Carvedilol tablet and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and discloses carvedilol tablets and a preparation method thereof.The carvedilol tablets are prepared through the following steps that 1, carvedilol is granulated through part of a first adhesive solution, and first particles are obtained; (2) coating the obtained first particles with a second adhesive solution to obtain second particles; (3) granulating the first filling agent, the second filling agent, the first disintegrating agent and the second particles through the remaining first adhesive solution to obtain third particles; (4) mixing the obtained third particles with a second disintegrating agent; mixing the obtained mixture with a lubricant; tabletting and coating; the first adhesive is polyvinyl alcohol, and the second adhesive is hydroxypropyl methylcellulose. The carvedilol active component is granulated with the polyvinyl alcohol aqueous solution and then coated with the isolating layer, so that direct contact of carvedilol with lactose and corn starch is avoided while release of the active component is not affected, and the stability of the product is greatly improved.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to a stable carvedilol tablet and a preparation method thereof. Background Art

[0002] Carvedilol, with the chemical name 1-(9H-carbazole-4-oxy)-3-[2-(2-methoxyphenoxy)ethylamino]-2-propanol, is a third-generation non-selective adrenergic β-receptor blocker. It also has blocking effects on α1, β1 and β2 receptors. It is clinically used to treat primary hypertension, angina pectoris and heart failure. With the deepening of research, carvedilol has also been found to have cardiovascular protection, antioxidant and calcium ion channel blocking effects.

[0003] Carvedilol tablets were first developed by Roche and launched in the United States in 1990. Starch, sucrose and lactose are widely used fillers in the pharmaceutical industry, among which lactose has excellent fluidity, low hygroscopicity and compressibility. Lactose was used as a filler in the original formulation, but lactose easily reacts directly with the active substance carvedilol to produce Maillard reaction, causing drug degradation and corresponding impurities. Such impurities often continue to grow during stability studies, bringing risks to the quality control of the formulation.

[0004] Chinese patent application number CN201310682021.1 discloses a method for preparing carvedilol tablets, which uses lactose as a filler, poloxamer as a surfactant, starch as a binder, talcum powder as a lubricant, and micro-powdered silica gel as a glidant. After being evenly mixed, they are added to a tablet press and pressed into tablets with the characteristics of rapid release. However, carvedilol and lactose are directly mixed and contacted, which easily causes the Maillard reaction to produce impurities.

[0005] Chinese patent application number CN201410447344.7 discloses a wet granulation process for preparing carvedilol tablets, which uses microcrystalline cellulose and sodium starch glycolate as fillers and disintegrants, respectively. Sodium lauryl sulfate is dissolved in starch slurry as a binder after premixing, and the dry granules are mixed with lubricant magnesium stearate for tableting after wet granulation. The starch slurry as a binder is in direct contact with carvedilol to form a soft material, and the high temperature and high humidity environment of the drying step makes it very easy for the Maillard reaction to produce impurities during the preparation process.

[0006] Chinese patent application number CN201410736946.4 discloses a method for preparing a lyophilized tablet of a carvedilol composition. The lyophilized tablet is prepared by adding carvedilol to a corn starch-sucrose solution and performing vacuum freeze drying. The auxiliary materials starch and sucrose are both susceptible to Maillard reaction with carvedilol to produce corresponding impurities.

[0007] The three impurity structures produced by the Maillard reaction of carvedilol and lactose are as follows Figure 1 As shown, the presence of these three impurities will affect the quality of the preparation, reduce the content of carvedilol and the therapeutic effect of the preparation. In summary, in the existing preparation process, lactose, starch or sucrose directly contacted with carvedilol as a filler increases the risk of Maillard impurities. The research results of the inventors show that conventional tablets will significantly increase Maillard impurities under high temperature and high humidity conditions of 60°C and 60°C+RH75%. Therefore, it is necessary to develop a carvedilol tablet preparation process that avoids direct contact between carvedilol and lactose to ensure and improve the quality of the preparation and reduce the risk of impurity control. Previously, there have been no publicly published carvedilol tablet preparation methods and patents that reduce the content of impurities produced by the Maillard reaction. Summary of the invention

[0008] Purpose of the invention: The technical problem to be solved by the present invention is to provide a carvedilol tablet and a preparation method thereof in view of the deficiencies in the prior art.

