A baclofen tablet and its preparation method

Abstract

The present 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 in parts by weight: 10 parts of baclofen, 100 - 150 parts of a filler, 4.8 - 10.8 parts of a binder, 0.1 - 0.8 parts of a glidant, and 0.3 - 1.5 parts of a lubricant. The baclofen tablet is prepared by the following method, which includes: granulating the mixed material of baclofen and the internal addition filler by top spraying with a binder solution, sizing, and then adding the external addition filler, glidant, and lubricant and mixing. The stable baclofen tablet provided by the present invention provides a baclofen tablet with stable quality, good mixing uniformity and dissolution rate, and a preparation method thereof. By granulating part of the microcrystalline cellulose by internal addition through one-step granulation in a fluidized bed, controlling the temperature of the fluidized bed and the flow rate of the spraying slurry, while controlling the generation of impurities, the stability of the product is improved.

Description

Technical Field

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

[0002] Baclofen is a derivative of α-aminobutyric acid (GABA), and is the first selective GABAβ receptor agonist applied clinically, used for treating muscles 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, possibly by stimulating GABA receptors and inhibiting the release of excitatory amino acids. It is mainly applied to treat muscles caused by cerebrovascular accident, cerebral palsy, meningitis, multiple sclerosis (MS), spinal cord injury and head trauma. It is rapidly and completely absorbed after oral administration, and its plasma protein binding rate is about 30%. Most of this product is excreted in the original form. Within 72 hours, 75% of the intake is excreted through the kidneys, and the rest is excreted from the feces.

[0003] The baclofen tablet was first developed and produced by Novartis Pharma Schweiz AG, and was first launched in Switzerland in September 1970.

[0004] Chinese Patent Application No. CN118436629A discloses a pharmaceutical composition of baclofen and a preparation method thereof. The main production process is wet granulation. Corn starch and microcrystalline cellulose are mainly used as fillers and disintegrants, polyvinylpyrrolidone is used as a binder, and purified water is added for granulation. After wet granulation, the dry granules are mixed with a glidant colloidal silicon dioxide and a lubricant magnesium stearate and pressed into tablets.

[0005] Currently, almost all the production processes of this product on the market adopt wet granulation. However, the baclofen raw material is unstable to both high temperature and high humidity, and it is easy to affect the stability of the product during the wet granulation process. It is more sensitive to process parameters, and is prone to characteristics such as poor content uniformity and large dissolution differences; and the dissolution rate will drop significantly during the stability period. Summary of the Invention

[0006] Object 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 of the prior art.

[0007] To solve the above technical problems, the present invention discloses the following technical solutions:

[0008] In the first aspect, the present invention discloses a baclofen tablet.

[0009] In some embodiments, the baclofen tablet is made from raw materials including the following weight parts:

[0010] Baclofen 10 parts

[0011] Filler 100-150 parts

[0012] Adhesive 4.8-10.8 parts

[0013] Flow aid 0.1-0.8 parts

[0014] Lubricant 0.3-1.5 parts.

[0015] In some embodiments, the baclofen tablet is prepared by the following method:

[0016] (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;

[0017] (2) adding an external filler, a flow aid and a lubricant to the obtained granules and mixing them to obtain an intermediate material;

[0018] (3) The intermediate material obtained is tableted.

[0019] In a second aspect, the present invention discloses a method for preparing baclofen tablets.

[0020] The baclofen tablets are made from the following raw materials in parts by weight:

[0021] Baclofen 10 parts

[0022] Filler 100-150 parts

[0023] Adhesive 4.8-10.8 parts

[0024] Flow aid 0.1-0.8 parts

[0025] Lubricant 0.3-1.5 parts.

[0026] The preparation method comprises:

[0027] (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;

[0028] (2) adding an external filler, a flow aid and a lubricant to the obtained granules and mixing them to obtain an intermediate material;

[0029] (3) The intermediate material obtained is tableted.

