Isosorbide mononitrate sustained-release tablet and preparation method thereof

Abstract

An isosorbide mononitrate sustained-release tablet and a preparation method thereof belong to the technical field of pharmaceutical preparations. The preparation adopts a method combining drug application on micro-pills and spray coating on the bottom of a fluidized bed to prepare drug-loaded micro-pills to achieve the purpose of sustained release. The invention comprises the following steps: (1) dissolving isosorbide mononitrate and hydroxypropyl cellulose in purified water, and spraying the drug on the bottom of a fluidized bed; (2) coating the sustained-release layer to prepare sustained-release coated micro-pills; (3) mixing the sustained-release coated micro-pills with the added excipients evenly, and pressing the tablets; (4) coating the obtained plain tablets with a moisture-proof coating material (Opadry AMB) to prepare film-coated tablets. The sustained-release tablets prepared by the invention have the advantages of stable drug release, high bioavailability, good stability, and simple preparation process.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an isosorbide mononitrate sustained-release tablet and a preparation method thereof. Background Art

[0002] Isosorbide mononitrate is a new generation of nitrate antianginal drugs. Its chemical name is 3,6-dianhydro-D-sorbitol-5-nitrate, and its molecular formula is C 6 H 9 NO 6 , molecular weight 191.14, structural formula is as follows:

[0003]

[0004] Isosorbide mononitrate is a white needle-shaped crystal or crystalline powder. It is easily soluble in methanol or acetone, soluble in chloroform or water, and almost insoluble in hexane. Isosorbide mononitrate, also known as 5-isosorbide mononitrate, is a long-acting nitrate anti-angina and coronary heart disease treatment drug. Its main pharmacological action is to relax vascular smooth muscle, dilate arteries and veins, and mainly dilates veins. Isosorbide mononitrate is the main active metabolite of isosorbide nitrate in the body. It is rapidly and completely absorbed orally and has no first-pass metabolic effect in the liver, which reduces the difference in blood drug concentration within and between individuals, making the clinical effect of the drug predictable and reproducible. The elimination half-life of isosorbide mononitrate is about 5 hours. It can be used for long-term treatment of coronary heart disease, prevention of angina pectoris, treatment of persistent angina pectoris after myocardial infarction, etc. It is currently one of the best drugs for the prevention and treatment of angina pectoris.

[0005] At present, the clinical dosage forms of isosorbide mononitrate include ordinary tablets, sustained-release preparations and injections. Ordinary isosorbide mononitrate tablets or capsules are frequently administered (need to be taken 2 to 3 times a day) and have large fluctuations in blood drug concentration. When the body's blood drug concentration drops to the lowest level in the late night or early morning, angina pectoris is prone to occur, and frequent administration is prone to drug resistance. However, isosorbide mononitrate sustained-release preparations are administered once a day during the medication period, which reduces the number of medications and basically does not cause drug resistance. At the same time, the unique drug release system of isosorbide mononitrate sustained-release preparations conforms to the circadian rhythm of cardiovascular events. It not only takes effect quickly but also provides long-term protection, thereby greatly reducing the probability of nocturnal angina pectoris in patients and improving patient compliance. For chronic diseases such as coronary heart disease and angina pectoris that require long-term medication, safe and effective isosorbide mononitrate sustained-release tablets are a better choice of medication.

[0006] The existing technology on the market controls the diffusion rate of the drug through skeleton diffusion, coating membrane diffusion or the combination of the two, thereby achieving a sustained release effect. The widely used clinical sustained-release preparations of isosorbide mononitrate include skeleton tablets, membrane-controlled release tablets, sustained-release pellets, etc., and their release preparations are mainly traditional skeleton-type drug release and membrane-controlled drug release. Skeleton-type sustained-release tablets have problems such as uneven drug release, prone to sudden release or incomplete drug release. Summary of the invention

[0007] The invention provides an isosorbide mononitrate sustained-release tablet and a preparation method thereof. The invention adopts a membrane controlled-release method, and provides an isosorbide mononitrate sustained-release tablet with stable drug release and high stability by constructing a drug-coated micropill and a sustained-release coating system. It is found through research that the weight gain of the sustained-release layer coating has a great influence on the dissolution result of the product, but the problem of poor dissolution can be effectively solved by adding an ethyl cellulose membrane containing a pore-forming agent, polyvidone, in a suitable ratio; in addition, the drug sustained-release effect and stability can be effectively achieved by reasonably matching the ratio of the sustained-release preparation to other pharmaceutical excipients.

