Mabazavir oral soluble film agent and preparation method thereof

Abstract

The invention discloses a macloxvir oral soluble film agent and a preparation method thereof, and relates to the technical field of medicines. The macloxvir oral soluble film agent comprises the following components in percentage by weight: 10%-20% of macloxvir, 10%-70% of a film-forming material, 3%-15% of a disintegrating agent, 2%-25% of a plasticizer, 0%-5% of a flavoring agent and 0%-3% of an auxiliary material. The macloxvir oral soluble film preparation has the advantages of no irritant taste, smooth surface, uniform drug content, fast disintegration speed, fast absorption, convenient administration, and improvement of the compliance of patients. The film agent can be used for resisting viruses.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology and also relates to a mabaloxavir orodispersible film-dissolving preparation and a preparation method thereof. Background Art

[0002] Influenza is an acute respiratory infection caused by influenza A and B viruses, with outbreaks of varying severity occurring almost every winter in temperate climates and mid-year. Influenza viruses are highly contagious, spread effectively from person to person in the community, and have the potential to cause pandemics. Their severe morbidity and mortality pose a major public health challenge. [Children are susceptible to influenza] Children under 5 to 12 years old have a high risk of related severe complications due to their weak personal protection awareness and physiological characteristics. They are also an important factor in the risk of transmission in families, early childhood education institutions, and schools, and the need to quickly control influenza is more urgent; [Higher incidence in children aged 5 to 12] The incidence of influenza in people aged 5-12 is second only to that of patients aged 0-4, with an incidence rate of 21.7%; [Urgent need for children-specific dosage forms] There is a shortage of children-specific drugs in my country, and non-specific drugs have unclear dosages, which can easily lead to overdose or underdose; poor medication compliance, difficulty swallowing, vomiting, etc. seriously affect the treatment of children. Therefore, dosage forms such as tablets often cannot play a role in such patients.

[0003] Mabaloxavir was jointly developed by Shionogi, Genentech and Roche Pharmaceuticals Co., Ltd. of Japan, and its dosage forms include tablets, granules and dry suspensions. Baloxavir ester is a new prodrug that selectively inhibits cap-dependent endonucleases, an influenza virus-specific enzyme in the polymerase acidic (PA) subunit of the viral RNA polymerase complex, by converting it into an active form through metabolism (hydrolysis), thereby inhibiting the replication of influenza viruses. For both indications (treatment and prevention of influenza), mabaloxavir is administered as a single oral dose. Therefore, the market prospects of mabaloxavir are unanimously optimistic, and its development prospects are extremely good.

[0004] As is well known, when considering dosage forms for pediatric patients, ensuring patient compliance is particularly important. Children may often have difficulty swallowing tablets or capsules, and there is a risk of choking, so it is particularly important to provide a dosage form that is easy to apply to children and has uniform content. Dry suspensions and granules take effect quickly, but may stick to the bag when pouring, and mabaloxavir is a hydrophobic substance. When brewing, the particles may float or settle, so the patient will not be given the full dose. In comparison, the dosage of film is more accurate. As a new type of drug preparation, film is particularly suitable for children, the elderly and patients with dysphagia caused by digestive tract diseases, etc., and is also particularly suitable for patients who are not convenient to get water during business trips. Whether the orodispersible film used can be compatible with specific active ingredients, the orodispersible film is a new type of oral drug delivery system, which has the advantages of rapid dissolution, easy to carry, and easy to use. However, the existing orodispersible film has problems such as poor solubility, inaccurate dosage, and low drug loading, which limits its clinical application. Therefore, developing an orodispersible film-forming agent with good solubility, accurate dosage, and high drug loading is of great significance for improving drug efficacy and patient compliance.

[0005] Mabaloxavir API is a white or off-white crystalline powder, which is almost insoluble in water, belongs to BCS class 2 or 4 drugs, and has a strong bitter taste, which can cause significant irritation in the oral mucosa. Mabaloxavir ordinary tablets must disintegrate in the stomach to start releasing the drug, and the onset of action is slow, thereby limiting bioavailability. It is also inconvenient to take, especially for children. The population with this indication is poor in cooperating with treatment, and is prone to refusing treatment, vomiting, etc. Therefore, it is urgent to develop a dosage form of mabaloxavir that is easy to take, has good patient compliance, high bioavailability, and is suitable for industrial production. Summary of the invention

[0006] In view of the above technical problems, the present invention provides a mabaloxavir orodispersible film-forming agent and a preparation method thereof.

