Apactamide solid dispersion as well as preparation method and application thereof

Abstract

The invention provides an apattamide solid dispersion as well as a preparation method and application thereof. The apattamide solid dispersion comprises apattamide and hydroxypropyl methylcellulose acetate succinate (HPMCAS) in a mass ratio of 1: (3.0-3.5). The D90 particle size of the solid dispersion is 60-90 [mu] m, and the D50 particle size of the solid dispersion is 30-45 [mu] m. According to the dispersoid, by adjusting the ratio of the apattamide to the HPMCAS and selecting a proper particle size range, a preparation which can be dissolved out well is obtained. Experimental results show that the D90 particle size of the solid dispersion is 61-87 [mu] m, the D50 particle size is 30-43 [mu] m, the 60 min dissolution rate in SDS with the pH value of 4.5 + 0.2% is 90% or above, meanwhile, the similarity of a dissolution curve and a commercially available product is high, and the relatively close in-vivo absorption speed and degree are predicted.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to an apalutamide solid dispersion and a preparation method and application thereof. Background Art

[0002] Apalutamide, chemical name: 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide, has the following structural formula:

[0003]

[0004] Apalutamide belongs to the BCS2 class of drugs, with low solubility and high permeability. It is almost insoluble in aqueous media within the pH range of 1 to 12. If it is directly prepared into an oral solid preparation, the drug dissolution rate is extremely slow and the bioavailability is low, thus limiting the therapeutic effect of its oral preparation.

[0005] Apalutamide tablets were first approved by the FDA in the United States on February 14, 2018, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) at high risk of metastasis. The product uses a spray drying process to prepare a solid dispersion, converting crystalline drugs into amorphous forms with higher solubility, thereby increasing the solubility of the drug and improving its bioavailability.

[0006] CN106999431A (application number 201580066233.4) discloses a solid dispersion prepared from a solid dispersion of ARN-509 and HPMCAS (the weight ratio is 1:3 optimal), using dichloromethane and methanol as solvents, and using spray drying technology to prepare apalutamide solid dispersion. This method can convert crystalline drugs into amorphous with higher solubility, thereby improving the solubility of the drug and improving bioavailability. However, after actual investigation, it was found that the solid dispersion material prepared by spray drying was fluffy and had poor fluidity, so subsequent dry granulation and other process means were required to obtain particles with better fluidity. Summary of the invention

[0007] In view of this, the object of the present invention is to provide an apalutamide solid dispersion and a preparation method and application thereof. The dispersion is prepared by adjusting the ratio of apalutamide to HPMCAS and selecting a suitable particle size range to obtain a preparation with better dissolution.

[0008] The present invention provides an apalutamide solid dispersion, comprising apalutamide and hydroxypropyl methylcellulose acetate succinate (HPMCAS) in a mass ratio of 1:3.0 to 3.5;

[0009] The D90 particle size of the solid dispersion is 60 to 90 μm, and the D50 particle size is 30 to 45 μm.

[0010] The mass ratio of apalutamide to hypromellose acetate succinate is 1:3.3-3.5. In a specific embodiment, the mass ratio of apalutamide to hypromellose acetate succinate is 1:3.0; 1:3.3 or 1:3.5.

[0011] The D90 particle size of the solid dispersion is preferably 61 to 87 μm, and the D50 particle size is preferably 30 to 43 μm; more preferably, the D90 particle size of the solid dispersion is 80 to 87 μm, and the D50 particle size is 30 to 43 μm.

[0012] The present invention provides a method for preparing the apalutamide solid dispersion described in the above technical solution, comprising the following steps:

[0013] Apalutamide and hydroxypropyl methylcellulose acetate succinate are mixed, hot-melt extruded, and then needle-milled using liquid nitrogen as a milling aid to obtain apalutamide solid dispersion.

[0014] The temperature of the hot melt extrusion of the present invention is 170-180° C.; the screw speed used in the hot melt extrusion is 300-500 rpm.

[0015] In the present invention, the pulverization adopts a combination of needle-type pulverization and liquid nitrogen pulverization; the rotation speed of the pulverizer used in the needle-type pulverization is 14000-16000 rpm; in a specific embodiment, the rotation speed is 14000 rpm, 15000 rpm or 16000 rpm.

[0016] In a specific embodiment, the specific operation of crushing is: start the crusher, and simultaneously pour liquid nitrogen and materials into the feed port of the needle crusher for crushing.

