A kind of medicine sustained-release tablet and preparation method thereof

Abstract

The present invention discloses a drug sustained-release tablet and a preparation method thereof. The preparation method of the drug sustained-release tablet adopts direct powder compression or dry granulation for preparation, and the preparation process does not include a heating step; the raw materials of the drug sustained-release tablet include a lipid material, a hydrophobic lubricant and a highly soluble drug; wherein the lipid material includes a waxy material, and the particle size D90 of the waxy material is less than 150 μm; and the raw materials do not contain a solvent. In the present invention, no additional solvent is introduced, and no heating is required, and a drug sustained-release tablet of qualified quality can be well prepared, the process is simple, the production efficiency is high, and the active pharmaceutical ingredient in the drug sustained-release tablet is stable.

Description

Technical Field

[0001] The invention relates to a drug sustained-release tablet and a preparation method thereof. Background Art

[0002] Highly hygroscopic drugs are generally highly water-soluble drugs. When the humidity exceeds a certain level, they will quickly absorb moisture, causing the drug to dissolve and release quickly. Therefore, it is very difficult to prepare sustained-release preparations for such drugs. At present, there are many methods for preparing water-soluble drugs into sustained-release tablets, such as membrane-controlled type and skeleton type. The membrane-controlled type controls the release of the drug by the type, thickness and amount of pore-forming agent of the coating film. The preparation process is relatively complicated. It is necessary to prepare the plain tablet first and then coat it. In addition, due to environmental protection requirements, most coating materials are aqueous dispersions. Therefore, during the coating process, highly hygroscopic drug tablets will cause the tablet core to absorb moisture quickly, thereby causing drug release during the coating process. Skeleton tablets are usually prepared using some insoluble polymer materials, such as ethyl cellulose. Ethyl cellulose skeleton tablets usually release drugs in a diffusion manner. The content of drug components in the tablet is small, resulting in a large weight of high-dose drug tablets, and the micropores of the tablets are easy to absorb moisture during storage, making the sustained-release effect of water-soluble drug skeleton tablets poor.

[0003] Patent CN101652128B uses a sustained-release composition prepared from a waxy material and CN102202654B chewable sustained-release preparations, both of which have a common problem, that is, solvents are introduced. Drying after wet granulation of wax or plant protein is a very slow process, which requires continuous drying at a high temperature for dozens of hours, and the drying process requires step-by-step drying, and the production efficiency is very low. And many raw materials are not stable under high temperature and humidity conditions, and are easily degraded, thereby affecting the quality of the product. Patent CN102258496B pyridostigmine bromide sustained-release tablets and preparation methods thereof require coating during preparation, which increases costs.

[0004] Therefore, there is an urgent need for a drug sustained-release tablet that can achieve the slow release of water-soluble drugs, has a simple production process, does not introduce additional solvents, does not require heating, does not affect the stability of drug raw materials, and is suitable for industrial production and ensures a uniform content of active drug components. Summary of the invention

[0005] In order to overcome the problems of poor sustained-release effect of water-soluble drugs, complex preparation process, low production efficiency and unstable active pharmaceutical ingredients, the present invention provides a sustained-release drug tablet and a preparation method thereof, which can prepare qualified sustained-release drug tablets without introducing additional solvents or heating, has a simple process, high production efficiency and stable active pharmaceutical ingredients in the sustained-release drug tablets.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] The present invention provides a method for preparing a sustained-release drug tablet, which is prepared by direct compression of powder or dry granulation, and the preparation process does not include a heating step;

[0008] The raw materials of the drug sustained-release tablet include lipid material, hydrophobic lubricant and highly soluble drug;

[0009] Wherein, the lipid material comprises a waxy material, the D90 particle size of the waxy material is less than 150 μm, and the raw material does not contain a solvent.

[0010] In the present invention, the wax material is conventionally selected in the art, and preferably includes one or more of carnauba wax, glyceryl stearate, and insect wax.

[0011] In the present invention, preferably, the D90 particle size of the waxy material is less than 90 μm, more preferably, less than 60 μm.

