Cariprazine orally disintegrating film compositions, methods of making and use thereof

Abstract

The application provides a cariprazine orally dissolving film composition, a preparation method and application thereof. The orally dissolving film composition comprises an active ingredient, a film forming material and a plasticizer, wherein the active ingredient is selected from a mixture of one or more of cariprazine, a pharmaceutically acceptable salt of cariprazine and an inclusion compound thereof. The orally dissolving film composition has the advantages of thin thickness, good taste, stable property, instant dissolving in the oral cavity without drinking water, fast oral absorption speed, simple process, high drug loading, good drug content uniformity, and the like. The orally dissolving film composition helps to improve the poor compliance, hiding and spitting of patients with schizophrenia, and is particularly suitable for patients with difficulty in swallowing, and has a good market prospect.

Description

[0001] This application claims the priority of the prior Chinese patent applications with the application numbers 202110576389.4, 202110576670.8 and 202110576703.9, filed on May 26, 2021, with the State Intellectual Property Office of China. The entire contents of the above-mentioned prior applications are incorporated herein by reference. TECHNICAL FIELD

[0002] The present application relates to a cariprazine orally disintegrating film composition, a preparation method and application thereof, and belongs to the field of pharmaceutical compositions. BACKGROUND

[0003] Cariprazine is an oral, once-daily atypical antipsychotic drug. The drug has been approved for marketing by FDA in 2015, with the trade name Vraylar. The indications approved so far include: (1) for the emergency treatment of manic or mixed episodes in adult patients with bipolar I disorder (manic depression), the recommended dosage range is 3-6 mg / day; (2) for the treatment of adult patients with schizophrenia, the recommended dosage range is 1.5-6.0 mg / day.

[0004]

[0005] Cariprazine is a D3 / D2 receptor partial agonist, which preferentially binds to D3 receptors. At the same time, it can also act as an antagonist with high / intermediate affinity to serotonin 5-HT2B and T-HT2A receptors, histamine H1 receptor, but has low affinity to 5-HT2C and α1A-adrenergic receptors, and has no significant affinity to adrenergic receptors. Compared with traditional antipsychotic drugs, it has the advantage of low incidence of extrapyramidal symptoms.

[0006] Cariprazine is a white or white-like powder, which is hardly soluble in water. The ordinary cariprazine tablets in the prior art must be disintegrated in the stomach to start releasing the drug, which leads to slow onset and limits the bioavailability, and is not convenient to take. As a treatment drug for mental illness, the patient population in this indication is poor in cooperating with treatment, and is prone to refuse treatment, hide medicine and vomit medicine, etc. Patent document CN107970217A discloses a cariprazine orally disintegrating tablet and a preparation method thereof, which contains cariprazine and is prepared into an orally disintegrating tablet by using ordinary tabletting technology, so that it disintegrates rapidly and dissolves quickly. However, the sample prepared by this technology still has a strong grit feeling when taken by patients, and the disintegration speed of different excipients will have a large difference. At the same time, it is difficult to maintain the balance between tablet hardness and disintegration time limit during tabletting.

[0007] Therefore, it is an urgent technical problem to find a cariprazine dosage form with good drug compliance, high solubility, stable properties and high bioavailability. SUMMARY

[0008] To improve the above technical problems, the present application provides a cariprazine orally dissolving film composition, which comprises an active ingredient, a film-forming material and a plasticizer, wherein the active ingredient contains a mixture of one or more selected from cariprazine, a pharmaceutically acceptable salt of cariprazine and an inclusion compound thereof.

[0009] According to an embodiment of the present application, the cariprazine is N'-[trans-4-[2-[4-(2,3-dichlorophenyl)-1-piperazinyl]ethyl]cyclohexyl]-N,N-dimethylurea as shown in Formula I:

[0010]

[0011] According to an embodiment of the present application, the active ingredient is selected from a mixture of one or more of an inclusion compound of cariprazine and an inclusion compound of a pharmaceutically acceptable salt of cariprazine, for example, selected from a mixture of one or more of an inclusion compound of cariprazine and an inclusion compound of a pharmaceutically acceptable salt of cariprazine. Preferably, the inclusion compound is a cyclodextrin inclusion compound, for example, selected from a mixture of one or more of a cyclodextrin inclusion compound of cariprazine and a cyclodextrin inclusion compound of a pharmaceutically acceptable salt of cariprazine.

