Pharmaceutical composition of benzbromarone or salt thereof and preparation method thereof

Abstract

The invention discloses a pharmaceutical composition of benzbromarone and a preparation method thereof, and by optimizing prescription components and a process of a benzbromarone pharmaceutical oral preparation, the provided pharmaceutical composition of benzbromarone or salts thereof is pure white in color, complete and bright in surface and good in dissolution performance. The preparation method of the pharmaceutical composition of the benzbromarone or the salt thereof is simple and convenient, an organic solution containing the benzbromarone or the salt thereof does not need to be prepared, the risk of organic solvent residue does not exist, the granulation process window is large, and industrial production is easy; the particles obtained by the process are uniform, compact and good in flowability; the tablets obtained by the process are pure white in color, complete and bright in surface, small in weight difference and good in dissolution performance.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a pharmaceutical composition of benzbromarone or its salt and a method for preparing the same. Background Technology

[0002] Gout is a recurrent inflammatory disease caused by increased purine biosynthesis and metabolism, excessive uric acid production, or poor uric acid excretion, leading to elevated blood urea levels and the precipitation of urate crystals in the synovial membrane, bursae, cartilage, and other tissues of the joints. In my country, with the improvement of people's living standards in recent years, the number of gout patients has been increasing, and the clinical demand for anti-gout drugs is also growing. Currently available anti-gout drugs include colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), probenecid, and allopurinol.

[0003] Benzbromarone is a potent benzofuran derivative that deuriccates uric acid. Its chemical name is (3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-3-benzofuranyl)methyl ketone, and its molecular structure is shown in Formula I.

[0004]

[0005] This compound not only inhibits the reabsorption of uric acid by the renal tubules and promotes uric acid excretion, but it is also a good purine oxidase inhibitor that can inhibit the production of uric acid. It has a dual function of reducing blood uric acid concentration and is used clinically to treat primary and secondary hyperuricemia, as well as gout caused by various reasons.

[0006] Chinese patent CN102429881B describes benzbromarone as a white or almost white crystalline powder, insoluble in water and slightly soluble in ethanol, resulting in poor dissolution when made into tablets. This patent controls the particle size of benzbromarone raw material to less than 5μm using airflow milling. Then, a portion of the surfactant ethanol solution is sprayed onto the benzbromarone raw material through a fluidized bed to reduce static electricity and ensure bridging between the surfactant and the raw material. Another portion of the surfactant is added during granulation, and the resulting granules are then compressed into tablets.

[0007] Chinese patent CN107823160B discloses a solid dispersion tablet containing allopurinol and benzbromarone. The solid dispersion is prepared by mixing and stirring benzbromarone, polyethylene glycol and ethanol, evaporating to remove the ethanol, and then mixing with silica.

[0008] Chinese patent application CN118717689A discloses a method for preparing benzbromarone tablets, including recrystallization of the active pharmaceutical ingredient acetone, preparation of soft material, mixing, granulation, tableting, and drying.

[0009] Currently, there are few reports on the development and research of benzbromarone tablets. It is still necessary to develop a pharmaceutical composition of benzbromarone or its salt and its preparation method, and to optimize the formulation and process, so as to facilitate the industrial production of the product and ensure the stability of product quality. Summary of the Invention

[0010] On one hand, the present invention provides a pharmaceutical composition of benzbromarone or its salt, characterized in that the pharmaceutical composition comprises benzbromarone or its salt, a diluent, a binder and a lubricant, the diluent comprising lactose and corn starch, the lubricant excluding talc, and the particle size distribution of the benzbromarone or its salt conforming to D(V,0.5)≤20μm and D(V,0.9)≤60μm.

[0011] In some embodiments, the particle size distribution of the benzbromarone or its salts conforms to 5 μm ≤ D(V,0.5) ≤ 20 μm; in some typical embodiments, the particle size distribution of the benzbromarone or its salts conforms to 5 μm ≤ D(V,0.5) ≤ 18 μm; in some more typical embodiments, the particle size distribution of the benzbromarone or its salts conforms to 5 μm ≤ D(V,0.5) ≤ 15 μm; and in some most typical embodiments, the particle size distribution of the benzbromarone or its salts conforms to 6 μm ≤ D(V,0.5) ≤ 15 μm.

