A formulation of finerenone and a method of preparing the same

Abstract

The present application relates to a kind of preparation of finerenone and its preparation method, belong to the technical field of pharmaceutical preparation.The present application adds disintegrant and filler in the form of inside and outside, improves the disintegrant disintegration performance, so as to improve the dissolution effect of finerenone preparation;In addition, the present application adjusts the mass ratio of first filler and second filler, reduces the mass of inside material, reduces the liquid spraying time in preparation process and expands production batch, so as to shorten production time and reduce production cost.The preparation method of the present application is short in preparation time, the finerenone preparation obtained by the preparation method of the present application is uniform and has good dissolution effect, has good industrial application value.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical preparations, in particular to a finerenone preparation and a preparation method thereof. BACKGROUND

[0002] Finerenone is a non-steroidal high-selectivity mineralocorticoid receptor antagonist, which shows in preclinical studies that it can block the harmful effects of excessive activation of the mineralocorticoid receptor, and is suitable for adult patients with type 2 diabetes-related chronic kidney disease (with proteinuria) to reduce the risk of persistent 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 kidney function, which can reduce the symptoms of hypertension in patients with chronic kidney disease, delay further damage to kidney function by reducing the excretion of urinary protein, and accelerate the excretion of water and sodium in urine, effectively improve the symptoms such as edema caused by water and sodium retention while ensuring the glomerular filtration rate.

[0003] Finerenone is a third-generation new type, high selectivity, non-steroidal mineralocorticoid receptor antagonist (MRA) developed by Bayer. It has higher specificity and affinity for mineralocorticoid receptors than the first and second generations of MRA, and can selectively bind to mineralocorticoid receptors. Finerenone is the first non-steroidal mineralocorticoid receptor antagonist for reducing the incidence of cardiovascular death events in patients with diabetic nephropathy, which fills a major gap in the market and provides patients with better options, greatly improving the quality of life of patients with diabetic nephropathy.

[0004] The general process for preparing finerenone tablets in the prior art is to add hydroxypropyl methylcellulose, sodium dodecyl sulfate and micronized finerenone into purified water to prepare a binder-raw material suspension; mix microcrystalline cellulose, lactose monohydrate and cross-linked sodium carboxymethyl cellulose uniformly, and then spray the binder-raw material suspension into the fluidized bed for granule preparation and drying; then sieve and granulate the prepared granules, mix with magnesium stearate, and then press and coat tablets. This process adds all the fillers and disintegrants internally, the internal material is large, the water required for spraying the binder-raw material suspension is also increased accordingly, the spraying time is long, and the production time is relatively long; at the same time, the internal material is large, the drug dissolution effect is limited, and the batch production is affected, and the increase of production time and the limitation of batch will increase the production cost. Therefore, it is urgent to improve the long production time and poor dissolution effect of finerenone preparation. SUMMARY

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

[0006] To solve the above technical problems, the application provides a preparation of finerenone and a preparation method thereof, the preparation method of the application adds a disintegrant and a filler in the form of internal addition and external addition, improves the disintegration performance of the disintegrant, and thus improves the dissolution effect of the preparation of finerenone; in addition, the application adjusts the mass ratio of the first filler and the second filler, reduces the mass of the internal added material, reduces the spraying time in the preparation process, and increases the production batch, so as to shorten the production time and reduce the production cost. The preparation method of the application has a short preparation time, the preparation of finerenone prepared by the preparation method of the application has uniform particles and good dissolution effect, and has good industrial application value.

[0007] The first object of the application is to provide a preparation method of finerenone, which comprises the following steps:

[0008] S1, mixing finerenone, 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 added material;

[0009] S2, uniformly mixing the internal added material with a second filler, a second disintegrant and a lubricant and tabletting to obtain the preparation of finerenone;

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

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

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

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

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

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

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

[0017] Further, the solvent comprises purified water, and the solvent is added in an amount of the sum of the mass of the first filler and the first disintegrant.

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

[0019] Further, the first disintegrant and the second disintegrant are independently selected from one or more of crospovidone, croscarmellose sodium, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose.

[0020] Further, the binder is selected from one or more of povidone K30, hydroxypropyl cellulose, hydroxypropyl methyl cellulose.

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

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

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

[0024] Further, the finerenone is uniformly mixed with the first filler, the first disintegrant, the binder, and the solubilizer in the presence of the solvent, and is dried to obtain an internal additive.

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

[0026] Advantages of the present application:

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

[0028] The present application will be further described below in conjunction with specific examples, so that those skilled in the art can better understand the present application and implement it. However, the examples are not limiting to the present application.