[0012] According to an embodiment of the present application, the cyclodextrin is selected from a mixture of one or more of cyclodextrin or its derivatives, preferably, α-cyclodextrin, β-cyclodextrin, hydroxypropyl-β-cyclodextrin and sulfobutyl-β-cyclodextrin.

[0013] According to an embodiment of the present application, in the inclusion compound, the molar ratio of the active ingredient to the cyclodextrin is selected from (0.25-2.00):1.

[0014] According to an embodiment of the present application, the active ingredient can have a particle size D 90 ≤30μm. Preferably, when the active ingredient is selected from a mixture of one or more of cariprazine and a pharmaceutically acceptable salt of cariprazine, the particle size D 90 ≤30μm, for example, 1μm≤D 90 ≤29μm, for example, 1.7μm, 8.4μm, 17.3μm or 28.4μm.

[0015] According to embodiments of the present application, the active ingredient can have a mass percentage content of 1.00% to 30.00%, for example, 2.00% to 28.00%, such as 4.00% to 20.00%, and examples thereof can be 4.90%, 16.70%, 14.30%, 18.90%, or 19.0%, wherein the mass percentage content refers to the mass of the active ingredient accounting for the percentage of the total mass of the orally dissolving film composition.

[0016] According to embodiments of the present application, the orally dissolving film composition can further comprise a combination of one or more of a sweetening agent, an absorption enhancer, a disintegrating agent, a saliva stimulant, a filler, and a coloring agent.

[0017] According to embodiments of the present application, the film-forming material is a carrier for a drug. As an example, the film-forming material is selected from one or more of gelatin, xanthan gum, shellac, gum arabic, starch, dextrin, agar, sodium alginate, zein, hypromellose, hydroxypropyl cellulose, polyvinyl alcohol, polyoxyethylene, acrylic acid copolymer, povidone, polylactic acid, and silicone rubber.

[0018] According to embodiments of the present application, the film-forming material can have a mass percentage content of 30.00% to 75.00%, for example, 30.00% to 70.00%, and examples thereof can be 26.50%, 49.00%, 49.20%, 53.30%, 60.00%, 66.30%, or 70.40%, wherein the mass percentage content refers to the mass of the film-forming material accounting for the percentage of the total mass of the orally dissolving film composition.

[0019] According to embodiments of the present application, the plasticizer is a substance for lowering the glass transition temperature of the film, increasing plasticity and toughness, and improving the elongation rate. As an example, the plasticizer is selected from one or more of polyethylene glycol, glycerol, propylene glycol, silicone oil, dimethyl silicone oil, polypropylene glycol, and hexylene glycol.

[0020] According to embodiments of the present application, the plasticizer can have a mass percentage content of 5.00% to 30.00%, for example, 8.00% to 25.00%, and examples thereof can be 9.00%, 14.30%, 14.70%, 16.50%, 19.00%, 20.80%, wherein the mass percentage content refers to the mass of the plasticizer accounting for the percentage of the total mass of the orally dissolving film composition.

[0021] According to embodiments of the present application, the sweetening agent is a substance that plays a flavoring role in the film agent. As an example, the sweetening agent can be selected from one or more of aspartame, sucralose, fructose, sucrose, stevioside, glycyrrhizin, essence, flavoring, saccharin, and sodium saccharin.

[0022] According to an embodiment of the present application, the sweetening agent can have a mass percentage content of 0.05% to 1.00%, for example, 0.10%, 0.20%, 0.50%, 0.71%, 0.83%, or 0.95%, the mass percentage content referring to the percentage of the mass of the sweetening agent with respect to the total mass of the oral film composition.

[0023] According to an embodiment of the present application, the disintegrant refers to an auxiliary material that promotes rapid disintegration of a drug into small particles in the gastrointestinal tract. As an example, the disintegrant is selected from one or more of low-substituted hydroxypropyl cellulose, cross-linked povidone, cross-linked sodium carboxymethyl cellulose, cross-linked sodium carboxymethyl starch, starch, microcrystalline cellulose, and pregelatinized starch.

