Dapagliflozin and metformin sustained release tablet and preparation method thereof

Abstract

The invention relates to a dapagliflozin and metformin sustained-release tablet, the sustained-release tablet comprises a metformin hydrochloride sustained-release tablet core, the sustained-release tablet core is sequentially coated with an isolation coating layer and a dapagliflozin quick-release coating layer, the dapagliflozin quick-release coating layer comprises dapagliflozin or a pharmaceutically acceptable salt thereof and a first adhesive, and the metformin hydrochloride sustained-release tablet core comprises a metformin hydrochloride sustained-release tablet core, a metformin hydrochloride sustained-release tablet core, a metformin hydrochloride sustained-release tablet core and a metformin hydrochloride sustained-release tablet core, the first binder is not hydroxypropyl methyl cellulose. According to the dapagliflozin sustained-release tablet and the preparation method thereof, by optimizing the types of adhesives in a dapagliflozin quick-release coating layer, the sustained-release tablet with the in-vitro release degree consistent with that of dapagliflozin in an original commercially-available preparation # imgabs0 # imgabs1 # is obtained. In addition, the dapagliflozin and metformin sustained-release tablet disclosed by the invention is simple in preparation process and easy for large-scale production.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical preparations, and in particular to a dapagliflozin metformin sustained-release tablet. Background Art

[0002] Dapagliflozin is a new sodium-glucose transport protein 2 (SGLT2) inhibitor, which was officially approved for marketing by the China Food and Drug Administration in 2017. Dapagliflozin reduces the reabsorption of glucose by the kidneys, allowing excess glucose to be excreted in the urine, thereby reducing glycated hemoglobin and blood sugar in patients with type 2 diabetes mellitus (T2DM). In addition, dapagliflozin has benefits in lowering lipids, lowering blood pressure, improving nonalcoholic fatty liver disease (NAFLD), treating heart failure, protecting kidney function, and reducing uric acid. Dapagliflozin is highly safe, with the main adverse reaction being urogenital tract infection, but the incidence is low. It is a new type of hypoglycemic drug with broad prospects.

[0003] Metformin is a commonly used oral hypoglycemic drug. Its mechanism of action is that hepatic gluconeogenesis (in liver cells) is controlled, insulin resistance is improved, and blood sugar levels decrease. However, as the course of diabetes prolongs, the progressive decline in the body's pancreatic β-cell function will seriously affect the efficacy. Actively improving oral drug treatment plans in clinical practice is of great clinical significance, and a combination drug plan is proposed to improve the efficacy. Relevant clinical studies have confirmed that dapagliflozin combined with metformin is effective in treating type 2 diabetes, can lower patients' blood sugar, improve oxidative stress response and regulate lipid metabolism function, and significantly improve patients' pancreatic islet function, with high clinical application value.

[0004] The original product of dapagliflozin metformin extended-release tablets was developed by AstraZeneca and was approved by the FDA for marketing in October 2014 under the trade name Xigduo XR. In June 2023, dapagliflozin metformin extended-release tablets were approved by NMPA under the trade name Used to improve blood sugar control in adult patients with type 2 diabetes. Dapagliflozin metformin extended-release tablets are taken once a day, one tablet at a time, which helps improve patients' medication compliance. Compared with ordinary tablets, dapagliflozin metformin extended-release tablets have a more gradual change in blood drug concentration and a lower incidence of gastrointestinal adverse reactions.

[0005] The original dapagliflozin metformin sustained-release tablets (Xigduo XR, Anda-release) use a double-layer tablet, including a metformin hydrochloride sustained-release layer and a dapagliflozin immediate-release layer. Since the method for preparing double-layer tablets has high requirements for excipients, is difficult to compress, and requires special equipment, it is not conducive to industrialization. Therefore, it is necessary to develop a dapagliflozin metformin sustained-release tablet with a simple preparation process, easy large-scale production, similar in vitro release behavior to the original formulation, and in vivo bioequivalence. Summary of the invention

[0006] To solve the above technical problems, the present invention includes the following aspects:

[0007] The first aspect of the present invention provides a dapagliflozin metformin sustained-release tablet, which comprises a metformin hydrochloride sustained-release tablet core, and the exterior of the sustained-release tablet core is sequentially coated with an isolation coating layer and a dapagliflozin immediate-release coating layer, and the dapagliflozin immediate-release coating layer comprises the dapagliflozin active ingredient and a first adhesive, and the first adhesive is not hydroxypropyl methylcellulose.

