Blonanserin orally disintegrating tablet composition and preparation method thereof

Abstract

The invention discloses a blonanserin orally disintegrating tablet composition and a preparation method thereof, and relates to the technical field of preparations. The blonanserin orally disintegrating tablet composition is prepared from the following components in parts by weight: 4 parts of blonanserin micro powder, 60 to 100 parts of a diluent, 10 to 30 parts of a disintegrating agent, 0.5 to 2 parts of an adhesive, 1 to 3 parts of a flow aid, 1 to 5 parts of a sweetening agent, 0.5 to 5 parts of a lubricating agent and 0.5 to 1.5 parts of a solubilizer, the disintegrating agent is a composition of low-substituted hydroxypropyl cellulose and polyvinylpolypyrrolidone, and the mass ratio of the addition amount of the low-substituted hydroxypropyl cellulose to the addition amount of the polyvinylpolypyrrolidone is (20-1): (10-5) in parts by weight of the disintegrating agent. The blonanserin and the solubilizer are matched for use, so that the dissolution rate of the blonanserin is greatly improved, and the disintegration time limit is further prolonged by matching with other components, namely the low-substituted hydroxy propyl cellulose and the cross-linked povidone, in the material.

Description

[0001] This application is a divisional application of the invention patent application with application number CN202211213800.2, application date September 30, 2022, and invention name “A Bunanserin orally disintegrating tablet composition and its preparation method”. Technical Field

[0002] The present invention relates to the technical field of medicine, and in particular to a Blonanserin orally disintegrating tablet composition and a preparation method thereof. Background Art

[0003] Blonanserin is a serotonin and dopamine antagonist clinically used to treat schizophrenia. Oral disintegrating tablets have a bitter taste and a long disintegration time, making them difficult to swallow orally. Orally disintegrating tablets, a novel pharmaceutical formulation, rapidly disintegrate into fine particles on the tongue, offering a sweet taste and ease of administration. No water is required after taking the tablet, making them particularly suitable for special populations.

[0004] However, blonanserin is pH-dependent, being readily soluble in acid but practically insoluble in neutral and alkaline media. Blonanserin orally disintegrating tablets prepared using existing technologies suffer from long orally disintegrating time and poor dissolution. Summary of the Invention

[0005] The present invention aims to provide a composition of a Blonanserin orally disintegrating tablet and a preparation method thereof, so as to overcome the problems of Blonanserin orally disintegrating tablets in the prior art, such as long oral disintegration time and poor dissolution effect.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] In a first aspect, the present invention provides a blonanserin orally disintegrating tablet composition, which comprises the following components, in parts by weight: 4 parts of blonanserin micropowder, 60-100 parts of a diluent, 10-30 parts of a disintegrant, 0.5-2 parts of a binder, 1-3 parts of a glidant, 1-5 parts of a sweetener, 0.5-5 parts of a lubricant, and 0.5-1.5 parts of a solubilizer.

[0008] Furthermore, the disintegrant is selected from one or a combination of cross-linked carboxymethyl cellulose sodium, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, and sodium carboxymethyl starch.

[0009] Furthermore, the disintegrant is a composition of low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone, wherein the mass ratio of the low-substituted hydroxypropyl cellulose to the cross-linked polyvinylpyrrolidone added is (20-1):(10-5) based on the weight of the disintegrant.

[0010] Furthermore, the flow aid is selected from a material with a specific surface area of ​​500 to 1000 m 2 / g of silicon dioxide, with a specific surface area of ​​300 to 500m2 / g of one or two kinds of micro powder silica gel.

[0011] Furthermore, the diluent is selected from one or a combination of lactose, mannitol, pregelatinized starch, corn starch, and microcrystalline cellulose; and / or,

[0012] The binder is selected from one or a combination of povidone, hydroxypropyl cellulose and hypromellose; and / or,

[0013] The sweetener is selected from one or a combination of aspartame, acesulfame potassium, saccharin sodium, and sucralose; and / or,

[0014] The lubricant is selected from one or a combination of magnesium stearate, stearic acid and talc.

[0015] Furthermore, the Blonanserin micropowder is a Blonanserin micropowder having a particle size of less than 10 μm; and / or,

[0016] The solubilizer has a specific surface area of ​​20 to 600 m 2 / g of silica.

