Rebaudioside p tablet and preparation method thereof

Abstract

The application discloses a reba piate tablet and a preparation method thereof. The tablet comprises reba piate, a carrier material, a filler, a binder, a disintegrant, a lubricant and pharmaceutically acceptable excipients. The carrier material is glyceryl behenate and poloxamer copolymer. The reba piate tablet of the application avoids the increase of impurities in a high-temperature and high-humidity environment, reduces the agglomeration of the raw drug caused by static electricity, adjusts the release rate of the reba piate tablet, and has a simple preparation process and is suitable for industrial mass production.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of pharmaceutical preparations, in particular to a rebamipide tablet and a preparation method thereof. BACKGROUND

[0002] The mucosa is the first barrier of the body. In recent years, the prevalence of gastrointestinal mucosal injury diseases such as gastrointestinal ulcers and intestinal inflammation has shown an increasing trend year by year. Peptic ulcer is commonly seen in gastric and duodenal ulcers, mainly manifested as patients with rhythmic abdominal pain, which can be accompanied by symptoms such as nausea, vomiting, loss of appetite, etc., which can affect normal work and life, resulting in a lower quality of life for patients.

[0003] Rebamipide is an endogenous mucosal protective agent, mainly used for the treatment of gastric ulcers, ulcerative colitis, and postoperative ulcers after endoscopic submucosal dissection. Rebamipide tablets are developed and produced by Otsuka Pharmaceutical Co., Ltd. of Japan. The chemical name of rebamipide is (±) 2-(4-chlorobenzamide)-3-[2(1H)-quinolone-4-yl] propionic acid, and the chemical structure is as follows:

[0004]

[0005] Rebamipide is a BCS IV drug, and its extremely low solubility and permeability are not conducive to its dissolution and absorption in the body. Rebamipide is a pH-dependent type, and it is insoluble in acidic conditions. As the pH increases, the solubility increases. It is slightly soluble in N, N-dimethylformamide, extremely insoluble in methanol or ethanol, and almost insoluble in water, and has a certain hygroscopicity. After taking on an empty stomach, rebamipide is almost insoluble after disintegration in the stomach, in a molecular state, but has good permeability. In the intestinal tract, the solubility increases, and it is in an ionic state, with poor permeability. In summary, rebamipide has low bioavailability.

[0006] During preparation, rebamipide has poor solubility, poor disintegration and dissolution, large static electricity, small bulk density, and difficult granulation and tabletting. In addition, the dissolution rate is inconsistent with the original drug developed by Otsuka Pharmaceutical Co., Ltd. of Japan, resulting in unstable drug quality and no guarantee of clinical effectiveness and safety during taking.

[0007] Chinese Patent CN202111391417.1 discloses a rebamipide tablet. The particle size D90 of rebamipide is controlled at 3-30 μm, and a water solution of a binder with a weight percentage of 3-10% is added to stir into a soft material. By adjusting the proportion of each material and the addition method, the problem of uneven content of the compressed tablet caused by the self-aggregation of the main drug due to static electricity and the difficulty of uniform mixing is avoided.

[0008] Rebamipide structure contains amide bond, amide bond is easy to break down to generate p-chlorobenzoic acid impurity (impurity A), the inventors found that the stability of rebamipide was investigated, and the appearance of impurity A was obviously increased under the condition of accelerated test (40℃±2℃ / 75%RH±5%RH).

[0009]

[0010] In summary, due to the large static electricity of rebamipide raw material, small bulk density, difficult granulation and tabletting, and the characteristics of heat and moisture sensitivity, a large amount of water needs to be added to prepare wet briquettes in the extrusion granulation, and the extrusion production equipment generates heat during the extrusion process, which can easily lead to the increase of related impurities. SUMMARY

[0011] In view of the deficiencies of the prior art, the purpose of the present application is to provide a rebamipide tablet and a preparation method thereof, which can avoid the self-aggregation of rebamipide due to static electricity during preparation, and the problem of uneven content of the compressed tablet caused by the difficulty of uniform mixing of raw and auxiliary materials due to the difference in particle size. The obtained rebamipide tablet has good impurity condition and stable drug release.