[0029] Example 1

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

[0031] (1) Finerenone micronization: micronize the finerenone to a particle size of ≤ 30 microns.

[0032] (2) Weigh each of the internal and external additive materials according to the prescription column in Table 1, respectively.

[0033] (3) Binder-raw material suspension preparation: add the hydroxypropyl cellulose, sodium dodecyl sulfate, and micronized finerenone in the internal additive materials into purified water in sequence to prepare the binder-raw material suspension, wherein the amount of purified water is the sum of the amounts of the internal filler and disintegrant;

[0034] (4) Internal granule preparation: add the microcrystalline cellulose, lactose monohydrate, and low-substituted hydroxypropyl cellulose in the internal additive materials into a fluidized bed in sequence, spray the binder-raw material suspension prepared in step (3) to prepare granules, and dry to a moisture content of ≤ 2.5%; pass the internal granules through a 24-60 mesh screen for sizing to obtain internal granules with uniform particle size.

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

[0036] (6) tablet the mixture obtained in step (5), and coat the tablets.

[0037] Example 2

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

[0039] (1) Finerenone micronization: micronize the finerenone to a particle size of ≤ 30 microns.

[0040] (2) Weigh each of the internal and external additive materials according to the prescription column in Table 1, respectively.

[0041] (3) Binder-raw material suspension preparation: add the hydroxypropyl cellulose, sodium dodecyl sulfate, and micronized finerenone in the internal additive materials into purified water in sequence to prepare the binder-raw material suspension, wherein the amount of purified water is the sum of the amounts of the internal filler and disintegrant;

[0042] (4) Inner granulation: microcrystalline cellulose, lactose monohydrate, and low-substituted hydroxypropyl cellulose in the inner material are sequentially added into a fluidized bed, and the inner granulation is prepared by spraying the binder-raw material suspension prepared in step (3), and dried to moisture≤2.5%; the inner granulation is sieved through a 24-60 mesh screen for granulation to obtain the inner granulation with uniform particles.

[0043] (5) Mixing: the inner granulation obtained in step (4) is uniformly mixed with microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and magnesium stearate in the outer material;

[0044] (6) The mixture obtained in step (5) is tabletted, and the tablets are coated.

[0045] Example 3

[0046] The preparation method of the finerenone tablets of the present example comprises the following steps:

[0047] (1) Finerenone micronization: micronize the finerenone to a particle size≤30 microns.

[0048] (2) Each inner material and outer material is weighed according to the prescription in Table 1.

[0049] (3) Binder-raw material suspension preparation: hydroxypropyl cellulose, sodium dodecyl sulfate, and micronized finerenone in the inner material are sequentially added into purified water for binder-raw material suspension preparation, wherein the amount of purified water is the total amount of the inner filler and disintegrant;

[0050] (4) Inner granulation: microcrystalline cellulose, lactose monohydrate, and low-substituted hydroxypropyl cellulose in the inner material are sequentially added into a fluidized bed, and the inner granulation is prepared by spraying the binder-raw material suspension prepared in step (3), and dried to moisture≤2.5%; the inner granulation is sieved through a 24-60 mesh screen for granulation to obtain the inner granulation with uniform particles.

[0051] (5) Mixing: the inner granulation obtained in step (4) is uniformly mixed with microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and magnesium stearate in the outer material;

[0052] (6) The mixture obtained in step (5) is tabletted, and the tablets are coated.

[0053] Table 1 Formulation of Examples 1-3

[0054]

[0055] Example 4

[0056] The preparation method of the finerenone tablets of the present example comprises the following steps:

[0057] (1) Finely micronize the finasteride to a particle size of < 30 microns.

[0058] (2) Weigh each of the internal and external ingredients according to the prescription list in Table 2, respectively.

[0059] (3) Binder-ingredient suspension preparation: add the hydroxypropyl cellulose, sodium lauryl sulfate, and micronized finasteride in the internal ingredients into purified water in sequence to prepare the binder-ingredient suspension, wherein the amount of purified water is the sum of the amounts of the internal filler and disintegrant;

[0060] (4) Internal granule preparation: add the microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the internal ingredients into a fluidized bed in sequence, spray the binder-ingredient suspension prepared in step (3) into the fluidized bed to prepare granules, and dry to a moisture content of < 2.5%; pass the internal granules through a 24-60 mesh screen to size, to obtain granules of the internal ingredients that are uniform in size.