[0017] In a second aspect, the present invention further provides a method for preparing a Blonanserin orally disintegrating tablet composition, which is applied to the above-mentioned Blonanserin orally disintegrating tablet composition, comprising the following steps:

[0018] Mixing the diluent, disintegrant, binder, glidant, and sweetener uniformly according to the formula ratio to obtain a first mixture;

[0019] emulsifying the blonanserin micropowder and the solubilizer with water at high shear speed for a certain period of time to obtain a second mixture;

[0020] The second mixture is wet-granulated and added to the first mixture. After drying, a lubricant is added, and the mixture is mixed and tabletted to obtain a Blonanserin orally disintegrating tablet composition.

[0021] Compared with the prior art, the beneficial effects of the preparation method of the Blonanserin orally disintegrating tablet composition provided by the present invention are the same as those of the Blonanserin orally disintegrating tablet composition of the above technical solution, which will not be described in detail here.

[0022] Furthermore, after mixing the bulk drug blonanserin micropowder with a solubilizer, the mixture is emulsified with water at high shear speed for a certain period of time to obtain a second mixture, which includes the following steps:

[0023] Micronizing the raw material drug blonanserin to less than 10 microns to obtain blonanserin micropowder;

[0024] The bunanserin is mixed with a specific surface area of ​​500 to 1000 m 2 / g of solubilizer, added to 30-55 parts of water at a low speed of 2krpm-5krpm, slowly adjusted the speed to a high speed of 8krpm-11krpm at the low speed rate, and high-speed shear emulsification for a certain time to obtain a second mixture.

[0025] Furthermore, the certain time is 5 to 15 minutes.

[0026] Furthermore, the micronized bunanserin was pulverized using a jet mill, with a feed pressure of 0.5-0.6 MPa and a pulverization pressure of 0.2 MPa.

[0027] Compared with the prior art, the Bunanserin orally disintegrating tablet composition and preparation method provided by the present invention have the following beneficial effects:

[0028] (1) Compared with the prior art, the orally disintegrating tablet composition of Bunanserin provided by the present invention is characterized in that, in the technical solution of the present invention, a solubilizer is first mixed with Bunanserin micropowder, and the solubilizer and Bunanserin micropowder act together to increase the dissolution rate and dissolution rate of Bunanserin micropowder, and the synergistic effect of other components is combined to finally ensure that the core hardness of the Bunanserin orally disintegrating tablet composition of the present invention is 40 to 60 N, the friability is qualified, the disintegration time is completely within 1 minute, the dissolution rate is fast, the mouthfeel is non-gritty, and the smell is sweet.

[0029] (2) The orally disintegrating tablet composition of blonanserin provided by the present invention further comprises a disintegrant preferably comprising a combination of low-substituted hydroxypropylcellulose and cross-linked polyvinylpyrrolidone. By selecting the composition and specific ratio of the two disintegrants, the orally disintegrating tablet of blonanserin can be made to meet the disintegration time requirements. Testing has shown that the orally disintegrating tablet composition of the present invention completely disintegrates within 1 minute, has a fast dissolution rate, and has a non-gritty mouthfeel. This avoids the problem of using a single disintegrant, where a large amount of disintegrant affects the mouthfeel of the orally disintegrating tablet composition, and where a small amount of disintegrant fails to meet the disintegration time requirements.

[0030] (3) The Bunanserin orally disintegrating tablet composition provided by the present invention is further prepared by selecting a specific surface area of ​​500 to 1000 m 2 / g of silicon dioxide, with a specific surface area of ​​300 to 500m 2 One or two kinds of micro powder silica gel of / g are used as flow aids to improve flow, thereby improving the fluidity of the particles. The increase in the fluidity of the particles facilitates tableting of the composition material.

[0031] (4) The orally disintegrating tablet composition of Blonanserin provided by the present invention is further prepared by selecting Blonanserin micropowder with a particle size of less than 10 μm and a specific surface area of ​​20 to 600 m 2 / g of silica solubilizer, the blonanserin micropowder of a specific particle size interacts with the solubilizer of a specific specific surface area, and through certain technical means, the two are brought into an emulsified state. At this time, after the emulsified emulsion is mixed with other excipients, on the one hand, the emulsion is more easily mixed with the other excipients more evenly, thereby ensuring the uniformity of the drug content. On the other hand, the blonanserin micropowder, as a hydrophobic API, interacts with the hydrophilic excipient silica, and then is mixed with other excipients for tableting, which can greatly improve the dissolution rate and solubility of the hydrophobic API in the blonanserin orally disintegrating tablets.

