A multi-tinoretic acid oral tablet and a preparation method thereof

Abstract

This invention provides a dotenoroxetine oral tablet and its preparation method. The oral tablet uses hydroxypropyl methylcellulose and polyethylene glycol as a composite binder, sodium carboxymethyl starch and low-substituted hydroxypropyl cellulose as disintegrants, and optimizes the ratio of key excipients and adopts a preparation method combining wet granulation and fluidized bed drying. This improves the in vitro release of dotenoroxetine tablets, and while not affecting the rapid dissolution of the active pharmaceutical ingredient, it has good hydrothermal stability, significantly improves drug stability and content uniformity, and is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a dotenoxanil oral tablet and its preparation method. Background Technology

[0002] Dotinurad is a highly selective URAT1 inhibitor, chemically named (3,5-dichloro-4-hydroxyphenyl)(1,1-dioxo-1,2-dihydro-3H-1λ). 6 -1,3-benzothiazol-3-yl) works by inhibiting the reabsorption of uric acid in the proximal convoluted tubule of the kidney and promoting uric acid excretion. It is used for gout with hyperuricemia and is also suitable for patients with asymptomatic hyperuricemia.

[0003] Patent CN 120305210A discloses a highly efficient dissolution dotenoradine tablet and its preparation method. The tablet is composed of 5-20 parts of dotenoradine active ingredient, 10-30 parts of disintegrant, 40-70 parts of filler, 0.5-5 parts of surfactant, 0.5-3 parts of lubricant, 1-5 parts of binder, and 0.5-1 parts of antioxidant. However, it cannot solve the problem of the growth of related substances under humid and hot conditions. Furthermore, because the required process requires the micronization of intermediate particles, the intermediates in the product have poor flowability. This can lead to insufficient filling during the tableting process, thus affecting the tablet weight and product content, and consequently affecting product quality.

[0004] Patent CN120732799A discloses an oral solid dosage form for treating gout and its preparation method. The method involves sieving a filler, disintegrant, binder, and dotenoradine to obtain a sieved material; mixing the sieved material with a lubricant and then compressing it into tablets to obtain an oral solid dosage form for treating gout. The filler is lactose, mannitol, and microcrystalline cellulose; the binder includes one or more of polyvinylpyrrolidone, hydroxypropyl cellulose, and hydroxypropyl methylcellulose. The prepared tablets can improve the drug's dissolution and bioavailability, thereby improving efficacy, but the problem of related substance growth under humid and hot conditions is not solved. Summary of the Invention

[0005] The purpose of this invention is to provide a dotenoradine oral tablet based on existing technology, using hydroxypropyl methylcellulose and polyethylene glycol as a composite binder, sodium carboxymethyl starch and low-substituted hydroxypropyl cellulose as disintegrants, and optimizing the ratio of key excipients and adopting a preparation method combining wet granulation and fluidized bed drying, which improves the in vitro release of dotenoradine tablets, while not affecting the rapid dissolution of the active pharmaceutical ingredient, and has good hydrothermal stability, significantly improving drug stability and content uniformity, making it suitable for industrial production.

[0006] A second objective of this invention is to provide a method for preparing the above-mentioned dotenoradine oral tablets.

[0007] The technical solution of the present invention is as follows: A dotenoroxetine oral tablet, comprising the following components in parts by weight: 0.5-2 parts dotenoroxetine, 80-100 parts microcrystalline cellulose, 40-60 parts lactose, 20-30 parts mannitol, 5-20 parts sodium carboxymethyl starch, 2-10 parts low-substituted hydroxypropyl cellulose, 4-12 parts hydroxypropyl methylcellulose, 1-10 parts polyethylene glycol, 0.3-1.5 parts sodium dodecyl sulfate, and 1-3 parts magnesium stearate; wherein the molecular weight of polyethylene glycol is 200-2000.

[0008] In this invention, the active ingredient is dotenorazole, and the excipients include a composite filler, a composite disintegrant, a composite binder, a surfactant, and a lubricant. The composite filler consists of microcrystalline cellulose, lactose, and mannitol; the composite disintegrant is sodium carboxymethyl starch and low-substituted hydroxypropyl cellulose, wherein sodium carboxymethyl starch is an internal disintegrant and low-substituted hydroxypropyl cellulose is an external disintegrant. The composite binder consists of hydroxypropyl methylcellulose and polyethylene glycol. The surfactant is sodium dodecyl sulfate. The lubricant is magnesium stearate.

