Aspirin enteric-coated tablet and preparation method thereof

Abstract

The invention relates to an aspirin enteric-coated tablet and a preparation method thereof.The aspirin enteric-coated tablet comprises a tablet core and a coating wrapping the tablet core, the tablet core is composed of aspirin, powdery cellulose, corn starch and hydroxypropyl starch, and the coating is an enteric-coated layer and can effectively improve the flowability, compressibility and mixing uniformity of dry powder; meanwhile, the coating layer can resist gastric acid for a long time, so that the release of aspirin in the stomach is reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to an enteric-coated aspirin tablet and a preparation method thereof. Background Art

[0002] Aspirin (acetylsalicylic acid) is widely used to treat fever, pain, rheumatism, and other symptoms, as well as for anti-thrombotic therapy, particularly in the prevention of cardiovascular and cerebrovascular diseases. Aspirin, a white crystalline or crystalline powder, is stable in dry air but slowly hydrolyzes into salicylic acid and acetic acid when exposed to moisture, which can affect aspirin's stability and efficacy. The resulting salicylic acid can cause headaches, dizziness, nausea, vomiting, tinnitus, and decreased vision and hearing. In severe cases, it can even cause mental confusion and coma. Aspirin also decomposes easily in acidic environments, increasing its toxic side effects and reducing its efficacy.

[0003] US20140248352A1 discloses a chewable enteric-coated aspirin tablet comprising enteric-coated aspirin granules and a matrix comprising a directly compressible sugar or sugar alcohol and a high-intensity sweetener, wherein the tablet contains less than 5% fat and the matrix is substantially free of a non-sugar, water-soluble polymer binder. CN108743555A discloses an enteric-coated aspirin tablet and a method for preparing the same, wherein the aspirin tablet core is coated with a first enteric coating layer and a second enteric coating layer, effectively preventing external moisture from penetrating, preventing aspirin hydrolysis, and preventing aspirin from disintegrating in gastric fluid, while ensuring the disintegration and dissolution of aspirin in intestinal fluid. CN105796524A discloses an enteric-coated aspirin tablet. Through extensive experiments, ethyl cellulose and polyethylene glycol stearate were selected as coating materials for the isolation coating layer. Adding an isolation coating layer between the tablet core and the enteric coating layer can increase the stability of the active ingredient aspirin. The tablet core includes aspirin, anhydrous calcium hydrogen phosphate, D-mannitol, sodium kaolin, and L-alanine. CN105193762A discloses an enteric-coated aspirin tablet, which consists of a core layer and an enteric coating layer. The core layer is prepared from the following components in parts by weight: 100 parts aspirin, 18-25 parts starch, 95-105 parts 8% starch slurry, 8-15 parts microcrystalline cellulose, 0.008-0.012 parts edetate disodium, and 1-2 parts protective agent; the enteric coating layer is prepared from the following components in parts by weight: 3.6-4.2 parts polyacrylic acid resin II, 2.0-2.5 parts polyacrylic acid resin III, 2.2-2.8 parts castor oil, 1.2-1.8 parts anti-adhesive agent, and 95-105 parts 95% ethanol. The tablet core layer formula solves the problem of excessive free salicylic acid caused by the degradation of aspirin during long-term storage by adding a protective agent composed of hydropropyl methylcellulose acetate succinate and ammonium oxalate; the added excipients also avoid the sticking problem caused by long-term and large-scale tablet pressing, reduce material loss, and the surface of the prepared tablets is smooth and uniform in color; the enteric coating layer formula significantly improves the release rate of enteric-coated aspirin tablets by adding an anti-adhesive composed of monostearate glyceryl and talcum powder, so that the release rate of enteric-coated aspirin tablets can still meet the requirements after long-term storage.