[0008] Preferably, the metformin hydrochloride sustained-release tablet core comprises metformin hydrochloride, a sustained-release excipient, a second adhesive and a lubricant.

[0009] Preferably, the weight percentage of metformin hydrochloride in the metformin hydrochloride sustained-release tablet core is 60-80%. More preferably, the weight percentage of metformin hydrochloride in the metformin hydrochloride sustained-release tablet core is 65-75%. Further preferably, the weight percentage of metformin hydrochloride in the metformin hydrochloride sustained-release tablet core is 70-73%.

[0010] Preferably, the sustained-release excipient in the metformin hydrochloride sustained-release tablet core is one or more of hydroxypropyl methylcellulose, methylcellulose, and polyethylene oxide. More preferably, the sustained-release excipient is hydroxypropyl methylcellulose. Further preferably, the sustained-release excipient is hydroxypropyl methylcellulose K100M.

[0011] Preferably, the weight percentage of the sustained-release excipient in the metformin hydrochloride sustained-release tablet core is 10-30%. More preferably, the weight percentage of the sustained-release excipient in the metformin hydrochloride sustained-release tablet core is 15-28%. Further preferably, the weight percentage of the sustained-release excipient in the metformin hydrochloride sustained-release tablet core is 20-25%.

[0012] Preferably, the second binder in the metformin hydrochloride sustained-release tablet core is one or more of povidone, sodium carboxymethyl cellulose, and hydroxypropyl cellulose. More preferably, the second binder is povidone. Further preferably, the second binder is povidone K-90.

[0013] Preferably, the weight percentage of the second binder in the metformin hydrochloride sustained-release tablet core is 1-10%. More preferably, the weight percentage of the second binder in the metformin hydrochloride sustained-release tablet core is 2-8%. Further preferably, the weight percentage of the second binder in the metformin hydrochloride sustained-release tablet core is 3-5%.

[0014] Preferably, the lubricant in the metformin hydrochloride sustained-release tablet core is one or more of magnesium stearate, micro-powder silica gel, and talcum powder. More preferably, the lubricant is magnesium stearate.

[0015] Preferably, the weight percentage of the lubricant in the metformin hydrochloride sustained-release tablet core is 0.05-1%. More preferably, the weight percentage of the lubricant in the metformin hydrochloride sustained-release tablet core is 0.1-0.8%. Further preferably, the weight percentage of the lubricant in the metformin hydrochloride sustained-release tablet core is 0.2-0.5%.

[0016] Preferably, the coating material in the isolation coating layer is hydroxypropyl methylcellulose. More preferably, the coating material is hydroxypropyl methylcellulose E5.

[0017] Preferably, the coating material in the isolation coating layer accounts for 0.5-3% of the weight of the metformin hydrochloride sustained-release tablet core. More preferably, the coating material in the isolation coating layer accounts for 0.8-2% of the weight of the metformin hydrochloride sustained-release tablet core. Further preferably, the coating material in the isolation coating layer accounts for 1-1.5% of the weight of the metformin hydrochloride sustained-release tablet core.

[0018] Preferably, the dapagliflozin active ingredient in the dapagliflozin immediate-release coating layer is dapagliflozin, a pharmaceutically acceptable salt thereof or dapagliflozin propylene glycol hydrate.

