An aspirin enteric microtablet and a method for preparing the same

Abstract

The application provides an aspirin enteric microtablet and a preparation method thereof, wherein the auxiliary materials are selected from the group consisting of silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose and acid stabilizer fumaric acid, water hydrolysis is avoided from the source, the increment of salicylic acid is less than 0.1% in a 6-month accelerated test, and high-voltage electrostatic auxiliary technology is introduced in the coating and drying processes, so that the adhesion and caking problems of the microtablet in the coating process are fundamentally solved, the coating yield is greater than 98%, the coating film is complete and uniform, no coating layer breakage phenomenon occurs in 2h acid resistance, the drug loading of aspirin in the tablet is greatly improved, the obtained microtablet has good stability, high swallowing compliance and small gastric irritation, a new drug administration option is provided for the cardiovascular disease population with poor swallowing compliance, has significant clinical practical value, and the process is feasible and suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to an enteric-coated aspirin microtablet and its preparation method. Background Technology

[0002] Aspirin is a nonsteroidal antipyretic, analgesic, and anti-inflammatory drug, widely used clinically for its antipyretic, analgesic, and antiplatelet aggregation effects. However, aspirin is chemically unstable and readily hydrolyzes in water to form salicylic acid and acetic acid, which not only reduces its efficacy but also causes severe irritation to the gastric mucosa. Currently available enteric-coated aspirin tablets are mostly ordinary tablets with a diameter of 6-8 mm, making them difficult for children and patients with swallowing difficulties to swallow. Breaking them can damage the outer enteric coating, causing the drug to be released into the stomach and triggering adverse reactions. Micro-tablets (generally less than 3 mm in diameter), on the other hand, are smaller, overcoming the difficulty of swallowing for children and patients with swallowing difficulties, and are therefore particularly suitable for these groups.

[0003] Aspirin has poor compressibility, and wet granulation introduces moisture, leading to hydrolysis. Microplates have a large specific surface area, making them prone to adhesion during coating, and requiring extremely high coating uniformity. Incomplete coating can cause a sour taste or stomach irritation upon release in the mouth or stomach. Patent CN120694963A discloses an enteric-coated aspirin composition and its preparation method, using centrifugal granulation to obtain tablet cores. However, the aspirin drug loading is only about 32%, requiring patients to increase the number of tablets ingested to achieve the same dosage, which is unfriendly to patients with swallowing difficulties. Furthermore, the use of purified water as a coating solvent increases the risk of aspirin forming salicylic acid during stability testing. Patent CN112353784A discloses enteric-coated aspirin microplate capsules, increasing the drug loading to approximately 55%, but still using capsule administration (sizes 2-3), purified water as a coating solvent, and failing to solve the problem of microplate adhesion.

[0004] Therefore, developing an enteric-coated aspirin microtablet that is simple to manufacture, highly stable, easy to swallow, and has a complete coating is of great clinical significance. Summary of the Invention

[0005] The purpose of this invention is to provide an enteric-coated aspirin microtablet based on existing technology. The excipients used are silicified microcrystalline cellulose with extremely low hygroscopicity, low-substituted hydroxypropyl cellulose, and the acid stabilizer fumaric acid, eliminating hydrolysis at the source. Accelerated testing showed a salicylic acid increase of <0.1% over 6 months. Furthermore, high-voltage electrostatic assistance technology is introduced during the coating and drying processes, fundamentally solving the problem of microtablet adhesion and clumping during coating. The coating yield is >98%, and the coating film is intact and uniform. No coating layer rupture was observed during 2 hours of acid resistance, significantly increasing the aspirin loading in the tablets. The resulting microtablets exhibit good stability, high swallowing compliance, and minimal gastric irritation, providing a new drug administration option for cardiovascular disease patients with poor swallowing compliance. This invention has significant clinical value, and the process is feasible and suitable for industrial production.

[0006] A second objective of this invention is to provide a method for preparing the above-mentioned enteric-coated aspirin microtablets.