[0032] (5) The preparation method of the orally disintegrating tablet composition of blonanserin provided by the present invention comprises the following steps: mixing the raw material blonanserin micropowder with a solubilizer, and then dispersing the mixture by high-shear emulsification with water, thereby improving the mixing uniformity of the blonanserin micropowder and the solubilizer, and allowing the blonanserin micropowder to be fully coated with the solubilizer. The emulsion obtained by high-shear emulsification with water is added to the first mixture of excipients by a wet method. Compared with the micropowder addition in the prior art, the wet method can greatly improve the content uniformity of the drug. In addition, the blonanserin micropowder and the solubilizer work together to improve the dissolution rate and solubility of the blonanserin drug. The tablets obtained according to the present invention disintegrate within 1 minute, have a sweet smell, and are free of gritty sensation. The solubility of the blonanserin drug in a pH 6.0 medium can reach 80% in 30 minutes.

[0033] (6) The preparation method of the orally disintegrating tablet composition provided by the present invention comprises the following steps: micronizing the raw material drug to a particle size of less than 10 μm, mixing the micronized blonanserin powder with a specific surface area of ​​20 to 600 m 2 / g of solubilizing agent is mixed and added to 30-55 parts of water at a low speed of 2krpm-5krpm. The low speed is first added to ensure that the blonanserin micropowder and the solubilizing agent are fully wetted by water. Then, the speed is slowly adjusted to a high speed of 8krpm-11krpm at a low speed. During the slow adjustment of the speed, the blonanserin micropowder and the solubilizing agent can be further evenly mixed, and the solubilizing agent is further coated on the surface of the blonanserin micropowder. Then, at a high speed, high shear emulsification is performed for 5-15 minutes to obtain an emulsion. After the emulsion is added as a wetting agent, on the one hand, it can ensure that the present invention has a non-gritty taste and a good taste, and on the other hand, it can greatly improve the dissolution rate of the raw material drug. DETAILED DESCRIPTION

[0034] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0035] Example 1

[0036] The present invention provides a blonanserin orally disintegrating tablet composition, which comprises the following components in parts by weight: 4 parts of blonanserin micropowder with a particle size of less than 10 microns, 60 parts of lactose, 11 parts of low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone, wherein the mass ratio of low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone added in the disintegrant is 1:10, 0.5 parts of polyvinylpyrrolidone K30, and the specific surface area is 500m 2 / g of silicon dioxide glidant 1 part, aspartame 1 part, magnesium stearate 0.5 parts, specific surface area 20m 2 / g of silica solubilizing agent 0.5 parts.

[0037] In this embodiment, the preparation method of the Bunanserin orally disintegrating tablet composition comprises the following steps:

[0038] Step S1: according to the formula ratio, lactose diluent, cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose disintegrant, polyvinylpyrrolidone K30 binder, specific surface area of ​​500m 2 / g of silicon dioxide glidant and aspartame sweetener are mixed evenly to obtain a first mixture;

[0039] Step S2: Mix the ingredients according to the formula ratio, and mix the bunanserin powder with a specific surface area of ​​20m 2 / g of silica solubilizing agent, added to 40 parts of water at a speed of 2krpm, slowly adjusted the speed from 2krpm to 8krpm, and high-speed shear emulsification was performed for 15 minutes to obtain a second mixture; wherein, in this embodiment, the blonanserin was micronized using a jet mill for pulverization, with a feed pressure of 0.5 MPa and a pulverization pressure of 0.2 MPa to obtain blonanserin micropowder with a particle size of less than 10 microns;

[0040] Step S3: wet-granulate the second mixture and add it to the first mixture. After drying, add the formulated amount of magnesium stearate lubricant, mix, and tablet to obtain a blonanserin orally disintegrating tablet composition.

[0041] After testing, the average hardness of the Buonanserin orally disintegrating tablet composition in Example 1 was 4.94 kg, and the disintegration time was 33 s.