[0008] Specifically, the technical solution of the present invention is achieved as follows:

[0009] An isosorbide mononitrate sustained-release tablet, comprising sustained-release coated micropellets and external excipients, wherein the sustained-release coated micropellets are composed of drug-containing micropellets and sustained-release coating materials; the external excipients include fillers, disintegrants, lubricants, and film coating materials; the preparation method comprises first mixing the sustained-release coated micropellets and the external excipients and then pressing the tablets, and then coating the cores to form film-coated tablets.

[0010] Furthermore, the above-mentioned medicine micro-pills are composed of isosorbide mononitrate, microcrystalline cellulose pellet cores, and a binder; and the sustained-release coating material is composed of an ethyl cellulose film containing a pore-forming agent.

[0011] Furthermore, the binder is hydroxypropyl cellulose, and the weight ratio is isosorbide mononitrate:hydroxypropyl cellulose=8:1; and the pore-forming agent is povidone.

[0012] Furthermore, the mass percentage of the ethyl cellulose film in the upper medicine pellets is 24-33%.

[0013] Furthermore, the mass percentage of the ethyl cellulose film in the upper medicine pellets is 30%.

[0014] Furthermore, the filler is selected from one of lactose and microcrystalline cellulose KG-802, among which microcrystalline cellulose KG-802 has the best effect.

[0015] Furthermore, the disintegrant is selected from two of cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose, and the ratio of the two is 1:0.5-1.

[0016] Furthermore, the disintegrant is selected from two of cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose, and the ratio of the two is 1:1.

[0017] Furthermore, the weight gain of the film coating layer is 3-4%.

[0018] In the technical solution of the present invention, the isosorbide mononitrate sustained-release tablets are prepared by the following steps:

[0019] (1) dissolving isosorbide mononitrate and hydroxypropyl cellulose in purified water to prepare a drug solution, placing microcrystalline cellulose pellets in a fluidized bed for bottom spraying, controlling the material temperature at 30-40° C., and sieving the drug pellets with a 40-mesh sieve;

[0020] (2) preparing a sustained-release solution with ethyl cellulose and povidone, placing the drug-coated pellets in a fluidized bed for bottom spray coating, controlling the material temperature at 30-35° C. to prepare sustained-release coated pellets, and sieving the sustained-release coated pellets with a 40-mesh sieve;

[0021] (3) mixing the sustained-release coated pellets and the external excipients uniformly, and tableting to prepare plain tablet cores;

[0022] (4) Weigh the prescription amount Add 10-12 times the amount of 10% ethanol to the film coating premix and stir evenly to obtain the coating solution;

[0023] (5) coating the sustained-release tablet core obtained in step (3), and drying at 35-40° C. to increase the tablet weight by 3-4%.

[0024] The isosorbide mononitrate sustained-release tablets are obtained.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The preparation process is simple. The method comprises dissolving isosorbide mononitrate and part of a binder in purified water to prepare an upper drug solution, performing bottom spray coating to obtain an upper drug pill, performing sustained-release coating on the upper drug pill, mixing the coated sustained-release micro-pellets with an additional auxiliary material uniformly, and then pressing the tablets, and then performing film coating to obtain an isosorbide mononitrate sustained-release tablet. The drug release is stable, the stability is good, and the bioavailability is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 : Effects of different dosages of hydroxypropyl cellulose on the total impurity content of isosorbide mononitrate sustained-release tablets under the same conditions. Specific embodiments

[0028] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0029] Example 1 (1000 pieces prepared)

[0030] An isosorbide mononitrate sustained-release tablet, the composition of which is shown in the following table:

[0031]

[0032] Preparation process:

[0033] (1) Drug application: Dissolve 40g of isosorbide mononitrate and 5g of hydroxypropyl cellulose in 155g of purified water to prepare a drug application solution, and then place the microcrystalline cellulose pellets in a fluidized bed for bottom spraying. During the spraying process, set the inlet air temperature to 35-45°C and the inlet air volume to 25-35m 3 / h, peristaltic pump speed 3-6Hz, spray pressure 0.20MPa, control material temperature 30-40℃. After spraying, keep the material temperature at 40℃ and dry for 10min;

