Film agent of lumepirone or salt thereof and preparation method of film agent

Abstract

The invention provides a film agent of lumepirone or salt thereof and a preparation method of the film agent, and relates to the technical field of medicines. The lumepirone injection comprises the following raw materials in parts by mass: 2-30 parts of lumepirone or pharmaceutically acceptable salt thereof, 40-95 parts of a film-forming material, 1-30 parts of a plasticizer and 0.1-5 parts of an antioxidant, the antioxidant is selected from at least one of butylated hydroxyanisole, butylated hydroxytoluene and sodium hydrogen sulfite. The film agent is used for drug delivery through oral mucosa or a sublingual way, so that the bioavailability of the drug can be remarkably improved, the blood concentration can be increased, the drug content in the brain and the D2 target spot occupancy rate can be increased, and the curative effect of the film agent can be effectively enhanced.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a film preparation of lumepirone or a salt thereof and a preparation method thereof. Background Art

[0002] Lumateperone tosylate (Caplyta) is a new atypical antipsychotic drug developed by Intra-Cellular Therapies.

[0003] In December 2019, the U.S. Food and Drug Administration (FDA) approved lumepirone tosylate for the treatment of schizophrenia in adults. In December 2021, the FDA further approved the expanded indication of lumepirone tosylate, which can be used alone or in combination with lithium / valproate to treat depressive episodes associated with bipolar I or II in adults, making it the first and only drug with the above indication.

[0004] Its structural formula is as follows:

[0005]

[0006] Lumiperone tosylate is a 5-hydroxytryptamine isoform 2A (5-HT 2A ) receptor antagonist, D2 receptor presynaptic partial agonist and postsynaptic antagonist, D1 receptor-dependent glutamate modulator, and serotonin reuptake inhibitor.

[0007] Due to the uncertainty of the onset time of schizophrenia and the poor compliance of patients when the disease occurs, it is necessary to give the drug to the patient as soon as possible. Therefore, it is very important to prepare lumepirone into a dosage form that is easy to carry, easy to take and can take effect quickly. Lumiperone tosylate is available in the market in the form of capsules, and some companies are developing orodispersible tablets to improve patient compliance.

[0008] For example, Chinese patent CN118557536A specifically relates to a lumeperone orodisintegrating tablet composition, a preparation method and an application thereof. The raw materials of the lumeperone orodisintegrating tablet composition include, by mass percentage: 16%-20% of lumeperone tosylate, 40%-60% of a hydrophilic diluent, 10%-20% of an alkaline diluent, 5%-15% of a disintegrant, 3%-9% of a flavoring agent, 0.5%-1% of a glidant and 0.2%-2% of a lubricant.

[0009] Although lumepirone tosylate has satisfactory efficacy, tolerability and safety, and has relatively little effect on weight management, cardiovascular metabolism and extrapyramidal symptoms. However, the drug also faces some challenges. "New Antipsychotic Drug: Lumeperone (Sheng Qinrun, Shen Yifeng, Li Huafang)" records that the absolute bioavailability of a capsule dosage form of lumepirone in humans is 4.4%. Due to its low bioavailability and high first-pass metabolism rate, there are significant differences in the bioavailability of the drug in different patients, which leads to uncertainty in efficacy. In addition, since increasing the dose does not linearly increase the exposure of the drug, it is impossible to achieve a better therapeutic effect by increasing the dose. And the occupancy rate of lumepirone tosylate at the D2 target is much lower than that of conventional psychiatric drugs, which is only 39%. Therefore, it is difficult to obtain a higher blood exposure by oral lumepirone tosylate capsules.

[0010] In summary, developing a lumepirone tosylate preparation and innovating its preparation method and administration form in order to improve its bioavailability and increase its D2 target occupancy rate is the research focus of researchers in this field. Summary of the invention

[0011] In view of the above problems, the present invention provides a lumepirone tosylate film, the preparation process of which is to add appropriate amounts of film-forming materials, plasticizers, disintegrants and stabilizers and other excipients, and deliver the drug through the oral mucosa or sublingual route. With the preparation developed by the present invention, this administration method can not only significantly improve the bioavailability of the drug, increase the blood drug concentration, increase the drug content in the brain and the D2 target occupancy rate, but also effectively enhance its therapeutic effect, and bring a more efficient and convenient treatment experience to patients.

