Remegapam sulfate orally disintegrating tablet and preparation method thereof

Abstract

The invention provides a remegapam sulfate orally disintegrating tablet and a preparation method thereof, and the remegapam sulfate orally disintegrating tablet is prepared from an active component remegapam sulfate orally disintegrating tablet, a filler mannitol and microcrystalline cellulose, a disintegrating agent polyvinylpolypyrrolidone, an adhesive low-substituted hydroxypropyl cellulose, a flavoring agent sucralose and a lubricant magnesium stearate. The problems of poor material flowability, sticking, easy cracking during tabletting and the like during tabletting are solved, the tablet has the advantages of rapid disintegration, rapid dissolution, better compressibility, better stability, good taste, simple preparation method and the like, is more suitable for patients with dysphagia, especially the old and children, has great clinical significance, and is worthy of popularization and application. The method is suitable for large-scale industrial production.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicine preparation, and particularly relates to a rimegepant sulfate orally disintegrating tablet and a preparation method thereof. BACKGROUND

[0002] Migraine is the third most common disease in the world, and is a periodic disease. A series of complex symptoms will occur when each headache attack occurs. As a rimegepant sulfate for treating migraine, it is a calcitonin gene-related peptide (CGRP) receptor antagonist, which can effectively block the effect of CGRP in the central nervous system, and is suitable for acute treatment of migraine with or without aura in adults, and prophylactic treatment of episodic migraine.

[0003] The rimegepant sulfate orally disintegrating tablet was first marketed in the United States in February 2020, and the trade name is ODT, which is used for acute treatment of migraine in adults, and the indication was expanded to prophylactic treatment of episodic migraine in adults in May 2021. The existing patents CN114010608A and CN118662463A are both freeze-dried orally disintegrating tablets, which can disintegrate quickly, but the orally disintegrating tablets have poor mechanical strength, so that the tablets are easy to break and have poor folding resistance, and therefore there is a possibility of fragmentation during production and transportation. The freeze-drying machine used for the freeze-drying orally disintegrating tablets has high energy consumption, long production cycle, and high cost per tablet.

[0004] The solid preparation prepared by the existing patents CN112153969A and CN118340731A solves the problems of tablet breakage and poor folding resistance, but the ordinary tablets prepared by the preparation method have the defects of slow drug release, difficulty in oral swallowing, and the like, and are not suitable for acute treatment of migraine. Meanwhile, the preparation method of CN118340731A is complex, and high-shear dispersion of the raw material drug is required, which not only changes the particle size of the raw material drug, but also causes problems such as uneven mixing due to the dry direct compression process. The fast-dispersing tablets prepared by the preparation method provided by the patents CN112153969A and CN115335051A have the disadvantages of easy moisture absorption, poor stability, complex process, and high production cost, and are not suitable for industrial production. The solid preparation orally dissolving film prepared by the patent CN117414352A has good toughness and no irritating taste, but the production process of the orally dissolving film is complex, special materials and equipment are required, the production cost is high, and the economic burden of patients is increased. SUMMARY

[0005] The present application aims to provide a remegel sulfate orally disintegrating tablet, which is made of active ingredient remegel sulfate orally disintegrating tablet, filler mannitol and microcrystalline cellulose, disintegrating agent cross-linked polyvinylpyrrolidone, adhesive low-substituted hydroxypropyl cellulose, flavoring agent sucralose and lubricant magnesium stearate, solves the problems of poor material flowability, sticking, and tablet cracking during tabletting, has the advantages of rapid disintegration, rapid dissolution, good compressibility, good stability, good taste, simple preparation method, etc., is more suitable for patients with difficulty in swallowing, especially the elderly and children, has great clinical significance, and is suitable for large-scale industrial production.

[0006] The second object of the present application is to provide a preparation method of the remegel sulfate orally disintegrating tablet.

[0007] The technical scheme of the present application is as follows:

[0008] The remegel sulfate orally disintegrating tablet is made of remegel sulfate, a filler, a disintegrating agent, an adhesive, a flavoring agent and a lubricant, wherein the filler is mannitol and microcrystalline cellulose, the disintegrating agent is cross-linked polyvinylpyrrolidone, the adhesive is low-substituted hydroxypropyl cellulose, the flavoring agent is sucralose, and the lubricant is magnesium stearate, and the remegel sulfate orally disintegrating tablet is made of the following components by weight: 60-90 parts of remegel sulfate, 35-80 parts of mannitol, 35-80 parts of microcrystalline cellulose, 3-20 parts of cross-linked polyvinylpyrrolidone, 8-30 parts of low-substituted hydroxypropyl cellulose, 1-5 parts of sucralose, and 1-5 parts of magnesium stearate.