[0012] To achieve the above purpose, through a large number of experimental research and improvement on the existing preparation prescription and process, it is found that when glyceryl behenate and poloxamer copolymer are combined in a certain proportion as a carrier, the particle size of rebamipide raw material does not need to be crushed or other special treatment, and the influence of high temperature factor can be avoided during granulation. The increase of impurities under high temperature and humidity is avoided, the release rate of rebamipide tablet is adjusted, the situation of burst release or incomplete release is reduced, and the quality stability is ensured.

[0013] Specifically, the rebamipide tablet according to the present application comprises rebamipide, carrier material, filler, binder, disintegrant, lubricant and pharmaceutically acceptable adjuvant, wherein the carrier material is glyceryl behenate and poloxamer copolymer.

[0014] In the present application, the presence of the carrier material is one of the important technical keys to achieve the technical effect. In the preparation process of rebamipide tablets, due to the static electricity of the raw materials, it is easy to cause aggregation into groups, and the bulk density of the raw materials is small, so that there are certain difficulties in granulation and tabletting. At present, the particle size of rebamipide raw materials can be controlled to improve the flowability, but the uneven mixing of the raw materials caused by the difference in particle size will cause the content of the compressed tablets to be uneven. Glycerol monobehenate and poloxamer copolymer as the carrier material of rebamipide can effectively solve the above problems. Glycerol monobehenate can be suitable for heat-labile and moisture-absorbing drugs, and the operation temperature is low during granulation, without solvent, which can ensure the smooth release of the drug and does not affect the stability of the drug. Poloxamer as a water-soluble carrier material has good dispersing ability, and as a surfactant, it can increase the wettability of the drug in the drug composition, prevent the aggregation and caking of rebamipide raw material particles, and has a relatively low melting point and good physical stability. The inventors found that when glycerol monobehenate and poloxamer are used as carrier materials, the raw material particle size does not need to be crushed, and the high temperature factor can be avoided during granulation, which avoids the increase of impurities in the high temperature and high humidity environment, and at the same time can improve the solubility of rebamipide, change the dissolution rate, achieve smooth release, and improve the bioavailability. Further, during granulation, a large amount of water is not needed to extrude soft material, which can effectively control the impurities generated by heat and humidity.

[0015] In the present application, the mass ratio of glycerol monobehenate and poloxamer is one of the key factors to achieve the technical effect. When the mass ratio of glycerol monobehenate and poloxamer is 1.5-5:1, the release of rebamipide tablets is optimal, and the comprehensive performance of rebamipide in drug loading, stability and dispersibility is better. Preferably, the mass ratio of glycerol monobehenate and poloxamer is 2.5:1.

[0016] In the present application, the mass ratio of rebamipide and carrier material is one of the key factors to achieve the technical effect. When the mass ratio of rebamipide and carrier material is too low, that is, the content of the carrier material is too high, it will cause the release of rebamipide to be difficult, and when the mass ratio of rebamipide and carrier material is too high, part of the raw materials will appear aggregation phenomenon, which will cause subsequent granulation and tabletting difficult, and cause waste of rebamipide raw materials. When the mass ratio of rebamipide and carrier material is 1:1.0-1.3, the drug loading and drug release of the carrier material achieve the optimal effect. Preferably, the mass ratio of rebamipide and carrier material is 1:1.2.

[0017] In the present application, the adhesive is one of the important factors to achieve the technical effect. As described above, the static electricity of rebamipide raw material is large, which is easy to cause aggregation. The use of a single adhesive can easily exacerbate the occurrence of aggregation. Therefore, a composite adhesive is used, that is, a suitable polyethylene glycol is added to the adhesive hydroxypropyl cellulose, which can reduce the occurrence of aggregation and ensure that there is no sticking and loose tablets during tabletting, ensure smooth tabletting operation, and improve the appearance of tablets. When the mass ratio of hydroxypropyl cellulose to polyethylene glycol is 5-10:1, the adhesive effect is better, and the aggregation of the raw material does not occur. Preferably, the mass ratio of hydroxypropyl cellulose to polyethylene glycol is 8:1.