[0012] In some embodiments, the particle size distribution of the benzbromarone or its salts conforms to 10 μm ≤ D(V,0.9) ≤ 60 μm; in some typical embodiments, the particle size distribution of the benzbromarone or its salts conforms to 15 μm ≤ D(V,0.9) ≤ 60 μm; in some more typical embodiments, the particle size distribution of the benzbromarone or its salts conforms to 25 μm ≤ D(V,0.9) ≤ 60 μm; in some even more typical embodiments, the particle size distribution of the benzbromarone or its salts conforms to 27 μm ≤ D(V,0.9) ≤ 60 μm; and in some most typical embodiments, the particle size distribution of the benzbromarone or its salts conforms to 27 μm ≤ D(V,0.9) ≤ 58 μm.

[0013] In some embodiments, the weight of benzbromarone or its salt accounts for 20-40% of the total weight of the pharmaceutical composition.

[0014] In some embodiments, the diluent accounts for 40-90% of the total weight of the pharmaceutical composition.

[0015] In some embodiments, the adhesive comprises 0.5% to 5% of the total weight of the pharmaceutical composition.

[0016] In some embodiments, the lubricant accounts for 0.5% to 12% of the total weight of the pharmaceutical composition.

[0017] In some embodiments, the filler is a mixture of lactose and corn starch; in some typical embodiments, the filler is a mixture of lactose monohydrate and corn starch; in some embodiments, the weight ratio of lactose to corn starch in the mixture is 1:1 to 1:6.

[0018] In some embodiments, the adhesive is hydroxypropyl cellulose and / or the lubricant is magnesium stearate.

[0019] In some embodiments, the present invention provides a pharmaceutical composition of benzbromarone or a salt thereof, the pharmaceutical composition comprising benzbromarone, lactose, corn starch, hydroxypropyl cellulose and magnesium stearate.

[0020] On the other hand, the present invention provides a pharmaceutical composition of benzbromarone, the pharmaceutical composition comprising the components shown in the table below, and the percentage of each component by weight of the total weight of the pharmaceutical composition shown in the table below:

[0021] Components weight percentage, % Benzbromarone 20～40 lactose 30～60 corn starch 10～30 Hydroxypropyl cellulose 0.5～5 magnesium stearate 0.5～12 .

[0022] In some embodiments, the present invention provides a pharmaceutical composition of benzbromarone, the pharmaceutical composition comprising the components shown in the table below, and the weight percentage of each component in the total weight of the pharmaceutical composition as shown in the table below:

[0023] Components weight percentage Benzbromarone 33.3 lactose 35～55 corn starch 10～30 Hydroxypropyl cellulose 0.5～5 magnesium stearate 0.5～1.5

[0024] Among them, the particle size distribution of benzbromarone meets the requirements of D(V,0.5)≤20μm and D(V,0.9)≤60μm.

[0025] In some implementations, D(V,0.5) and D(V,0.9) conform to the particle size distributions described above.

[0026] Thirdly, the present invention also provides a method for preparing a pharmaceutical composition of benzbromarone or a salt thereof, the method comprising the following steps:

[0027] (1) Prepare adhesive solution: Add adhesive to water and stir until dissolved;

[0028] (2) Add benzbromarone or its salt and filler to a fluidized bed, and then spray the binder solution prepared in step 1) to granulate wet granules.

[0029] (3) Dry the wet granules, sieve them, and granulate them to obtain dry granules;

[0030] (4) Add lubricant to the dry particles obtained in step (3) and mix them together to obtain mixed particles;

[0031] (5) Optionally, the total mixed particles obtained in step (4) are compressed into tablets.

[0032] In some embodiments, the preparation method of the pharmaceutical composition of benzbromarone or its salt includes the following steps:

[0033] (1) Preparation of adhesive solution: Add hydroxypropyl cellulose to water and stir until dissolved;

[0034] (2) Add benzbromarone, lactose and corn starch to a fluidized bed, and then spray the binder solution prepared in step 1) to granulate wet granules.

