Brivaracetam oral dissolving film immediate-release formulation composition, and formulation and use thereof

Abstract

A brivaracetam oral dissolving film immediate-release formulation composition, comprising brivaracetam or a pharmaceutically acceptable salt thereof, a prodrug thereof, a metabolite thereof, a solvate thereof, a crystal thereof, or a deuterated substance thereof, and an excipient. The weight percentage of brivaracetam or the pharmaceutically acceptable salt thereof, the prodrug thereof, the metabolite thereof, the solvate thereof, the crystal thereof, or the deuterated substance thereof in the composition is 1%-60%. The brivaracetam oral dissolving film immediate-release formulation has the characteristics of fast disintegration, good taste, and good stability.

Description

Brivaracetam oral film-dissolving rapid-release preparation composition, preparation and use thereof Technical Field

[0001] The present invention belongs to the field of pharmaceutical preparations, and specifically relates to a brivaracetam oral film-dissolving rapid-release preparation which shortens the onset time of brivaracetam and can be used for acute medication of epilepsy patients, as well as a preparation method, preparation and use thereof. Background Art

[0002] Brivaracetam, also known as brivaracetam, is a new generation of anti-epileptic drugs developed by the Belgian pharmaceutical company UCB. It is currently available in three dosage forms: oral solution, tablets, and intravenous solution. In August 2021, the U.S. Food and Drug Administration (FDA) approved the expanded indications of Briviact: it can be used as monotherapy or adjuvant therapy for patients as young as 1 month old to treat partial-onset epilepsy. It is worth mentioning that this is the first time that Briviact intravenous preparations have been provided to pediatric patients when oral administration is temporarily not feasible. It is also the only intravenous preparation approved by the FDA in the past 7 years for the treatment of partial-onset epilepsy in pediatric patients 1 month and older. Intravenous injections have poor compliance with medication for patients, especially children, and new child-friendly dosage forms are urgently needed. In addition, patients with epilepsy need long-term medication, and how to improve the privacy of patients' medication is also an important need for patients.

[0003] Oral fast-dissolving film is easy to use, releases drugs quickly, and can be quickly absorbed through the oral mucosa to take effect. It has the advantages of being convenient for children to use drugs, preventing vomiting of drugs, and meeting the privacy requirements of adults.

[0004] According to FDA data, brivaracetam is a white to off-white crystalline powder, classified as BCS Class I. It is highly soluble in water, buffer solutions (pH 1.2, 4.5, 6.8, and 7.4), ethanol, methanol, and glacial acetic acid, freely soluble in acetonitrile and acetone, soluble in toluene, and very slightly soluble in n-hexane. Experiments have also revealed that brivaracetam has a bitter taste and tends to stick.

[0005] Brivaracetam's marketed formulations primarily include tablets, oral solutions, and injections. Tablets can lead to poor compliance in patients with dysphagia, and precise dosing control in children is difficult, impacting therapeutic efficacy. Oral solutions are unstable and often contain preservatives, making them difficult to prepare and meet relevant standards. Intravenous solutions rely on healthcare professionals, present significant limitations, and are unsuitable for long-term daily administration. Furthermore, they can cause skin redness, pain, and even inflammation during use.

[0006] In actual drug administration, brivaracetam has also been found to have the following issues: The brivaracetam API has a very pronounced bitter taste. Furthermore, brivaracetam has a very high water solubility (over 1g / mL), allowing it to dissolve rapidly in the mouth. Taste is a significant factor influencing patient compliance with medication. Therefore, masking the unpleasant taste in the formulation is crucial, but conventional taste-masking techniques present significant challenges.

