Didrogesterone tablet and preparation process thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and particularly discloses a didrogesterone tablet and a preparation process thereof. The invention relates to a didrogesterone tablet, which is prepared from the following raw materials in parts by weight: 7 to 10 parts of didrogesterone, 30 to 40 parts of filling agent, 12 to 18 parts of lecithin, 3 to 5 parts of amphiphilic block copolymer, 0.2 to 0.8 part of adhesive and 0.1 to 0.5 part of lubricating agent. The didrogesterone tablet provided by the invention has small irritation to gastrointestinal tracts when being taken, can be taken before meals, is not easy to cause gastrointestinal reactions such as nausea, vomiting and abdominal pain, and has a good curative effect.

Description

Technical Field

[0001] The present application relates to the technical field of pharmaceutical preparations, and more specifically, to a dydrogesterone tablet and a preparation process thereof. Background Art

[0002] Dydrogesterone tablets are a progestin drug that is mainly used to treat various gynecological diseases caused by endogenous progesterone deficiency, including endometriosis, dysfunctional uterine bleeding, dysmenorrhea, habitual abortion, premenstrual syndrome, secondary amenorrhea, and threatened abortion caused by progesterone deficiency.

[0003] As a commonly used traditional luteal support drug, dydrogesterone can be administered through multiple routes such as intramuscular injection, vaginal administration, and oral administration. Among them, oral preparations are highly favored in the market due to their good patient acceptance and low-dose administration. The two mainstream dydrogesterone products on the market are single dydrogesterone tablets (Daphaston) and compound estradiol tablets / estradiol dydrogesterone tablets (Fentaton). The sales of these two products in the global and Chinese markets continue to grow, showing the huge market demand and development space for dydrogesterone drugs.

[0004] In view of the above-mentioned related technologies, the inventors found that although dydrogesterone has many advantages, it still has some side effects, especially the irritation to the gastric mucosa which cannot be ignored. Patients who take dydrogesterone tablets for a long time may suffer from gastric ulcer and duodenal ulcer due to dydrogesterone inhibiting gastric mucus secretion and increasing gastric acid production.

[0005] For patients with good gastrointestinal function, it is usually recommended that patients take dydrogesterone tablets before meals, which can not only promote the absorption of dydrogesterone, but also help to effectively exert the efficacy of the drug. However, for some patients with poor gastrointestinal function, taking dydrogesterone tablets before meals will cause gastrointestinal reactions such as nausea, vomiting, and abdominal pain. This is due to the drug inhibiting gastrointestinal motility or irritating the gastrointestinal tract. Therefore, it can only be taken about half an hour after a meal to reduce the irritation of the patient's gastrointestinal tract by dydrogesterone tablets. However, compared with taking it before meals, taking it after meals can reduce the irritation of the patient's gastrointestinal tract by dydrogesterone tablets to a certain extent, but due to the influence of food, the bioavailability of dydrogesterone tablets will be relatively reduced. Summary of the invention

[0006] In order to reduce the irritation of dydrogesterone tablets to the gastrointestinal tract and improve the efficacy of dydrogesterone tablets, the present application provides a dydrogesterone tablet and a preparation process thereof.

[0007] In the first aspect, the present application provides a dydrogesterone tablet, which adopts the following technical solution: A dydrogesterone tablet comprises, by weight percentage, 10% dydrogesterone, 60-65% filler, 19-23% lecithin, 5.1-6.7% amphiphilic block copolymer, 0.2-0.8% adhesive and 0.1-0.5% lubricant.

[0008] The inventors found that dydrogesterone is almost insoluble in water, while lecithin and the amphiphilic block copolymer are both amphiphilic active substances. Due to the hydrophobic nature of dydrogesterone, it can aggregate with the hydrophobic ends of lecithin and the amphiphilic block copolymer through hydrophobic interaction.