[0017] The present invention also provides a preparation containing apalutamide solid dispersion, comprising the apalutamide solid dispersion described in the above technical solution and pharmaceutically acceptable excipients.

[0018] The preparation is a conventional oral preparation, such as granules, tablets or capsules;

[0019] The pharmaceutically acceptable excipients of the present invention are selected from one or more of the following excipients: fillers, binders, disintegrants, lubricants, glidants, and flavoring agents.

[0020] The apalutamide solid dispersion-containing preparation of the present invention is preferably a tablet; the tablet comprises the following components by mass fraction:

[0021] 30% to 40% apalutamide solid dispersion, 40% to 50% microcrystalline cellulose, 10% to 20% microcrystalline cellulose colloidal silicon dioxide, 3% to 7% cross-linked sodium carboxymethyl cellulose, 0.5% to 1.5% colloidal silicon dioxide and 0.2% to 1.0% magnesium stearate.

[0022] In a specific embodiment, the apalutamide solid dispersion tablet comprises, by weight:

[0023] 1680 parts of apalutamide solid dispersion containing apalutamide and HPMCAS in a weight ratio of 1:3.0, 1985.9 parts of microcrystalline cellulose, 794.5 parts of microcrystalline cellulose colloidal silicon dioxide co-processed product, 245.0 parts of croscarmellose sodium, 39.2 parts of colloidal silicon dioxide and 29.4 parts of magnesium stearate;

[0024] or comprising 1806 parts of apalutamide solid dispersion containing apalutamide and HPMCAS in a weight ratio of 1:3.3, 1985.9 parts of microcrystalline cellulose, 794.5 parts of microcrystalline cellulose colloidal silicon dioxide co-processed product, 245.0 parts of croscarmellose sodium, 39.2 parts of colloidal silicon dioxide and 29.4 parts of magnesium stearate;

[0025] or comprising 1890 parts of apalutamide solid dispersion containing apalutamide and HPMCAS in a weight ratio of 1:3.5, 1985.9 parts of microcrystalline cellulose, 794.5 parts of microcrystalline cellulose colloidal silicon dioxide co-processed product, 245.0 parts of croscarmellose sodium, 39.2 parts of colloidal silicon dioxide and 29.4 parts of magnesium stearate;

[0026] The tablets can be prepared by conventional tableting techniques, such as wet granulation, dry granulation, or direct tableting, and may also be coated.

[0027] Advantages of the present invention:

[0028] 1. The existing process uses spray drying to prepare apalutamide solid dispersion. The solid dispersion provided by this method is relatively fluffy and has poor fluidity. It needs to be dry granulated to improve the properties of the particles before mixing with other excipients to complete tableting. The solid dispersion prepared by hot melt extrusion has a solid texture and good fluidity of the particles after crushing. It can be directly mixed and tableted without the need for a granulation process, which can reduce the production process and reduce the production cost. Therefore, hot melt extrusion is used to prepare the solid dispersion.

[0029] When the inventors used the hot melt extrusion method to prepare the solid dispersion, they found that the extruded solid dispersion had high hardness and uneven particle size after crushing, and it was difficult to achieve the particle size of 20 to 50 μm described in the existing process.

[0030] Therefore, the applicant adjusted the amount of HPMCAS and found that the particle size could be controlled within the range of 60 to 90 μm for D90 and 30 to 45 μm for D50 by using a combination of a pin grinder and liquid nitrogen for pulverization.

[0031] 2. Due to the inherent properties of HPMCAS, the solid dispersion after hot melt extrusion is solid and extremely difficult to crush. Liquid nitrogen + hammer crushing, simple needle crushing, and air flow crushing cannot crush to a suitable particle size, which greatly affects the in vitro dissolution and in vivo bioavailability of the preparation. Using liquid nitrogen as a crushing aid and a needle crusher to crush apalutamide solid dispersion can significantly improve production efficiency while ensuring the optimal crushing particle size. At the same time, the material does not heat up during the crushing process, which is a commercially viable crushing method.