[0009] In this invention, hydroxypropyl methylcellulose and polyethylene glycol are used as composite adhesives. Hydroxypropyl methylcellulose provides the adhesive effect, while polyethylene glycol with a lower molecular weight provides certain adhesion and good film-forming properties, effectively improving the stability of the active pharmaceutical ingredient and the compressibility of intermediate particles, without affecting the rapid release of the active ingredient.

[0010] In this invention, the active ingredient dotenoramide is pulverized using micronization technology, and the particle size D90 of dotenoramide is controlled to be ≤20μm during pulverization.

[0011] In this invention, microcrystalline cellulose, lactose, and mannitol are used as composite fillers, wherein the mass ratio of lactose to mannitol is 1-3:1; preferably, the mass ratio of lactose to mannitol is 1.5-2.5:1; more preferably, the mass ratio of lactose to mannitol is 2:1.

[0012] In this invention, sodium carboxymethyl starch and low-substituted hydroxypropyl cellulose are used as a composite disintegrant, wherein sodium carboxymethyl starch is an internal disintegrant and low-substituted hydroxypropyl cellulose is an external disintegrant. The mass ratio of sodium carboxymethyl starch to low-substituted hydroxypropyl cellulose is 1-3:1; preferably, the mass ratio is 1.5-2.5:1; more preferably, the mass ratio is 2:1.

[0013] In this invention, hydroxypropyl methylcellulose and polyethylene glycol are used as composite adhesives, wherein the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol is 1:0.1-1.2; preferably, the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol is 1:0.25-1.

[0014] For the purposes of this invention, the polyethylene glycol is a polyethylene glycol with a lower molecular weight, ranging from 200 to 1500; preferably, the molecular weight of the polyethylene glycol is 400 to 1000.

[0015] The oral tablets of dotenoroxetine provided by this invention are prepared by first dissolving hydroxypropyl methylcellulose, polyethylene glycol and sodium dodecyl sulfate in purified water to form a binder solution, then mixing it with dotenoroxetine, microcrystalline cellulose, lactose, mannitol and sodium carboxymethyl starch for granulation, drying, granulation, and then mixing it with low-substituted hydroxypropyl cellulose and magnesium stearate, and compressing it into tablets to obtain oral tablets.

[0016] In a preferred embodiment, the dotenoroxetine oral tablets provided by the present invention are made from the following components in parts by weight: 0.5-1.5 parts dotenoroxetine, 85-95 parts microcrystalline cellulose, 45-55 parts lactose, 22-28 parts mannitol, 8-15 parts sodium carboxymethyl starch, 4-8 parts low-substituted hydroxypropyl cellulose, 6-10 parts hydroxypropyl methylcellulose, 2-8 parts polyethylene glycol, 0.8-1.2 parts sodium dodecyl sulfate, and 1.5-2.5 parts magnesium stearate; wherein the mass ratio of lactose to mannitol is 1-3:1; the mass ratio of sodium carboxymethyl starch to low-substituted hydroxypropyl cellulose is 1-3:1; the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol is 1:0.1-1.2; and the molecular weight of polyethylene glycol is 400-1500.

[0017] In a preferred embodiment, the dotenoroxetine oral tablets provided by the present invention are made from the following components in parts by weight: 0.8-1.2 parts dotenoroxetine, 87-93 parts microcrystalline cellulose, 49-51 parts lactose, 24-26 parts mannitol, 11-13 parts sodium carboxymethyl starch, 5-7 parts low-substituted hydroxypropyl cellulose, 7-9 parts hydroxypropyl methylcellulose, 2-8 parts polyethylene glycol, 0.9-1.1 parts sodium dodecyl sulfate, and 1.9-2.1 parts magnesium stearate; wherein the mass ratio of lactose to mannitol is 1.5-2.5:1; the mass ratio of sodium carboxymethyl starch to low-substituted hydroxypropyl cellulose is 1.5-2.5:1; the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol is 1:0.25-1; and the molecular weight of polyethylene glycol is 400-1000.

[0018] For example, the dotenoroxetine oral tablets provided by the present invention are made from the following components in parts by weight: 1 part dotenoroxetine, 91 parts microcrystalline cellulose, 50 parts lactose, 25 parts mannitol, 12 parts sodium carboxymethyl starch, 6 parts low-substituted hydroxypropyl cellulose, 8 parts hydroxypropyl methylcellulose, 4 parts polyethylene glycol 400, 1 part sodium dodecyl sulfate, and 2 parts magnesium stearate; wherein the mass ratio of lactose to mannitol is 2:1; the mass ratio of sodium carboxymethyl starch to low-substituted hydroxypropyl cellulose is 2:1; and the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol 400 is 1:0.5.