[0018] In the present application, the selection of the prescription is one of the factors to achieve the technical effect. Specifically, the increase of the amount of adjuvant is beneficial to increase the compressibility and reduce the possibility of sticking, but the increase of the amount of adjuvant will lead to the weight of the tablet being too large, which is not conducive to the patient's taking. Unless otherwise specified, the amount of active ingredient in the prescription of the preparation of the present application is calculated by the mass of rebamipide. The filler is one or more of lactose, anhydrous lactose, microcrystalline cellulose, mannitol or starch. The disintegrant is one or more of low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch or cross-linked povidone. The lubricant is one or more of magnesium stearate, calcium stearate or sodium stearyl fumarate. Preferably, the filler is microcrystalline cellulose, the disintegrant is low-substituted hydroxypropyl cellulose, and the lubricant is magnesium stearate.

[0019] Further, when the mass fraction of rebamipide is 1, the mass ratio of rebamipide to filler is 1:0.4-0.8, the mass ratio of rebamipide to adhesive is 1:0.025-0.050, the mass ratio of rebamipide to disintegrant is 1:0.15-0.25, and the mass ratio of rebamipide to lubricant is 1:0.005-0.020. Preferably, the mass ratio of rebamipide to filler is 1:0.5, the mass ratio of rebamipide to adhesive is 1:0.028, the mass ratio of rebamipide to disintegrant is 1:0.20, and the mass ratio of rebamipide to lubricant is 1:0.01.

[0020] According to the actual production of the preparation, it is well known to those skilled in the art that there is a certain error range in the mass ratio between the raw materials and the adjuvants. The mass ratio error range in the present application can be ±0.5%.

[0021] The present application also provides a rebamipide tablet comprising the following components. The prescription is the preferred technical solution of the present application, which simultaneously solves the aggregation of raw materials, the increase of impurities and the release-related problems of rebamipide tablets during preparation. The obtained preparation has excellent quality, no sticking, loose tablets, and the like, good dissolution performance, good stability, and meets the effect of drug use.

[0022] A rebamipide tablet comprising the following components,

[0023] Name Parts by mass Rebaudioside 1 Carrier material 1.2 Microcrystalline cellulose 0.50 Hydroxypropyl cellulose and polyethylene glycol mixture 0.028 Low-substituted hydroxypropyl cellulose 0.20 Magnesium stearate 0.01

[0024] The carrier material is glyceryl behenate and poloxamer copolymer.

[0025] Specifically, a rebaipate tablet comprises the following components,

[0026] Name Content mg / tablet Rebaudioside 100.00 Glyceryl behenate 85.71 Poloxamer 34.29 Microcrystalline cellulose 50.00 Hydroxypropyl cellulose 2.49 Polyethylene glycol 0.31 Low-substituted hydroxypropyl cellulose 20.00 Magnesium stearate 1.00

[0027] A second object of the present application is to provide a preparation method of the aforementioned rebaipate tablet, which comprises the following steps:

[0028] 1) Hydroxypropyl cellulose and polyethylene glycol are added into purified water and mixed uniformly to obtain a hydroxypropyl cellulose and polyethylene glycol solution;

[0029] 2) Rebaipate, microcrystalline cellulose, glyceryl behenate and poloxamer are placed in a granulator, and the raw materials are preheated; when the material temperature reaches 40-42℃, the slurry is sprayed and granulated; the inlet air temperature is 60±10℃, and the fan frequency is 25-30Hz; the material temperature is ≤50℃;

[0030] 3) The granules are mixed with magnesium stearate and low-substituted hydroxypropyl cellulose;

[0031] 4) Die, tabletting.

[0032] Compared with the prior art, the present application has the following outstanding advantages and beneficial effects:

[0033] 1) The copolymer of glyceryl behenate and poloxamer is used in the present application as a carrier in a specific proportion, without the need for special treatment such as crushing of the raw material particles, and the influence of high temperature factors can be avoided during the granulation process, which avoids the increase of impurities in a high temperature and high humidity environment, reduces the agglomeration of raw materials due to static electricity, adjusts the release rate of rebaipate tablets, and reduces the situation of incomplete release or burst release.

[0034] 2) The use of hydroxypropyl cellulose and polyethylene glycol as a composite binder in the present application can further reduce the occurrence of agglomeration of raw materials, while ensuring that sticking does not occur during tabletting, ensuring smooth tabletting operation and improving the appearance of the tablets.