[0009] When dispersed in the aqueous phase, the hydrophobic tails of lecithin tend to aggregate together to form a tail-to-tail structure to avoid the aqueous phase, and the hydrophilic head is exposed in the aqueous phase to form a head-to-head structure. This aggregation mode forms a hollow vesicle with a bimolecular lipid layer structure. Similarly, amphiphilic copolymers self-assemble in the aqueous phase to form micelles with a core-shell structure, in which the hydrophobic part forms the core and the hydrophilic part forms the shell. The combination of lecithin and amphiphilic block copolymers can form a mixed liposome structure drug carrier with a hollow core in the aqueous phase, and the hydrophobic drug dydrogesterone is loaded inside.

[0010] Compared with a single lecithin bilayer liposome carrier for loading dydrogesterone, the mixed liposome can, on the one hand, further enhance the structural stability of the liposome carrier, increase the drug loading capacity, prevent damage to the liposome, and improve drug stability; on the other hand, the mixed liposome structure is easier to regulate the release behavior of dydrogesterone, so that dydrogesterone is released at the most appropriate rate in the body circulation, thereby ensuring the efficacy of the drug.

[0011] Through the above technical solution, the solubility and bioavailability of dydrogesterone can be effectively improved, the cell permeability of dydrogesterone can be increased, and it can be more easily entered into the blood circulation through the gastrointestinal tract and absorbed by the body without causing excessive stimulation to the gastric mucosa, which helps to accelerate the onset of the drug and improve its therapeutic effect.

[0012] Optionally, the amphiphilic block copolymer is selected from any one of PEG-b-PAA, PLA-PEG, and PS-b-PEO.

[0013] Optionally, the amphiphilic block copolymer is selected from any one of PEG-b-PtBA, PEG-b-PS, and PS-b-PAA.

[0014] By adopting the above technical solution, the inventors found that PEG-based block copolymers, PLA-based block copolymers and PS-based block copolymers all have good biocompatibility and biodegradability, and as drug carrier shell materials, they can effectively increase the loading amount of hydrophobic dydrogesterone and regulate its release behavior. This helps to reduce the irritation of dydrogesterone to the gastric mucosa, thereby reducing the side effects of dydrogesterone tablets and improving the bioavailability of the drug.

[0015] Optionally, the filler includes corn starch, chitosan, oligofructose and sodium carboxymethyl starch.

[0016] Optionally, the mass ratio of the corn starch, chitosan, oligofructose and sodium carboxymethyl starch is (3-7):(10-15):(1-3):(2-6).

[0017] By adopting the above technical solution, the inventors found that chitosan and oligofructose are both natural polysaccharides. Chitosan can form a gel-like substance after entering the gastrointestinal tract, adhere to the stomach wall to form a protective film, and effectively prevent dydrogesterone from irritating and corroding the gastric mucosa. In addition, chitosan molecules contain amino groups and are alkaline. Ammonium salts can be generated under the condition of gastric acid, which can turn the pH value in the gastrointestinal tract into alkaline and improve acidic constitution.

[0018] Oligofructose is a prebiotic that can regulate intestinal flora, enhance the gastrointestinal barrier immunity, reduce gastrointestinal inflammatory response, enhance the body's immunity, further reduce the irritation and impact of drugs on the gastrointestinal tract, and promote and ensure the absorption of dydrogesterone.

[0019] Optionally, the particle size distribution of the dydrogesterone is D90≤40 μm.

[0020] Optionally, the binder is selected from any one or more combinations of polyvinyl pyrrolidone, hydroxypropyl methylcellulose and copovidone.

[0021] Optionally, the lubricant is selected from any one or more combinations of zinc stearate, magnesium stearate and calcium stearate.