[0012] In the present invention, the hydrophobic lubricant is conventionally selected in the art, and preferably includes one or more of magnesium stearate, stearic acid, and micro-powdered silica gel.

[0013] In the Chinese Pharmacopoeia, "very soluble, easily soluble, soluble, slightly soluble, slightly soluble, very slightly soluble, almost insoluble or insoluble" are used to describe the solubility properties of drugs in different solvents; in the present invention, the highly soluble drug is classified as a highly soluble drug according to the Chinese Pharmacopoeia, which means that 1g (mL) of the solute can be dissolved in less than 1mL of solvent; preferably, the highly soluble drug is pyridostigmine bromide.

[0014] In the present invention, preferably, the raw material further comprises plant protein and / or an adsorbent;

[0015] Wherein, the plant protein is conventionally selected in the art, preferably, the plant protein is corn protein, more preferably, corn protein with a moisture content ≤2.5%, and most preferably, corn protein with a moisture content ≤1.5%, and the percentages are mass percentages.

[0016] In the present invention, the adsorbent is conventionally selected in the art, preferably, includes one or more of anhydrous lactose, pregelatinized starch, calcium phosphate, and calcium hydrogen phosphate.

[0017] In the present invention, preferably,

[0018] The content of the lipid material accounts for 8.1-58.5% of the raw material, for example: 8.1%, 16.1%, 19.4%, 21.0%, 22.6%, 24.4%, 27.0%, 32.1%, 32.3%, 35.5%, 36.8%, 38.5%, 45.0%, 45.5%, 48.4%, 56.5%, 58.5%;

[0019] The content of the hydrophobic lubricant is 1.6% to 10.8% of the raw material, for example: 1.6%, 2.5%, 3.2%, 3.6%, 3.8%, 4.4%, 4.6%, 4.8%, 5.9%, 6.5%, 6.8%, 10.8%;

[0020] The content of the highly soluble drug accounts for 13.6-40.0% of the raw material; for example: 13.6%, 15.0%, 16.2%, 21.4%, 27.7%, 29.0%, 35.3%, 38.5%, 40.0%;

[0021] When the raw material includes vegetable protein and / or adsorbent:

[0022] The content of the vegetable protein accounts for 0-48.4% of the raw material, excluding 0%; for example: 9.2%, 11.4%, 16.1%, 16.9%, 17.7%, 18.9%, 19.2%, 20.0%, 22.1%, 24.4%, 25.8%, 28.6%, 29.0%, 32.3%, 48.4%;

[0023] The content of the adsorbent is 0-30.6% of the raw material, excluding 0%; for example: 6.4%, 6.7%, 8.1%, 9.7%, 12.3%, 12.9%, 14.3%, 16.1%, 17.5%, 17.7%, 19.4%, 21.0%, 22.7%, 27.0%, 30.6%;

[0024] The percentages mentioned are all by mass.

[0025] In the present invention, the direct compression of the powder is a conventional preparation method in the art, preferably, it comprises the following steps: step S1: mixing the highly soluble drug with the lipid material, sieving to obtain a premixed powder, and then sieving the other raw materials separately for standby use; step S2: mixing the raw materials other than the hydrophobic lubricant with the premixed powder; or adding part of the hydrophobic lubricant and mixing with the premixed powder; step S3: adding the remaining hydrophobic lubricant, continuing to mix, and tableting.

[0026] The equipment used in the mixing operation may be conventional equipment in the art, including a square cone mixer and a three-dimensional mixer.

[0027] The mixing time may be 8 to 20 minutes, preferably 15 minutes.

[0028] In the present invention, the dry granulation is a conventional preparation method in the art, suitable for large-scale commercial production, and preferably comprises the following steps:

[0029] The raw materials are sieved separately, and the raw materials except the hydrophobic lubricant are mixed, for example, for 20 minutes; then a part of the hydrophobic lubricant is added, for example, 50% of the hydrophobic lubricant; the mixing is continued, for example, for 10 minutes; and the mixed material is granulated by a dry granulator, the oil pressure is controlled, and the obtained granules are mixed evenly with the remaining hydrophobic lubricant, and then tabletted.

