CN-122005473-A - Dapagliflozin tablet and preparation method thereof

Abstract

The application relates to the technical field of pharmaceutical preparations, in particular to a dapagliflozin tablet and a preparation method thereof; the application discloses a dapagliflozin tablet and a preparation method thereof, wherein the dapagliflozin tablet is prepared from 1-5 parts by weight of dapagliflozin, 50-80 parts by weight of filler, 5-15 parts by weight of disintegrating agent, 1-5 parts by weight of adhesive, 0.5-3 parts by weight of stabilizer and 0.5-2 parts by weight of lubricant.

Inventors

• YU ZHIYUAN
• TANG JIAN
• WU QINGGUO
• ZHANG WEI
• DAI QIANG
• ZHANG XIAOMING
• WANG YONGJUN
• LIANG LEI
• CHEN LI
• XUE KAIYUAN
• WANG BIN
• WANG SUYUN

Assignees

• 江苏亚邦爱普森药业有限公司

Dates

Publication Date

20260512

Application Date

20260320

Claims (10)

1. 1. The dapagliflozin tablet is characterized by comprising the following raw materials in parts by weight: 1-5 parts of dapagliflozin; 50-80 parts of filler; 5-15 parts of disintegrating agent; 1-5 parts of adhesive; 0.5-3 parts of stabilizer; 0.5-2 parts of lubricant.
2. 2. A dapagliflozin tablet according to claim 1, wherein said filler comprises mannitol and microcrystalline cellulose.
3. 3. A dapagliflozin tablet according to claim 2, wherein the mass ratio of mannitol to microcrystalline cellulose is (1-3): 1.
4. 4. A dapagliflozin tablet according to claim 1, wherein said disintegrant comprises crospovidone, said binder comprises hypromellose, and said lubricant comprises magnesium stearate.
5. 5. A dapagliflozin tablet according to claim 1, wherein said stabilizer comprises disodium hydrogen phosphate and vitamin E.
6. 6. A dapagliflozin tablet according to claim 5, wherein the mass ratio of disodium hydrogen phosphate to vitamin E is (2-4): 1.
7. 7. A process for preparing a dapagliflozin tablet according to any one of claims 1 to 6, comprising the steps of: (1) Sieving mannitol, microcrystalline cellulose, crospovidone, disodium hydrogen phosphate and vitamin E with 80 mesh sieve respectively for use; (2) Mixing dapagliflozin with 1/2 amount of mannitol and disodium hydrogen phosphate, and performing jet milling to obtain a mixture I; (3) Mixing the mixture I with 1/3 of the amount of the crosslinked povidone and the vitamin E to obtain a mixture II; (4) Mixing the mixture II with 2/3 of crospovidone, 1/2 of mannitol and microcrystalline cellulose to obtain a mixture III; (5) Mixing hydroxypropyl methylcellulose and water to obtain a mixed solution with the mass concentration of 5% -8%, adding the mixture III into the mixed solution, mixing, granulating, drying and sieving; (6) Mixing the sieved particles with magnesium stearate to obtain total mixed particles; (7) Tabletting the total mixed particles to obtain the Gleditsline tablet.
8. 8. The method of claim 7, wherein in the step (2), D 90 of the mixture I is 55-75 μm.
9. 9. The method of claim 7, wherein in the step (2), the pulverizing pressure is 0.6-0.8MPa, the air flow speed is 180-230m/s, the feeding rate is 5-10kg/h, and the pulverizing cavity temperature is less than or equal to 40 ℃.
10. 10. A method for preparing dapagliflozin tablet as claimed in claim 7, wherein: The mixing time in the step (3) is 10-15 minutes; the mixing time in the step (4) is 20-25 minutes; The mixing time in the step (6) is 5-8 minutes; the drying step in the step (5) is as follows, the granules are dried at 45-55 ℃ until the moisture content is 2.0-3.0%.