[0009] In the preparation process of the remegel sulfate orally disintegrating tablet, the microcrystalline cellulose, the cross-linked polyvinylpyrrolidone and the sucralose are uniformly mixed, a drug-containing solution made of low-substituted hydroxypropyl cellulose, remegel sulfate and purified water is added for granulation, the obtained wet granules are dried, mixed with mannitol and magnesium stearate after granulation, and then tabletted to obtain the orally disintegrating tablet.

[0010] In the present application, the remegel sulfate is micronized, and after the micronization treatment, the particle size of the remegel sulfate is D 90 ≤10 μm, D 50 ≤8 μm, D 10 ≤5 μm; preferably, D 90 ≤8 μm, D 50 ≤5 μm, D 10 ≤3 μm; more preferably, D 90 ≤5 μm, D 50 ≤3 μm, D 10 ≤1 μm.

[0011] In a preferred embodiment, the orally disintegrating tablet of rimexolane sulfate provided by the present application is made from the following components in parts by weight: rimexolane sulfate 70-80 parts, mannitol 45-75 parts, microcrystalline cellulose 45-75 parts, crospovidone 5-15 parts, low-substituted hydroxypropyl cellulose 10-25 parts, sucralose 1.5-3.5 parts, and magnesium stearate 1.5-3.5 parts.

[0012] In a more preferred embodiment, the orally disintegrating tablet of rimexolane sulfate provided by the present application is made from the following components in parts by weight: rimexolane sulfate 75 parts, mannitol 45-75 parts, microcrystalline cellulose 45-75 parts, crospovidone 5-15 parts, low-substituted hydroxypropyl cellulose 10-25 parts, sucralose 2 parts, and magnesium stearate 2 parts.

[0013] For example, the orally disintegrating tablet of rimexolane sulfate provided by the present application is made from the following components in parts by weight: rimexolane sulfate 75 parts, mannitol 45 parts, microcrystalline cellulose 75 parts, crospovidone 9 parts, low-substituted hydroxypropyl cellulose 17 parts, sucralose 2 parts, and magnesium stearate 2 parts.

[0014] For example, the orally disintegrating tablet of rimexolane sulfate provided by the present application is made from the following components in parts by weight: rimexolane sulfate 75 parts, mannitol 52.5 parts, microcrystalline cellulose 67.5 parts, crospovidone 9 parts, low-substituted hydroxypropyl cellulose 17 parts, sucralose 2 parts, and magnesium stearate 2 parts.

[0015] For example, the orally disintegrating tablet of rimexolane sulfate provided by the present application is made from the following components in parts by weight: rimexolane sulfate 75 parts, mannitol 60 parts, microcrystalline cellulose 60 parts, crospovidone 9 parts, low-substituted hydroxypropyl cellulose 17 parts, sucralose 2 parts, and magnesium stearate 2 parts.

[0016] For example, the orally disintegrating tablet of rimexolane sulfate provided by the present application is made from the following components in parts by weight: rimexolane sulfate 75 parts, mannitol 67.5 parts, microcrystalline cellulose 52.5 parts, crospovidone 9 parts, low-substituted hydroxypropyl cellulose 17 parts, sucralose 2 parts, and magnesium stearate 2 parts.

[0017] For example, the orally disintegrating tablet of rimexolane sulfate provided by the present application is made from the following components in parts by weight: rimexolane sulfate 75 parts, mannitol 75 parts, microcrystalline cellulose 45 parts, crospovidone 9 parts, low-substituted hydroxypropyl cellulose 17 parts, sucralose 2 parts, and magnesium stearate 2 parts.

[0018] For example, the orally disintegrating tablet of rimexolane sulfate provided by the present application is made from the following components in parts by weight: rimexolane sulfate 75 parts, mannitol 60 parts, microcrystalline cellulose 60 parts, crospovidone 5 parts, low-substituted hydroxypropyl cellulose 17 parts, sucralose 2 parts, and magnesium stearate 2 parts.