[0004] However, the cores of these enteric-coated aspirin tablets are typically directly compressed from powder, resulting in unstable tablet content uniformity. Furthermore, due to individual patient differences, the gastric fluid environment can vary, potentially lower than normal gastric pH, or patients with diabetic gastroparesis are prone to prolonged gastric retention. These issues can cause the enteric coating of the tablets to rupture in the stomach, leading to the release of aspirin and damage to the gastric mucosa. While multi-layer coating can reduce the impact of gastric fluid, the layers are not integrally formed, making them prone to looseness. This can lead to partial detachment and rupture of the coating layers under prolonged gastric fluid conditions, and the multi-layer coating process is complex. Summary of the Invention

[0005] To solve the above problems, the present invention provides an enteric-coated aspirin tablet and a preparation method thereof, which can effectively improve the fluidity, compressibility and mixing uniformity of the dry powder. At the same time, the coating layer can resist gastric acid for a long time, reducing the release of aspirin in the stomach.

[0006] In a first aspect, the present invention provides an enteric-coated aspirin tablet, comprising a tablet core and a coating covering the tablet core, wherein the tablet core is composed of aspirin, powdered cellulose, corn starch and hydroxypropyl starch, and the coating comprises Eudragit L30D-55, triethyl citrate, cross-linked polyvinylpyrrolidone and dimethicone.

[0007] The tablet core is formed by dry pressing; the tablet core is formed by mixing aspirin, powdered cellulose, corn starch and hydroxypropyl starch to prepare a total mixed powder, and then dry pressing it.

[0008] The angle of repose of the total mixed powder is less than 36° and greater than 30°; the Carr index is 10%-13%, preferably 11-12%; the particle size distribution of the total mixed powder is: 40-60 mesh accounts for 25-32%, 60-80 mesh accounts for 60-75%, and 80-100 mesh accounts for 2-5%.

[0009] The aspirin particle size range is: greater than 50 mesh ≤ 5.0%, 50-120 mesh ≥ 75%, less than 120 mesh ≤ 20%.

[0010] Calculated based on the total weight of the tablet core, the aspirin comprises 80%-85%, the powdered cellulose comprises 5%-8%, the corn starch comprises 9%-12%, and the hydroxypropyl starch comprises 0.8%-1.2%.

[0011] The weight ratio of corn starch to hydroxypropyl starch is (10-12):1, preferably 12:1.

[0012] Based on the weight of the coating, the following ingredients are used: 40-80 parts by weight of Eudragit L30D-55, 4-8 parts by weight of triethyl citrate, 2-4 parts by weight of cross-linked polyvinylpyrrolidone, and 1-2 parts by weight of dimethyl silicone oil.

[0013] Preferably, 40 parts by weight of Eudragit L30D-55, 4 parts by weight of triethyl citrate, 2 parts by weight of cross-linked polyvinylpyrrolidone and 1 part by weight of dimethyl silicone oil are used.

[0014] The coating further comprises an anti-adhesive agent, which is selected from talc powder. The weight ratio of the talc powder to Eudragit L30D-55 is (0.9-1.2):1, preferably 1:1; or preferably 40-80 weight parts are added.

[0015] The present invention also provides a method for preparing the above-mentioned enteric-coated aspirin tablets, which comprises the following preparation steps:

[0016] (1) Tablet core preparation: After crushing aspirin, first mix 1 / 2 of the prescribed amount of aspirin, powdered cellulose, corn starch, and hydroxypropyl starch, then add the remaining amount of aspirin in a multi-directional motion mixer and mix them. After the mixture is evenly mixed, the dry powder is directly compressed into tablets to prepare the tablet core;

[0017] (2) Coating: Add triethyl citrate, cross-linked polyvinylpyrrolidone and dimethyl silicone oil to water in sequence, then add Eudragit L30D-55, stirring while adding to prepare a coating solution; pour the tablet core into the coating machine for preheating, and then start spraying the coating solution to coat the tablet core to obtain enteric-coated aspirin tablets.

[0018] More preferably, an anti-adhesive agent is added to the coating solution in step (2), and the anti-adhesive agent is talc.

