Pharmaceutical composition and preparation method thereof

Abstract

The invention discloses a pharmaceutical composition and a preparation method thereof. The invention provides a pharmaceutical composition which comprises the following components in percentage by mass: 1-4% of tibolone, 1-9% of povidone, 3-30% of microcrystalline cellulose, 60-86.8% of lactose, 0.1-0.3% of a stabilizer and 0.2-1% of a lubricant. The tibolone tablet prepared from the pharmaceutical composition disclosed by the invention can be stable without being coated. The tibolone tablet prepared by the preparation method disclosed by the invention is better in stability.

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition and a preparation method thereof. Background Art

[0002] Tibolone is mainly used to treat various symptoms caused by the decrease of estrogen after natural and surgical menopause, such as hot flashes, mood changes, night sweats, sleep disorders, dizziness, tingling, muscle, joint and bone pain, etc.

[0003] It has been reported in the literature that during the long-term storage of tibolone tablets, the main degradation product (7a, 17a)-17-hydroxy-7-methyl-19-norprogesterone-4-ene-20-ene-3-one (Org OM-38) will gradually increase, and the maximum content of OM-38 is 5%. Through the test of the influencing factors of tibolone-containing tablets, it was found that tibolone is very easy to degrade into OM-38 under high temperature, light, and acidic and alkaline environments. Therefore, it is necessary to find a way to reduce the formation of OM-38 to obtain a better storage period.

[0004] The original research enterprise disclosed in patent application number 200380103690.3 that product stability can be improved by coating, but coating increases production hours and has high requirements on appearance, which is not conducive to commercial production. Summary of the invention

[0005] In view of the difficulties or shortcomings of the prior art, the present invention provides a pharmaceutical composition and a preparation method thereof. The Tibolone tablets prepared by the pharmaceutical composition of the present invention are stable without coating. The Tibolone tablets prepared by the preparation method of the present invention have better stability.

[0006] The invention provides a pharmaceutical composition, which comprises the following components, measured by mass percentage: 1-4% of tibolone, 1-9% of povidone, 3-30% of microcrystalline cellulose, 60-86.8% of lactose, 0.1-0.3% of a stabilizer and 0.2-1% of a lubricant.

[0007] In certain preferred embodiments of the present invention, the components in the pharmaceutical composition are defined as follows, and components not mentioned are the same as those described in any scheme of the present invention (referred to as "a certain scheme").

[0008] In one embodiment, the pharmaceutical composition is composed of the following raw materials, calculated by mass percentage: 1-4% tibolone, 1-9% povidone, 3-30% microcrystalline cellulose, 60-86.8% lactose, 0.1-0.3% stabilizer and 0.2-1% lubricant.

[0009] In a certain embodiment, the content of tibolone may be 1%-4% by weight of the pharmaceutical composition, for example 2.5%.

[0010] In one embodiment, the povidone may be povidone K25 or povidone K90, for example, povidone K25.

[0011] In a certain embodiment, the content of the povidone may be 1-9% by weight of the pharmaceutical composition, such as 3% or 7%.

[0012] In one embodiment, the microcrystalline cellulose is selected from Avicel ® PH101, Avicel ® PH102, Avicel ® PH301, Avicel ® UF702, Avicel ® UF711, Avicel ® KG802 and Avicel ® One or more of KG1000, such as Avicel ® PH101.

[0013] In a certain embodiment, the content of the microcrystalline cellulose may be 3-30% by weight of the pharmaceutical composition, preferably, for example, 25%.

[0014] In a certain embodiment, the lactose is selected from one or more of ground lactose 80 mesh, ground lactose 120 mesh, ground lactose 200 mesh and spray-dried lactose, for example, ground lactose 200 mesh.

[0015] In a certain embodiment, the lactose content may be 60-86.8% by weight of the pharmaceutical composition, preferably, for example, 68.8%.

[0016] In one embodiment, the stabilizer can be ascorbyl palmitate or ascorbyl stearate, such as ascorbyl palmitate.

[0017] In a certain embodiment, the content of the stabilizer may be 0.1-0.3% by weight of the pharmaceutical composition, for example 0.2%.

[0018] In a certain embodiment, the lubricant can be stearate, glyceryl monostearate or talc, such as magnesium stearate.

