Brexanolone tablet and preparation method thereof

Abstract

The application provides a brexpiprazole tablet and a preparation method thereof, and belongs to the technical field of medicines. First, brexpiprazole raw medicine and excipients are pretreated, then premixed, and then mixed with other components for total mixing, tabletting and coating. The components are mixed more uniformly, the type of the filler is controlled, the brexpiprazole tablet has low friability, the dissolution speed of the finished product is fast, and the disintegration time is short.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to an ibuprofen tablet and its preparation method. Background Technology

[0002] Brexpiprazole, 7-(4-(4-(benzo[b]thiophene)-4-yl-piperazin-1-yl)butoxy)-1H-quinoline-2-one, can be used to treat or as an adjunct therapy for schizophrenia, depression, and Alzheimer's disease. Its structural formula is shown in the figure below:

[0003]

[0004] Current methods for preparing biriperazole tablets primarily involve wet granulation, where raw materials are mixed in powder form, sprayed with a binder for granulation, and then compressed and coated. However, this method is highly dependent on the processing technology, resulting in complex manufacturing processes, long production cycles, low yields, and high energy consumption. Therefore, there is an urgent need for a simpler, lower-cost, higher-yield, and lower-energy-consumption method for preparing biriperazole tablets. Summary of the Invention

[0005] The purpose of this invention is to provide an ibuprofen tablet and its preparation method. The preparation method provided by this invention is simple, low-cost, and low-energy-consumption, and the prepared ibuprofen tablet has a high yield, uniform composition, low friability, and fast disintegration and dissolution rate.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides a method for preparing birepiperazole tablets, comprising the following steps:

[0008] (1) Mix the buripiperazole raw material with the excipient and pre-treat it by sieving or granulation machine to obtain the pre-treated material;

[0009] (2) The pretreated material obtained in step (1) is premixed to obtain a premixed material;

[0010] (3) The premix obtained in step (2) is mixed with filler, disintegrant and lubricant and then compressed into tablets to obtain bripiprazole tablets; the filler includes at least one of pregelatinized starch, direct-pressed starch and superfluid starch;

[0011] (4) Coating the buripiperazole tablets obtained in step (3) with a coating solution to obtain buripiperazole tablets.

[0012] Preferably, the particle size of the burepiperazole raw material in step (1) is 10-50 μm.

[0013] Preferably, the excipient in step (1) includes at least one of lactose, starch lactose, cellulose lactose and anhydrous calcium hydrogen phosphate.

[0014] Preferably, the mesh size of the screen used in the granulator pretreatment in step (1) is 0.5 to 2 mm.

[0015] Preferably, the disintegrant in step (3) includes at least one of sodium carboxymethyl starch, croscarmellose sodium, and low-substituted hydroxypropyl cellulose.

[0016] Preferably, the lubricant in step (3) includes at least one of magnesium stearate, sodium stearate fumarate, and talc.

[0017] Preferably, the total mixing rate in step (3) is 5-10 rpm and the total mixing time is 5-20 min.

[0018] Preferably, based on the total mass of the birepiperazole raw material, excipients, fillers, disintegrants, and lubricants in step (1) as 100%, the mass percentages of the birepiperazole raw material, excipients, fillers, disintegrants, and lubricants are 0.3-5%, 30-60%, 30-60%, 5-15%, and 0.5-2%, respectively.

[0019] Preferably, the coating solution in step (4) includes coating material and water; the solid content of the coating solution is 10-20%.

[0020] The present invention also provides birepiperazole tablets prepared by the preparation method described in the above technical solution.