[0007] The technical solution of the present invention is as follows: An enteric-coated aspirin microtablet comprises, from the inside out, a microtablet core, an isolating coating layer, and an enteric coating layer. The microtablet core is made of aspirin, a filler, a solid acid stabilizer, a disintegrant, and a lubricant. The isolating coating layer is made of a film-forming material and an anti-adhesive agent. The enteric coating layer is made of an enteric polymer, a plasticizer, and an anti-adhesive agent. In this invention, the filler is one or more of silicified microcrystalline cellulose, microcrystalline cellulose, or powdered cellulose, preferably silicified microcrystalline cellulose. The solid acid stabilizer is one or more of fumaric acid, citric acid, or succinic acid, preferably fumaric acid; the disintegrant is one or more of low-substituted hydroxypropyl cellulose, croscarmellose sodium, croscarmellose, or carboxymethyl starch sodium, preferably low-substituted hydroxypropyl cellulose; the lubricant is one or more of colloidal silica, sodium stearate fumarate, or talc, preferably colloidal silica; and the film-forming material is acrylic resin, preferably EPO acrylic resin (Utex). ® EPO); the anti-adhesive is nano-colloidal silica; the enteric polymer is a methacrylic acid copolymer, preferably Eutrich. ® L100-55; the plasticizer is triethyl citrate.

[0008] In one embodiment, the aspirin enteric-coated microtablet provided by the present invention comprises, from the inside out, a microtablet core, an isolation coating layer, and an enteric coating layer. The microtablet core is composed of the following components in parts by weight: 10-23 parts aspirin, 2-15 parts silicified microcrystalline cellulose, 0.1-0.5 parts fumaric acid, 0.4-0.8 parts low-substituted hydroxypropyl cellulose, and 0.05-0.15 parts colloidal silica. The isolation coating layer is composed of the following components in parts by weight: [The text abruptly ends here, so the translation stops here as well.] ®EPO 0.5-1.5 parts and nano-colloidal silica 0.1-0.5 parts; the enteric coating layer is made of the following components in parts by weight: Eutrich ® L100-55 1-5 parts, triethyl citrate 0.1-0.5 parts and nano colloidal silica 0.4-0.8 parts.

[0009] In a preferred embodiment, the aspirin enteric-coated microtablet provided by the present invention comprises, from the inside out, a microtablet core, an isolation coating layer, and an enteric coating layer. The microtablet core is composed of the following components in parts by weight: 10-23 parts aspirin, 2-15 parts silanized microcrystalline cellulose, 0.2-0.4 parts fumaric acid, 0.5-0.7 parts low-substituted hydroxypropyl cellulose, and 0.08-0.12 parts colloidal silica. The isolation coating layer is composed of the following components in parts by weight: [The text abruptly ends here, so the translation stops here as well.] ® EPO 0.8-1.1 parts and nano-colloidal silica 0.2-0.4 parts; the enteric coating layer is made of the following components in parts by weight: Eutrich ® 2-4 parts of L100-55, 0.2-0.4 parts of triethyl citrate, and 0.5-0.7 parts of nano-colloidal silica.

[0010] In a more preferred embodiment, the aspirin enteric-coated microtablet provided by the present invention comprises, from the inside out, a microtablet core, an isolation coating layer, and an enteric coating layer, wherein the microtablet contains 10-23 parts aspirin, 2-15 parts silicified microcrystalline cellulose, 0.3 parts fumaric acid, 0.6 parts low-substituted hydroxypropyl cellulose, and 0.1 parts colloidal silica; the isolation coating layer is made of the following components in parts by weight: [unclear - possibly a specific ingredient or ingredient]. ® 0.9 parts EPO and 0.3 parts nano-colloidal silica; the enteric coating layer is made of the following components in parts by weight: Eutrich ® 3 parts L100-55, 0.3 parts triethyl citrate, and 0.6 parts nano-colloidal silica.

[0011] The aspirin enteric-coated microtablets provided by this invention are prepared by first mixing aspirin, filler, solid acid stabilizer, disintegrant and lubricant evenly, and then directly compressing them into microtablet cores; then using a film-forming material and an anti-adhesion agent to make a separation coating liquid and an enteric coating liquid made of enteric polymer, plasticizer and anti-adhesion agent, and combining high voltage electrostatic assisted technology to sequentially perform separation coating and enteric coating on the obtained microtablet cores, and then drying them to obtain the final product.