[0019] In one embodiment, the content of the lubricant may be 0.2-1.0% by weight of the pharmaceutical composition, for example 0.5%.

[0020] In one embodiment, the pharmaceutical composition is composed of 2.5% Tibolone, 3% Povidone K25, 25% Avicel ® PH101, 68.8% ground lactose 200 mesh, 0.2% ascorbyl palmitate and 0.5% magnesium stearate.

[0021] In one embodiment, the pharmaceutical composition is composed of 2.5% Tibolone, 3% Povidone K25, 25% Avicel ® PH101, 68.8% ground lactose 200 mesh, 0.2% ascorbyl palmitate and 0.5% magnesium stearate.

[0022] In one embodiment, the pharmaceutical composition is composed of 2.5% Tibolone, 7% Povidone K25, 21% Avicel ® PH101, 68.8% ground lactose 200 mesh, 0.2% ascorbyl palmitate and 0.5% magnesium stearate.

[0023] In one embodiment, the pharmaceutical composition is composed of 2.5% Tibolone, 3% Povidone K90, 25% Avicel ® PH101, 68.8% ground lactose 200 mesh, 0.2% ascorbyl palmitate and 0.5% magnesium stearate.

[0024] In one embodiment, the pharmaceutical composition may be a Tibolone tablet without coating;

[0025] In a second aspect, the present invention further provides a Tibolone tablet, wherein the contents and definitions of the components of the Tibolone tablet are as described in the aforementioned pharmaceutical composition.

[0026] In one embodiment, the tibolone tablet does not contain a coating.

[0027] The present invention also provides a method for preparing the tibolone tablets as described above, comprising the following steps:

[0028] S1: the filler and the aqueous solution of povidone are granulated in a fluidized bed; the humidity is controlled during the granulation process; the humidity is 1g / kg-15g / kg;

[0029] S2: drying and granulating after the granulation to obtain dry granules;

[0030] S3: stirring tibolone, a stabilizer and dry particles; mixing with a lubricant after stirring, and tableting to obtain the tibolone tablets;

[0031] The filler, the povidone, the stabilizer and the lubricant are defined as above.

[0032] In a certain embodiment, the polyvidone aqueous solution comprises the polyvidone and the water.

[0033] In one embodiment, the concentration of the polyvidone aqueous solution may be 5-15%, for example 10%.

[0034] In one embodiment, the aqueous solution of povidone is atomized and then sprayed into a fluidized bed for granulation.

[0035] In one embodiment, the peristaltic pump of the fluidized bed can rotate at a speed of 15-25 rpm, for example, 20 rpm.

[0036] In one embodiment, the atomization pressure of the atomization may be 1-3 bar, for example 2 bar.

[0037] In one embodiment, the drying air volume can be 1000~2000m 3 / h, 1500m 3 / h.

[0038] In one embodiment, the drying air inlet temperature may be 60-80°C, 70°C.

[0039] In one embodiment, the drying is stopped until the material temperature reaches 35-45°C, for example 40°C.

[0040] In a certain embodiment, the tabletting die may be a 6 mm round punch.

[0041] In one embodiment, the tabletting pressure may be 30-60N, for example 50N.

[0042] In a certain embodiment, the preparation method of the Tibolone tablets comprises the following steps:

[0043] S1: Grind 200 mesh lactose, Avicel® PH101 and 10% povidone K25 aqueous solution in a fluidized bed for granulation;

[0044] The humidity was controlled at 15 g / kg during granulation;

[0045] The polyvidone aqueous solution is atomized and sprayed into a fluidized bed for granulation;

[0046] The povidone is povidone K25;

[0047] The peristaltic pump speed of the fluidized bed is 20 rpm; the atomization pressure of the atomization is 2 bar;

[0048] S2: drying and granulating after the granulation to obtain dry granules;

[0049] The drying air volume is 1500m 3 / h;

[0050] The drying air inlet temperature is 70°C;

[0051] The drying is stopped until the material temperature reaches 40°C;

[0052] The sieve for granulation is 1 mm sieve;

[0053] The moisture content of the whole grain is ≤4%;

[0054] The granulation rate is 8.4 kg / h;

[0055] S3: stirring tibolone, ascorbyl palmitate and the dry particles for 10 min;

[0056] Then add magnesium stearate, mix for 10 minutes, and compress into tablets;

[0057] The tabletting die is a 6 mm round punch; the tabletting pressure is 50 N;

[0058] The tibolone tablets are obtained.