[0007] Furthermore, according to official reports, publicly available brivaracetam preparations are associated with adverse reactions such as drowsiness, dizziness, fatigue, nausea, vomiting, and headache. Overall, existing brivaracetam preparations suffer from several deficiencies: 1. They exhibit the most common psychiatric adverse reactions, such as drowsiness, dizziness, fatigue, headache, nausea, and vomiting, which severely impact patients' quality of life; 2. They exhibit unsatisfactory taste-masking effects; and 3. They suffer from poor medication compliance. Therefore, there is a need for a brivaracetam preparation with fewer side effects, improved efficacy, a pleasant taste, and good stability to address the shortcomings of existing technologies. Summary of the Invention

[0008] The present invention aims to provide a brivaracetam rapid-release oral dissolving film comprising the active ingredient brivaracetam or a salt thereof and excipients. This preparation exhibits rapid disintegration, excellent mouthfeel, and good stability. It is also convenient to administer, enabling precise dosing for children, effectively improving medication compliance among children, the elderly, and other patients with difficulty swallowing, while enhancing privacy for adults. It also has the potential to alleviate brivaracetam-induced side effects such as drowsiness, dizziness, and fatigue.

[0009] One or more embodiments of the present application provide a brivaracetam oral film-dissolving rapid-release preparation composition, which comprises brivaracetam or a pharmaceutically acceptable salt, prodrug, metabolite, solvate, crystal, or deuterated product thereof and excipients, wherein the weight percentage of brivaracetam or a pharmaceutically acceptable salt, prodrug, metabolite, solvate, crystal, or deuterated product thereof in the composition is 1%-60% (e.g., 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%); the excipients include a film-forming material and a flavoring agent.

[0010] In one or more embodiments, the weight percentage of the film-forming material in the composition is 1-50% (e.g., 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%), and the weight percentage of the flavoring agent in the composition is 1-10% (e.g., 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%).

[0011] In one or more embodiments, the auxiliary material further includes a thickener and a plasticizer.

[0012] In one or more embodiments, the weight percentage of the thickener in the composition is 0-20% (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%), and the weight percentage of the plasticizer in the composition is 0-15% (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%).

[0013] In one or more embodiments, the film-forming material is hydroxypropyl methylcellulose (HPMC), One or more of IR, hydroxypropyl cellulose, gelatin, pullulan, maltodextrin, polyvinyl alcohol, sodium alginate, gum arabic, povidone, acrylic acid copolymer, hydroxypropyl cellulose, polyoxyethylene, shellac, starch, agar, zein, polylactic acid, and silicone rubber.

[0014] In one or more embodiments, the film-forming material is HPMC, IR, hydroxypropylcellulose, pullulan, polyoxyethylene, or polyvinyl alcohol.

[0015] In one or more embodiments, the HPMC is HPMC E30, HPMC E15, or HPMC E5.

[0016] In one or more embodiments, the thickener is One or more of MAE 30DP, xanthan gum, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), tragacanth gum, povidone, carbomer, carrageenan, guar gum, agar, methylcellulose, ethylcellulose, polyethylene oxide, and polyacrylic acid.

[0017] In one or more embodiments, the thickener is MAE 30DP, polyvinylpyrrolidone (PVP), xanthan gum, or sodium carboxymethylcellulose.

[0018] In one or more embodiments, the plasticizer is glycerol, polyethylene glycol or triethyl citrate.

[0019] In one or more embodiments, the flavoring agent is one or more of neotame, aspartame, sucralose, cyclamate, sucrose, mannitol, xylitol, sorbitol, stevioside, syrup, flavor, saccharin sodium, acesulfame potassium, citric acid, malic acid, lactic acid, and tartaric acid.

[0020] In one or more embodiments, the flavoring agent is sucrose, mannitol, neotame, aspartame, saccharin sodium, sucralose, acesulfame potassium, or essence.

[0021] In one or more embodiments, the flavor is one or more of banana flavor, lemon flavor, sweet orange flavor, tangerine flavor, and strawberry flavor.

[0022] One or more embodiments of the present application provide a brivaracetam oral film-dissolving preparation, which is prepared from the brivaracetam oral film-dissolving rapid-release preparation composition of the present application.