[0012] The method for preparing enteric-coated aspirin microtablets provided by this invention includes the following steps: (1) Micro-tablet core: Aspirin, filler, solid acid stabilizer, disintegrant and lubricant are mixed evenly, granulated, and directly compressed into tablets using a micro-tablet press to make micro-tablet core; (2) Isolation coating solution: The film-forming material and anti-adhesion agent are dissolved in a solvent to prepare the isolation coating solution; (3) Enteric coating solution: The enteric polymer, plasticizer and anti-adhesive are dissolved in a solvent to prepare an enteric coating solution; (4) Coating and drying: The obtained micro-chip is placed in a fluidized bed and the electrostatic generator is turned on. First, the isolation coating liquid is sprayed onto the obtained micro-chip by bottom spray coating to perform isolation coating and make isolation coated chip core; then, the enteric coating liquid is sprayed onto the obtained isolation coated chip core by bottom spray coating to perform enteric coating. After drying, enteric micro-chip is obtained.

[0013] The filler is one or more of silicified microcrystalline cellulose, microcrystalline cellulose, or powdered cellulose, preferably silicified microcrystalline cellulose. The solid acid stabilizer is one or more of fumaric acid, citric acid, or succinic acid, preferably fumaric acid; the disintegrant is one or more of low-substituted hydroxypropyl cellulose, croscarmellose sodium, croscarmellose, or carboxymethyl starch sodium, preferably low-substituted hydroxypropyl cellulose; the lubricant is one or more of colloidal silica, sodium stearate fumarate, or talc, preferably colloidal silica; the film-forming material is acrylic resin, preferably EPO acrylic resin (Utec). ® EPO); the anti-adhesive is nano-colloidal silica; the enteric polymer is a methacrylic acid copolymer, preferably Eutrich. ® L100-55; the plasticizer is triethyl citrate.

[0014] In this invention, in step (1), aspirin, filler, solid acid stabilizer, disintegrant and lubricant are mixed evenly in an environment with relative humidity <30% and granulated through a 20-60 mesh sieve; preferably, granulated through a 40 mesh sieve.

[0015] In this invention, in step (1), the diameter of the punch of the micro-tablet press is controlled to be 2.0-3.0 mm, preferably 3.0 mm; during tableting, the core hardness is controlled to be 30-50 N.

[0016] In this invention, during the isolation and enteric coating process in the fluidized bed in step (3), the inlet air temperature is controlled at 30~40℃ and the material temperature at 25~30℃.

[0017] In this invention, during the isolation coating process in step (3), the weight gain is controlled to be 3.5%-4.5%, preferably 5%.

[0018] In this invention, during the enteric coating process in step (3), the weight gain is controlled to be 14.5%-15.5%, preferably 15%.

[0019] In this invention, when the electrostatic generator is turned on in step (3), the control voltage is 5 kV-10 kV.

[0020] The advantages of using the technical solution of this invention are as follows: (1) High stability: Anhydrous powder is directly compressed into tablets. The excipients are siliconized microcrystalline cellulose with extremely low hygroscopicity, low-substituted hydroxypropyl cellulose and acidic stabilizer fumaric acid, which eliminates hydrolysis from the source and accelerates the increase of salicylic acid by <0.1% in 6 months.

[0021] (2) Swallowing friendly: The micro-pieces are 3.0 mm in diameter and can be swallowed with water or sprinkled in yogurt. No chewing is required, which solves the problem of children and patients with dysphagia having difficulty swallowing.

[0022] (3) Excellent anti-blocking properties: Addressing the global challenge of micro-flake coating, this innovative technology introduces high-voltage electrostatic assistance during the fluidized bed coating and drying stages. By enabling the micro-flakes to carry the same charge and generate electrostatic repulsion, combined with the anti-blocking agent nano-colloidal silica, the nano-sized particles can be more uniformly embedded in the extremely thin coating film, providing a finer surface texture and stronger anti-blocking ability without affecting the density and gloss of the coating film. It is especially suitable for micro-flakes of 2-3 mm. This fundamentally solves the problem of adhesion and clumping of micro-flakes during the coating process, with a coating yield of >98%, and the coating film is intact and uniform. No coating layer rupture was observed during 2 hours of acid resistance.