[0022] In a second aspect, the present application provides a preparation process of dydrogesterone tablets, which adopts the following technical solution: A preparation process of dydrogesterone tablets comprises the following steps: S1: firstly, lecithin and amphiphilic block copolymer are mixed, ethanol is added, and the mixture is heated in a water bath at 60-70°C with stirring, then citric acid-sodium citrate buffer with a pH value of 3 at the same temperature is added, and heating and stirring in a constant temperature water bath are continued, and finally ultrasonically crushed and filtered to obtain blank liposomes, and then, in an ice-water bath, a Na3PO4 solution is used to adjust the pH value of the in vitro aqueous phase of the blank liposomes to 6-7 to form gradient liposomes; S2: dissolving dydrogesterone in ethanol to form a dydrogesterone solution, then adding blank liposomes to the dydrogesterone solution, heating to 60-65° C. to carry out drug loading for 20-30 min, then stopping drug loading in an ice water bath for 2-5 min, and obtaining liposomes loaded with dydrogesterone; S3: mixing the liposome loaded with dydrogesterone and the filler, stirring with ethanol as a wetting agent, adding a binder to granulate, drying, and then adding a lubricant to form a mixture, and tableting the mixture and coating it.

[0023] In the above technical scheme, by adopting the active drug loading method with setting pH gradient, the mixed liposomes of lecithin and amphiphilic block copolymer are prepared, which can effectively improve the coverage rate of hydrophobic dydrogesterone and reduce the irritation of dydrogesterone tablets to gastric mucosa, thereby reducing the side effects of dydrogesterone tablets and improving the bioavailability of the active ingredients.

[0024] In summary, this application has the following beneficial effects: 1. Since the present application adopts a hollow inner shell formed by a mixed liposome of lecithin and an amphiphilic block copolymer to load the hydrophobic dydrogesterone and prepare the tablet, the solubility and bioavailability of dydrogesterone are effectively improved, which is conducive to faster passage of dydrogesterone through the gastrointestinal tract and entering the blood circulation, and is released at an appropriate dissolution rate without excessive stimulation to the gastric mucosa. It can be eaten before meals to ensure the absorption of dydrogesterone and the exertion of its efficacy.

[0025] 2. In the present application, chitosan is preferably used as one of the raw materials of the filler. In the fasting state, chitosan can form a gel-like substance after entering the gastrointestinal tract, adhere to the stomach wall to form a protective film, and effectively prevent dydrogesterone from irritating and corroding the gastric mucosa.

[0026] 3. The method of the present application adopts an active drug loading method with a pH gradient, and combines ultrasonic crushing and ice-water bath treatment to prepare mixed liposomes of lecithin and amphiphilic block copolymers, thereby obtaining a uniform mixed liposome size, reducing the aggregation and precipitation of the mixed liposomes, and better encapsulating dydrogesterone. DETAILED DESCRIPTION

[0027] The following examples further illustrate the present application in detail.

[0028] raw material Unless otherwise specified, the raw materials used in the examples and comparative examples of this application are all commercially available products of pharmaceutical grade and can be used for the preparation of pharmaceutical preparations, specifically: Dydrogesterone, particle size distribution D90 ≤ 40 μm, average particle size 35.7 μm; PEG-b-PAA, molecular formula: HO(CH2 CH 2 O) n (CH 2 CH 2 O)[CH 2 C(CH 3 ) 3 COO] m H, molecular weight is 3.4k; PLA-PEG, molecular formula: HO(COCHCH 3 O) y (CH 2 CH 2 O) x (COCHCH 3 O) y H, molecular weight 3k; PS-b-PEO is PS150-b-PEO114, and its molecular formula is: (CH 3 CH(C 6 H 5 )) 150 -(CH 2 CH 2 OH) 114 ; Fructooligosaccharide, selected from Shaanxi Panier Biotechnology, pharmaceutical grade, HPLC ≥ 99%. Example

[0029] Example 1 A dydrogesterone tablet, wherein the raw materials and amounts are shown in Table 1, wherein the amphiphilic block copolymer is a PEG-based block copolymer, PEG-b-PAA; the filler comprises corn starch, chitosan, oligofructose and sodium carboxymethyl starch in a mass ratio of 3:10:1:2; the binder comprises hydroxypropyl methylcellulose and copovidone in a mass ratio of 1.2:1; and the lubricant is magnesium stearate.

