Canbustine tablet and preparation method thereof

Abstract

The invention relates to a Canbustine tablet and a preparation method thereof. The Cangbustine tablet comprises a tablet core and a film coating layer coated on the tablet core, the tablet core is prepared from the following raw material components in percentage by weight: 32 to 63.5 percent of an active component, 32 to 48 percent of a filling agent, 4 to 12 percent of a flow aid, 2 to 6 percent of a disintegrating agent and 0.5 to 7 percent of a lubricating agent, wherein the active component is combobustine; the film coating layer is prepared from a film-forming agent, polyethylene glycol, an additive and water, wherein the mass ratio of the film-forming agent to the polyethylene glycol to the additive is (2-6.4): 1: (1.7-5.3). Compared with the prior art, the preparation process is simple, and the obtained combobustine tablet has good dissolution rate, stability and bioequivalence and is easy for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceuticals, and in particular relates to a Combustine tablet and a preparation method thereof. Background Art

[0002] Combustine, with the chemical formula shown below, is chemically named disodium 2-methoxy-5-[cis-2-(3,4,5-trimethoxyphenyl)vinyl]-phenylphosphonate. As an active anti-tumor ingredient, Combustine can interfere with the mitotic process of tumor vascular endothelial cells, exhibiting potent anti-vascular effects, inhibiting cancer cell growth, inhibiting microtubule aggregation, and enhancing chemoradiotherapy sensitization. Compared to diphenylethylene derivatives or fluorodiphenylethane derivatives, Combustine exhibits stronger anti-tumor activity and is a water-soluble prodrug molecule, making it easier to administer in vivo.

[0003]

[0004] CN106137946A discloses a method of using a polypeptide as a carrier to spontaneously form a stable nanostructure with certain physical and chemical properties through the action of non-covalent bonds between molecules, and to encapsulate combustine in an aqueous solution through hydrophobic interaction. The method is simple and easy to use and can achieve a certain sustained-release effect, belonging to the intravenous administration method. CN110025790A discloses a reduction-responsive amphiphilic polymer drug precursor of combustine, its preparation method, and application. The provided drug precursor can achieve targeted drug delivery, retaining the advantages of the nano drug delivery system while leveraging the characteristics of specific degradation of disulfide bonds at the tumor site.

[0005] However, all of the aforementioned Combustine delivery systems are liquid-phase systems, often requiring intravenous injection in practice. This is complex and has poor compliance. Furthermore, these nano-liquid formulations exhibit poor physicochemical stability and are relatively expensive to manufacture. Therefore, it is necessary to develop an oral solid formulation of Combustine that exhibits excellent physicochemical stability and is easy to administer. Summary of the Invention

[0006] The purpose of the present invention is to provide a Combustine tablet and a preparation method thereof in order to overcome the defects of the existing Combustine drug delivery system, such as poor physical and chemical stability, inconvenience in administration and high manufacturing cost.

[0007] The purpose of the present invention can be achieved by the following technical solutions:

[0008] A first aspect of the present invention provides a Combustine tablet, comprising a tablet core and a film coating layer coated on the tablet core;

[0009] The tablet core comprises the following raw material components by weight percentage: 32-63.5% active ingredient, 32-48% filler, 4-12% glidant, 2-6% disintegrant, 0.5-7% lubricant, wherein the active ingredient is Combustine;

[0010] The film coating layer is made of a film-forming agent, polyethylene glycol, an additive and water, wherein the mass ratio of the film-forming agent, polyethylene glycol and the additive is (2-6.4):1:(1.7-5.3).

[0011] Furthermore, the tablet core comprises the following raw material components by weight percentage: 40-52% active ingredient, 36-45% filler, 4.2-10% glidant, 2-4% disintegrant, and 0.5-2% lubricant.

[0012] Furthermore, the filler includes one or more of lactose, glucose, dextrin, calcium carbonate, mannitol, sucrose, hydroxypropyl methylcellulose, microcrystalline cellulose, sodium carboxymethyl cellulose, corn starch, sorbitol, and sodium alginate.

[0013] Furthermore, the filler is preferably microcrystalline cellulose.

[0014] Furthermore, the average particle size of the microcrystalline cellulose is 110 to 230 μm, preferably 130 μm.