[0023] In one or more embodiments, the thickness of the brivaracetam oral-soluble film is within 20-100 microns (eg, 30, 40, 50, 60, 70, 80, 90 microns).

[0024] In one or more embodiments, the brivaracetam oral-dissolving film disintegrates within 10-60 s (eg, 20, 30, 40, 50 s).

[0025] In one or more embodiments, the brivaracetam oral-dissolving film disintegrates within 2-25 s (eg, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 s).

[0026] One or more embodiments of the present application provide a method for preparing a brivaracetam oral film, which comprises the following steps:

[0027] (1) Weighing brivaracetam or its pharmaceutically acceptable salt, prodrug, metabolite, solvate, crystal, or deuterated form, a soluble film-forming material, a flavoring agent, and optionally a thickener and a plasticizer;

[0028] (2) Add the above excipients to water and stir to dissolve;

[0029] (3) Weighing a prescribed amount of a poorly soluble film-forming material and adding it to the above solution, heating and stirring continuously to uniformly disperse it to obtain a glue solution; preferably, heating to 50-70° C. (e.g., 60° C.);

[0030] (4) vacuum degassing the glue overnight;

[0031] (5) pouring the glue onto the release film for coating;

[0032] (6) vacuum drying the coated release film at 40-60° C. (e.g., 50° C.);

[0033] (7) Cut the membrane and repack.

[0034] In one or more embodiments, the coating temperature is 25° C.-50° C. (eg, 30, 40, 45° C.), and the coating speed is 10-20 mm / s (eg, 15 mm / s).

[0035] One or more embodiments of the present application provide a kit comprising the brivaracetam oral-dissolving film of the present application.

[0036] In one or more embodiments, the packaging of the kit is printed with a dosage scale for accurately taking a corresponding dosage according to the patient's weight.

[0037] One or more embodiments of the present application provide the brivaracetam oral film-dissolving rapid-release preparation composition of the present application or the use of the brivaracetam oral film-dissolving preparation of the present application in the preparation of a drug for treating epilepsy.

[0038] One or more embodiments of the present application provide a brivaracetam oral film-dissolving composition, a preparation method and use thereof.

[0039] One or more embodiments of the present application provide a brivaracetam oral film-soluble composition comprising brivaracetam or a pharmaceutically acceptable salt thereof, one or more of a film-forming material, a thickener, a plasticizer, and a flavoring agent.

[0040] The brivaracetam oral film-dissolving composition obtained by the present invention, which can be accurately dosed, has precise dosage markings, a fast dissolution rate, no gritty feeling after dissolving in the oral cavity, a uniform appearance, good flexibility, a good taste-masking effect, and does not require water for administration. It is convenient for the elderly, children, and other patients with difficulty swallowing or special conditions to take the composition, and improves the privacy of adults taking the medicine. At the same time, no sedimentation occurs during the film liquid preparation process, and the content uniformity meets the requirements.

[0041] The present invention also provides a method for preparing the brivaracetam rapid-release oral dissolving film, which is simple, easy to control, low in cost, environmentally friendly, and suitable for large-scale industrial production.

[0042] To achieve at least one of the above objectives, the present invention adopts the following technical solutions:

[0043] In a first aspect, the present invention provides a brivaracetam rapid-release oral dissolving film comprising an active ingredient brivaracetam or a salt thereof and excipients, wherein the excipients include a film-forming agent, a thickener, a plasticizer, and a flavoring agent.

[0044] More preferably, the weight percentage of the active ingredient in the oral dissolving film is 1-60%, preferably, the weight percentage of the active ingredient in the oral dissolving film is 50%.

[0045] Further preferably, the content of the film-forming agent is 1-50% by weight of the oral film, the content of the thickener is 1-20% by weight of the oral film, the content of the plasticizer is 1-15% by weight of the oral film, and the content of the flavoring agent is 1-10% by weight of the oral film.

