A blonanserin orally disintegrating tablet composition and a preparation method thereof

Abstract

The present invention discloses a buclizine hydrochloride orally disintegrating tablet composition and a preparation method thereof, which relates to the technical field of preparations. The buclizine hydrochloride orally disintegrating tablet composition, calculated by weight parts, comprises the following components: 4 parts of buclizine hydrochloride fine powder, 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 sweetening agent, 0.5-5 parts of a lubricant, and 0.5-1.5 parts of a solubilizer. The present invention uses buclizine hydrochloride in combination with a solubilizer, so that the dissolution of buclizine hydrochloride is greatly improved. In combination with other components in the material, low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone, the disintegration time limit is further improved.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and particularly relates to a blonanserin orally disintegrating tablet composition and a preparation method thereof. Background Art

[0002] Blonanserin is a serotonin and dopamine antagonist, and is clinically used for the treatment of schizophrenia. The ordinary tablets of blonanserin have a bitter taste and too long disintegration time limit, and are not easy to be taken orally in the mouth. As a new type of pharmaceutical preparation, the orally disintegrating tablet can quickly disintegrate into fine particles on the tongue surface, has a sweet taste and is easy to take, and does not need to drink water after taking, so it is particularly suitable for special populations, such as Alzheimer's disease, psychosis, etc.

[0003] However, blonanserin has pH dependence, and it is easily soluble in acid and almost insoluble in neutral and alkaline media. The blonanserin orally disintegrating tablets prepared by the existing technology have problems of long orally disintegrating time limit and poor dissolution effect. Summary of the Invention

[0004] The purpose of the present invention is to provide a blonanserin orally disintegrating tablet composition and a preparation method thereof, which are used to overcome the problems of long orally disintegrating time limit and poor dissolution effect existing in the blonanserin orally disintegrating tablets in the prior art.

[0005] In order to achieve the above purpose, the present invention provides the following technical solutions:

[0006] In the 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 fine powder, 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.

[0007] Further, the disintegrant is selected from one or a combination of several of croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, and sodium carboxymethyl starch.

[0008] Further, the disintegrant is a composition of low-substituted hydroxypropyl cellulose and crospovidone, and in terms of the weight parts of the disintegrant, the mass ratio of the addition amounts of low-substituted hydroxypropyl cellulose and crospovidone is (20-1):(10-5).

[0009] Further, the glidant is selected from one or two of silica with a specific surface area of 500-1000 m 2 / g and microcrystalline silica gel with a specific surface area of 300-500 m 2 / g.

[0010] Further, the diluent is selected from one or a combination of lactose, mannitol, pregelatinized starch, corn starch, and microcrystalline cellulose; and / or,

[0011] The binder is selected from one or a combination of povidone, hydroxypropyl cellulose, and hydroxypropyl methylcellulose; and / or,

[0012] The sweetener is selected from one or a combination of aspartame, acesulfame potassium, sodium saccharin, and sucralose; and / or,

[0013] The lubricant is selected from one or a combination of magnesium stearate, stearic acid, and talc powder.

[0014] Furthermore, the blonanserin micropowder is blonanserin micropowder with a particle size less than 10 microns; and / or,

[0015] The solubilizer is silica with a specific surface area of 20 - 600 m 2 / g.

[0016] In a second aspect, the present invention also provides a preparation method of a blonanserin orally disintegrating tablet composition, which is applied to the above-mentioned blonanserin orally disintegrating tablet composition, and includes the following steps:

[0017] Weigh the ingredients according to the formula ratio, and uniformly mix the diluent, disintegrant, binder, glidant, and sweetener to obtain a first mixture;

[0018] High - speed shear emulsify the blonanserin micropowder and the solubilizer with water for a certain period of time to obtain a second mixture;

[0019] Add the second mixture prepared by wet granulation to the first mixture, dry it, add the lubricant, mix and press to obtain the blonanserin orally disintegrating tablet composition.

[0020] 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 in the above technical solution, and will not be elaborated here.

