Double-layer tablet and preparation method thereof

Abstract

The invention provides a double-layer tablet and a preparation method thereof. The double-layer tablet comprises a first layer and a second layer, the first layer is prepared from 50 parts of dotegravir or pharmaceutically acceptable salt (based on dotegravir), 30 to 60 parts of modified mesoporous silicon dioxide, 60 to 80 parts of first filling agent, 30 to 50 parts of first disintegrating agent, 300 parts of lamivudine, 80 to 120 parts of second filling agent, 20 to 30 parts of second flow aid, 400 to 700 parts of third filling agent, 100 to 150 parts of third disintegrating agent, 150 to 200 parts of first sweetening agent and 40 to 60 parts of third flow aid; and the second layer comprises 600 parts of abacavir or pharmaceutically acceptable salt (based on abacavir), 950-1200 parts of a fourth filling agent, 120-150 parts of a fourth disintegrating agent, 30-50 parts of a fourth flow aid and 30-40 parts of a second sweetening agent. The first layer is prepared by adopting a direct powder compression method, and then the raw materials of the second layer are mixed and compressed onto the first layer to obtain the double-layer tablet. The operation is simplified, the production efficiency of the medicinal preparation is improved, and industrial large-scale production and manufacturing are facilitated.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and in particular to a double-layer tablet and a preparation method thereof. Background Art

[0002] AIDS, or acquired immunodeficiency syndrome, is a fatal infectious disease caused by the human immunodeficiency virus (HIV). The disease severely damages the human immune system and can cause various symptoms such as bleeding, high fever, swollen lymph nodes, and weakness. The onset of the disease is generally related to factors such as blood infection and sexual contact, and some infants and young children are generally infected through mother-to-child transmission. The use of anti-HIV drugs to effectively prolong the life of HIV-infected people or AIDS patients and improve their quality of life by inhibiting viral replication or invasion. The combined use of antiviral drugs is called highly active combined antiretroviral therapy (HAART), which is currently the most effective method for treating AIDS. This method uses three or more anti-HIV drugs for combined treatment, which can reduce the drug resistance caused by single drug use and improve the antiviral efficacy.

[0003] Dolutegravir is an integrase strand transfer inhibitor (INSTI) that can inhibit HIV integrase and block the strand transfer process of HIV genome integration into host cell DNA, thereby inhibiting HIV replication and protein expression. Dolutegravir sodium is approved for use in HIV patient populations. And because of its efficacy, high resistance to drug resistance and tolerance, it is recommended for first-line treatment of adults infected with HIV-1. Lamivudine is a nucleoside antiviral drug, and nucleotides are the raw materials for synthesizing human genetic material DNA and RNA. Nucleoside analogs structurally mimic the structure of nucleotides, but do not have the function of nucleotides. Therefore, during the DNA synthesis process, nucleoside analogs can be incorporated, but they cannot synthesize normally functional nucleic acid chains, thereby terminating viral replication. Lamivudine has a competitive inhibitory effect on the synthesis and extension of viral DNA chains. Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI), and abacavir sulfate is approved for use in combination with other HIV drugs to treat patients infected with HIV.

[0004] Each tablet of TRIUMEQ contains 50 mg of dolutegravir sodium (calculated as dolutegravir), 600 mg of abacavir sulfate (calculated as abacavir) and 300 mg of lamivudine. In the prior art, when preparing dolutegravir tablets, dolutegravir is mixed with lamivudine and excipients after wet granulation, fluidized bed drying, dry grinding and the like, which is a complicated process and not conducive to large-scale production. Summary of the invention

[0005] In view of this, the present invention aims to provide a double-layer tablet and a preparation method thereof, so as to solve the problem of complicated process in preparing a double-layer tablet containing three drugs: dolutegravir, lamivudine and abacavir.

[0006] To achieve the above object, the technical solution of the present invention is achieved as follows:

[0007] In one aspect, the present invention provides a double-layer tablet, comprising a first layer and a second layer, wherein the first layer comprises the following components in parts by weight: 50 parts of dolutegravir or a pharmaceutically acceptable salt thereof (calculated as dolutegravir), 30-60 parts of modified mesoporous silica, 60-80 parts of a first filler, 30-50 parts of a first disintegrant, 300 parts of lamivudine, 80-120 parts of a second filler, 20-30 parts of a second glidant, and 100 parts of a second disintegrant. The third filler comprises 400-700 parts, the third disintegrant comprises 100-150 parts, the first sweetener comprises 150-200 parts and the third glidant comprises 40-60 parts; the second layer comprises the following components in parts by weight: 600 parts of abacavir or a pharmaceutically acceptable salt thereof (calculated as abacavir), 950-1200 parts of a fourth filler, 120-150 parts of a fourth disintegrant, 30-50 parts of a fourth glidant and 30-40 parts of a second sweetener.