[0059] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0060] The preparation method provided by the present invention can significantly reduce the impurity level of OM-38, and the in vitro dissolution is consistent with that of the reference preparation. There is no need to increase the product stability through an additional coating process, which is more conducive to the commercial production of the product. DETAILED DESCRIPTION

[0061] The present invention is further described below by the methods of the examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are selected according to conventional methods and conditions, or according to the product specifications.

[0062] The raw and auxiliary materials used in each example are as follows:

[0063]

[0064] The mass fractions of the components of the Tibolone tablets in the following Examples 1-6 are as follows:

[0065]

[0066] The remaining materials are commercially available

[0067] Embodiment 1:

[0068] The fluidized bed granulation parameters of the present invention are as follows:

[0069]

[0070] The process is as follows:

[0071] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K25 and pure water into a slurry with a concentration of 10%, spray the atomized slurry into the fluidized bed for granulation, add a humidifier to the air handling unit of the fluidized bed to ensure that the humidity is within the range of 1g / kg during the granulation process, and dry it after the granulation is completed (the air volume is 1500m 3 / h, the inlet air temperature is 70℃. Drying under this parameter until the material temperature reaches 40℃ and then stop), 1mm sieve granulation, control the moisture ≤4%, granulation amount is 8.4kg / h, and granulation is completed in one hour.

[0072] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0073] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0074] (4) Tableting: 6 mm round punch, press 50 N.

[0075] Embodiment 2:

[0076] The fluidized bed granulation parameters of the present invention are as follows:

[0077]

[0078] The process is as follows:

[0079] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K25 and pure water into a slurry with a concentration of 10%, spray the atomized slurry into the fluidized bed for granulation, and dry it after granulation (the air volume is 1500m 3 / h, the inlet air temperature is 70℃. Drying under this parameter until the material temperature reaches 40℃ and then stop. ), 1mm sieve granulation, control the moisture ≤4%, granulation amount is 8.4kg / h, and granulation is completed in one hour.

[0080] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0081] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0082] (4) Tableting: 6 mm round punch, press 50 N.

[0083] Embodiment 3:

[0084] The fluidized bed granulation parameters of the present invention are as follows:

[0085]

[0086] The process is as follows:

[0087] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K25 and pure water into a slurry with a concentration of 10%, spray the atomized slurry into the fluidized bed for granulation, and dry it after granulation (the air volume is 1500m 3 / h, the inlet air temperature is 70℃. Drying under this parameter until the material temperature reaches 40℃ and then stop. ), 1mm sieve granulation, control the moisture ≤4%, granulation amount is 8.4kg / h, and granulation is completed in one hour.

[0088] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0089] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0090] (4) Tableting: 6 mm round punch, press 50 N.

[0091] Embodiment 4:

[0092] The fluidized bed granulation parameters of the present invention are as follows:

[0093]

[0094] The process is as follows:

[0095] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K25 and pure water into a slurry with a concentration of 10%, spray the atomized slurry into the fluidized bed for granulation, and dry it after granulation (the air volume is 2000m 3 / h, the inlet air temperature is 70℃. Drying under this parameter until the material temperature reaches 40℃ and then stop. ), 1mm sieve granulation, control the moisture ≤4%, granulation amount is 8.4kg / h, and granulation is completed in one hour.

[0096] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0097] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0098] (4) Tableting: 6 mm round punch, press 50 N.

[0099] Embodiment 5:

[0100] The fluidized bed granulation parameters of the present invention are as follows:

[0101]

[0102] The process is as follows:

[0103] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K25 and pure water into a slurry with a concentration of 10%, spray the atomized slurry into the fluidized bed for granulation, and dry it after granulation (the air volume is 2000m 3 / h, the inlet air temperature is 70℃. Drying under this parameter until the material temperature reaches 40℃ and then stop. ), 1mm sieve granulation, control the moisture ≤4%, granulation amount is 8.4kg / h, and granulation is completed in one hour.

[0104] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0105] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0106] (4) Tableting: 6 mm round punch, press 50 N.