[0009] In order to solve the above technical problems, the present invention discloses the following technical solutions: In a first aspect, the present invention discloses a carvedilol tablet.

[0010] Wherein, the carvedilol tablets are prepared by the following method, which comprises: (1) granulating carvedilol with a portion of the first binder solution to obtain first granules; (2) coating the obtained first particles with a second binder solution to obtain second particles; (3) granulating the first filler, the second filler, the first disintegrant and the second granules with the remaining first binder solution to obtain third granules; (4) mixing the obtained third granules with the second disintegrant; mixing the obtained mixture with a lubricant; and tableting and coating.

[0011] In a second aspect, the present invention discloses a method for preparing carvedilol tablets, comprising: (1) granulating carvedilol with a portion of the first binder solution to obtain first granules; (2) coating the obtained first particles with a second binder solution to obtain second particles; (3) granulating the first filler, the second filler, the first disintegrant and the second granules with the remaining first binder solution to obtain third granules; (4) mixing the obtained third granules with the second disintegrant; mixing the obtained mixture with a lubricant; and tableting and coating.

[0012] In the above first and second aspects, In step (1), the particle size D of carvedilol is 90The size of the carvedilol is 10 μm to 80 μm, such as 20 μm, 70 μm; in some embodiments, the carvedilol is sieved through a 40-mesh sieve before use.

[0013] In step (1), the first adhesive is polyvinyl alcohol, and the solid content of the first adhesive solution is 8%-12%, such as 10%.

[0014] In step (1), the portion of the first adhesive is 20%-40% of the total mass of the first adhesive, such as 25%, 30%, 35%.

[0015] In step (1), the granulation is carried out in a fluidized bed, carvedilol is placed in a fluidized bed, and when the temperature reaches above 35°C, part of the first binder solution is added for top spray granulation; in some embodiments, when the temperature reaches above 40°C, part of the first binder solution is added for top spray granulation; in some embodiments, the spraying speed is 5-19 rpm, such as 12 rpm.

[0016] In step (2), the second adhesive is hypromellose.

[0017] In step (2), the coating is performed in a fluidized bed, the first particles are placed in a fluidized bed, and when the temperature reaches above 40°C, part of the first binder solution is added for bottom spray coating; in some embodiments, when the temperature reaches above 45°C, part of the first binder solution is added for bottom spray coating; in some embodiments, the spraying speed is 5-19 rpm, such as 14 rpm.

[0018] In step (3), the first filler is lactose; the second filler is corn starch and / or mannitol.

[0019] In step (3), the first disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, or a combination of any of the foregoing, preferably low-substituted hydroxypropyl cellulose.

[0020] In step (3), the first filler, the second filler, and the first disintegrant are first passed through a 20-28 mesh sieve to obtain a mixture, and then granulated with the second granules; in some embodiments, the first filler, the second filler, and the first disintegrant are passed through a 24 mesh sieve.

[0021] In step (3), the granulation is performed in a fluidized bed, wherein a mixture of the first filler, the second filler, the first disintegrant and the second particles are placed in a fluidized bed, and when the temperature reaches above 35°C, the remaining first binder solution is added for top spray granulation; in some embodiments, when the temperature reaches above 40°C, the remaining first binder solution is added for top spray granulation; in some embodiments, the spraying speed is 5-19 rpm, such as 12 rpm.

[0022] In step (4), the second disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, or a combination of any of the foregoing, preferably cross-linked sodium carboxymethyl cellulose. In some embodiments, the second disintegrant is passed through a 35-42 mesh sieve, such as a 40 mesh sieve.