[0030] Table 1 The preparation process of the dydrogesterone tablets comprises the following steps: S1: firstly, lecithin and the amphiphilic block copolymer are mixed, anhydrous ethanol is added, and the mixture is heated in a water bath at 65° C. After the lecithin and the amphiphilic block copolymer are completely dissolved, a magnetic stirring bar is added to stir and most of the anhydrous ethanol is evaporated; Then, citric acid-sodium citrate buffer at 65°C and pH 3 was added, and stirring was continued at 60 rpm in a 65°C constant temperature water bath for 30 min; Finally, ultrasonic cell crusher was used to perform ultrasonic crushing for 5 min at 200 W, and blank liposomes were obtained by filtration. Then, Na 3 PO 4 The solution adjusts the in vitro aqueous phase pH of the blank liposome to 6 to form a gradient liposome; S2: dissolving dydrogesterone in 96% ethanol to form a dydrogesterone solution, then adding the blank liposome to the dydrogesterone solution, heating to 65°C for drug loading for 25 minutes, and then terminating the drug loading in an ice water bath for 3 minutes to obtain liposomes loaded with dydrogesterone; S3: mixing the liposomes loaded with dydrogesterone and the filler, stirring with 96% ethanol as a wetting agent, adding a binder to granulate, drying, and then adding a lubricant to mix to form a mixture, and the mixture is tableted and coated to obtain a dydrogesterone content of 10 mg / tablet.

[0031] Example 2 A dydrogesterone tablet, which is different from Example 1 in that the raw materials and amounts are as shown in Table 1, wherein the filler comprises corn starch, chitosan, oligofructose and sodium carboxymethyl starch in a mass ratio of 5:12:2:6; the binder comprises hydroxypropyl methylcellulose and polyvinyl pyrrolidone in a mass ratio of 1.5:1; and the lubricant is zinc stearate.

[0032] The preparation process of the dydrogesterone tablets comprises the following steps: S1: firstly, lecithin and the amphiphilic block copolymer are mixed, anhydrous ethanol is added, and the mixture is heated in a water bath at 60° C. After the lecithin and the amphiphilic block copolymer are completely dissolved, a magnetic stirring bar is added to stir and most of the anhydrous ethanol is evaporated; Then, citric acid-sodium citrate buffer at 60°C and pH 3 was added, and stirring was continued at 60 rpm in a 60°C constant temperature water bath for 30 min; Finally, ultrasonic cell crusher was used to perform ultrasonic crushing for 5 min at 200 W, and blank liposomes were obtained by filtration. Then, Na 3 PO 4 The solution adjusts the in vitro aqueous phase pH of the blank liposome to 7 to form a gradient liposome; S2: dissolving dydrogesterone in 96% ethanol to form a dydrogesterone solution, then adding the blank liposome to the dydrogesterone solution, heating to 60°C for drug loading for 25 minutes, and then terminating the drug loading in an ice water bath for 5 minutes to obtain liposomes loaded with dydrogesterone; S3: mixing the liposomes loaded with dydrogesterone and the filler, stirring with 96% ethanol as a wetting agent, adding a binder to granulate, drying, and then adding a lubricant to mix to form a mixture, and the mixture is tableted and coated to obtain a dydrogesterone content of 10 mg / tablet.

[0033] Example 3 A dydrogesterone tablet, which is different from Example 1 in that the raw materials and amounts are as shown in Table 1, wherein the filler comprises corn starch, chitosan, oligofructose and sodium carboxymethyl starch in a mass ratio of 7:15:3:4; The preparation process of the dydrogesterone tablets comprises the following steps: S1: firstly, lecithin and the amphiphilic block copolymer are mixed, anhydrous ethanol is added, and the mixture is heated in a water bath at 70° C. After the lecithin and the amphiphilic block copolymer are completely dissolved, a magnetic stirring bar is added to stir and most of the anhydrous ethanol is evaporated; Then, 70°C citric acid-sodium citrate buffer with a pH of 3 was added, and the mixture was stirred at 60 rpm in a 70°C constant temperature water bath for 30 min; Finally, ultrasonic cell crusher was used to perform ultrasonic crushing for 5 min at 200 W, and blank liposomes were obtained by filtration. Then, Na 3 PO 4 The solution adjusts the in vitro aqueous phase pH of the blank liposome to 6 to form a gradient liposome; S2: dissolving dydrogesterone in 96% ethanol to form a dydrogesterone solution, then adding the blank liposome to the dydrogesterone solution, heating to 65°C for drug loading for 30 minutes, and then terminating the drug loading in an ice water bath for 2 minutes to obtain liposomes loaded with dydrogesterone; S3: mixing the liposomes loaded with dydrogesterone and the filler, stirring with 96% ethanol as a wetting agent, adding a binder to granulate, drying, and then adding a lubricant to mix to form a mixture, and the mixture is tableted and coated to obtain a dydrogesterone content of 10 mg / tablet.