[0021] Furthermore, after mixing the blonanserin micropowder of the active pharmaceutical ingredient with the solubilizer, high - speed shear emulsifying with water for a certain period of time to obtain a second mixture includes the following steps:

[0022] Micronize the blonanserin micropowder of the active pharmaceutical ingredient to less than 10 microns to obtain blonanserin micropowder;

[0023] Mix the blonanserin with a solubilizer having a specific surface area of 500 - 1000 m 2 / g, add it to 30 - 55 parts of water at a low rotation speed of 2 krpm - 5 krpm, and slowly adjust the rotation speed to a high rotation speed of 8 krpm - 11 krpm at the rate of the low rotation speed, and perform high - speed shear emulsification for a certain period of time to obtain a second mixture.

[0024] Furthermore, the certain period of time is 5 - 15 min.

[0025] Furthermore, the micronization of blonanserin is carried out using a jet mill, with the feeding air pressure being 0.5 - 0.6 Mpa and the crushing air pressure being 0.2 Mpa.

[0026] Compared with the prior art, the blonanserin orally disintegrating tablet composition provided by the present invention and its preparation method have the following beneficial effects:

[0027] (1) For the blonanserin orally disintegrating tablet composition provided by the present invention, compared with the prior art, in the technical solution of the present invention, a solubilizer is first mixed with micronized blonanserin. The solubilizer and micronized blonanserin act together to increase the dissolution rate and dissolution degree of micronized blonanserin. With the synergistic effect of other components, finally, the core hardness of the blonanserin orally disintegrating tablet composition of the present invention is 40 - 60 N, the friability is qualified, the disintegration time limit is completely disintegrated within 1 min, the dissolution rate is fast, the taste has no gritty feeling, and the smell is sweet.

[0028] (2) For the blonanserin orally disintegrating tablet composition provided by the present invention, further, the disintegrant preferably comprises a composition of low-substituted hydroxypropyl cellulose and crospovidone. By selecting the composition and specific ratio of the two disintegrants, the prepared blonanserin orally disintegrating tablet can meet the requirements of the disintegration time limit. After testing, the blonanserin orally disintegrating tablet composition of the present invention has a disintegration time limit of being completely disintegrated within 1 min, a fast dissolution rate, and a taste without a gritty feeling. It avoids the problems that when using a single disintegrant, if the amount of the disintegrant added is large, it will affect the taste of the blonanserin orally disintegrating tablet composition during oral administration, and if the amount of the disintegrant added is small, the requirements of the disintegration time limit cannot be met.

[0029] (3) For the blonanserin orally disintegrating tablet composition provided by the present invention, further, by selecting one or two of silica with a specific surface area of 500 - 1000 m 2 / g and colloidal silica with a specific surface area of 300 - 500 m 2 / g as the glidant, it has the effect of improving the flowability, and further improves the fluidity of the granules. The increase in the fluidity of the granules facilitates the tabletting of the composition material.

[0030] (4) For the blonanserin orally disintegrating tablet composition provided by the present invention, further, by selecting micronized blonanserin with a particle size less than 10 microns, and a specific surface area of 20 - 600 m 2Silica solubilizer at [X] g, the micronized blonanserin with a specific particle size interacts with the solubilizer with a specific specific surface area. Through certain technical means, the two reach an emulsified state. At this time, when the emulsified product in the emulsified state is mixed with other excipients, on the one hand, the emulsified product is more convenient to be mixed more uniformly with other excipients, thus ensuring the content uniformity of the drug. On the other hand, blonanserin micron powder, as a hydrophobic API, acts together with the hydrophilic excipient silica, and then is mixed with other excipients and compressed into tablets, which can greatly improve the dissolution rate and dissolution degree of the hydrophobic API in the blonanserin orally disintegrating tablets.

[0031] (5) The preparation method of the blonanserin orally disintegrating tablet composition provided by the present invention can improve the mixing uniformity of blonanserin micron powder and solubilizer by mixing the micronized blonanserin as the API with the solubilizer and then performing high-shear emulsification and dispersion with water, so that the blonanserin micron powder is fully coated by the solubilizer. The emulsified product obtained by high-shear emulsification with water is added to the first mixture of excipients by wet method. Compared with the addition of micron powder in the prior art, the wet addition can greatly improve the content uniformity of the drug. In addition, the combined action of blonanserin micron powder and solubilizer can improve the dissolution rate and dissolution degree of blonanserin drug. The disintegration time limit of the tablets obtained according to the present invention is within 1 min, with a sweet smell and no gritty feeling, and the dissolution degree of blonanserin drug in pH 6.0 medium can reach 80% in 30 min.

