Baclofen tablet and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and discloses a baclofen tablet and a preparation method thereof, the baclofen tablet comprises the following components by weight: 10 parts of baclofen, 100-150 parts of a filler, 4.8-10.8 parts of an adhesive, 0.1-0.8 parts of a flow aid, and 0.3-1.5 parts of a lubricant; the baclofen tablet is prepared by the following method, and the method comprises the following steps: carrying out top spray granulation and size stabilization on a mixed material of baclofen and an internally added filler through an adhesive solution, then adding an externally added filler, a flow aid and a lubricant, and mixing. According to the stable baclofen tablet provided by the invention, the baclofen tablet which is stable in quality and relatively good in mixing uniformity and dissolution rate and the preparation method of the baclofen tablet are provided, part of microcrystalline cellulose is subjected to internal granulation through fluidized bed one-step granulation, the temperature of a fluidized bed and the flow speed of guniting are controlled, and the content of the microcrystalline cellulose is controlled while the generation of impurities is controlled; and the stability of the product is improved.

Description

Technical Field

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

[0002] Baclofen is a derivative of α-aminobutyric acid (GABA). It is the first selective GABAβ receptor agonist used in clinical practice. It is used to treat muscle pain caused by cerebrovascular accident, cerebral palsy, meningitis, multiple sclerosis (MS), spinal cord injury and head trauma. Its mechanism of action is to inhibit monosynaptic and polysynaptic transmission, which may be through stimulating GABA receptors and inhibiting the release of excitatory amino acids. It is mainly used to treat muscle pain caused by cerebrovascular accident, cerebral palsy, meningitis, multiple sclerosis (MS), spinal cord injury and head trauma. It is absorbed rapidly and completely after oral administration, and its plasma protein binding rate is about 30%. Most of this product is excreted in prototype. Within 72 hours, 75% of the intake is excreted through the kidneys, and the rest is excreted from the feces.

[0003] Baclofen tablets were first developed and produced by Novartis Pharma Schweiz AG and were first launched in Switzerland in September 1970.

[0004] Chinese patent application number CN118436629A discloses a pharmaceutical composition of baclofen and a preparation method thereof. The main production process is wet granulation, mainly using corn starch and microcrystalline cellulose as fillers and disintegrants, povidone as a binder, and adding purified water for granulation. After wet granulation, the dry granules are mixed with a glidant, colloidal silicon dioxide, and a lubricant, magnesium stearate, and tableted.

[0005] Currently, the production process of this product on the market almost all adopts wet granulation. However, the baclofen raw material is unstable to high temperature and high humidity, which can easily affect the stability of the product during the wet granulation process. It is sensitive to process parameters and is prone to poor content uniformity and large dissolution differences. Moreover, the solubility will drop significantly during the stability period. Summary of the invention

[0006] Purpose of the invention: The technical problem to be solved by the present invention is to provide a stable baclofen tablet and a preparation method thereof in view of the deficiencies in the prior art.

[0007] 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 baclofen tablet.

[0008] In some embodiments, the baclofen tablet is made of the following raw materials in parts by weight: Baclofen 10 parts Filler 100-150 parts Adhesive 4.8-10.8 parts Flow aid 0.1-0.8 parts Lubricant 0.3-1.5 parts.

[0009] In some embodiments, the baclofen tablet is prepared by the following method: (1) After the baclofen API and the internal filler are uniformly mixed, a binder solution is added to perform top spray granulation, and after the granulation is completed, granulation is performed to obtain granules; (2) adding an external filler, a flow aid and a lubricant to the obtained granules and mixing them to obtain an intermediate material; (3) The intermediate material obtained is tableted.

[0010] In a second aspect, the present invention discloses a method for preparing baclofen tablets.

[0011] The baclofen tablets are made from the following raw materials in parts by weight: Baclofen 10 parts Filler 100-150 parts Adhesive 4.8-10.8 parts Flow aid 0.1-0.8 parts Lubricant 0.3-1.5 parts.

