Fenerenone preparation and preparation method thereof

Abstract

The invention relates to a fenerenone preparation and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. According to the invention, the disintegrating agent and the filling agent are added in the form of internal addition and external addition, so that the disintegration performance of the disintegrating agent is improved, and the dissolution effect of the finerenone preparation is improved; in addition, the mass ratio of the first filling agent to the second filling agent is adjusted, the mass of the internally added materials is reduced, the liquid spraying time in the preparation process is shortened, the production batch is expanded, and therefore the production time is shortened, and the production cost is reduced. The preparation method disclosed by the invention is short in preparation time, and the finerenone preparation prepared by the preparation method disclosed by the invention is uniform in particle and good in dissolution effect, and has a good industrial application value.

Description

Technical Field

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

[0002] Finerenone is a non-steroidal and highly selective mineralocorticoid receptor antagonist, which shows in pre-clinical studies that it can block the harmful effects caused by the over-activation of mineralocorticoid receptors. It is applicable to adult patients with chronic kidney disease related to type 2 diabetes (with proteinuria) to reduce the risk of continuous decline in estimated glomerular filtration rate (eGFR), end-stage renal disease, cardiovascular death and hospitalization due to heart failure. Finerenone is a drug that can effectively improve renal function. It can relieve the hypertension symptoms of patients with chronic kidney disease, delay the further damage of renal function by reducing the excretion of urinary protein, and at the same time can accelerate the urinary excretion of water and sodium salts, and effectively improve symptoms such as edema caused by water and sodium retention while ensuring the glomerular filtration rate.

[0003] Finerenone is the third-generation new, highly selective, non-steroidal corticosteroid receptor antagonist (MRA) developed by Bayer. It has higher mineralocorticoid receptor specificity and affinity than the first-generation and second-generation MRAs, and can selectively bind to mineralocorticoid receptors. Finerenone is the first non-steroidal mineralocorticoid receptor antagonist used to reduce the incidence of cardiovascular death events in patients with diabetic kidney disease, making up for a major defect in the market and providing better choices for patients, greatly improving the quality of life of patients with diabetic kidney disease.

[0004] The general process for preparing finerenone tablets in the prior art is as follows: hydroxypropyl methylcellulose, sodium lauryl sulfate and micronized finerenone are added to purified water to prepare an adhesive-raw material suspension; after mixing microcrystalline cellulose, lactose monohydrate and croscarmellose sodium evenly, the adhesive-raw material suspension is sprayed into a fluidized bed for granule preparation and drying; then the prepared granules are screened and sized, magnesium stearate is added for mixing, and then tableting and coating are carried out. In this process, all the fillers and disintegrants are added internally, the amount of internally added materials is large, and the amount of water required for the sprayed adhesive-raw material suspension will also increase accordingly, the spraying time is long, and the production time is correspondingly long; at the same time, with more internally added materials, the drug dissolution effect is limited, and it affects batch production. The extension of production time and the limitation of batch will both increase the production cost. Therefore, there is an urgent need to solve the problems of long production time and poor dissolution effect of finerenone preparations. Summary of the Invention

[0005] Therefore, the technical problem to be solved by the present invention is to overcome the problems of long preparation time and poor dissolution performance of finerenone tablets in the preparation process in the prior art.

[0006] To solve the above technical problems, the present invention provides a finerenone preparation and a preparation method thereof. The present invention adds a disintegrant and a filler in an internal addition and an external addition manner, improving the disintegration performance of the disintegrant, thereby enhancing the dissolution effect of the finerenone preparation. In addition, the present invention adjusts the mass ratio of the first filler and the second filler, reducing the mass of the internally added materials, shortening the spraying time during the preparation process and expanding the production batch, thus shortening the production time and reducing the production cost. The preparation method of the present invention has a short preparation time. The finerenone preparation obtained by the preparation method of the present invention has uniform particles and good dissolution effect, and has good industrial application value.