[0061] (5) Mixing: mix the internal granules obtained in step (4) with the microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the external ingredients uniformly;

[0062] (6) Tablet the mixture obtained in step (5), and coat the tablets.

[0063] Example 5

[0064] The method for preparing the finasteride tablets of this example comprises the following steps:

[0065] (1) Finely micronize the finasteride to a particle size of < 30 microns.

[0066] (2) Weigh each of the internal and external ingredients according to the prescription list in Table 2, respectively.

[0067] (3) Binder-ingredient suspension preparation: add the hydroxypropyl cellulose, sodium lauryl sulfate, and micronized finasteride in the internal ingredients into purified water in sequence to prepare the binder-ingredient suspension, wherein the amount of purified water is the sum of the amounts of the internal filler and disintegrant;

[0068] (4) Internal granule preparation: add the microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the internal ingredients into a fluidized bed in sequence, spray the binder-ingredient suspension prepared in step (3) into the fluidized bed to prepare granules, and dry to a moisture content of < 2.5%; pass the internal granules through a 24-60 mesh screen to size, to obtain granules of the internal ingredients that are uniform in size.

[0069] (5) Mixing: mix the internal granules obtained in step (4) with the microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the external ingredients uniformly;

[0070] (6) Compressing the mixture obtained in step (5) into tablets, and coating the tablets.

[0071] Example 6

[0072] The preparation method of the finerenone tablets of this embodiment comprises the following steps:

[0073] (1) Finerenone micronization: Finerenone was micronized to a particle size of ≤30 μm.

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

[0075] (3) Preparation of binder-raw material suspension: Hydroxypropyl cellulose, sodium lauryl sulfate and micronized phenerenone in the internal materials are sequentially added to purified water to prepare the binder-raw material suspension, wherein the amount of purified water is the sum of the amounts of the internal filler and disintegrant;

[0076] (4) Preparation of internally added granules: Microcrystalline cellulose, lactose monohydrate, and cross-linked sodium carboxymethyl cellulose in the internally added materials are sequentially added into a fluidized bed, and the binder-raw material suspension prepared in step (3) is sprayed therein to prepare granules, and the granules are dried to a moisture content of ≤2.5%; the internally added granules are sieved through a 24-60 mesh sieve to obtain uniformly sized internally added granules.

[0077] (5) Mixing: uniformly mixing the internal granules obtained in step (4) with the microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose, and magnesium stearate in the external materials;

[0078] (6) Compressing the mixture obtained in step (5) into tablets, and coating the tablets.

[0079] Table 2 Formulations of Examples 4-6

[0080]

[0081] Example 7

[0082] The preparation method of the finerenone tablets of this embodiment comprises the following steps:

[0083] (1) Finerenone micronization: Finerenone was micronized to a particle size of ≤30 μm.

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

[0085] (3) Preparation of binder-raw material suspension: Hydroxypropyl methylcellulose, sodium lauryl sulfate and micronized phenerenone in the internal materials are sequentially added to purified water to prepare the binder-raw material suspension, wherein the amount of purified water is the sum of the amounts of the internal filler and disintegrant;

[0086] (4) Intragranular particle preparation: The microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the intragranular material are sequentially added into a fluidized bed, and the binder-raw material suspension prepared in step (3) is sprayed for particle preparation, and dried to a moisture content of <2.5%; the intragranular particles are sieved through a 24-60 mesh screen for sizing, to obtain intragranular particles with uniform granules.

[0087] (5) Mixing: the intragranular particles obtained in step (4) are mixed uniformly with the microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the extragranular material;

[0088] (6) The mixture obtained in step (5) is tabletted, and the tablets are coated.

[0089] Example 8

[0090] The preparation method of the finerenone tablets of this example comprises the following steps:

[0091] (1) Finerenone micronization: micronize the finerenone to a particle size of <30 microns.

[0092] (2) Each intragranular material and extragranular material is weighed according to the prescription in Table 3.

[0093] (3) Binder-raw material suspension preparation: the hypromellose, sodium dodecyl sulfate, and micronized finerenone in the intragranular material are sequentially added into purified water for binder-raw material suspension preparation, wherein the amount of purified water is the total amount of the intragranular filler and disintegrant;

[0094] (4) Intragranular particle preparation: the microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the intragranular material are sequentially added into a fluidized bed, and the binder-raw material suspension prepared in step (3) is sprayed for particle preparation, and dried to a moisture content of <2.5%; the intragranular particles are sieved through a 24-60 mesh screen for sizing, to obtain intragranular particles with uniform granules.