[0007] The invention discloses a mabaloxavir orodispersible film preparation, which comprises, by weight percentage, 10% to 20% of mabaloxavir, 10% to 70% of a film-forming material, 3% to 15% of a disintegrant, 2% to 25% of a plasticizer, 0% to 5% of a flavoring agent and 0% to 3% of an auxiliary material.

[0008] Furthermore, the mabaloxavir orodispersible film-forming agent comprises, by weight percentage, 10% to 20% of mabaloxavir, 20% to 60% of film-forming material, 5% to 10% of disintegrant, 5% to 20% of plasticizer, 1% to 5% of flavoring agent and 1% to 3% of auxiliary materials.

[0009] Furthermore, the mabaloxavir orodispersible film-forming agent comprises, by weight percentage, 10% to 20% of mabaloxavir, 30% to 50% of film-forming material, 6% to 8% of disintegrant, 10% to 20% of plasticizer, 2% to 5% of flavoring agent and 2% to 3% of auxiliary materials.

[0010] Furthermore, the flavoring agent is citric acid, malic acid or tartaric acid; wherein the weight percentage of citric acid is at least 3%.

[0011] Furthermore, the auxiliary materials are sweeteners and colorants; the sweeteners are saccharin sodium, fructose, mannitol, sucrose, menthol, xylitol or sucralose; the colorants are titanium dioxide, yellow iron oxide, red iron oxide or black iron oxide.

[0012] Furthermore, the film-forming material is one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol, polyethylene oxide, gum arabic, xanthan gum, and agar.

[0013] Furthermore, the plasticizer is one or more of polyethylene glycol, propylene glycol, glycerol, and Tween 80.

[0014] Furthermore, the disintegrant is cross-linked carboxymethyl cellulose sodium.

[0015] Furthermore, the mabaloxavir orodispersible film-forming agent completely dissolves in 25° C. water within 60 seconds.

[0016] A method for preparing a mabaloxavir orodispersible film-dissolving agent of the present invention is carried out as follows:

[0017] (1) grinding, sieving or jet milling mabaloxavir to control the average particle size D90 to be less than 10 μm;

[0018] (2) dispersing the mabaloxavir obtained in step (1) in purified water or solvent-water, adding a flavoring agent and stirring evenly, then adding a film-forming material and mixing evenly to obtain a glue solution;

[0019] (3) degassing the glue solution obtained in step (2) by centrifugation or static degassing under vacuum conditions;

[0020] (4) applying the glue obtained in step (3) onto a PET tape, drying to obtain a film, peeling the film from the PET tape, cutting, and sealing to obtain a mabaloxavir orosoluble film.

[0021] The present invention has the following beneficial effects:

[0022] The film preparation of the present invention increases the content of the raw material drug, selects appropriate flavoring agents and film-forming materials, and controls the particle size of the raw material drug, thereby obtaining a film preparation with non-irritating taste, smooth surface, uniform drug content, fast disintegration speed, and fast absorption, which is convenient to take and improves patient compliance. The film preparation of the present invention can be used for antiviral purposes. DETAILED DESCRIPTION

[0023] In order to make the objectives, technical solutions and advantages of the embodiments of the present invention more clearly understood, the spirit of the contents disclosed by the present invention will be described in detail below. After understanding the embodiments of the contents of the present invention, any technician in the relevant technical field can change and modify them according to the techniques taught by the contents of the present invention without departing from the spirit and scope of the contents of the present invention.

[0024] The exemplary embodiments of the present invention and the description thereof are used to explain the present invention but are not intended to limit the present invention.

[0025] Note: In the examples, comparative examples and blank samples herein, the raw materials used without any description are all raw materials crushed by air flow mill, and the average particle size is less than 10 μm. Of course, the particle size can also be controlled to be less than 10 μm by grinding and sieving.

[0026] Embodiment 1:

[0027] In this embodiment: 1) citric acid and sucralose are used as flavoring agents to effectively mask the bitter taste; 2) the content of the main drug is 15%, and the surface of the prepared film has no ice flower-like dots; 3) the average particle size of the raw material is less than 10 μm, and the surface of the prepared film is smooth without roughness; 4) the film-forming material is hydroxypropyl methylcellulose, which has good film-forming properties; 5) cross-linked carboxymethyl cellulose sodium is used as a disintegrant, and the amount is 5%.