[0015] Furthermore, the bulk density of the microcrystalline cellulose is 0.25 to 0.45 g / mL, preferably 0.28 to 0.33 g / mL.

[0016] Furthermore, the glidant includes one or more of micro-powdered silica gel, silicone resin, silicon dioxide, stearate, maltodextrin, sodium lauryl sulfate, talc, low molecular weight polyethylene, and behenic acid glyceride.

[0017] Furthermore, the flow aid is preferably micropowder silica gel.

[0018] Furthermore, the BET specific surface area of the micropowder silica gel is 90 to 190 m 2 / g, preferably 110m 2 / g.

[0019] Furthermore, the average particle size of the micropowder silica gel is 3 to 20 nm, preferably 12 nm.

[0020] Furthermore, the disintegrant includes one or more of sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, xanthan gum, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, sodium starch glycolate, and crystalline cellulose, preferably cross-linked sodium carboxymethyl cellulose.

[0021] Furthermore, the lubricant includes one or more of magnesium stearate, calcium stearate, paraffin, polyethylene glycol 400, polyethylene glycol 6000, sodium stearyl fumarate, stearyl alcohol, butyl stearate, talc, and hydrogenated vegetable oil, preferably sodium stearyl fumarate.

[0022] Furthermore, the film-forming agent includes one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, copovidone, polyvinyl acetate, and methacrylic acid, preferably hydroxypropyl methylcellulose.

[0023] Furthermore, the additive includes one or more of talc, titanium dioxide, magnesium stearate, pyrogenic silica, iron oxide, and silicon dioxide, preferably titanium dioxide.

[0024] Furthermore, the molecular weight of the polyethylene glycol is 400-600, preferably 400. The role of polyethylene glycol is to ensure the quality and functionality of the coating film by plasticizing, adjusting rheological properties, preventing adhesion and optimizing drug release performance.

[0025] Furthermore, the mass ratio of the film-forming agent, polyethylene glycol and additive is (2-6):1:(2-5), and more preferably 3:1:3 or 2.4:1:2.4.

[0026] Furthermore, the total weight of the film-forming agent, polyethylene glycol and additives in the film coating layer is 1.7-5.5% of the weight of the tablet core, preferably 2-5%, and more preferably 2.8%.

[0027] Furthermore, the total solid content of the film-forming agent, polyethylene glycol and additives in the film coating layer is 10-15 wt %, preferably 11-13 wt %.

[0028] The present invention also provides a method for preparing Combustine tablets, which comprises the following steps:

[0029] S1: The active ingredient and the glidant are mixed and sieved to obtain a mixture 1; the filler and the disintegrant are mixed and sieved to obtain a mixture 2;

[0030] S2: Mixing material 1 and material 2, adding a lubricant, and then tableting to obtain a tablet core;

[0031] S3: Coating the core tablets obtained in S2 to obtain Combustine tablets.

[0032] Furthermore, in steps S1 and S2, the mixing time is 5 to 10 minutes.

[0033] Furthermore, in steps S1 and S2, the average particle size of the sieve during screening is 60-100 mesh.

[0034] Furthermore, in step S2, the tableting hardness is 6-8 kg.

[0035] Furthermore, in step S3, the atomization pressure during coating is 0.3-1.0 MPa, the inlet temperature is 45-80°C, and the tablet bed temperature is controlled at 35-65°C.

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] (1) The present invention prepares Combustine tablet cores by mixing the active ingredient Combustine with a filler, a glidant, a disintegrant, and a lubricant in a specific manner, and then directly compressing the dry powder into tablets. The tablet cores are then coated with a specific film coating technology, thereby finally preparing Combustine oral tablets with good hardness, good dissolution effect, high stability, and low moisture absorption.

[0038] (2) The Combustine tablets prepared by the present invention have a smooth appearance, good hardness, small tablet weight difference, uniform content, fast in vitro dissolution rate, high bioavailability, good stability, are not easy to absorb moisture, and can be stored stably for more than 6 months.