[0008] Furthermore, the first filler, the second filler, the third filler and the fourth filler are selected from at least one of mannitol, lactose and microcrystalline cellulose.

[0009] Furthermore, the first disintegrant, the third disintegrant and the fourth disintegrant are selected from at least one of cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, starch and cross-linked polyvinylpyrrolidone.

[0010] Furthermore, the second glidant and the third glidant are selected from at least one of magnesium stearate, colloidal silicon dioxide and talc.

[0011] Furthermore, the first sweetener and the second sweetener are selected from sucrose.

[0012] On the other hand, the present invention also provides a method for preparing a double-layer tablet, the preparation method comprising the following steps:

[0013] S1. mixing dolutegravir or a pharmaceutically acceptable salt thereof and mesoporous silica and dissolving them in an appropriate amount of anhydrous ethanol, evaporating the anhydrous ethanol, taking out the residue, vacuum drying, and grinding to obtain a dolutegravir solid dispersion;

[0014] S2. mixing the dolutegravir solid dispersion, the first filler and the first disintegrant to obtain a first mixture;

[0015] S3. After lamivudine is micronized, a second filler and a second glidant are added and mixed to obtain a second mixture;

[0016] S4. After mixing the second mixture, the third filler and the third disintegrant, the first mixture and the first sweetener are added simultaneously to obtain a third mixture;

[0017] S5. Mixing the third mixture and the third glidant together, and tableting to form a first layer of a bilayer tablet;

[0018] S6. Abacavir or a pharmaceutically acceptable salt thereof, a fourth filler, a fourth disintegrant, a fourth glidant and a second sweetener are blended and compressed onto the first layer to obtain a bilayer tablet;

[0019] S7. Coating the bilayer tablets.

[0020] Furthermore, in step S3, lamivudine is micronized into powder with a particle size of 20-100 μm.

[0021] Furthermore, in step S7, the double-layer tablet is coated until the coating weight gain is 2%-4% w / w.

[0022] Specifically, the coating materials and coating techniques can refer to the existing technology and will not be described in detail here.

[0023] Compared with the prior art, the tablet and the preparation method thereof described in the present invention have the following advantages:

[0024] (1) When preparing the first layer of the double-layer tablet, a powder direct tableting method is adopted, which simplifies the operation, improves the production efficiency of the drug preparation, and facilitates industrial large-scale production.

[0025] (2) Without increasing the amount of sweetener, the taste of the double-layer tablet is improved, making it more suitable for children. DETAILED DESCRIPTION

[0026] The present invention will be further described below in conjunction with specific embodiments. It should be noted that the data in the following experimental examples are obtained by the inventor through a large number of experiments. Due to space limitations, only a part of them is shown in the specification, and those of ordinary skill in the art can understand and implement the present invention under these data. These embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these changes or modifications also fall within the scope protected by the present application.

[0027] A double-layer tablet of the present invention comprises a first layer and a second layer, wherein the first layer comprises the following components: 50 parts of dolutegravir or a pharmaceutically acceptable salt thereof (calculated as dolutegravir), 30-60 parts of modified mesoporous silica, 60-80 parts of a first filler, 20-30 parts of a first disintegrant, 300 parts of lamivudine, 50-100 parts of a second filler, 20-30 parts of a second glidant, 300-600 parts of a third filler, 100-150 parts of a third disintegrant, 130-200 parts of a first sweetener and 40-60 parts of a third glidant; and the second layer comprises the following components in parts by weight: 600 parts of abacavir or a pharmaceutically acceptable salt thereof (calculated as abacavir), 100-130 parts of a fourth filler, 100-150 parts of a fourth disintegrant and 30-40 parts of a second sweetener.

[0028] Specifically, when preparing the double-layer tablet, the airflow milling method can be used to ultrafinely grind lamivudine into powder with a particle size of 20-100 μm.