[0030] In the above first and second aspects,

[0031] In some embodiments, the weight parts 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 part of lubricant; in some embodiments, the weight parts of each component are 10 parts of baclofen, 120 parts of filler, 8.8 parts of binder, 0.3 part of glidant, and 0.7 part of lubricant.

[0032] In some embodiments, the particle size D of the baclofen 90 is 20 - 60 μm.

[0033] In some embodiments, the filler includes any one or a combination of wheat starch, corn starch, pregelatinized starch, and microcrystalline cellulose. In some embodiments, the filler passes through a 60 - mesh sieve. 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 to microcrystalline cellulose in the internal filler 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 internal and external fillers.

[0034] In some embodiments, the bulk density of microcrystalline cellulose in the internal filler is 0.38 - 0.44 g / cm 3 , such as 0.40, 0.42 g / cm 3 , the average particle size is 45 - 55 μm, such as 47, 49, 51, 53 μm, and the angle of repose is 40 - 43°; in some embodiments, it is microcrystalline cellulose (PH - 301). In some embodiments, the bulk density of microcrystalline cellulose in the external filler is 0.16 - 0.26 g / cm 3 , such as 0.19, 0.21 g / cm 3 , the average particle size is 45 - 55 μm, such as 47, 49, 51, 53 μm, and the angle of repose is 40 - 43°; in some embodiments, it is microcrystalline cellulose (KG - 802).

[0035] In some embodiments, the binder is povidone.

[0036] In some embodiments, the glidant is colloidal silica. In some embodiments, the glidant passes through an 80 - mesh sieve.

[0037] In some embodiments, the lubricant is magnesium stearate. In some embodiments, the lubricant passes through an 80 - mesh sieve.

[0038] In step (1), the mixing is completed in a fluidized bed, and the temperature is controlled at 40°C - 50°C.

[0039] In step (1), the mixed material of baclofen and internal filler is preheated to 42 - 48 °C in a fluidized bed. Above 45 °C, a binder solution is added for top - spray granulation. The spraying speed is 4 - 10 rpm, such as 6 or 8 rpm, and the temperature of the material in the fluidized bed is maintained at 40 - 50 °C to obtain granules.

[0040] In step (1), the binder solution is an aqueous solution of povidone. The solid content of the binder in the binder solution is 10% - 20%, preferably 15%.

[0041] In step (1), the screening is carried out in a screening machine; in some embodiments, the rotation speed of the screening machine is 500 - 1000 rpm, such as 800 rpm; in some embodiments, the screen of the screening machine is a round - hole screen with a pore diameter of 0.8 mm, 1.0 mm, or 1.2 mm.

[0042] In step (2), the mixing of the granules, external filler, glidant, and lubricant is carried out in a mixer. The loading coefficient 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.

[0043] In step (3), during the tableting process, the weight variation of tablets is controlled within ±5%, and the hardness is 4.0 - 8.0 kg.

[0044] In some embodiments, the baclofen tablets comprise 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 part of lubricant;

[0045] The baclofen tablets are prepared by the following method, which includes: preheating the mixed material of baclofen with particle size D 90 of 20 - 60 μm and internal filler to 42 - 48 °C in a fluidized bed, adding an aqueous binder solution (i.e., aqueous povidone solution) with a solid content of 13 - 18% wt for top - spray granulation, with a spraying speed of 4 - 10 rpm, and maintaining the temperature of the material in the fluidized bed at 40 - 50 °C to obtain granules; after screening the obtained granules, external filler, glidant colloidal silica, and lubricant magnesium stearate are added for mixing, tableting, and packaging;

[0046] 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.