[0019] Preferably, the weight percentage of the active ingredient of dapagliflozin in the metformin hydrochloride sustained-release tablet core is 0.3-1.5%. More preferably, the weight percentage of the active ingredient of dapagliflozin in the metformin hydrochloride sustained-release tablet core is 0.5-1%. Further preferably, the weight percentage of the active ingredient of dapagliflozin in the metformin hydrochloride sustained-release tablet core is 0.6-0.8%.

[0020] Preferably, the first binder in the dapagliflozin immediate-release coating layer is one or more of polyvinyl alcohol or povidone. More preferably, the first binder is povidone K-29 / 32 or polyvinyl alcohol 4-88. Further preferably, the first binder is povidone K-29 / 32.

[0021] Preferably, the weight percentage of the first binder in the metformin hydrochloride sustained-release tablet core is 1-5%. More preferably, the weight percentage of the first binder in the metformin hydrochloride sustained-release tablet core is 1.2-4%. Further preferably, the weight percentage of the first binder in the metformin hydrochloride sustained-release tablet core is 2.5-3%.

[0022] Preferably, the dapagliflozin immediate-release coating layer is further coated with a color coating layer.

[0023] Preferably, the coating material in the color coating layer is Opadry. More preferably, the coating material in the color coating layer is Opadry II Yellow 85G62626.

[0024] Preferably, the coating material in the color coating layer accounts for 0.5-3% of the weight of the metformin hydrochloride sustained-release tablet core. More preferably, the coating material in the color coating layer accounts for 0.8-2% of the weight of the metformin hydrochloride sustained-release tablet core. Further preferably, the coating material in the color coating layer accounts for 1-1.5% of the weight of the metformin hydrochloride sustained-release tablet core.

[0025] Preferably, the dapagliflozin metformin sustained-release tablets are similar to commercially available preparations. The dissolution similarity factor f2 value of dapagliflozin in is greater than 50. More preferably, the dissolution similarity factor f2 value is greater than 55. Further preferably, the dissolution similarity factor f2 value is greater than 60. Further preferably, the dissolution similarity factor f2 value is greater than 65. Further preferably, the dissolution similarity factor f2 value is greater than 70. Most preferably, the dissolution similarity factor f2 value is greater than 75.

[0026] Preferably, the dapagliflozin metformin sustained-release tablet comprises a metformin hydrochloride sustained-release tablet core, the exterior of the sustained-release tablet core is sequentially coated with an isolation coating layer, a dapagliflozin immediate-release coating layer and a color coating layer, the sustained-release tablet core comprises 1000 mg of metformin hydrochloride, 60 mg of povidone K-90, 330 mg of hydroxypropyl methylcellulose K100M and 3 mg of magnesium stearate, the isolation coating layer comprises 20 mg of hydroxypropyl methylcellulose E5, the dapagliflozin immediate-release coating layer comprises 10 mg of dapagliflozin and 20 mg of polyvinyl alcohol 4-88, and the color coating layer comprises 20 mg of Opadry II Yellow 85G62626.

[0027] Preferably, the dapagliflozin metformin sustained-release tablets comprise a metformin hydrochloride sustained-release tablet core, the exterior of the sustained-release tablet core is sequentially coated with an isolation coating layer, a dapagliflozin immediate-release coating layer and a color coating layer, the sustained-release tablet core comprises 1000 mg of metformin hydrochloride, 60 mg of povidone K-90, 330 mg of hydroxypropyl methylcellulose K100M and 3 mg of magnesium stearate, the isolation coating layer comprises 20 mg of hydroxypropyl methylcellulose E5, the dapagliflozin immediate-release coating layer comprises 10 mg of dapagliflozin and 40 mg of polyvinyl alcohol 4-88, and the color coating layer comprises 20 mg of Opadry II Yellow 85G62626.