[0042] Example 2

[0043] The embodiment of the present invention provides a blonanserin orally disintegrating tablet composition, which comprises the following components in parts by weight: 4 parts of blonanserin micropowder with a particle size of less than 10 microns, 60 parts of mannitol, 20 parts of low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone, wherein the mass ratio of low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone added in the disintegrant is 4:1, 0.7 parts of hydroxypropyl cellulose, and a specific surface area of ​​700 m 2 / g of silicon dioxide glidant 1.4 parts, acesulfame potassium 2.1 parts, magnesium stearate 1 part, specific surface area of ​​600m 2 / g of silica solubilizing agent 0.7 parts.

[0044] In this embodiment, the preparation method of the Bunanserin orally disintegrating tablet composition comprises the following steps:

[0045] Step S1: according to the formula ratio, mannitol diluent, cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose disintegrant, hydroxypropyl cellulose binder, specific surface area of ​​700m 2 / g of silicon dioxide glidant and acesulfame potassium sweetener are mixed evenly to obtain a first mixture;

[0046] Step S2: Mix the ingredients according to the formula ratio, and mix the bunanserin powder with a specific surface area of ​​600m 2 / g of silica solubilizing agent, added to 40 parts of water at a rotation speed of 3krpm, slowly adjusted the rotation speed from 3krpm to 9krpm, and high-speed shear emulsification was performed for 10 minutes to obtain a second mixture; wherein, in this embodiment, the blonanserin was micronized using a jet mill for pulverization, the feed pressure was 0.5 MPa, and the pulverization pressure was 0.2 MPa, to obtain blonanserin powder with a particle size of less than 10 microns;

[0047] Step S3: wet-granulate the second mixture and add it to the first mixture. After drying, add the formulated amount of magnesium stearate lubricant, mix, and tablet to obtain a blonanserin orally disintegrating tablet composition.

[0048] After testing, the average hardness of the Buonanserin orally disintegrating tablet composition in Example 2 was 4.99 kg, and the disintegration time was 40 s.

[0049] Example 3

[0050] The embodiment of the present invention provides a blonanserin orally disintegrating tablet composition, which comprises the following components in parts by weight: 4 parts of blonanserin fine powder with a particle size of less than 10 microns, 70 parts of pregelatinized starch, 17 parts of low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone, wherein the mass ratio of low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone added in the disintegrant is 10:7, 0.8 parts of hypromellose, and the specific surface area is 800m 2 / g of silicon dioxide glidant 1.7 parts, saccharin sodium 3 parts, magnesium stearate 3 parts, specific surface area of ​​500m 2 / g of silica solubilizing agent 1.0 part.

[0051] In this embodiment, the preparation method of the Bunanserin orally disintegrating tablet composition comprises the following steps:

[0052] Step S1: according to the formula ratio, pregelatinized starch diluent, cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose disintegrant, hydroxypropyl methylcellulose binder, specific surface area of ​​800m 2 / g of silicon dioxide glidant and saccharin sodium sweetener are mixed evenly to obtain a first mixture;

[0053] Step S2: Mix the ingredients according to the formula ratio, and mix the bunanserin powder with a specific surface area of ​​500m 2 / g of silica solubilizing agent, added to 55 parts of water at a speed of 4krpm, slowly adjusted the speed from 4krpm to 10krpm, and high-speed shear emulsification was performed for 7 minutes to obtain a second mixture; wherein, in this embodiment, the blonanserin was micronized using a jet mill for pulverization, the feed pressure was 0.6MPa, and the pulverization pressure was 0.2MPa, to obtain blonanserin micropowder with a particle size of less than 10 microns;

[0054] Step S3: wet-granulate the second mixture and add it to the first mixture. After drying, add magnesium stearate as a lubricant, mix, and tablet to obtain a Bunanserin orally disintegrating tablet composition.

[0055] After testing, the average hardness of the Buonanserin orally disintegrating tablet composition in Example 3 was 5.11 kg, and the disintegration time was 30 s.