[0030] Wherein, the parameters of the dry granulator meet one or more of the following conditions:

[0031] (1) The gap between the pressure rollers can be 0.6-1.5 mm, preferably 0.7-1.2 mm, and more preferably 0.8-1.0 mm.

[0032] (2) The temperature of the pressure roller is not more than 35°C, preferably not more than 30°C, and more preferably not more than 25°C;

[0033] (3) The oil pressure of the whole pellet machine can be 10-60 bar, preferably 20-50 bar, and more preferably 25-35 bar;

[0034] (4) The sieve aperture of the granulator can be 0.6-1.5 mm, preferably 0.8-1.2 mm, and more preferably 0.8-1.0 mm;

[0035] (5) The rotation speed of the pelletizer can be 70 to 200 rpm, preferably 100 to 150 rpm, and more preferably 100 to 120 rpm.

[0036] The present invention also provides a drug sustained-release tablet, which is prepared by the preparation method of the drug sustained-release tablet.

[0037] On the basis of being in accordance with the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0038] The reagents and raw materials used in the present invention are commercially available.

[0039] The positive and progressive effects of the present invention are:

[0040] 1. The method for preparing the sustained-release drug tablet provided by the present invention has simple process and high production efficiency.

[0041] 2. No additional solvent is introduced during the preparation process, and the temperature does not need to be increased during the production process. It is also possible to prepare qualified sustained-release drug tablets. Drugs that are sensitive to moisture and heat can also be produced using this process, which can greatly reduce the related substances of the product and ensure the stability of the active ingredients of the drug.

[0042] 3. The present invention achieves the purpose of adjusting the release rate and moisture resistance of the drug by regulating the type and content of each component in the drug sustained-release tablet.

[0043] 4. The dry granulation method described in the present invention is particularly suitable for commercial production and has good uniformity of the content of active pharmaceutical ingredients. DETAILED DESCRIPTION

[0044] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0045] The examples and comparative examples are shown in Table 1:

[0046] Examples 1 to 17 and Example 22 adopt a powder direct compression method to prepare drug sustained-release tablets.

[0047] Among them, the preparation processes of Examples 1, 5 to 11, and 16 to 17 are specifically as follows:

[0048] ① Place the active pharmaceutical ingredient (hereinafter referred to as API) and wax material into a square cone mixer, mix for 15 minutes, pass through a 60-mesh sieve, mark as premixed powder 1, and set aside.

[0049] ② Pass the remaining materials through a 40-mesh sieve and set aside.

[0050] ③ Add the raw materials except the hydrophobic lubricant to the square cone mixer in the order of adding so that the premixed powder 1 is in the middle. Mix for 15 minutes.

[0051] ④ Add the hydrophobic lubricant into the square cone mixer and continue mixing for 10 minutes.

[0052] ⑤ Compress the above mixed powder into tablets.

[0053] The preparation process of Examples 2 and 3 is as follows:

[0054] ① Place API and wax material into a square cone mixer, premix for 15 minutes, pass through a 60-mesh sieve, mark as premix powder 1, and set aside.

[0055] ② Pass the remaining raw materials through a 40-mesh sieve and set aside.

[0056] ③ Add all materials except stearic acid into the square cone mixer in the order that premixed powder 1 is in the middle. Mix for 15 minutes.

[0057] ④ Add stearic acid into the square cone mixer and continue mixing for 10 minutes.

[0058] ⑤ Compress the above mixed powder into tablets.

[0059] The preparation process of Example 4 is as follows:

[0060] ① Place API and wax material into a square cone mixer, premix for 15 minutes, pass through a 60-mesh sieve, mark as premix powder 1, and set aside.

[0061] ② Pre-mix the micro powder silica gel and corn protein and pass through a 40 mesh sieve for later use.

[0062] ③ Add all the raw materials except magnesium stearate into the square cone mixer in the order that premixed powder 1 is in the middle. Mix for 15 minutes.

[0063] ④ Add magnesium stearate into the square cone mixer and continue mixing for 10 minutes.