[0107] Embodiment 6:

[0108] The fluidized bed granulation parameters of the present invention are as follows:

[0109]

[0110] The process is as follows:

[0111] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K25 and pure water into a slurry with a concentration of 10%, spray the atomized slurry into the fluidized bed for granulation, and dry it after granulation (the air volume is 2000m 3 / h, the inlet air temperature is 70℃. Drying under this parameter until the material temperature reaches 40℃ and then stop. ), 1mm sieve granulation, control the moisture ≤4%, granulation amount is 8.4kg / h, and granulation is completed in one hour.

[0112] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0113] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0114] (4) Tableting: 6 mm round punch, press 50 N.

[0115] Embodiment 7:

[0116] The raw materials of Example 7 are as follows:

[0117]

[0118] The process is as follows:

[0119] Fluidized bed granulation parameters:

[0120]

[0121] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K25 into a 10% slurry and then spray it into the granulator. After granulation, dry it and sieve it with a 1mm mesh to control the moisture content to ≤4%.

[0122] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0123] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0124] (4) Tableting: 6 mm round punch, press 50 N.

[0125] Embodiment 8:

[0126] The raw materials of Example 8 are as follows:

[0127]

[0128] The process is as follows:

[0129] Fluidized bed granulation parameters:

[0130]

[0131] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K90 into a 10% slurry and then spray it into the granulation. After the granulation is completed, dry it and sieve it with a 1mm mesh to control the moisture content to ≤4%.

[0132] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0133] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0134] (4) Tableting: 6 mm round punch, press 50 N.

[0135] Comparative Example 1:

[0136] According to the following raw materials, the process of Example 6 was prepared

[0137] The raw and auxiliary materials of Comparative Example 1 are composed as follows

[0138]

[0139] The process is as follows:

[0140] Fluidized bed granulation parameters:

[0141]

[0142] (1): 86.8 parts of lactose and 7 parts of potato starch were added to the fluidized bed. 3 parts of potato starch was slurried and sprayed into the granulation. After the granulation was completed, it was dried and sieved with a 1mm sieve to control the moisture content to ≤4%.

[0143] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with 2.5 parts of tibolone and 0.2 parts of ascorbyl palmitate for 10 minutes.

[0144] (3) Mixing 2: Add 0.5 parts of magnesium stearate and mix for 10 minutes.

[0145] (4) Tableting: 6 mm round punch, press 50 N.

[0146] Comparative Example 2:

[0147] The raw material composition of Comparative Example 2 is as follows

[0148]

[0149] The process is as follows:

[0150] Fluidized bed granulation parameters:

[0151]

[0152] (1): Add lactose to the fluidized bed, prepare povidone K25 into a 10% slurry and then spray it into the granulator. After granulation, dry it and sieve it with a 1mm mesh to control the moisture content to ≤4%.

[0153] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0154] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0155] (4) Tableting: 6 mm round punch, press 50 N.

[0156] Comparative Example 3:

[0157] The raw material composition of Comparative Example 3 is as follows

[0158]

[0159] The process is as follows:

[0160] Fluidized bed granulation parameters:

[0161]

[0162] (1): Add lactose to the fluidized bed, prepare povidone K90 into a 10% slurry and then spray it into the granulator. After granulation, dry it and sieve it with a 1mm mesh to control the moisture content to ≤4%.

[0163] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0164] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0165] (4) Tableting: 6 mm round punch, press 50 N.

[0166] Comparative Example 4:

[0167] The raw and auxiliary materials of Comparative Example 4 are composed as follows

[0168]

[0169] The process is as follows:

[0170] Fluidized bed granulation parameters:

[0171]

[0172] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K25 into a 10% slurry and then spray it into the granulator. After granulation, dry it and sieve it with a 1mm mesh to control the moisture content to ≤4%.

[0173] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0174] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0175] (4) Tableting: 6 mm round punch, press 50 N.

[0176] Comparative Example 5:

[0177] The raw material composition of Comparative Example 5 is as follows

[0178]

[0179] The process is as follows:

[0180] Fluidized bed granulation parameters:

[0181]

[0182] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K25 into a 10% slurry and then spray it into the granulator. After granulation, dry it and sieve it with a 1mm mesh to control the moisture content to ≤4%.

[0183] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0184] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0185] (4) Tableting: 6 mm round punch, press 50 N.