[0095] (5) Mixing: the intragranular particles obtained in step (4) are mixed uniformly with the microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the extragranular material;

[0096] (6) The mixture obtained in step (5) is tabletted, and the tablets are coated.

[0097] Example 9

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

[0099] (1) Finerenone micronization: micronize the finerenone to a particle size of <30 microns.

[0100] (2) Each of the internal and external materials was weighed according to the prescription column in Table 3.

[0101] (3) Binder-raw material suspension preparation: The hydroxypropyl methylcellulose, sodium lauryl sulfate, and micronized finerenone in the internal material were sequentially added to purified water for binder-raw material suspension preparation, wherein the amount of purified water was the sum of the amounts of the internal filler and disintegrant;

[0102] (4) Internal granule preparation: The microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium in the internal material were sequentially added to a fluidized bed, and the binder-raw material suspension prepared in step (3) was sprayed in for granule preparation, and dried to a moisture content of <2.5%; the internal granules were sieved through a 24-60 mesh screen for sizing, to obtain granules of the internal material that were uniform in size.

[0103] (5) Mixing: The internal granules obtained in step (4) were mixed with the microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the external material;

[0104] (6) The mixture obtained in step (5) was tableted, and the tablets were coated.

[0105] Table 3 Formulation of Examples 7-9

[0106]

[0107] Comparative Example 1

[0108] The preparation method of the finerenone tablets of the present example comprises the following steps:

[0109] (1) Finerenone micronization: The finerenone was micronized to a particle size of <30 microns.

[0110] (2) Each of the internal and external materials was weighed according to the prescription column in Table 4.

[0111] (3) Binder-raw material suspension preparation: The hydroxypropyl cellulose, sodium lauryl sulfate, and micronized finerenone in the internal material were sequentially added to purified water for binder-raw material suspension preparation, wherein the amount of purified water was the sum of the amounts of the internal filler and disintegrant;

[0112] (4) Internal granule preparation: The microcrystalline cellulose, lactose monohydrate, and low-substituted hydroxypropyl cellulose in the internal material were sequentially added to a fluidized bed, and the binder-raw material suspension prepared in step (3) was sprayed in for granule preparation, and dried to a moisture content of <2.5%; the internal granules were sieved through a 24-60 mesh screen for sizing, to obtain granules of the internal material that were uniform in size.

[0113] (5) Mixing: The internal granules obtained in step (4) were mixed with the magnesium stearate;

[0114] (6) The mixture obtained in step (5) is tableted, and the tablets are coated.

[0115] Table 4 Formulation of Comparative Example 1

[0116]

[0117] Granulation phenomenon and test results

[0118] Granulation, tableting and coating were carried out according to 3000 tablets / batch; dissolution curves of tablets of Example 1-3 and Comparative Example 1 were determined: 900 mL of acetic acid buffer solution (pH 4.5) (take sodium acetate trihydrate 2.99 g, add water about 500 mL to stir to dissolve, add glacial acetic acid 1.6 mL, dilute to 1000 mL with water, mix well) as the dissolution medium, paddle method, 50 rpm, according to the operation, take 10 mL sample at 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, and determine the dissolution at different time, the results are shown in Table 7. The calculation method of f2 is described in the Technical Guidelines for General Oral Solid Preparation Dissolution Test. According to the f2 value, it can be seen that the f2 of Example 1-3 and Comparative Example 1 is greater than 50, which is consistent with the dissolution curve of the reference preparation, but the similarity of Example 1-3 and the reference preparation is higher. In addition, the spraying time of Comparative Example 1 is significantly higher than that of Example 1-3.

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

[0120]

[0121] Comparative Example 2

[0122] (1) Finely micronize finerenone: micronize finerenone to a particle size of < 30 microns.

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

[0124] (3) Preparation of binder-raw material suspension: add hydroxypropyl cellulose, sodium dodecyl sulfate and micronized finerenone in the internal additive to purified water in sequence to prepare the binder-raw material suspension, wherein the amount of purified water is the total amount of internal filler and disintegrant;

[0125] (4) Internal granule preparation: add microcrystalline cellulose, lactose monohydrate and croscarmellose sodium in the internal additive to the fluidized bed in sequence, spray the binder-raw material suspension prepared in step (3) to prepare granules, and dry to a moisture content of < 2.5%; pass the internal granules through a 24-60 mesh screen for sizing to obtain granules of uniform internal granules.

[0126] (5) Mixing: the intra-granular particles obtained in step (4) are mixed with magnesium stearate.

[0127] (6) The mixture obtained in step (5) is tableted, and the tablets are coated.