[0035] (3) Dry the wet granules, sieve them, and granulate them to obtain dry granules;

[0036] (4) Add magnesium stearate to the dry granules obtained in step (3) and mix them together to obtain mixed granules.

[0037] (5) Optionally, the total mixed particles obtained in step (4) are compressed into tablets.

[0038] In some embodiments, the preparation method of the pharmaceutical composition of benzbromarone or its salt includes the following steps:

[0039] (1) Preparation of adhesive solution: Add hydroxypropyl cellulose to water and stir until dissolved;

[0040] (2) Add benzbromarone, lactose and corn starch to a fluidized bed, and then spray the binder solution prepared in step 1) to granulate wet granules.

[0041] (3) Dry the wet granules, sieve them, and granulate them to obtain dry granules;

[0042] (4) Add magnesium stearate to the dry granules obtained in step (3) and mix them together to obtain mixed granules.

[0043] (5) Compress the total mixed particles obtained in step (4) into tablets.

[0044] In some embodiments, the weight ratio of adhesive to water in the adhesive solution is 1:10 to 15; in some typical embodiments, the adhesive is hydroxypropyl cellulose, and the weight ratio of hydroxypropyl cellulose to water is 1:10 to 15.

[0045] In some embodiments, in step (2), the granulation parameters are set as follows: the inlet air temperature of the fluidized bed granulator is 55.0±10.0℃; and the inlet air volume is controlled at 2000±500m³. 3 / h; control the spraying speed to 50~220g / min; atomization pressure 0.20~4.0bar.

[0046] In some embodiments, in step (3), the air inlet temperature is set to 22-27°C during drying, the LOD of the material is controlled to be ≤2.0%, and the dried granules are granulated by passing through a φ1.0 or 1.2mm screen and 500±200rpm in a dry granulator to obtain dry granules.

[0047] The pharmaceutical composition of benzbromarone or its salts provided by this invention is pure white in color, has a complete and glossy surface, and exhibits good dissolution properties. The preparation method of the pharmaceutical composition of benzbromarone or its salts provided by this invention is simple, requiring no preparation of an organic solution containing benzbromarone or its salts, eliminating the risk of organic solvent residue, providing a large granulation process window, and facilitating industrial production. The granules obtained by this process are uniform, compact, and have good flowability; the tablets obtained by this process are pure white in color, have a complete and glossy surface, exhibit small weight variations, and possess good dissolution properties.

[0048] Unless otherwise specified, all materials used in this invention are commercially available.

[0049] Unless otherwise specified, the terms used in this invention have the following meanings:

[0050] In this invention, all numerical ranges should be understood to include the listed endpoint values. Those skilled in the art will understand that numerical deviations caused by experimental errors in measurement techniques are still within the scope of protection of this invention. Unless otherwise specified, the tolerance for deviation is ±10%, but industry-recognized error standards for specific measurement methods should be applied preferentially. The aforementioned experimental errors include, but are not limited to, technical errors, instrument errors, environmental errors, or methodological errors.

[0051] In this invention, unless otherwise specified, % is a percentage of weight / weight (w / w).

[0052] In this invention, unless otherwise specified, a pharmaceutical composition refers to a mixture system made by mixing benzbromarone with one or more pharmaceutical excipients in a certain proportion, and may be granules or tablets.

[0053] In this invention, unless otherwise specified, lactose includes, but is not limited to, anhydrous lactose and lactose monohydrate; when it exists as lactose monohydrate, its weight percentage is calculated as lactose monohydrate; when it exists as anhydrous lactose, its weight percentage is calculated as anhydrous lactose.

[0054] In this invention, LOD refers to loss on drying, which is the percentage of weight lost after drying under specified conditions.

[0055] In this invention, micronization refers to a powder processing technology that reduces the particle size of materials to the micrometer or even submicrometer level through specific processes, such as air jet milling, ball milling, and spray drying.

[0056] In this invention, μm refers to micrometer, a commonly used unit of length for characterizing the particle size of powders or particles.

[0057] In this invention, the granulation process window refers to the range of key process parameters that enable the stable production of particles that meet the preset critical quality attributes (CQAs) during the granulation process.