[0023] In step (4), the third granules and the second disintegrant are mixed in a mixer; the rotation speed of the mixer is 5-19 rpm, such as 12 rpm; and the mixing time is 3-8 min, such as 5 min.

[0024] In step (4), the lubricant is selected from magnesium stearate, talc, calcium stearate, zinc stearate, sodium stearate fumarate or any combination thereof. In some embodiments, the lubricant is passed through an 80-mesh sieve.

[0025] In step (4), the tableting process controls the tablet weight difference to be ±3% and the hardness to be 2-6 kg, such as 2.5-4 kg.

[0026] In some embodiments, the weight proportions of the components in the carvedilol tablets are as follows: 10 parts of carvedilol, 75-95 parts of the first filler, 13-44 parts of the second filler, 9-13 parts of the first disintegrant, 0.9-2.1 parts of the second disintegrant, 4-7 parts of the first binder, 1.4-2.6 parts of the second binder, 1.4-2.6 parts of the lubricant, and 3.9-5.1 parts of the coating powder; in some embodiments, the weight proportions of the components in the carvedilol tablets are as follows: 10 parts of carvedilol, 80-90 parts of the first filler, 23.5-33.5 parts of the second filler, 10-12 parts of the first disintegrant, 1.2-1.8 parts of the second disintegrant, 5-6 parts of the first binder, 1.7-2.3 parts of the second binder, 1.7-2.3 parts of the lubricant, and 4.2-4.8 parts of the coating powder.

[0027] In some embodiments, the method comprises: (1) in a fluidized bed, top-spraying carvedilol with a portion of a first binder solution to obtain first granules; (2) In a fluidized bed, the first particles are bottom-sprayed with a second binder solution to obtain second particles; (3) in a fluidized bed, top-spraying the second granules and the mixture of the first filler, the second filler and the first disintegrant through a 20-28 mesh screen with the remaining first binder solution to obtain third granules; (4) mixing the obtained third granules with the second disintegrant; mixing the obtained mixture with a lubricant; tableting and coating; In step (1), the portion of the first adhesive is 20%-40% of the total mass of the first adhesive; The solid contents of the first binder solution and the second binder solution are independently selected from 8% to 12%; The first binder is polyvinyl alcohol, and the second binder is hypromellose.

[0028] In some embodiments, after coating, polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil are used for packaging.

[0029] The present invention prepares carvedilol tablets by the method. The Maillard reaction impurities of the tablets increase slower than those of conventional tablets under the conditions of 0 day, 60°C high temperature, and 60°C+RH75% high temperature and high humidity, and the tablets have better stability than conventional tablets and can be dissolved quickly.

[0030] Beneficial effects:

[0031] The stable carvedilol tablet provided by the present invention is composed of an active ingredient carvedilol, a filler, a binder, a disintegrant, a lubricant and a coating material. The present invention granulates the carvedilol active ingredient with a polyvinyl alcohol aqueous solution and then coats the isolation layer, so as to avoid direct contact between carvedilol and lactose and corn starch without affecting the release of the active ingredient, thereby greatly improving the stability of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become more clear.

[0033] Figure 1 These are the three impurity structures produced by the Maillard reaction of carvedilol and lactose.

[0034] Figure 2 The dissolution curves of the preparations obtained in Example 1 and Comparative Examples 1-3 in 0.1 M hydrochloric acid are shown.

[0035] Figure 3 The dissolution curves of the preparations obtained in Example 1 and Comparative Example 1 at pH 1.2 are shown.

[0036] Figure 4 The dissolution curves of the preparations obtained in Example 1 and Comparative Example 1 at pH 4.0 are shown. DETAILED DESCRIPTION

[0037] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0038] The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0039] In the following examples, the lactose is GranuLac 200 (200 mesh) produced by Megler GmbH & Co. KG, Germany; the corn starch manufacturer is Anhui Shanhe; the low-substituted hydroxypropyl cellulose is low-substituted hydroxypropyl cellulose (model LH-21) produced by Shin-Etsu Chemical; the hydroxypropyl methylcellulose is hydroxypropyl methylcellulose (model E5) produced by DuPont; the polyvinyl alcohol is polyvinyl alcohol (model PE-05JPS) produced by Japan Vam Poral Co. LTD; and the coating powder is the gastric-soluble film coating premix 03F630028-CN produced by Colorcon.