[0046] Further preferably, the film-forming agent is selected from one or more of HPMC, gelatin, pullulan, maltodextrin, polyvinyl alcohol, sodium alginate, gum arabic, povidone, shellac, starch, agar, zein, hydroxypropyl cellulose, polyoxyethylene, acrylic acid copolymer, polylactic acid and silicone rubber, preferably one or more of HPMC, polyvinyl alcohol and polyoxyethylene;

[0047] Further preferably, the thickener is selected from xanthan gum, sodium carboxymethylcellulose, tragacanth gum, HPMC, sodium alginate, povidone, carbomer, carrageenan, guar gum, agar, methylcellulose, ethylcellulose, hydroxypropyl cellulose, polyoxyethylene, polyacrylic acid, etc., preferably xanthan gum, sodium carboxymethylcellulose, and povidone.

[0048] Further preferably, the plasticizer is selected from glycerol and polyethylene glycol.

[0049] Further preferably, the flavoring agent is selected from any one or more of neotame, aspartame, sucralose, cyclamate, sucrose, mannitol, xylitol, sorbitol, stevioside, syrup, flavor, saccharin sodium, and acesulfame potassium, preferably sucrose, mannitol, neotame, aspartame, sucralose, acesulfame potassium, and flavor; and the flavor is selected from apple flavor, banana flavor, sweet orange flavor, tangerine flavor, and strawberry flavor.

[0050] The oral film-dissolving agent of the present invention can be prepared by a coating method. In another aspect of the present invention, a method for preparing a brivaracetam oral film-dissolving agent comprising the active ingredient brivaracetam or a salt thereof and excipients is provided, which is prepared specifically by the following steps:

[0051] 1. Weigh the prescribed amount of active ingredient, soluble film-forming material, thickener, plasticizer and flavoring agent;

[0052] 2. Add the above excipients to the prescribed amount of water and stir to dissolve;

[0053] 3. Weigh the prescribed amount of insoluble film-forming material and add it to the above solution, heat it to 60°C and continue stirring to make it evenly dispersed;

[0054] 4. Vacuum degassing the obtained glue overnight;

[0055] 5. Pour the glue onto the release film and apply it;

[0056] 6. After coating, transfer the release film to a vacuum drying oven at 50°C for drying;

[0057] 7. Cut the film and repack.

[0058] In one or more embodiments, the specifications of the brivaracetam oral film are: 10 mg, 25 mg, 50 mg, 75 mg and 100 mg.

[0059] In one or more embodiments, the dosage and administration of brivaracetam oral dissolving film: For patients with epilepsy aged over 1 month, the oral dosage is as shown in the following table with reference to FDA-approved recommendations. The dosage is to be taken according to the doctor's instructions or under the guidance of a doctor.

[0060] Table 1 FDA recommended dosage of brivaracetam

[0061] The precise dosage is calculated based on body weight, and a film of precise dosage is cut out according to the scale line on the oral dissolving film. The film is placed in the mouth without the need for water, and the film quickly disintegrates in the mouth to release the drug.

[0062] By using the above technical solution, the film thickness and disintegration time of the brivaracetam rapid-release oral dissolving film are limited. The present invention has at least one of the following beneficial effects:

[0063] 1. The rapid-release oral dissolving film of the present application has a thickness of less than 100 microns through the design of its formulation, ensuring that the film has no gritty feeling in the oral cavity.

[0064] 2. The disintegration time in the oral cavity is within 60 seconds (e.g., 30 seconds). The preparation process of the optimized formulation is simple, the production cost is low, and it is suitable for large-scale industrial production.

[0065] 3. Experiments have shown that the brivaracetam rapid-release preparation provided by the present invention has a good taste, masks the unpleasant taste of brivaracetam, is easy to control the dosage, and is convenient for the elderly, children and other patients with difficulty swallowing or special conditions to take.