[0019] For example, the dotenoroxetine oral tablets provided by the present invention are made from the following components in parts by weight: 1 part dotenoroxetine, 87 parts microcrystalline cellulose, 50 parts lactose, 25 parts mannitol, 12 parts sodium carboxymethyl starch, 6 parts low-substituted hydroxypropyl cellulose, 8 parts hydroxypropyl methylcellulose, 8 parts polyethylene glycol 400, 1 part sodium dodecyl sulfate, and 2 parts magnesium stearate; wherein the mass ratio of lactose to mannitol is 2:1; the mass ratio of sodium carboxymethyl starch to low-substituted hydroxypropyl cellulose is 2:1; and the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol 400 is 1:1.

[0020] For example, the dotenoroxetine oral tablets provided by the present invention are made from the following components in parts by weight: 1 part dotenoroxetine, 93 parts microcrystalline cellulose, 50 parts lactose, 25 parts mannitol, 12 parts sodium carboxymethyl starch, 6 parts low-substituted hydroxypropyl cellulose, 8 parts hydroxypropyl methylcellulose, 2 parts polyethylene glycol 400, 1 part sodium dodecyl sulfate, and 2 parts magnesium stearate; wherein the mass ratio of lactose to mannitol is 2:1; the mass ratio of sodium carboxymethyl starch to low-substituted hydroxypropyl cellulose is 2:1; and the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol 400 is 1:0.25.

[0021] For example, the dotenoroxetine oral tablets provided by the present invention are made from the following components in parts by weight: 1 part dotenoroxetine, 91 parts microcrystalline cellulose, 50 parts lactose, 25 parts mannitol, 12 parts sodium carboxymethyl starch, 6 parts low-substituted hydroxypropyl cellulose, 8 parts hydroxypropyl methylcellulose, 4 parts polyethylene glycol 1000, 1 part sodium dodecyl sulfate, and 2 parts magnesium stearate; wherein the mass ratio of lactose to mannitol is 2:1; the mass ratio of sodium carboxymethyl starch to low-substituted hydroxypropyl cellulose is 2:1; and the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol 1000 is 1:0.5.

[0022] The method for preparing dotenoxetine oral tablets provided by the present invention includes the following steps: (1) The active ingredient dotenoroxetine was pulverized using micronization technology, and the excipients were sieved and set aside for later use; (2) Preparation of adhesive solution: Hydroxypropyl methylcellulose, polyethylene glycol and sodium dodecyl sulfate are dissolved in purified water and stirred evenly to prepare adhesive solution; (3) Granulation, tableting and coating: Mix the pulverized dotenorphine, microcrystalline cellulose, lactose, mannitol and sodium carboxymethyl starch evenly, slowly add it to the binder solution to make soft material, granulate, transfer the obtained wet granules to a fluidized bed for drying, then granulate, and then mix with low-substituted hydroxypropyl cellulose and magnesium stearate, and compress to obtain oral tablets.

[0023] In step (1), the active ingredient dotenoramide is pulverized using micronization technology, and the particle size D90 of dotenoramide is controlled to be ≤20μm during pulverization. The excipients are passed through a 20-40 mesh sieve, preferably a 30 mesh sieve.

[0024] In step (3), granulation is performed using a 15-25 mesh sieve, preferably a 20 mesh sieve; granulation is performed using a 20-30 mesh sieve, preferably a 24 mesh sieve.

[0025] In step (3), during fluidized bed drying, the inlet air temperature is controlled at 55-65℃ and the particle moisture content is controlled at 2.0-3.5%.

[0026] The advantages of using the technical solution of this invention are as follows: This invention provides a dotenoradine oral tablet using hydroxypropyl methylcellulose and polyethylene glycol as a composite binder, sodium carboxymethyl starch and low-substituted hydroxypropyl cellulose as disintegrants, and optimizes the ratio of key excipients and adopts a preparation method combining wet granulation and fluidized bed drying. This improves the in vitro release of dotenoradine tablets, and while not affecting the rapid dissolution of the active pharmaceutical ingredient, it also has good hydrothermal stability, significantly improving drug stability and content uniformity, making it suitable for industrial production.

[0027] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0028] Examples 1-4 A dotenoroxetine oral tablet is made from the following components in parts by weight, as shown in Table 1.