[0039] (3) The present invention adopts direct tableting of dry powder, eliminating the need for granulation and drying, which saves energy and time, achieves the effect of protecting drug stability, and has the characteristics of a high degree of industrial automation. At the same time, under the synergistic effect of glidants, fillers, etc., the specific surface area of the raw material is increased, which helps to disperse the raw material and improve bioavailability. It overcomes the electrostatic agglomeration effect between raw materials and avoids the problems of uneven mixing and tablet sticking during tableting, significantly improving the dissolution rate, stability and mechanical strength of Combustine tablets.

[0040] (4) The present invention takes into account the characteristics of Combustine being hygroscopic and easily decomposed under light, and adopts a specific film coating formula to coat the tablet core. Hydroxypropyl methylcellulose is selected as the basic film-forming agent and mixed with titanium dioxide to form a uniform light-proof layer, which has both moisture-proof and light-isolating functions, thereby further improving the stability of the tablet. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 The present invention is a flow chart of the preparation method of Combustine tablets.

[0042] Figure 2 The dissolution curves of Combustine tablets prepared in Example 1 in different solvents.

[0043] Figure 3 The dissolution curves of the three groups of Combustine tablets in water at different sampling time points in Example 1.

[0044] Figure 4 The dissolution curves of three groups of Combustine tablets in Example 1 in water after 6 months under the accelerated test. DETAILED DESCRIPTION

[0045] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0046] Unless otherwise specified, the reagents, methods, instruments and equipment used in the present invention are conventional reagents, methods, instruments and equipment in the art. Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0047] Example 1:

[0048] This embodiment provides a tablet containing Combustine, comprising a tablet core and a film coating layer.

[0049] The raw materials for preparing the tablet core include, by weight percentage, 49% active ingredient, 43% filler, 4.62% glidant, 2% disintegrant, and 1.38% lubricant.

[0050] The film coating layer is made of a film-forming agent, polyethylene glycol, additives and water, wherein the mass ratio of the film-forming agent, polyethylene glycol and additives is 3:1:1, the total solid content is 12.1wt%, and the total weight of the film-forming agent, polyethylene glycol and additives in the film coating layer is 2.8% of the weight of the tablet core.

[0051] The active ingredient in this example is Combustine, and the particle size range is ≤60 mesh.

[0052] The filler in this embodiment is microcrystalline cellulose, which has an average particle size of 130 μm and a bulk density of 0.28 to 0.33 g / mL.

[0053] The flow aid in this embodiment is micro powder silica gel. The BET specific surface area of micro powder silica gel is 110m 2 / g, and the average particle size is 12nm.

[0054] The disintegrant in this embodiment is cross-linked carboxymethyl cellulose sodium.

[0055] The lubricant in this embodiment is sodium stearyl fumarate.

[0056] The film-forming agent in this embodiment is hypromellose.

[0057] The average molecular weight of the polyethylene glycol in this embodiment is 400.

[0058] The additive in this embodiment is titanium dioxide.

[0059] The preparation process of Combustine tablets in this embodiment is as follows: Figure 1 Considering Combustine's hygroscopicity, a test conducted according to Appendix XIX J, "Guidelines for Hygroscopicity Testing," of the Chinese Pharmacopoeia (2005 Edition), Part II, revealed a hygroscopicity rate of 8.5%. Therefore, a relatively small tablet was selected for development.

[0060] The preparation method of the Combustine tablets of this embodiment specifically comprises the following steps:

[0061] S1. The active ingredient and the glidant are mixed, premixed, and sieved to obtain a mixture 1; the filler and disintegrant are mixed, premixed, and sieved to obtain a mixture 2;

[0062] S2. Mixture 1 and mixture 2 are mixed, a lubricant is added and mixed, and then tableted to obtain a core;

[0063] S3. The obtained tablet cores are coated by a high-speed coating machine to obtain Combustine tablets.

[0064] In steps S1 and S2, the mixing time is 10 minutes, the average particle size of the sieve during sieving is 60 mesh, and the hardness of the tablet during tableting is 7 kg.

[0065] The coating parameters in step S3 are: atomization pressure of 0.6 MPa, inlet temperature of 60° C., tablet bed temperature controlled at 45° C., and coating weight gain of 3%.

[0066] Example 2:

[0067] This embodiment provides a tablet containing Combustine, comprising a tablet core and a film coating layer.