[0012] The preparation method comprises: (1) After the baclofen API and the internal filler are uniformly mixed, a binder solution is added to perform top spray granulation, and after the granulation is completed, granulation is performed to obtain granules; (2) adding an external filler, a flow aid and a lubricant to the obtained granules and mixing them to obtain an intermediate material; (3) The intermediate material obtained is tableted.

[0013] In the above first and second aspects, In some embodiments, the weight proportions of each component are 10 parts of baclofen, 110-135 parts of filler, 6.8-9.8 parts of binder, 0.2-0.5 parts of glidant and 0.5-1 parts of lubricant; in some embodiments, the weight proportions of each component are 10 parts of baclofen, 120 parts of filler, 8.8 parts of binder, 0.3 parts of glidant and 0.7 parts of lubricant.

[0014] In some embodiments, the particle size D of the baclofen 90 20-60μm.

[0015] In some embodiments, the filler includes any one or more combinations of wheat starch, corn starch, pregelatinized starch and microcrystalline cellulose. In some embodiments, the filler is sieved through a 60-mesh screen. In some embodiments, the internal filler is a combination of wheat starch and / or corn starch and microcrystalline cellulose; in some embodiments, the mass ratio of wheat starch and / or corn starch in the internal filler to microcrystalline cellulose is 1:0.2-0.6, such as 1:0.3, 1:0.4, 1:0.5. In some embodiments, the external filler is microcrystalline cellulose. In some embodiments, the wheat starch and / or corn starch accounts for 50-60%wt of the total amount of internal and external fillers.

[0016] In some embodiments, the bulk density of the microcrystalline cellulose in the internal filler is 0.38-0.44 g / cm 3 , such as 0.40, 0.42 g / cm 3 , with an average particle size of 45-55 μm, such as 47, 49, 51, 53 μm, and an angle of repose of 40-43°; in some embodiments, it is microcrystalline cellulose (PH-301). In some embodiments, the bulk density of the microcrystalline cellulose in the added filler is 0.16-0.26 g / cm 3 , such as 0.19, 0.21g / cm 3 , an average particle size of 45-55 μm, such as 47, 49, 51, 53 μm, and a repose angle of 40-43°; in some embodiments, it is microcrystalline cellulose (KG-802).

[0017] In some embodiments, the binder is povidone.

[0018] In some embodiments, the glidant is colloidal silicon dioxide. In some embodiments, the glidant is passed through an 80 mesh screen.

[0019] In some embodiments, the lubricant is magnesium stearate. In some embodiments, the lubricant is passed through an 80 mesh screen.

[0020] In step (1), the mixing is completed in a fluidized bed, and the temperature is controlled at 40°C-50°C.

[0021] In step (1), the mixture of baclofen and the internal filler is preheated to 42-48°C, such as above 45°C, in a fluidized bed, and a binder solution is added for top spray granulation. The spraying speed is 4-10 rpm, such as 6 or 8 rpm. The material temperature in the fluidized bed is maintained at 40-50°C to obtain granules.

[0022] In step (1), the binder solution is a polyvidone aqueous solution, and the solid content of the binder in the binder solution is 10%-20%, preferably 15%.

[0023] In step (1), the granulation is carried out in a granulator; in some embodiments, the rotation speed of the granulator is 500-1000 rpm, such as 800 rpm; in some embodiments, the screen of the granulator is a round hole screen with a pore size of 0.8 mm, 1.0 mm, or 1.2 mm.

[0024] In step (2), the particles, the additional filler, the flow aid and the lubricant are mixed in a mixer, the loading factor of the mixer is preferably 40%-80%, the rotation speed of the mixer is preferably 10-20 rpm, and the mixing time of the mixer is preferably 1-7 min.

[0025] In step (3), during the tableting process, the tablet weight difference is controlled to be within ±5% and the hardness is controlled to be within 4.0-8.0 kg.