[0064] ⑤ Compress the above mixed powder into tablets.

[0065] The preparation process of Example 12 is as follows:

[0066] ① Place API and wax material into a square cone mixer, premix for 15 minutes, pass through a 60-mesh sieve, mark as premix powder 1, and set aside.

[0067] ② Premix the micro powder silica gel and calcium phosphate, pass through a 40-mesh sieve, and mark as premixed powder 2. Pass the remaining raw materials through a 40-mesh sieve respectively and set aside.

[0068] ③ Add premixed powder 2, premixed powder 1 and corn protein into the square cone mixer in sequence and mix for 20 minutes.

[0069] ④ Add magnesium stearate into the square cone mixer and continue mixing for 5 minutes.

[0070] ⑤ Compress the above mixed powder into tablets.

[0071] The preparation process of Examples 13 to 15 is as follows:

[0072] ① Place API and wax material into a square cone mixer, premix for 15 minutes, pass through a 60-mesh sieve, mark as premix powder 1, and set aside.

[0073] ② Pass the remaining materials through a 40-mesh sieve and set aside.

[0074] ③ Add all the raw materials except magnesium stearate into the square cone mixer in the order that premixed powder 1 is in the middle. Mix for 20 minutes.

[0075] ④ Add magnesium stearate into the square cone mixer and continue mixing for 8 minutes.

[0076] ⑤ Compress the above mixed powder into tablets.

[0077] Embodiment 22

[0078] ① Place API and wax material into a three-dimensional mixer, premix for 20 minutes, pass through a 60-mesh sieve, mark as premix powder 1, and set aside.

[0079] ② Premix the micro powder silica gel and calcium phosphate, pass through a 40-mesh sieve, and mark as premixed powder 2. Pass the remaining raw materials through a 40-mesh sieve respectively and set aside.

[0080] ③ Add premixed powder 2, premixed powder 1 and corn protein into the three-dimensional mixer in sequence and mix for 10 minutes.

[0081] ④ Add magnesium stearate into the three-dimensional mixer and continue mixing for 10 minutes.

[0082] ⑤ Compress the above mixed powder into tablets.

[0083] In Examples 18 to 21 and Example 23, a dry granulator was used to prepare sustained-release drug tablets. The specific steps are as follows:

[0084] ①Put the highly soluble drug and waxy material into a square cone mixer, premix for 10 minutes, pass through a 40-mesh sieve, mark as premixed powder 1, and set aside.

[0085] ② Pass the remaining materials through a 40-mesh sieve and set aside.

[0086] ③ Add the materials except the hydrophobic lubricant and premixed powder 1 into the square cone mixer, then add 50% micro powder silica gel and 50% magnesium stearate, and finally add premixed powder 1 and mix for 20 minutes.

[0087] ④ Use a dry granulator for granulation. The control parameters during the preparation process are as follows:

[0088] (1) The gap between the rollers is initially 1.2-1.5 mm, maintained at 0.8-1.0 mm during granulation, and 0.6-0.8 mm at the end.

[0089] (2) Control the roller temperature to no more than 25°C. If the temperature is too high, slow down the dry granulation speed and turn on the chiller.

[0090] (3) The initial setting of the oil pressure of the pelletizing machine is 25 bar, and the oil pressure is controlled at 25-35 bar during the process.

[0091] (4) Granulator screen aperture: 0.6 mm, 0.8 mm, 1.0 mm and 1.2 mm were selected in Examples 18-21, respectively, and 1.0 mm was selected in Example 23.

[0092] (5) The initial speed of the pelletizer is set at 150 rpm, which is adjusted to 10-120 rpm during the process and to 150-200 rpm at the end.

[0093] ⑤ Add the remaining micro-powder silica gel, magnesium stearate and dry granulated granules into the square cone mixer and mix for 10 minutes.

[0094] ⑥ The mixed granules are tableted.