[0040] The solid content described in the present invention is mass percentage.

[0041] Example 1 The method for preparing carvedilol tablets comprises the following steps when producing 10,000 tablets: (1) Weighing and sieving: Weigh each raw material and auxiliary material according to the weight ratio.

[0042] 10 parts of carvedilol, 85 parts of lactose, 28.5 parts of corn starch, 11 parts of low-substituted hydroxypropyl cellulose, 1.5 parts of cross-linked carboxymethyl cellulose sodium, 5.5 parts of polyvinyl alcohol, 2.0 parts of hypromellose, 2.0 parts of magnesium stearate, and 4.5 parts of coating powder.

[0043] Among them, lactose, corn starch and low-substituted hydroxypropyl cellulose are passed through 24 meshes to obtain a lactose corn starch low-substituted hydroxypropyl cellulose mixture; cross-linked carboxymethyl cellulose sodium is passed through 40 meshes; magnesium stearate is passed through 80 meshes; carvedilol D90 is 20-70 μm and passed through 40 meshes.

[0044] (2) Granulation of API: Take 30% of the formulated amount of polyvinyl alcohol and add water to prepare a binder solution with a solid content of 10%; take the formulated amount of carvedilol and place it in a fluidized bed. When the temperature reaches above 40°C, add the binder solution for top spray granulation at a spraying speed of 12 rpm to obtain carvedilol polyvinyl alcohol granules.

[0045] (3) Granular isolation layer coating: Take a formulated amount of hydroxypropyl methylcellulose and add water to prepare an isolation coating solution with a solid content of 10%; place the carvedilol polyvinyl alcohol granules in a fluidized bed, and when the temperature reaches above 45°C, begin adding the isolation coating solution for bottom spray coating at a spraying speed of 14 rpm to obtain carvedilol polyvinyl alcohol hydroxypropyl methylcellulose granules.

[0046] (4) Top spray granulation: Take 70% of the formula amount of polyvinyl alcohol and add water to prepare a binder solution with a solid content of 10%; place the carvedilol polyvinyl alcohol hydroxypropyl methylcellulose granules and the lactose corn starch low-substituted hydroxypropyl cellulose mixture in a fluidized bed. When the temperature reaches above 40°C, add the binder solution and start top spray granulation. The spraying speed is 12 rpm to obtain intermediate particles A.

[0047] (5) Mixing: Add the intermediate granules A of step (4) and the cross-linked sodium carboxymethyl cellulose of step (1) into a mixer in sequence and mix at 12 rpm for 5 minutes.

[0048] (6) Lubrication: Add magnesium stearate to the mixture obtained in step (5), mix at 12 rpm for 3 minutes, and take a sample to detect the content of intermediate B.

[0049] (7) Tableting: The intermediate B obtained in step (6) is installed in a mold, and the tablet weight is calculated based on the content of the intermediate B. The tablet weight difference is controlled within ±3%, and the hardness is between 2.5 kg and 4.0 kg.

[0050] (8) Coating: Place the plain tablets obtained in step (7) in a coating pan for coating, with the coating weight gain being 2% to 3%.

[0051] (9) Packaging: Polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil packaging.

[0052] Comparative Example 1 The preparation method is replaced by a common one-step granulation, which includes the following steps when producing 10,000 tablets: (1) Weighing and sieving: Weigh each raw material and auxiliary material according to the weight ratio.

[0053] 10 parts of carvedilol, 87 parts of lactose, 28.5 parts of corn starch, 11 parts of low-substituted hydroxypropyl cellulose, 1.5 parts of cross-linked carboxymethyl cellulose sodium, 5.5 parts of polyvinyl alcohol, 2.0 parts of magnesium stearate, and 4.5 parts of coating powder.