[0029] The preparation method of the modified mesoporous silica is as follows: mesoporous silica is configured into a suspension with a mass concentration of 10-15% by ultrasonic oscillation technology, the suspension is directly treated with an air atmospheric pressure plasma jet device, and then centrifuged to obtain a precipitate, washed with anhydrous ethanol, and vacuum freeze-dried to obtain modified mesoporous silica. The ultrasonic treatment time is 20-40min, and the ultrasonic treatment temperature is 20-30°C; the air atmospheric pressure plasma jet treatment time is 1-7min, the power is 650-850W, and the height is 14.13mm; the centrifugal speed is 2000-3000rpm, the centrifugal time is 10-15min; and the anhydrous ethanol is washed 3-5 times. Specifically, the preparation method of modified mesoporous silica can refer to CN111991558B.

[0030] Example 1

[0031] Modified mesoporous silica was prepared by weighing 50 g of dolutegravir and 30 g of modified mesoporous silica, mixing them and dissolving them in anhydrous ethanol. The anhydrous ethanol was evaporated and removed. The residue was taken out and vacuum dried and ground to obtain a dolutegravir solid dispersion.

[0032] The dolutegravir solid dispersion, 80 g of microcrystalline cellulose and 30 g of croscarmellose sodium were mixed to obtain a first mixture.

[0033] 300 g of lamivudine was micronized into powder with a particle size of 20-100 μm, and 100 g of microcrystalline cellulose and 30 g of colloidal silicon dioxide were added and premixed to obtain a second mixture.

[0034] After the second mixture, 600 g of microcrystalline cellulose and 150 g of cross-linked sodium carboxymethyl cellulose were mixed, the first mixture and 200 g of sucrose were added simultaneously to obtain a third mixture.

[0035] The third mixture was mixed with 40 g of colloidal silicon dioxide and tableted at a rotation speed of 5 rpm to form the first layer of a double-layer tablet.

[0036] 702 g of abacavir sulfate, 1090 g of microcrystalline cellulose, 120 g of croscarmellose sodium, 50 g of colloidal silicon dioxide and 40 g of sucrose were blended and compressed onto the first layer to obtain a double-layer tablet, which was coated to a coating weight gain of 2%-4% w / w.

[0037] Example 2

[0038] Modified mesoporous silica was prepared by weighing 50 g of dolutegravir and 60 g of modified mesoporous silica, mixing them and dissolving them in anhydrous ethanol. The anhydrous ethanol was evaporated and removed. The residue was taken out and vacuum dried and ground to obtain a dolutegravir solid dispersion.

[0039] The dolutegravir solid dispersion, 80 g of lactose and 40 g of cross-linked polyvinylpyrrolidone were mixed to obtain a first mixture.

[0040] 300 g of lamivudine was micronized into powder with a particle size of 20-100 μm, and 100 g of lactose and 20 g of magnesium stearate were added and premixed to obtain a second mixture.

[0041] After mixing the second mixture, 550 g of lactose and 150 g of cross-linked polyvinylpyrrolidone, the first mixture and 200 g of sucrose were added simultaneously to obtain a third mixture.

[0042] The third mixture was mixed with 60 g of magnesium stearate and tableted at a rotation speed of 10 rpm to form the first layer of a double-layer tablet.

[0043] 702 g of abacavir sulfate, 1200 g of lactose, 120 g of crospovidone, 30 g of magnesium stearate and 30 g of sucrose were blended and compressed onto the first layer to obtain a double-layer tablet, which was coated to a coating weight gain of 2%-4% w / w.

[0044] Example 3

[0045] Modified mesoporous silica was prepared by weighing 50 g of dolutegravir and 50 g of modified mesoporous silica, mixing them and dissolving them in anhydrous ethanol. The anhydrous ethanol was evaporated and removed. The residue was taken out and vacuum dried and ground to obtain a dolutegravir solid dispersion.

[0046] The dolutegravir solid dispersion, 78 g of mannitol and 34 g of starch were mixed to obtain a first mixture.

[0047] 300 g of lamivudine was micronized into powder with a particle size of 20-100 μm, and 90 g of mannitol and 28 g of talc were premixed to obtain a second mixture.

[0048] After mixing the second mixture, 600 g of mannitol and 150 g of starch, the first mixture and 180 g of sucrose were added simultaneously to obtain a third mixture.