[0028] The prescription quantity is 1000 tablets (specification 10mg) or 500 tablets (specification 20mg)

[0029] prescription:

[0030] Mabaloxavir: 1.5 g (15%)

[0031] Hydroxypropyl methylcellulose: 6.5 g (65%)

[0032] Cross-linked carboxymethyl cellulose sodium: 0.5 g (5%)

[0033] Glycerol: 0.7 g (7%)

[0034] Citric acid: 0.4 g (4%)

[0035] Sucralose: 0.4 g (4%)

[0036] Purified water: 25.0g

[0037] Weigh 1.5g of Mabaloxavir and add it to 25.0g of purified water, stir and disperse it evenly, then weigh 0.4g of citric acid, 0.4g of sucralose, 0.5g of cross-linked carboxymethyl cellulose sodium, and 0.7g of glycerol, respectively, add them to purified water, stir and disperse them evenly, weigh 6.5g of hydroxypropyl methylcellulose and add it to the evenly dispersed solution, stir and dissolve it to form a glue solution, and degas the glue solution by vacuum centrifugation. Inject the glue solution into a coating machine and apply film. Cut according to specifications and package.

[0038] Embodiment 2:

[0039] In this embodiment, compared with embodiment 1: 1) xylitol is added as a flavoring agent, with an amount of 4%, and the taste is good;

[0040] 2) The film-forming material is polyvinyl pyrrolidone, with a dosage of 52%, and has good film-forming properties; 3) Cross-linked sodium carboxymethyl cellulose is used as a disintegrant, with a dosage of 5%, and has a good appearance.

[0041] The prescription quantity is 1000 tablets (specification 10mg) or 500 tablets (specification 20mg)

[0042] prescription:

[0043] Mabaloxavir: 1.5 g (15%)

[0044] Polyvinylpyrrolidone: 6.0 g (60%)

[0045] Cross-linked carboxymethyl cellulose sodium: 0.5 g (5%)

[0046] Glycerol: 0.7 g (7%)

[0047] Citric acid: 0.4 g (4%)

[0048] Sucralose: 0.4 g (4%)

[0049] Xylitol: 0.5g (5%)

[0050] Purified water: 25.0g

[0051] Weigh 1.5g of Mabaloxavir and add it to 25.0g of purified water, stir and disperse it evenly, then weigh 0.4g of citric acid, 0.4g of sucralose, 0.5g of cross-linked sodium carboxymethyl cellulose, 0.7g of glycerol, and 0.5g of xylitol, respectively, add them to purified water, stir and disperse them evenly, weigh 6.0g of polyvinyl pyrrolidone and add it to the evenly dispersed solution, stir and dissolve it fully to form a glue solution, and degas the glue solution by vacuum centrifugation. Inject the glue solution into a coating machine and apply film. Cut according to specifications and package.

[0052] Embodiment 3:

[0053] In this embodiment, compared with embodiment 2: 1) strawberry essence is added as a fragrance agent, with an amount of 2%, and the taste is good;

[0054] 2) The film-forming material is polyoxyethylene, with a dosage of 65%, and good film-forming properties; 3) No colorant is added.

[0055] The prescription quantity is 1000 tablets (specification 10mg) or 500 tablets (specification 20mg)

[0056] prescription:

[0057] Mabaloxavir: 1.5 g (15%)

[0058] Polyoxyethylene: 6.5 g (65%)

[0059] Cross-linked carboxymethyl cellulose sodium: 0.5 g (5%)

[0060] Glycerol: 0.7 g (7%)

[0061] Citric acid: 0.2 g (2%)

[0062] Sucralose: 0.2 g (2%)

[0063] Xylitol: 0.2g (2%)

[0064] Strawberry flavor: 0.2g (2%)

[0065] Purified water: 25.0g

[0066] Weigh 1.5g of Mabaloxavir and add it to 25.0g of purified water, stir and disperse it evenly, then weigh 0.2g of citric acid, 0.2g of sucralose, 0.5g of cross-linked sodium carboxymethyl cellulose, 0.7g of glycerol, 0.2g of strawberry essence, and 0.2g of xylitol and add them to purified water, stir and disperse them evenly, weigh 6.5g of polyoxyethylene and add it to the evenly dispersed solution, stir and dissolve it to form a glue solution, and degas the glue solution by vacuum centrifugation. Inject the glue solution into a coating machine and apply film. Cut according to specifications and package.