[0047] Beneficial effects:

[0048] The stable baclofen tablets provided by the present invention. The present invention provides a baclofen tablet with stable quality, good mixing uniformity and dissolution rate, and a preparation method thereof. By one-step granulation in a fluidized bed, part of the microcrystalline cellulose is granulated internally first, and the temperature of the fluidized bed and the flow rate of the spraying slurry are controlled. While controlling the generation of impurities, the stability of the product is improved. It solves the problems in the prior art that the stability of the product is easily affected during the wet granulation process, it is more sensitive to process parameters, and there are problems such as poor content uniformity and large dissolution differences; and the dissolution rate will drop significantly during the stability period. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The following further specifically describes the present invention in conjunction with the drawings and specific embodiments, and the above and / or other advantages of the present invention will become clearer.

[0050] Figure 1 It is the dissolution curve of the preparations obtained in Example 1 and Comparative Examples 1-3 in 0.1M hydrochloric acid medium. SPECIFIC EMBODIMENTS

[0051] According to the following embodiments, the present invention can be better understood. However, those skilled in the art can easily understand that the content described in the embodiments is only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0052] In the following embodiments, the experimental methods are all conventional methods unless otherwise specified; the reagents and materials can be obtained from commercial channels unless otherwise specified.

[0053] In the following embodiments, the manufacturer of wheat starch is Changling Jilong Bio-pharmaceutical Co., Ltd., the manufacturer of microcrystalline cellulose is Asahi Kasei (models PH-301, KG-802), polyvinylpyrrolidone K30 is BASF, and the manufacturer of colloidal silica is Evonik (Evolink).

[0054] The solid content described in the present invention is in mass percentage.

[0055] Example 1

[0056] A preparation method of a stable baclofen tablet, when producing 1000 tablets, includes the following steps:

[0057] (1) Pretreatment of raw materials and auxiliary materials: Weigh each raw material and auxiliary material according to the weight ratio.

[0058] 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 polyvinylpyrrolidone K30, 0.3 parts of colloidal silicon dioxide, 0.7 parts of magnesium stearate. Among them, wheat starch and microcrystalline cellulose pass through a 60-mesh sieve; colloidal silicon dioxide and magnesium stearate pass through an 80-mesh sieve; the particle size of baclofen is 20 - 60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15%. 90 The particle size of 90 is 20 - 60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15%.

[0059] (2) Mixing and preheating: Take the formulated amount of baclofen, wheat starch, and microcrystalline cellulose (PH-301) and place them in a fluidized bed to make the material in a boiling state for preheating until the material temperature reaches above 45°C.

[0060] (3) Top-spray granulation: Add the formulated amount of binder solution for top-spray granulation, with a spraying speed of 8 rpm, and keep the material temperature in the fluidized bed at 40 - 50°C to obtain intermediate granules.

[0061] (4) Screening: Screen the intermediate granules with a screening machine using a 1.0 mm round-hole sieve, and set the rotation speed at 800 rpm.

[0062] (5) Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide, and magnesium stearate to the granules obtained in step (4), and mix them with a mixer at 12 revolutions per minute, with a loading coefficient of 40% - 80%, and mix for 3 minutes. Obtain intermediate materials, and detect the mixing uniformity and content of the intermediate materials.

[0063] (6) Tabletting: Install the intermediate materials obtained in step (5) in a mold, and calculate the tablet weight to be pressed according to the intermediate content result, control the tablet weight difference within ±5%, and the hardness within 4.0 kg - 8.0 kg.

[0064] (7) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil for packaging.

[0065] Example 2

[0066] A preparation method of a stable baclofen tablet, when producing 1000 tablets, includes the following steps:

[0067] (1) Pretreatment of raw materials and excipients: Weigh each raw material and excipient according to the weight ratio.

[0068] 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 polyvinylpyrrolidone K30, 0.3 part of colloidal silicon dioxide, and 0.7 part of magnesium stearate. Among them, wheat starch and microcrystalline cellulose pass through a 60-mesh sieve; colloidal silicon dioxide and magnesium stearate pass through an 80-mesh sieve; the particle size of baclofen is 20-60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15%. 90 The particle size of baclofen is 20-60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15%.