[0024] According to an embodiment of the present application, the saliva stimulant refers to a substance that stimulates saliva production. As an example, the saliva stimulant is selected from one or more of citric acid, tartaric acid, malic acid, and mannitol.

[0025] According to an embodiment of the present application, the coloring agent refers to a substance that can improve the appearance color of a preparation, can be used to identify a preparation, can distinguish application methods, and can reduce the aversion of patients to medication. As an example, the coloring agent is selected from one or more of titanium dioxide, pigments, and lakes.

[0026] According to an embodiment of the present application, the cariprazine oral film composition has a thickness of 10 μm to 100 μm.

[0027] According to an embodiment of the present application, the cariprazine oral film composition provided by the present application can be completely dissolved in simulated saliva at 37 ± 1 °C within 30 seconds and release cariprazine.

[0028] The present application also provides a method for preparing the cariprazine oral film composition, which comprises mixing the active ingredient and other ingredients in the cariprazine oral film composition.

[0029] According to an embodiment of the present application, the cariprazine oral film composition comprises an active ingredient, a film-forming material, a plasticizer, an absorption enhancer, and a sweetening agent, the active ingredient contains cariprazine and / or a pharmaceutically acceptable salt thereof, and the particle size of the active ingredient is preferably D 90 ≤ 30 μm.

[0030] According to an embodiment of the present application, the active ingredient has a mass percentage content of preferably 1.00% to 30.00%, for example, 16.70%, 14.30%, 18.90%, or 19.0%, the mass percentage content referring to the percentage of the mass of the active ingredient with respect to the total mass of the cariprazine oral film.

[0031] According to an embodiment of the present application, the particle size of the active ingredient is preferably D 90≤ 30 pm, for example 1.7 pm, 8.4 pm, 17.3 pm or 28.4 pm.

[0032] According to an embodiment of the present application, the mass percentage of the film- forming material is preferably 30.00% to 75.00%, for example 53.30%, 60.00%, 66.30% or 70.40%, the mass percentage referring to the mass of the film-forming material as a percentage of the total mass of the orally dissolving film composition.

[0033] According to an embodiment of the present application, the mass percentage of the plasticizer is preferably 5.00% to 30.00%, for example 20.80%, 14.30%, 14.70%, 19.00%, the mass percentage referring to the mass of the plasticizer as a percentage of the total mass of the orally dissolving film composition.

[0034] According to an embodiment of the present application, the mass percentage of the absorption enhancer is preferably 0.10% to 15.00%, for example 8.30%, 10.70% or 9.50%, the mass percentage referring to the mass of the sweetener as a percentage of the total mass of the orally dissolving film composition.

[0035] According to an embodiment of the present application, the mass percentage of the sweetener is preferably 0.05% to 1.00%, for example 0.83%, 0.71% or 0.95%, the mass percentage referring to the mass of the sweetener as a percentage of the total mass of the orally dissolving film composition.

[0036] According to an exemplary embodiment of the present application, the cariprazine orally dissolving film composition is selected from one of the following formulations:

[0037] Formulation a1 : 16.70% cariprazine, 45.00% hypromellose, 8.30% polyvinyl alcohol, 20.80% glycerol, 0.83% sucralose;

[0038] Formulation a2: 14.30% cariprazine, 13.60% hypromellose, 46.40% polyvinyl alcohol, 10.70% polysorbate 80, 14.30% glycerol, 0.71% sucralose;

[0039] Formulation a3: 14.30% cariprazine, 60.00% gelatin, 10.70% polysorbate 80, 14.30% glycerol, 0.71% sucralose;

[0040] Formulation a4: 16.70% cariprazine, 53.30% xanthan gum, 8.30% polysorbate 80, 20.80% glycerol, 0.83% sucralose;

[0041] Formulation a5: 19.00% cariprazine, 37.10% hypromellose, 33.30% gelatin, 9.50% polysorbate 80, 19.00% glycerol, 0.95% sucralose.