[0128] Table 5 Comparative Example 2 Formulation

[0129]

[0130] Granule preparation, tableting and coating are carried out according to 3000 tablets / batch; dissolution curves of tablets of Examples 4-6 and Comparative Example 2 are determined: 900 mL of acetic acid buffer solution (pH 4.5) (take sodium acetate trihydrate 2.99 g, add water about 500 mL, stir to dissolve, add glacial acetic acid 1.6 mL, dilute with water to 1000 mL, mix well) as the dissolution medium, paddle method, 50 rpm, according to the operation, take 10 mL sample at 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, and measure the dissolution at different times, the results are shown in Table 8. According to the f2 value, it can be seen that the f2 values of Examples 4-6 and Comparative Example 2 are all greater than 50, which are consistent with the dissolution curves of the reference preparation, but the similarity of Examples 4-6 with 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 phenomenon and dissolution results of Examples 4-6 and Comparative Example 2

[0132]

[0133]

[0134] Comparative Example 3

[0135] (1) Finely micronize the finasteride to a particle size of <30 microns.

[0136] (2) Weigh each intra-granular and extra-granular material according to the formulation in Table 6.

[0137] (3) Binder-raw material suspension preparation: hydroxypropyl methylcellulose, sodium dodecyl sulfate and micronized finasteride in the intra-granular material are sequentially added to purified water for binder-raw material suspension preparation, wherein the amount of purified water is the sum of the amounts of intra-granular filler and disintegrant.

[0138] (4) Inner granule preparation: The microcrystalline cellulose, lactose monohydrate and croscarmellose sodium in the inner additive are added into the fluid bed in turn, and the granules are prepared by spraying the binder-raw material suspension prepared in step (3) and dried to moisture content of less than 2.5%. The inner granules are sieved through 24-60 mesh screen to obtain the inner granules with uniform size.

[0139] (5) Mixing: The inner granules obtained in step (4) are mixed with magnesium stearate.

[0140] (6) The mixture obtained in step (5) is tabletted, and the tablets are coated.

[0141] Table 6: Formulation of Comparative Example 3

[0142]

[0143] The granule preparation, tableting and coating are carried out for 3000 tablets per batch. The dissolution curves of the tablets of Examples 7-9 and Comparative Example 3 are determined: 900 mL of acetic acid buffer solution (pH 4.5) (2.99 g of sodium acetate trihydrate is dissolved in about 500 mL of water, 1.6 mL of glacial acetic acid is added, and the solution is diluted to 1000 mL with water and mixed) is used as the dissolution medium, the paddle method is used at 50 rpm, and the operation is carried out according to the procedure. 10 mL of sample is taken at 5 min, 10 min, 15 min, 20 min, 30 min, 45 min and 60 min, and the dissolution rate at different times is determined. The results are shown in Table 9. According to the f2 value, the f2 values of Examples 7-9 and Comparative Example 3 are all greater than 50, which are consistent with the dissolution curve of the reference preparation. However, the spraying time of Examples 7-9 is significantly lower than that of Comparative Example 3.

[0144] Table 9: Granulation phenomenon and dissolution results of Examples 7-9 and Comparative Example 3

[0145]

[0146] Obviously, the above examples are merely examples for clarity and do not limit the embodiments. Based on the above description, other different forms of changes or variations can be made by those of ordinary skill in the art. All embodiments need not be exhaustively listed here. The obvious changes or variations derived therefrom are still within the protection scope of the present application.

Claims

1. A method for preparing a finerenone preparation, characterized in that: The following steps are involved: S1. Mixing finerenone with a binder and sodium lauryl sulfate in the presence of a solvent to obtain a first mixture, mixing microcrystalline cellulose, lactose monohydrate 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 microcrystalline cellulose, a second disintegrant and a lubricant, and compressing the mixture to obtain the finerenone preparation; wherein the sum of the total mass of the microcrystalline cellulose and lactose monohydrate described in S1 and the mass of the microcrystalline cellulose described in S2 is 40-90% of the mass of the finerenone preparation, and the total mass of the microcrystalline cellulose and lactose monohydrate described in S1 is 20-60% of the mass of the finerenone preparation; The first disintegrant and the second disintegrant are independently selected from cross-linked carboxymethyl cellulose sodium or low-substituted hydroxypropyl cellulose; the binder is selected from hydroxypropyl cellulose or hypromellose.

2. 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.

3. 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.

4. 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; and the mass of the first disintegrant is 0.5-5% of the mass of the finerenone preparation.

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

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

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