[0007] The first object of the present invention is to provide a preparation method of a finerenone preparation, comprising the following steps:

[0008] S1. Mix finerenone with a binder and a solubilizer in the presence of a solvent to obtain a first mixture, mix a first filler and a first disintegrant to obtain a second mixture, spray the first mixture into the second mixture and dry to obtain an internally added substance;

[0009] S2. Mix the internally added substance with a second filler, a second disintegrant and a lubricant evenly and press into tablets to obtain the finerenone preparation;

[0010] Wherein, the sum of the masses of the first filler and the second filler is 40 - 90% of the mass of the finerenone preparation, and the mass of the first filler is 20 - 60% of the mass of the finerenone preparation; the mass of the solvent is the sum of the masses of the first filler and the first disintegrant.

[0011] Further, the mass of the finerenone is 5 - 20% of the mass of the finerenone preparation.

[0012] Further, the sum of the masses of the first filler and the second filler is 40 - 90% of the finerenone preparation.

[0013] Further, the sum of the masses of the first disintegrant and the second disintegrant is 2% - 10% of the mass of the finerenone preparation.

[0014] Further, the mass of the binder is 2 - 5% of the mass of the finerenone preparation.

[0015] Further, the mass of the solubilizer is 0.1 - 2% of the mass of the finerenone preparation.

[0016] Further, the mass of the lubricant is 0.1 - 3% of the finerenone preparation.

[0017] Further, the solvent includes purified water, and the addition amount of the solvent is the sum of the masses of the first filler and the first disintegrant.

[0018] Further, the first filler and the second filler are each independently selected from one or more of lactose, starch, microcrystalline cellulose, mannitol, pregelatinized starch, maltodextrin, cyclodextrin, silicified cellulose, glucose, and calcium hydrogen phosphate.

[0019] Further, the first disintegrant and the second disintegrant are each independently selected from one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose.

[0020] Further, the binder is selected from one or more of polyvinylpyrrolidone K30, hydroxypropyl cellulose, and hydroxypropyl methylcellulose.

[0021] Further, the solubilizer is selected from one or more of sodium dodecyl sulfate, Tween 20, and poloxamer.

[0022] Further, the lubricant is selected from one or more of magnesium stearate, calcium stearate, sodium stearyl fumarate, glyceryl monostearate, talc, and colloidal silicon dioxide.

[0023] Further, the finerenone particle size is less than or equal to 30 μm.

[0024] Further, finerenone is mixed uniformly with the first filler, the first disintegrant, the binder, and the solubilizer in the presence of a solvent and dried, and then sieved through a 24-60 mesh sieve to obtain an internal additive.

[0025] The second object of the present invention is to provide a finerenone preparation prepared by the above preparation method.

[0026] Advantages of the present invention:

[0027] In the present invention, the disintegrant and the filler are added in the form of internal addition and external addition, which improves the disintegration performance of the disintegrant, thereby improving the dissolution effect of the finerenone preparation; in addition, the present invention adjusts the mass ratio of the first filler and the second filler, reduces the spraying time during the preparation process and expands the production batch, thereby shortening the production time and reducing the production cost. The preparation method of the present invention has a short preparation time, and the finerenone preparation prepared by the preparation method of the present invention has uniform particles and good dissolution effect, and has good industrial application value. Specific embodiments

[0028] The following is a further description of the present invention with reference to specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the specific embodiments cited are not intended to limit the present invention.

[0029] Example 1

[0030] The preparation method of finerenone tablets in this example includes the following steps:

[0031] (1) Micronization of finerenone: Micronize finerenone to a particle size ≤ 30 microns.

[0032] (2) Weigh each internal addition material and external addition material separately according to the prescription column in Table 1.