[0058] In this invention, particle size distribution refers to the percentage of particles with different particle size distributions in a powder sample, as reflected by specific instruments and methods.

[0059] In this invention, D(V,0.5) refers to the particle size value corresponding to the cumulative particle size distribution percentage of a sample reaching 50%. Its physical meaning is that particles with a diameter greater than and less than this value each account for 50%, also known as D50, median diameter, or median particle size.

[0060] In this invention, D(V,0.9) refers to the particle size value corresponding to the cumulative particle size distribution percentage of a sample reaching 90%. Its physical meaning is that particles smaller than this value account for 90%, while particles larger than this value account for 10%, also known as D90.

[0061] In this invention, the dissolution of pharmaceutical compositions of benzbromarone or its salts, particularly benzbromarone tablets, can be examined using the following analytical methods:

[0062] Dissolution conditions: 1000 ml of phosphate buffer (12.5 g disodium hydrogen phosphate, 1.46 g potassium dihydrogen phosphate, and 2.5 g sodium dodecyl sulfate, dissolved in water and diluted to 1000 ml, pH adjusted to 7.5 with 2 mol / L sodium hydroxide solution or dilute phosphoric acid) was used as the dissolution medium. The rotation speed was 100 rpm, and the temperature was 37 ± 0.5 °C. The procedure was followed, and samples were taken at 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min.

[0063] Chromatographic conditions: Octadecylsilane-bonded silica gel was used as the stationary phase (Welch Ultimate XB-C18 4.6×50mm, 3μm or equivalent column recommended); methanol-acetonitrile-water-glacial acetic acid (990:25:300:5) was used as the mobile phase; the flow rate was 1.5 mL / min; the detection wavelength was 231 nm; the column temperature was 30 °C; the injection volume was 20 μL; and the run time was 8 min.

[0064] In this invention, the particle size distribution of benzbromarone or its salts was measured using Malvern Mastersizer 2000 laser diffraction; the equipment parameters were: air pressure 4 bar, injection rate 30%, and ordinary Venturi tube.

[0065] The tablet weight variation test method in this invention is based on General Chapter 0101 of Part IV of the 2025 edition of the Chinese Pharmacopoeia. The test method involves taking 20 tablets of the sample, accurately weighing the total weight, calculating the average tablet weight, and then accurately weighing each tablet separately. The weight of each tablet is compared with the average tablet weight (for tablets without content determination or for traditional Chinese medicine tablets with labeled tablet weight, the weight of each tablet should be compared with the labeled tablet weight). According to the provisions in the table, no more than 2 tablets shall exceed the weight variation limit, and no tablet shall exceed the limit by more than 1 time.

[0066]

[0067] The Hanssen sodium ratio is a compressibility coefficient and an important indicator of powder flowability. Its magnitude reflects the bulk density, particle size and morphology, surface area, cohesiveness, and softness of the powder. The formula for its calculation is tapped density / bulk density. USP <1174> POWDER FLOW (United States Pharmacopeia) <1174> The evaluation of the flowability of powders on the material's flowability properties is shown in Table 1.

[0068] Table 1: Evaluation Indicators of Material Flow Performance

[0069] Flowing energy Hausen sodium ratio very good 1.00-1.11 good 1.12-1.18 Good or average 1.19-1.25 acceptable 1.26-1.34 Difference 1.35-1.45 Very bad 1.46-1.59 Very, very bad >1.60 Detailed Implementation

[0070] The specific embodiments of the present invention will be described in further detail below with reference to the examples. These examples are for illustrative purposes only and are not intended to limit the scope of the invention.

[0071] Example 1:

[0072] Prescription composition:

[0073] Component Name Single tablet component weight (mg) Weight percentage of each component (w / w%) Benzbromarone 50 33.3 Lactose monohydrate 62.5 41.7 corn starch 30 20 Hydroxypropyl cellulose 6 4 magnesium stearate 1.5 1 total 150 100

[0074] The particle size distribution of benzbromarone active pharmaceutical ingredient is 8 μm (D(V,0.5)) and 27 μm (D(V,0.9)).