[0035] 3) The process of the present application is simple, and one-step granulation is used, which can effectively avoid the direct contact of rebaipate with a large amount of water, without the need for preparation by melting extrusion or melting method, and the preparation process is simple, suitable for industrial large-scale production, ensures the slow release of the obtained rebaipate tablets, is suitable for commercial scale production, and has greater application value. BRIEF DESCRIPTION OF DRAWINGS

[0036] Figure 1 The release curve of the rebaipate tablets prepared in Example 1 and Comparative Example 3 of the present application. Detailed Implementation

[0037] The present invention will be further described in detail below with reference to embodiments, but the implementation of the invention is not limited thereto.

[0038] Example 1: Preparation of Rebamipide Tablets

[0039] The formulation of 1000 tablets of Rebamipide

[0040] Name Amount (g) Rebaudioside 100.00 Glyceryl behenate 85.71 Poloxamer 34.29 Microcrystalline cellulose 50.00 Hydroxypropyl cellulose 2.49 Polyethylene glycol 0.31 Low-substituted hydroxypropyl cellulose 20.00 Magnesium stearate 1.00

[0041] Preparation method:

[0042] 1) Prepare a 10% hydroxypropyl cellulose and polyethylene glycol solution. Slowly add the prescribed amount of hydroxypropyl cellulose and polyethylene glycol to a beaker containing the prescribed amount of purified water (room temperature) while stirring. After adding all the water, continue stirring for 20 minutes at a stirring speed of 500 rpm (two-blade impeller). After stirring, set aside.

[0043] 2) Place rebamipide, microcrystalline cellulose, behenicol glyceryl ester and poloxamer in a granulator. Preheat the raw materials and start spray granulation when the material temperature reaches 40-42℃.

[0044] 3) Spray granulation: air inlet temperature 60±10℃, fan frequency 25-30Hz; material temperature ≤50℃, liquid supply rate approximately 1.0kg / min; atomization pressure 0.3MPa, particle moisture content controlled at 2.0%-4.0%;

[0045] 4) Use a Φ1.5mm sieve for granulation, and the granulation frequency is 10.0Hz;

[0046] 5) Add low-substituted hydroxypropyl cellulose and mix for 10 min at a mixing speed of 8 rpm; then add magnesium stearate and mix for 5 min at a mixing speed of 8 rpm.

[0047] 6) Use Φ8.0mm die to press the sheet, and the sheet hardness is 30-50N.

[0048] Example 2: Preparation of Rebamipide Tablets (Formulation composition of 1000 tablets of the Rebamipide tablets)

[0049] Name Amount (g) Rebaudioside 100.00 Glyceryl behenate 66.00 Poloxamer 44.00 Microcrystalline cellulose 40.00 Hydroxypropyl cellulose 2.08 Polyethylene glycol 0.42 Low-substituted hydroxypropyl cellulose 15.00 Magnesium stearate 0.50

[0050] The preparation method is as described in Example 1.

[0051] Example 3: Preparation of Rebamipide Tablets

[0052] The formulation of 1000 tablets of Rebamipide

[0053] Name Amount (g) Rebaudioside 100.00 Glyceryl behenate 108.33 Poloxamer 21.67 Microcrystalline cellulose 80.00 Hydroxypropyl cellulose 4.55 Polyethylene glycol 0.45 Low-substituted hydroxypropyl cellulose 25.00 Magnesium stearate 2.00

[0054] The preparation method is as in Example 1.

[0055] Example 4 Preparation of Rebamipide Tablets

[0056] Prescription composition of 1000 tablets of the Rebamipide Tablets

[0057] Name Amount (g) Rebaudioside 100.00 Glyceryl behenate 75.00 Poloxamer 25.00 Lactose 60.00 Hydroxypropyl cellulose 3.06 Polyethylene glycol 0.44 Croscarmellose sodium 20.00 Calcium stearate 1.50

[0058] The preparation method is as in Example 1.

[0059] Example 5 Preparation of Rebamipide Tablets

[0060] Prescription composition of 1000 tablets of the Rebamipide Tablets

[0061] Name Amount (g) Rebaudioside 100.00 Glyceryl behenate 96.00 Poloxamer 24.00 Mannitol 70.00 Hydroxypropyl cellulose 4.05 Polyethylene glycol 0.45 Sodium carboxymethyl starch 20.00 Sodium stearyl fumarate 1.00

[0062] The preparation method is as in Example 1.