[0029]

[0030] The method for preparing the oral tablets in Example 1 includes the following steps: (1) The active ingredient dotenorolac is pulverized using micronization technology, and the particle size D90 of dotenorolac is controlled to be ≤20μm. The excipients are then passed through a 30-mesh sieve for later use. (2) Preparation of adhesive solution: Hydroxypropyl methylcellulose, polyethylene glycol 400 and sodium dodecyl sulfate were dissolved in purified water and stirred evenly to prepare adhesive solution; (3) Granulation, tableting and coating: Mix the pulverized dotenorphine, microcrystalline cellulose, lactose, mannitol and sodium carboxymethyl starch evenly, slowly add to the binder solution to make soft material, granulate through a 20-mesh sieve, transfer the obtained wet granules to a fluidized bed for drying, control the inlet air temperature to 55-65℃, control the granule moisture to 2.0-3.5%, then granulate through a 24-mesh sieve, mix with low-substituted hydroxypropyl cellulose and magnesium stearate, and compress to obtain oral tablets.

[0031] The tablets in Examples 2-3 were prepared in the same way as in Example 1. The difference between Example 4 and Example 1 is that polyethylene glycol 400 was replaced with polyethylene glycol 1000.

[0032] Comparative Example 1 Dotenorazole tablets were prepared according to the formulation and preparation method in Example 1 of patent CN 120305210 A.

[0033] Comparative Example 2 Dotenorazole tablets were prepared according to the formulation and preparation method in Example 1 of patent CN 120732799 A.

[0034] Comparative Examples 3-7 A dotenoroxetine oral tablet is made from the following components in parts by weight, as shown in Table 2.

[0035]

[0036] The preparation method of the oral tablets in Comparative Example 3 includes the following steps: (1) The active ingredient dotenorolac is pulverized using micronization technology, and the particle size D90 of dotenorolac is controlled to be ≤20μm. The excipients are then passed through a 30-mesh sieve for later use. (2) Preparation of adhesive solution: Hydroxypropyl methylcellulose and sodium dodecyl sulfate are dissolved in purified water and stirred evenly to prepare adhesive solution; (3) Granulation, tableting and coating: Mix the pulverized dotenorphine, microcrystalline cellulose, lactose, mannitol and sodium carboxymethyl starch evenly, slowly add to the binder solution to make soft material, granulate through a 20-mesh sieve, transfer the obtained wet granules to a fluidized bed for drying, control the inlet air temperature to 55-65℃, control the granule moisture to 2.0-3.5%, then granulate through a 24-mesh sieve, mix with low-substituted hydroxypropyl cellulose and magnesium stearate, and compress to obtain oral tablets.

[0037] The tablets in Examples 2-3 were prepared in the same way as in Example 1. The difference between Example 4 and Example 1 is that polyethylene glycol 400 was replaced with polyethylene glycol 1000.

[0038] The tablet preparation method in Comparative Example 4 was the same as that in Example 1; the difference between Comparative Example 5 and Example 1 was that polyethylene glycol 400 was replaced with polyethylene glycol 3350; the difference between Comparative Example 6 and Example 1 was that polyethylene glycol 400 was replaced with povidone; the difference between Comparative Example 7 and Example 1 was that sodium carboxymethyl starch was replaced with croscarmellose sodium.

[0039] Effect verification 1. The angle of repose of the particles in the examples and comparative examples before tableting was investigated (refer to the Chinese Pharmacopoeia 2025, Part IV, General Chapter 9604, Powder Flowability Guidelines for Determination). The flowability of the samples was measured, as shown in Table 3.

[0040]

[0041] As shown in Table 3, except for Comparative Example 1, the other samples have good flowability and no significant difference. This is because the particles in Comparative Example 1 need to be micronized, resulting in smaller particles that affect the flowability of the product. However, this does not have a significant impact on the intermediate particles.

[0042] 2. Dissolution test The experiment was conducted in pH 5.5 acetate buffer (900 ml, 37℃±0.5℃) and pH 6.8 phosphate buffer media. The dissolution test method II (paddle method) of the Chinese Pharmacopoeia 2025 edition was adopted. The rotation speed was 50 rpm and after 45 min, the sample was filtered through a 0.45 μm filter membrane and the content of dotenoradine was determined by HPLC. The details are shown in Table 4.