[0021] This invention provides a method for preparing bripiprazole tablets, comprising the following steps: (1) mixing bripiprazole raw material with excipients, and pre-treating by sieving or granulation to obtain pre-treated material; (2) pre-mixing the pre-treated material obtained in step (1) to obtain premix; (3) compressing the premix obtained in step (2) with filler, disintegrant and lubricant to obtain bripiprazole tablets; wherein the filler includes at least one of pregelatinized starch, direct-pressed starch and superfluid starch; (4) coating the bripiprazole tablets obtained in step (3) with a coating solution to obtain bripiprazole tablets. This invention first pre-treats the bripiprazole raw material with excipients, then pre-mixes them, and then mixes them with other components for total mixing, tableting and coating. This results in more uniform mixing of the components, while controlling the type of filler, leading to lower brittleness of the bripiprazole tablets, faster dissolution rate, and shorter disintegration time. The results of the examples show that the buripiperazole tablets prepared by the preparation method provided by the present invention have uniform composition, a friability of 0.1% in the raw tablets, and the finished product meets the dissolution requirements and has a short disintegration time. Detailed Implementation

[0022] This invention provides a method for preparing birepiperazole tablets, comprising the following steps:

[0023] (1) Mix the buripiperazole raw material with the excipient and pre-treat it by sieving or granulation machine to obtain the pre-treated material;

[0024] (2) The pretreated material obtained in step (1) is premixed to obtain a premixed material;

[0025] (3) The premix obtained in step (2) is mixed with filler, disintegrant and lubricant and then compressed into tablets to obtain bripiprazole tablets; the filler includes at least one of pregelatinized starch, direct-pressed starch and superfluid starch;

[0026] (4) Coating the buripiperazole tablets obtained in step (3) with a coating solution to obtain buripiperazole tablets.

[0027] Unless otherwise specified, the present invention does not impose any special restrictions on the source of the raw materials, and commercially available products well known to those skilled in the art can be used.

[0028] This invention involves mixing buripiperazole raw material with excipients and pre-treating it through a sieve or granulator to obtain pre-treated material.

[0029] In this invention, the particle size of the buripiperazole raw material is preferably 10-50 μm, more preferably 20-50 μm, and even more preferably 20-40 μm.

[0030] In this invention, the mass percentage of the birepiperazole active pharmaceutical ingredient (API), excipients, fillers, disintegrants, and lubricants is preferably 0.3% to 5%, based on the total mass of 100%. In embodiments of this invention, the mass percentage of the birepiperazole API may specifically be 0.3%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or 5%.

[0031] In this invention, the excipient preferably includes at least one selected from lactose, starch lactose, cellulose lactose, and anhydrous calcium hydrogen phosphate, more preferably lactose. This invention does not impose any particular limitation on the source of the excipient; commercially available products well-known to those skilled in the art can be used. In an embodiment of this invention, the lactose is from Jiangsu Daoning Pharmaceutical Co., Ltd.; the lactose has a mesh size of 80 mesh.

[0032] In this invention, based on the total mass of the birepiperazole raw material, excipients, fillers, disintegrants, and lubricants as 100%, the mass percentage content of the excipients is preferably 30% to 60%. In embodiments of this invention, the mass percentage content of the excipients may specifically be 30%, 35%, 40%, 45%, 50%, 55%, or 60%. By controlling the type and amount of excipients within the above range, this invention can further improve the compressibility and disintegration properties of birepiperazole tablets.

[0033] In this invention, the aperture of the sieve during sieving is preferably 0.5 to 2 mm.

[0034] In this invention, the aperture of the sieve used in the granulator pretreatment is preferably 0.5–2 mm, that is, the aperture of the sieve in the granulator is preferably 0.5–2 mm; the rotation speed of the granulator is preferably 100–300 rpm, more preferably 150–250 rpm. This invention pretreatment of the birepiperazole raw material and excipients can improve the mixing uniformity of the components.

[0035] After obtaining the pretreated material, the present invention premixes the pretreated material to obtain a premixed material.

[0036] In this invention, the premixing rate is preferably 5-10 rpm, more preferably 6-9 rpm, and even more preferably 7-8 rpm; the premixing time is preferably 5-15 min, more preferably 10 min. By performing premixing and controlling the premixing rate and time, this invention can further improve the mixing uniformity of the components.