[0012] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0013] In one aspect, the present invention provides a film preparation of lumepirone or a salt thereof, comprising the following raw materials, measured by weight: 2-30 parts of lumepirone or a pharmaceutically acceptable salt thereof, 40-95 parts of a film-forming material, 1-30 parts of a plasticizer, and 0.1-5 parts of an antioxidant;

[0014] The film-forming material is selected from at least one of copolyvidone, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, povidone, hydroxypropyl methylcellulose, polyvinyl alcohol, polyoxyethylene, polyethylene glycol, hydroxypropyl cellulose and hydroxyethyl cellulose;

[0015] The plasticizer is selected from at least one of polyethylene glycol, glycerol, propylene glycol, triacetin, triethyl citrate, sorbitol, mannitol, dibutyl phthalate, Span and Tween;

[0016] The antioxidant is selected from at least one of butylated hydroxyanisole, butylated hydroxytoluene and sodium bisulfite.

[0017] Preferably, the following raw materials are included, by weight: 2-25 parts of lumepirone or a pharmaceutically acceptable salt thereof, 40-92 parts of a film-forming material, 1-20 parts of a plasticizer, and 0.2-5 parts of an antioxidant;

[0018] Further preferably, the following raw materials are included, by weight: 2-12 parts of lumepirone or a pharmaceutically acceptable salt thereof, 45-92 parts of a film-forming material, 1-15 parts of a plasticizer, and 0.2-4 parts of an antioxidant;

[0019] Preferably, the film-forming material is selected from at least one of copovidone, polyoxyethylene and hydroxypropyl methylcellulose; further preferably, the film-forming material is selected from at least one of copovidone and polyoxyethylene; more preferably, the film-forming material is copovidone and polyoxyethylene.

[0020] Preferably, the mass ratio of copovidone to polyoxyethylene is 2-8:2-8.

[0021] Preferably, the plasticizer is selected from at least one of polyethylene glycol, propylene glycol and polyvinyl pyrrolidone; further preferably, the plasticizer is polyethylene glycol.

[0022] Preferably, the antioxidant is sodium bisulfite.

[0023] Preferably, the raw materials of the film dosage form may also include flavoring agents.

[0024] Preferably, the flavoring agent is selected from at least one of sucralose, essence, citric acid, and tartaric acid. More preferably, the flavoring agent is selected from at least one of sucralose and essence.

[0025] Preferably, the composition comprises the following raw materials in parts by mass: 2-30 parts of lumepirone or a pharmaceutically acceptable salt thereof, 40-95 parts of a film-forming material, 1-30 parts of a plasticizer, 0.1-5 parts of an antioxidant and 0.1-3 parts of a flavoring agent.

[0026] Preferably, the film is used for drug delivery via the oral mucosa or sublingual route.

[0027] Preferably, the lumepirone or a pharmaceutically acceptable salt thereof is lumepirone tosylate.

[0028] On the other hand, the present invention provides a method for preparing the above-mentioned film, which is a hot melt method and comprises the following steps:

[0029] After the raw materials are mixed, they are extruded at a speed of 0.01-100kg / h and stretched into a film.

[0030] Preferably, the hot melt method comprises the following steps:

[0031] (1) Mixing of raw materials and auxiliary materials;

[0032] (2) adding the mixture into a hot melt extruder at a rate of 0.01-100 kg / h, with the die temperature of the hot melt extruder being 130-190° C. After extrusion, stretching is performed to form a film, and the rotation speed of the film-stretching device is adjusted to obtain films of different thicknesses and widths;

[0033] (3) The prepared film is cut into films of different sizes and shapes by a film cutting machine.

[0034] Preferably, the screw speed of the hot melt extrusion is 20-800 rpm.

[0035] Preferably, when the preparation method is a hot melt method, the raw materials of the film agent, in parts by mass, include the following components:

[0036] 2-28 parts of lumiperone tosylate, 40-66 parts of copovidone, 40-66 parts of polyoxyethylene, 2-10 parts of polyethylene glycol, 0.1-0.5 parts of BHT, and 0.1-1.5 parts of sucralose.

[0037] In another aspect, the present invention provides a method for preparing the above-mentioned film, which is a solvent method.

[0038] Preferably, the solvent method comprises the following steps:

[0039] Step 1: Mix the film-forming material with the solvent, add the solubilizer and the flavoring agent, and stir to obtain a glue solution;

[0040] Step 2: Spread the glue evenly to form a film.

[0041] Preferably, the solvent is selected from water or alcohol.