[0034] Example 4 A dydrogesterone tablet, which is different from Example 1 in that the raw materials and amounts are as shown in Table 1, wherein the filler comprises corn starch, chitosan, oligofructose and sodium carboxymethyl starch in a mass ratio of 4:11:3:3; The preparation process of the dydrogesterone tablets comprises the following steps: S1: firstly, lecithin and the amphiphilic block copolymer are mixed, anhydrous ethanol is added, and the mixture is heated in a water bath at 60° C. After the lecithin and the amphiphilic block copolymer are completely dissolved, a magnetic stirring bar is added to stir and most of the anhydrous ethanol is evaporated; Then, citric acid-sodium citrate buffer at 60°C and pH 3 was added, and stirring was continued at 60 rpm in a 60°C constant temperature water bath for 30 min; Finally, ultrasonic cell crusher was used to perform ultrasonic crushing for 5 min at 200 W, and blank liposomes were obtained by filtration. Then, Na 3 PO 4The solution adjusts the in vitro aqueous phase pH of the blank liposome to 7 to form a gradient liposome; S2: dissolving dydrogesterone in 96% ethanol to form a dydrogesterone solution, then adding the blank liposome to the dydrogesterone solution, heating to 65°C for drug loading for 20 minutes, and then terminating the drug loading in an ice water bath for 4 minutes to obtain liposomes loaded with dydrogesterone; S3: mixing the liposomes loaded with dydrogesterone and the filler, stirring with 96% ethanol as a wetting agent, adding a binder to granulate, drying, and then adding a lubricant to mix to form a mixture, and the mixture is tableted and coated to obtain a dydrogesterone content of 10 mg / tablet.

[0035] Example 5 A dydrogesterone tablet, which is different from Example 1 in that the amphiphilic block copolymer is a PLA-based block copolymer, PLA-PEG, and the other steps are the same as Example 1.

[0036] Example 6 A dydrogesterone tablet, which is different from Example 1 in that the amphiphilic block copolymer is a PS-based block copolymer, PS-b-PEO, and the other steps are the same as those of Example 1.

[0037] Example 7 A dydrogesterone tablet, which differs from Example 1 in that oligofructose is not added, the oligofructose in the raw material filler is replaced by corn starch of the same mass, and the other steps are the same as those in Example 1.

[0038] Example 8 A dydrogesterone tablet, which differs from Example 1 in that chitosan is not added, the chitosan in the raw material filler is replaced by corn starch of the same mass, and the other steps are the same as those in Example 1.

[0039] Example 9 A dydrogesterone tablet, which differs from Example 1 in that oligofructose and chitosan are not added, oligofructose and chitosan in the raw material filler are replaced with corn starch of equal mass, and other steps are the same as Example 1.

[0040] Comparative Example Comparative Example 1 A dydrogesterone tablet, which differs from Example 1 in that no amphiphilic block copolymer is used, the amphiphilic block copolymer in the raw material is replaced by an equal mass of cholesterol, and the rest is the same as Example 1.

[0041] Comparative Example 2 A dydrogesterone tablet, which differs from Example 1 in that no amphiphilic block copolymer is used, the amphiphilic block copolymer in the raw material is replaced by lecithin of equal mass, and the rest is the same as Example 1.