[0032] (6) The preparation method of the blonanserin orally disintegrating tablet composition provided by the present invention micronizes the API to a particle size below 10 μm, mixes the blonanserin micron powder with a solubilizer having a specific surface area of 20 - 600 m 2 / g, and adds it to 30 - 55 parts of water at a low rotation speed of 2 krpm - 5 krpm. First, add it at a low rotation speed to ensure that the blonanserin micron powder and the solubilizer can be fully wetted by water, and then slowly adjust the rotation speed from the low rotation speed rate to a high rotation speed of 8 krpm - 11 krpm. During the process of slowly adjusting the rotation speed, the blonanserin micron powder and the solubilizer can be further uniformly mixed, and the solubilizer is further coated on the surface of the blonanserin micron powder. Then, at a high rotation speed, it is high-shear emulsified for 5 - 15 min, and at this time, an emulsion can be obtained. After the emulsion is added as a wetting agent, on the one hand, it can ensure that the taste of the present invention has no gritty feeling and good taste, and on the other hand, it can greatly improve the dissolution rate of the API. Detailed implementation mode

[0033] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention clearer, the present invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0034] Example 1

[0035] An embodiment of the present invention provides a buclizine hydrochloride orally disintegrating tablet composition, which comprises the following components in parts by weight: 4 parts of buclizine hydrochloride fine powder with a particle size less than 10 microns, 60 parts of lactose, 11 parts of low-substituted hydroxypropyl cellulose and cross-linked povidone, wherein the mass ratio of the added amounts of low-substituted hydroxypropyl cellulose and cross-linked povidone in the disintegrant is 1:10, 0.5 part of povidone K30, 1 part of silica flow aid with a specific surface area of 500 m 2 / g, 1 part of aspartame, 0.5 part of magnesium stearate, and 0.5 part of silica solubilizer with a specific surface area of 20 m 2 / g.

[0036] In this embodiment, the preparation method of the buclizine hydrochloride orally disintegrating tablet composition comprises the following steps:

[0037] Step S1: Weigh according to the formula ratio, and uniformly mix the lactose diluent, cross-linked povidone and low-substituted hydroxypropyl cellulose disintegrant, povidone K30 binder, silica flow aid with a specific surface area of 500 m 2 / g, and aspartame sweetener to obtain a first mixture;

[0038] Step S2: Weigh according to the formula ratio, mix the buclizine hydrochloride fine powder with silica solubilizer with a specific surface area of 20 m 2 / g, add it to 40 parts of water at a rotation speed of 2 krpm, slowly adjust the rotation speed to 8 krpm at a rate of 2 krpm, and perform high-speed shear emulsification for 15 min to obtain a second mixture; wherein, in this embodiment, the buclizine hydrochloride is micronized by a jet mill, with a feed air pressure of 0.5 Mpa and a pulverizing air pressure of 0.2 Mpa, to obtain buclizine hydrochloride fine powder with a particle size less than 10 microns;

[0039] Step S3: Add the wet granulation of the second mixture to the first mixture, dry it, add the formulated amount of magnesium stearate lubricant, mix and table it to obtain the buclizine hydrochloride orally disintegrating tablet composition.

[0040] After testing, the average hardness of the buclizine hydrochloride orally disintegrating tablet composition in Example 1 is 4.94 kg, and the disintegration time limit is 33 s.

[0041] Example 2

[0042] An embodiment of the present invention provides a buclizine hydrochloride orally disintegrating tablet composition, which comprises the following components in parts by weight: 4 parts of buclizine hydrochloride fine powder with a particle size less than 10 microns, 60 parts of mannitol, 20 parts of low-substituted hydroxypropyl cellulose and cross-linked povidone, wherein the mass ratio of the added amounts of low-substituted hydroxypropyl cellulose and cross-linked povidone in the disintegrant is 4:1, 0.7 part of hydroxypropyl cellulose, 1 part of silica flow aid with a specific surface area of 700 m 21.4 parts of silica flow aid per g, 2.1 parts of acesulfame potassium, 1 part of magnesium stearate, with a specific surface area of 600 m 2 0.7 parts of silica solubilizer per g.