[0054] Among them, lactose, corn starch and low-substituted hydroxypropyl cellulose are passed through 24 meshes to obtain a lactose corn starch low-substituted hydroxypropyl cellulose mixture, cross-linked sodium carboxymethyl cellulose is passed through 40 meshes, magnesium stearate is passed through 80 meshes, and carvedilol D90 is 20-70 μm and passed through 40 meshes.

[0055] (2) Top spray granulation: Take the polyvinyl alcohol in step (1) and add water to prepare a binder solution with a solid content of 10%; premix carvedilol and a mixture of lactose corn starch and low-substituted hydroxypropyl cellulose in a wet granulator, and then place the mixture in a fluidized bed. When the temperature reaches above 40°C, add the binder solution and perform top spray granulation at a spraying speed of 12 rpm to obtain intermediate granules A.

[0056] (3) Mixing: Add the intermediate granules A of step (2) and the cross-linked sodium carboxymethyl cellulose of step (1) into a mixer in sequence and mix at 12 rpm for 5 minutes.

[0057] (4) Lubrication: Add magnesium stearate to the mixture obtained in step (3), mix at 12 rpm for 3 minutes, and take a sample to detect the content of intermediate B.

[0058] (5) Tableting: The intermediate B obtained in step (4) is installed in a mold, and the tablet weight is calculated based on the content of the intermediate B. The tablet weight difference is controlled within ±3%, and the hardness is between 2.5 kg and 4.0 kg.

[0059] (6) Coating: Place the plain tablets obtained in step (5) in a coating pan for coating, with the coating weight gain being 2% to 3%.

[0060] (7) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil packaging.

[0061] Example 2 Same as Example 1, except that 5.5 parts of polyvinyl alcohol and 2.0 parts of hydroxypropyl methylcellulose are replaced with other adhesives, as follows: Example 2-1, replaced with 5.5 parts of polyvinyl alcohol and 2.0 parts of povidone; Example 2-2, replaced with 5.5 parts of hydroxypropyl cellulose and 2.0 parts of hypromellose.

[0062] Example 3 The same as Example 1, except that 11 parts of low-substituted hydroxypropyl cellulose and 1.5 parts of cross-linked carboxymethyl cellulose sodium are replaced with other disintegrants, as follows: Example 3-1, replaced with 11 parts of sodium carboxymethyl starch and 1.5 parts of cross-linked sodium carboxymethyl cellulose; Example 3-2, replaced with 11 parts of low-substituted hydroxypropyl cellulose and 1.5 parts of cross-linked polyvinylpyrrolidone.

[0063] Example 4 Same as Example 1, except that the amounts of each component are different, as follows: Example 4-1: 10 parts of carvedilol, 75 parts of lactose, 43.8 parts of corn starch, 9 parts of low-substituted hydroxypropyl cellulose, 0.9 parts of cross-linked sodium carboxymethyl cellulose, 4 parts of polyvinyl alcohol, 1.4 parts of hypromellose, 1.4 parts of magnesium stearate, and 4.5 parts of coating powder.

[0064] Example 4-2: 10 parts of carvedilol, 95 parts of lactose, 13.2 parts of corn starch, 13 parts of low-substituted hydroxypropyl cellulose, 2.1 parts of cross-linked sodium carboxymethyl cellulose, 7 parts of polyvinyl alcohol, 2.6 parts of hypromellose, 2.6 parts of magnesium stearate, and 4.5 parts of coating powder.

[0065] Example 4-3: 10 parts of carvedilol, 105 parts of lactose, 8.5 parts of corn starch, 6 parts of low-substituted hydroxypropyl cellulose, 6.5 parts of cross-linked sodium carboxymethyl cellulose, 5.5 parts of polyvinyl alcohol, 2.0 parts of hypromellose, 2.0 parts of magnesium stearate, and 4.5 parts of coating powder.