[0042] Formulation a6: 18.90% cariprazine, 28.40% hypromellose, 37.90% polyvinyl alcohol, 14.20% glycerol, 0.50% simethicone, 0.10% sucralose, cariprazine D90 1.7 μm;

[0043] Formulation a7: 18.90% cariprazine, 28.40% hypromellose, 37.90% polyvinyl alcohol, 14.20% glycerol, 0.50% simethicone, 0.10% sucralose, cariprazine D90 8.4 μm;

[0044] Formulation a8: 18.90% cariprazine, 28.40% hypromellose, 37.90% polyvinyl alcohol, 14.20% glycerol, 0.50% simethicone, 0.10% sucralose, cariprazine D90 17.3 μm;

[0045] Formulation a9: 18.90% cariprazine, 28.40% hypromellose, 37.90% polyvinyl alcohol, 14.20% glycerol, 0.50% simethicone, 0.10% sucralose, cariprazine D90 28.4 μm.

[0046] Formulation a10: 18.90% cariprazine, 28.40% hypromellose, 37.90% polyvinyl alcohol, 14.20% glycerol, 0.50% simethicone, 0.10% sucralose, cariprazine D90 39.4 μm.

[0047] The present application also provides a preparation method of the cariprazine oral film composition, comprising the following steps:

[0048] a1) dissolving the filler, plasticizer and sweetener in water to form a mixture;

[0049] a2) mixing the mixture obtained in step a1) with the film-forming material, heating and stirring at 60-70°C, and dissolving to obtain a blank glue solution;

[0050] a3) placing the active ingredient in the blank glue solution obtained in step a2), stirring until uniformly dispersed, and stirring to remove bubbles under vacuum to obtain a drug-containing glue;

[0051] a4) uniformly coating the drug-containing glue solution obtained in step a3) after degassing on a polyester tape with a scraper, heating, drying and cutting to obtain a cariprazine oral film composition.

[0052] According to an embodiment of the present application, the cariprazine orally disintegrating film composition is selected from the group consisting of cariprazine inclusion orally disintegrating film compositions comprising an active ingredient inclusion, a film forming material, a plasticizer, and a sweetening agent;

[0053] wherein the active ingredient inclusion is composed of an active ingredient and a cyclodextrin inclusion;

[0054] the active ingredient is selected from the group consisting of cariprazine and / or pharmaceutically acceptable salts thereof;

[0055] the cyclodextrin is selected from the group consisting of one or more of a-cyclodextrin, β-cyclodextrin, hydroxypropyl-β-cyclodextrin, and sulfobutyl-β-cyclodextrin.

[0056] According to an embodiment of the present application, the molar ratio of the active ingredient to the cyclodextrin is preferably (0.25-2.00): 1.

[0057] According to an embodiment of the present application, the mass percentage of the active ingredient is preferably 1.00-30.00%, for example 4.90%, the mass percentage referring to the mass of the active ingredient as a percentage of the total mass of the orally disintegrating film composition.

[0058] According to an embodiment of the present application, the mass percentage of the film forming material is preferably 30.00-70.00%, for example 49.00%, 26.50%, or 49.20%, the mass percentage referring to the mass of the film forming material as a percentage of the total mass of the orally disintegrating film composition.

[0059] According to an embodiment of the present application, the mass percentage of the plasticizer is preferably 5.00-30.00%, for example 9.00% or 16.50%, the mass percentage referring to the mass of the plasticizer as a percentage of the total mass of the orally disintegrating film composition.

[0060] According to an embodiment of the present application, the mass percentage of the sweetening agent is preferably 0.05-0.50%, for example 0.20%, the mass percentage referring to the mass of the sweetening agent as a percentage of the total mass of the orally disintegrating film composition.

[0061] According to an exemplary embodiment of the present application, the cariprazine inclusion orally disintegrating film composition is selected from one of the following formulations:

[0062] Formulation b1 : 4.90% cariprazine, 13.10% β-cyclodextrin, 24.50% hypromellose, 24.50% polyvinyl alcohol, 24.50% mannitol, 8.20% glycerol, 0.20% dimethicone, 0.20% sucralose;

[0063] Formulation b2: 4.90% cariprazine, 13.10% a-cyclodextrin, 32.70% polyvinyl alcohol, 16.3% gelatin, 24.50% mannitol, 8.20% glycerol, 0.20% dimethicone, 0.20% sucralose;

[0064] Formulation b3: 4.90% cariprazine, 13.10% hydroxypropyl-β-cyclodextrin, 2.00% hydroxypropyl methylcellulose, 24.50% gelatin, 16.30% mannitol, 16.30% glycerol, 0.20% dimethicone, 0.20% sucralose;

[0065] Formulation b4: 4.90% cariprazine, 13.10% sulfobutyl β-cyclodextrin, 49.20% polyvinyl alcohol, 16.30% mannitol, 16.30% glycerol, 0.20% dimethicone, 0.20% sucralose.