[0033] (3) Preparation of binder - raw material suspension: Add hydroxypropyl cellulose, sodium lauryl sulfate and micronized finerenone in the internal addition materials to purified water in sequence for preparing the binder - raw material suspension, wherein the amount of purified water used is the sum of the amounts of internal addition filler and disintegrant;

[0034] (4) Preparation of internal addition granules: Add microcrystalline cellulose, lactose monohydrate, low - substituted hydroxypropyl cellulose in the internal addition materials into the fluidized bed in sequence, spray the binder - raw material suspension prepared in step (3) for granule preparation, and dry to a moisture content ≤ 2.5%; Screen the internal addition granules through a 24 - 60 - mesh sieve for sizing to obtain uniformly sized internal addition granules.

[0035] (5) Mixing: Mix the internal addition granules obtained in step (4) with microcrystalline cellulose, low - substituted hydroxypropyl cellulose and magnesium stearate in the external addition materials evenly;

[0036] (6) Tableting the mixture obtained in step (5) and coating the tablets.

[0037] Example 2

[0038] The preparation method of finerenone tablets in this example includes the following steps:

[0039] (1) Micronization of finerenone: Micronize finerenone to a particle size ≤ 30 microns.

[0040] (2) Weigh each internal addition material and external addition material separately according to the prescription column in Table 1.

[0041] (3) Preparation of binder - raw material suspension: Add hydroxypropyl cellulose, sodium lauryl sulfate and micronized finerenone in the internal addition materials to purified water in sequence for preparing the binder - raw material suspension, wherein the amount of purified water used is the sum of the amounts of internal addition filler and disintegrant;

[0042] (4) Preparation of internal addition granules: Add microcrystalline cellulose, lactose monohydrate, and low-substituted hydroxypropyl cellulose in the internal addition materials into the fluidized bed in sequence, spray the binder-raw material suspension prepared in step (3) for granule preparation, and dry until the moisture content ≤ 2.5%; screen the internal addition granules through a 24-60 mesh sieve for sizing to obtain uniform internal addition granules.

[0043] (5) Mixing: Mix the internal addition granules obtained in step (4) with microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and magnesium stearate in the external addition materials evenly;

[0044] (6) Compress the mixture obtained in step (5) into tablets and coat the tablets.

[0045] Example 3

[0046] The preparation method of the finerenone tablets in this example includes the following steps:

[0047] (1) Micronization of finerenone: Micronize finerenone until the particle size ≤ 30 microns.

[0048] (2) Weigh each internal addition material and external addition material separately according to the prescription column in Table 1.

[0049] (3) Preparation of binder-raw material suspension: Add hydroxypropyl cellulose, sodium lauryl sulfate, and micronized finerenone in the internal addition materials into purified water in sequence for the preparation of the binder-raw material suspension, where the amount of purified water used is the sum of the amounts of the internal addition fillers and disintegrants;

[0050] (4) Preparation of internal addition granules: Add microcrystalline cellulose, lactose monohydrate, and low-substituted hydroxypropyl cellulose in the internal addition materials into the fluidized bed in sequence, spray the binder-raw material suspension prepared in step (3) for granule preparation, and dry until the moisture content ≤ 2.5%; screen the internal addition granules through a 24-60 mesh sieve for sizing to obtain uniform internal addition granules.

[0051] (5) Mixing: Mix the internal addition granules obtained in step (4) with microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and magnesium stearate in the external addition materials evenly;

[0052] (6) Compress the mixture obtained in step (5) into tablets and coat the tablets.

[0053] Table 1 Formulations of Examples 1-3

[0054]

[0055] Example 4

[0056] The preparation method of the finerenone tablets in this example includes the following steps:

[0057] (1) Micronization of finerenone: Micronize finerenone to a particle size ≤ 30 microns.

[0058] (2) Weigh each internal additive material and external additive material separately according to the prescription columns in Table 2.

[0059] (3) Preparation of binder - raw material suspension: Add hydroxypropyl cellulose, sodium lauryl sulfate, and micronized finerenone in the internal additive materials to purified water in sequence for the preparation of the binder - raw material suspension, where the amount of purified water used is the sum of the amounts of internal additive filler and disintegrant;

[0060] (4) Preparation of internal additive granules: Add microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the internal additive materials to the fluidized bed in sequence, spray the binder - raw material suspension prepared in step (3) for granule preparation, and dry to a moisture content ≤ 2.5%; Screen the internal additive granules through a 24 - 60 mesh sieve for sizing to obtain uniform internal additive granules.