[0043] In this example, the preparation method of the blonanserin orally disintegrating tablet composition includes the following steps:

[0044] Step S1: Weigh according to the formula ratio, mix the mannitol diluent, cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose disintegrants, hydroxypropyl cellulose binder, silica flow aid with a specific surface area of 700 m 2 / g evenly to obtain the first mixture;

[0045] Step S2: Weigh according to the formula ratio, mix the blonanserin fine powder with silica solubilizer with a specific surface area of 600 m 2 / g, add it to 40 parts of water at a rotation speed of 3 krpm, slowly adjust the rotation speed to 9 krpm at a rate of 3 krpm, and perform high-speed shear emulsification for 10 min to obtain the second mixture; among them, in this example, the blonanserin micronization is carried out by using a jet mill, with a feeding air pressure of 0.5 Mpa and a crushing air pressure of 0.2 Mpa, to obtain blonanserin fine powder with a particle size less than 10 microns;

[0046] Step S3: Add the wet granulation of the second mixture to the first mixture, after drying, add the formulated amount of magnesium stearate lubricant, mix and tableting to obtain the blonanserin orally disintegrating tablet composition.

[0047] After testing, the average hardness of the blonanserin orally disintegrating tablet composition in Example 2 is 4.99 kg, and the disintegration time limit is 40 s.

[0048] Example 3

[0049] The embodiment of the present invention provides a blonanserin orally disintegrating tablet composition, which includes the following components by weight: 4 parts of blonanserin fine powder with a particle size less than 10 microns, 70 parts of pregelatinized starch, 17 parts of low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone, among which the mass ratio of the addition amount of low-substituted hydroxypropyl cellulose and cross-linked polyvinylpyrrolidone in the disintegrant is 10:7, 0.8 parts of hydroxypropyl methylcellulose, silica flow aid with a specific surface area of 800 m 2 1.7 parts per g, 3 parts of saccharin sodium, 3 parts of magnesium stearate, silica solubilizer with a specific surface area of 500 m 2 1.0 parts per g.

[0050] In this example, the preparation method of the blonanserin orally disintegrating tablet composition includes the following steps:

[0051] Step S1: Weigh the ingredients according to the formulation ratio. Mix the pregelatinized starch diluent, crospovidone and low-substituted hydroxypropyl cellulose disintegrants, hypromellose binder, silicon dioxide glidant with a specific surface area of 800 m 2 / g, and saccharin sodium sweetener evenly to obtain the first mixture;

[0052] Step S2: Weigh the ingredients according to the formulation ratio. Mix the blonanserin micropowder with silicon dioxide solubilizer with a specific surface area of 500 m 2 / g. Add it to 55 parts of water at a rotational speed of 4 krpm, and slowly adjust the rotational speed to 10 krpm at a rate of 4 krpm, and perform high-speed shear emulsification for 7 min to obtain the second mixture. Among them, in this embodiment, the blonanserin micropowder is pulverized using a jet mill, with a feed air pressure of 0.6 Mpa and a pulverizing air pressure of 0.2 Mpa to obtain blonanserin micropowder with a particle size less than 10 microns;

[0053] Step S3: Add the wet granulation of the second mixture to the first mixture. After drying, add magnesium stearate lubricant, mix and tableting to obtain the blonanserin orally disintegrating tablet composition.

[0054] After testing, the average hardness of the blonanserin orally disintegrating tablet composition in this Example 3 is 5.11 kg, and the disintegration time limit is 30 s.

[0055] Example 4

[0056] The embodiment of the present invention provides a blonanserin orally disintegrating tablet composition, which includes the following components in parts by weight: 4 parts of blonanserin micropowder with a particle size less than 10 microns, 80 parts of microcrystalline cellulose, 24 parts of crospovidone and sodium carboxymethyl starch with a mass ratio of added amount of 2:1, 1.2 parts of polyvinylpyrrolidone K30, 2.0 parts of silicon dioxide glidant with a specific surface area of 1000 m 2 / g, 2 parts of sucralose, 4 parts of talc powder, and 1.2 parts of silicon dioxide solubilizer with a specific surface area of 400 m 2 / g.