[0019] For example, the orally disintegrating tablets of retamipine sulfate provided by the present invention are made from the following components in parts by weight: 75 parts of retamipine sulfate, 60 parts of mannitol, 60 parts of microcrystalline cellulose, 15 parts of crospovidone, 17 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate.

[0020] For example, the orally disintegrating tablets of retamipine sulfate provided by the present invention are made from the following components in parts by weight: 75 parts of retamipine sulfate, 60 parts of mannitol, 60 parts of microcrystalline cellulose, 9 parts of crospovidone, 10 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate.

[0021] For example, the orally disintegrating tablets of retamipine sulfate provided by the present invention are made from the following components in parts by weight: 75 parts of retamipine sulfate, 60 parts of mannitol, 60 parts of microcrystalline cellulose, 9 parts of crospovidone, 20 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate.

[0022] For example, the orally disintegrating tablets of retamipine sulfate provided by the present invention are made from the following components in parts by weight: 75 parts of retamipine sulfate, 60 parts of mannitol, 60 parts of microcrystalline cellulose, 9 parts of crospovidone, 25 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate.

[0023] The present invention also provides a method for preparing the above-mentioned remdesivir orally disintegrating tablets, comprising the following steps:

[0024] (1) Preparation of drug-containing solution: Add low-substituted hydroxypropyl cellulose to purified water to make a binder solution. Add micronized retinoic acid to the obtained binder solution and disperse evenly to make a drug-containing solution for later use.

[0025] (2) Granulation: Mix microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose evenly, add the drug-containing solution obtained in step (1) to granulate, dry the obtained wet granules and then granulate them.

[0026] (3) Mixing and tableting: Mix the granules obtained in step (2) with mannitol and lubricant magnesium stearate, and compress them into tablets to obtain Remiglitol sulfate orally disintegrating tablets.

[0027] For the purposes of this invention, in step (1), the mass content of low-substituted hydroxypropyl cellulose in the adhesive solution is 1-3%, preferably 2%.

[0028] In step (1), the particle size of the micronized retinoic acid is D. 90 ≤10μm, D 50 ≤8μm, D 10 ≤5μm; preferably, D 90 ≤8μm, D 50 ≤5μm, D 10≤3 μm; more preferably, D 90 ≤5 μm, D 50 ≤3 μm, D 10 ≤1 μm.

[0029] For the present application, in step (2), the microcrystalline cellulose, crosslinked polyvinylpyrrolidone and sucralose are mixed uniformly, the stirring speed is 400-800 rpm, preferably 600 rpm, and the mixing time is 10-30 min, preferably 20 min.

[0030] In step (2), the atomization pressure is set to 0.1-0.3 MPa, preferably 0.2 MPa, when granulating.

[0031] In step (2), the drying temperature is ≤70°C, and the moisture content is ≤1% when drying; preferably, the drying temperature is ≤60°C.

[0032] The technical scheme of the present application has the following advantages:

[0033] The present application provides a rimegepant sulfate orally disintegrating tablet, which is made of active ingredient rimegepant sulfate orally disintegrating tablet, filler mannitol and microcrystalline cellulose, disintegrant crosslinked polyvinylpyrrolidone, binder low-substituted hydroxypropyl cellulose, flavoring agent sucralose and lubricant magnesium stearate. The rimegepant sulfate orally disintegrating tablet solves the problems of poor material flowability, sticking and pressing, and easy cracking during tablet pressing, has the advantages of rapid disintegration, rapid dissolution, good compressibility, good stability, good taste, simple preparation method, etc., is more suitable for patients with difficulty in swallowing, especially the elderly and children, has great clinical significance, and is suitable for large-scale industrial production. DETAILED DESCRIPTION

[0034] The present application can be better understood according to the following examples. However, those skilled in the art will readily understand that the content described in the examples is only used to illustrate the present application and should not and will not limit the present application described in detail in the claims.

[0035] Examples 1-9

[0036] A rimegepant sulfate orally disintegrating tablet is made of the following components by weight, and the components and weights in examples 1-10 are shown in Table 1.