[0063] Preparation of Rebamipide Tablets

[0064] Prescription composition of 1000 tablets of the Rebamipide Tablets

[0065]

[0066]

[0067] The preparation method is as in Example 1. In the prescription of Comparative Example 1, the amounts of the carrier materials glyceryl behenate and poloxamer copolymer, the amount of the composite binder mixture of hydroxypropyl cellulose and polyethylene glycol, and the amounts of the filler, disintegrant, and lubricant are all less than the amounts in the prescription of Example 1.

[0068] Preparation of Rebamipide Tablets

[0069] Prescription composition of 1000 tablets of the Rebamipide Tablets

[0070] Name Amount (g) Rebaudioside 100.00 Glyceryl behenate 60.00 Poloxamer 60.00 Microcrystalline cellulose 50.00 Hydroxypropyl cellulose 2.24 Polyethylene glycol 0.56 Low-substituted hydroxypropyl cellulose 20.00 Magnesium stearate 1.00

[0071] The preparation method is as in Example 1. In the prescription of Comparative Example 2, the mass ratio of glyceryl behenate to poloxamer in the carrier material is lower, and the mass ratio of hydroxypropyl cellulose to polyethylene glycol in the composite binder is lower.

[0072] Preparation of Rebamipide Tablets

[0073] Prescription composition of 1000 tablets of the Rebamipide Tablets

[0074]

[0075]

[0076] The preparation method is as in Example 1, and the prescription in Comparative Example 3, the amount of carrier material glyceryl behenate and poloxamer copolymer is too much, the amount of composite binder hydroxypropyl cellulose and polyethylene glycol mixture is too much, the amount of filler, disintegrant and lubricant is also too much.

[0077] Preparation of rebaipate tablets in Comparative Example 4

[0078] Prescription composition of 1000 tablets of the rebaipate tablets

[0079] Name Amount (g) Rebaudioside 100.00 Glyceryl behenate 102.86 Poloxamer 17.14 Microcrystalline cellulose 50.00 Hydroxypropyl cellulose 2.57 Polyethylene glycol 0.23 Low-substituted hydroxypropyl cellulose 20.00 Magnesium stearate 1.00

[0080] The preparation method is as in Example 1, and the prescription in Comparative Example 4, the mass ratio of glyceryl behenate and poloxamer in the carrier material is too high, and the mass ratio of hydroxypropyl cellulose and polyethylene glycol in the composite binder is too high.

[0081] Preparation of rebaipate tablets in Comparative Example 5

[0082] Prescription composition of 1000 tablets of the rebaipate tablets

[0083] Name Amount (g) Rebaudioside 100.00 Glyceryl behenate 85.71 Poloxamer 34.29 Microcrystalline cellulose 50.00 Hydroxypropyl cellulose 2.80 Low-substituted hydroxypropyl cellulose 20.00 Magnesium stearate 1.00

[0084] The preparation method is as in Example 1, and the prescription in Comparative Example 5, only hydroxypropyl cellulose is used in the binder, and polyethylene glycol is not used.

[0085] Preparation of rebaipate tablets in Comparative Example 6

[0086] Prescription composition of 1000 tablets of the rebaipate tablets

[0087] Name Amount (g) Rebaudioside 100.00 Microcrystalline cellulose 50.00 Hydroxypropyl cellulose 2.49 Polyethylene glycol 0.31 Low-substituted hydroxypropyl cellulose 20.00 Magnesium stearate 1.00

[0088] The preparation method is as in Example 1, and the prescription in Comparative Example 6, no carrier material is used.