[0026] In some embodiments, the baclofen tablet comprises the following components in parts by weight: 10 parts of baclofen, 110-135 parts of filler, 6.8-9.8 parts of binder, 0.2-0.5 parts of glidant and 0.5-1 parts of lubricant; The baclofen tablets are prepared by the following method, which comprises: 90 A mixture of baclofen with a size of 20-60 μm and an internal filler is preheated to 42-48° C. in a fluidized bed, and an aqueous binder solution (i.e., a polyvidone aqueous solution) with a solid content of 13-18% wt is added for top spray granulation. The spraying speed is 4-10 rpm, and the material temperature in the fluidized bed is maintained at 40-50° C. to obtain granules; after the obtained granules are granulated, an external filler, a glidant colloidal silicon dioxide and a lubricant magnesium stearate are added, mixed, tableted, and packaged; The internal filler is a combination of wheat starch and / or corn starch and microcrystalline cellulose; the external filler is microcrystalline cellulose; the mass ratio of wheat starch and / or corn starch in the internal filler to microcrystalline cellulose is 1:0.2-0.5; the internal filler accounts for 73%-77% of the total mass of the filler.

[0027] Beneficial effects: The present invention provides a stable baclofen tablet, and provides a baclofen tablet with stable quality, good mixing uniformity and dissolution and a preparation method thereof. The present invention uses a fluidized bed one-step granulation to first add part of the microcrystalline cellulose for granulation, and controls the fluidized bed temperature and the flow rate of the spraying to control the generation of impurities while improving the stability of the product. The invention solves the problems in the prior art that the wet granulation process is easy to affect the stability of the product, is relatively sensitive to process parameters, is prone to poor content uniformity, has large dissolution differences, and the dissolution rate will drop significantly during the stability period. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] 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.

[0029] Figure 1 The dissolution curves of the preparations obtained in Example 1 and Comparative Examples 1-3 in 0.1 M hydrochloric acid medium are shown. DETAILED DESCRIPTION

[0030] 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.

[0031] 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.

[0032] The wheat starch manufacturer described in the following examples is Changling Jilong Biopharmaceuticals, the microcrystalline cellulose manufacturer is Asahi Kasei (models PH-301 and KG-802), the povidone K30 is BASF, and the colloidal silicon dioxide manufacturer is Evolink.

[0033] The solid content described in the present invention is a mass percentage.

[0034] Example 1 A method for preparing a stable baclofen tablet, when producing 1000 tablets, comprises the following steps: (1) Pre-treatment of raw and auxiliary materials: Weigh each raw material and auxiliary material according to the weight ratio.

[0035] 10 parts of baclofen, 60 parts of wheat starch, 30 parts of microcrystalline cellulose (PH-301), 30 parts of microcrystalline cellulose (KG-802), 8.8 parts of povidone K30, 0.3 parts of colloidal silicon dioxide, and 0.7 parts of magnesium stearate. Wheat starch and microcrystalline cellulose are sieved through 60 mesh; colloidal silicon dioxide and magnesium stearate are sieved through 80 mesh; baclofen D 90 The particle size is 20-60 μm and the particle size is 40 mesh. Preparation of adhesive: Take the formulated amount of povidone K30 and purified water and put them into a beaker to prepare an adhesive solution with a solid content of 15%.

[0036] (2) Mixing and preheating: Place the formulated amount of baclofen, wheat starch, and microcrystalline cellulose (PH-301) in a fluidized bed and preheat the materials in a boiling state until the material temperature reaches above 45°C.

[0037] (3) Top spray granulation: Add the formulated amount of binder solution for top spray granulation, the spraying speed is 8 rpm, and the material temperature in the fluidized bed is maintained at 40-50°C to obtain intermediate particles.

[0038] (4) Granulation: The intermediate granules are sized using a granulator, 1.0 mm round hole sieve, and the rotation speed is set at 800 rpm.

[0039] (5) Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide and magnesium stearate to the granules obtained in step (4), and mix them in a mixer at 12 rpm, with a loading factor of 40%-80%, for 3 minutes. Obtain the intermediate material, and test the mixing uniformity and content of the intermediate material.

[0040] (6) Tableting: The intermediate material obtained in step (5) is installed in a mold, and the tablet weight is calculated based on the intermediate content result, and the tablet weight difference is controlled within ±5%, and the hardness is between 4.0kg and 8.0kg.

[0041] (7) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil packaging.