[0028] Preferably, the dapagliflozin metformin sustained-release tablets comprise a metformin hydrochloride sustained-release tablet core, the exterior of the sustained-release tablet core is sequentially coated with an isolation coating layer, a dapagliflozin immediate-release coating layer and a color coating layer, the sustained-release tablet core comprises 1000 mg of metformin hydrochloride, 60 mg of povidone K-90, 330 mg of hydroxypropyl methylcellulose K100M and 3 mg of magnesium stearate, the isolation coating layer comprises 20 mg of hydroxypropyl methylcellulose E5, the dapagliflozin immediate-release coating layer comprises 10 mg of dapagliflozin and 20 mg of povidone K-29 / 32, and the color coating layer comprises 20 mg of Opadry II Yellow 85G62626.

[0029] Preferably, the dapagliflozin metformin sustained-release tablets contain a metformin hydrochloride sustained-release tablet core, and the exterior of the sustained-release tablet core is sequentially coated with an isolation coating layer, a dapagliflozin immediate-release coating layer and a color coating layer, the sustained-release tablet core contains 1000 mg of metformin hydrochloride, 60 mg of povidone K-90, 330 mg of hydroxypropyl methylcellulose K100M and 3 mg of magnesium stearate, the isolation coating layer contains 20 mg of hydroxypropyl methylcellulose E5, the dapagliflozin immediate-release coating layer contains 10 mg of dapagliflozin and 40 mg of povidone K-29 / 32, and the color coating layer contains 20 mg of Opadry II Yellow 85G62626.

[0030] The second aspect of the present invention provides a method for preparing the above-mentioned dapagliflozin metformin sustained-release tablets, the preparation method comprising the following steps:

[0031] (1) adding metformin hydrochloride, a sustained-release excipient, a second binder and water into a wet granulator to prepare wet granules, adding a lubricant after drying, and tableting after mixing to obtain metformin hydrochloride sustained-release tablet cores;

[0032] (2) adding the isolation layer coating material into water and completely dissolving it to obtain an isolation layer coating solution, and using the isolation layer coating solution to coat the metformin hydrochloride sustained-release tablets obtained in step (1) in a coating pan;

[0033] (3) adding the dapagliflozin active ingredient and the first binder into water and dissolving them to obtain a drug coating solution, and using the drug coating solution to coat the metformin hydrochloride sustained-release tablets coated with the isolation layer obtained in step (2) with the dapagliflozin immediate-release layer in a coating pan to obtain dapagliflozin metformin sustained-release tablets;

[0034] (4) adding the color layer coating material to water to obtain a coating suspension, and using the coating suspension to perform a color layer coating on the dapagliflozin metformin sustained-release tablets obtained in step (3) in a coating pan.

[0035] The third aspect of the present invention provides use of the above-mentioned dapagliflozin metformin sustained-release tablets in the preparation of a medicament for treating diabetes.

[0036] Preferably, the diabetes is type 2 diabetes.

[0037] The fourth aspect of the present invention provides the use of a release modifier in improving the release rate of dapagliflozin in the above-mentioned dapagliflozin metformin sustained-release tablets, wherein the release modifier makes the dapagliflozin metformin sustained-release tablets different from the commercially available preparations. The f2 value of the dissolution similarity factor of dapagliflozin was greater than 50.

[0038] Preferably, the dissolution similarity factor f2 value is greater than 55. More preferably, the dissolution similarity factor f2 value is greater than 60. Further preferably, the dissolution similarity factor f2 value is greater than 65. Further preferably, the dissolution similarity factor f2 value is greater than 70. Most preferably, the dissolution similarity factor f2 value is greater than 75.

[0039] Preferably, the dapagliflozin metformin sustained-release tablets comprise a metformin hydrochloride sustained-release tablet core, the exterior of the sustained-release tablet core is sequentially coated with an isolation coating layer, a dapagliflozin immediate-release coating layer and a color coating layer, the release modifier is the first adhesive in the dapagliflozin immediate-release coating layer, and the first adhesive is one or more of polyvinyl alcohol or povidone.

[0040] Preferably, the first adhesive is povidone K-29 / 32 or polyvinyl alcohol 4-88. More preferably, the first adhesive is povidone K-29 / 32.