Description

Dapagliflozin tablet and preparation method thereof Technical Field The application relates to the technical field of pharmaceutical preparations, in particular to a dapagliflozin tablet and a preparation method thereof. Background Dapagliflozin (Dapagliflozin) is an SGLT2 inhibitor for treating diseases such as type 2 diabetes, heart failure and the like, and has the chemical name of (2S, 3R,4R,5S, 6R) -2- [ 4-chloro-3- (4-ethoxybenzyl) phenyl ] -6- (hydroxymethyl) tetrahydro-2H-pyran-3, 4, 5-triol, and the chemical structure is as follows: Dapagliflozin molecules contain a plurality of hydroxyl groups, and are easy to degrade under damp and hot conditions to generate degradation impurities such as dehydration products and oxidation products, so that the stability of the preparation is reduced, the drug effect is influenced, and the safety risk is possibly increased. The conventional dapagliflozin tablet, such as a raw ground product, mostly adopts conventional auxiliary materials, such as microcrystalline cellulose only as a filler, no specific stabilizer is adopted, and after the dapagliflozin tablet is stored for 6 months under the acceleration condition of 40 ℃ and 75% RH, the content of related substances can exceed 0.5%, the pharmacopoeia limit is not met, and the stability still needs to be improved. In addition, dapagliflozin has low solubility, the solubility in water is about 1.0mg/mL, and conventional tablets may have the problem of low dissolution, which affects bioavailability. Therefore, there is a need to develop dapagliflozin tablets with high stability and good dissolution. Disclosure of Invention Aiming at the defects of poor stability, easily exceeding related substances and uneven dissolution of the conventional dapagliflozin tablet, the application provides the dapagliflozin tablet and the preparation method thereof, and the prepared dapagliflozin tablet can remarkably improve the stability of dapagliflozin, reduce the generation of related substances in the storage process and improve the dissolution of medicines. The application discloses a dapagliflozin tablet and a preparation method thereof, which have similar dissolution characteristics as those of the original preparation in vitro, and have better uniformity than the original preparation, no remarkable increase of related substances of the preparation, good stability, simple preparation process and suitability for large-scale low-cost production and application. In a first aspect, the present application provides a dapagliflozin tablet, which adopts the following technical scheme: The dapagliflozin tablet comprises the following raw materials in parts by weight: 1-5 parts of dapagliflozin; 50-80 parts of filler; 5-15 parts of disintegrating agent; 1-5 parts of adhesive; 0.5-3 parts of stabilizer; 0.5-2 parts of lubricant. Preferably, the filler comprises mannitol and microcrystalline cellulose. Preferably, the mass ratio of mannitol to microcrystalline cellulose is (1-3): 1. By adopting the technical scheme, the dissolution performance of the tablet can be improved by adding mannitol, the formability of the tablet can be enhanced by adding microcrystalline cellulose, and both dissolution and forming can be combined. Preferably, the disintegrant comprises crospovidone. By adopting the technical scheme, the added crospovidone has strong disintegrating capability, is insoluble in water, can effectively disperse the raw materials and avoid agglomeration. Preferably, the binder comprises hypromellose. By adopting the technical scheme, the hydroxypropyl methylcellulose is used as the adhesive, the viscosity is moderate, a stable particle structure can be formed, and the dissolution of the bulk drug is not influenced. Preferably, the stabilizer comprises disodium hydrogen phosphate and vitamin E. Preferably, the mass ratio of the disodium hydrogen phosphate to the vitamin E is (2-4): 1. By adopting the technical scheme, the added disodium hydrogen phosphate can adjust the ionic strength of the preparation, shield the surface charge of molecules, reduce aggregation and maintain stable crystal forms, can complex metal ions introduced by raw materials or production equipment, eliminate metal catalysis, effectively reduce the growth of related substances, and the added vitamin E can resist oxidation, prevent the oxidative degradation of the raw materials and cooperatively improve the stability. Preferably, the lubricant comprises magnesium stearate. By adopting the technical scheme, the lubricant is added, so that the friction between particles and equipment can be reduced, the hardness uniformity of the tablet is improved, and the dissolution is prevented from being influenced by excessive amount. In a second aspect, the application provides a preparation method of dapagliflozin tablets, which adopts the following technical scheme: A method for preparing dapagliflozin tablets, comprising the following steps: (1) Sieving mannitol, microcry