[0049] The third mixture was mixed with 50 g of magnesium stearate and tableted at a rotation speed of 8 rpm to form the first layer of a double-layer tablet.

[0050] 702 g of abacavir sulfate, 950 g of mannitol, 150 g of starch, 50 g of talc and 40 g of sucrose were blended and compressed onto the first layer to obtain a double-layer tablet, which was then coated to a coating weight gain of 2%-4% w / w.

[0051] Example 4

[0052] Modified mesoporous silica was prepared by weighing 50 g of dolutegravir and 30 g of modified mesoporous silica, mixing them and dissolving them in anhydrous ethanol. The anhydrous ethanol was evaporated and removed. The residue was taken out and vacuum dried and ground to obtain a dolutegravir solid dispersion.

[0053] The dolutegravir solid dispersion, 60 g of lactose and 50 g of sodium carboxymethylcellulose were mixed to obtain a first mixture.

[0054] 300 g of lamivudine was micronized into powder with a particle size of 20-100 μm, and 80 g of lactose and 30 g of colloidal silicon dioxide were added and premixed to obtain a second mixture.

[0055] After the second mixture, 700 g of microcrystalline cellulose and 100 g of cross-linked sodium carboxymethyl cellulose were mixed, the first mixture and 150 g of sucrose were added simultaneously to obtain a third mixture.

[0056] The third mixture was mixed with 60 g of magnesium stearate and tableted at a rotation speed of 5 rpm to form the first layer of a double-layer tablet.

[0057] 702 g of abacavir sulfate, 1085 g of lactose, 140 g of cross-linked carboxymethyl cellulose sodium, 40 g of magnesium stearate and 35 g of sucrose were blended and compressed onto the first layer to obtain a double-layer tablet, which was coated to a coating weight gain of 2%-4% w / w.

[0058] Comparative Example 1

[0059] Modified mesoporous silica was prepared by weighing 50 g of dolutegravir and 30 g of modified mesoporous silica, mixing them and dissolving them in anhydrous ethanol. The anhydrous ethanol was evaporated and removed. The residue was taken out and vacuum dried and ground to obtain a dolutegravir solid dispersion.

[0060] The dolutegravir solid dispersion, 80 g of microcrystalline cellulose and 30 g of croscarmellose sodium were mixed to obtain a first mixture.

[0061] 300 g of lamivudine was micronized into powder with a particle size of 20-100 μm, and 700 g of microcrystalline cellulose, 30 g of colloidal silicon dioxide, and 150 g of cross-linked sodium carboxymethyl cellulose were added and mixed, and then the first mixture and 200 g of sucrose were added to obtain a third mixture.

[0062] The third mixture was mixed with 40 g of colloidal silicon dioxide and tableted at a rotation speed of 5 rpm to form the first layer of a double-layer tablet.

[0063] The preparation method of the first layer of Comparative Example 1 is the same as that of Example 1, except that the micronized lamivudine is not premixed, but directly mixed with 700 g of microcrystalline cellulose, 30 g of colloidal silicon dioxide, and 150 g of cross-linked sodium carboxymethyl cellulose, and then the first mixture and 200 g of sucrose are added.

[0064] Comparative Example 2

[0065] Modified mesoporous silica was prepared by weighing 50 g of dolutegravir and 30 g of modified mesoporous silica, mixing them and dissolving them in anhydrous ethanol. The anhydrous ethanol was evaporated and removed. The residue was taken out and vacuum dried and ground to obtain a dolutegravir solid dispersion.

[0066] The dolutegravir solid dispersion, 80 g of microcrystalline cellulose and 30 g of croscarmellose sodium were mixed to obtain a first mixture.

[0067] 300 g of lamivudine was passed through a 30-50 mesh sieve, and 100 g of microcrystalline cellulose and 30 g of colloidal silicon dioxide were added and premixed to obtain a second mixture.

[0068] After the second mixture, 600 g of microcrystalline cellulose and 150 g of cross-linked sodium carboxymethyl cellulose were mixed, the first mixture and 200 g of sucrose were added simultaneously to obtain a third mixture.

[0069] The third mixture was mixed with 40 g of colloidal silicon dioxide and tableted at a rotation speed of 5 rpm to form the first layer of a double-layer tablet.

[0070] The preparation method of the first layer of Comparative Example 2 is the same as that of Example 1, except that lamivudine is passed through a 30-50 mesh sieve instead of being micronized in Example 1.