[0066] The present application also provides a preparation method of the cariprazine inclusion complex oral dissolving film composition, comprising the following steps:

[0067] b1) preparing a cariprazine inclusion complex by adding the active ingredient into a cyclodextrin aqueous solution (the concentration of cyclodextrin is 5-40% w / v);

[0068] b2) adding a filler, a plasticizer and a sweetener into the cariprazine inclusion complex obtained in step b1), stirring to obtain a solution A;

[0069] b3) adding a film-forming agent into solution A, swelling sufficiently, mixing, and defoaming to obtain a drug-containing glue solution;

[0070] b4) uniformly coating the drug-containing glue solution obtained in step b3) on a polyester tape, drying after heating, and cutting into a certain size to obtain the cariprazine inclusion complex oral dissolving film composition.

[0071] The present application also provides a cariprazine oral film, which comprises the cariprazine oral dissolving film composition. Preferably, the thickness of the cariprazine oral film is 10-100 μm.

[0072] The present application also provides the use of the cariprazine oral dissolving film composition in the preparation of a drug for treating and / or preventing psychosis, bipolar disorder, acute mania.

[0073] The present application also provides a method for treating and / or preventing psychosis, bipolar disorder, acute mania, which comprises administering a therapeutically effective amount of the cariprazine oral dissolving film composition or oral film to a patient in need.

[0074] In the context of the present application, the expression "one or more" when used, means two or more, such as 2, 3, 4, 5, 6 or more.

[0075] In the context of the present application, "oral dissolving film" means Oral Dissolving Film (ODF).

[0076] The reagents and raw materials used in the present application are commercially available.

[0077] Advantages

[0078] The cariprazine oral dissolving film composition provided by the present application has the advantages of thin thickness, good taste, stable properties, immediate dissolution in the oral cavity without the need for drinking water, and fast oral absorption speed. The cariprazine oral dissolving film composition or cariprazine oral film provided by the present application has a good dissolution rate, does not have a sand-like feeling after dissolving in the oral cavity, and can improve the taste of the drug and increase the compliance of patients. At the same time, the film appearance of the oral film is uniform and has good flexibility. Moreover, no sedimentation occurs during the preparation of the film liquid of the oral film, and the content uniformity meets the requirements.

[0079] The cariprazine oral dissolving film composition or cariprazine oral film provided by the present application helps to improve the poor drug compliance, hiding of medicine and spitting of medicine of patients with schizophrenia, and is particularly suitable for patients with difficulty in swallowing, and has a good market prospect.

[0080] Moreover, the raw materials of the cariprazine oral dissolving film composition or cariprazine oral film of the present application are easy to obtain, the preparation process is simple, the operation is simple, the drug loading capacity is high, the drug content uniformity is good, and it is suitable for industrialized production. DETAILED DESCRIPTION

[0081] The present application will be further described below by way of examples, but the present application is not limited in the scope of the examples. The reagents and raw materials used in the following examples are commercially available, and the experimental methods not specified in the specific conditions are selected according to the conventional methods and conditions, or according to the product instructions.

[0082] Examples A1-A10

[0083] 1. Prescription of cariprazine oral dissolving film composition

[0084] The prescription composition of examples A1-A10 is shown in the following table, wherein the percentage marked in each component is the mass percentage content of the component in the prescription after drying, calculated according to the mass:

[0085]

[0086]

[0087] removed during the process

[0088] 2. Preparation method

[0089] 1) Dissolve the above-mentioned amount of sucralose, glycerol, dimethicone and polysorbate 80 in water to form a mixture;

[0090] 2) Add a film-forming material to the mixture obtained in step 1), heat and stir at 60-70°C, and after melting, obtain a blank glue solution;

[0091] 3) Place the active ingredient in the blank glue solution obtained in step 2), stir until evenly dispersed, and then stir and degas under vacuum to obtain a drug-containing glue;

[0092] 4) Uniformly coat the drug-containing glue solution obtained in step 3) on a polyester tape using a doctor blade, heat, dry, and cut to obtain a cariprazine oral film.