[0042] Example 2 A method for preparing a stable baclofen tablet, when producing 1000 tablets, comprises the following steps: (1) Pre-treatment of raw and auxiliary materials: Weigh each raw material and auxiliary material according to the weight ratio.

[0043] 10 parts of baclofen, 70 parts of wheat starch, 20 parts of microcrystalline cellulose (PH-301), 30 parts of microcrystalline cellulose (KG-802), 8.8 parts of povidone K30, 0.3 parts of colloidal silicon dioxide, and 0.7 parts of magnesium stearate. Wheat starch and microcrystalline cellulose are sieved through 60 mesh; colloidal silicon dioxide and magnesium stearate are sieved through 80 mesh; baclofen D 90 The particle size is 20-60 μm and the particle size is 40 mesh. Preparation of adhesive: Take the formulated amount of povidone K30 and purified water and put them into a beaker to prepare an adhesive solution with a solid content of 15%.

[0044] (2) Mixing and preheating: Place the formulated amount of baclofen, wheat starch, and microcrystalline cellulose (PH-301) in a fluidized bed and preheat the materials in a boiling state until the material temperature reaches above 45°C.

[0045] (3) Top spray granulation: Add the formulated amount of binder solution for top spray granulation, the spraying speed is 8 rpm, and the material temperature in the fluidized bed is maintained at 40-50°C to obtain intermediate particles.

[0046] (4) Granulation: The intermediate granules are sized using a granulator, 1.0 mm round hole sieve, and the rotation speed is set at 800 rpm.

[0047] (5) Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide and magnesium stearate to the granules obtained in step (4), and mix them in a mixer at 12 rpm, with a loading factor of 40%-80%, for 3 minutes. Obtain the intermediate material, and test the mixing uniformity and content of the intermediate material.

[0048] (6) Tableting: The intermediate material obtained in step (5) is installed in a mold, and the tablet weight is calculated based on the intermediate content result, and the tablet weight difference is controlled within ±5%, and the hardness is between 4.0kg and 8.0kg.

[0049] (7) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil packaging.

[0050] Example 3 A method for preparing a stable baclofen tablet, when producing 1000 tablets, comprises the following steps: (1) Pre-treatment of raw and auxiliary materials: Weigh each raw material and auxiliary material according to the weight ratio.

[0051] 10 parts of baclofen, 60 parts of corn starch, 30 parts of microcrystalline cellulose (PH-301), 30 parts of microcrystalline cellulose (KG-802), 8.8 parts of povidone K30, 0.3 parts of colloidal silicon dioxide, and 0.7 parts of magnesium stearate. Among them, corn starch and microcrystalline cellulose are sieved through 60 mesh; colloidal silicon dioxide and magnesium stearate are sieved through 80 mesh; baclofen D 90 The particle size is 20-60 μm and the particle size is 40 mesh. Preparation of adhesive: Take the formulated amount of povidone K30 and purified water and put them into a beaker to prepare an adhesive solution with a solid content of 15%.

[0052] (2) Mixing and preheating: Place the formulated amount of baclofen, corn starch, and microcrystalline cellulose (PH-301) in a fluidized bed and preheat the materials in a boiling state until the material temperature reaches above 45°C.

[0053] (3) Top spray granulation: Add the formulated amount of binder solution for top spray granulation, the spraying speed is 8 rpm, and the material temperature in the fluidized bed is maintained at 40-50°C to obtain intermediate particles.

[0054] (4) Granulation: The intermediate granules are sized using a granulator, 1.0 mm round hole sieve, and the rotation speed is set at 800 rpm.

[0055] (5) Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide and magnesium stearate to the granules obtained in step (4), and mix them in a mixer at 12 rpm, with a loading factor of 40%-80%, for 3 minutes. Obtain the intermediate material, and test the mixing uniformity and content of the intermediate material.

[0056] (6) Tableting: The intermediate material obtained in step (5) is installed in a mold, and the tablet weight is calculated based on the intermediate content result, and the tablet weight difference is controlled within ±5%, and the hardness is between 4.0kg and 8.0kg.

[0057] (7) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil packaging.