[0095] In Comparative Example 1, a melt granulation preparation method is used to prepare a drug sustained-release tablet. Comparative Example 1 is prepared according to the raw material content in Table 1. The melt granulation preparation method used is the following steps:

[0096] First, the raw materials are sieved separately, the carnauba wax is heated to 80°C to melt, and the drug powder is added with continuous stirring, stirred and mixed, and the mixture is taken out after being mixed evenly, dried in an oven at 60°C for 2 hours, cooled to room temperature, further crushed through a 60-mesh sieve, and finally mixed evenly with other materials in the formula and tableted.

[0097] Dry granulation is a continuous process operation, and the parameters are adjusted within the parameters mentioned above during the production process.

[0098] In the above embodiments and comparative examples:

[0099] 1) D90 particle size of waxy materials: D90 particle size of carnauba wax is not more than 60 μm; D90 particle size of wax wax is 100-150 μm; D90 particle size of stearic acid glyceryl is not more than 60 μm in Example 1; 70-100 μm in Examples 7 and 9; and 100-150 μm in Examples 19 and 20.

[0100] 2) Water content of corn gluten: In Examples 6 to 8 and 10 to 15, the water content of corn gluten was 1.9 to 2.5%, and in the remaining Examples, the water content of corn gluten was ≤ 1.5%.

[0101] 3) The RSD of the uniformity of the active ingredient content of the granules mixed before tableting in Example 22 was 4.9%.

[0102] The RSD of the uniformity of the active pharmaceutical ingredient content of the granules mixed in step ⑤ of Example 23 was 1.3%.

[0103] The RSD of uniformity of the active pharmaceutical ingredient content of the mixed granules before tableting in Example 24 was 1.9%.

[0104] 4) The production batches of Examples 1 to 21 are relatively small, ranging from 100 to 1000 pieces per batch.

[0105] Examples 22 to 24 are commercial production batches, with 120,000 pieces per batch.

[0106] Table 1 Composition and content of the examples

[0107]

[0108]

[0109]

[0110] Effect Example 1

[0111] Testing of relevant substance content

[0112] The drug sustained-release tablets prepared in the example were ground into fine powder, and an appropriate amount of fine powder (equivalent to 50 mg of pyridostigmine bromide) was taken, and the fine powder was placed in a 50 mL volumetric flask, and an appropriate amount of mobile phase was added to dissolve the pyridostigmine bromide, and then diluted to the scale with the mobile phase, shaken well, filtered, and the filtered solution was taken as the test solution.

[0113] An appropriate amount of pyridostigmine bromide reference substance and pyridin-3-yldimethylcarbamate were accurately weighed, added to the mobile phase to dissolve them, and diluted with the mobile phase to prepare a 5.0 μg / mL solution as the system suitability solution.

[0114] Accurately weigh an appropriate amount of pyridostigmine bromide reference substance, add an appropriate amount of mobile phase to dissolve it, and dilute it with the mobile phase to prepare 5 μg / mL reference solution 1 and 60 μg / mL reference solution 2.

[0115] Sampling was carried out according to the high performance liquid chromatography method (General Rules 0512 of Part IV of the Chinese Pharmacopoeia), using a chromatographic column with octadecylsilane bonded silica gel as filler (recommended XB-C18 specification: 4.6×250mm, 5μm or column efficiency equivalent); 4.3g / L sodium dodecyl sulfate solution (pH adjusted to 2.0 with phosphoric acid): acetonitrile = 70:30 as mobile phase, flow rate of 1.1mL / min, column temperature of 25℃, detection wavelength of 220nm. The separation degree of pyridostigmine bromide peak and impurity A was not less than 1.5; the relative standard deviation of the control solution 1 was not more than 5.0%, and the signal-to-noise ratio of the sensitive solution was not less than 10.

[0116] Impurity limit requirements: (Peaks less than 0.04% are ignored).