[0093] 3. Film formation test

[0094]

[0095]

[0096] The experimental data of the above Examples A1-A10 show that the cariprazine oral film composition provided by the present application has the advantages of thin thickness, good taste, stable properties, immediate dissolution in the oral cavity without the need for drinking water, and fast oral absorption speed, and the process is simple, the drug loading capacity is high, and the drug content uniformity is good. The cariprazine D 90 ≤ 30 μm, which can improve the taste and appearance of the oral film, and the smaller the particle size, the better the content uniformity.

[0097] 3. Disintegration time measurement of oral film

[0098] Take 6 pieces of oral film of Examples A1-A10, and measure the disintegration time of the oral film. The test method is as follows: 100 ml of artificial saliva is added to 6 150 ml beakers, and heated to 37±1°C. 6 pieces of oral film are gently placed in the 6 beakers at the same time, and the time for all 6 pieces of oral film of each example to completely disintegrate is recorded under static conditions as follows:

[0099]

[0100] The experimental data of the above Examples A1-A10 show that the cariprazine oral film composition has the advantages of thin thickness, good taste, stable properties, immediate dissolution in the oral cavity without the need for drinking water, and fast oral absorption speed.

[0101] Examples B1-B5

[0102] 1. Formulation of cariprazine orally dissolving film composition

[0103] The formulation compositions of Examples B1-B5 are shown in the following table, in which the percentage of each component is the mass percentage content of the component in the formulation after drying, calculated according to the mass thereof:

[0104]

[0105] * Removed during the doctor blade drying process.

[0106] 2. Preparation method

[0107] 1) Cariprazine is added to an aqueous cyclodextrin solution and heated to complete dissolution at 40-70°C to obtain a cariprazine cyclodextrin inclusion compound;

[0108] 2) Mannitol, plasticizer, and sweetener are weighed and added to the cariprazine β-cyclodextrin inclusion compound, and stirred until uniform to obtain solution A;

[0109] 3) The film-forming agent is added to solution A, and heated and stirred at 40-70°C to allow it to swell fully. When it cools to room temperature, it is stirred and degassed under vacuum to obtain a drug-containing glue solution;

[0110] 4) The drug-containing glue solution obtained in step 3) is uniformly coated on a polyester belt using a doctor blade, and after heating and drying, it is cut to a certain size to obtain a cariprazine oral fast-dissolving film.

[0111] 3. Film-forming property detection

[0112]

[0113] The experimental data of the above Examples B1-B5 show that the cariprazine orally dissolving film inclusion compound provided by the present application has the advantages of good film-forming property, good taste, stable properties, and fast oral absorption speed; and has the advantages of simple preparation process, high drug loading, and good drug content uniformity.

[0114] 4. Mechanical strength detection

[0115] The cariprazine oral fast-dissolving film obtained in Examples B1-B5 is placed in the two clamps of an electronic tensile testing machine, and the testing machine is started at a speed of 50 mm / min to investigate the mechanical strength of the drug film, and the results are shown in the following table.

[0116]

[0117] The above mechanical strength results of the drug film show that the cariprazine oral fast-dissolving film prepared in Examples B1-B5 has a certain degree of tensile strength and flexibility, and can overcome external pressure during cutting, packaging, and transportation.

[0118] The above has been described by way of example with reference to specific embodiments of the present application. However, the scope of protection of the present application is not limited to the above-described example embodiments. Any modifications, equivalent replacements, improvements, etc. made by those skilled in the art within the spirit and principle of the present application should be included in the scope of protection of the claims of the present application.