[0186] Comparative Example 6:

[0187] The raw and auxiliary materials of Comparative Example 6 are composed as follows

[0188]

[0189] The process is as follows:

[0190] Fluidized bed granulation parameters:

[0191]

[0192] (1): Add lactose and microcrystalline cellulose to the fluidized bed, prepare povidone K90 into a 10% slurry and then spray it into the granulation. After the granulation is completed, dry it and sieve it with a 1mm mesh to control the moisture content to ≤4%.

[0193] (2) Mixing 1: The dry granules prepared in the fluidized bed were mixed with tibolone and ascorbyl palmitate for 10 min.

[0194] (3) Mixing 2: Add magnesium stearate and mix for 10 minutes.

[0195] (4) Tableting: 6 mm round punch, press 50 N.

[0196] The tibolone tablets prepared in Examples 1 to 8 and Comparative Examples 1 to 6 were compared in vitro with a reference preparation (batch number: W011003, manufacturer: NV Organon) (reference reagents mainly include: tibolone, lactose, potato starch, ascorbyl palmitate, magnesium stearate). The in vitro dissolution method is the Chinese Pharmacopoeia dissolution test method, paddle method, medium: 500 ml of water medium, rotation speed of 50 rpm.

[0197] The dissolution results are as follows:

[0198]

[0199]

[0200] Comparative Example 1: Samples were prepared according to the reference preparation formula. Similarity factors f 2Small, not similar or basically similar to the reference preparation; the curves of Examples 1 to 8 are similar to the reference preparation, among which Examples 1 to 6 are more similar; and therefore, related substances are detected in Comparative Example 1 and Examples 1 to 6.

[0201] The stability results are compared as follows (temperature: 40°C, humidity: 75%)

[0202] Comparing the contents of related substances in Examples 1 to 6 in October: In October, the total impurities in Examples 3 and 6 were the smallest, indicating that when the humidity was set to 15 g / kg, the content of impurity OM-38 could be significantly reduced and the product stability could be improved.

[0203] Comparison of the contents of related substances in Example 6 and Comparative Example 1 shows that, under the same process, the use of the materials of Example 6 can improve the stability of the product.

[0204] Comparing the growth rates of related substances in various embodiments within 3 months, under different processes, the growth rates of related substances in various embodiments are basically the same. Therefore, the stability can be improved by controlling the initial impurity content in 0 month.

[0205]

[0206]

[0207] The effects of Examples 3 and 6 of the present invention are the best, the in vitro dissolution curves are basically consistent with the reference preparation curves, and the contents of related substances at 0 months are low, and the product stability is good.

Claims

1. A pharmaceutical composition, characterized in that The invention comprises the following components: by mass percentage, 1-4% of tibolone, 1-9% of povidone, 3-30% of microcrystalline cellulose, 60-86.8% of lactose, 0.1-0.3% of a stabilizer and 0.2-1% of a lubricant.

2. The pharmaceutical composition according to claim 1, characterized in that The raw materials are composed of the following components: by mass percentage, 1-4% of tibolone, 1-9% of povidone, 3-30% of microcrystalline cellulose, 60-86.8% of lactose, 0.1-0.3% of stabilizer and 0.2-1% of lubricant.

3. The pharmaceutical composition according to claim 1, characterized in that It meets one or more of the following conditions: (1) The tibolone is 1-4% by weight of the pharmaceutical composition, for example 2.5%; (2) The povidone is povidone K25 or povidone K90, for example, povidone K25; (3) The content of the povidone is 1-9% by weight of the pharmaceutical composition, such as 3% or 7%, and further such as 3%; (4) The microcrystalline cellulose is Avicel ® PH101, Avicel ® PH102, Avicel ® PH301, Avicel ® UF702, Avicel ® UF711, Avicel ® KG802 and Avicel ® One or more of KG1000, such as Avicel ® PH101; (5) The content of the microcrystalline cellulose is 3-30% by weight of the pharmaceutical composition, for example 25%; (6) The lactose is one or more of ground lactose 80 mesh, ground lactose 120 mesh, ground lactose 200 mesh and spray-dried lactose, for example, ground lactose 200 mesh; (7) The lactose content is 60-86.8% by weight of the pharmaceutical composition, for example 68.8%; (8) The stabilizer is ascorbyl palmitate or ascorbyl stearate, for example ascorbyl palmitate; (9) The content of the stabilizer is 0.1-0.3% by weight of the pharmaceutical composition, for example 0.2%; (10) The lubricant is stearate, glyceryl monostearate or talc, such as magnesium stearate; (11) The content of the lubricant is 0.2-1.0% by weight of the pharmaceutical composition, for example 0.5%; (12) The pharmaceutical composition is a non-coated tibolone tablet.