[0066] Example 4-4: 10 parts of carvedilol, 105 parts of lactose, 8.5 parts of corn starch, 11 parts of low-substituted hydroxypropyl cellulose, 1.5 parts of cross-linked sodium carboxymethyl cellulose, 5.5 parts of polyvinyl alcohol, 2.0 parts of hypromellose, 2.0 parts of magnesium stearate, and 4.5 parts of coating powder.

[0067] Comparative Example 2 The same as Example 1, except that step (5) is omitted and cross-linked sodium carboxymethyl cellulose is directly added in step (4), that is, (4) Top spray granulation: Take 70% of the formula amount of polyvinyl alcohol and add water to prepare a binder solution with a solid content of 10%; place carvedilol polyvinyl alcohol hydroxypropyl methylcellulose granules, lactose corn starch low-substituted hydroxypropyl cellulose mixture, and cross-linked sodium carboxymethyl cellulose in a fluidized bed. When the temperature reaches above 40°C, add the binder solution and perform top spray granulation at a spraying speed of 12 rpm to obtain intermediate granules A.

[0068] Comparative Example 3 The same as Example 1, except that the particle size of carvedilol is different, the carvedilol D90 is 100-150 μm, and passes through 40 mesh.

[0069] Test 1 The samples prepared in Example 1 and Comparative Example 1 were subjected to multi-media dissolution curve determination, and the dissolution was determined at 37°C using a Chinese Pharmacopoeia dissolution apparatus 1 in 0.1M hydrochloric acid solution, pH 1.2 hydrochloric acid solution medium, pH 4.0 sodium acetate-acetic acid buffer, 900 ml. The experimental results are shown in Tables 1 and Figure 2-4As shown, the dissolution curves of the samples prepared in Example 1 of the present invention and Comparative Example 1 are relatively similar in different media, and both are rapidly dissolved. When the disintegrant cross-linked carboxymethyl cellulose sodium is added internally in Comparative Example 2, and the particle size of the raw material drug is increased in Comparative Example 3, the dissolution rates of the preparations obtained in Comparative Example 2 and Comparative Example 3 are both slowed down.

[0070] Table 1 Dissolution of the preparations obtained in Example 1 and Comparative Example 1 in different media (%)

[0071] Test 2 The coated tablets prepared in Example 1 and Comparative Example 1 were placed under the influence factors (high temperature 60°C, high temperature and high humidity 60°C + RH75%), and the properties, related substances and contents were compared. The related substance detection method is the area normalization method. Liquid phase method: chromatographic column: Kromasil 100-5-C18 4.6×250mm, 5μm; mobile phase A: 0.1% formic acid; mobile phase B: acetonitrile; column temperature: 35°C; flow rate: 1.0ml / min; injection volume: 10μL; diluent: 0.1% formic acid-acetonitrile (75:25); sample concentration: 1.0mg / ml; gradient is as shown in Table 2 below.

[0072] Table 2

[0073] Sample preparation: Take 2 carvedilol tablets and place them in a 20ml volumetric flask, add diluent, shake and sonicate for 15 minutes, make up to volume with diluent and shake well, filter with 0.45μm nylon membrane, discard 2ml of the initial filtrate, and take the subsequent filtrate.

[0074] Results The properties of the products of Example 1 and Comparative Example 1 at each time point were similar. The content of Example 1 on the 10th and 30th days was higher than that of Comparative Example 1. The change trend of the related substances in Example 1 was significantly better than that in Comparative Example 1, as shown in Table 3 below.

[0075] Table 3

[0076] The other examples and comparative examples were tested according to Test 2, and the results are shown in Table 4. After the binder was replaced, the impurities in Example 2 were significantly higher than those in Example 1; after the disintegrant was replaced, the impurities in Example 3 were not significantly affected; the impurities in Examples 4-1 and 4-2 were not significantly affected, and the impurities in Examples 4-3 and 4-4 were slightly higher than those in Example 1; the impurities in Comparative Example 2 in which the disintegrant sodium carboxymethyl cellulose was added internally were not significantly affected; the impurities in Comparative Example 3 in which the particle size of the raw material drug was increased were slightly higher than those in Example 1.