[0042] Preferably, when the preparation method is a solvent method, the raw materials of the film preparation, in parts by mass, comprise the following components:

[0043] 10-30 parts of lumepirone tosylate, 45-65 parts of film-forming material, 5-10 parts of propylene glycol, 5-15 parts of polyvinyl pyrrolidone, 1-2 parts of sucralose, and 0.3-0.8 parts of fruit flavor.

[0044] Preferably, the film-forming material is selected from polyvinyl alcohol or hydroxypropyl methylcellulose.

[0045] Preferably, the weight of the film is 25 mg or 50 mg.

[0046] Preferably, the dosage of API in the film is 2 mg or 4 mg (calculated as lumiperone).

[0047] Compared with the prior art, the present invention has the following beneficial effects:

[0048] 1. The present invention introduces an innovative lumepirone tosylate film, which delivers drugs through the oral mucosa or sublingual route. With the preparation developed by the present invention, this administration method can not only significantly improve the bioavailability of the drug, quickly increase the blood drug concentration, increase the drug content in the brain and the D2 target occupancy rate, but also effectively enhance its efficacy and bring patients a more efficient and convenient treatment experience.

[0049] 2. The film prepared by the present invention is prepared by adding appropriate amounts of film-forming materials, plasticizers, disintegrants, stabilizers and other auxiliary materials to prepare a film with smooth appearance, uniform thickness, rapid disintegration, good mechanical properties, and lumepirone tosylate in amorphous or microcrystalline form. It has good solubility and stability, and its bioavailability is significantly higher than that of the original capsule.

[0050] 3. The lumepirone tosylate oral film of the present invention has good solubility, can be completely disintegrated within 30 seconds, and is rapidly absorbed by the oral mucosa. DETAILED DESCRIPTION

[0051] In order to make the technical means, creative features, purpose and effect of the present invention easy to understand, the present invention is further explained below in conjunction with specific embodiments, but the following embodiments are only preferred embodiments of the present invention, not all. Based on the embodiments in the implementation mode, other embodiments obtained by those skilled in the art without making creative work all belong to the protection scope of the present invention. It is worth noting that the raw materials used in the present invention are all common commercial products, and their sources are not specifically limited. The technology and scientific terms used in the embodiments have the meanings commonly understood by those of ordinary skill in the art to which the present invention belongs.

[0052] Source of raw materials:

[0053] Lumiperone tosylate was purchased from Wuhan Hanxiang Biotechnology Co., Ltd.

[0054] Copolyvidone was purchased from BASF with a molecular weight of 45000-70000.

[0055] Polyoxyethylene was purchased from Dow Chemical Company, USA, with a molecular weight of about 200,000.

[0056] Polyethylene glycol was purchased from Jiangxi Alpha Hi-Tech Pharmaceutical Co., Ltd. with a molecular weight of 5000-7000.

[0057] Example 1

[0058] A film preparation of lumepirone or its salt

[0059] The prescription is as follows:

[0060] Table 1. Example 1 prescription

[0061]

[0062] The preparation method is hot melt method:

[0063] Weighing: Accurately weigh the raw and auxiliary materials of the batch prescription and set aside;

[0064] Mixing: First take the raw material and copovidone, and pass through a 30-mesh sieve; then add the remaining materials and pass through a 30-mesh sieve together with the above materials.

[0065] Hot melt extrusion: The experiment was carried out using a hot melt extruder to prepare lumepirone tosylate film, with extrusion temperatures set at 80, 100, 125, 145, 145, 145, 145°C, film mouth temperature set at 145°C, feed rate set at 0.6kg / h, screw speed set at 50rpm, and film pulling speed set at 2rpm. The parameters were subsequently adjusted according to the material state.

[0066] Cutting: The prepared film is cut into films of different sizes and shapes by a film cutting machine.

[0067] Embodiment 2-4

[0068] A film preparation of lumepirone or its salt

[0069] The prescription is as follows:

[0070] Table 2. Prescriptions for Examples 2-4

[0071]

[0072] The preparation method is the same as that in Example 1.

[0073] Embodiment 5-6

[0074] A film preparation of lumepirone or its salt

[0075] The prescription is as follows:

[0076] Table 3. Prescriptions for Examples 5-6

[0077]

[0078] The preparation method is the same as that in Example 1.