[0069] (2) Mixing and preheating: Take the formulated amount of baclofen, wheat starch, and microcrystalline cellulose (PH-301) and place them in a fluidized bed to make the materials in a boiling state for preheating until the material temperature reaches above 45°C.

[0070] (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.

[0071] (4) Screening: Screen the intermediate particles with a screening machine using a 1.0-mm round-hole sieve, and set the rotation speed at 800 rpm.

[0072] (5) Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide, and magnesium stearate to the particles obtained in step (4), and mix them with a mixer at 12 revolutions per minute. The loading coefficient is 40%-80%, and mix for 3 minutes. Obtain intermediate materials, and detect the mixing uniformity and content of the intermediate materials.

[0073] (6) Tabletting: Install the intermediate materials obtained in step (5) in a mold, and calculate the tablet weight to be pressed according to the intermediate content result, controlling the tablet weight difference within ±5% and the hardness within 4.0 kg - 8.0 kg.

[0074] (7) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil for packaging.

[0075] Example 3

[0076] A preparation method of a stable baclofen tablet, when producing 1000 tablets, includes the following steps:

[0077] (1) Pretreatment of raw materials and excipients: Weigh each raw material and excipient according to the weight ratio.

[0078] 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 polyvinylpyrrolidone K30, 0.3 part of colloidal silicon dioxide, and 0.7 part of magnesium stearate. Among them, corn starch and microcrystalline cellulose pass through a 60-mesh sieve; colloidal silicon dioxide and magnesium stearate pass through an 80-mesh sieve; the particle size of baclofen is 20-60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15%. 90 The particle size of baclofen is 20-60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15%.

[0079] (2)Mixing and preheating: Take the formulated amount of baclofen, corn starch, and microcrystalline cellulose (PH-301) and place them in a fluidized bed to make the materials in a boiling state for preheating until the material temperature reaches above 45°C.

[0080] (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.

[0081] (4)Screening: Screen the intermediate particles with a screening machine using a 1.0-mm round-hole sieve, and set the rotation speed at 800 rpm.

[0082] (5)Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide, and magnesium stearate to the particles obtained in step (4), and mix them with a mixer at 12 revolutions per minute. The loading coefficient is 40%-80%, and mix for 3 minutes. Obtain intermediate materials, and detect the mixing uniformity and content of the intermediate materials.

[0083] (6)Tabletting: Install the intermediate materials obtained in step (5) in a mold, and calculate the tablet weight to be pressed according to the intermediate content result, control the tablet weight difference within ±5%, and the hardness within 4.0 kg - 8.0 kg.

[0084] (7)Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil for packaging.

[0085] Comparative Example 1

[0086] Same as Example 1, the difference is that the proportion of the internal filler microcrystalline cellulose is different. When producing 1000 tablets, it includes the following steps:

[0087] (1)Pretreatment of raw and auxiliary materials: Weigh each raw material and auxiliary material according to the weight ratio.

[0088] 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 polyvinylpyrrolidone K30, 0.3 part of colloidal silicon dioxide, and 0.7 part of magnesium stearate. Among them, wheat starch and microcrystalline cellulose pass through a 60-mesh sieve; colloidal silicon dioxide and magnesium stearate pass through an 80-mesh sieve; the particle size of baclofen is 20-60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15%. 90 The particle size of baclofen is 20-60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15%.

[0089] (2) Mixing and preheating: Take the formulated amount of baclofen, wheat starch, and microcrystalline cellulose (PH-301) and place them in a fluidized bed to make the materials in a boiling state for preheating until the material temperature reaches above 45°C.

[0090] (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.

[0091] (4) Screening: Screen the intermediate particles with a screening machine using a 1.0-mm round-hole sieve, and set the rotation speed at 800 rpm.