[0037] Table 1 Components and amounts

[0038]

[0039]

[0040] The preparation method of the rimegepant sulfate orally disintegrating tablet in example 1 comprises the following steps:

[0041] (1) Preparation of drug-containing solution: the binder (low-substituted hydroxypropyl cellulose) was added to purified water to prepare a binder solution with a mass content of 2% of low-substituted hydroxypropyl cellulose, and the micronized ramelteon sulfate was added to the obtained binder solution, and after uniform dispersion, a drug-containing solution was prepared for use; wherein the particle size of the micronized ramelteon sulfate was: D 90 ≤ 10 μm, D 50 ≤ 8 μm, D 10 ≤ 5 μm;

[0042] (2) Granulation: the filler microcrystalline cellulose, the disintegrant crospovidone and the flavoring agent sucralose were stirred and mixed uniformly at a stirring speed of 600 rpm for 20 min, and the drug-containing solution obtained in step (1) was added to the obtained mixture for granulation, and the atomization pressure was set to 0.2 MPa; the obtained wet granules were added to a fluidized bed for drying at a drying temperature of ≤ 60 °C until the moisture content was ≤ 1%, and the granules were sized with a screen aperture of 1.0 mm.

[0043] (3) Mixing and tabletting: the granules obtained in step (2) were stirred and mixed with the filler mannitol and the lubricant magnesium stearate at a stirring speed of 10 rpm for 20 min, and the obtained mixture was tabletted to control the tablet hardness to 1-6 kg, and the ramelteon sulfate orally disintegrating tablets were obtained.

[0044] In the preparation process, compared with Example 1, the difference of Examples 2-10 lies in the different amounts of the filler (mannitol and microcrystalline cellulose), the disintegrant (crospovidone) and the binder (low-substituted hydroxypropyl cellulose).

[0045] Comparative Examples 1-4

[0046] An orally disintegrating tablet of ramelteon sulfate was prepared from the following components by weight, and the components and weights of Comparative Examples 1-4 are shown in Table 2.

[0047] Table 2 Components and amounts

[0048] Component Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Remoglifazene sulfate 75 75 75 75 Mannitol 33.75 86.25 60 60 Microcrystalline cellulose 86.25 33.75 60 60 Crospovidone 9 9 2 9 Low-substituted hydroxypropyl cellulose 17 17 17 5 Sucralose 2 2 2 2 Magnesium stearate 2 2 2 2

[0049] In the preparation process, compared with Example 1, the difference of Comparative Examples 1-4 lies in the different amounts of the filler (mannitol and microcrystalline cellulose), the disintegrant (crospovidone) and the binder (low-substituted hydroxypropyl cellulose).

[0050] The disintegration time, hardness, content uniformity, Carr index, tableting condition and dissolution data of the orally disintegrating tablets obtained in the examples and comparative examples were investigated, and the results are shown in Tables 3 and 4.

[0051] Table 3 Test results

[0052] Test item Disintegration time Hardness Content uniformity Karl index Tabletability Standard ≤60s 2-5 kg A + 2.2 S < 15 ≤35％ N / A Comparative Example 1 66s 1.3 kg 16.8 36％ Tabletability was good Example 1 12s 3.8 kg 2.7 9％ Tabletability was good Example 2 15s 3.7 kg 2.4 9％ Tabletability was good Example 3 12s 3.1 kg 2.2 11％ Tabletability was good Example 4 13s 3.5 kg 8.5 21％ Tabletability was good Example 5 17s 3.1 kg 10.1 27％ Tabletability was relatively good Comparative Example 2 124s 1.0 kg 6.3 20％ Tabletability was relatively good Comparative Example 3 97s 4.5 kg 3.7 37％ Tabletability was good Example 6 42s 3.2 kg 3.5 15％ Tabletability was good Example 7 8s 3.3 kg 4.1 15％ Tabletability was good Comparative Example 4 15s 1.5 kg 7.5 46％ Poor compressibility, difficult to form Example 8 16s 2.4 kg 4.5 19％ Good compressibility Example 9 14s 4.4 kg 2.6 8％ Tabletability was good Example 10 12s 4.0 kg 3.7 11％ Tabletability was good

[0053] Note: <10%, good flowability; 10%-20%, better flowability; 20%-35%, general flowability; 35%-45%, poor flowability; more than 45%, very poor flowability.

[0054] As can be seen from Table 3, the samples in Examples 1-10 have a disintegration time of less than 60s, rapid disintegration, good hardness, content uniformity and flowability, smooth tabletting, and good compressibility.

[0055] In the sample of Comparative Example 1, the amount of mannitol in the filler is low and the amount of microcrystalline cellulose in the filler is high, which ensures the compressibility but results in unqualified content uniformity due to poor flowability and unqualified tablet hardness due to poor compressibility. In the sample of Comparative Example 2, the amount of mannitol in the filler is high and the amount of microcrystalline cellulose in the filler is low, which ensures the flowability but results in unqualified hardness after applying a large tabletting pressure, and the large pressure leads to excessive heat generation, which causes the mannitol to melt and results in slow disintegration.