[0023] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0024] Examples 1-4 An enteric-coated aspirin microtablet, comprising, from the inside out, a microtablet core, an isolation coating layer, and an enteric coating layer, wherein the microtablet core, the isolation coating layer, and the enteric coating layer are made of the following components by weight, the specific components and weights of which are shown in Table 1.

[0025]

[0026] The preparation method of aspirin enteric-coated microtablets in Example 1 includes the following steps: (1) Micro-tablet core: After the aspirin raw material passes through an 80-mesh sieve, it is mixed evenly with silicified microcrystalline cellulose, fumaric acid, low-substituted hydroxypropyl cellulose and colloidal silica in an environment with a relative humidity of <30%, and then granulated by passing through a 40-mesh sieve. The tablet core is then compressed using a micro-tablet press with a punch diameter of 3.0 mm to produce micro-tablet cores, and the hardness of the tablet core is controlled at 30~50N.

[0027] (2) Isolation coating solution: Apply Eutrich ®EPO and nano-colloidal silica are dissolved in ethanol to prepare an isolation coating solution.

[0028] (3) Enteric coating solution: [The following text appears to be a separate, unrelated sentence fragment: "Ultrazuril..."] ® L100-55, triethyl citrate, and nano-colloidal silica are dissolved in isopropanol to prepare an enteric coating solution.

[0029] (4) Coating and drying: The obtained micro-flake cores are placed in a fluidized bed for isolation and enteric coating, and the electrostatic generator is turned on. During the coating process, the air inlet temperature is controlled at 30~40℃ and the material temperature is controlled at 25~30℃. First, the isolation coating liquid is sprayed onto the obtained micro-flake cores by bottom spray coating to carry out isolation coating, and the weight gain is controlled at 4% to make isolation coated flake cores. The voltage is controlled at 8kV, and the enteric coating liquid is sprayed onto the obtained isolation coated flake cores by bottom spray coating again to carry out enteric coating, and the weight gain is controlled at 15%. After drying, enteric micro-flakes are obtained.

[0030] The preparation methods of aspirin enteric-coated microtablets in Examples 2-4 are the same as those in Example 1.

[0031] Comparative Example 1: Wet Granulation Microflakes An enteric-coated aspirin microtablet, comprising, from the inside out, a microtablet core, an isolation coating layer, and an enteric coating layer, wherein the microtablet core, the isolation coating layer, and the enteric coating layer are made of the following components by weight, the specific components and weights of which are shown in Table 2.

[0032] The preparation method of aspirin enteric-coated microtablets in Comparative Example 1 includes the following steps: (1) After the aspirin raw material passes through an 80-mesh sieve, it is mixed with silicified microcrystalline cellulose and fumaric acid, and a low-substituted hydroxypropyl cellulose aqueous solution is added to make a soft material. It is then granulated by passing through a 20-mesh sieve, dried and granulated at 50°C, and then colloidal silica is added and mixed evenly. The tablets are then compressed into tablets using a micro-tablet press with a punch diameter of 3.0 mm to make micro-tablet cores, and the hardness of the tablet cores is controlled at 30~50N.

[0033] The processes of isolating the coating solution in step (2), entering the coating solution in step (3), and coating and drying in step (4) are the same as those in step (2), step (3), and step (4) in Example 1.

[0034] Comparative Example 2: Single-layer enteric-coated microflakes without an isolation layer An enteric-coated aspirin microtablet, comprising a microtablet core and an enteric coating layer from the inside out, wherein the microtablet core and the enteric coating layer are made of the following components by weight, the specific components and weights of which are shown in Table 2.

[0035]

[0036] The preparation method of aspirin enteric-coated microtablets in Comparative Example 2 includes the following steps: (1) Micro-chip: Same as in Example 1, specifically as follows: After aspirin raw material passes through an 80-mesh sieve, it is mixed evenly with silicified microcrystalline cellulose, fumaric acid, low-substituted hydroxypropyl cellulose and colloidal silica in an environment with a relative humidity of <30%, granulated through a 40-mesh sieve, and tableted using a micro-chip tableting machine with a punch diameter of 3.0 mm to make micro-chips, controlling the hardness of the chip core to be 30~50N.

[0037] (2) Enteric coating solution: Eutrich ® L100-55, triethyl citrate, and nano-colloidal silica are dissolved in isopropanol to prepare an enteric coating solution.