[0068] The difference from Example 1 is that the raw materials for preparing the tablet core of this embodiment include, by weight percentage, 52% active ingredient, 36% filler, 8% glidant, 2% disintegrant, and 2% lubricant.

[0069] In the preparation method of this embodiment, in steps S1 and S2, the mixing time is 10 minutes, the average particle size of the sieve during sieving is 80 mesh, and the hardness of the tablet during tableting is 7 kg.

[0070] The coating parameters in step S3 are: atomization pressure of 0.6 MPa, inlet temperature of 60° C., tablet bed temperature controlled at 45° C., and coating weight gain of 3%.

[0071] Example 3:

[0072] This embodiment provides a tablet containing Combustine, comprising a tablet core and a film coating layer.

[0073] The difference from Example 1 is that the raw materials for preparing the tablet core of this example include, by weight percentage, 47% active ingredient, 41% filler, 6% glidant, 4% disintegrant, and 2% lubricant. The preparation method is similar to that of Example 1.

[0074] Example 4:

[0075] This embodiment provides a tablet containing Combustine, comprising a tablet core and a film coating layer.

[0076] The difference from Example 1 is that the raw materials for preparing the tablet core of this example include, by weight percentage, 40% active ingredient, 42% filler, 9% glidant, 2% disintegrant, and 7% lubricant. The preparation method is similar to that of Example 1.

[0077] Example 5:

[0078] This embodiment provides a tablet containing Combustine, comprising a tablet core and a film coating layer.

[0079] The difference from Example 1 is that the raw materials for preparing the tablet core of this example include, by weight percentage, 43% active ingredient, 44% filler, 8% glidant, 3% disintegrant, and 2% lubricant. The preparation method is similar to that of Example 1.

[0080] The mass ratio of the film-forming agent, polyethylene glycol, and additives in this embodiment is 2.4:1:2.4.

[0081] The total weight of the film-forming agent, polyethylene glycol, and additives in the film coating layer of this embodiment is 2.8% of the weight of the tablet core.

[0082] Example 6:

[0083] This embodiment provides a tablet containing Combustine, comprising a tablet core and a film coating layer.

[0084] The difference from Example 1 is that the raw materials for preparing the tablet core of this example include, by weight percentage, 38% active ingredient, 45% filler, 10% glidant, 6% disintegrant, and 1% lubricant. The preparation method is similar to that of Example 1.

[0085] The total weight of the film-forming agent, polyethylene glycol, and additives in the film coating layer of this embodiment is 2.0% of the weight of the tablet core.

[0086] Comparative Example 1:

[0087] This comparative example provides a tablet containing Combustine, comprising a tablet core and a film coating layer.

[0088] The difference from Example 1 is that the raw materials for preparing the tablet core of this comparative example include, by weight percentage, 37% active ingredient, 50% filler, 8% glidant, 3% disintegrant, and 2% lubricant. The preparation method is similar to that of Example 1.

[0089] Comparative Example 2:

[0090] This comparative example provides a tablet containing Combustine, comprising a tablet core and a film coating layer.

[0091] The difference from Example 1 is that the raw materials for preparing the tablet core of this comparative example include, by weight percentage, 57% active ingredient, 30% filler, 8% glidant, 3% disintegrant, and 2% lubricant. The preparation method is similar to that of Example 1.

[0092] The formulas of the Combustine tablets in Examples 1 to 6 and Comparative Examples 1 to 2 are summarized in Table 1.

[0093] Table 1 Summary of the formula of Combustine tablets (unit: g)

[0094]

[0095] The present invention carries out the following tests on the above-mentioned embodiment and comparative example:

[0096] (1) Tablet performance test: According to Part IV of the Pharmacopoeia of the People's Republic of China, the angle of repose, disintegration time, hardness, and friability were measured. The hardness tester was a YPD-200C tablet hardness tester (Tianjin Tianda Tianfa Co., Ltd.), and the disintegration tester was from Shanghai Huanghai Drug Testing Instrument Co., Ltd.