[0037] In this invention, the premixing is preferably carried out in a master mixer. This invention does not specify a particular model of master mixer; any commercially available product well-known to those skilled in the art can be used.

[0038] After obtaining the premix, the present invention mixes the premix with fillers, disintegrants and lubricants and then compresses it into tablets to obtain bripiprazole tablets.

[0039] In this invention, the filler includes at least one of pregelatinized starch, direct-pressed starch, and superfluid starch, preferably superfluid starch. This invention does not have a specific limitation on the source of the filler; commercially available products well-known to those skilled in the art can be used. In an embodiment of this invention, the superfluid starch is derived from Calcon.

[0040] In this invention, based on the total mass of the birepiperazole raw material, excipients, fillers, disintegrants, and lubricants as 100%, the mass percentage of the filler is preferably 30-60%. In embodiments of this invention, the mass percentage of the filler may specifically be 30%, 35%, 40%, 45%, 50%, 55%, or 60%. By controlling the type and amount of filler within the above range, this invention can further improve the disintegration and other properties of birepiperazole tablets.

[0041] In this invention, the disintegrant preferably includes at least one selected from sodium carboxymethyl starch, croscarmellose sodium, and low-substituted hydroxypropyl cellulose, more preferably low-substituted hydroxypropyl cellulose. This invention does not impose any particular limitation on the source of the disintegrant; commercially available products well-known to those skilled in the art can be used. In an embodiment of this invention, the low-substituted hydroxypropyl cellulose is from Nippon Soda, model LH21.

[0042] In this invention, based on the total mass of the birepiperazole raw material, excipients, fillers, disintegrants, and lubricants as 100%, the mass percentage content of the disintegrant is preferably 5-15%. In embodiments of this invention, the mass percentage content of the disintegrant can specifically be 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15%. By controlling the type and amount of disintegrant within the above range, this invention can further improve the disintegration and other properties of birepiperazole tablets.

[0043] In this invention, the lubricant preferably comprises at least one of magnesium stearate, sodium stearate fumarate, and talc, more preferably sodium stearate fumarate or magnesium stearate. This invention does not impose any particular limitation on the source of the lubricant; commercially available products well-known to those skilled in the art can be used. In an embodiment of this invention, the sodium stearate fumarate is sourced from JRS, Germany.

[0044] In this invention, based on the total mass of the birepiperazole raw material, excipients, fillers, disintegrants, and lubricants as 100%, the mass percentage content of the lubricant is preferably 0.5% to 2%. In embodiments of this invention, the mass percentage content of the lubricant may specifically be 0.5%, 0.8%, 1%, 1.5%, or 2%. By controlling the type and amount of lubricant within the above range, this invention can further improve the flowability of each component and enhance the appearance quality of the birepiperazole tablets.

[0045] In this invention, the mixing rate is preferably 5-10 rpm, more preferably 6-9 rpm, and even more preferably 7-8 rpm; the mixing time is preferably 5-20 min, more preferably 10-20 min. By controlling the mixing rate and time, this invention can further improve the mixing uniformity of each component.

[0046] In this invention, the mixing is preferably carried out in a mixer. This invention does not specify a particular model of mixer; any commercially available product well-known to those skilled in the art can be used.

[0047] In this invention, the main pressure of the tablet compression is preferably 3 to 10 kN. In embodiments of this invention, the main pressure of the tablet compression can specifically be 3 kN, 4 kN, 5 kN, 6 kN, 7 kN, 8 kN, 9 kN, or 10 kN. In this invention, the main pressure is the value of the main pressure of the tablet press (Beijing Chuangbojiawei Technology Co., Ltd.) when pressing birepiperazole tablets of the corresponding hardness (approximately 50 N).

[0048] In this invention, the rotational speed of the tableting feed press is preferably 20-50 rpm. In embodiments of this invention, the rotational speed of the tableting feed press can specifically be 20 rpm, 30 rpm, 40 rpm, or 50 rpm.