[0038] (3) Coating and drying: The obtained micro-flake cores are placed in a fluidized bed for enteric coating. During the coating process, the air inlet temperature is controlled at 30~40℃ and the material temperature is controlled at 25~30℃. At the same time, the electrostatic generator is turned on and the voltage is controlled at 8kV. The enteric coating liquid is sprayed onto the obtained micro-flake cores by bottom spray coating to carry out enteric coating. The weight gain is controlled at 18%. After drying, enteric micro-flakes are obtained.

[0039] Comparative Example 3: Magnesium stearate was used as a lubricant, and the colloidal silica in Example 1 was replaced with an equal amount of magnesium stearate. An enteric-coated aspirin microtablet, comprising, from the inside out, a microtablet core, an isolation coating layer, and an enteric coating layer, wherein the microtablet core, the isolation coating layer, and the enteric coating layer are made of the following components by weight, the specific components and weights of which are shown in Table 2.

[0040] The preparation method of aspirin enteric-coated microplates in Comparative Example 3 is the same as that in Example 1, except that the colloidal silica in step (1) is replaced with an equal amount of magnesium stearate.

[0041] Comparative Example 4: Studies with Higher Drug Loading An enteric-coated aspirin microtablet, comprising, from the inside out, a microtablet core, an isolation coating layer, and an enteric coating layer, wherein the microtablet core, the isolation coating layer, and the enteric coating layer are made of the following components by weight, the specific components and weights of which are shown in Table 2.

[0042] The preparation method of aspirin enteric-coated microplates in Comparative Example 4 is the same as that in Example 1, except that silanized microcrystalline cellulose is not used.

[0043] Comparative Example 5: Granules were prepared according to the formulation and preparation method in Example 5 of Patent CN 120694963 A.

[0044] Comparative Example 6: Coated tablets were prepared according to the formulation and preparation method in Example 2 of Patent CN 112353784 A, and the resulting coated tablets were inserted into gelatin empty capsules.

[0045] The content, free salicylic acid and dissolution of the samples in the examples and comparative examples were detected, and the experimental data are shown in Tables 3 and 4.

[0046]

[0047]

[0048] As shown in Tables 3 and 4, the aspirin enteric-coated microtablets prepared in Examples 1-4 of this invention use silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and fumaric acid as excipients with extremely low hygroscopicity, thus preventing hydrolysis at the source. The salicylic acid increase was <0.1% after 6 months of accelerated testing. Furthermore, high-voltage electrostatic assisted technology was introduced during the coating and drying processes, fundamentally solving the problem of microtablet adhesion and clumping during coating. The coating yield was >98%, and the coating film was intact and uniform. No coating layer rupture was observed during 2 hours of acid resistance, greatly increasing the aspirin loading in the tablets. The resulting microtablets exhibited good stability, high swallowing compliance, and minimal gastric irritation, providing a new drug administration option for cardiovascular disease patients with poor swallowing compliance. This demonstrates significant clinical value, and the process is feasible and suitable for industrial production.

[0049] Compared with Example 1, Comparative Example 1 used purified water as the granulation solvent. During the stability acceleration period, the content and dissolution rate showed a decreasing trend, while the free salicylic acid gradually increased and failed to meet the standard after 2 months of acceleration. However, Example 1 did not show the above situation, indicating that the direct powder compression method of the present invention is beneficial to the control of product quality.

[0050] Compared with Example 1, Comparative Example 2 did not use an isolation layer for isolation coating. During the stability acceleration period, the acid dissolution value gradually increased and failed after 2 months of acceleration. However, Example 1 did not show the above situation. This shows that the use of an isolation layer for isolation coating in this invention helps to control the integrity of the enteric coating and the quality of the product.

[0051] Compared with Example 1, Comparative Example 3, which uses magnesium stearate as a lubricant for tableting, showed a decreasing trend in content and dissolution during the stability acceleration period. At the same time, free salicylic acid gradually increased and failed to meet the standard after 3 months of acceleration. However, the above situation did not occur in Example 1. This is because magnesium stearate is weakly alkaline and has hygroscopic properties that may catalyze the hydrolysis of aspirin. This indicates that the use of colloidal silica as a lubricant for tableting in this invention helps to control product quality.