[0066] Therefore, the present application provides a brivaracetam rapid-release formulation that meets various needs. DETAILED DESCRIPTION

[0067] The present invention will be further described below with reference to the embodiments. The following description is only for explaining the present invention and does not limit its contents in any way.

[0068] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or those recommended by the manufacturer. All reagents or instruments used, if the manufacturer is not specified, are commercially available conventional products.

[0069] The brivaracetam oral dissolving film and its preparation method according to the embodiment of the present invention are described in detail below.

[0070] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0071] Examples 1 to 12

[0072] HPMC is used as a film-forming agent; glycerin is used as a plasticizer; strawberry flavor, lemon flavor, orange flavor, citric acid, malic acid, lactic acid, tartaric acid, sucralose, and neotame are used as flavoring agents; the specific prescription dosage is shown in Tables 2-3.

[0073] Table 2 Formulations of Brivaracetam Oral Dissolving Films of Examples 1 to 8

[0074] Table 3 Formulations of the Brivaracetam Oral Dissolving Films of Examples 9 to 12

[0075] The specific preparation method is as follows:

[0076] Dissolve brivaracetam, glycerin, and flavoring agents in the prescribed amount of water. Add HPMC and continue stirring at 60°C to achieve a uniform dispersion. Vacuum the resulting adhesive solution to remove bubbles overnight, then pour it onto a release film and apply the coating. After coating, transfer the release film to a vacuum drying oven at 50°C to dry. Peel the film, cut it, and package it into a bag with printed dimensions.

[0077] The characterization method of the obtained oral dissolving film is described in detail as follows:

[0078] Film thickness measurement: Use a micrometer to measure the thickness of ten films (average value and SD)

[0079] Disintegration time determination: Take a piece of drug film, clamp it with a paper clip, put it into the disintegration instrument, and check it according to the disintegration time test method 0921 of the fourth part of the "Pharmacopoeia of the People's Republic of China (2020 edition)".

[0080] Disintegration Test Method A

[0081] Apparatus: Consists of a 200 ml glass beaker and an overhead stirrer (100 rpm).

[0082] step

[0083] 1. Add 100 ml of solvent (e.g. water, saliva, gastric juice) to a 200 ml glass beaker.

[0084] 2. Heat the solvent to 37°C.

[0085] 3. Set the overhead stirrer to 100 rpm, but do not turn on the stirrer.

[0086] 4. Place the beaker under the overhead stirrer with the stirrer head immersed in the solvent.

[0087] 5. Measure the thickness of the oral film samples (n>10; mean and SD).

[0088] 6. Place the sample on the inner wall of the beaker. Make sure the sample is completely immersed in the solvent.

[0089] 7. Turn on the overhead stirrer.

[0090] 8. Record the time required for the film sample to completely disintegrate. Start timing when the overhead stirrer is turned on.

[0091] 9. Repeat this process 2 more times and calculate the average time.

[0092] Disintegration Test Method B

[0093] Micropipette method

[0094] step

[0095] 1. Heat the solvent (e.g. water, saliva, gastric juice) to 37°C.

[0096] 2. Measure the thickness of the ODF samples (n>10, mean and SD).

[0097] 3. Place the sample on a clean, flat surface.

[0098] 4. Use a pipette to transfer 300 μl of solvent to the center of the sample.

[0099] 5. Record the time required for the solvent drop to completely penetrate the sample. Start timing when the solvent drop is placed on the sample.

[0100] 6. Repeat this process 2 more times and calculate the average time.

[0101] Disintegration Test Method C

[0102] Device: Petri dish

[0103] step

[0104] 1. Heat the solvent (distilled water or any suitable medium, such as saliva, gastric juice) to 37°C.

[0105] 2. Measure the thickness of oral film samples (n>10, mean and SD).

[0106] 3. Place 5 ml of solvent in a Petri dish.

[0107] 4. Place the film sample on the solvent surface.