[0097] (2) Dissolution test: The dissolution curves of Combustine tablets in distilled water, 0.1 mol / L hydrochloric acid solution and pH=6.8 phosphate buffer solution. The dissolution conditions are: 900 mL dissolution medium, 75 rpm, 37°C. One tablet was placed in each dissolution cup, and samples were taken at 5, 10, 15, 20, 30 and 40 min, with 6 parallel samples. The samples were filtered and the peak area at 288 nm was determined by HPLC. The concentration of Combustine in the dissolution cup was calculated by the concentration and peak area standard curve, and the dissolved amount was calculated by multiplying it by the volume of the dissolution medium. The dissolved amount was divided by the amount of Combustine specified in each tablet to obtain the dissolution rate of Combustine tablets.

[0098] (3) Stability Test: Taking the Combustine tablets prepared in Example 1 as an example, the dissolution curves of the Combustine tablets after 6 months of storage under accelerated test conditions were compared with those before storage. The dissolution conditions were: slurry method, 900 mL of distilled water, rotation speed of 75 rpm, 37°C, and the specific operation was the same as the dissolution test. The accelerated test conditions were: temperature of 40±2°C, relative humidity of 75±5%. The results showed that the difference in the tablet dissolution curves before and after the test was very small.

[0099] Table 2 shows the performance test results of the Combustine tablets prepared in Examples 1 to 6 and Comparative Examples 1 to 2.

[0100] Table 2 Summary of performance test results of Combustine tablets

[0101] sample Angle of repose (°) Disintegration time (min) Hardness (kg) Friability (%) Example 1 36.5 4.36 6.99 0.50 Example 2 40.0 3.21 7.36 0.54 Example 3 38.2 4.20 8.02 0.47 Example 4 36.2 2.59 7.68 0.46 Example 5 38.8 3.99 7.36 0.59 Example 6 36.4 4.36 8.00 0.41 Comparative Example 1 35.2 10.3 11.2 0.23 Comparative Example 2 48.3 2.25 3.14 1.99

[0102] As can be seen from the table above, the tablets obtained in Examples 1 to 6 all passed the test, while some indicators of the tablets obtained in Comparative Examples 1 to 2 did not meet the requirements. The angle of repose is the maximum angle between the inclined surface of the cone formed when the powder is naturally piled and the horizontal plane. A value less than 40° indicates that the powder has good fluidity and can be used for tableting. The disintegration time refers to the maximum time required for the tablet to completely disintegrate into particles and pass through the screen under specified conditions. A value less than 15 minutes is considered qualified, indicating that the tablets obtained in the above examples all passed the test. Tablet hardness refers to the tablet's ability to resist external compression or crushing, generally between 6 and 8 kg. Tablet friability refers to the tablet's ability to resist vibration, friction, or impact, and is specified to be ≤1%. The friability of the Combustine tablets obtained in Examples 1 to 6 above all met the requirements. However, in Comparative Example 1, due to the excessive amount of filler, the disintegration time and hardness were too large. The excessive disintegration time was not conducive to the dissolution of the drug, and the excessive hardness directly affected the bioavailability and therapeutic effect. In Comparative Example 2, due to the insufficient amount of filler, the angle of repose of the powder and the hardness and friability of the tablets were unqualified. The excessive angle of repose was not conducive to the compression of the tablets, and the low hardness of the tablets would cause loose tablets, which seriously affected the subsequent coating, packaging and transportation processes.

[0103] Figure 2 The following are the dissolution curves of the Combustine tablets in Example 1 in different solvents. As can be seen from the figure, the Combustine tablets prepared in Example 1 exhibit good dissolution in distilled water, 0.1 mol / L hydrochloric acid solution, and pH 6.8 phosphate buffer solution. The tablets exhibited roughly the same dissolution curves in all three solvents, with dissolution rates reaching 90% at 30 minutes and complete dissolution at 40 minutes, fully meeting the specified tablet dissolution standards.

[0104] Figure 3The dissolution curves of the three groups of Combustine tablets in Example 1 at different sampling time points in water are shown. As can be seen, the dissolution rates of the three groups of tablets exceeded 85% at 20 minutes and reached saturation at 30 minutes, meeting the expected values. This demonstrates that the excipient combination in the Combustine tablet formulation is rational and the preparation process is stable.

[0105] Figure 4 The following is a graph showing the dissolution curves of the three groups of Combustine tablets in Example 1 after six months of use under accelerated test conditions. As can be seen from the graph, the dissolution curves of the three groups of Combustine tablets after six months are essentially the same as those before use. There is also no noticeable difference in the appearance of the tablets, indicating no deterioration due to prolonged storage, indicating that the tablets are of stable and reliable quality.