[0042] Comparative Example 3 A dydrogesterone tablet, the raw materials of which include 10% dydrogesterone, 68% lactose, 13% corn starch, 3% sodium carboxymethyl starch, 2% hydroxypropyl methylcellulose, 1% povidone K30, 2.5% colloidal silicon dioxide and 0.5% magnesium stearate; The preparation process of the dydrogesterone tablets comprises the following steps: Take about 1 / 2 of the prescription amount of dydrogesterone and about 1 / 2 of the prescription amount of filler, add them to the wet granulator and mix for 6 minutes, start stirring and shearing, add half of the binder solution prepared to a mass concentration of 12% within 2 minutes, and continue granulating for 2 minutes, continue to add the remaining dydrogesterone and filler, add 12% of the binder solution within the same time, and continue granulating for 2 minutes, pass the wet granules through a 4×4mm sieve, dry them in a fluidized bed after sieving, until the moisture content does not exceed 3%, then mix the dried granules with the added colloidal silicon dioxide, pass them through a 1.5mm sieve, mix them with the added magnesium stearate 0.5g for 5 minutes, and obtain them after tableting and coating. Performance Testing Test Example 1 According to the relevant standard provisions of the dissolution test method (the second method of Part IV of the 2020 edition of the Chinese Pharmacopoeia, 0931), a dydrogesterone tablet obtained in Example 1-9 and Comparative Example 1-3 was tested for dissolution. Each group of tests was performed 3 times, and the average value of the 3 experiments was taken as the final result. The final result is recorded in Table 2.

[0043] The dissolution conditions were set as follows: 500 mL of 0.8% sodium dodecyl sulfate was used as the dissolution medium, the rotation speed was 50 rpm, samples were taken for measurement after 5 min, 10 min, 20 min, 30 min and 40 min, and the cumulative dissolution was calculated.

[0044] Table 2 According to the performance test results in Table 2, it can be seen that the hollow inner shell formed by the mixed liposomes of lecithin and amphiphilic block copolymer is loaded with hydrophobic dydrogesterone to prepare tablets. Compared with the preparation of dydrogesterone tablets by single liposomes or cholesterol-stabilized lecithin liposomes, the mixed liposome drug carrier structure is more stable, not easily destroyed, and can better protect the loaded drug.

[0045] The hollow inner shell formed by the mixed liposomes of lecithin and amphiphilic block copolymers is used to load hydrophobic dydrogesterone to prepare tablets, which can effectively improve the solubility and bioavailability of dydrogesterone and regulate the release rate of dydrogesterone, so that dydrogesterone is dissolved at an appropriate rate, thereby reducing the stimulation of the gastrointestinal tract of patients by dydrogesterone tablets, avoiding excessive dissolution and rapid stimulation of the stomach and intestines, causing a series of adverse reactions in the body, and ensuring the effective exertion of the drug effect.

[0046] According to the performance test results of Examples 1-4 and Examples 7-8, it can be seen that the addition of chitosan can further regulate the dissolution rate of dydrogesterone. This may be because chitosan forms a gel-like substance in a liquid environment, which plays a protective role, thereby limiting the release of dydrogesterone.

[0047] Test Example 2 The following animal experiments were conducted on a dydrogesterone tablet (each tablet containing 10 mg of dydrogesterone) of Example 1, Examples 7-9 and Comparative Examples 1-3. When conducting animal experiments, all animal experiments complied with the animal protection regulations and relevant laws and regulations to ensure that the animals received proper care and treatment during the experiments.

[0048] 1. Selection of experimental subjects: Healthy SD female mice weighing 200±10g were selected as experimental subjects for the experiment. 70 SD mice were randomly divided into 7 groups, with 10 mice in each group as the experimental group. 10 SD mice were selected under the same conditions as the control group. Both the experimental group and the control group were housed in separate cages under the same conditions.

[0049] 2. Experimental methods: Experimental group: In the fasting state of SD female mice, the female mice of Example 1, Examples 7-9 and Comparative Examples 1-2 were respectively administered with a dosage of 0.005 tablets of dydrogesterone tablets.