[0052] Compared with Example 1, Comparative Example 4 showed no significant changes in content and dissolution during the stability acceleration period at a higher drug loading. However, as can be seen from the data in Table 5, further increasing the drug loading based on the present invention would lead to risks such as poor compressibility and unacceptable brittleness.

[0053] Compared with Example 1, Comparative Example 5 used purified water as a solvent to prepare particles as a coating substrate. At day 0, the free salicylic acid in the sample was 6 months higher than that in Example 1, and the dissolution rate in the acid was not up to standard. In addition, there were particles in this example, and some particles adhered and broke during the coating process. This invention does not have this risk.

[0054] Compared with Example 1, Comparative Example 6 used No. 3 gelatin empty capsules for administration, and no isolation layer was used for coating. During the stability acceleration period, the acid dissolution value gradually increased and failed the test after 2 months of acceleration. At the same time, the No. 3 gelatin empty capsules had a diameter of about 5.8 mm and a width of about 15.7 mm, which is much larger than the requirement of ≤3 mm for micro-tablet size, making it difficult for children and patients with swallowing difficulties to swallow.

[0055] The compressibility, brittleness, and flowability of the samples in the examples and comparative examples were tested, and the experimental data are shown in Table 5.

[0056]

[0057] As shown in Table 5, compared with Example 1, the only difference between Examples 2-4 and Comparative Examples 1-6 is the increase in drug loading, which affects compressibility and brittleness during the tableting process.

[0058] The yield of the samples in the examples and comparative examples was tested by weighing and counting mode, and the experimental data are shown in Table 6.

[0059]

[0060] As shown in Table 6, compared with Examples 1-4, Comparative Example 6 did not activate high-voltage electrostatic removal during the coating process, which resulted in some flakes sticking together and breaking, leading to a decrease in yield. In contrast, the present invention innovatively introduces high-voltage electrostatic auxiliary technology in the fluidized bed coating and drying stages, thereby improving the overall yield.

[0061] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications may still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions may be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An enteric-coated aspirin microtablet, characterized in that, The microplate consists of, from the inside out, a microplate core, an isolation coating layer, and an enteric coating layer. The microplate core is made of aspirin, a filler, a solid acid stabilizer, a disintegrant, and a lubricant. The isolation layer is made of a film-forming material and an anti-adhesive. The enteric coating layer is made of an enteric polymer, a plasticizer, and an anti-adhesive. The filler is one or more of silicified microcrystalline cellulose, microcrystalline cellulose, or powdered cellulose. The solid acid stabilizer is one or more of fumaric acid, citric acid, or succinic acid. The disintegrant is one or more of low-substituted hydroxypropyl cellulose, croscarmellose sodium cellulose, croscarmellose, or carboxymethyl starch sodium. The lubricant is one or more of colloidal silica, sodium stearate fumarate, or talc. The film-forming material is acrylic resin. The anti-adhesive is nano-colloidal silica. The enteric polymer is a methacrylic acid copolymer. The plasticizer is triethyl citrate.

2. The aspirin enteric-coated microtablets according to claim 1, characterized in that, In its preparation process, aspirin, filler, solid acid stabilizer, disintegrant and lubricant are first mixed evenly and directly compressed into micro-tablet cores; the resulting micro-tablet cores are then coated with a separation coating solution made of film-forming material and anti-adhesion agent and an enteric coating solution made of enteric polymer, plasticizer and anti-adhesion agent, and combined with high voltage electrostatic assisted technology to sequentially perform separation coating and enteric coating, and then dried to obtain the final product.

3. The aspirin enteric-coated microtablets according to claim 2, characterized in that, The filler is silicified microcrystalline cellulose; the solid acid stabilizer is fumaric acid; the disintegrant is low-substituted hydroxypropyl cellulose; the lubricant is colloidal silica; and the film-forming material is eutectic. ® EPO; the enteric polymer is Eutrapeptide. ® L100-55.

4. The enteric-coated aspirin microtablets according to claim 3, characterized in that, The microchip is made of the following components in parts by weight: 10-23 parts aspirin, 2-15 parts silicified microcrystalline cellulose, 0.1-0.5 parts fumaric acid, 0.4-0.8 parts low-substituted hydroxypropyl cellulose, and 0.05-0.15 parts colloidal silica; the insulating coating layer is made of the following components in parts by weight: [unclear - possibly a specific ingredient or ingredient]. ® EPO 0.5-1.5 parts and nano-colloidal silica 0.1-0.5 parts; the enteric coating layer is made of the following components in parts by weight: EPO ® L100-55 1-5 parts, triethyl citrate 0.1-0.5 parts and nano colloidal silica 0.4-0.8 parts.