[0079] Embodiment 7-8

[0080] A film preparation of lumepirone or its salt

[0081] The prescription is as follows:

[0082] Table 4. Prescriptions for Examples 7-8

[0083]

[0084] Preparation method, solvent method:

[0085] Accurately weigh the prescribed amount of polyvinyl alcohol, add 10 times the amount of purified water of polyvinyl alcohol, stir thoroughly to make it swell; then slowly add the prescribed amount of propylene glycol, lumepirone tosylate, polyvinyl pyrrolidone, sucralose, and fruit flavor, stir at 1000rpm for 1h to obtain the glue solution. Use a coating machine to coat, install the backing material, adjust the coating thickness so that the film thickness is about 80±5μm, set the coating speed to 10rpm, evenly coat the glue solution on the backing to make a film, and dry at 40±5℃. After drying, the film is complete, and the flexibility and mechanical strength are good.

[0086] Cutting: The prepared film is cut into films of different sizes and shapes by a film cutting machine.

[0087] Examples 9-10

[0088] A film preparation of lumepirone or its salt

[0089] The prescription is as follows:

[0090] Table 5. Prescriptions for Examples 9-10

[0091]

[0092]

[0093] Preparation method, solvent method:

[0094] Accurately weigh the prescribed amount of hydroxypropyl methylcellulose, add 8 times the amount of 60% ethanol aqueous solution, stir thoroughly to make it swell; then slowly add the prescribed amount of propylene glycol, lumepirone tosylate, polyvinyl pyrrolidone, sucralose, and fruit flavor, stir at 1000rpm for 1h to prepare the glue solution. Use a coating machine to apply, install the backing material, adjust the coating thickness so that the film thickness is about 80±5μm, set the coating speed to 10rpm, evenly apply the glue solution on the backing to form a film, and dry at 40±5℃. After drying, the film is complete, and the flexibility and mechanical strength are good.

[0095] Cutting: The prepared film is cut into films of different sizes and shapes by a film cutting machine.

[0096] Examples 11-13

[0097] A film preparation of lumepirone or its salt

[0098] The prescription is as follows:

[0099] Table 6. Prescriptions for Examples 11-13

[0100]

[0101] The preparation method is the same as Example 1.

[0102] Examples 14-16

[0103] A film preparation of lumepirone or its salt

[0104] The prescription is as follows:

[0105] Table 7. Prescriptions for Examples 14-15

[0106]

[0107] The preparation method is the same as Example 1.

[0108] Example 16

[0109] A film preparation of lumepirone or its salt

[0110] The prescription is as follows:

[0111] Table 8. Prescription of Example 16

[0112] prescription Example 16 Name of raw materials Prescription ratio (%) Lumeperone Tosylate 11.50 Copolyvidone 33.30 Polyoxyethylene 48.96 Polyethylene glycol 5.0 Sucralose 1.0 BHT 0.24

[0113] Preparation method, hot melt method:

[0114] Weighing: Accurately weigh the raw and auxiliary materials of the batch prescription and set aside;

[0115] Mixing: First take the raw material and copovidone, and pass through a 30-mesh sieve; then add the remaining materials and pass through a 30-mesh sieve together with the above materials.

[0116] Hot melt extrusion:

[0117] The experiment was carried out using a hot melt extruder to prepare lumepirone tosylate film, and the temperature, feed speed, and film drawing speed were set as shown in Table 9.

[0118] Table 9. Parameters of Example 16

[0119]

[0120] Examples 17-20

[0121] A film preparation of lumepirone or its salt

[0122] The prescription is as follows:

[0123] Table 10. Prescriptions for Examples 17-20

[0124]

[0125]

[0126] Preparation method, hot melt method: same as Example 1.

[0127] Comparative Example 1

[0128] A film preparation of lumepirone or its salt

[0129] The prescription is as follows:

[0130] Table 11. Comparative Example 1 Prescription

[0131]

[0132] The preparation method is the same as Example 1.

[0133] Comparative Example 2

[0134] A film preparation of lumepirone or its salt

[0135] The prescription is as follows:

[0136] Table 12. Comparative Example 2 Prescription

[0137]

[0138] The preparation method is the same as Example 1.

[0139] Comparative Example 3

[0140] A film preparation of lumepirone or its salt

[0141] The prescription is as follows:

[0142] Table 13. Comparative Example 3 Prescription

[0143]

[0144] The preparation method is the same as Example 1.

[0145] Comparative Example 4

[0146] A film preparation of lumepirone or its salt

[0147] The prescription is as follows:

[0148] Table 14. Comparative Example 4 Prescription

[0149] prescription Comparative Example 4 Name of raw materials Prescription ratio (%) Lumeperone Tosylate 11.50 Copolyvidone 33.50 Polyoxyethylene 49.00 Polyethylene glycol 5.00 Sucralose 1.0 BHT / BHA / Sodium bisulfite /

[0150] The preparation method is the same as Example 1.