[0057] In this embodiment, the preparation method of the blonanserin orally disintegrating tablet composition includes the following steps:

[0058] Step S1: Weigh the ingredients according to the formulation ratio. Mix the microcrystalline cellulose diluent, crospovidone and sodium carboxymethyl starch disintegrants, polyvinylpyrrolidone K30 binder, silicon dioxide glidant with a specific surface area of 1000 m 2 / g, and sucralose sweetener evenly to obtain the first mixture;

[0059] Step S2: Weigh the ingredients according to the formulation ratio. Mix the blonanserin micropowder with silicon dioxide solubilizer with a specific surface area of 400 m 2Mix with 1.5 parts of silica solubilizer per gram, add to 30 parts of water at a rotational speed of 5 krpm, slowly adjust the rotational speed to 11 krpm at a rate of 5 krpm, and carry out high-speed shear emulsification for 5 minutes to obtain a second mixture; wherein, in this example, the micronization of blonanserin is carried out using a jet mill, with a feed air pressure of 0.5 Mpa and a pulverizing air pressure of 0.2 Mpa, to obtain blonanserin micropowder with a particle size less than 10 microns;

[0060] Step S3: Add the wet granulated second mixture to the first mixture, after drying, add the formulated amount of talc lubricant, mix and tabletten to obtain the blonanserin orally disintegrating tablet composition.

[0061] After testing, the average hardness of the blonanserin orally disintegrating tablet composition in Example 4 is 4.60 g, and the disintegration time limit is 50 s.

[0062] Example 5

[0063] An embodiment of the present invention provides a blonanserin orally disintegrating tablet composition, which includes the following components by weight: 4 parts of blonanserin micropowder with a particle size less than 10 microns, 90 parts of corn starch, 10 parts of cross-linked polyvinylpyrrolidone, 1.5 parts of polyvinylpyrrolidone K30 and hydroxypropyl cellulose with a mass ratio of 1:1 in the added amount, and a specific surface area of 300 m 2 2.6 parts of silica micropowder glidant per gram, 3.3 parts of aspartame and acesulfame K with a mass ratio of 1:1 in the added amount, 5 parts of stearic acid, and a specific surface area of 300 m 2 1.5 parts of silica solubilizer per gram.

[0064] In this example, the preparation method of the blonanserin orally disintegrating tablet composition includes the following steps:

[0065] Step S1: Weigh according to the formula ratio, and uniformly mix corn starch, cross-linked polyvinylpyrrolidone disintegrant, polyvinylpyrrolidone K30 and hydroxypropyl cellulose binder, silica micropowder glidant with a specific surface area of 300 m 2 per gram, aspartame and acesulfame K sweeteners to obtain a first mixture;

[0066] Step S2: Weigh according to the formula ratio, mix blonanserin micropowder with silica solubilizer with a specific surface area of 300 m 2 per gram, add to 40 parts of water at a rotational speed of 3 krpm, slowly adjust the rotational speed to 10 krpm at a rate of 3 krpm, and carry out high-speed shear emulsification for 10 minutes to obtain a second mixture; wherein, in this example, the micronization of blonanserin is carried out using a jet mill, with a feed air pressure of 0.5 Mpa and a pulverizing air pressure of 0.2 Mpa, to obtain blonanserin micropowder with a particle size less than 10 microns;

[0067] Step S3: Add the wet granulated second mixture to the first mixture. After drying, add the formulated amount of stearic acid lubricant, mix and table, to obtain the buclizine hydrochloride orally disintegrating tablet composition.

[0068] After testing, the average hardness of the buclizine hydrochloride orally disintegrating tablet composition in this Example 5 is 4.52 kg, and the disintegration time limit is 50 s.

[0069] Example 6

[0070] An embodiment of the present invention provides a buclizine hydrochloride orally disintegrating tablet composition, which, by weight, comprises the following components: 4 parts of buclizine hydrochloride fine powder with a particle size less than 10 microns, 100 parts of lactose, 30 parts of low-substituted hydroxypropyl cellulose, 2 parts of hydroxypropyl cellulose, 3 parts of microcrystalline silica flow aid with a specific surface area of 500 m 2 / g, 5 parts of acesulfame potassium, 4 parts of talc powder, and 0.8 parts of silica solubilizer with a specific surface area of 200 m 2 / g.