[0061] (5) Mixing: Mix the internal additive granules obtained in step (4) with microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the external additive materials evenly;

[0062] (6) Tableting the mixture obtained in step (5) and coating the tablets.

[0063] Example 5

[0064] The preparation method of finerenone tablets in this example includes the following steps:

[0065] (1) Micronization of finerenone: Micronize finerenone to a particle size ≤ 30 microns.

[0066] (2) Weigh each internal additive material and external additive material separately according to the prescription columns in Table 2.

[0067] (3) Preparation of binder - raw material suspension: Add hydroxypropyl cellulose, sodium lauryl sulfate, and micronized finerenone in the internal additive materials to purified water in sequence for the preparation of the binder - raw material suspension, where the amount of purified water used is the sum of the amounts of internal additive filler and disintegrant;

[0068] (4) Preparation of internal additive granules: Add microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the internal additive materials to the fluidized bed in sequence, spray the binder - raw material suspension prepared in step (3) for granule preparation, and dry to a moisture content ≤ 2.5%; Screen the internal additive granules through a 24 - 60 mesh sieve for sizing to obtain uniform internal additive granules.

[0069] (5) Mixing: Mix the internal additive granules obtained in step (4) with microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the external additive materials evenly;

[0070] (6) Tablet pressing is carried out on the mixture obtained in step (5), and the tablets are coated.

[0071] Example 6

[0072] The preparation method of finerenone tablets in this example includes the following steps:

[0073] (1) Micronization of finerenone: Micronize finerenone to a particle size ≤ 30 microns.

[0074] (2) Weigh each internal addition material and external addition material separately according to the prescription column in Table 2.

[0075] (3) Preparation of binder - raw material suspension: Add hydroxypropyl cellulose, sodium lauryl sulfate and micronized finerenone in the internal addition materials to purified water in sequence for preparing the binder - raw material suspension, where the amount of purified water used is the sum of the amounts of internal addition filler and disintegrant;

[0076] (4) Preparation of internal addition granules: Add microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the internal addition materials to the fluidized bed in sequence, spray the binder - raw material suspension prepared in step (3) for granule preparation, and dry to a moisture content ≤ 2.5%; Screen the internal addition granules through a 24 - 60 mesh sieve for sizing to obtain uniformly sized internal addition granules.

[0077] (5) Mixing: Mix the internal addition granules obtained in step (4) with microcrystalline cellulose, croscarmellose sodium and magnesium stearate in the external addition materials evenly;

[0078] (6) Tablet pressing is carried out on the mixture obtained in step (5), and the tablets are coated.

[0079] Table 2 Formulations of Examples 4 - 6

[0080]

[0081] Example 7

[0082] The preparation method of finerenone tablets in this example includes the following steps:

[0083] (1) Micronization of finerenone: Micronize finerenone to a particle size ≤ 30 microns.

[0084] (2) Weigh each internal addition material and external addition material separately according to the prescription column in Table 3.

[0085] (3) Preparation of binder - raw material suspension: Add hydroxypropyl methylcellulose, sodium lauryl sulfate and micronized finerenone in the internal addition materials to purified water in sequence for preparing the binder - raw material suspension, where the amount of purified water used is the sum of the amounts of internal addition filler and disintegrant;

[0086] (4) Preparation of internal addition granules: The microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the internal addition materials were sequentially added into the fluidized bed, and the binder - raw material suspension prepared in step (3) was sprayed in for granule preparation, and dried until the moisture content ≤ 2.5%; the internal addition granules were screened through a 24 - 60 - mesh sieve for sizing to obtain uniformly granulated internal addition granules.

[0087] (5) Mixing: The internal addition granules obtained in step (4) were uniformly mixed with the microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the external addition materials;

[0088] (6) Tableting the mixture obtained in step (5) and coating the tablets.