[0056] In the sample of Comparative Example 3, the amount of cross-linked povidone as a good disintegrant is low, which results in prolonged disintegration time and unqualified disintegration time limit.

[0057] In the sample of Comparative Example 4, the amount of low-substituted hydroxypropyl cellulose as a binder is low, which results in failure to granulate, poor flowability due to the presence of a large amount of powder, and unqualified hardness due to the reduced adhesion between particles under the same tabletting pressure.

[0058] Table 4 Test Results

[0059]

[0060] As can be seen from Table 4, the samples in Examples 1-10 have a fast dissolution rate and complete dissolution, which meets the requirement of 15min≥85%.

[0061] In the sample of Comparative Example 1, the amount of mannitol in the filler is low and the amount of microcrystalline cellulose in the filler is high, which results in slow dissolution rate and low dissolution endpoint, which is consistent with the phenomenon of accumulation of microcrystalline cellulose at the bottom of the dissolution cup, leading to incomplete release.

[0062] In the sample of Comparative Example 2, the amount of mannitol in the filler is high and the amount of microcrystalline cellulose in the filler is low, which results in prolonged disintegration time of the tablet, slow dissolution rate and low dissolution endpoint due to overloading of the pressure.

[0063] In the sample of Comparative Example 3, the amount of cross-linked povidone as a disintegrant is low, which results in slow disintegration of the tablet, slow dissolution rate and incomplete dissolution.

[0064] The sample in Comparative Example 4 has a low amount of the adhesive low-substituted hydroxypropyl cellulose, which results in a very fast dissolution rate.

[0065] The samples in the examples and comparative examples were placed in accelerated conditions (40±2℃, relative humidity 75±5%) to compare the stability, and the data are shown in the following table:

[0066] Table 5 Results of accelerated test items

[0067]

[0068]

[0069]

[0070] As shown in Table 5, the samples in Examples 1-10 have low content, moisture, disintegration time limit and related substance content at 0 days, and the increase in content, moisture, disintegration time limit and related substance content is small after 6 months of acceleration, and the stability is good.

[0071] The samples in Comparative Examples 1-4 have high content, moisture, disintegration time limit and related substance content at 0 days, and the increase in content, moisture, disintegration time limit and related substance content is large after 6 months of acceleration, and the stability is poor, which is significantly worse than the samples in the examples.

[0072] The above examples are only used to illustrate the technical solutions of the present application, but not limit the present application; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that the technical solutions recorded in the foregoing examples can still be modified, or some technical features can be replaced by equivalents; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the examples of the present application.

Claims

1. A pan-disintegrating tablet of retamiprid sulfate, characterized in that, It is made from the following components in parts by weight: 60-90 parts of Remepiride sulfate, 35-80 parts of mannitol, 35-80 parts of microcrystalline cellulose, 3-20 parts of crospovidone, 8-30 parts of low-substituted hydroxypropyl cellulose, 1-5 parts of sucralose, and 1-5 parts of magnesium stearate.

2. The pandisintegrating tablets of retamiprid sulfate according to claim 1, characterized in that, In its preparation process, microcrystalline cellulose, crospovidone and sucralose are first mixed evenly, and then a drug-containing solution made of low-substituted hydroxypropyl cellulose, retrimazole sulfate and purified water is added for granulation. The resulting wet granules are dried, granulated and then mixed with mannitol and magnesium stearate, and compressed into tablets to obtain orally disintegrating tablets.

3. The pan-disintegrating tablets of retamiprid sulfate according to claim 2, characterized in that, The particle size of Remegapan sulfate is D 90 ≤10μm, D 50 ≤8μm, D 10 ≤5μm; preferably, D 90 ≤8μm, D 50 ≤5μm, D 10 ≤3μm; Even Preferably, D 90 ≤5μm, D 50 ≤3μm, D 10 ≤1μm.

4. The pandisintegrating tablets of retamiprid sulfate according to claim 3, characterized in that, It is made from the following components in parts by weight: 70-80 parts of Remepiride sulfate, 45-75 parts of mannitol, 45-75 parts of microcrystalline cellulose, 5-15 parts of crospovidone, 10-25 parts of low-substituted hydroxypropyl cellulose, 1.5-3.5 parts of sucralose, and 1.5-3.5 parts of magnesium stearate.