[0034] (2) Screening of drug pellets: Collect the drug pellets that pass through a 40-mesh sieve;

[0035] (3) Sustained-release coating: Dissolve 28.8 g of ethyl cellulose and 7.2 g of povidone in 204 g of 80% ethanol solution to prepare a sustained-release solution. Place the drug pellets in a fluidized bed for bottom spray coating. During the spraying process, set the air inlet temperature to 35-40°C and the air volume to 25-35 m 3 / h, peristaltic pump speed 4Hz, spray pressure 0.20MPa, control material temperature at 30-35℃. After spraying, keep material temperature at 35℃ and dry for 10min;

[0036] (4) Screening of sustained-release coated pellets: Collect the sustained-release coated pellets that pass through a 40-mesh sieve;

[0037] (5) Mixing: Mixing the sustained-release coated pellets and the added excipients uniformly;

[0038] (6) Tableting: preparing plain tablet cores;

[0039] (7) Weigh the prescription amount The film coating premix is ​​added with 10-12 times the amount of 10% ethanol and stirred evenly to obtain a coating solution; the plain tablet core obtained in step (6) is coated, and the tablet weight increases by 3-4% after drying at 35-40° C., thereby obtaining the isosorbide mononitrate sustained-release tablet.

[0040] Example 2 (1000 pieces prepared)

[0041] An isosorbide mononitrate sustained-release tablet, the composition of which is shown in the following table:

[0042]

[0043] Preparation process:

[0044] (1) Drug application: Dissolve 40g of isosorbide mononitrate and 5g of hydroxypropyl cellulose in 155g of purified water to prepare a drug application solution, and then place the microcrystalline cellulose pellets in a fluidized bed for bottom spraying. During the spraying process, set the inlet air temperature to 35-45°C and the inlet air volume to 25-35m 3 / h, peristaltic pump speed 3-6Hz, spray pressure 0.20MPa, control material temperature 30-40℃. After spraying, keep the material temperature at 40℃ and dry for 10min;

[0045] (2) Screening of drug pellets: Collect the drug pellets that pass through a 40-mesh sieve;

[0046] (3) Sustained-release coating: 35.2 g of ethyl cellulose and 8.8 g of povidone were dissolved in 249 g of 80% ethanol solution to prepare a sustained-release solution. The drug pellets were placed in a fluidized bed for bottom spray coating. During the spraying process, the air inlet temperature was set at 35-40 °C and the air volume was set at 25-35 m 3 / h, peristaltic pump speed 4Hz, spray pressure 0.20MPa, control material temperature at 30-35℃. After spraying, keep material temperature at 35℃ and dry for 10min;

[0047] (4) Screening of sustained-release coated pellets: Collect the sustained-release coated pellets that pass through a 40-mesh sieve;

[0048] (5) Mixing: Mixing the sustained-release coated pellets and the added excipients uniformly;

[0049] (6) Tableting: preparing plain tablet cores;

[0050] (7) Weigh the prescription amount The film coating premix is ​​added with 10-12 times the amount of 10% ethanol and stirred evenly to obtain a coating solution; the plain tablet core obtained in step (6) is coated, and the tablet weight increases by 3-4% after drying at 35-40° C., thereby obtaining the isosorbide mononitrate sustained-release tablet.

[0051] Example 3 (1000 pieces prepared)

[0052] An isosorbide mononitrate sustained-release tablet, the composition of which is shown in the following table:

[0053]

[0054] Preparation process:

[0055] (1) Drug application: Dissolve 40g of isosorbide mononitrate and 5g of hydroxypropyl cellulose in 155g of purified water to prepare a drug application solution, and then place the microcrystalline cellulose pellets in a fluidized bed for bottom spraying. During the spraying process, set the inlet air temperature to 35-45°C and the inlet air volume to 25-35m 3 / h, peristaltic pump speed 3-6Hz, spray pressure 0.20MPa, control material temperature 30-40℃. After spraying, keep the material temperature at 40℃ and dry for 10min;

[0056] (2) Screening of drug pellets: Collect the drug pellets that pass through a 40-mesh sieve;