[0041] Preferably, the sustained-release tablet core comprises metformin hydrochloride, povidone K-90, hydroxypropyl methylcellulose K100M and magnesium stearate, the isolation coating layer comprises hydroxypropyl methylcellulose E5, the dapagliflozin immediate-release coating layer comprises dapagliflozin and polyvinyl alcohol 4-88 or povidone K-29 / 32, and the color coating layer comprises Opadry.

[0042] Preferably, the sustained-release tablet core contains 1000 mg of metformin hydrochloride, 60 mg of povidone K-90, 330 mg of hydroxypropyl methylcellulose K100M and 3 mg of magnesium stearate, the isolation coating layer contains 20 mg of hydroxypropyl methylcellulose E5, the dapagliflozin immediate-release coating layer contains 10 mg of dapagliflozin and 20 mg of polyvinyl alcohol 4-88, and the color coating layer contains 20 mg of Opadry II Yellow 85G62626.

[0043] Preferably, the sustained-release tablet core contains 1000 mg of metformin hydrochloride, 60 mg of povidone K-90, 330 mg of hydroxypropyl methylcellulose K100M and 3 mg of magnesium stearate, the isolation coating layer contains 20 mg of hydroxypropyl methylcellulose E5, the dapagliflozin immediate-release coating layer contains 10 mg of dapagliflozin and 40 mg of polyvinyl alcohol 4-88, and the color coating layer contains 20 mg of Opadry II Yellow 85G62626.

[0044] Preferably, the sustained-release tablet core contains 1000 mg of metformin hydrochloride, 60 mg of povidone K-90, 330 mg of hydroxypropyl methylcellulose K100M and 3 mg of magnesium stearate, the isolation coating layer contains 20 mg of hydroxypropyl methylcellulose E5, the dapagliflozin immediate-release coating layer contains 10 mg of dapagliflozin and 20 mg of povidone K-29 / 32, and the color coating layer contains 20 mg of Opadry II Yellow 85G62626.

[0045] Preferably, the sustained-release tablet core contains 1000 mg of metformin hydrochloride, 60 mg of povidone K-90, 330 mg of hydroxypropyl methylcellulose K100M and 3 mg of magnesium stearate, the isolation coating layer contains 20 mg of hydroxypropyl methylcellulose E5, the dapagliflozin immediate-release coating layer contains 10 mg of dapagliflozin and 40 mg of povidone K-29 / 32, and the color coating layer contains 20 mg of Opadry II Yellow 85G62626.

[0046] The technical effects produced by the present invention are:

[0047] The dapagliflozin metformin sustained-release tablets of the present invention comprise a metformin hydrochloride sustained-release tablet core, an isolation coating layer, a dapagliflozin immediate-release coating layer and a color coating layer. The present invention optimizes the type of binder in the dapagliflozin immediate-release coating layer to obtain a similar composition to the original commercially available preparation. In addition, the dapagliflozin metformin sustained-release tablets of the present invention have a simple preparation process and are easy to mass produce. DETAILED DESCRIPTION

[0048] The present invention is further described below in conjunction with examples, but the embodiments of the present invention are not limited thereto. The experimental methods used in the following examples are conventional methods unless otherwise specified.

[0049] Test Example 1: In vitro dissolution screening test of dapagliflozin metformin sustained-release tablets with different prescriptions

[0050] 1. Test methods

[0051] 1.1. Preparation of sustained-release tablets

[0052] (1) Prescription

[0053] Table 1 Prescription of Dapagliflozin Metformin Sustained-Release Tablets Examples 1-4 (mg / tablet)

[0054]

[0055] Table 2 Dapagliflozin Metformin Sustained-Release Tablets Comparative Examples 1-3 Prescription (mg / tablet)

[0056]

[0057]

[0058] (2) Preparation process

[0059] Examples 1-4 and Comparative Examples 1-3 were prepared using the following method to obtain dapagliflozin metformin sustained-release tablets.