[0071] Comparative Example 3

[0072] 52.6 g of dolutegravir sodium, 110 g of microcrystalline cellulose, and 30 g of croscarmellose sodium were mixed to obtain a first mixture.

[0073] 300 g of lamivudine was micronized into powder with a particle size of 20-100 μm, and 100 g of microcrystalline cellulose and 30 g of colloidal silicon dioxide were added and premixed to obtain a second mixture.

[0074] After the second mixture, 600 g of microcrystalline cellulose and 150 g of cross-linked sodium carboxymethyl cellulose were mixed, the first mixture and 200 g of sucrose were added simultaneously to obtain a third mixture.

[0075] The third mixture was mixed with 40 g of colloidal silicon dioxide and tableted at a rotation speed of 5 rpm to form the first layer of a double-layer tablet.

[0076] The preparation method of the first layer of Comparative Example 3 is the same as that of Example 1, except that the step of mixing dolutegravir or its pharmaceutically acceptable salt with modified mesoporous silica to prepare dolutegravir solid dispersion is omitted, and dolutegravir sodium is directly used for subsequent treatment.

[0077] Comparative Example 4

[0078] The preparation method of the double-layer tablet of Comparative Example 4 is the same as that of Example 1, except that the sweetener sucrose is replaced by potassium acesulfame.

[0079] 1000 tablets were obtained from each of the above Examples 1 to 4 and Comparative Examples 1 to 4.

[0080] Comparative Example 5

[0081] The preparation method of Comparative Example 5 is the same as that of CN115803018A.

[0082] When synthesizing the preparation of Comparative Example 5, it is necessary to go through the steps of high-speed shearing, wet granulation, and particle drying to prepare dolutegravir particles, which not only requires the use of multiple equipment, increases the cost, but also makes the preparation process more complicated. A double-layer tablet and a preparation method thereof of the present invention respectively adopt specific treatment methods according to the characteristics of different raw materials, and prepare a dolutegravir solid dispersion by mixing dolutegravir with a relatively small content and modified mesoporous silica, and pre-mixing the lamivudine with a relatively large content with a filler and a glidant after micronization, and then by combining the excipients, the first layer of the dolutegravir and lamivudine layers can be prepared by a powder direct tableting method, eliminating the steps of wet granulation and particle drying.

[0083] The powder formed by mixing the third mixture and the third flow aid prepared in Examples 1-4 and the powder formed by mixing the third mixture and the third flow aid prepared in Comparative Examples 1-3 (i.e., the powder used for tableting to form the first layer) were taken, and the angle of repose was measured by the fixed cone bottom method, the cone bottom diameter (2R) was 5.2 cm, and the stacking height h of the above powder was measured. Wherein, the angle of repose α = arctg (h / R). The specific experimental results are shown in Table 1.

[0084] Table 1

[0085]

[0086] As shown in Table 1, the powders obtained in Examples 1-4 of the present invention have good fluidity and good compressibility, and the surface of the first layer of the prepared double-layer tablets is smooth and free of cracking. The double-layer tablets obtained by compressing abacavir or its pharmaceutically acceptable salt onto the first layer are also smoothly tableted without cracking. However, the powder formed by mixing the third mixture and colloidal silicon dioxide in Comparative Example 1 has poor fluidity. For lamivudine, although micronization can increase the specific surface area of ​​the raw material to improve dissolution and help to better mix with other components, it will also reduce fluidity and cannot be directly mixed with other excipients for tableting. Therefore, after lamivudine is micronized, the present invention first mixes it with a certain amount of the second filler and the second glidant to obtain a second mixture, and then adds a large amount of the third filler and the third disintegrant, which helps to improve fluidity. Comparative Example 1 changes the order of adding lamivudine and pharmaceutical excipients, has no effect on improving the fluidity of lamivudine, and tableting is difficult. In Comparative Example 2, the lamivudine was directly screened instead of the micronization treatment of the present invention. Compared with dolutegravir in the pharmaceutical preparation, the amount of lamivudine was relatively large, and it was extremely easy to mix unevenly with other excipients, which affected the tableting process, and the surface of the first layer of the finished product was not smooth. Comparative Example 3 omitted the preparation of the solid dispersion of telavir using modified mesoporous silica of the present invention, and the drug particles were easy to agglomerate, and the obtained powder was dry. Comparative Example 3 was directly tableted, and the tablet compressibility was poor.