[0043]

[0044] As shown in Table 4, in Examples 1-4, when the polyethylene glycol (PEG) in the composite adhesive was 400 or 1000, controlling the amount of PEG 400 or PEG 1000 resulted in faster release of dotenoradine tablets in phosphate media at pH 4.5 and media at pH 6.8. In Comparative Example 4, the amount of PEG 400 in the composite adhesive was too high, affecting the release of the sample and resulting in slower release. In Comparative Example 5, the PEG in the composite adhesive was 3350, which had a higher adhesive effect, affecting the release of dotenoradine tablets. In Comparative Example 7, the disintegrant was cross-linked sodium carboxymethyl cellulose, which had a worse disintegrant effect than sodium carboxymethyl starch under the same dosage conditions, thus affecting the release of dotenoradine tablets.

[0045] 3. Accelerated stability test The samples from the examples and comparative examples were packaged in aluminum-plastic blister packs at 40℃±2℃ / 75%RH±5% for 0, 1, 3, and 6 months. The specific test data are shown in Table 5.

[0046]

[0047] As shown in Table 5, in Examples 1-4, the samples using hydroxypropyl methylcellulose and polyethylene glycol 400 or 1000 as composite binders exhibited relatively small increases in related substances and good stability, indicating that the composite binder of the present invention can significantly improve product stability. Compared to Examples 1-4, the samples in Comparative Examples 1 and 2 showed relatively large increases in related substances and poor stability. In Comparative Example 3, only hydroxypropyl methylcellulose was used as a binder, which did not have a good film-forming effect, resulting in a relatively large increase in related substances and poor stability.

[0048] In Comparative Example 4, the amount of polyethylene glycol 400 used in the composite adhesive was too high. In Comparative Example 5, the polyethylene glycol used in the composite adhesive was 3350. Polyethylene glycol 3350 has a higher molecular weight and better adhesion. Although the higher amount of polyethylene glycol 400 and the higher molecular weight of polyethylene glycol 3350 significantly improved stability, they significantly affected the release rate of dotenorazole tablets.

[0049] In Comparative Example 6, hydroxypropyl methylcellulose and povidone were used as binders, which also did not have a good film-forming effect, resulting in a relatively large increase in related substances and poor stability.

[0050] The oral tablets of this invention are uncoated tablets, which are not protected by a coating layer. The products are more susceptible to the effects of moisture and heat. When the single binder or composite binder is povidone, it does not have a good film-forming effect and cannot provide further protection for the raw materials, resulting in poor tablet stability.

[0051] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications may still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions may be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A polythienoisoindoline oral tablet, characterized by, The tablet is made from the following components in parts by weight: 0.5-2 parts dotenoradine, 80-100 parts microcrystalline cellulose, 40-60 parts lactose, 20-30 parts mannitol, 5-20 parts sodium carboxymethyl starch, 2-10 parts low-substituted hydroxypropyl cellulose, 4-12 parts hydroxypropyl methylcellulose, 1-10 parts polyethylene glycol, 0.3-1.5 parts sodium dodecyl sulfate, and 1-3 parts magnesium stearate; wherein the molecular weight of the polyethylene glycol is 200-2000.

2. The oral tablet of doranid according to claim 1, characterized in that, The particle size D90 of the dotenorazole is ≤20μm; the mass ratio of lactose to mannitol is 1-3:1, preferably 1.5-2.5:1, more preferably 2:1; the mass ratio of sodium carboxymethyl starch to low-substituted hydroxypropyl cellulose is 1-3:1, preferably 1.5-2.5:1, more preferably 2:1; the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol is 1:0.1-1.2, preferably 1:0.25-1; the molecular weight of the polyethylene glycol is 400-1500, preferably 400-1000.

3. The oral tablet of doranid according to claim 2, characterized in that, In its preparation process, hydroxypropyl methylcellulose, polyethylene glycol and sodium dodecyl sulfate are first dissolved in purified water to prepare a binder solution. Then, it is mixed with dotenorfat, microcrystalline cellulose, lactose, mannitol and sodium carboxymethyl starch for granulation, drying, granulation, and then mixed with low-substituted hydroxypropyl cellulose and magnesium stearate, and compressed into tablets to obtain oral tablets.

4. The oral tablet of doranid according to claim 3, characterized in that, The tablet is made from the following components in parts by weight: 0.5-1.5 parts dotenorazole, 85-95 parts microcrystalline cellulose, 45-55 parts lactose, 22-28 parts mannitol, 8-15 parts sodium carboxymethyl starch, 4-8 parts low-substituted hydroxypropyl cellulose, 6-10 parts hydroxypropyl methylcellulose, 2-8 parts polyethylene glycol, 0.8-1.2 parts sodium dodecyl sulfate, and 1.5-2.5 parts magnesium stearate; wherein the mass ratio of lactose to mannitol is 1-3:1; the mass ratio of sodium carboxymethyl starch to low-substituted hydroxypropyl cellulose is 1-3:1; the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol is 1:0.1-1.2; and the molecular weight of polyethylene glycol is 400-1500.