[0117] Impurities Limit not exceeding NMT (%) Impurity B 0.2 Impurity A 0.2 Other degradation impurities 0.2 Total Miscellaneous 0.5

[0118] The test results of the relevant substance content are shown in Table 2. Impurity A is pyridin-3-yldimethylcarbamate, and impurity B is 3-hydroxy-1-methylpyridine Salt-1-ammonium bromide (3-hydroxy-1-methylpyridinium-1-ium bromide), wherein impurity B is a degradation impurity. The accelerated test is carried out in accordance with the Chinese Pharmacopoeia Part IV 9001 Guidelines for Stability Tests of Raw Materials and Preparations. The temperature is 40°C ± 2°C and the relative humidity is 75% ± 5%. As shown in Table 2, the drug sustained-release tablets prepared by the preparation method of the present invention have better stability than the conventional melt granulation method.

[0119] Table 2 Test results of relevant substance content

[0120]

[0121]

[0122]

[0123] Effect Example 2

[0124] Dissolution test

[0125] Take the drug sustained-release tablet prepared in the example, and conduct an experiment according to the dissolution and release determination method (General Rule 0931 Method 2), with 900mL of water as the dissolution medium, the rotation speed is 50 revolutions per minute, and after 0.25h / 0.5h / 1h / 2h / 4h / 6h / 8h / 12h / 18h, take 5mL of solution respectively, and immediately replenish the dissolution medium of the same temperature and the same volume, filter, accurately measure 20μL of the filtrate, and detect it by liquid chromatograph according to the chromatographic conditions in Effect Example 1, and record the chromatogram;

[0126] Take about 20 mg of pyridostigmine bromide reference substance, weigh accurately, place in a 100 mL volumetric flask, add 50 mL of water, sonicate, dissolve, dilute to scale with dissolution medium, shake well, and measure with the second method of general rule 0931. Calculate the dissolution amount of each tablet at different times. The dissolution test results are shown in Table 3.

[0127] It can be seen from Table 3 that the drug sustained-release tablets prepared by the preparation method of the present invention have a comparable sustained-release effect compared to conventional melt granulation.

[0128] Table 3 Dissolution test results

[0129]

[0130]

[0131] Effect Example 3 Detection of moisture content

[0132] The drug sustained-release tablets prepared in the example were ground into fine powder and measured according to the moisture determination method (Chinese Pharmacopoeia General Rules 0832 Method 1). The test results of moisture content are shown in Table 4. According to Table 4, the drug sustained-release tablets prepared by the preparation method of the present invention have a considerable moisture resistance effect compared with conventional melt granulation.

[0133] Table 4 Test results of moisture content

[0134]

[0135]

Claims

1. A method for preparing a sustained-release drug tablet, characterized in that: The preparation is carried out by direct compression of powder or dry granulation, and the preparation process does not include a heating step; The raw materials of the drug sustained-release tablet are composed of lipid material, hydrophobic lubricant, high-solubility drug, plant protein and adsorbent; Or, the raw materials of the drug sustained-release tablet are composed of lipid material, hydrophobic lubricant, highly soluble drug and plant protein; Or, the raw materials of the drug sustained-release tablet are composed of lipid material, hydrophobic lubricant, highly soluble drug and adsorbent; Wherein, the lipid material comprises a waxy material, and the D90 particle size of the waxy material is less than 150 μm; the raw material does not contain a solvent; The highly soluble drug is pyridostigmine bromide; The adsorbent is selected from one or more of anhydrous lactose, pregelatinized starch, calcium phosphate and calcium hydrogen phosphate; The wax material includes one or more of carnauba wax, stearyl glyceryl and beet wax; The hydrophobic lubricant includes one or more of magnesium stearate, stearic acid and micro-powder silica gel; The plant protein is corn protein with a moisture content of ≤2.5%; The content of the lipid material accounts for 8.1-58.5% of the raw material; The content of the hydrophobic lubricant accounts for 1.6% to 10.8% of the raw material; The content of the highly soluble drug accounts for 13.6-40.0% of the raw material; The content of the vegetable protein is 0 to 48.4% of the raw material, excluding 0%; The adsorbent content is 0 to 30.6% of the raw material, excluding 0%; The percentages mentioned are all mass percentages; The powder direct compression comprises the following steps: step S1: mixing the highly soluble drug and the lipid material, sieving them to obtain a premixed powder, and then sieving the other raw materials separately for standby use; step S2: mixing the raw materials other than the hydrophobic lubricant with the premixed powder; or adding part of the hydrophobic lubricant and mixing with the premixed powder; step S3: adding the remaining hydrophobic lubricant, continuing to mix, and tableting; The equipment used in the mixing operation includes a square cone mixer and a three-dimensional mixer; the mixing time is 8 to 20 minutes; Or, the dry granulation comprises the following steps: The raw materials are sieved separately, and the raw materials other than the hydrophobic lubricant are mixed for 20 minutes; 50% of the hydrophobic lubricant is then added; the mixing is continued for 10 minutes; the mixed material is granulated by a dry granulator, the oil pressure is controlled, the obtained granules are evenly mixed with the remaining hydrophobic lubricant, and then tabletted.