Claims

1. A cariprazine orally dissolving film composition, characterized in that: The oral dissolving film composition comprises an active ingredient, a film-forming material, and a plasticizer; The active ingredient is carilarazine, the film-forming material is a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol, and the plasticizer is selected from a mixture of glycerin and dimethicone. The active ingredient has a mass percentage content of 1.00% to 30.00%, where the mass percentage content refers to the percentage of the mass of the active ingredient relative to the total mass of the oral disintegrating film composition; The mass percentage of the film-forming material is 30.00% to 75.00%, where the mass percentage refers to the percentage of the mass of the film-forming material to the total mass of the oral dissolving film composition. The plasticizer has a mass percentage content of 5.00% to 30.00%, where mass percentage refers to the percentage of the mass of the plasticizer to the total mass of the oral dissolving film composition; The particle size D of the active ingredient 90 ≤17.3μm.

2. The cariprazine orally dissolving film composition according to claim 1, characterized in that: The particle size of the active ingredient is 1μm≤D 90 ≤17.3μm.

3. The cariprazine orally dissolving film composition according to claim 1, characterized in that: The active ingredient has a mass percentage content of 2.00% to 28.00%.

4. The cariprazine orally dissolving film composition according to claim 1, characterized in that: The active ingredient has a mass percentage content of 4.00% to 20.00%.

5. The cariprazine orally dissolving film composition as described in claim 1, characterized in that: The oral film composition further comprises one or more combinations of sweeteners, absorption enhancers, disintegrants, saliva stimulants, fillers, and colorants.

6. The cariprazine orally dissolving film composition as described in claim 5, characterized in that: The sweetener is selected from one or more of aspartame, sucralose, fructose, sucrose, steviol glycoside, glycyrrhizin, saccharin, and sodium saccharin. The disintegrant is selected from one or more of the following: low-substituted hydroxypropyl cellulose, crospovidone, crospovidone sodium carboxymethyl cellulose, crospovidone sodium carboxymethyl starch, starch, microcrystalline cellulose, and pregelatinized starch. The saliva stimulant is selected from one or more of citric acid, tartaric acid, malic acid, and mannitol; The colorant is selected from pigments.

7. The caliraline orally disintegrating film composition according to claim 6, characterized in that: The colorant is selected from titanium dioxide or lake.

8. The cariprazine orally dissolving film composition as described in claim 1, characterized in that: The film-forming material has a mass percentage content of 30.00% to 70.00%; and / or, the plasticizer has a mass percentage content of 8.00% to 25.00%.

9. The cariprazine orally dissolving film composition as described in claim 5, characterized in that: The sweetener has a mass percentage content of 0.05% to 1.00%, where mass percentage refers to the percentage of the sweetener's mass relative to the total mass of the oral dissolving film composition.

10. The cariprazine orally dissolving film composition according to any one of claims 1-9, characterized in that, The cariprazine orally disintegrating film composition is selected from one of the following formulations: Formula a6: 18.90% cariprazine, 28.40% hydroxypropyl methylcellulose, 37.90% polyvinyl alcohol, 14.20% glycerin, 0.50% dimethicone, 0.10% sucralose, with a cariprazine D90 of 1.7 μm; Formula a7: 18.90% cariprazine, 28.40% hydroxypropyl methylcellulose, 37.90% polyvinyl alcohol, 14.20% glycerin, 0.50% dimethicone, 0.10% sucralose, with a cariprazine D90 of 8.4 μm; Formula a8: 18.90% cariprazine, 28.40% hydroxypropyl methylcellulose, 37.90% polyvinyl alcohol, 14.20% glycerin, 0.50% dimethicone, 0.10% sucralose, with a cariprazine D90 of 17.3 μm.

11. The method for preparing the cariprazine orally dissolving film composition according to any one of claims 1-10, characterized in that: The preparation method includes mixing the active ingredient in the carilarazine orally dissolving film composition with other ingredients.

12. A cariprazine oral film, characterized in that, The carilarazine oral film comprises the carilarazine oral film composition according to any one of claims 1-10.

13. The cariprazine oral film as described in claim 12, characterized in that, The thickness of the carilarazine oral film is 10 μm to 100 μm.

14. The use of the cariprazine orally disintegrating film composition according to any one of claims 1-10 or the cariprazine oral film preparation according to any one of claims 12-13 in the preparation of a medicament for treating psychosis.

15. The application as described in claim 14, characterized in that, The mental illness described is bipolar disorder or acute mania.

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