[0077] Table 4 Impurity content of each group / (%)

[0078] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A carvedilol tablet, characterized in that: Prepared by the following method, the method comprising: (1) granulating carvedilol with a portion of the first binder solution to obtain first granules; (2) coating the obtained first particles with a second binder solution to obtain second particles; (3) granulating the first filler, the second filler, the first disintegrant and the second granules with the remaining first binder solution to obtain third granules; (4) mixing the obtained third granules with the second disintegrant to obtain a mixture; mixing the obtained mixture with a lubricant; tableting, and coating; In step (1), the portion of the first adhesive is 20%-40% of the total mass of the first adhesive; The first binder is polyvinyl alcohol, and the second binder is hypromellose.

2. A method for preparing carvedilol tablets, characterized in that: include: (1) granulating carvedilol with a portion of the first binder solution to obtain first granules; (2) coating the obtained first particles with a second binder solution to obtain second particles; (3) granulating the first filler, the second filler, the first disintegrant and the second granules with the remaining first binder solution to obtain third granules; (4) mixing the obtained third granules with the second disintegrant to obtain a mixture; and mixing the obtained mixture with a lubricant; Tableting and coating; In step (1), the portion of the first adhesive is 20%-40% of the total mass of the first adhesive; The first binder is polyvinyl alcohol, and the second binder is hypromellose.

3. The carvedilol tablet according to claim 1 or the method according to claim 2, characterized in that: The particle size D of carvedilol 90 10μm~80μm.

4. The carvedilol tablet according to claim 1 or the method according to claim 2, characterized in that: In step (3), the first filler is lactose; the second filler is corn starch and / or mannitol.

5. The carvedilol tablet according to claim 1 or the method according to claim 2, characterized in that: In step (3), the first filler is 75-95 parts and the second filler is 13-44 parts.

6. The carvedilol tablet according to claim 1 or the method according to claim 2, characterized in that: The first disintegrant and the second disintegrant are independently selected from low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, or any combination thereof.

7. The carvedilol tablet according to claim 1 or the method according to claim 2, characterized in that: The first disintegrant is low-substituted hydroxypropyl cellulose, and the second disintegrant is cross-linked carboxymethyl cellulose sodium.

8. The carvedilol tablet according to claim 1 or the method according to claim 2, characterized in that: The lubricant is selected from magnesium stearate, talc, calcium stearate, zinc stearate, sodium stearyl fumarate or any combination thereof.

9. The carvedilol tablet according to claim 1 or the method according to claim 2, characterized in that: The weight proportions of the components in the carvedilol tablets are as follows: 10 parts of carvedilol, 75-95 parts of a first filler, 13-44 parts of a second filler, 9-13 parts of a first disintegrant, 0.9-2.1 parts of a second disintegrant, 4-7 parts of a first binder, 1.4-2.6 parts of a second binder, 1.4-2.6 parts of a lubricant, and 3.9-5.1 parts of a coating powder.

10. The carvedilol tablet according to claim 1 Or the method according to claim 2, characterized in that, The method comprises: (1) in a fluidized bed, top-spraying carvedilol with a portion of a first binder solution to obtain first granules; (2) In a fluidized bed, the first particles are bottom-sprayed with a second binder solution to obtain second particles; (3) in a fluidized bed, top-spraying the second granules and the mixture of the first filler, the second filler and the first disintegrant through a 20-28 mesh screen with the remaining first binder solution to obtain third granules; (4) mixing the obtained third granules with the second disintegrant; mixing the obtained mixture with a lubricant; tableting and coating; In step (1), the portion of the first adhesive is 20%-40% of the total mass of the first adhesive; The solid contents of the first binder solution and the second binder solution are independently selected from 8% to 12%; The first binder is polyvinyl alcohol, and the second binder is hypromellose.

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