[0071] In this embodiment, the preparation method of the buclizine hydrochloride orally disintegrating tablet composition comprises the following steps:

[0072] Step S1: According to the above formula ratio, mix lactose, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, microcrystalline silica flow aid with a specific surface area of 500 m 2 / g, and acesulfame potassium evenly to obtain the first mixture;

[0073] Step S2: According to the above formula ratio, add the buclizine hydrochloride fine powder and the silica solubilizer with a specific surface area of 200 m 2 / g to 40 parts of water at a rotation speed of 3 krpm, and slowly adjust the rotation speed to 10 krpm at a rate of 3 krpm, and perform high-speed shear emulsification for 10 min to obtain the second mixture; wherein, in this embodiment, the buclizine hydrochloride is micronized using a jet mill, with a feed air pressure of 0.6 Mpa and a crushing air pressure of 0.2 Mpa, to obtain buclizine hydrochloride fine powder with a particle size less than 10 microns;

[0074] Step S3: Add the wet granulated second mixture to the first mixture. After drying, add the formulated amount of talc powder, mix and table, to obtain the buclizine hydrochloride orally disintegrating tablet composition.

[0075] After testing, the average hardness of the buclizine hydrochloride orally disintegrating tablet composition in this Example 6 is 4.68 kg, and the disintegration time limit is 57 s.

[0076] Comparative Example 1

[0077] Compared with Example 3, only the solubilizer in Example 3 is removed, and other components remain unchanged.

[0078] The preparation method of the orally disintegrating tablet composition of blonanserin in Comparative Example 1 was the same as that in Example 3.

[0079] After testing, the average hardness of the orally disintegrating tablet composition of blonanserin in Comparative Example 1 was 5.02 kg, and the disintegration time limit was 52 s.

[0080] Comparative Example 2

[0081] Comparative Example 2 was different from Example 3 only in the preparation method. In Comparative Example 2, the differences in the preparation method of the orally disintegrating tablet composition of blonanserin compared with Example 3 were as follows:

[0082] Step S2: According to the above formula ratio, micronized blonanserin and silica solubilizer with a specific surface area of 500 m 2 / g were stirred evenly with 40 parts of water at a rotation speed of 800 rpm to obtain a second mixture;

[0083] Step S3: The second mixture was wet granulated and added to the first mixture. After drying, the formulated amount of talc powder was added, and then mixed and tabletted to obtain the orally disintegrating tablet composition of blonanserin.

[0084] After testing, the average hardness of the orally disintegrating tablet composition of blonanserin in Comparative Example 2 was 4.71 kg, and the disintegration time limit was 1 min 10 s.

[0085] Comparative Example 3

[0086] Comparative Example 3 was different from Example 3 only in the preparation method. In Comparative Example 3, the differences in the preparation method of the orally disintegrating tablet composition of blonanserin compared with Example 3 were as follows:

[0087] Step S2: According to the above formula ratio, micronized blonanserin and silica solubilizer with a specific surface area of 500 m 2 / g were mixed evenly to obtain a second mixture;

[0088] Step S3: The second mixture was directly added to the first mixture, and then magnesium stearate lubricant was added. After passing through an 80-mesh sieve and mixing evenly, it was placed in a fluidized bed. The fluidized bed granulation parameters were set as follows: inlet air temperature 40 - 60 °C, inlet air volume: 5 - 30 m3 / h, material temperature: 20 - 40 °C, atomization pressure: 0.2 - 2 kg / cm 2 , and the moisture content of drying was controlled at 2 - 5%, and then mixed and tabletted to obtain the orally disintegrating tablet composition of blonanserin.

[0089] After testing, the average hardness of the orally disintegrating tablet composition of blonanserin in Comparative Example 3 was 4.64 kg, and the disintegration time limit was 30 s.

[0090] Comparative Example 4

[0091] Comparative Example 4 is different from Example 3 only in the particle size of blonanserin micropowder. In Comparative Example 4, blonanserin micropowder with a particle size of 20 microns is used, and other components remain unchanged.