[0019] The coating increases weight by 15-20%. The particle size range of aspirin pulverization is: greater than 50 mesh ≤ 5.0%, 50-120 mesh ≥ 75%, and less than 120 mesh ≤ 20%.

[0020] It is further preferred that the angle of repose of the total mixed powder is less than 36° and greater than 30°; the Carr index is 10%-13%; and the particle size distribution of the total mixed powder is: 40-60 mesh accounts for 25-32%, 60-80 mesh accounts for 60-75%, and 80-100 mesh accounts for 2-5%.

[0021] Beneficial technical effects:

[0022] 1. The enteric-coated aspirin tablets of the present invention use powdered cellulose, corn starch and hydroxypropyl starch as tablet core excipients, and are simultaneously formulated with a coating layer comprising Eudragit L30D-55, triethyl citrate, cross-linked polyvinylpyrrolidone and dimethyl silicone oil, which can effectively improve the flowability, compressibility and mixing uniformity of the dry powder. At the same time, the coating layer is effectively acid-resistant, thereby reducing the release of aspirin in the stomach.

[0023] 2. The enteric-coated tablets of the present invention have a simple preparation process and do not require multiple layers of coating, providing long-term resistance to gastric acid. This is particularly true for individual patient differences, or for patients with diabetic gastroparesis who are prone to prolonged gastric retention. The enteric coating of the enteric-coated tablets of the present invention can remain in the stomach for extended periods without rupture, thus reducing gastric damage. DETAILED DESCRIPTION

[0024] Example 1

[0025] Core composition

[0026]

[0027] Coating composition

[0028]

[0029] Preparation method: (1) Tablet core preparation: Grind aspirin to obtain a powder particle size within the following ranges: greater than 50 mesh ≤ 5.0%, 50-120 mesh ≥ 75%, less than 120 mesh ≤ 20%. Weigh the prescribed amount of aspirin, powdered cellulose, corn starch, and hydroxypropyl starch. Then, mix approximately 1 / 2 of the prescribed amount of aspirin, powdered cellulose, corn starch, and hydroxypropyl starch in sequence. Then, add the remaining amount of aspirin to a multi-directional motion mixer and mix at a speed of 40 Hz for 15 minutes. After the mixture is uniformly mixed, directly press the mixture into tablets to obtain the tablet core.

[0030] (2) Coating

[0031] Coating solution preparation: Weigh the coating ingredients from the above formula and add triethyl citrate, talc, crospovidone, and dimethicone to water in that order. Add Eudragit L30D-55 and stir while adding at 9-11 Hz for at least 1 hour. Filter the prepared coating solution through an 80-mesh sieve and use it for coating.

[0032] Pour the plain tablets into the coating machine for preheating and start spraying. Turn on the stirring device of the stirring barrel and rotate the stirring paddle slowly to create a small vortex on the liquid surface to maintain the uniformity of the coating. Keep the coating weight gain at 17% to obtain enteric-coated aspirin tablets.

[0033] Example 2

[0034] Core composition

[0035]

[0036] Coating composition

[0037]

[0038] The preparation method is the same as that of Example 1.

[0039] Example 3

[0040] Core composition

[0041]

[0042] Coating composition

[0043]

[0044]

[0045] The preparation method is the same as that of Example 1.

[0046] Example 4

[0047] Core composition

[0048]

[0049] Coating composition

[0050]

[0051] The preparation method is the same as that of Example 1.

[0052] Comparative Example 1

[0053] The corn starch in Example 1 was replaced by an equal amount of wheat starch, and the rest was the same as in Example 1.

[0054] Comparative Example 2

[0055] The corn starch in Example 1 was replaced with an equal amount of pea starch, and the rest were the same as in Example 1.

[0056] Comparative Example 3

[0057] The powdered cellulose in Example 1 was replaced with an equal amount of microcrystalline cellulose, and the rest was the same as in Example 1.