[0049] In this invention, the tableting speed is preferably 50,000 to 300,000 tablets / h. In embodiments of this invention, the tableting speed may specifically be 50,000 tablets / h, 100,000 tablets / h, 150,000 tablets / h, 200,000 tablets / h, 250,000 tablets / h, or 300,000 tablets / h.

[0050] In this invention, the hardness of the birepiperazole tablets is preferably 20-70 N. In embodiments of this invention, the hardness of the birepiperazole tablets can specifically be 20 N, 30 N, 40 N, 50 N, 60 N, or 70 N. By controlling the parameters during tableting within the above range, this invention enables the birepiperazole tablets to have better hardness and surface quality, further improving their disintegration and dissolution properties.

[0051] After obtaining birepiperazole tablets, the present invention uses a coating solution to coat the birepiperazole tablets to obtain birepiperazole tablets.

[0052] In this invention, the coating liquid preferably comprises a coating material and water.

[0053] In this invention, the coating material preferably includes hydroxypropyl methylcellulose, yellow iron oxide, black iron oxide, and talc. This invention does not have a specific limitation on the source of the coating material; commercially available products well-known to those skilled in the art can be used. In an embodiment of this invention, the coating material is Calcare / 03A610007-CN, which is green.

[0054] In this invention, the water is preferably purified water.

[0055] In this invention, the solid content of the coating solution is preferably 10-20%. In embodiments of this invention, the solid content of the coating solution may specifically be 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%.

[0056] In this invention, the coating solution is preferably prepared fresh for use. This invention does not impose any particular limitation on the preparation method of the coating solution; any method that can uniformly mix the coating material and water is acceptable. Preferably, the preparation method of the coating solution involves adding the coating material to water and mixing under stirring conditions to obtain the coating solution. This invention does not impose any particular limitation on the stirring method and rate; any stirring method and rate well known to those skilled in the art can be used. In this invention, the mixing time is preferably 45–60 minutes.

[0057] In this invention, the preferred mass of the coating material in the coating solution is 2-4% of the mass of the birepiperazole tablets. In embodiments of this invention, the mass of the coating material in the coating solution may specifically be 2%, 3%, or 4% of the mass of the birepiperazole tablets. By controlling the amount of coating material in the coating solution within the above range, this invention achieves a better coating effect.

[0058] In this invention, the coating is preferably performed in a high-efficiency coating machine. Preferably, the ibuprofen tablets are placed in a porous coating pan of the high-efficiency coating machine, and then the coating solution is sprayed on. After the coating solution is sprayed, the tablets are dried in the high-efficiency coating pan to obtain ibuprofen tablets. This invention does not have a specific limitation on the model of the high-efficiency coating machine; any commercially available product well-known to those skilled in the art can be used.

[0059] In this invention, the drying temperature is preferably 40-60°C, more preferably 50°C; the drying time is preferably 5-15 min, more preferably 10 min.

[0060] In this invention, the preferred weight of a single ibuprofen tablet is 80-100 mg.

[0061] This invention uses a direct powder compression method to prepare birepiperazole tablets. The preparation process does not require granulation and drying, making the process simple, low-cost, and yielding a high product. Direct powder compression ensures the particle size and compressibility of the material, guaranteeing rapid tablet disintegration and drug dissolution, and the drug is not affected by damp heat. By controlling the types and amounts of each component, the product exhibits rapid disintegration and dissolution rates and good stability, making it suitable for industrial production.

[0062] This invention also provides birepiperazole tablets prepared by the method described in the above technical solution. The birepiperazole tablets prepared by this invention exhibit rapid disintegration and dissolution rates and good stability.