5. The oral tablet of doranid according to claim 4, characterized in that, The tablet is made from the following components in parts by weight: 0.8-1.2 parts dotenoradine, 87-93 parts microcrystalline cellulose, 49-51 parts lactose, 24-26 parts mannitol, 11-13 parts sodium carboxymethyl starch, 5-7 parts low-substituted hydroxypropyl cellulose, 7-9 parts hydroxypropyl methylcellulose, 2-8 parts polyethylene glycol, 0.9-1.1 parts sodium dodecyl sulfate, and 1.9-2.1 parts magnesium stearate; wherein the mass ratio of lactose to mannitol is 1.5-2.5:1; the mass ratio of sodium carboxymethyl starch to low-substituted hydroxypropyl cellulose is 1.5-2.5:1; the mass ratio of hydroxypropyl methylcellulose to polyethylene glycol is 1:0.25-1; and the molecular weight of polyethylene glycol is 400-1000.

6. The oral tablet of doranid according to claim 5, characterized in that, This tablet is made from the following components in parts by weight: Dotenoride 1 part, microcrystalline cellulose 91 parts, lactose 50 parts, mannitol 25 parts, sodium carboxymethyl starch 12 parts, low-substituted hydroxypropyl cellulose 6 parts, hydroxypropyl methylcellulose 8 parts, polyethylene glycol 400 4 parts, sodium dodecyl sulfate 1 part, magnesium stearate 2 parts. Dotenoride 1 part, microcrystalline cellulose 87 parts, lactose 50 parts, mannitol 25 parts, sodium carboxymethyl starch 12 parts, low-substituted hydroxypropyl cellulose 6 parts, hydroxypropyl methylcellulose 8 parts, polyethylene glycol 400 8 parts, sodium dodecyl sulfate 1 part, magnesium stearate 2 parts. Dotenoride 1 part, microcrystalline cellulose 93 parts, lactose 50 parts, mannitol 25 parts, sodium carboxymethyl starch 12 parts, low-substituted hydroxypropyl cellulose 6 parts, hydroxypropyl methylcellulose 8 parts, polyethylene glycol 400 2 parts, sodium dodecyl sulfate 1 part, magnesium stearate 2 parts. Dotenoramide 1 part, microcrystalline cellulose 91 parts, lactose 50 parts, mannitol 25 parts, sodium carboxymethyl starch 12 parts, low-substituted hydroxypropyl cellulose 6 parts, hydroxypropyl methylcellulose 8 parts, polyethylene glycol 1000 4 parts, sodium dodecyl sulfate 1 part, magnesium stearate 2 parts.

7. The method of preparing the oral tablet of doranid as claimed in claim 1, characterized in that, Includes the following steps: (1) The active ingredient dotenoroxetine was pulverized using micronization technology, and the excipients were sieved and set aside for later use; (2) Preparation of adhesive solution: Hydroxypropyl methylcellulose, polyethylene glycol and sodium dodecyl sulfate are dissolved in purified water and stirred evenly to prepare adhesive solution; (3) Granulation, tableting and coating: Mix the pulverized dotenorphine, microcrystalline cellulose, lactose, mannitol and sodium carboxymethyl starch evenly, slowly add it to the binder solution to make soft material, granulate, transfer the obtained wet granules to a fluidized bed for drying, then granulate, and then mix with low-substituted hydroxypropyl cellulose and magnesium stearate, and compress to obtain oral tablets.

8. The method for preparing dotenorazole oral tablets according to claim 7, characterized in that, In step (1), the particle size D90 of dotenoroxetine is controlled to be ≤20μm during pulverization; the excipients are passed through a 20-40 mesh sieve, preferably a 30 mesh sieve.

9. The method for preparing dotenorazole oral tablets according to claim 7, characterized in that, In step (3), granulation is performed using a 15-25 mesh sieve, preferably a 20 mesh sieve; granulation is performed using a 20-30 mesh sieve, preferably a 24 mesh sieve.

10. The method for preparing dotenoradine oral tablets according to claim 7, characterized in that, In step (3), during fluidized bed drying, the inlet air temperature is controlled at 55-65℃ and the particle moisture content is controlled at 2.0-3.5%.

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