[0058] Comparative Example 4

[0059] The cross-linked polyvinylpyrrolidone in Example 1 was removed, and the rest was the same as in Example 1.

[0060] Comparative Example 5

[0061] The cross-linked polyvinylpyrrolidone in Example 1 was replaced with polyvinylpyrrolidone, and the rest was the same as in Example 1.

[0062] Comparative Example 6

[0063] The hydroxypropyl starch in Example 1 was replaced with pregelatinized starch, and the rest was the same as in Example 1.

[0064] Comparative Example 7

[0065] Core composition

[0066] Aspirin 100g

[0067] Powdered cellulose 8g

[0068] 12g corn starch

[0069] Coating composition

[0070]

[0071] The preparation method is the same as that of Example 1.

[0072] Comparative Example 8

[0073] The cross-linked polyvinylpyrrolidone and dimethicone in Example 1 were removed, and the rest was the same as in Example 1.

[0074] Experimental Example 1

[0075] Tablet core powder science investigation

[0076] The flowability, compressibility and particle size distribution uniformity of the total mixed powder before tableting were tested respectively.

[0077] Table 1 Powder Science Test

[0078]

[0079] The experimental results show that the dry powder of the tablet core of the present invention has better fluidity and compressibility than the comparative example, and the particle size distribution is more uniform.

[0080] Experimental Example 2

[0081] Tablet content uniformity test: 10 samples each of Example 1, Comparative Examples 2, 3, 6, and 7 were taken, and the content uniformity was determined according to the pharmacopoeia method.

[0082] Table 2 Tablet content uniformity determination

[0083] sample Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 6 Comparative Example 7 Sample 1 101.3 106.4 98.5 101.0 100.0 Sample 2 100.8 99.3 102.6 100.6 103.9 Sample 3 101.5 98.4 101.0 99.4 97.0 Sample 4 102.6 104.3 108.6 102.9 98.4 Sample 5 102.2 102.5 106.8 98.1 101.8 Sample 6 102.7 96.2 98.8 100.0 99.9 Sample 7 101.8 99.7 101.1 97.5 98.5 Sample 8 100.7 104.8 99.6 87.8 103.2 Sample 9 101.9 95.5 100.6 92.7 96.0 Sample 10 100.9 99.6 101.8 97.1 98.2 Content average (%) 101.6 100.7 101.9 97.7 99.7 A+2.2S 3.2 8.8 9.3 12.1 6.0

[0084] The above experimental results show that compared with other fillers, the present invention uses corn starch and a small amount of hydroxypropyl starch as fillers, which can significantly improve the uniformity of dry mixing and thus improve the content uniformity of dry tableting.

[0085] Experimental Example 3

[0086] Samples of Example 1 and Comparative Examples 1, 4, 5, 6, 7, and 8 were placed in a 0.1 M HCl gastric environment simulation medium using a basket method at a rotation speed of 100 rpm and a temperature maintained at 37 ± 0.5 ° C. The dissolution of aspirin and the membrane rupture phenomenon were observed and measured within 150 minutes to investigate the acid resistance of the enteric-coated preparation under the prolonged action of gastric acid.

[0087] Table 3 Dissolution and membrane rupture detection

[0088]

[0089] Table 4 Dissolution and membrane rupture detection

[0090]

[0091] The above experimental results show that although the addition of hydroxypropyl starch can significantly improve the mixing uniformity and compressibility of the dry powder, the results of Comparative Example 8 show that as the coating dissolves, moisture may erode into the tablet core, and the addition of hydroxypropyl starch may aggravate the expansion of the tablet core, thereby causing the coating film to rupture.

[0092] Example 1 was placed in an intestinal environment simulation medium (buffer pH 6.8) and the basket method was used at a rotation speed of 100 rpm and a temperature maintained at 37±0.5° C. to measure its dissolution in the intestine.