[0108] 5. Record the time required for the sample to break into small particles. Start timing when the sample is placed in the Petri dish.

[0109] 6. Repeat this process 2 more times and calculate the average time.

[0110] Content determination: HPLC is used for content determination. The content of brivaracetam should be 90.0% to 110.0% of the labeled amount;

[0111] Table 4 Brivaracetam oral film content detection method (HPLC)

[0112] The above characterization results show that the HPMC type significantly affects the viscosity of the resulting adhesive. Adhesives prepared with HPMC types such as K100M, K15M, K4M, and E50 have excessive viscosity and are difficult to apply. Adhesives prepared with E30, E15, E5, and E3 have moderate viscosity and are easy to apply. However, the oral film prepared with E3 has poor friability and is difficult to cut. The preferred types are E30, E15, and E5.

[0113] Taking HPMC E15 as an example, a screening of flavoring agents (Table 3) revealed that the addition of neotame / sucralose and flavorings all provided excellent flavor correction. Furthermore, the prepared oral dissolving film had a smooth surface, a brivaracetam loading of up to 50%, a uniform thickness of less than 100 microns, a uniform content, good toughness, a disintegration time of less than 60 seconds, and a pleasant mouthfeel (test participants gave it an average score of 4 out of 5).

[0114] Examples 13 to 17

[0115] On the basis of the above HPMC E15, other film-forming materials such as hydroxypropyl cellulose, pullulan, thickeners such as PVP, When MAE 30DP was used, glycerin was used as the plasticizer, and sucralose / neotame was used as the flavoring agent, the resulting film also met the requirements: smooth surface, uniform thickness, good toughness, uniform content, and sweet taste (the subjects gave the test an average score of 4 out of 5).

[0116] Table 5 Formulations and disintegration times of brivaracetam oral dissolving films 13 to 17 in Examples

[0117] Examples 18 to 22

[0118] Polyoxyethylene is used as a film-forming agent; strawberry essence, citric acid, malic acid, lactic acid, tartaric acid, and neotame are used as flavoring agents; the prepared oral dissolving film has a smooth surface, a drug loading of up to 50% of the API brivaracetam, uniform thickness, good toughness, uniform content, and a good taste (the test subjects gave an average score of 4 out of 5).

[0119] Table 6 Formulations and disintegration times of the brivaracetam oral dissolving films of Examples 18 to 22

[0120] Examples 23 to 26

[0121] With polyvinyl alcohol, IR and pullulan are used as film-forming agents; strawberry essence, citric acid, malic acid, lactic acid, tartaric acid, and neotame are used as flavoring agents; the prepared oral dissolving film has a smooth surface, uniform thickness, good toughness, uniform content, and excellent taste (the subjects gave an average score of 4 points out of a full score of 5).

[0122] Table 7 Formulations and disintegration times of the brivaracetam oral dissolving films of Examples 23 to 26

[0123] Example 27 Stability Test of Brivaracetam Oral Dissolving Film

[0124] This study selected the products obtained in Examples 13, 14, 19, 23, 24, and 26 as examples and conducted a stability investigation.

[0125] The stability test shows that the brivaracetam oral film-dissolving composition of the present application has good stability.

Claims

1. A rapid-release buccal soluble film preparation composition of brivaracetam, which comprises brivaracetam or a pharmaceutically acceptable salt, prodrug, metabolite, solvate, crystal, or deuterated compound thereof, and excipients. The weight percentage of brivaracetam or a pharmaceutically acceptable salt, prodrug, metabolite, solvate, crystal, or deuterated compound thereof in the composition is 1% - 60%; the excipients include a film-forming material and a flavoring agent; preferably, the weight percentage of the film-forming material in the composition is 1 - 50%, and the weight percentage of the flavoring agent in the composition is 1 - 10%.