[0089] Example 8

[0090] The preparation method of the finerenone preparation in this example includes the following steps:

[0091] (1) Micronization of finerenone: Micronize finerenone to a particle size ≤ 30 microns.

[0092] (2) Weigh each internal addition material and external addition material separately according to the prescription list in Table 3.

[0093] (3) Preparation of binder - raw material suspension: Hydroxypropyl methylcellulose, sodium lauryl sulfate, and micronized finerenone in the internal addition materials were sequentially added to purified water for preparing the binder - raw material suspension, where the amount of purified water used was the sum of the amounts of the internal addition filler and disintegrant;

[0094] (4) Preparation of internal addition granules: The microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the internal addition materials were sequentially added into the fluidized bed, and the binder - raw material suspension prepared in step (3) was sprayed in for granule preparation, and dried until the moisture content ≤ 2.5%; the internal addition granules were screened through a 24 - 60 - mesh sieve for sizing to obtain uniformly granulated internal addition granules.

[0095] (5) Mixing: The internal addition granules obtained in step (4) were uniformly mixed with the microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the external addition materials;

[0096] (6) Tableting the mixture obtained in step (5) and coating the tablets.

[0097] Example 9

[0098] The preparation method of the finerenone tablets in this example includes the following steps:

[0099] (1) Micronization of finerenone: Micronize finerenone to a particle size ≤ 30 microns.

[0100] (2) Weigh each internal additive material and external additive material separately according to the prescription columns in Table 3.

[0101] (3) Preparation of binder - raw material suspension: Add hypromellose, sodium lauryl sulfate and micronized finerenone in the internal additive materials to purified water in sequence for preparing the binder - raw material suspension, where the amount of purified water used is the sum of the amounts of internal filler and disintegrant;

[0102] (4) Preparation of internal additive granules: Add microcrystalline cellulose, lactose monohydrate, croscarmellose sodium in the internal additive materials to the fluidized bed in sequence, spray the binder - raw material suspension prepared in step (3) for granule preparation, and dry to a water content of ≤2.5%; Screen the internal additive granules through a 24 - 60 mesh sieve for granule sizing to obtain uniformly sized internal additive granules.

[0103] (5) Mixing: Mix the internal additive granules obtained in step (4) evenly with microcrystalline cellulose, croscarmellose sodium and magnesium stearate in the external additive materials;

[0104] (6) Compress the mixture obtained in step (5) into tablets and coat the tablets.

[0105] Table 3 Formulations of Examples 7 - 9

[0106]

[0107] Comparative Example 1

[0108] The preparation method of the finerenone tablets in this example includes the following steps:

[0109] (1) Micronization of finerenone: Micronize finerenone to a particle size of ≤30 microns.

[0110] (2) Weigh each internal additive material and external additive material separately according to the prescription columns in Table 4.

[0111] (3) Preparation of binder - raw material suspension: Add hydroxypropyl cellulose, sodium lauryl sulfate and micronized finerenone in the internal additive materials to purified water in sequence for preparing the binder - raw material suspension, where the amount of purified water used is the sum of the amounts of internal filler and disintegrant;

[0112] (4) Preparation of internal additive granules: Add microcrystalline cellulose, lactose monohydrate, low - substituted hydroxypropyl cellulose in the internal additive materials to the fluidized bed in sequence, spray the binder - raw material suspension prepared in step (3) for granule preparation, and dry to a water content of ≤2.5%; Screen the internal additive granules through a 24 - 60 mesh sieve for granule sizing to obtain uniformly sized internal additive granules.

[0113] (5) Mixing: Mix the internal additive granules obtained in step (4) evenly with magnesium stearate;

[0114] (6) Tablet pressing is performed on the mixture obtained in step (5), and the tablets are coated.