[0058] Comparative Example 1 The same as Example 1, except that the ratio of the amount of microcrystalline cellulose added as a filler is different, and the production of 1000 tablets includes the following steps: (1) Pre-treatment of raw and auxiliary materials: Weigh each raw material and auxiliary material according to the weight ratio.

[0059] 10 parts of baclofen, 50 parts of wheat starch, 40 parts of microcrystalline cellulose (PH-301), 30 parts of microcrystalline cellulose (KG-802), 8.8 parts of povidone K30, 0.3 parts of colloidal silicon dioxide, and 0.7 parts of magnesium stearate. Wheat starch and microcrystalline cellulose are sieved through 60 mesh; colloidal silicon dioxide and magnesium stearate are sieved through 80 mesh; baclofen D 90 The particle size is 20-60 μm and the particle size is 40 mesh. Preparation of adhesive: Take the formulated amount of povidone K30 and purified water and put them into a beaker to prepare an adhesive solution with a solid content of 15%.

[0060] (2) Mixing and preheating: Place the formulated amount of baclofen, wheat starch, and microcrystalline cellulose (PH-301) in a fluidized bed and preheat the materials in a boiling state until the material temperature reaches above 45°C.

[0061] (3) Top spray granulation: Add the formulated amount of binder solution for top spray granulation, the spraying speed is 8 rpm, and the material temperature in the fluidized bed is maintained at 40-50°C to obtain intermediate particles.

[0062] (4) Granulation: The intermediate granules are sized using a granulator, 1.0 mm round hole sieve, and the rotation speed is set at 800 rpm.

[0063] (5) Mixing: Add colloidal silicon dioxide and magnesium stearate to the granules obtained in step (4), and mix them in a mixer at 12 rpm, with a loading factor of 40%-80%, for 3 minutes. Obtain the intermediate material, and test the mixing uniformity and content of the intermediate material.

[0064] (6) Tableting: The intermediate material obtained in step (5) is installed in a mold, and the tablet weight is calculated based on the intermediate content result, and the tablet weight difference is controlled within ±5%, and the hardness is between 4.0kg and 8.0kg.

[0065] (7) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil packaging.

[0066] Comparative Example 2 The same as Example 1, except that the temperature and the spraying speed are different during the fluidized granulation process, the production of 1000 tablets includes the following steps: (1) Pre-treatment of raw and auxiliary materials: Weigh each raw material and auxiliary material according to the weight ratio.

[0067] 10 parts of baclofen, 60 parts of wheat starch, 30 parts of microcrystalline cellulose (PH-301), 30 parts of microcrystalline cellulose (KG-802), 8.8 parts of povidone K30, 0.3 parts of colloidal silicon dioxide, and 0.7 parts of magnesium stearate. Wheat starch and microcrystalline cellulose are sieved through 60 mesh; colloidal silicon dioxide and magnesium stearate are sieved through 80 mesh; baclofen D 90 The particle size is 20-60 μm and the particle size is 40 mesh. Preparation of adhesive: Take the formulated amount of povidone K30 and purified water and put them into a beaker to prepare an adhesive solution with a solid content of 15%.

[0068] (2) Mixing and preheating: Place the formulated amount of baclofen, wheat starch, and microcrystalline cellulose (PH-301) in a fluidized bed and preheat the materials in a boiling state until the material temperature reaches above 55°C.

[0069] (3) Top spray granulation: Add the formulated amount of binder solution for top spray granulation, the spraying speed is 15 rpm, and the material temperature in the fluidized bed is maintained at 55-65°C to obtain intermediate particles.

[0070] (4) Granulation: The intermediate granules are sized using a granulator, 1.0 mm round hole sieve, and the rotation speed is set at 800 rpm.

[0071] (5) Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide and magnesium stearate to the granules obtained in step (4), and mix them in a mixer at 12 rpm, with a loading factor of 40%-80%, for 3 minutes. Obtain the intermediate material, and test the mixing uniformity and content of the intermediate material.

[0072] (6) Tableting: The intermediate material obtained in step (5) is installed in a mold, and the tablet weight is calculated based on the intermediate content result, and the tablet weight difference is controlled within ±5%, and the hardness is between 4.0kg and 8.0kg.