[0089] Preparation of rebaipate tablets in Comparative Example 7

[0090] Prescription composition of 1000 tablets of the rebaipate tablets

[0091] Name Amount (g) Rebaudioside 100.00 Low-substituted hydroxypropyl cellulose 20.00 Hydroxypropyl cellulose 2.49 Microcrystalline cellulose 50.00 Magnesium stearate 1.00

[0092] Preparation method:

[0093] Take the microcrystalline cellulose and 50% of the required amount of hydroxypropyl cellulose, add 30% of the weight of the microcrystalline cellulose purified water stirring, make the mixed excipients slightly wet, then add rebamipide stirring mixed, 18 mesh dispersion, continue to mix evenly, add a 2% low-substituted hydroxypropyl cellulose aqueous solution, stirring to make a soft material with suitable viscosity, 18 mesh granulation, 80°C drying, the moisture content of the granules is controlled within 3.0% of the dry matter, 18 mesh whole grain, finally add the remaining 50% hydroxypropyl cellulose and an appropriate amount of magnesium stearate, mix evenly, press into tablets, and rebamipide tablets are prepared.

[0094] Example 6

[0095] Take the rebamipide tablets prepared in Examples 1-5 and Comparative Examples 1-6, and perform quality inspection, and the results are as follows:

[0096] Table 1 Quality inspection of rebamipide tablets

[0097]

[0098] From the above results, it can be seen that the rebamipide tablets prepared in Examples 1-5 and Comparative Examples 1-6 are all white or white-like in shape, but in Comparative Example 1, sticking, loose tablets and cracking, and content uniformity were observed during tabletting. Analysis shows that in Comparative Example 1, the amount of carrier material is too small, the amount of binder is too small, and part of the raw materials agglomerate, causing uneven mixing and sticking during tabletting. In Comparative Example 2, the amount of glyceryl behenate in the carrier material is too small, and the amount of hydroxypropyl cellulose in the binder is too small, resulting in loose tablets and cracking during tabletting. In Comparative Example 4, due to the high content of glyceryl behenate and hydroxypropyl cellulose, sticking and uneven mixing occur, resulting in a slightly higher content uniformity. In Comparative Example 5, due to the large static electricity of rebamipide raw materials, it is easy to cause aggregation into a group, and only using hydroxypropyl cellulose as a binder exacerbates the aggregation phenomenon, so sticking occurs during tabletting. In Comparative Example 6, due to the absence of carrier material, rebamipide aggregates into a group, and the particle size difference between the raw and auxiliary materials causes uneven mixing, so the content uniformity is slightly higher than the standard. Examples 1-5 are the preferred scheme in this scheme, and the various parameters in Example 1, including the types and proportions of excipients, are the most preferred. If a more suitable carrier material is used, the binder is increased with an appropriate amount of polyethylene glycol, the resulting tablet core has higher quality, and thus better compressibility. The combination of the above conditions enables rebamipide tablets to achieve the best during preparation.

[0099] Example 7

[0100] The rebamipide tablets prepared in Examples 1-5, Comparative Example 7 and the commercially available rebamipide tablets were placed in a condition of temperature 40℃±2℃, humidity 75%RH±5%RH, and the samples were measured at 0 days and 10 days, respectively, to determine the contents (%) of impurity A and total impurities, and the results are shown in Table 2.

[0101] Table 2 Contents (%) of impurity A and total impurities

[0102]

[0103]

[0104] From the above results, it can be seen that the rebamipide tablets prepared in Examples 1-5 have lower contents of impurity A and total impurities at 0 days and 10 days than the rebamipide tablets prepared in Comparative Example 7 and the commercially available rebamipide tablets. Further, the rebamipide tablets prepared in Examples 1-5 have smaller changes in the content of impurity A from 0 days to 10 days. Furthermore, the rebamipide tablets prepared in Example 1 have the lowest contents of impurity A and total impurities, which proves that the use of glyceryl behenate and poloxamer as carrier materials can effectively control the content of impurities under the condition of low temperature and without the use of a large amount of water.

[0105] Example 8

[0106] The rebamipide tablets prepared in Example 1 and Comparative Example 3 were subjected to dissolution and release determination according to the method (Chinese Pharmacopoeia 2020 edition 0931), using the device of the second method of dissolution determination, 900 ml of water as the solvent, pH 6.8 medium, and a rotation speed of 50 revolutions per minute, and the dissolution determination was performed according to the method. The in vitro dissolution determination results are shown in Table 3 and Figure 1 .