[0063] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0064] Example 1

[0065] A method for preparing biriperazole tablets is as follows: (1) Mix 145.5g lactose (Jiangsu Daoning Pharmaceutical Co., Ltd., 80 mesh) and 10g biriperazole raw material (20-40μm), pre-treat through a 1.0mm sieve, then pre-mix at 8rpm for 10min in a mixer, then add 245g superfluid starch (Calcon), 45g low-substituted hydroxypropyl cellulose (Japan Soda, LH21) and 4.5g sodium stearate fumarate (Germany JRS), mix at 8rpm for 10min, and then compress into tablets to obtain... The tablets are packaged in batches of 5000 tablets. The main compression pressure is 7.2 kN, the speed of the tableting feeder is 20 rpm, the compression speed is 50,000 tablets / h, and the hardness of the tablets is 55 N. Based on the total mass of lactose, birepiperazole raw material, superfluid starch, low-substituted hydroxypropyl cellulose, and sodium stearate as 100%, the mass percentages of lactose, birepiperazole raw material, superfluid starch, low-substituted hydroxypropyl cellulose, and sodium stearate are 32.33%, 2.22%, 54.45%, 10%, and 1%, respectively.

[0066] (2) Under stirring conditions, the coating material (Calcon / 03A610007-CN, green) was added to purified water and mixed for 45 min to obtain a coating solution with a solid content of 10%. The biriperazole tablets were placed in the porous coating pan of a high-efficiency coating machine, and then 135 g of coating solution (including 13.5 g of coating material) was sprayed. After the coating solution was sprayed, it was dried in the high-efficiency coating pan at 50 °C for 10 min to obtain biriperazole tablets. The mass of the coating material in the coating solution was 3% of the mass of the biriperazole tablets.

[0067] Example 2

[0068] In step (1) of Example 1, the mass percentages of lactose, birepiperazole raw material, superfluid starch, low-substituted hydroxypropyl cellulose, and sodium stearate fumarate were replaced with 54.45%, 2.22%, 32.33%, 10%, and 1%, respectively. The main pressure during tableting was replaced with 6.3 kN. At this time, the hardness of the birepiperazole tablet was 53 N. All other parameters were the same as in Example 1.

[0069] Example 3

[0070] In Example 1, sodium stearate in step (1) was replaced with magnesium stearate, and the main pressure during tableting was replaced with 7.1 kN. At this time, the hardness of the bripiprazole tablet was 51 N, and other parameters were the same as in Example 1.

[0071] Example 4

[0072] The sieving pretreatment in step (1) of Example 1 is replaced with granulator pretreatment. The rotation speed of the granulator is 200 rpm, the screen aperture of the granulator is 1 mm, and the main pressure during tableting is replaced with 6.5 kN. At this time, the hardness of the biriperazole tablet is 51 N. All other parameters are the same as in Example 1.

[0073] Example 5

[0074] Replace the total mixing time in step (1) of Example 1 with 15 min, and keep all other parameters the same as in Example 1.

[0075] Example 6

[0076] Replace the total mixing time in step (1) of Example 1 with 20 min, and keep all other parameters the same as in Example 1.

[0077] Comparative Example 1

[0078] In Example 1, step (1) is modified by replacing lactose with mannitol, replacing superfluid starch with corn starch, and changing the main pressure during tableting to 8.5 kN. At this time, the hardness of the bripiprazole tablet is 45 N. All other parameters are the same as in Example 1.

[0079] Comparative Example 2

[0080] The superfluid starch in step (1) of Example 1 was replaced with microcrystalline cellulose, and the main pressure during tableting was replaced with 5.3 kN. At this time, the hardness of the bripiprazole tablet was 47 N, and other parameters were the same as in Example 1.

[0081] Comparative Example 3

[0082] The pretreatment and premixing in step (1) of Example 1 are omitted. The components are directly mixed in a mixer at a rate of 8 rpm for 10 min. The main pressure during tableting is replaced with 6.9 kN. At this time, the hardness of the birepiperazole tablet is 48 N. All other parameters are the same as in Example 1.

[0083] Comparative Example 4

[0084] Replace the particle size of the birepiperazole raw material in step (1) of Example 1 with D. 90 >50μm, the main pressure during tableting is replaced with 7.5kN, at which point the hardness of the bripiprazole tablet is 50N, and other parameters are the same as in Example 1.