5. The pandisintegrating tablets of retamiprid sulfate according to claim 4, characterized in that, It is made from the following components in parts by weight: 75 parts of Remepiride sulfate, 45-75 parts of mannitol, 45-75 parts of microcrystalline cellulose, 5-15 parts of crospovidone, 10-25 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate.

6. The pan-disintegrating tablets of retamiprid sulfate according to claim 5, characterized in that, It is made from the following components in parts by weight: Remepiquat sulfate 75 parts, mannitol 45 parts, microcrystalline cellulose 75 parts, crospovidone 9 parts, low-substituted hydroxypropyl cellulose 17 parts, sucralose 2 parts, magnesium stearate 2 parts. Remepiquat sulfate 75 parts, mannitol 52.5 parts, microcrystalline cellulose 67.5 parts, crospovidone 9 parts, low-substituted hydroxypropyl cellulose 17 parts, sucralose 2 parts, magnesium stearate 2 parts; 75 parts of Remepiride sulfate, 60 parts of mannitol, 60 parts of microcrystalline cellulose, 9 parts of crospovidone, 17 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate. Remepiride sulfate 75 parts, mannitol 67.5 parts, microcrystalline cellulose 52.5 parts, crospovidone 9 parts, low-substituted hydroxypropyl cellulose 17 parts, sucralose 2 parts, magnesium stearate 2 parts; 75 parts of Remepiride sulfate, 75 parts of mannitol, 45 parts of microcrystalline cellulose, 9 parts of crospovidone, 17 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate. 75 parts of Remepiride sulfate, 60 parts of mannitol, 60 parts of microcrystalline cellulose, 5 parts of crospovidone, 17 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate. 75 parts of Remepiride sulfate, 60 parts of mannitol, 60 parts of microcrystalline cellulose, 15 parts of crospovidone, 17 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate. 75 parts of Remepiride sulfate, 60 parts of mannitol, 60 parts of microcrystalline cellulose, 9 parts of crospovidone, 10 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate. 75 parts of Remepiride sulfate, 60 parts of mannitol, 60 parts of microcrystalline cellulose, 9 parts of crospovidone, 20 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate. 75 parts of Remepiride sulfate, 60 parts of mannitol, 60 parts of microcrystalline cellulose, 9 parts of crospovidone, 25 parts of low-substituted hydroxypropyl cellulose, 2 parts of sucralose, and 2 parts of magnesium stearate.

7. The method for preparing the orally disintegrating tablets of remdesivir sulfate according to claim 1, characterized in that, Includes the following steps: (1) Preparation of drug-containing solution: Add low-substituted hydroxypropyl cellulose to purified water to make a binder solution. Add micronized retinoic acid to the obtained binder solution and disperse evenly to make a drug-containing solution for later use. (2) Granulation: Mix microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose evenly, add the drug-containing solution obtained in step (1) to granulate, dry the obtained wet granules and then granulate them. (3) Mixing and tableting: Mix the granules obtained in step (2) with mannitol and lubricant magnesium stearate, and compress them into tablets to obtain Remiglitol sulfate orally disintegrating tablets.

8. The method for preparing palliative tablets of retamiprid sulfate according to claim 7, characterized in that, In step (1), the mass content of low-substituted hydroxypropyl cellulose in the adhesive solution is 1-3%, preferably 2%; the particle size of the micronized remigelpam sulfate is D. 90 ≤10μm, D 50 ≤8μm, D 10 ≤5μm; preferably, D 90 ≤8μm, D 50 ≤5μm, D 10 ≤3μm; more preferably, D 90 ≤5μm, D 50 ≤3μm, D 10 ≤1μm.

9. The method for preparing palliative tablets of retamiprid sulfate according to claim 7, characterized in that, In step (2), during mixing, the stirring speed is 400-800 rpm, preferably 600 rpm, and the mixing time is 10-30 min, preferably 20 min; during granulation, the atomization pressure is set to 0.1-0.3 MPa, preferably 0.2 MPa.

10. The method for preparing remdesivir sulfate orally disintegrating tablets according to claim 7, characterized in that, In step (2), the drying temperature is ≤70℃, and the moisture content is dried to ≤1%; preferably, the drying temperature is ≤60℃.

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