[0032] 3. The ratio of raw materials and auxiliary materials in the solid dispersion has a great influence on dissolution. If the ratio of HPMCAS is too low, the transformation of crystalline drugs to amorphous drugs will be incomplete, and dissolution will be incomplete; if the ratio of HPMCAS is too high, the dissolution will be too fast in the early stage and too slow in the later stage, and it will be difficult to obtain an ideal dissolution curve by adjusting the crushing particle size. The present invention limits the ratio of raw materials and auxiliary materials and limits the particle size range to ensure that the dissolution curve is similar to that of commercially available products. DETAILED DESCRIPTION

[0033] To further illustrate the present invention, an apalutamide solid dispersion, a preparation method and applications thereof provided by the present invention are described in detail below in conjunction with examples, but they should not be construed as limiting the scope of protection of the present invention.

[0034] Example 1

[0035] Apalutamide solid dispersion (raw material to excipient ratio 1:3.0)

[0036] 1. Composition: See Table 1:

[0037] Table 1: Prescribing information of apalutamide solid dispersion

[0038] Material Name Prescription amount (g) Weight ratio of apalutamide and HPMCAS Apalutamide 420 1 HPMCAS 1260 3.0 total 1680 /

[0039] 2. Preparation process:

[0040] Preparation of solid dispersion by hot melt extrusion: The prescribed amount of apalutamide and HPMCAS were mixed using a hopper mixer, and then extruded using a twin-screw hot melt extruder. The working conditions were: the maximum working temperature was 170° C., the screw speed was 300 rpm, and an extruded strip was obtained.

[0041] 3. Properties: The extruded strips are transparent amber, indicating the formation of an amorphous solid dispersion.

[0042] Example 2: Apalutamide solid dispersion (raw material to excipient ratio 1:3.3)

[0043] 1. Composition: See Table 2:

[0044] Table 2: Prescribing information of apalutamide solid dispersion

[0045] Material Name Prescription amount (g) Weight ratio of apalutamide and HPMCAS Apalutamide 420 1 HPMCAS 1386 3.3 total 1806 /

[0046] 2. Preparation process:

[0047] Preparation of solid dispersion by hot melt extrusion: The prescribed amount of apalutamide and HPMCAS were mixed using a hopper mixer, and then extruded using a twin-screw hot melt extruder. The working conditions were: maximum working temperature of 175° C., screw speed of 400 rpm, to obtain an extruded strip.

[0048] 3. Properties: The extruded strips are transparent amber, indicating the formation of an amorphous solid dispersion.

[0049] Example 3: Apalutamide solid dispersion (raw material to excipient ratio 1:3.5)

[0050] 1. Composition: See Table 3:

[0051] Table 3: Prescribing information of apalutamide solid dispersion

[0052] Material Name Prescription amount (g) Weight ratio of apalutamide and HPMCAS Apalutamide 420 1 HPMCAS 1470 3.5 total 1890 /

[0053] 2. Preparation process:

[0054] Preparation of solid dispersion by hot melt extrusion: The prescribed amount of apalutamide and HPMCAS were mixed using a hopper mixer, and then extruded using a twin-screw hot melt extruder at an operating temperature of 180° C. and a screw speed of 500 rpm to obtain an extruded strip.

[0055] 3. Properties: The extruded strips are transparent amber, indicating the formation of an amorphous solid dispersion.

[0056] Comparative Example 1: Apalutamide solid dispersion (ratio of raw materials to auxiliary materials 1:2.5)

[0057] 1. Composition: See Table 4:

[0058] Table 4: Prescribing information of apalutamide solid dispersion

[0059] Material Name Prescription amount (g) Weight ratio of apalutamide and HPMCAS Apalutamide 420 1 HPMCAS 1050 2.5 total 1470 /

[0060] 2. Preparation process:

[0061] Preparation of solid dispersion by hot melt extrusion: The prescribed amount of apalutamide and HPMCAS were mixed using a hopper mixer, and then extruded using a twin-screw hot melt extruder at an operating temperature of 175° C. and a screw speed of 500 rpm to obtain an extruded strip.

[0062] 3. Properties: The extruded strips are translucent yellow-white, indicating that the amorphous solid dispersion has not been fully formed.

[0063] Comparative Example 2: Apalutamide solid dispersion (raw material to excipient ratio 1:4)

[0064] 1. Composition: See Table 5:

[0065] Table 5: Prescribing information of apalutamide solid dispersion

[0066] Material Name Prescription amount (g) Weight ratio of apalutamide and HPMCAS Apalutamide 420 1 HPMCAS 1680 4 total 2100 /

[0067] 2. Preparation process:

[0068] Preparation of solid dispersion by hot melt extrusion: The prescribed amount of apalutamide and HPMCAS were mixed using a hopper mixer, and then extruded using a twin-screw hot melt extruder at an operating temperature of 175° C. and a screw speed of 500 rpm to obtain an extruded strip.