5. The enteric-coated aspirin microtablets according to claim 4, characterized in that, The microchip is made of the following components in parts by weight: 10-23 parts aspirin, 2-15 parts silicified microcrystalline cellulose, 0.2-0.4 parts fumaric acid, 0.5-0.7 parts low-substituted hydroxypropyl cellulose, and 0.08-0.12 parts colloidal silica; the insulating coating is made of the following components in parts by weight: [unclear - possibly a specific ingredient or ingredient]. ® EPO 0.8-1.1 parts and nano-colloidal silica 0.2-0.4 parts; the enteric coating layer is made of the following components in parts by weight: Eutrich ® 2-4 parts of L100-55, 0.2-0.4 parts of triethyl citrate, and 0.5-0.7 parts of nano-colloidal silica.

6. The aspirin enteric-coated microtablets according to claim 5, characterized in that, The microchip is made of the following components in parts by weight: 10-23 parts aspirin, 2-15 parts silicified microcrystalline cellulose, 0.3 parts fumaric acid, 0.6 parts low-substituted hydroxypropyl cellulose, and 0.1 parts colloidal silica; the insulating coating layer is made of the following components in parts by weight: [unclear - possibly a specific ingredient or product name]. ® 0.9 parts EPO and 0.3 parts nano-colloidal silica; the enteric coating layer is made of the following components in parts by weight: Eutrich ® 3 parts L100-55, 0.3 parts triethyl citrate, and 0.6 parts nano-colloidal silica.

7. The method for preparing aspirin enteric-coated microtablets according to claim 1, characterized in that, Includes the following steps: (1) Microcapsule core: Aspirin, filler, solid acid stabilizer, disintegrant and lubricant are mixed evenly, granulated, and directly compressed into tablets using a microcapsule tablet press to make microcapsule core; (2) Isolation coating solution: The film-forming material and anti-adhesion agent are dissolved in a solvent to prepare the isolation coating solution; (3) Enteric coating solution: The enteric polymer, plasticizer and anti-adhesive are dissolved in a solvent to prepare an enteric coating solution; (4) Coating and drying: The obtained micro-chip is placed in a fluidized bed and the electrostatic generator is turned on. First, the isolation coating liquid is sprayed onto the obtained micro-chip by bottom spray coating to perform isolation coating and make isolation coated chip core; then, the enteric coating liquid is sprayed onto the obtained isolation coated chip core by bottom spray coating to perform enteric coating. After drying, enteric micro-chip is obtained.

8. The method for preparing enteric-coated aspirin microtablets according to claim 7, characterized in that, The filler is silicified microcrystalline cellulose; the solid acid stabilizer is fumaric acid; the disintegrant is low-substituted hydroxypropyl cellulose; the lubricant is colloidal silica; and the film-forming material is eutectic. ® EPO; the enteric polymer is Eutrapeptide. ® L100-55; the solvent is one or more of ethanol, isopropanol or methanol, preferably ethanol or isopropanol.

9. The method for preparing enteric-coated aspirin microtablets according to claim 7, characterized in that, In step (1), the mixture is mixed evenly in an environment with a relative humidity of <30%, and then granulated through a 20-60 mesh sieve, preferably 40 mesh; the diameter of the punch of the micro-tablet press is controlled to be 2.0-3.0 mm, preferably 3.0 mm; during tableting, the core hardness is controlled to be 30-50 N.

10. The method for preparing enteric-coated aspirin microtablets according to claim 7, characterized in that, In step (3), when performing isolation and enteric coating in the fluidized bed, the inlet air temperature is controlled at 30~40℃ and the material temperature at 25~30℃; when performing isolation coating, the weight gain is controlled at 3.5%-4.5%, preferably 4%; when performing enteric coating, the weight gain is controlled at 14.5%-15.5%, preferably 15%; when turning on the electrostatic generator, the voltage is controlled at 5 kV-10 kV.

Images