[0085] Ten tablets of birepiperazole prepared in Examples 1-4 and Comparative Examples 1-4 were taken respectively, and their hardness (average value), friability, and disintegration time were measured. Hardness was measured using a hardness tester (Tianjin Tianda Tianfa Technology Co., Ltd.). The disintegration time was determined according to the 2020 edition of the Chinese Pharmacopoeia, Part IV, 0921. Friability was determined according to the 2020 edition of the Chinese Pharmacopoeia, Part IV, 0923. The results are shown in Table 1.

[0086] Table 1. Hardness, friability, and disintegration time of bripiprazole tablets prepared in Examples 1-4 and Comparative Examples 1-4.

[0087] Main pressure (kN) Hardness (N) Friability (%) Disintegration timeout (seconds) Example 1 7.2 55 0.1 65 Example 2 6.3 53 0.1 72 Example 3 7.1 51 0.1 59 Example 4 6.5 51 0.1 61 Comparative Example 1 8.5 45 0.3 57 Comparative Example 2 5.3 47 0.1 83 Comparative Example 3 6.9 48 0.1 67 Comparative Example 4 7.5 50 0.1 69

[0088] Table 1 shows that Comparative Example 1 had a higher weight loss due to brittleness, which is attributed to the poor abrasion resistance of corn starch. In Comparative Example 1, increasing the main pressure did not significantly improve tablet hardness, and cracking occurred during compression, indicating that its compressibility was inferior to Example 1. Compared to Example 1, Comparative Example 2 showed improved compressibility, but also the longest tablet disintegration time. Other examples and comparative examples demonstrate that the particle size of the active pharmaceutical ingredient, the ratio of lactose to superfluid starch, and the amounts of magnesium stearate and sodium stearate fumarate do not affect the compressibility or tablet disintegration of the total mixture.

[0089] The yields of the biriperazole tablets prepared in Examples 1-4 and Comparative Examples 1-4 were tested, and the results are shown in Table 2.

[0090] Table 2. Yields of the finished products prepared from biriperazole tablets in Examples 1-4 and Comparative Examples 1-4

[0091] Example 1 Example 2 Example 3 Example 4 yield 97％ 97％ 95％ 99％ Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 yield 98％ 97％ 96％ 97％

[0092] Samples were taken from 11 different locations in the hopper of the total mixing stage in Example 1, Example 4 and Comparative Example 3 (1) to obtain the particle content at different locations and examine the mixing uniformity of the material. The results are shown in Table 3.

[0093] Table 3. Mixing homogeneity of Examples 1, 4 and Comparative Example 3

[0094]

[0095] As shown in Table 3, Examples 1 and 4 exhibited good mixing effects, indicating that both sieving and granulation can be used for the pretreatment and dispersion of lactose and active pharmaceutical ingredients. The large differences in the sampling results at the 11 locations in Comparative Example 3 indicate that the mixture was not uniform, suggesting that the lack of pretreatment of lactose and active pharmaceutical ingredients significantly impacts the mixing effect. This is because the micronized active pharmaceutical ingredient exhibits static electricity, leading to agglomeration. Furthermore, these agglomerated clumps possess a certain strength, necessitating the use of sieving or granulation to break them up.

[0096] The dissolution rate of the biriperazole tablets prepared in Examples 1-4 and Comparative Examples 1, 2, and 4 was tested according to FDA-specified methods. 900 mL of sodium acetate aqueous solution at pH 4.3 was used as the medium, and a paddle method was employed at 50 rpm. Simultaneously, the original drug product was measured. The dissolution rate was measured, and the results are shown in Table 4.