[0092] (5) Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide, and magnesium stearate to the particles obtained in step (4), and mix them with a mixer at 12 revolutions per minute. The loading coefficient is 40%-80%, and mix for 3 minutes. Obtain intermediate materials, and detect the mixing uniformity and content of the intermediate materials.

[0093] (6) Tabletting: Install the intermediate materials obtained in step (5) in a mold, and calculate the tablet weight to be pressed according to the intermediate content result, controlling the tablet weight difference within ±5% and the hardness within 4.0 kg-8.0 kg.

[0094] (7) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil for packaging.

[0095] Comparative Example 2

[0096] Same as Example 1, the difference lies in the different temperature and spraying speed during the fluidized granulation process. When producing 1000 tablets, it includes the following steps:

[0097] (1) Pretreatment of raw and auxiliary materials: Weigh each raw material and auxiliary material according to the weight ratio.

[0098] 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 polyvinylpyrrolidone K30, 0.3 parts of colloidal silicon dioxide, and 0.7 parts of magnesium stearate. Among them, wheat starch and microcrystalline cellulose pass through a 60-mesh sieve; colloidal silicon dioxide and magnesium stearate pass through an 80-mesh sieve; the particle size of baclofen is 20 - 60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15%. 90 The particle size of baclofen is 20 - 60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15%.

[0099] (2) Mixing and preheating: Take the formulated amount of baclofen, wheat starch, and microcrystalline cellulose (PH-301) and place them in a fluidized bed to make the materials in a boiling state for preheating until the material temperature reaches above 55°C.

[0100] (3) Top-spray granulation: Add the formulated amount of binder solution for top-spray granulation, with a spraying speed of 15 rpm, and keep the material temperature in the fluidized bed at 55 - 65°C to obtain intermediate particles.

[0101] (4) Screening: Screen the intermediate particles with a screening machine using a 1.0-mm round-hole sieve, and set the rotation speed at 800 rpm.

[0102] (5) Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide, and magnesium stearate to the particles obtained in step (4), and mix them with a mixer at 12 revolutions per minute, with a loading coefficient of 40% - 80%, and mix for 3 minutes. Obtain intermediate materials, and detect the mixing uniformity and content of the intermediate materials.

[0103] (6) Tabletting: Install the intermediate materials obtained in step (5) in a mold, and calculate the tablet weight to be pressed according to the intermediate content result, control the tablet weight difference within ±5%, and the hardness within 4.0 kg - 8.0 kg.

[0104] (7) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard sheets and pharmaceutical aluminum foil for packaging.

[0105] Comparative Example 3

[0106] When the preparation method is replaced with the ordinary wet method, when producing 10,000 tablets, it includes the following steps:

[0107] (1) Pretreatment of raw and auxiliary materials: Weigh each raw material and auxiliary material according to the weight ratio.

[0108] 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 polyvinylpyrrolidone K30, 0.3 parts of colloidal silicon dioxide, 0.7 parts of magnesium stearate. Among them, wheat starch and microcrystalline cellulose pass through a 60-mesh sieve; colloidal silicon dioxide and magnesium stearate pass through an 80-mesh sieve; the particle size of baclofen is 20 - 60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15% by mass. 90 The particle size of baclofen is 20 - 60 μm and it passes through a 40-mesh sieve. Preparation of the binder: Take the formulated amount of polyvinylpyrrolidone K30 and purified water and place them in a beaker to prepare a binder solution with a solid content of 15% by mass.

[0109] (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 at 200 rpm, the chopping blade speed at 600 rpm, and the time at 180 s. After premixing, prepare the soft material.

[0110] (3) Preparing the soft material: Add the binder solution to the wet granulator. Set the stirring blade speed at 200 rpm, the chopping blade speed at 600 rpm, the binder addition time at 60 s, and the granulation time at 90 s.

[0111] (4) Drying: Dry the wet granules in an oven. Set the drying temperature at 50 °C and dry until the water content is less than 4.0%.