[0075] Preparation method:

[0076] 1) Preparation of adhesive solution: Add an appropriate amount of purified water to a mixing tank, then add the prescribed amount of hydroxypropyl cellulose and stir until dissolved;

[0077] 2) Preparation of wet granules: Add the prescribed amounts of benzbromarone, lactose monohydrate, and corn starch to a fluidized bed, and then spray the binder solution obtained in step 1) onto the fluidized bed for granulation to obtain wet granules;

[0078] The process parameters for the fluidized bed are: inlet air temperature 55.0±10.0℃; controlled inlet air volume 2000±500 m³ / h. 3 / h; control the spraying speed to 40-180g / min; atomization pressure 1.5bar-3.5bar.

[0079] 3) Dry pellet preparation: During drying, the inlet air temperature is set to 22-27℃. After drying the obtained wet pellets and controlling the LOD of the material to ≤2.0%, the dried pellets are granulated through a dry granulator through a φ1.0 or 1.2mm screen at 500±200rpm to obtain dry pellets.

[0080] 4) Total mixing: Add the obtained dry granules to the prescribed amount of magnesium stearate for total mixing to obtain total mixed granules.

[0081] 5) Tableting: Tableting is performed using a tablet press.

[0082] Example 2:

[0083] Prescription composition:

[0084] Component Name Single tablet component weight (mg) Weight percentage of each component (w / w%) Benzbromarone 50 33.3 Lactose monohydrate 77.5 51.7 corn starch 16 10.7 Hydroxypropyl cellulose 5 3.3 magnesium stearate 1.5 1 total 150 100

[0085] The particle size distribution of benzbromarone was 15 μm (D(V,0.5)) and 58 μm (D(V,0.9)). The preparation method was the same as in Example 1.

[0086] Example 3:

[0087] Prescription composition:

[0088] Component Name Single tablet component weight (mg) Weight percentage of each component (w / w%) Benzbromarone 50 33.3 Lactose monohydrate 57.5 38.3 corn starch 40 26.7 Hydroxypropyl cellulose 1 0.7 magnesium stearate 1.5 1 total 150 100

[0089] The particle size distribution of benzbromarone was 6 μm (D(V,0.5)) and 15 μm (D(V,0.9)). The preparation method was the same as in Example 1.

[0090] Comparative Example 1:

[0091] Prescription composition:

[0092] Component Name Single tablet component weight (mg) Weight percentage of each component (w / w%) Benzbromarone 50 33.3 Lactose monohydrate 60.5 40.3 corn starch 20 13.3 Hydroxypropyl cellulose 16.5 11 magnesium stearate 1.5 1 talcum powder 1.5 1 total 150 100

[0093] The particle size distribution of benzbromarone is 8 μm (D(V,0.5)) and 27 μm (D(V,0.9)).

[0094] Preparation method:

[0095] 1) Preparation of adhesive solution: Add purified water to a mixing tank, then add hydroxypropyl cellulose and stir until dissolved;

[0096] 2) Preparation of wet granules: The prescribed amounts of benzbromarone, lactose monohydrate, and corn starch are added to a fluidized bed, and then the binder solution is sprayed onto the fluidized bed for granulation to obtain wet granules. The process parameters of the fluidized bed are: inlet air temperature of 55.0±10.0℃; and inlet air volume of 2000±500 m³ / h.3 / h; control the spraying speed at 100g / min; atomization pressure at 3.0 bar;

[0097] 3) Dry pellet preparation: After drying the obtained wet pellets, they are granulated through a sieve to obtain dry pellets. During drying, the inlet air temperature is set to 22-27℃. After drying the obtained wet pellets and controlling the LOD of the material to ≤2.0%, the dried pellets are granulated through a dry granulator through a φ1.0 or 1.2mm sieve at 500±200rpm to obtain dry pellets.

[0098] 4) Total mixing: Add the obtained dry granules to the prescribed amount of magnesium stearate for total mixing to obtain total mixed granules.

[0099] 5) Tableting: Tableting is performed using a tablet press.