[0067] Comparative Example 1

[0068] In this comparative example, malic acid and sucrose are used as flavor correctors, and the prepared film has a bitter taste and cannot effectively mask the taste.

[0069] The prescription quantity is 1000 tablets (specification 10mg) or 500 tablets (specification 20mg)

[0070] prescription:

[0071] Mabaloxavir: 1.5 g

[0072] Hydroxypropyl methylcellulose: 6.5g

[0073] Cross-linked carboxymethyl cellulose sodium: 0.3g

[0074] Glycerol: 0.7g

[0075] Malic acid: 0.4g

[0076] Sucralose: 0.4 g

[0077] Purified water: 25.0g

[0078] Weigh 1.5g of Mabaloxavir and add it to 25.0g of purified water, stir and disperse it evenly, then weigh 0.4g of malic acid, 0.5g of cross-linked carboxymethyl cellulose sodium, 0.4g of sucralose, and 0.7g of glycerol respectively and add them to purified water, stir and disperse them evenly, weigh 5.5g of hydroxypropyl methylcellulose and add it to the evenly dispersed solution, stir and dissolve it fully to form a glue solution, and degas the glue solution by vacuum centrifugation. Inject the glue solution into a coating machine and apply a film. Cut according to specifications and package.

[0079] Comparative Example 2

[0080] This comparative example uses tartaric acid and sucralose as flavor correctors, which have a bitter taste and cannot effectively mask the taste.

[0081] The prescription quantity is 1000 tablets (specification 10mg) or 500 tablets (specification 20mg)

[0082] prescription:

[0083] Mabaloxavir: 1.5 g

[0084] Hydroxypropyl methylcellulose: 6.5g

[0085] Cross-linked carboxymethyl cellulose sodium: 0.3g

[0086] Glycerol: 0.7g

[0087] Tartaric acid: 0.4g

[0088] Sucralose: 0.4 g

[0089] Purified water: 25.0g

[0090] Weigh 1.5g of Mabaloxavir and add it to 25.0g of purified water, stir and disperse it evenly, then weigh 0.4g of tartaric acid, 0.5g of cross-linked carboxymethyl cellulose sodium, 0.4g of sucralose, and 0.7g of glycerol respectively and add them to purified water, stir and disperse them evenly, weigh 5.5g of hydroxypropyl methylcellulose and add it to the evenly dispersed solution, stir and dissolve it fully to form a glue solution, and degas the glue solution by vacuum centrifugation. Inject the glue solution into a coating machine and apply a film. Cut according to specifications and package.

[0091] Comparative Example 3

[0092] This comparative example uses sodium citrate and sucralose as flavor correctors, which have a bitter taste and cannot effectively mask the taste.

[0093] The prescription quantity is 1000 tablets (specification 10mg) or 500 tablets (specification 20mg)

[0094] prescription:

[0095] Mabaloxavir: 1.5 g

[0096] Hydroxypropyl methylcellulose: 6.5g

[0097] Cross-linked carboxymethyl cellulose sodium: 0.3g

[0098] Glycerol: 0.7g

[0099] Sodium citrate: 0.4g

[0100] Sucralose: 0.4 g

[0101] Purified water: 25.0g

[0102] Weigh 1.5g of Mabaloxavir and add it to 25.0g of purified water, stir and disperse it evenly, then weigh 0.4g of sodium citrate, 0.5g of cross-linked sodium carboxymethyl cellulose, 0.4g of sucralose, and 0.7g of glycerol respectively and add them to purified water, stir and disperse them evenly, weigh 5.5g of hydroxypropyl methylcellulose and add it to the evenly dispersed solution, stir and dissolve it to form a glue solution, and degas the glue solution by vacuum centrifugation. Inject the glue solution into a coating machine and apply a film. Cut and package according to specifications.