[0112] (5) Screening: Screen the dried granules with a granule screen. Use a 1.0 mm round-hole sieve and set the rotation speed at 800 rpm.

[0113] (6) Mixing: Add microcrystalline cellulose (KG-802), colloidal silicon dioxide, and magnesium stearate to the dry granules obtained in step (5). Use a mixer to mix at 12 revolutions per minute, with a loading coefficient of 40% - 80%, and mix for 2 minutes. Obtain the intermediate material and detect the mixing uniformity and content of the intermediate material.

[0114] (7) Tableting: Install the intermediate material obtained in step (6) in a mold, and calculate the tablet weight to be pressed according to the intermediate content result. Control the tablet weight difference within ±5% and the hardness within 4.0 kg - 8.0 kg.

[0115] (8) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard sheets and pharmaceutical aluminum foil for packaging.

[0116] Experiment 1

[0117] The mixing uniformity of the samples of the above Examples 1 - 3 and Comparative Examples 1 and 3 was determined, and the experimental results are shown in the following table. The RSD results of the samples with uniform content in Examples 1 - 3 were 0.84%, 1.27%, and 1.03%; the RSD result measured for Comparative Example 1 was 3.14%. The RSD of the Examples was much smaller than that of Comparative Example 1 and Comparative Example 3, and the product was more uniform and stable.

[0118] Table 1: Summary Table of Sample Mixing Uniformity Results of Examples 1 - 3 and Comparative Example 1

[0119]

[0120] Test 2

[0121] The influencing factor (high temperature and high humidity, 60°C + RH75%) placement study was carried out simultaneously on the above Example 1 and Comparative Examples 1 - 2, with comparisons of appearance, content, dissolution, and related substances. The results showed that the appearance of the products of Example 1 and Comparative Examples 1 - 2 was similar at each time point. At the 15th day and the 30th day, the content in Example 1 was higher than that in Comparative Examples 1 - 2. The change trends of dissolution and related substances in Example 1 were significantly better than those in Comparative Examples 1 - 3. The results are shown in Table 2 below.

[0122] Table 2

[0123]

[0124] Test 3

[0125] The stability study (accelerated at 40°C / RH75%, long - term at 30°C / RH60%) placement study was carried out simultaneously on the above Example 1 and Comparative Example 1, with comparisons of appearance, dissolution, and related substances. The results showed that during the stability period of the products of Example 1 and Comparative Example 1, the dissolution of Example 1 was stable, while the dissolution of Comparative Example 1 and Comparative Example 3 showed an obvious 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.

[0126] Table 3

[0127]

[0128] Test 4

[0129] The dissolution curves of the samples prepared from Examples 1 - 2 and Comparative Example 3 were determined according to the dissolution and release determination method (Method 2 of General Rule 0931). The paddle method was used with a rotation speed of 50 rpm, and the dissolution conditions were 0.1 M hydrochloric acid medium and 37°C. The experimental results showed that the dissolution curves of the preparations of Examples 1 - 2 of the present invention were all stable and met the requirements, and the dissolution differences of the curves were small. The dissolution curve result of Comparative Example 3 was relatively slow, and the dissolution differences were large. The results are shown in Table 4 and Figure 1 .

[0130] Table 4 Cumulative dissolution rate %

[0131]

[0132] The above-described embodiments merely represent several implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the patent for the present invention. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all fall within the protection scope of the present invention. Therefore, the protection scope of the patent for the present invention shall be subject to the appended 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: 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 and mixing; The internal filler is a combination of wheat starch and / or corn starch and 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; and the external filler is microcrystalline cellulose.

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 binder is povidone, the glidant is colloidal silicon dioxide, and the lubricant is magnesium stearate.

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

6. 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.

7. 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 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 particles; after the obtained particles are granulated, an external filler, a flow aid and a lubricant are added and mixed; The internal filler is a combination of wheat starch and / or corn starch and 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; and the external filler is microcrystalline cellulose.

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