[0057] (3) Sustained-release coating: 38.4 g of ethyl cellulose and 9.6 g of povidone were dissolved in 272 g of 80% ethanol solution to prepare a sustained-release solution. The drug pellets were placed in a fluidized bed for bottom spray coating. During the spraying process, the air inlet temperature was set at 35-40 °C and the air volume was set at 25-35 m 3 / h, peristaltic pump speed 4Hz, spray pressure 0.20MPa, control material temperature at 30-35℃. After spraying, keep material temperature at 35℃ and dry for 10min;

[0058] (4) Screening of sustained-release coated pellets: Collect the sustained-release coated pellets that pass through a 40-mesh sieve;

[0059] (5) Mixing: Mixing the sustained-release coated pellets and the added excipients uniformly;

[0060] (6) Tableting: preparing plain tablet cores;

[0061] (7) Weigh the prescription amount The film coating premix is ​​added with 10-12 times the amount of 10% ethanol and stirred evenly to obtain a coating solution; the plain tablet core obtained in step (6) is coated, and the tablet weight increases by 3-4% after drying at 35-40° C., thereby obtaining the isosorbide mononitrate sustained-release tablet.

[0062] Example 4 (1000 pieces prepared)

[0063] An isosorbide mononitrate sustained-release tablet, the composition of which is shown in the following table:

[0064]

[0065] Preparation process:

[0066] (1) Drug application: Dissolve 40g of isosorbide mononitrate and 5g of hydroxypropyl cellulose in 155g of purified water to prepare a drug application solution, and then place the microcrystalline cellulose pellets in a fluidized bed for bottom spraying. During the spraying process, set the inlet air temperature to 35-45°C and the inlet air volume to 25-35m3 / h, peristaltic pump speed 3-6Hz, spray pressure 0.20MPa, control material temperature 30-40℃. After spraying, keep the material temperature at 40℃ and dry for 10min;

[0067] (2) Screening of drug pellets: Collect the drug pellets that pass through a 40-mesh sieve;

[0068] (3) Sustained-release coating: 35.2 g of ethyl cellulose and 8.8 g of povidone were dissolved in 249 g of 80% ethanol solution to prepare a sustained-release solution. The drug pellets were placed in a fluidized bed for bottom spray coating. During the spraying process, the air inlet temperature was set at 35-40 °C and the air volume was set at 25-35 m 3 / h, peristaltic pump speed 4Hz, spray pressure 0.20MPa, control material temperature at 30-35℃. After spraying, keep material temperature at 35℃ and dry for 10min;

[0069] (4) Screening of sustained-release coated pellets: Collect the sustained-release coated pellets that pass through a 40-mesh sieve;

[0070] (5) Mixing: Mixing the sustained-release coated pellets and the added excipients uniformly;

[0071] (6) Tableting: preparing plain tablet cores;

[0072] (7) Weigh the prescription amount The film coating premix is ​​added with 10-12 times the amount of 10% ethanol and stirred evenly to obtain a coating solution; the plain tablet core obtained in step (6) is coated, and the tablet weight increases by 3-4% after drying at 35-40° C., thereby obtaining the isosorbide mononitrate sustained-release tablet.

[0073] Example 5 (1000 pieces prepared)

[0074] An isosorbide mononitrate sustained-release tablet, the composition of which is shown in the following table:

[0075]

[0076] Preparation process:

[0077] (1) Drug application: Dissolve 40g of isosorbide mononitrate and 5g of hydroxypropyl cellulose in 155g of purified water to prepare a drug application solution, and then place the microcrystalline cellulose pellets in a fluidized bed for bottom spraying. During the spraying process, set the inlet air temperature to 35-45°C and the inlet air volume to 25-35m 3 / h, peristaltic pump speed 3-6Hz, spray pressure 0.20MPa, control material temperature 30-40℃. After spraying, keep the material temperature at 40℃ and dry for 10min;

[0078] (2) Screening of drug pellets: Collect the drug pellets that pass through a 40-mesh sieve;

[0079] (3) Sustained-release coating: 35.2 g of ethyl cellulose and 8.8 g of povidone were dissolved in 249 g of 80% ethanol solution to prepare a sustained-release solution. The drug pellets were placed in a fluidized bed for bottom spray coating. During the spraying process, the air inlet temperature was set at 35-40 °C and the air volume was set at 25-35 m 3 / h, peristaltic pump speed 4Hz, spray pressure 0.20MPa, control material temperature at 30-35℃. After spraying, keep material temperature at 35℃ and dry for 10min;