[0050] Control group: When the SD female mice were in the fasting state, the female mice in the control group were not given dydrogesterone tablets, but only given an equal amount of normal saline.

[0051] 5min, 15min, 30min, 45min and 60min after administration, the female mice were observed for adverse reactions such as licking lips, drooling, vomiting, etc., and the observation results of the experimental group and the control group were recorded in Table 3.

[0052] Table 3 According to the experimental results of the experimental group and the control group in Table 3, it can be seen that the present application uses a hollow inner shell formed by a mixed liposome of lecithin and an amphiphilic block copolymer to load the hydrophobic dydrogesterone and prepare tablets. Compared with a single liposome as a drug carrier, the amphiphilic block copolymer helps to improve the structural stability of the liposome carrier, increase the drug loading capacity, and at the same time regulate the release rate of dydrogesterone, so that dydrogesterone is released at an appropriate rate and exerts its efficacy.

[0053] According to the female rats' taking reactions in Examples 1 and 7-9, it can be seen that chitosan and oligofructose are both natural polysaccharides. Chitosan can form a gel-like substance after entering the gastrointestinal tract, adhere to the stomach wall to form a protective film, effectively prevent dydrogesterone from irritating and corroding the gastric mucosa, and reduce the side effects of dydrogesterone tablets. Oligofructose is a prebiotic that enhances the barrier immunity of the gastrointestinal tract by regulating the intestinal flora, and further reduces the irritation and impact of drugs on the gastrointestinal tract.

[0054] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. A dydrogesterone tablet, characterized in that: According to mass percentage, the raw materials of the tablet include 10% dydrogesterone, 60-65% filler, 19-23% lecithin, 5.1-6.7% amphiphilic block copolymer, 0.2-0.8% binder and 0.1-0.5% lubricant.

2. The dydrogesterone tablet according to claim 1, characterized in that The amphiphilic block copolymer is selected from any one of PEG-b-PAA, PLA-PEG and PS-b-PEO.

3. The dydrogesterone tablet according to claim 1, characterized in that The fillers include corn starch, chitosan, oligofructose and sodium carboxymethyl starch.

4. The dydrogesterone tablet according to claim 3, characterized in that The mass ratio of the corn starch, chitosan, oligofructose and sodium carboxymethyl starch is (3-7):(10-15):(1-3):(2-6).

5. The dydrogesterone tablet according to claim 1, characterized in that The particle size distribution of the dydrogesterone is D90≤40 μm.

6. The dydrogesterone tablet according to claim 1, characterized in that The binder is selected from any one or more combinations of polyvinyl pyrrolidone, hydroxypropyl methylcellulose and copovidone.

7. The dydrogesterone tablet according to claim 1, characterized in that The lubricant is selected from any one or more combinations of zinc stearate, magnesium stearate and calcium stearate.

8. A process for preparing a dydrogesterone tablet according to any one of claims 1 to 7, characterized in that: The following steps are involved: S1: firstly, lecithin and amphiphilic block copolymer are mixed, ethanol is added, and the mixture is heated in a water bath at 60-70°C with stirring, then citric acid-sodium citrate buffer with a pH value of 3 at the same temperature is added, and heating and stirring in a constant temperature water bath are continued, and finally ultrasonically crushed and filtered to obtain blank liposomes, and then, in an ice-water bath, a Na3PO4 solution is used to adjust the pH value of the in vitro aqueous phase of the blank liposomes to 6-7 to form gradient liposomes; S2: dissolving dydrogesterone in ethanol to form a dydrogesterone solution, then adding blank liposomes to the dydrogesterone solution, heating to 60-65° C. to carry out drug loading for 20-30 min, then stopping drug loading in an ice water bath for 2-5 min, and obtaining liposomes loaded with dydrogesterone; S3: mixing the liposome loaded with dydrogesterone and the filler, stirring with ethanol as a wetting agent, adding a binder to granulate, drying, and then adding a lubricant to form a mixture, and tableting the mixture and coating it.

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