[0056] Example 4

[0057] The embodiment of the present invention provides a blonanserin orally disintegrating tablet composition, which comprises the following components in parts by weight: 4 parts of blonanserin fine powder with a particle size of less than 10 microns, 80 parts of microcrystalline cellulose, 24 parts of cross-linked polyvinylpyrrolidone and sodium carboxymethyl starch in an added amount in a mass ratio of 2:1, 1.2 parts of povidone K30, and a specific surface area of ​​1000m 2 / g of silicon dioxide glidant 2.0 parts, sucralose 2 parts, talc 4 parts, specific surface area 400m 2 / g of silica solubilizer 1.2 parts.

[0058] In this embodiment, the preparation method of the Bunanserin orally disintegrating tablet composition comprises the following steps:

[0059] Step S1: According to the formula ratio, microcrystalline cellulose diluent, cross-linked polyvinylpyrrolidone and sodium carboxymethyl starch disintegrant, polyvinylpyrrolidone K30 binder, specific surface area of ​​1000m 2 / g of silicon dioxide glidant and sucralose sweetener are mixed evenly to obtain a first mixture;

[0060] Step S2: Mix the ingredients according to the formula ratio, and mix the bunanserin powder with a specific surface area of ​​400m 2 / g of silica solubilizing agent, added to 30 parts of water at a rotation speed of 5krpm, slowly adjusted the rotation speed from 5krpm to 11krpm, and high-speed shear emulsification was performed for 5 minutes to obtain a second mixture; wherein, in this embodiment, the blonanserin was micronized using a jet mill for pulverization, with a feed pressure of 0.5 MPa and a pulverization pressure of 0.2 MPa to obtain blonanserin micropowder with a particle size of less than 10 microns;

[0061] Step S3: wet-granulate the second mixture and add it to the first mixture. After drying, add a formulated amount of talc lubricant, mix, and tablet to obtain a Bunanserin orally disintegrating tablet composition.

[0062] After testing, the average hardness of the Buonanserin orally disintegrating tablet composition in Example 4 was 4.60 g, and the disintegration time was 50 s.

[0063] Example 5

[0064] The embodiment of the present invention provides a blonanserin orally disintegrating tablet composition, which comprises the following components in parts by weight: 4 parts of blonanserin micropowder with a particle size of less than 10 microns, 90 parts of corn starch, 10 parts of cross-linked polyvinylpyrrolidone, 1.5 parts of polyvinylpyrrolidone K30 and hydroxypropyl cellulose in a mass ratio of 1:1, and a specific surface area of ​​300 m 2 / g micro powder silica gel flow aid 2.6 parts, added mass ratio of aspartame and acesulfame potassium 3.3 parts, stearic acid 5 parts, specific surface area 300m 2 / g of silica solubilizer 1.5 parts.

[0065] In this embodiment, the preparation method of the Bunanserin orally disintegrating tablet composition comprises the following steps:

[0066] Step S1: corn starch, cross-linked polyvinylpyrrolidone disintegrant, polyvinylpyrrolidone K30 and hydroxypropyl cellulose binder are mixed according to the formula ratio, and the specific surface area is 300m 2 / g of micro-powdered silica gel glidant, aspartame and acesulfame potassium sweetener are uniformly mixed to obtain a first mixture;

[0067] Step S2: Mix the ingredients according to the formula ratio, and mix the Bhunanserin powder with a specific surface area of ​​300m 2 / g of silica solubilizing agent, added to 40 parts of water at a rotation speed of 3krpm, slowly adjusted the rotation speed from 3krpm to 10krpm, and high-speed shear emulsification was performed for 10 minutes to obtain a second mixture; wherein, in this embodiment, the blonanserin was micronized using a jet mill for pulverization, the feed pressure was 0.5 MPa, and the pulverization pressure was 0.2 MPa, to obtain blonanserin micropowder with a particle size of less than 10 microns;

[0068] Step S3: wet-granulate the second mixture and add it to the first mixture. After drying, add a formulated amount of stearic acid lubricant, mix, and tablet to obtain a bunanserin orally disintegrating tablet composition.

[0069] After testing, the average hardness of the Buonanserin orally disintegrating tablet composition in Example 5 was 4.52 kg, and the disintegration time was 50 s.

[0070] Example 6

[0071] The embodiment of the present invention provides a composition of orally disintegrating blonanserin tablets, which comprises the following components in parts by weight: 4 parts of blonanserin micropowder with a particle size of less than 10 microns, 100 parts of lactose, 30 parts of low-substituted hydroxypropyl cellulose, 2 parts of hydroxypropyl cellulose, and a specific surface area of ​​500m 2 / g micro powder silica gel flow aid 3 parts, acesulfame potassium 5 parts, talc 4 parts, specific surface area of ​​200m 2 / g of silica solubilizing agent 0.8 parts.