[0080] (4) Screening of sustained-release coated pellets: Collect the sustained-release coated pellets that pass through a 40-mesh sieve;

[0081] (5) Mixing: Mixing the sustained-release coated pellets and the added excipients uniformly;

[0082] (6) Tableting: preparing plain tablet cores;

[0083] (7) Weigh the prescription amount The film coating premix is ​​added with 10-12 times the amount of 10% ethanol and stirred evenly to obtain a coating solution; the plain tablet core obtained in step (6) is coated, and the tablet weight increases by 3-4% after drying at 35-40° C., thereby obtaining the isosorbide mononitrate sustained-release tablet.

[0084] Comparative Example 1 (1000 pieces prepared)

[0085] An isosorbide mononitrate sustained-release tablet, the composition of which is shown in the following table:

[0086]

[0087]

[0088] Preparation process:

[0089] (1) Drug application: Dissolve 40g of isosorbide mononitrate and 5g of hydroxypropyl cellulose in 155g of purified water to prepare a drug application solution, and then place the microcrystalline cellulose pellets in a fluidized bed for bottom spraying. During the spraying process, set the inlet air temperature to 35-45°C and the inlet air volume to 25-35m 3 / h, peristaltic pump speed 3-6Hz, spray pressure 0.20MPa, control material temperature 30-40℃. After spraying, keep the material temperature at 40℃ and dry for 10min;

[0090] (2) Screening of drug pellets: Collect the drug pellets that pass through a 40-mesh sieve;

[0091] (3) Sustained-release coating: 35.2 g of ethyl cellulose and 8.8 g of hydroxyethyl cellulose were dissolved in 249 g of 80% ethanol solution to prepare a sustained-release solution. The drug pellets were placed in a fluidized bed for bottom spray coating. During the spraying process, the air inlet temperature was set at 35-40°C and the air volume was set at 25-35 m 3 / h, peristaltic pump speed 4Hz, spray pressure 0.20MPa, control material temperature at 30-35℃. After spraying, keep material temperature at 35℃ and dry for 10min;

[0092] (4) Screening of sustained-release coated pellets: Collect the sustained-release coated pellets that pass through a 40-mesh sieve;

[0093] (5) Mixing: Mixing the sustained-release coated pellets and the added excipients uniformly;

[0094] (6) Tableting: preparing plain tablet cores;

[0095] (7) Weigh the prescription amount The film coating premix is ​​added with 10-12 times the amount of 10% ethanol and stirred evenly to obtain a coating solution; the plain tablet core obtained in step (6) is coated, and the tablet weight increases by 3-4% after drying at 35-40° C., thereby obtaining the isosorbide mononitrate sustained-release tablet.

[0096] Verification Example

[0097] 1. Determination of dissolution of isosorbide mononitrate sustained-release tablets: refer to the Chinese Pharmacopoeia 2020 edition

[0098] Take this product, follow the dissolution and release determination method (General Rule 0931 Method 1), use 500mL of water as the dissolution medium, rotate at 50 revolutions per minute, operate according to the method, take 5mL of solution after 1 hour, 4 hours and 8 hours, filter, and immediately add the same temperature and volume of dissolution medium, according to the chromatographic conditions under the content determination item, accurately measure 20μL of the filtrate, inject it into the liquid chromatograph, and record the chromatogram; take another isosorbide mononitrate reference substance, accurately weigh it, dissolve it in water and quantitatively dilute it to make a solution containing about 80μg per 1mL, as the reference substance solution, and determine it in the same way. Calculate the dissolution amount of each tablet at different times by peak area according to the external standard method. The dissolution amount of each tablet of this product in 1 hour, 4 hours and 8 hours should be 15%-40%, 40%-75% and more than 75% of the labeled amount, respectively.