[0093] Table 5 Dissolution in simulated intestinal environment

[0094] time 15min 30min 45min 60min Example 1 41.4％ 82.3％ 95.4％ 99.6％

[0095] The above experimental results show that the enteric-coated tablets of the present invention can be rapidly dissolved in the intestinal environment and have an enteric effect.

[0096] Experimental Example 4

[0097] Stability test

[0098] The enteric-coated tablets of Examples 1 and 3 were placed at a temperature of 40° C. and a humidity of 75% for 10 and 30 days, respectively. The aspirin content, free salicylic acid content, and impurities were determined according to the quality test method for enteric-coated aspirin tablets specified in the Pharmacopoeia.

[0099] The enteric-coated tablets of Examples 1 and 7 were placed at a temperature of 40°C and a humidity of 75% for 30 days, and then placed in an intestinal environment simulation medium (buffer pH 6.8) using a paddle method at a speed of 50 rpm and a temperature maintained at 37±0.5°C to determine their intestinal dissolution stability.

[0100] Table 6 Aspirin content, free salicylic acid content and impurities

[0101]

[0102] The experimental results show that the enteric-coated aspirin tablets of the present invention have an extremely low free salicylic acid content, no obvious impurities and stable quality during storage.

Claims

1. An enteric-coated aspirin tablet, characterized in that: It includes a tablet core and a coating covering the tablet core, wherein the tablet core is composed of aspirin, powdered cellulose, corn starch and hydroxypropyl starch, and the coating comprises Eudragit L30D-55, triethyl citrate, cross-linked polyvinylpyrrolidone and dimethyl silicone oil.

2. The enteric-coated aspirin tablet according to claim 1, wherein: The tablet core is formed by dry compression.

3. The enteric-coated aspirin tablet according to claim 1, wherein: The aspirin particle size range is: greater than 50 mesh ≤ 5.0%, 50-120 mesh ≥ 75%, less than 120 mesh ≤ 20%.

4. The enteric-coated aspirin tablet according to claim 1, wherein: Calculated based on the total weight of the tablet core, the aspirin comprises 80%-85%, the powdered cellulose comprises 5%-8%, the corn starch comprises 9%-12%, and the hydroxypropyl starch comprises 0.8%-1.2%.

5. The enteric-coated aspirin tablet according to claim 4, wherein: The weight ratio of corn starch to hydroxypropyl starch is (10-12):

1.

6. The enteric-coated aspirin tablet according to claim 1, wherein: Based on the weight of the coating, the following ingredients are used: 40-80 parts by weight of Eudragit L30D-55, 4-8 parts by weight of triethyl citrate, 2-4 parts by weight of cross-linked polyvinylpyrrolidone, and 1-2 parts by weight of dimethyl silicone oil.

7. The enteric-coated aspirin tablet according to claim 1, wherein The coating also includes an antiblocking agent.

8. The method for preparing enteric-coated aspirin tablets according to claim 1, wherein It includes the following preparation steps: (1) Tablet core preparation: crush aspirin, first mix 1 / 2 of the prescribed amount of aspirin, powdered cellulose, corn starch, and hydroxypropyl starch, then add the remaining amount of aspirin in a multi-directional motion mixer and mix them. After the mixture is evenly mixed, the dry powder is directly compressed into tablets to prepare the tablet core; (2) Coating: Add triethyl citrate, cross-linked polyvinylpyrrolidone and dimethyl silicone oil to water in sequence, then add Eudragit L30D-55, stirring while adding to prepare a coating solution; pour the tablet core into the coating machine for preheating, and then start spraying the coating solution to coat the tablet core to obtain enteric-coated aspirin tablets.

9. The preparation method according to claim 8, characterized in that: The coating had a weight gain of 15-20%.

10. The preparation method according to claim 8, characterized in that: The particle size range of aspirin is: larger than 50 mesh ≤ 5.0%, 50-120 mesh ≥ 75%, smaller than 120 mesh ≤ 20%.

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