[0072] In this embodiment, the preparation method of the Bunanserin orally disintegrating tablet composition comprises the following steps:

[0073] Step S1: according to the above formula ratio, lactose, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, with a specific surface area of ​​500m 2 / g of micro-powdered silica gel glidant and acesulfame potassium are mixed evenly to obtain a first mixture;

[0074] Step S2: According to the above formula ratio, the bunanserin powder and the specific surface area of ​​200m 2 / g of silica solubilizer was added to 40 parts of water at a rotation speed of 3krpm, and the rotation speed was slowly adjusted from 3krpm to 10krpm, and high-speed shear emulsification was performed for 10 minutes to obtain a second mixture; wherein, in this embodiment, the blonanserin was micronized using a jet mill for pulverization, the feed pressure was 0.6 MPa, and the pulverization pressure was 0.2 MPa, to obtain blonanserin micropowder with a particle size of less than 10 microns;

[0075] Step S3: wet-granulate the second mixture and add it to the first mixture. After drying, add the formulated amount of talc, mix, and tablet to obtain a Bunanserin orally disintegrating tablet composition.

[0076] After testing, the average hardness of the Buonanserin orally disintegrating tablet composition in Example 6 was 4.68 kg, and the disintegration time was 57 s.

[0077] Comparative Example 1

[0078] Compared with Example 3, only the solubilizing agent in Example 3 was removed, and the other components remained unchanged.

[0079] The preparation method of the orally disintegrating tablet composition of Comparative Example 1 is the same as that of Example 3.

[0080] After testing, the average hardness of the Buonanserin orally disintegrating tablet composition in Comparative Example 1 was 5.02 kg, and the disintegration time was 52 s.

[0081] Comparative Example 2

[0082] Comparative Example 2 differs from Example 3 only in the preparation method. In Comparative Example 2, the preparation method of the Blonanserin orally disintegrating tablet composition differs from that of Example 3 in the following points:

[0083] Step S2: According to the above formula ratio, the bunanserin powder and the specific surface area of ​​500m 2 / g of silica solubilizer, 40 parts of water, and stirring at 800 rpm to obtain a second mixture;

[0084] Step S3: wet-granulate the second mixture and add it to the first mixture. After drying, add the formulated amount of talc, mix, and tablet to obtain a Bunanserin orally disintegrating tablet composition.

[0085] After testing, the average hardness of the Buonanserin orally disintegrating tablet composition in Comparative Example 2 was 4.71 kg, and the disintegration time was 1 min 10 s.

[0086] Comparative Example 3

[0087] Comparative Example 3 differs from Example 3 only in the preparation method. In Comparative Example 3, the preparation method of the Blonanserin orally disintegrating tablet composition differs from that of Example 3 in the following points:

[0088] Step S2: According to the above formula ratio, the micro powder of Bhunanserin and the specific surface area of ​​500m 2 / g of silica solubilizer were mixed evenly to obtain a second mixture;

[0089] Step S3: Add the second mixture directly to the first mixture, add magnesium stearate lubricant, pass through an 80-mesh sieve and mix evenly, place in a fluidized bed, and set the fluidized bed granulation parameters: inlet air temperature 40-60°C, inlet air volume: 5-30m3 / h, material temperature: 20-40°C, atomization pressure: 0.2-2kg / cm 2 , the drying moisture is controlled at 2-5%, mixed and tableted to obtain the Bunanserin orally disintegrating tablet composition.

[0090] After testing, the average hardness of the Buonanserin orally disintegrating tablet composition in Comparative Example 3 was 4.64 kg, and the disintegration time was 30 s.

[0091] Comparative Example 4

[0092] Comparative Example 4 is compared with Example 3, except that the particle size of the Bunanserin micropowder is different. In Comparative Example 4, the Bunanserin micropowder with a particle size of 20 μm is used, and the other components remain unchanged.

[0093] The preparation method of the Zhongbunanserin orally disintegrating tablet composition of Comparative Example 4 is the same as that of Example 3.