[0097] Table 4. Ibuprofen tablets prepared in Examples 1-4 and Comparative Examples 1, 2, and 4, and the original product. dissolution

[0098]

[0099] As shown in Table 4, Examples 1 and 4 demonstrate that micronization makes the formulation more similar to the original. Examples 1, 2, and 3 all meet the dissolution requirements. Comparative Example 1 shows rapid dissolution. Comparative Example 2 shows rapid dissolution in the early stages but incomplete dissolution in the later stages, possibly due to adsorption or sedimentation of the microcrystalline cellulose.

[0100] The uniformity of total mixing in Examples 1 and 5-6 was examined. At different total mixing time points of 10 min, 15 min, and 20 min, samples were taken from 11 locations at the top, middle, and bottom of the total mixing hopper to measure the uniformity of mixing. The results are shown in Table 5.

[0101] Table 5. Mixing uniformity at different total mixing times in Examples 1, 5-6

[0102]

[0103]

[0104] As shown in Table 5, the sample content at all sampling points was within ±10% of the average content, and the RSD was less than 5.0%, indicating that the mixing uniformity was qualified. This suggests that a total mixing time of 10–20 minutes is sufficient to mix the materials uniformly.

[0105] The biriperazole tablets prepared in Example 1 and the original product were compared. Samples were taken and the content of relevant substances was determined after being placed at 60℃ for 10 days and 30 days.

[0106] Take ibuprofen tablets or the original brand product. 20 tablets were accurately weighed and ground into a fine powder using an agate mortar. An appropriate amount of the fine powder (equivalent to 10 mg of ibuprofen) was accurately weighed and placed in a 20 mL volumetric flask. An appropriate amount of methanol was added, and the mixture was sonicated for 20 min to dissolve the ibuprofen. The mixture was cooled, diluted to the mark with methanol, shaken well, filtered, and the filtrate was used as the test solution. The results are shown in Table 6.

[0107] Table 6. Biriperazole tablets prepared in Example 1 and the original product. Results of related substances at different numbers of days at 60℃

[0108]

[0109] As can be seen from Table 6, the impurity growth rate in Example 1 is higher than that in the original drug. The slow speed indicates that the birepiperazole tablets prepared using this method have high stability.

[0110] In summary, the buripiperazole tablets prepared by this invention meet the dissolution requirements and have high stability.

[0111] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing biriperazole tablets, comprising the following steps: (1) The buripiperazole raw material is mixed with an excipient and pretreated by a sieve or granulator to obtain a pretreated material; the particle size of the buripiperazole raw material is 10-50 μm; the excipient includes at least one of lactose, starch lactose, cellulose lactose and anhydrous calcium hydrogen phosphate. (2) The pretreated material obtained in step (1) is premixed to obtain a premixed material; (3) The premix obtained in step (2) is mixed with filler, disintegrant and lubricant and then compressed into tablets to obtain bripiprazole tablets; the filler is superfluid starch; the disintegrant includes at least one of sodium carboxymethyl starch, croscarmellose sodium and low-substituted hydroxypropyl cellulose; the lubricant includes at least one of magnesium stearate, sodium stearate fumarate and talc. (4) Coating the buripiperazole tablets obtained in step (3) with a coating solution to obtain buripiperazole tablets.

2. The preparation method according to claim 1, characterized in that, The mesh size of the screen used in the granulator pretreatment in step (1) is 0.5 to 2 mm.

3. The preparation method according to claim 1, characterized in that, In step (3), the total mixing rate is 5-10 rpm and the total mixing time is 5-20 min.

4. The preparation method according to claim 1, characterized in that, Based on the total mass of birepiperazole raw material, excipients, fillers, disintegrants and lubricants in step (1) as 100%, the mass percentages of birepiperazole raw material, excipients, fillers, disintegrants and lubricants are 0.3-5%, 30-60%, 30-60%, 5-15% and 0.5-2%, respectively.

5. The preparation method according to claim 1, characterized in that, The coating solution in step (4) includes coating material and water; the solid content of the coating solution is 10-20%.

6. The buriperazole tablets prepared by the preparation method according to any one of claims 1 to 5.

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