[0103] According to Examples 1-3 of the present invention, the ability of citric acid, a pH regulator, and a flavoring agent, which are commonly used as stabilizers, to mask the irritating taste of Mabaloxavir was evaluated; Comparative Examples 1-5 evaluated the ability of flavors, sweeteners, and combinations thereof, which are commonly used as flavoring agents, to mask the irritating taste of Mabaloxavir orodispersible films. The irritating taste of the drug was evaluated by comparing it with a blank control to which no flavoring agent was added. 10 adult men and women aged 25-45 were selected as evaluators, and the film was orally administered. After taking the drug, the taste level was measured 1 minute after the drug was completely dissolved. The criteria for evaluating the taste are as follows, the total scores were added up to take the average value, and recorded in Table 1, and the higher the score, the heavier the irritating taste.

[0104] Table 1 Evaluation table of the irritation taste of Examples 1-3 and Comparative Examples 1-3

[0105] Evaluator blank Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 1 5 0 0 1 3 5 5 2 5 1 0 0 3 3 5 3 5 0 0 0 2 5 5 4 5 0 0 0 4 4 4 5 5 0 0 0 3 5 5 6 5 1 0 1 4 4 4 7 5 0 0 0 3 5 5 8 5 0 1 0 2 5 5 9 5 0 0 0 4 4 4 10 5 0 0 0 4 5 5 average 5 0.2 0.1 0.2 3.2 4.5 4.7

[0106] Note: The criteria for evaluating irritation are: 0: no irritation, 1: minimal irritation, 2: slight irritation, 3: strong irritation, 4: strong irritation, 5: unbearable irritation.

[0107] As shown in the table above, Comparative Examples 1, 2 and 3 used well-known flavoring agents, namely sucralose, tartaric acid, sodium citrate and malic acid as their ingredients, and the taste was slightly reduced after 1 minute of complete dissolution, however, the change value was the lowest, which indicated that sucralose, tartaric acid, sodium citrate and malic acid could not completely eliminate the pungent taste of mabaloxavir.

[0108] On the other hand, unexpected effects were obtained by using Examples 1-3 of the present invention. Citric acid and any sweetener, which are usually used as stabilizers and pH regulators in general drugs, almost eliminated the irritating taste and bitterness of mabaloxavir after being dissolved for 1 minute.

[0109] Therefore, it is proved that the oral thin film preparation of the present invention has a better bitterness masking effect than the film preparation containing traditional flavoring agents; and it is also proved that not all conventionally used stabilizers and pH adjusters have the ability to mask irritating taste and bitterness.

[0110] Test 1: Determination of melting time

[0111] Detection method: Place the mabaloxavir orodispersible film preparation of each example and comparative example in a culture dish containing 20 ml of purified water at 37°C±0.5°C, and record the time for the sample to be completely dissolved, which is the disintegration time.

[0112] Test 2: Determination of tensile strength

[0113] Testing method: Use intelligent electronic tensile testing machine for testing.

[0114] Tensile strength calculation formula: Tensile strength = applied stress / cross-sectional area

[0115] Test 3: Elongation determination

[0116] Testing method: Use intelligent electronic tensile testing machine for testing.

[0117] Elongation calculation formula: Elongation = length increase / original length x 100%

[0118] Inspection Project Melting time(s) Tensile strength(MPa) Elongation % Target ≤60 ＞1 ＞2 Example 1 40 2.9 7.1 Example 2 42 3.2 6.8 Example 3 45 2.7 5.5 Comparative Example 1 41 2.6 7.0 Comparative Example 2 34 2.8 6.9 Comparative Example 3 48 2.6 6.8

[0119] From this table, it can be seen that the proportion of active ingredients is within the range of 10%-15%, the proportion of film-forming materials is within the range of 10%-70%, and the proportion of plasticizers is within the range of 2%-25%, all of which meet the requirements. The disintegrant is cross-linked sodium carboxymethyl cellulose, which directly affects the disintegration, tensile strength and elongation of the film.

[0120] Experiment 4: Determination of content uniformity and comparison of appearance:

[0121]

[0122]

[0123] As described in the table above, the average particle size of the API is less than 10 μm, and the content range is 10%-20%. The prepared film has good content uniformity, smooth appearance, and is easily accepted by patients, which increases patient compliance and medication safety.

[0124] Test 5: Dissolution Study

[0125] The dissolution and release rate was determined according to the method for determination (Method 2, Part 4, General Rules 0931, Chinese Pharmacopoeia 2020 Edition).