[0073] (7) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil packaging.

[0074] Comparative Example 3 When the preparation method is replaced by the common wet method, the production of 10,000 tablets includes the following steps: (1) Pre-treatment of raw and auxiliary materials: Weigh each raw material and auxiliary material according to the weight ratio.

[0075] 10 parts of baclofen, 60 parts of wheat starch, 30 parts of microcrystalline cellulose (PH-301), 30 parts of microcrystalline cellulose (KG-802), 8.8 parts of povidone K30, 0.3 parts of colloidal silicon dioxide, and 0.7 parts of magnesium stearate. Wheat starch and microcrystalline cellulose are sieved through 60 mesh; colloidal silicon dioxide and magnesium stearate are sieved through 80 mesh; baclofen D 90 The particle size is 20-60 μm and the particle size is 40 mesh. Preparation of adhesive: Take the formulated amount of povidone K30 and purified water and put them into a beaker to prepare an adhesive solution with a mass solid content of 15%.

[0076] (2) Premixing: Take the formulated amount of baclofen, wheat starch, and microcrystalline cellulose (PH-301) and place them in a wet granulator for mixing. Set the stirring blade speed to 200 rpm and the chopping blade speed to 600 rpm for 180 s. After the premixing is completed, prepare the soft material.

[0077] (3) Preparation of soft material: Add binder solution into the wet granulator, set the stirring blade speed to 200 rpm, the chopping blade speed to 600 rpm, the binder addition time to 60 s, and the granulation time to 90 s.

[0078] (4) Drying: Dry the wet granules in an oven at a temperature of 50°C until the moisture content is less than 4.0%.

[0079] (5) Granulation: The dried granules are sized using a granulator with a 1.0 mm round hole sieve and a rotation speed of 800 rpm.

[0080] (6) Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide and magnesium stearate to the dry granules obtained in step (5), and mix them in a mixer at 12 rpm, with a loading factor of 40%-80%, for 2 minutes. Obtain the intermediate material, and test the mixing uniformity and content of the intermediate material.

[0081] (7) Tableting: The intermediate material obtained in step (6) is installed in a mold, and the tablet weight is calculated based on the intermediate content result, and the tablet weight difference is controlled within ±5%, and the hardness is 4.0kg-8.0kg.

[0082] (8) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil packaging.

[0083] Test 1 The mixing uniformity of the samples of Examples 1-3 and Comparative Examples 1 and 3 was measured, and the experimental results are shown in the following table. The RSD results of the samples with uniform content of Examples 1-3 were 0.84%, 1.27%, and 1.03%; the RSD result of Comparative Example 1 was 3.14%. The RSD of the embodiments was much smaller than that of Comparative Examples 1 and 3, and the product was more uniform and stable.

[0084] Table 1: Summary of sample mixing uniformity results of Examples 1-3 and Comparative Example 1

[0085] Test 2 The above Example 1 and Comparative Examples 1-2 were placed under the influence of factors (high temperature and high humidity 60°C + RH75%), and the properties, content, dissolution, and related substances were compared. The results showed that the properties of the products of Example 1 and Comparative Examples 1-2 were similar at each time point. The content of Example 1 on the 15th and 30th days was higher than that of Comparative Examples 1-2, and the dissolution and related substance change trends of Example 1 were significantly better than those of Comparative Examples 1-3. The results are shown in Table 2 below.

[0086] Table 2

[0087] Test 3 At the same time, the stability of the above Example 1 and Comparative Example 1 was investigated (accelerated 40°C / RH75%, long-term 30°C / RH60%), and the properties, dissolution, and related substances were compared. The results showed that during the stability period, the dissolution of Example 1 was stable, while the dissolution of Comparative Example 1 and Comparative Example 3 showed a significant downward trend, and the change trend of related substances in Example 1 was better than that in Comparative Example 1. The results are shown in Table 3 below.