2. The method for preparing a sustained-release drug tablet as claimed in claim 1, characterized in that: The waxy material has a D90 particle size of less than 90 μm.

3. The method for preparing a sustained-release drug tablet as claimed in claim 2, characterized in that: The waxy material has a D90 particle size of less than 60 μm.

4. The method for preparing a sustained-release drug tablet according to claim 1, characterized in that: The plant protein is corn protein with a moisture content of ≤1.5%, and the percentage is a mass percentage.

5. The method for preparing a sustained-release drug tablet according to claim 1, characterized in that: The lipid material comprises 8.1%, 16.1%, 19.4%, 21.0%, 22.6%, 24.4%, 27.0%, 32.1%, 32.3%, 35.5%, 36.8%, 38.5%, 45.0%, 45.5%, 48.4%, 56.5%, 58.5% of the raw material; Or, the content of the hydrophobic lubricant is 1.6%, 2.5%, 3.2%, 3.6%, 3.8%, 4.4%, 4.6%, 4.8%, 5.9%, 6.5%, 6.8%, 10.8% of the raw material; Or, the content of the highly soluble drug is 13.6%, 15.0%, 16.2%, 21.4%, 27.7%, 29.0%, 35.3%, 38.5%, 40.0% of the raw material; Or, the content of the vegetable protein is 9.2%, 11.4%, 16.1%, 16.9%, 17.7%, 18.9%, 19.2%, 20.0%, 22.1%, 24.4%, 25.8%, 28.6%, 29.0%, 32.3%, 48.4% of the raw material; Or, the content of the adsorbent is 6.4%, 6.7%, 8.1%, 9.7%, 12.3%, 12.9%, 14.3%, 16.1%, 17.5%, 17.7%, 19.4%, 21.0%, 22.7%, 27.0%, 30.6% of the raw material; The percentages mentioned are all by mass.

6. The method for preparing a sustained-release drug tablet according to claim 1, characterized in that: During the direct pressing of the powder, the mixing time is 15 minutes.

7. The method for preparing a sustained-release drug tablet according to claim 1, characterized in that: The parameters of the dry granulator meet one or more of the following conditions: (1) The gap between the rollers is 0.6 to 1.5 mm; (2) The temperature of the pressure roller is not more than 35°C; (3) The oil pressure of the whole pellet machine is 10-60 bar; (4) The aperture of the sieve of the granulator is 0.6 to 1.5 mm; (5) The speed of the pelletizing machine is 70-200 rpm.

8. The method for preparing a sustained-release drug tablet according to claim 7, characterized in that: The parameters of the dry granulator meet one or more of the following conditions: (1) The gap between the rollers is 0.7-1.2 mm; (2) The temperature of the pressure roller is not more than 30°C; (3) The whole oil pressure is 20-50 bar; (4) The aperture of the sieve of the granulator is 0.8 to 1.2 mm; (5) The speed of the pelletizing machine is 100-150 rpm.

9. The method for preparing a sustained-release drug tablet according to claim 8, characterized in that: The parameters of the dry granulator meet one or more of the following conditions: (1) The gap between the rollers is 0.8-1.0 mm; (2) The temperature of the pressure roller is not more than 25°C; (3) The whole oil pressure is 25-35 bar; (4) The aperture of the granulator screen is 0.8-1.0 mm; (5) The speed of the pelletizing machine is 100-120 rpm.

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