[0087] The double-layer tablets prepared in Examples 1-4 and the double-layer tablets of Comparative Examples 4-5 were orally taken by 20 male volunteers aged 20-35 and 20 female volunteers aged 20-35, respectively. Most of the volunteers responded that the amount of saliva secretion and the speed of secretion after the drug preparation entered the oral cavity could meet the requirements of drug swallowing. Among them, 98% of the volunteers believed that the double-layer tablets of Comparative Examples 4-5 had a weak bitter taste when taken, while the double-layer tablets of Examples 1-4 had no bad odor when taken. It is speculated that the possible reason is that modified mesoporous silica is added to the double-layer tablets prepared by the present invention, and there are oxygen-containing polar groups in the mesoporous silica, which improves the hydrophilicity of the mesoporous silica. Through the selection of a specific sweetener, namely sucrose, sucrose can be well adhered to the surface of the hydrophilic mesoporous silica. In addition, the dolutegravir raw material can be highly dispersed in the mesoporous silica, and the micronized lamivudine and dolutegravir solid dispersions are also highly dispersed, so that sucrose is evenly dispersed in the drug preparation, reducing the agglomeration of sucrose and better covering up the bad taste. Comparative Example 4 changed the type of sweetener and had a slight bitter taste when taken orally.

[0088] 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, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A double-layer tablet, characterized in that: The double-layer tablet comprises a first layer and a second layer, wherein the first layer comprises the following components in parts by weight: 50 parts of dolutegravir or a pharmaceutically acceptable salt thereof (calculated as dolutegravir), 30-60 parts of modified mesoporous silica, 60-80 parts of a first filler, 30-50 parts of a first disintegrant, 300 parts of lamivudine, 80-120 parts of a second filler, 20-30 parts of a second glidant, 400-700 parts of a third filler, 100-150 parts of a third disintegrant, 150-200 parts of a first sweetener and 40-60 parts of a third glidant; the second layer comprises the following components in parts by weight: 600 parts of abacavir or a pharmaceutically acceptable salt thereof (calculated as abacavir), 950-1200 parts of a fourth filler, 120-150 parts of a fourth disintegrant, 30-50 parts of a fourth glidant and 30-40 parts of a second sweetener.

2. The double-layer tablet according to claim 1, characterized in that The first filler, the second filler, the third filler and the fourth filler are selected from at least one of mannitol, lactose and microcrystalline cellulose.

3. The double-layer tablet according to claim 1, characterized in that The first disintegrant, the third disintegrant and the fourth disintegrant are selected from at least one of cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, starch and cross-linked polyvinylpyrrolidone.

4. The double-layer tablet according to claim 1, characterized in that The second glidant and the third glidant are selected from at least one of magnesium stearate, colloidal silicon dioxide and talc.

5. The double-layer tablet according to claim 1, characterized in that: The first sweetener and the second sweetener are selected from sucrose.

6. A method for preparing a double-layer tablet according to any one of claims 1 to 5, characterized in that: The preparation method comprises the following steps: S1. mixing dolutegravir or a pharmaceutically acceptable salt thereof and mesoporous silica and dissolving them in an appropriate amount of anhydrous ethanol, evaporating the anhydrous ethanol, taking out the residue, vacuum drying, and grinding to obtain a dolutegravir solid dispersion; S2. mixing the dolutegravir solid dispersion, the first filler and the first disintegrant to obtain a first mixture; S3. After lamivudine is micronized, a second filler and a second glidant are added and mixed to obtain a second mixture; S4. After mixing the second mixture, the third filler and the third disintegrant, the first mixture and the first sweetener are added simultaneously to obtain a third mixture; S5. Mixing the third mixture and the third glidant together, and tableting to form a first layer of a bilayer tablet; S6. Abacavir or a pharmaceutically acceptable salt thereof, a fourth filler, a fourth disintegrant, a fourth glidant and a second sweetener are blended and compressed onto the first layer to obtain a bilayer tablet; S7. Coating the bilayer tablets.

7. The method for preparing a double-layer tablet according to claim 6, characterized in that: In the step S3, lamivudine is micronized into powder with a particle size of 20-100 μm.

8. The method for preparing a double-layer tablet according to claim 6, characterized in that: In step S7, the double-layer tablet is coated until the coating weight gain is 2%-4% w / w.

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