[0100] Comparative Example 2:

[0101] Prescription composition:

[0102] Component Name Single tablet component weight (mg) Weight percentage of each component (w / w%) Benzbromarone 50 33.3 Lactose monohydrate 62.5 41.7 corn starch 30 20 Hydroxypropyl cellulose 6 4 magnesium stearate 1.5 1 total 150 100

[0103] The particle size distribution of benzbromarone is 28 μm (D(V,0.5)) and 100 μm (D(V,0.9)).

[0104] The preparation method is the same as in Example 1.

[0105] Comparative Example 3:

[0106] Prescription composition:

[0107] Component Name Single tablet component weight (mg) Weight percentage of each component (w / w%) Benzbromarone 50 33.3 Lactose monohydrate 62.5 41.7 corn starch 30 20 Hydroxypropyl cellulose 6 4 magnesium stearate 1.5 1 total 150 100

[0108] The particle size distribution of benzbromarone is 8 μm (D(V,0.5)) and 27 μm (D(V,0.9)).

[0109] Preparation method:

[0110] 1) Preparation of adhesive solution: Add ethanol to a mixing tank, then add hydroxypropyl cellulose and stir until dissolved;

[0111] 2) Preparation of wet granules: The prescribed amounts of benzbromarone, lactose monohydrate, and corn starch are added to a fluidized bed, and then the binder solution is sprayed onto the fluidized bed for granulation to obtain wet granules. The process parameters of the fluidized bed are: inlet air temperature of 35.0±10.0℃; and inlet air volume of 2000±500 m³ / h. 3 / h; control the spraying speed at 100g / min; atomization pressure at 2.0 bar;

[0112] 3) Dry granule preparation: After drying the obtained wet granules, they are granulated through a φ1.0mm sieve and a granulator with a rotation speed of 500rpm to obtain dry granules.

[0113] 4) Total mixing: Add the obtained dry granules to the prescribed amount of magnesium stearate for total mixing to obtain total mixed granules.

[0114] 5) Tableting: Tableting is performed using a tablet press.

[0115] Comparative Example 4:

[0116] Prescription composition:

[0117] Component Name Single-piece component mass (mg) Weight percentage of each component (w / w%) Benzbromarone 50 33.3 Lactose monohydrate 62.5 41.7 corn starch 30 20 Hydroxypropyl cellulose 6 4 magnesium stearate 1.5 1 total 150 100

[0118] The particle size distribution of benzbromarone is 8 μm (D(V,0.5)) and 27 μm (D(V,0.9)).

[0119] Preparation method:

[0120] (1) Total Mixing I: Add the prescribed amounts of benzbromarone, hydroxypropyl cellulose, lactose monohydrate, and corn starch to the total mixture to obtain mixed granules.

[0121] (2) Total Mixing II: Add the obtained Mixing I material to the prescribed amount of magnesium stearate for total mixing to obtain total mixed particles.

[0122] (3) Tableting: Tableting is performed in a tablet press.

[0123] Example 4:

[0124] The total mixed particle flowability (Hausen sodium ratio) of the samples obtained in Examples 1-3 and Comparative Examples 1-4 was tested; and the benzbromarone tablets obtained in Examples 1-3 and Comparative Examples 1-4 were subjected to visual inspection and residual solvent detection. The results are shown in Table 1.

[0125]

[0126] Example 5: Investigation of the dissolution results of benzbromarone tablets

[0127] The benzbromarone tablets obtained in Examples 1-3 and Comparative Examples 1-4 were subjected to a pH 7.5 medium with 0.25% SDS, 1000 mL, paddle method, 100 rpm, and a temperature of (37±0.5) °C, and samples were taken at 5, 10, 15, 20, 30, 45 and 60 minutes, respectively. The specific test results are shown in Table 2.

[0128] Table 2: Dissolution data of benzbromarone tablets obtained in Examples 1-3 and Comparative Examples 1-4

[0129]

[0130] Therefore, the technical solution provided by this invention can produce benzbromarone tablets that meet the quality requirements, with a complete and bright appearance and stable tablet weight; the production process is stable, and the absence of organic solvents in the production process can greatly reduce production costs and pollution, which is conducive to industrial production.