[0106] The above description of the embodiments is intended to facilitate understanding and use of the invention by those skilled in the art. It will be apparent that those skilled in the art can readily make various modifications to these embodiments and apply the general principles described herein to other embodiments without requiring inventive effort. Therefore, the present invention is not limited to the above-described embodiments. Improvements and modifications made by those skilled in the art based on the disclosure of the present invention, without departing from the scope of the present invention, should be within the scope of protection of the present invention.

Claims

1. A Combustine tablet, characterized in that: The Combustine tablet comprises a tablet core and a film coating layer coated on the tablet core; The tablet core comprises the following raw material components by weight percentage: 32-63.5% active ingredient, 32-48% filler, 4-12% glidant, 2-6% disintegrant, 0.5-7% lubricant, wherein the active ingredient is Combustine; The film coating layer is made of a film-forming agent, polyethylene glycol, an additive and water, wherein the mass ratio of the film-forming agent, polyethylene glycol and the additive is (2-6.4):1:(1.7-5.3).

2. A Combustine tablet according to claim 1, characterized in that: The filler includes one or more of lactose, glucose, dextrin, calcium carbonate, mannitol, sucrose, hydroxypropyl methylcellulose, microcrystalline cellulose, sodium carboxymethyl cellulose, corn starch, sorbitol, and sodium alginate; The glidant includes one or more of micro-powdered silica gel, silicone resin, silicon dioxide, stearate, maltodextrin, sodium lauryl sulfate, talc, low molecular weight polyethylene, and behenic acid glyceride; The disintegrant comprises one or more of sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, xanthan gum, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, sodium starch glycolate, and crystalline cellulose; The lubricant includes one or more of magnesium stearate, calcium stearate, paraffin, polyethylene glycol 400, polyethylene glycol 6000, sodium stearyl fumarate, stearyl alcohol, butyl stearate, talc, and hydrogenated vegetable oil.

3. A Combustine tablet according to claim 2, characterized in that: The filler is preferably microcrystalline cellulose; the average particle size of the microcrystalline cellulose is 110 to 230 μm, and the bulk density is 0.25 to 0.45 g / mL.

4. A Combustine tablet according to claim 2, characterized in that: The flow aid is preferably micropowder silica gel; the BET specific surface area of the micropowder silica gel is 90 to 190 m 2 / g, and the average particle size is 3 to 20 nm.

5. The Combustine tablet according to claim 1, characterized in that: The film-forming agent includes one or more of hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, copovidone, polyvinyl acetate, and methacrylic acid; The additives include one or more of talc, titanium dioxide, magnesium stearate, pyrogenic silica, iron oxide, and silicon dioxide.

6. A Combustine tablet according to claim 5, characterized in that: The film-forming agent is preferably hypromellose, and the additive is preferably titanium dioxide; The molecular weight of the polyethylene glycol is 400-600.

7. The Combustine tablet according to claim 1, characterized in that: The total weight of the film-forming agent, polyethylene glycol, and additives in the film coating layer is 1.7-5.5% of the weight of the tablet core; The total solid content of the film-forming agent, polyethylene glycol and additives in the film coating layer is 10-15 wt %.

8. A method for preparing the Combustine tablets according to claim 1, characterized in that: The preparation method comprises the following steps: S1: The active ingredient and the glidant are mixed and sieved to obtain a mixture 1; the filler and the disintegrant are mixed and sieved to obtain a mixture 2; S2: Mixing material 1 and material 2, adding a lubricant, and then tableting to obtain a tablet core; S3: Coating the core tablets obtained in S2 to obtain Combustine tablets.

9. The method for preparing Combustine tablets according to claim 8, characterized in that: In steps S1 and S2, the mixing time is 5 to 10 minutes, and the average particle size of the sieve during sieving is 60 to 100 mesh; In step S2, the tableting hardness is 6-8 kg.

10. The method for preparing Combustine tablets according to claim 8, characterized in that: In step S3, the atomization pressure during coating is 0.3-1.0 MPa, the inlet temperature is 45-80°C, and the tablet bed temperature is controlled at 35-65°C.

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