[0094] After testing, the hardness of the Buonanserin orally disintegrating tablet composition in Comparative Example 4 was 4.58 kg, and the disintegration time was 52 s.

[0095] Furthermore, the present invention further conducted the following performance tests on the Buonanserin orally disintegrating tablets prepared in Examples 1 to 6 and Comparative Examples 1 to 4.

[0096]

[0097]

[0098] The above test results show that: (1) The disintegration time is optimal when the low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone are combined; (2) When no solubilizer is added, the dissolution of the API is reduced and slow; (3) When the API is dispersed in the silica aqueous suspension using ordinary stirring, the dissolution rate is low and the API fails to dissolve. (4) The wet granulation process is superior to the fluidized bed granulation process. (5) The particle size of the API is too large, the dissolution is slow, and the dissolution endpoint cannot be reached.

[0099] The above are merely specific embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A Bunanselin orally disintegrating tablet composition, characterized in that: The composition comprises the following components in parts by weight: 4 parts of blonanserin micropowder, 60-100 parts of diluent, 10-30 parts of disintegrant, 0.5-2 parts of binder, 1-3 parts of glidant, 1-5 parts of sweetener, 0.5-5 parts of lubricant, and 0.5-1.5 parts of solubilizer; The disintegrant is a composition of low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone, wherein the mass ratio of the low-substituted hydroxypropyl cellulose to the cross-linked polyvinylpyrrolidone added is (20-1):(10-5) based on the weight of the disintegrant.

2. The orally disintegrating tablet composition of Blonanserin according to claim 1, characterized in that: The flow aid is selected from a specific surface area of ​​500 to 1000 m 2 / g of silicon dioxide, with a specific surface area of ​​300 to 500m 2 / g of one or two kinds of micro powder silica gel.

3. The orally disintegrating tablet composition of Blonanserin according to claim 1, characterized in that: The diluent is selected from one or a combination of lactose, mannitol, pregelatinized starch, corn starch, and microcrystalline cellulose; and / or, The binder is selected from one or a combination of povidone, hydroxypropyl cellulose and hypromellose; and / or, The sweetener is selected from one or a combination of aspartame, acesulfame potassium, saccharin sodium, and sucralose; and / or, The lubricant is selected from one or a combination of magnesium stearate, stearic acid, and talc.

4. The Blonanserin orally disintegrating tablet composition according to any one of claims 1 to 3, characterized in that The blonanserin micropowder is a blonanserin micropowder having a particle size of less than 10 microns; and / or, The solubilizing agent has a specific surface area of ​​20 to 600 m 2 / g of silica.

5. A method for preparing a Bunanselin orally disintegrating tablet composition, characterized in that: The Buonanserin orally disintegrating tablet composition according to any one of claims 1 to 4 comprises the following steps: Mixing the diluent, disintegrant, binder, glidant, and sweetener uniformly according to the formula ratio to obtain a first mixture; emulsifying the blonanserin micropowder and the solubilizer with water at high shear speed for a certain period of time to obtain a second mixture; The second mixture is wet-granulated and added to the first mixture. After drying, a lubricant is added, and the mixture is mixed and tableted to obtain the Bunanserin orally disintegrating tablet composition.

6. The method for preparing the Bunanserin orally disintegrating tablet composition according to claim 5, characterized in that: The step of mixing the bulk drug blonanserin micropowder with the solubilizer and then emulsifying with water at high speed for a certain period of time to obtain the second mixture comprises the following steps: micronizing blonanserin to less than 10 microns to obtain the blonanserin micropowder; The bunanserin is mixed with a specific surface area of ​​500 to 1000 m 2 / g of solubilizer, added to 30-55 parts of water at a low speed of 2krpm-5krpm, slowly adjusted the speed to a high speed of 8krpm-11krpm at the low speed rate, and high-speed shear emulsification for a certain time to obtain a second mixture.

7. The method for preparing the Bunanserin orally disintegrating tablet composition according to claim 6, characterized in that: The certain time is 5 to 15 minutes.

8. The method for preparing the Blonanserin orally disintegrating tablet composition according to any one of claims 5 to 7, characterized in that: Bunanserin was micronized using a jet mill with a feed pressure of 0.5-0.6 MPa and a crushing pressure of 0.2 MPa.

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