[0115] Table 4 Formulation of Comparative Example 1

[0116]

[0117] Granulation phenomenon and test results

[0118] Particle preparation, tablet pressing and coating are carried out at 3000 tablets / batch; the dissolution curves of the tablets of Examples 1-3 and Comparative Example 1 are determined: 900 mL of acetic acid buffer solution with pH 4.5 (take 2.99 g of sodium acetate trihydrate, add about 500 mL of water and stir to dissolve, add 1.6 mL of glacial acetic acid, dilute to 1000 mL with water and mix well) is used as the dissolution medium, paddle method, 50 rpm, and the operation is carried out according to the law. 10 mL of samples are taken at 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min, and the dissolution degrees at different times are measured. The results are shown in Table 7. The calculation method of f2 is referred to the "Technical Guidelines for Dissolution Test of Oral Solid Dosage Forms". It can be seen from the f2 value that f2 of Examples 1-3 and Comparative Example 1 are all greater than 50, and the dissolution curves are consistent with the reference preparation, but the similarity between Examples 1-3 and the reference preparation is higher. In addition, the spraying time of Comparative Example 1 is significantly higher than that of Examples 1-3.

[0119] Table 7: Granulation phenomenon and dissolution results of Examples 1-3 and Comparative Example 1

[0120]

[0121] Comparative Example 2

[0122] (1) Micronization of finerenone: Micronize finerenone to a particle size ≤ 30 microns.

[0123] (2) Weigh each internal addition material and external addition material separately according to the prescription in Table 5.

[0124] (3) Preparation of binder - raw material suspension: Hydroxypropyl cellulose, sodium lauryl sulfate and micronized finerenone in the internal addition materials are sequentially added to purified water for the preparation of binder - raw material suspension, where the amount of purified water used is the sum of the amounts of internal addition filler and disintegrant;

[0125] (4) Preparation of internal addition particles: Microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the internal addition materials are sequentially added into the fluidized bed, and the binder - raw material suspension prepared in step (3) is sprayed in for particle preparation and dried to a moisture content ≤ 2.5%; the internal addition particles are screened through a 24 - 60 mesh sieve for sizing to obtain uniformly sized internal addition particles.

[0126] (5) Mixing: Mix the internal addition granules obtained in step (4) and magnesium stearate evenly.

[0127] (6) Tableting the mixture obtained in step (5) and coating the tablets.

[0128] Table 5 Prescription of Comparative Example 2

[0129]

[0130] Prepare granules, tablets, and coatings at 3000 tablets per batch; determine the dissolution curves of the tablets of Examples 4 - 6 and Comparative Example 2: Use 900 mL of acetic acid buffer solution at pH 4.5 (take 2.99 g of sodium acetate trihydrate, add about 500 mL of water and stir to dissolve, add 1.6 mL of glacial acetic acid, dilute to 1000 mL with water, and mix evenly) as the dissolution medium, paddle method, 50 rpm, operate according to the law, take 10 mL of samples at 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min, and determine the dissolution at different times. The results are shown in Table 8. It can be seen from the f2 value that the f2 values of Examples 4 - 6 and Comparative Example 2 are both greater than 50, and the dissolution curves are consistent with the reference preparation, but the similarity between Examples 4 - 6 and the reference preparation is higher. In addition, the spraying time of Comparative Example 2 is significantly higher than that of Examples 4 - 6.

[0131] Table 8: Granulation Phenomena and Dissolution Results of Examples 4 - 6 and Comparative Example 2

[0132]

[0133]

[0134] Comparative Example 3

[0135] (1) Micronization of finerenone: Micronize finerenone to a particle size of ≤30 microns.

[0136] (2) Weigh each internal addition material and external addition material separately according to the prescription column in Table 6.

[0137] (3) Preparation of binder - raw material suspension: Add hypromellose, sodium lauryl sulfate, and micronized finerenone in the internal addition materials to purified water in sequence for the preparation of the binder - raw material suspension, where the amount of purified water used is the sum of the amounts of the internal addition filler and disintegrant.