[0126] The dissolution conditions were 0.07% hexadecyltrimethylammonium bromide (CTAB) phosphate buffer (3.40 g of potassium dihydrogen phosphate and 3.55 g of anhydrous disodium hydrogen phosphate were dissolved in water and diluted to 2000 ml, and 1.40 g of CTAB was added, dissolved and mixed) with 900 ml of dissolution medium at a speed of 50 revolutions per minute. The operation was carried out according to the method and samples were taken after 30 minutes.

[0127] The results are as follows

[0128] Dissolution % Example 1 101.7％ Example 2 79％ Example 3 60％ Comparative Example 1 99.1％ Comparative Example 2 100.2％ Comparative Example 3 98.9％

[0129] From the dissolution results in the above table, it can be seen that the mabaloxavir orodispersible film preparation prepared in the embodiment of the present invention can meet the technical effect of very rapid dissolution by using hypromellose, and the dissolution rate is above 85% within 30 minutes. When the film-forming material is changed in Examples 2 and 3, the solubility of the prepared mabaloxavir orodispersible film preparation in the dissolution medium is significantly reduced, and the technical effect of rapid dissolution cannot be achieved.

Claims

1. A mabaloxavir orodispersible film-dissolving agent, characterized in that The mabaloxavir orodispersible film-forming agent comprises, by weight percentage, 10% to 20% of mabaloxavir, 10% to 70% of film-forming material, 3% to 15% of disintegrant, 2% to 25% of plasticizer, 0% to 5% of flavoring agent and 0% to 3% of auxiliary material.

2. The mabaloxavir orodispersible film-dissolving preparation according to claim 1, characterized in that The mabaloxavir orodispersible film-forming agent comprises, by weight percentage, 10% to 20% of mabaloxavir, 20% to 60% of film-forming material, 5% to 10% of disintegrant, 5% to 20% of plasticizer, 1% to 5% of flavoring agent and 1% to 3% of auxiliary material.

3. The mabaloxavir orodispersible film-dissolving preparation according to claim 2, characterized in that The mabaloxavir orodispersible film-forming agent comprises, by weight percentage, 10% to 20% of mabaloxavir, 30% to 50% of film-forming material, 6% to 8% of disintegrant, 10% to 20% of plasticizer, 2% to 5% of flavoring agent and 2% to 3% of auxiliary material.

4. The mabaloxavir orodispersible film-dissolving formulation according to claim 1, 2 or 3, characterized in that The flavoring agent is citric acid, malic acid or tartaric acid; wherein the weight percentage of citric acid is at least 3%.

5. The mabaloxavir orodispersible film-dissolving preparation according to claim 1, 2 or 3, characterized in that The auxiliary materials are sweeteners and colorants; the sweeteners are saccharin sodium, fructose, mannitol, sucrose, menthol, xylitol or sucralose; the colorants are titanium dioxide, yellow iron oxide, red iron oxide or black iron oxide.

6. The mabaloxavir orodispersible film-dissolving preparation according to claim 1, 2 or 3, characterized in that The film-forming material is one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol, polyethylene oxide, gum arabic, xanthan gum, and agar.

7. The mabaloxavir orodispersible film-dissolving preparation according to claim 1, 2 or 3, characterized in that The plasticizer is one or more of polyethylene glycol, propylene glycol, glycerol and Tween 80.

8. The mabaloxavir orodispersible film-dissolving preparation according to claim 1, 2 or 3, characterized in that The disintegrant is cross-linked carboxymethyl cellulose sodium.

9. The mabaloxavir orodispersible film-forming agent according to claim 1, 2 or 3, characterized in that The mabaloxavir orodispersible film-forming agent is completely dissolved in 25° C. water within 60 seconds.

10. A method for preparing the mabaloxavir orodispersible film-dissolving preparation according to claim 1, 2 or 3, characterized in that The method described is carried out as follows: (1) grinding, sieving or jet milling mabaloxavir to control the average particle size D90 to be less than 10 μm; (2) dispersing the mabaloxavir obtained in step (1) in purified water or solvent-water, adding a flavoring agent and stirring evenly, then adding a film-forming material and mixing evenly to obtain a glue solution; (3) degassing the glue solution obtained in step (2) by centrifugation or static degassing under vacuum conditions; (4) applying the glue obtained in step (3) onto a PET tape, drying to obtain a film, peeling the film from the PET tape, cutting, and sealing to obtain a mabaloxavir orosoluble film.

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