[0099] The isosorbide mononitrate sustained-release tablets obtained from Examples 1 to 5 of the present invention are comparable to the isosorbide mononitrate sustained-release tablets (trade name: The dissolution test comparison results of retard (batch number: S001) are shown in Table 1

[0100] Table 1 Dissolution test results

[0101]

[0102] The above dissolution results show that: (1) the weight gain of the sustained-release layer coating has a great influence on the dissolution results of the product. The dissolution rate of Example 1 is too fast and does not meet the standard; the dissolution rate of Example 3 is too slow, and the dissolution effect is better than that of Example 2; (2) By comparing the dissolution results of Examples 2 and 4, it can be seen that the amount of disintegrant will affect the dissolution, and the result is better than that of Example 4. Based on the above selection process, the final prescriptions of Examples 4 and 5 of the present invention were finally determined.

[0103] 2. Stability test

[0104] The finished products and marketed products of Examples 4 and 5 were subjected to accelerated stability tests for 6 months (experimental conditions: temperature 40°C ± 2°C, relative humidity 75% ± 5%). The products met the current standards of the Chinese Pharmacopoeia in terms of content, related substances (isosorbide dinitrate and 2-isosorbide mononitrate), nitrate, isosorbide, solubility, etc.

[0105] Table 2 Stability test results

[0106]

[0107]

[0108] Therefore, it can be seen from the results of Table 1 and Table 2 that the isosorbide mononitrate sustained-release tablets of the present invention have better dissolution and better stability. Comparative Example 1 uses hydroxyethyl cellulose instead of povidone as a pore-forming agent. After 6 months of acceleration, its dissolution and stability effects are not as good as those of Examples 4 and 5 of the present invention.

[0109] Table 3 Amount of binder in sustained-release tablets

[0110]

[0111] The preparation process is the same as that in Example 1. The amount of hydroxypropyl cellulose was screened, and it was found that the larger the amount, the better. Instead, it has a comparative effect on the stability of isosorbide mononitrate within a certain range. For the determination of total impurities, the specific Figure 1 .

Claims

1. An isosorbide mononitrate sustained-release tablet, comprising sustained-release coated pellets and external excipients, wherein the sustained-release coated pellets are composed of drug pellets and sustained-release coating materials; the external excipients include fillers, disintegrants, lubricants, and film coating materials; the preparation method is to firstly mix the sustained-release coated pellets with the external excipients and then press them into tablets, and then coat the core to form film-coated tablets; the drug pellets are composed of isosorbide mononitrate, microcrystalline cellulose pellet cores, and a binder; the sustained-release coating material is composed of an ethyl cellulose film containing a pore-forming agent; the binder is hydroxypropyl cellulose; the pore-forming agent is povidone; the disintegrant is selected from cross-linked sodium carboxymethyl cellulose and sodium starch glycolate, and the amount calculated by weight ratio is as follows: 。 2. An isosorbide mononitrate sustained-release tablet, comprising sustained-release coated pellets and external excipients, wherein the sustained-release coated pellets are composed of drug pellets and sustained-release coating materials; the external excipients include fillers, disintegrants, lubricants, and film coating materials; the preparation method is to firstly mix the sustained-release coated pellets with the external excipients and then press them into tablets, and then coat the core to form film-coated tablets; the drug pellets are composed of isosorbide mononitrate, microcrystalline cellulose pellet cores, and a binder; the sustained-release coating material is composed of an ethyl cellulose film containing a pore-forming agent; the binder is hydroxypropyl cellulose; the pore-forming agent is povidone; the disintegrant is selected from cross-linked sodium carboxymethyl cellulose and sodium starch glycolate, and the amount calculated by weight ratio is as follows: 。 3. The method for preparing the isosorbide mononitrate sustained-release tablets according to any one of claims 1 or 2, characterized in that The steps include: (1) dissolving isosorbide mononitrate and hydroxypropyl cellulose in purified water to prepare a drug solution, placing microcrystalline cellulose pellets in a fluidized bed, and spraying the drug on the bottom to prepare drug-coated pellets; (2) preparing a sustained-release solution with ethyl cellulose and povidone, placing the drug-coated pellets in a fluidized bed for bottom spray coating, and preparing sustained-release coated pellets; (3) mixing the sustained-release coated pellets and the external excipients uniformly, and tableting to prepare plain tablet cores; (4) Weigh the prescribed amount of Opadry film coating premix, add 10-12 times the amount of 10% ethanol and stir evenly to obtain a coating solution; (5) coating the sustained-release tablet core obtained in step (3), and drying at 35-40° C. until the tablet weight increases by 3-4%, thereby obtaining the isosorbide mononitrate sustained-release tablet.

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