[0138] (4) Preparation of internal addition granules: Add microcrystalline cellulose, lactose monohydrate, and sodium carboxymethylcellulose cross-linked in sequence in the internal addition materials into the fluidized bed, spray the binder - raw material suspension prepared in step (3) for granule preparation, and dry until the moisture content ≤ 2.5%; screen the internal addition granules through a 24 - 60 mesh sieve for sizing to obtain uniform internal addition granules.

[0139] (5) Mixing: Mix the internal addition granules obtained in step (4) and magnesium stearate evenly.

[0140] (6) Press the mixture obtained in step (5) into tablets and coat the tablets.

[0141] Table 6: Prescription of Comparative Example 3

[0142]

[0143] Perform granule preparation, tableting, and coating at 3000 tablets / batch; measure the dissolution curves of the tablets of Examples 7 - 9 and Comparative Example 3: Use 900 mL of acetic acid buffer solution at pH 4.5 (take 2.99 g of sodium acetate trihydrate, add about 500 mL of water and stir to dissolve, add 1.6 mL of glacial acetic acid, dilute to 1000 mL with water, and mix well) as the dissolution medium, paddle method, 50 rpm, operate according to law, take 10 mL of samples at 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min, and measure the dissolution at different times. The results are shown in Table 9. It can be seen from the f2 value that the f2 values of Examples 7 - 9 and Comparative Example 3 are both greater than 50, and the dissolution curves are consistent with the reference preparation, but the similarity between Examples 7 - 9 and the reference preparation is higher. In addition, the spraying time of Comparative Example 3 is significantly higher than that of Examples 7 - 9.

[0144] Table 9 Granulation Phenomena and Dissolution Results of Examples 7 - 9 and Comparative Example 3

[0145]

[0146] Obviously, the above - mentioned examples are only illustrations for clear explanation and are not limitations on the implementation methods. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all implementation methods here. And the obvious changes or modifications derived therefrom are still within the protection scope of this invention.

Claims

1. A method for preparing a finerenone preparation, characterized in that: The following steps are involved: S1, mixing finerenone with a binder and a solubilizer in the presence of a solvent to obtain a first mixture, mixing a first filler and a first disintegrant to obtain a second mixture, spraying the first mixture into the second mixture and drying to obtain an internal addition; S2, mixing the internal additive with the second filler, the second disintegrant and the lubricant uniformly and pressing and molding to obtain the finerenone preparation; The sum of the masses of the first filler and the second filler is 40-90% of the mass of the finerenone preparation, and the mass of the first filler is 20-60% of the mass of the finerenone preparation.

2. The preparation method according to claim 1, characterized in that: The first filler and the second filler are independently selected from one or more of lactose, starch, microcrystalline cellulose, mannitol, pregelatinized starch, maltose, cyclodextrin, silicified cellulose, glucose, and calcium hydrogen phosphate.

3. The preparation method according to claim 1, characterized in that: The first disintegrant and the second disintegrant are independently selected from one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose.

4. The preparation method according to claim 1, characterized in that: The binder is selected from one or more of povidone K30, hydroxypropyl cellulose and hypromellose.

5. The preparation method according to claim 1, characterized in that: The solubilizing agent is selected from one or more of sodium lauryl sulfate, Tween 20 and poloxamer.

6. The preparation method according to claim 1, characterized in that: The lubricant is selected from one or more of magnesium stearate, calcium stearate, hard sodium fumarate, glyceryl mono- and distearate, talc, and colloidal silicon dioxide.

7. The preparation method according to claim 1, characterized in that: The mass of the finerenone is 5-20% of the mass of the finerenone preparation.

8. The preparation method according to claim 1, characterized in that: The sum of the mass of the first disintegrant and the second disintegrant is 2%-10% of the mass of the finerenone preparation; the mass of the first disintegrant is 0.5-5% of the mass of the finerenone preparation.

9. The preparation method according to claim 1, characterized in that: The finerenone particle size is less than or equal to 30 μm.

10. The finerenone preparation prepared by the preparation method according to any one of claims 1 to 9.

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