[0107] Table 3 Release determination results of the rebamipide tablets prepared in Example 1 and Comparative Example 3

[0108]

[0109] From the above results, it can be seen that the rebamipide tablets prepared in Example 1 are released smoothly and completely within 60 min, and have good in vitro release performance. However, the rebamipide tablets prepared in Comparative Example 3 cannot be completely released within 60 min. Analysis shows that the prescription, carrier material and excessive amount of binder in Comparative Example 3 affect the release of the rebamipide tablets, resulting in that the rebamipide tablets cannot be completely released within 60 min.

[0110] In summary, the rebaipide tablet prepared by the present application is simple to prepare, does not need special treatment such as crushing of the raw material drug particle size, reduces the agglomeration of the raw material drug due to static electricity, avoids the increase of impurities due to high temperature and high humidity in the extrusion process, and avoids sticking, cracking and other phenomena in the tabletting process, and the quality is qualified and stable, and the dissolution performance and stability are ensured.

[0111] The above embodiments are the preferred embodiments of the present application, but the embodiments of the present application are not limited to the above embodiments, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application should be equivalent replacement methods, and are all included in the protection scope of the present application.

Claims

1. A rebamipide tablet, characterized in that, The tablet contains rebamipide, a carrier material, fillers, binders, disintegrants, lubricants, and pharmaceutically acceptable excipients. The carrier material is a copolymer of glyceryl behenate and poloxamer. In the carrier material, the mass ratio of behenicol glyceryl ester to poloxamer is 1.5-5:

1. The mass ratio of rebapeptide to carrier material is 1:1.0-1.

3. The adhesive is a mixture of hydroxypropyl cellulose and polyethylene glycol, wherein the mass ratio of hydroxypropyl cellulose to polyethylene glycol is 5-10:

1.

2. The rebamipide tablet according to claim 1, characterized in that, In the carrier material, the mass ratio of behenicol glyceryl ester to poloxamer is 2.5:

1.

3. The rebamipide tablet according to claim 1, characterized in that, The mass ratio of rebapeptide to carrier material is 1:1.

2.

4. The rebamipide tablet according to claim 1, characterized in that, The mass ratio of hydroxypropyl cellulose to polyethylene glycol is 8:

1.

5. The rebamipide tablet according to claim 1, characterized in that, The filler is one or more of lactose, microcrystalline cellulose, mannitol or starch; the disintegrant is one or more of low-substituted hydroxypropyl cellulose, croscarmellose sodium, carboxymethyl starch sodium or croscarmellose; and the lubricant is one or more of magnesium stearate, calcium stearate or sodium stearate fumarate.

6. The rebamipide tablet according to claim 5, characterized in that, The filler is microcrystalline cellulose, the disintegrant is low-substituted hydroxypropyl cellulose, and the lubricant is magnesium stearate.

7. The rebamipide tablet according to claim 1, characterized in that, The mass ratio of rebamipide to filler is 1:0.4-0.8, the mass ratio of rebamipide to adhesive is 1:0.025-0.050, the mass ratio of rebamipide to disintegrant is 1:0.15-0.25, and the mass ratio of rebamipide to lubricant is 1:0.005-0.

020.

8. The rebamipide tablet according to claim 7, characterized in that, The mass ratio of rebamipide to filler is 1:0.5, the mass ratio of rebamipide to adhesive is 1:0.028, the mass ratio of rebamipide to disintegrant is 1:0.20, and the mass ratio of rebamipide to lubricant is 1:0.

01.

9. A rebamipide tablet, characterized in that, It contains the following components: The carrier material is a copolymer of behenicol and poloxamer, with a mass ratio of behenicol to poloxamer of 2.5:1, and the mass ratio of hydroxypropyl cellulose to polyethylene glycol of 8:

1.

10. The method for preparing rebamipide tablets according to claim 9, characterized in that, Includes the following steps: 1) Add hydroxypropyl cellulose and polyethylene glycol to purified water and mix well to obtain a hydroxypropyl cellulose and polyethylene glycol solution; 2) Place rebamipide, microcrystalline cellulose, behenicol glyceryl ester and poloxamer in a granulator. Preheat the raw materials and auxiliary materials. When the material temperature reaches 40-42℃, spray granulation is performed. The air inlet temperature is 60±10℃ and the fan frequency is 25-30Hz. The material temperature is ≤50℃. 3) Granulate the grains and mix with magnesium stearate and low-substituted hydroxypropyl cellulose; 4) Stamping and pressing.

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