[0069] 3. Properties: The extruded strips are transparent amber, indicating the formation of an amorphous solid dispersion.

[0070] Example 4: Pulverization of apalutamide solid dispersion

[0071] The pin mill was started, and when the grinding speed reached 16000 rpm, liquid nitrogen and apalutamide solid dispersion were simultaneously poured into the mill for grinding to obtain ground solid dispersion particles.

[0072] Example 5: Pulverization of apalutamide solid dispersion

[0073] The pin mill was started, and when the grinding speed reached 15000 rpm, liquid nitrogen and apalutamide solid dispersion were simultaneously poured into the mill for grinding to obtain ground solid dispersion particles.

[0074] Example 6: Pulverization of apalutamide solid dispersion

[0075] The pin mill was started, and when the grinding speed reached 14,000 rpm, liquid nitrogen and apalutamide solid dispersion were simultaneously poured into the mill for grinding to obtain ground solid dispersion particles.

[0076] Comparative Example 3: Pulverization of Apalutamide Solid Dispersion

[0077] The same as Example 4, except that liquid nitrogen is not injected. The specific operation method is as follows:

[0078] The pin mill was started, and when the grinding speed reached 16000 rpm, the apalutamide solid dispersion was poured into the mill and ground to obtain ground solid dispersion particles.

[0079] Comparative Example 4: Pulverization of Apalutamide Solid Dispersion

[0080] The same as Example 4, the difference is that a hammer mill is used instead of a pin mill, and the specific operation method is as follows:

[0081] The hammer mill was started, and when the milling speed reached 16000 rpm, the apalutamide solid dispersion and liquid nitrogen were simultaneously poured into the mill for milling to obtain milled solid dispersion particles.

[0082] Comparative Example 5: Pulverization of Apalutamide Solid Dispersion by Airflow Pulverizer

[0083] The air flow mill was started, the crushing pressure was set to 6 bar, and the feed pressure was set to 6.5 bar, and Example 1 was subjected to air flow crushing.

[0084] Comparative Example 6: Granulation of apalutamide solid dispersion

[0085] The granulator was started, the cutter speed was set to 1000 rpm, the screen aperture was set to 0.8 mm, and Example 1 was crushed.

[0086] The crushed particle sizes of the above embodiments and comparative examples were compared. The appearance of comparative example 1 showed that a solid dispersion could not be completely formed, indicating worse physical stability and dissolution performance, and the crushing investigation was no longer carried out; in comparative examples 5 and 6, the particle size after crushing did not decrease compared with that before crushing, and the particle size measurement was no longer carried out.

[0087] 1. Sample:

[0088] In Example 1, the ratio of apalutamide to HPMCAS was 1:3.0, and the pulverization schemes in Examples 4 to 6 and Comparative Examples 3 to 4 were used for processing.

[0089] Similarly, the samples provided in Example 2, Example 3 and Comparative Example 2 were processed using the pulverization schemes in Examples 4 to 6 and Comparative Examples 3 to 4, respectively.

[0090] 2. Crushing batch: 1600g.

[0091] 3. Test results: See Table 6 to Table 9:

[0092] Table 6: Particle size results of solid dispersion particles after crushing in Example 1 (ratio of raw materials to auxiliary materials 1:3.0)

[0093] Crushing method Example 4 Example 5 Example 6 Comparative Example 3 Comparative Example 4 Particle size after crushing D50 30μm 39μm 39μm 93μm 81μm Particle size after crushing D90 61μm 80μm 82μm 220μm 190μm

[0094] Table 7: Particle size results of solid dispersion particles after crushing in Example 2 (ratio of raw materials to auxiliary materials 1:3.3)

[0095] Crushing method Example 4 Example 5 Example 6 Comparative Example 3 Comparative Example 4 Particle size after crushing D50 34μm 42μm 40μm 102μm 99μm Particle size after crushing D90 67μm 84μm 82μm 233μm 210μm

[0096] Table 8: Particle size results of solid dispersion particles after crushing in Example 3 (ratio of raw materials to auxiliary materials 1:3.5)

