets to obtain piracetam hydrobromide tablets.

10. The method for preparing pyrazinib hydrobromide tablets as described in claim 9, characterized in that, In S1, the partial disintegrant is 40% to 60% of the prescribed amount of disintegrant; and / or In S2, the material temperature is maintained at 30℃~50℃ during the granulation process.

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