4. The pharmaceutical composition according to claim 3, characterized in that The pharmaceutical composition is composed of 2.5% Tibolone, 3% Povidone K25, 25% Avicel ® PH101, 68.8% ground lactose 200 mesh, 0.2% ascorbyl palmitate and 0.5% magnesium stearate.

5. The pharmaceutical composition according to claim 3, characterized in that The pharmaceutical composition is any of the following combinations: Combination 1: The pharmaceutical composition is composed of 2.5% Tibolone, 3% Povidone K25, 25% Avicel ® PH101, 68.8% ground lactose 200 mesh, 0.2% ascorbyl palmitate, and 0.5% magnesium stearate; Combination 2: The pharmaceutical composition is composed of 2.5% Tibolone, 7% Povidone K25, 21% Avicel ® PH101, 68.8% ground lactose 200 mesh, 0.2% ascorbyl palmitate, and 0.5% magnesium stearate; Combination 3: In terms of mass percentage, the pharmaceutical composition is composed of 2.5% Tibolone, 3% Povidone K90, 25% Avicel ® PH101, 68.8% ground lactose 200 mesh, 0.2% ascorbyl palmitate and 0.5% magnesium stearate.

6. A Tibolone tablet, characterized in that: The contents and definitions of the components of the tibolone tablets are the same as those of the pharmaceutical composition according to any one of claims 1 to 5.

7. The Tibolone tablet according to claim 6, characterized in that: The tibolone tablets do not contain a coating.

8. A method for preparing the Tibolone tablets as claimed in claim 6 or 7, characterized in that: It includes the following steps: S1: the filler and the aqueous solution of povidone are granulated in a fluidized bed; the humidity is controlled during the granulation process; the humidity is 1g / kg-15g / kg; S2: drying and granulating after the granulation to obtain dry granules; S3: mixing tibolone, a stabilizer and the dry particles; adding a lubricant and tableting to obtain the tibolone tablets; The filler, the povidone, the stabilizer and the lubricant are defined as the pharmaceutical composition according to any one of claims 1 to 5.

9. The method for preparing Tibolone tablets according to claim 8, characterized in that: It meets one or more of the following conditions: (1) The polyvidone aqueous solution comprises the polyvidone and the water; (2) The concentration of the povidone aqueous solution is 5-15%, for example, 10%; (3) the polyvidone aqueous solution is atomized and sprayed into a fluidized bed for granulation; (4) The peristaltic pump speed of the fluidized bed is 15-25 rpm, for example, 20 rpm; (5) The atomization pressure of the atomization is 1 to 3 bar, for example, 2 bar; (6) The air volume of the drying air is 1000~2000m 3 / h, 1500m 3 / h; (7) The inlet air temperature of the drying is 60~80℃, 70℃; (8) Drying is stopped until the material temperature reaches 35-45°C, for example, 40°C; (9) The tabletting die is a 6 mm round die; (10) The tabletting pressure is 30-60N, for example 50N.

10. The method for preparing Tibolone tablets according to claim 9, characterized in that: It consists of the following steps: S1: Grind 200 mesh lactose, Avicel® PH101 and 10% povidone aqueous solution in a fluidized bed for granulation; during the granulation process, the humidity is controlled to be 15 g / kg; the povidone aqueous solution is atomized and sprayed into the fluidized bed for granulation; the povidone is povidone K25; the peristaltic pump speed of the fluidized bed is 20 rpm; the atomization pressure of the atomization is 2 bar; S2: drying and granulating after the granulation to obtain dry granules; The drying air volume is 1500m 3 / h; The drying air inlet temperature is 70°C; The drying is stopped until the material temperature reaches 40°C; The sieve for granulation is 1 mm sieve; The moisture content of the whole grain is ≤4%; The granulation rate is 8.4 kg / h; S3: stirring tibolone, ascorbyl palmitate and the dry particles for 10 min; Then add magnesium stearate, mix for 10 minutes, and compress into tablets; The tabletting die is a 6 mm round punch; the tabletting pressure is 50 N; The tibolone tablets are obtained.

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