[0151] Comparative Example 5

[0152] A film preparation of lumepirone or its salt

[0153] The recipe is the same as that of Example 1, and the preparation method only changes its parameters, specifically:

[0154] The preparation method is hot melt method:

[0155] Weighing: Accurately weigh the raw and auxiliary materials of the batch prescription and set aside;

[0156] Mixing: First take the raw material and copovidone, and pass through a 30-mesh sieve; then add the remaining materials and pass through a 30-mesh sieve together with the above materials.

[0157] Hot melt extrusion: The experiment was carried out using a hot melt extruder to prepare lumepirone tosylate film. The extrusion temperatures were set at 80, 100, 115, 125, 125, 125, 125, 125°C, the film mouth temperature was set at 125°C, the screw speed was 50 rpm, and the film pulling speed was 2 rpm. The parameters were adjusted later according to the material status.

[0158] Cutting: The prepared film is cut into films of different sizes and shapes by a film cutting machine.

[0159] Test Example 1

[0160] Tensile strength and disintegration time test results

[0161] Disintegration time: Determined by the disintegration time test method in Appendix 0921 of the 2020 edition of the Chinese Pharmacopoeia;

[0162] Tensile strength: Use a medical packaging performance tester to conduct tensile tests on different batches of film preparations. Cut samples from each batch to a length of 5 cm, set the clamp spacing to 20 mm, and the test speed to 5 mm / min. Test 3 samples from each batch and record the average tensile strength.

[0163] Table 15. Results of Examples 1-10

[0164]

[0165] Table 16. Results of Examples 11-20

[0166]

[0167]

[0168] Table 17. Results of Example 16

[0169] prescription 16-1a 16-1b 16-1c 16-1d 16-1e Tensile strength (MPa) 28 27 28 27 26 Disintegration time(s) 9 10 9 9 8 Appearance normal normal normal normal normal

[0170] Table 18. Results of Comparative Examples 1-5

[0171]

[0172] As shown in the data of Tables 15-18, when the ratio of copolyvidone to polyoxyethylene exceeds the ratio range specified in this patent, both Comparative Examples 2 and 3 cannot successfully form a film. In addition, when the film drawing temperature deviates from the process parameter range specified in this patent, although Comparative Example 5 can form a film, there is a clear granular feeling on the surface of the film, and the appearance does not meet the product standards. Although the film morphology of Comparative Example 4 is normal, the related impurities grow too fast during the stability test and do not meet the quality requirements.

[0173] In contrast, the films of Examples 1 to 15 all had normal appearances, and their tensile strength and disintegration time all met the product standard requirements. This indicates that the quality and performance of the films can be effectively guaranteed under the conditions of strictly following the ratio range and process parameters defined in this patent.

[0174] Test Example 2

[0175] The films prepared in Examples 1, 14-15 and Comparative Example 4 were placed in aluminum bags, sealed and packaged, and placed in a stability box (55° C., RH 75%). The relevant substances were detected by high performance liquid chromatography, and the data were as follows:

[0176] Table 19. Stability

[0177]

[0178]

[0179] Test Example 3

[0180] Animals: 6 male albino guinea pigs, weighing 270-330 g.

[0181] Animal administration: After fasting for 12 hours, albino guinea pigs were orally administered 3 mg / kg (calculated as lumepirone) of lumepirone tosylate solution (6.516 mg of lumepirone tosylate powder was accurately weighed and placed in a 15 mL centrifuge tube, 4.530 mL of pure water was added, and ultrasonication was performed until dissolved to obtain a lumepirone tosylate solution.), and 0.3 mg / kg (calculated as lumepirone) of the lumepirone tosylate film prepared in Example 1 was sublingually administered.

[0182] Blood collection method: blood collection from the vascular plexus at the upper corner of the eye.

[0183] The specific dosage is as follows:

[0184] Table 20. Dosage

[0185]

[0186] Table 21. Results

[0187]

[0188] As shown in Table 20-21, the absorption of lumepirone tosylate film through sublingual administration is shorter and has a higher peak concentration (Cmax) than that of lumepirone tosylate solution administered by oral gavage. This administration method is more conducive to the rapid passage of lumepirone tosylate through the blood-brain barrier, thereby increasing its occupancy rate at the D2 target, thereby significantly improving the efficacy. In addition, relevant data also show that sublingual administration of lumepirone tosylate film can significantly improve the absolute bioavailability of the drug.