Claims

1. A pharmaceutical composition of benzbromarone or a salt thereof, characterized in that, The pharmaceutical composition comprises benzbromarone or a salt thereof, a diluent, a binder, and a lubricant, wherein the diluent comprises lactose and corn starch, the lubricant does not include talc, and the particle size distribution of the benzbromarone or its salt thereof conforms to D(V,0.5)≤20μm and D(V,0.9)≤60μm.

2. The pharmaceutical composition according to claim 1, characterized in that, The particle size distribution of the benzbromarone or its salts conforms to 5μm≤D(V,0.5)≤20μm and 10μm≤D(V,0.9)≤60μm.

3. The pharmaceutical composition according to claim 1, characterized in that, The weight of benzbromarone or its salt accounts for 20-40% of the total weight of the pharmaceutical composition; the weight of the diluent accounts for 40-90% of the total weight of the pharmaceutical composition; the weight of the binder accounts for 0.5-5% of the total weight of the pharmaceutical composition; and the weight of the lubricant accounts for 0.5-12% of the total weight of the pharmaceutical composition.

4. The pharmaceutical composition according to claim 1, characterized in that, The filler is a mixture of lactose and corn starch; preferably, the mixture is a mixture of lactose and corn starch, and the weight ratio of lactose to corn starch is 1:1 to 1:

6.

5. The pharmaceutical composition according to claim 1, characterized in that, The adhesive is hydroxypropyl cellulose and / or the lubricant is magnesium stearate.

6. The pharmaceutical composition according to claim 1, characterized in that, The pharmaceutical composition consists of benzbromarone, lactose, corn starch, hydroxypropyl cellulose, and magnesium stearate.

7. A pharmaceutical composition for benzbromarone, characterized in that, The pharmaceutical composition comprises the components shown in the table below, and the weight percentage of each component to the total weight of the pharmaceutical composition is shown in the table below: 。 8. The pharmaceutical composition according to claim 7, characterized in that, The pharmaceutical composition comprises the components shown in the table below, and the weight percentage of each component to the total weight of the pharmaceutical composition is shown in the table below: Among them, the particle size distribution of benzbromarone meets the requirements of D(V,0.5)≤20μm and D(V,0.9)≤60μm.

9. A method for preparing a pharmaceutical composition of benzbromarone or its salt, characterized in that, The method includes the following steps: (1) Prepare adhesive solution: Add adhesive to water and stir until dissolved; (2) Add benzbromarone or its salt and filler to a fluidized bed, and then spray the binder solution prepared in step 1) to granulate wet granules. (3) Dry the wet granules, sieve them, and granulate them to obtain dry granules; (4) Add lubricant to the dry particles obtained in step (3) and mix them together to obtain mixed particles; (5) Optionally, the total mixed particles obtained in step (4) are compressed into tablets.

10. The preparation method according to claim 9, characterized in that, The method includes the following steps: (1) Preparation of adhesive solution: Add hydroxypropyl cellulose to water and stir until dissolved; (2) Add benzbromarone, lactose and corn starch to a fluidized bed, and then spray the binder solution prepared in step 1) to granulate wet granules. (3) Dry the wet granules, sieve them, and granulate them to obtain dry granules; (4) Add magnesium stearate to the dry granules obtained in step (3) and mix them together to obtain mixed granules. (5) Compress the mixed particles obtained in step (4) into tablets.

11. The preparation method according to claim 9, characterized in that, The adhesive solution contains an adhesive to water ratio of 1:10 to 15; preferably, the adhesive is hydroxypropyl cellulose.

12. The preparation method according to claim 9 or 10, characterized in that, In step (2), the granulation parameters are set as follows: the inlet air temperature of the fluidized bed granulator is 55.0±10.0℃; and the inlet air volume is controlled at 2000±500m³. 3 / h; control the spraying speed to 50~220g / min; atomization pressure 0.20~4.0bar.

13. The preparation method according to claim 9 or 10, characterized in that, In step (3), the air inlet temperature is set to 22-27℃ during drying, and the LOD of the material is controlled to be ≤2.0%. The dried granules are granulated by passing through a φ1.0 or 1.2mm sieve and 500±200rpm through a dry granulator to obtain dry granules.

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