2. The rapid-release buccal soluble film preparation composition of brivaracetam according to claim 1, wherein the excipients further include a thickening agent and a plasticizer; preferably, the weight percentage of the thickening agent in the composition is 0 - 20%, and the weight percentage of the plasticizer in the composition is 0 - 15%.

3. The immediate-release buccal soluble film preparation composition according to claim 2, wherein the film-forming material is one or more of hydroxypropyl methylcellulose (HPMC), IR, hydroxypropyl cellulose, gelatin, pullulan, maltodextrin, polyvinyl alcohol, sodium alginate, gum arabic, polyvinylpyrrolidone, acrylic acid copolymer, hydroxypropyl cellulose, polyethylene oxide, shellac, starch, agar, zein, polylactic acid, and silicone rubber; preferably HPMC, IR, hydroxypropyl cellulose, pullulan, polyethylene oxide, or polyvinyl alcohol; more preferably, the HPMC is HPMC E30, HPMC E15, or HPMC E5.

4. The immediate-release buccal soluble film preparation composition according to claim 2, wherein the thickening agent is one or more of MAE 30DP, xanthan gum, sodium carboxymethyl cellulose, polyvinylpyrrolidone (PVP), tragacanth gum, povidone, carbomer, carrageenan, guar gum, agar, methylcellulose, ethylcellulose, polyethylene oxide, and polyacrylic acid; preferably MAE 30DP, polyvinylpyrrolidone (PVP), xanthan gum, or sodium carboxymethyl cellulose.

5. The rapid-release buccal soluble film preparation composition of brivaracetam according to claim 2, wherein the plasticizer is glycerol, polyethylene glycol, or triethyl citrate; preferably glycerol.

6. The rapid-release buccal soluble film preparation composition of brivaracetam according to claim 2, wherein the flavoring agent is one or more of neotame, aspartame, sucralose, sodium cyclamate, sucrose, mannitol, xylitol, sorbitol, stevioside, syrup, essence, sodium saccharin, acesulfame potassium, citric acid, malic acid, lactic acid, tartaric acid; preferably sucrose, mannitol, neotame, aspartame, sodium saccharin, sucralose, acesulfame potassium, or essence; preferably, the essence is one or more of banana essence, lemon essence, sweet orange essence, tangerine essence, and strawberry essence.

7. A brivaracetam buccal soluble film, which is prepared from the rapid-release buccal soluble film preparation composition of brivaracetam according to any one of claims 1 - 7; preferably, the thickness of the brivaracetam buccal soluble film is within 20 - 100 microns; preferably, the brivaracetam buccal soluble film disintegrates within 10 - 60 s, preferably 2 - 25 s.

8. A preparation method of the brivaracetam buccal soluble film according to claim 7, which comprises the following steps: (1) Weigh brivaracetam or a pharmaceutically acceptable salt, prodrug, metabolite, solvate, crystal, or deuterated compound thereof, and a flavoring agent, and optionally a thickening agent and a plasticizer; (2) Add the above excipients to water and stir to dissolve; (3) Weigh the prescribed amount of the film-forming material and add it to the above solution, heat and continue to stir to make it evenly dispersed to obtain a colloidal solution; preferably, heat to 50 - 70 °C; preferably 60 °C; (4) Remove bubbles from the colloidal solution under vacuum overnight; (5) Pour the colloidal solution onto a release film for coating; preferably, the coating temperature is 25 °C - 50 °C, and the coating speed is 10 - 20 mm / s; (6) Vacuum dry the coated release film at 40 - 60 °C, preferably 50 °C; (7) Cut the film and package it in portions.

9. A kit, which contains the brivaracetam buccal soluble film according to claim 7; preferably, the package of the kit is printed with dose scales for accurately taking corresponding doses according to the patient's weight.

10. Use of the brexipiprazole orally disintegrating film rapid release preparation composition according to any one of claims 1-6 or the brexipiprazole orally disintegrating film according to claim 7 in the preparation of a drug for treating epilepsy.

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