[0092] The preparation method of the blonanserin orally disintegrating tablet composition in Comparative Example 4 is the same as that in Example 3.

[0093] After testing, the hardness of the blonanserin orally disintegrating tablet composition in Comparative Example 4 is 4.58 kg, and the disintegration time limit is 52 s.

[0094] Furthermore, the present invention further conducts the following performance tests on the blonanserin orally disintegrating tablets prepared in Examples 1 to 6 and Comparative Examples 1 to 4.

[0095]

[0096]

[0097] From the above test results, it can be seen that: (1) The disintegration time limit is optimal when the composition is low-substituted hydroxypropyl cellulose and cross-linked povidone; (2) The dissolution of the active pharmaceutical ingredient decreases and is relatively slow when the solubilizer is not added; (3) When the active pharmaceutical ingredient is dispersed in the silicon dioxide aqueous suspension by ordinary stirring, the dissolution is low and the active pharmaceutical ingredient fails to dissolve; (4) The wet granulation process is superior to the fluidized bed granulation process; (5) When the particle size of the active pharmaceutical ingredient is too large, the dissolution is slow and the dissolution end point cannot be reached.

[0098] The above is only the specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention can easily think of changes or substitutions, which should all be covered by the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims

1. A blonanserin orally disintegrating tablet composition, characterized in that, Comprising the following components by weight parts: 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, 0.5 - 1.5 parts of solubilizer; The blonanserin fine powder is blonanserin fine powder with a particle size less than 10 microns, and the solubilizer is silica with a specific surface area of 20 to 600 m 2 / g; In the process of preparing the blonanserin orally disintegrating tablet composition, the blonanserin micropowder and the solubilizer are mixed and then emulsified by high-speed shearing with water; wherein, The disintegrant is a composition of low-substituted hydroxypropyl cellulose and crospovidone, and by weight parts of the disintegrant, the mass ratio of the addition amounts of low-substituted hydroxypropyl cellulose and crospovidone is (20 - 1):(10 - 5); The glidant is selected from one or two of silica with a specific surface area of 500 to 1000 m 2 / g and silica gel fine powder with a specific surface area of 300 to 500 m 2 / g; The diluent is selected from one or a combination of lactose, mannitol, pregelatinized starch, corn starch, microcrystalline cellulose; The binder is selected from one or a combination of povidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose; The sweetener is selected from one or a combination of aspartame, acesulfame potassium, sodium saccharin, sucralose; The lubricant is selected from one or a combination of magnesium stearate, stearic acid, talc powder.

2. A method for preparing a blonanserin orally disintegrating tablet composition, characterized in that, Applied to the blonanserin orally disintegrating tablet composition according to claim 1, comprising the following steps: Weigh the ingredients according to the formula ratio, and uniformly mix the diluent, disintegrant, binder, glidant, and sweetener to obtain a first mixture; Emulsify the blonanserin micropowder and the solubilizer by high-speed shearing with water for a certain time to obtain a second mixture; Add the second mixture prepared by wet granulation to the first mixture, after drying, add the lubricant, mix and tableting to obtain the blonanserin orally disintegrating tablet composition.

3. The preparation method of the blonanserin orally disintegrating tablet composition according to claim 2, characterized in that, The step of emulsifying the blonanserin micropowder and the solubilizer by high-speed shearing with water for a certain time to obtain a second mixture includes the following steps: Micronize the blonanserin to below 10 microns to obtain the blonanserin micropowder; Mix the blonanserin with a solubilizer having a specific surface area of 500 to 1000 m 2 / g, add it to 30 to 55 parts of water at a low rotation speed of 2 krpm to 5 krpm, slowly adjust the rotation speed to a high rotation speed of 8 krpm to 11 krpm at the rate of the low rotation speed, and perform high-speed shear emulsification for a certain time to obtain a second mixture.

4. The preparation method of the blonanserin orally disintegrating tablet composition according to claim 3, characterized in that, The certain time is 5 - 15 min.

5. The preparation method of the blonanserin orally disintegrating tablet composition according to any one of claims 2 to 4, characterized in that, The micronization of blonanserin micropowder is carried out by a jet mill, with the feeding air pressure of 0.5 - 0.6 Mpa and the pulverizing air pressure of 0.2 Mpa.

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