[0060] Step 1: Preparation of metformin hydrochloride sustained-release tablet core

[0061] Metformin hydrochloride, hydroxypropyl methylcellulose K100M and povidone K-90 in a single tablet prescription amount of 1500 times are added to a wet granulator and stirred evenly, and an appropriate amount of water is added as a granulation solvent, and stirring and cutting are performed at a stirring speed of 200 rpm and a cutting speed of 1800 rpm to prepare wet granules; the wet granules are dried in a fluidized bed at a drying temperature of 50° C. and dried to a moisture content of no more than 2.0%. The dried granules are sieved and crushed, and magnesium stearate in a single tablet prescription amount of 1500 times is added, and mixed at a speed of 20 rpm for 5 minutes to obtain a final mixture; the final mixture is tableted using an elliptical die to obtain a metformin hydrochloride sustained-release tablet core.

[0062] Step 2: Seal Coating

[0063] Hydroxypropyl methylcellulose E5 (1500 times the single tablet prescription amount) was added to 400 g of water and completely dissolved to obtain an isolation layer coating solution. The isolation layer coating solution was used to coat the metformin hydrochloride sustained-release tablets obtained in step 1 in a coating pan.

[0064] Step 3: Dapagliflozin immediate release layer coating

[0065] 1500 times the single-tablet prescription amount of dapagliflozin and a binder (polyvinyl alcohol 4-88 in Examples 1 and 2, povidone K-29 / 32 in Examples 3 and 4, and hydroxypropyl methylcellulose E5 in Comparative Examples 1-3) were added to 4 kg of water and completely dissolved to obtain a drug coating solution. The drug coating solution was used to coat the metformin hydrochloride sustained-release tablets coated with the isolation layer obtained in step 2 in a coating pan with dapagliflozin immediate-release layer to obtain dapagliflozin metformin sustained-release tablets.

[0066] Step 4: Color coating

[0067] Add 1500 times the single-tablet prescription amount of Opadry to 200 g of water and stir thoroughly to obtain a uniform Opadry suspension (Opadry II Yellow 85G62626). Use the Opadry suspension to coat the dapagliflozin metformin sustained-release tablets obtained in step 3 with a color layer in a coating pan to obtain color-coated dapagliflozin metformin sustained-release tablets.

[0068] 1.2. Release determination

[0069] Take the sustained-release tablets prepared in Examples 1-4 and Comparative Examples 1-3 and the reference preparation (trade name: Produced by AstraZeneca Pharmaceuticals LP; Specification: 10 mg / 1000 mg based on dapagliflozin and metformin hydrochloride). According to the dissolution determination method (General Rule 0931 of Part IV of the 2020 edition of the Chinese Pharmacopoeia), a dissolution method I apparatus (basket method) was used with a rotation speed of 100 rpm, pH 6.8 phosphate buffer was used as the release medium, the medium volume was 1000 ml, and the release medium temperature was 37°C ± 0.5°C. The release rate (%) of dapagliflozin was measured at 5, 10, 15, 30 and 45 minutes, and the release rate of each embodiment and comparative example compared with the reference preparation was calculated. The dissolution similarity factor f2.

[0070] 2. Test results

[0071] Table 3 shows the in vitro release data of dapagliflozin in the sustained-release tablets of Examples 1-4 and Comparative Examples 1-3.

[0072] Table 3 In vitro release of dapagliflozin in Examples 1-4 and Comparative Examples 1-3

[0073]

[0074] As can be seen from Table 3 above, the dissolution of dapagliflozin in the sustained-release tablets of Examples 1-4 is similar to that of the reference preparation (f2>50), among which the f2 value of Example 4 and the reference preparation is the highest, indicating that the release rate of dapagliflozin in the sustained-release tablet of Example 4 is closest to that of the reference preparation. In comparison, the f2 values ​​of the sustained-release tablets of Comparative Examples 1-3 and the reference preparation are less than or equal to 30, and the dissolution of dapagliflozin in the comparative examples is significantly slower than that of the reference preparation.