[0088] Table 3

[0089] Test 4 The samples prepared in Examples 1-2 and Comparative Example 3 were tested for dissolution curves according to the dissolution and release test method (General Rule 0931 Method 2), using the paddle method at 50 rpm, 0.1 M hydrochloric acid medium, and 37°C dissolution conditions. The experimental results show that the dissolution curves of the formulation Examples 1-2 of the present invention are stable and meet the requirements, and the dissolution differences of the curves are small. The dissolution curve results of Comparative Example 3 are relatively slow, and the dissolution differences are large. The results are shown in Tables 4 and Figure 1 .

[0090] Table 4 Cumulative dissolution %

[0091] 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 baclofen tablet, characterized in that: The invention comprises the following components in parts by weight: 10 parts of baclofen, 100-150 parts of filler, 4.8-10.8 parts of binder, 0.1-0.8 parts of glidant and 0.3-1.5 parts of lubricant; The baclofen tablets are prepared by the following method, which comprises: top-spraying granulation and granulation of a mixture of baclofen and an internal filler through a binder solution, and then adding an external filler, a glidant and a lubricant for mixing.

2. The baclofen tablet according to claim 1, characterized in that: The weight proportions of the components are 10 parts of baclofen, 110-135 parts of fillers, 6.8-9.8 parts of binders, 0.2-0.5 parts of glidants and 0.5-1 parts of lubricants.

3. The baclofen tablet according to claim 1, characterized in that: The particle size D of the baclofen 90 20-60μm.

4. The baclofen tablet according to claim 1, characterized in that: The filler comprises any one or more combinations of wheat starch, corn starch, pregelatinized starch and microcrystalline cellulose; the internal filler is a combination of wheat starch and / or corn starch and microcrystalline cellulose; and the external filler is microcrystalline cellulose.

5. The baclofen tablet according to claim 1, characterized in that: The mass ratio of wheat starch and / or corn starch in the internal filler to microcrystalline cellulose is 1:0.2-0.

6.

6. The baclofen tablet according to claim 1, characterized in that: The binder is povidone, the glidant is colloidal silicon dioxide, and the lubricant is magnesium stearate.

7. The baclofen tablet according to claim 1, characterized in that: The solid content of the binder solution is 10-20%wt.

8. The baclofen tablet according to claim 1, characterized in that: The mixture of baclofen and internal filler is preheated to 42-48° C. in a fluidized bed, and a binder solution is added for top spray granulation. The spraying speed is 4-10 rpm, and the material temperature in the fluidized bed is maintained at 40-50° C. to obtain granules; after the obtained granules are granulated, an external filler, a glidant and a lubricant are added and mixed.

9. A baclofen tablet, characterized in that: The invention comprises the following components in parts by weight: 10 parts of baclofen, 110-135 parts of filler, 6.8-9.8 parts of binder, 0.2-0.5 parts of glidant and 0.5-1 parts of lubricant; The baclofen tablets are prepared by the following method, which comprises: preheating a mixture of baclofen and an internal filler to 42-48° C. in a fluidized bed, adding a binder solution for top spray granulation, the spraying speed is 4-10 rpm, and the material temperature in the fluidized bed is maintained at 40-50° C. to obtain granules; after granulating the obtained granules, adding an external filler, a glidant and a lubricant, mixing, tableting and packaging; The particle size D of the baclofen 90 20-60μm; The internal filler is a combination of wheat starch and / or corn starch and microcrystalline cellulose; the external filler is microcrystalline cellulose; the mass ratio of wheat starch and / or corn starch to microcrystalline cellulose in the internal filler is 1:0.2-0.5; the internal filler accounts for 73%-77% of the total mass of the filler; The binder is povidone, the glidant is colloidal silicon dioxide, and the lubricant is magnesium stearate; The binder solution is a binder aqueous solution, and the solid content of the binder aqueous solution is 13-18%wt.

10. A method for preparing baclofen tablets, characterized in that: The baclofen tablet comprises the following components in parts by weight: 10 parts of baclofen, 100-150 parts of filler, 4.8-10.8 parts of binder, 0.1-0.8 parts of glidant and 0.3-1.5 parts of lubricant; The method comprises the steps of top-spraying granulation and granulation of a mixture of baclofen and an internal filler through a binder solution, and then adding an external filler, a glidant and a lubricant for mixing.

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