[0189] Test Example 4

[0190] Animals: Beagles, male, four, average weight 10 kg.

[0191] Animal administration: 10 mg (calculated as lumepirone) of the lumepirone tosylate film prepared in Example 1 and Comparative Examples 1-5 and Example 15 of CN110430879 was administered sublingually.

[0192] Table 22. Results

[0193]

[0194] As shown in Table 22, the lumepirone tosylate film prepared in Example 1 of the present invention can reach T faster. max And it is effective, which is conducive to increasing the occupancy of the D2 target and may provide better therapeutic effects. Compared with some sudden and acute psychotic symptoms, it can take effect faster.

[0195] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A film preparation of lumepirone or its salt, characterized in that: The composition comprises the following raw materials in parts by weight: 2-30 parts of lumepirone or a pharmaceutically acceptable salt thereof, 40-95 parts of a film-forming material, 1-30 parts of a plasticizer, and 0.1-5 parts of an antioxidant; The film-forming material is selected from at least one of copolyvidone, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, povidone, hydroxypropyl methylcellulose, polyvinyl alcohol, polyoxyethylene, polyethylene glycol, hydroxypropyl cellulose and hydroxyethyl cellulose; The plasticizer is selected from at least one of polyethylene glycol, glycerol, propylene glycol, triacetin, triethyl citrate, sorbitol, mannitol, dibutyl phthalate, Span and Tween; The antioxidant is selected from at least one of butylated hydroxyanisole, butylated hydroxytoluene and sodium bisulfite.

2. The film according to claim 1, characterized in that The invention comprises the following raw materials in parts by weight: 2-25 parts of lumepirone or a pharmaceutically acceptable salt thereof, 40-92 parts of a film-forming material, 1-20 parts of a plasticizer and 0.2-5 parts of an antioxidant.

3. The film according to claim 1, characterized in that The invention comprises the following raw materials in parts by weight: 2-12 parts of lumepirone or a pharmaceutically acceptable salt thereof, 45-92 parts of a film-forming material, 1-15 parts of a plasticizer and 0.2-4 parts of an antioxidant.

4. The film according to claim 1, characterized in that The film-forming material is selected from at least one of copovidone, polyoxyethylene and hypromellose.

5. The film according to claim 1, characterized in that The film-forming material is selected from at least one of copolyvidone and polyoxyethylene.

6. The film according to claim 1, characterized in that The film-forming material is copolyvidone and polyoxyethylene; the mass ratio of copolyvidone to polyoxyethylene is 2-8:2-8.

7. The film according to claim 1, characterized in that The plasticizer is selected from at least one of polyethylene glycol, propylene glycol and polyvinyl pyrrolidone.

8. The film according to claim 1, characterized in that The antioxidant is sodium bisulfite.

9. The film according to claim 1, characterized in that The raw materials of the film may further include flavoring agents.

10. The film according to claim 9, characterized in that: The flavoring agent is selected from at least one of sucralose, essence, citric acid and tartaric acid.

11. The film according to claim 9, characterized in that The invention comprises the following raw materials in parts by mass: 2-30 parts of lumepirone or a pharmaceutically acceptable salt thereof, 40-95 parts of a film-forming material, 1-30 parts of a plasticizer, 0.1-5 parts of an antioxidant and 0.1-3 parts of a flavoring agent.

12. The film according to claim 1, characterized in that: The film is used for drug delivery via the oral mucosa or sublingual route.

13. The film according to claim 1, characterized in that: The lumepirone or a pharmaceutically acceptable salt thereof is lumepirone tosylate.

14. The method for preparing the film according to any one of claims 1 to 13, characterized in that: It is a hot melt method, comprising the following steps: After the raw materials are mixed, they are extruded at a speed of 0.01-100kg / h and stretched into a film.

15. The preparation method according to claim 14, characterized in that: The screw speed of the hot melt extrusion is 20-800 rpm.

16. The preparation method according to claim 14, characterized in that: When the preparation method is a hot melt method, the raw materials of the film agent, calculated by weight, include the following components: 2-28 parts of lumiperone tosylate, 40-66 parts of copovidone, 40-66 parts of polyoxyethylene, 2-10 parts of polyethylene glycol, 0.1-0.5 parts of BHT, and 0.1-1.5 parts of sucralose.

17. The method for preparing the film according to any one of claims 1 to 13, characterized in that: It is the solvent method.

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