[0075] The above test results show that only by using the polyvinyl alcohol and povidone selected by the present invention as coating adhesives can a dissolution rate similar to that of the reference preparation be obtained, and it is expected that in vivo bioequivalence with the reference preparation can be achieved; while using hydroxypropyl methylcellulose commonly used in the art as a coating adhesive cannot obtain a dissolution rate similar to that of the reference preparation, and cannot achieve bioequivalence with the reference preparation.

[0076] Although specific embodiments of the present invention have been described, it will be appreciated by those skilled in the art that various changes and modifications may be made to the present invention without departing from the scope or spirit of the present invention. Therefore, the present invention is intended to cover all such changes and modifications that fall within the scope of the appended claims and their equivalents.

Claims

1. A dapagliflozin metformin sustained-release tablet, characterized in that: The sustained-release tablet comprises a metformin hydrochloride sustained-release tablet core, and the sustained-release tablet core is sequentially coated with an isolation coating layer and a dapagliflozin immediate-release coating layer, and the dapagliflozin immediate-release coating layer comprises the dapagliflozin active ingredient and a first adhesive, and the first adhesive is not hydroxypropyl methylcellulose.

2. The dapagliflozin metformin sustained-release tablet according to claim 1, characterized in that: The metformin hydrochloride sustained-release tablet core comprises metformin hydrochloride, a sustained-release excipient, a second adhesive and a lubricant.

3. The dapagliflozin metformin sustained-release tablets according to claim 2, characterized in that: The sustained-release excipient in the metformin hydrochloride sustained-release tablet core is one or more of hydroxypropyl methylcellulose, methylcellulose and polyethylene oxide.

4. The dapagliflozin metformin sustained-release tablets according to claim 2, characterized in that: The second binder in the metformin hydrochloride sustained-release tablet core is one or more of povidone, sodium carboxymethyl cellulose, and hydroxypropyl cellulose.

5. The dapagliflozin metformin sustained-release tablet according to claim 1, characterized in that: The coating material in the isolation coating layer is hydroxypropyl methylcellulose.

6. The dapagliflozin metformin sustained-release tablet according to claim 1, characterized in that: The first binder in the dapagliflozin immediate-release coating layer is one or more of polyvinyl alcohol or povidone.

7. The dapagliflozin metformin sustained-release tablet according to claim 1, characterized in that: The dapagliflozin rapid-release coating layer is further coated with a color coating layer.

8. The dapagliflozin metformin sustained-release tablets according to claims 1-7, characterized in that: The dapagliflozin metformin sustained-release tablets and commercially available preparations The dissolution similarity factor f2 value of dapagliflozin was greater than 50.

9. The method for preparing the dapagliflozin metformin sustained-release tablets according to any one of claims 1 to 8, characterized in that: The preparation method comprises the following steps: (1) adding metformin hydrochloride, a sustained-release excipient, a second binder and water into a wet granulator to prepare wet granules, adding a lubricant after drying, and tableting after mixing to obtain metformin hydrochloride sustained-release tablet cores; (2) adding the isolation layer coating material into water and completely dissolving it to obtain an isolation layer coating solution, and using the isolation layer coating solution to coat the metformin hydrochloride sustained-release tablets obtained in step (1) in a coating pan; (3) adding the dapagliflozin active ingredient and the first binder into water and dissolving them to obtain a drug coating solution, and using the drug coating solution to coat the metformin hydrochloride sustained-release tablets coated with the isolation layer obtained in step (2) with the dapagliflozin immediate-release layer in a coating pan to obtain dapagliflozin metformin sustained-release tablets; (4) adding the color layer coating material to water to obtain a coating suspension, and using the coating suspension to perform a color layer coating on the dapagliflozin metformin sustained-release tablets obtained in step (3) in a coating pan.

10. Use of the dapagliflozin metformin sustained-release tablets according to any one of claims 1 to 8 in the preparation of a medicament for treating diabetes.

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