[0097] Crushing method Example 4 Example 5 Example 6 Comparative Example 3 Comparative Example 4 Particle size after crushing D50 35μm 42μm 43μm 162μm 144μm Particle size after crushing D90 69μm 87μm 87μm 274μm 254μm

[0098] Table 9: Particle size results of solid dispersion after crushing in Comparative Example 2 (ratio of raw materials to auxiliary materials 1:4)

[0099] Crushing method Example 4 Example 5 Example 6 Comparative Example 3 Comparative Example 4 Particle size after crushing D50 37μm 44μm 44μm 208μm 153μm Particle size after crushing D90 70μm 85μm 89μm 282μm 277μm

[0100] The results in Tables 7 to 9 show that: when the method of Examples 4 to 6 is used for pulverization, the particle size D90 is 61 to 89 μm and the D50 is 30 to 44 μm; when the pulverization method of Comparative Example 3 (without adding liquid nitrogen) is used, the particle size range is: D90 is 220 to 282 μm, and D50 is 93 to 162 μm; when the pulverization method of Comparative Example 4 (a combination of hammer pulverization and liquid nitrogen) is used, the particle size range is: D90 is 190 to 277 μm, and D50 is 81 to 153 μm.

[0101] The results showed that the hot-melt extrudates of apalutamide and HPMCAS had a high hardness, and the conventional pulverization method had a poor effect. The pulverization ability of the combination of pin mill + liquid nitrogen was significantly better than that of liquid nitrogen + hammer mill or pin mill alone, and the particle size of the pulverized particles was controlled at D90 of 61-89 μm and D50 of 30-44 μm.

[0102] Examples 7 to 15, Comparative Examples 5 to 15: Preparation of Tablets Containing Apalutamide Solid Dispersion Granules

[0103] 1. Composition: See Tables 10 to 13

[0104] Table 10: Tablets containing apalutamide and HPMCAS solid dispersion in a weight ratio of 1:3.0

[0105]

[0106] Table 11: Tablets containing apalutamide and HPMCAS solid dispersion in a weight ratio of 1:3.3

[0107]

[0108] Table 12: Tablets containing apalutamide and HPMCAS solid dispersion in a weight ratio of 1:3.5

[0109]

[0110]

[0111] Table 13: Tablets containing apalutamide and HPMCAS solid dispersion in a weight ratio of 1:4

[0112]

[0113] 2. Preparation process:

[0114] Solid dispersion particles, microcrystalline cellulose, microcrystalline cellulose colloidal silicon dioxide co-processed product, cross-linked sodium carboxymethyl cellulose, colloidal silicon dioxide and magnesium stearate were weighed according to the proportions and placed in a hopper mixer for mixing for 10 minutes.

[0115] Use a rotary tablet press to press tablets at a speed of 40,000 tablets per hour, and control the tablet hardness at 20 to 30 kg.

[0116] Dissolution curve test:

[0117] 1. Sample: Commercially available Examples 7-15 and Comparative Examples 5-15.

[0118] 2. Detection method

[0119] The dissolution and release rate were determined according to the dissolution and release rate determination method (Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0931 Method 2). The key medium dissolution conditions are shown in Table 14.

[0120] Table 14: Dissolution curve determination method

[0121] Dissolution medium Dissolution conditions Speed Inspection time (min) pH 4.5 + 0.2% SDS 37℃, paddle method 75r / min 5、10、15、30、45、60

[0122] 3. Test results: see Tables 15 to 18

[0123] Table 15: Dissolution curve measurement data (weight ratio of apalutamide and HPMCAS 1:3.0)

[0124]

[0125] Table 16: Dissolution curve measurement data (weight ratio of apalutamide and HPMCAS 1:3.3)

[0126]

[0127] Table 17: Dissolution curve measurement data (weight ratio of apalutamide and HPMCAS 1:3.5)

[0128]

[0129] Table 18: Dissolution curve measurement data (weight ratio of apalutamide and HPMCAS 1:4)

[0130]

[0131] Results: The dissolution rates of Examples 7 to 15 (D90 particle size of the solid dispersion is 61 to 87 μm, and D50 particle size is 30 to 43 μm) in pH 4.5 + 0.2% SDS for 60 min were all above 90%, and the dissolution curves were highly similar to those of the commercially available products, indicating a relatively close in vivo absorption rate and degree. Among them, the dissolution values ​​of Examples 8 to 9, Examples 11 to 12, and Examples 14 to 15 (D90 particle size of the solid dispersion is 80 to 87 μm, and D50 particle size is 30 to 43 μm) at 5 min and 10 min were closer to those of the commercially available products, indicating a closer in vivo performance of the drug.

[0132] Compared with the commercially available products, the dissolution rates of Comparative Examples 5 to 10 and Comparative Examples 14 to 15 are significantly lower, with only about 30% dissolved in 60 minutes. The initial dissolution rates of Comparative Examples 11 to 13 are relatively fast.

[0133] Analysis results: Compared with commercially available preparations, Comparative Examples 5 to 10 were pulverized by conventional pulverization methods, and the particle size after pulverization was larger, the drug dissolution rate was slow, and the end point dissolution was incomplete. Comparative Examples 11 to 13 also used needle-type + liquid nitrogen combination pulverization, but due to the high proportion of HPMCAS, the late rate was relatively slow, indicating that the absorption speed and degree in the body were significantly different from those of commercial products.

[0134] Conclusion: By adjusting the dosage of apalutamide and HPMCAS (the ratio of apalutamide to hydroxypropylmethylcellulose acetate succinate is 1:3.0-3.5), and then using a pin grinder + liquid nitrogen combination to crush the solid dispersion to a reasonable particle size range (average particle size D50 between 30 and 45 μm, D90 between 60 and 90 μm), a more ideal dissolution effect can be obtained.

[0135] As can be seen from the above embodiments, the present invention provides an apalutamide solid dispersion, comprising apalutamide and hydroxypropyl methylcellulose acetate succinate (HPMCAS) in a mass ratio of 1:3.0 to 3.5; the D90 particle size of the solid dispersion is 60 to 90 μm, and the D50 particle size is 30 to 45 μm. The dispersion is adjusted by adjusting the ratio of apalutamide to HPMCAS and selecting a suitable particle size range to obtain a preparation with better dissolution. The experimental results show that: Results: Examples 7 to 15 (the D90 particle size of the solid dispersion is 61 to 87 μm, and the D50 particle size is 30 to 43 μm) have a 60 min dissolution rate of more than 90% in pH 4.5 + 0.2% SDS, and the dissolution curve is highly similar to the commercially available product, indicating a relatively close in vivo absorption rate and degree. Among them, the dissolution values ​​of Examples 8-9, Examples 11-12, and Examples 14-15 (D90 particle size of the solid dispersion is 80-87 μm, and D50 particle size is 30-43 μm) at 5 min and 10 min are closer to those of the commercially available products, indicating that the drug has a closer in vivo performance.

[0136] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. An apalutamide solid dispersion, comprising apalutamide and hypromellose acetate succinate in a mass ratio of 1:3.0 to 3.5; The D90 particle size of the solid dispersion is 60 to 90 μm, and the D50 particle size is 30 to 45 μm.

2. The apalutamide solid dispersion according to claim 1, characterized in that The mass ratio of apalutamide to hypromellose acetate succinate is 1:3.3-3.

5.

3. The apalutamide solid dispersion according to claim 1, characterized in that: The D90 particle size of the solid dispersion is 61-87 μm, and the D50 particle size is 30-43 μm.

4. A method for preparing the apalutamide solid dispersion according to any one of claims 1 to 3, comprising the following steps: Apalutamide and hydroxypropyl methylcellulose acetate succinate are mixed, hot-melt extruded, and then needle-milled using liquid nitrogen as a milling aid to obtain apalutamide solid dispersion.

5. The preparation method according to claim 4, characterized in that: The temperature of hot melt extrusion is 170-180°C; the screw speed used in hot melt extrusion is 300-500rpm.

6. The preparation method according to claim 4, characterized in that: The rotation speed of the needle crusher is 14000-16000 rpm.

7. A preparation containing apalutamide solid dispersion, comprising the apalutamide solid dispersion according to any one of claims 1 to 3 and a pharmaceutically acceptable excipient.

8. The preparation containing apalutamide solid dispersion according to claim 7, characterized in that: The preparation is a tablet; The tablet comprises the following components by mass fraction: 30% to 40% apalutamide solid dispersion, 40% to 50% microcrystalline cellulose, 10% to 20% microcrystalline cellulose colloidal silicon dioxide, 3% to 7% cross-linked sodium carboxymethyl cellulose, 0.5% to 1.5% colloidal silicon dioxide and 0.2% to 1.0% magnesium stearate.

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