Risperidone solid oral film agent as well as preparation method and application thereof

Abstract

The invention discloses a risperidone solid oral film as well as a preparation method and application thereof. According to the risperidone solid oral film agent, each dose unit of the oral film agent comprises 0.10% to 8.00% of risperidone, 5.00% to 40.00% of a flavoring agent, 5.00% to 40.00% of a stabilizing agent, 2.00% to 15.00% of a plasticizer, 0% to 45.00% of a filling agent, 2.00% to 8.00% of a coloring agent and 25.00% to 70.00% of a film forming material, and the risperidone solid oral film agent does not contain polyvinylpyrrolidone and a coating material. The risperidone solid oral film agent disclosed by the invention is instant and / or quick-release, is relatively fast in dissolution, is completely dissolved in four dissolution media for 10 minutes, and is relatively high in dissolution rate, and the preparation method is simple to operate, good in reproducibility and suitable for industrial production.

Description

[0001] This application claims the priority of the prior application with patent application number 202311186977.2 filed with the State Intellectual Property Office of China on September 14, 2023, and invention name “Risperidone solid oral film, preparation method and application thereof”. Technical Field

[0002] The invention relates to a solid oral risperidone film for administration via the gastrointestinal tract, and a preparation method and application thereof. Background Art

[0003] Risperidone is a 5-hydroxytryptamine / dopamine antagonist with a unique balancing mechanism. It is effective for both positive and negative symptoms of schizophrenia, and can also improve cognitive function, which is conducive to patients' reintegration into society. As an atypical new antipsychotic, risperidone can selectively inhibit the mesolimbic dopaminergic nervous system and will not produce severe extrapyramidal reactions like traditional antipsychotic drugs. It has few adverse reactions during clinical administration, high safety, and low price. It is currently one of the first choice drugs for anti-schizophrenia.

[0004] At present, the risperidone preparations used clinically in China mainly include tablets (1mg, 2mg and 3mg), dispersible tablets (1mg), capsules (1mg), oral solution (30mL: 30mg), orally disintegrating tablets (0.5mg, 1mg and 2mg) and microsphere injection (25mg, 37.5mg and 50mg), etc. The risperidone tablets produced by Xi'an Janssen Pharmaceutical Co., Ltd. under the trade name "Wei Si Tong" were the first domestically marketed variety and were approved for marketing in 2001.

[0005] Ordinary tablets and capsules need to be taken with water, which is inconvenient for children and elderly patients with dysphagia, and psychiatric patients often refuse to take medicine or spit it out. Although orodisintegrating tablets have solved the above problems to a certain extent, they have an unpleasant sandy feeling in the mouth when taken. In addition, orodisintegrating tablets are fragile during transportation, which can easily cause inaccurate dosage and have high requirements for production, packaging and storage. Oral liquids need to be taken with a special quantitative cup, which is inconvenient to carry, affecting its wide clinical application. According to the usage and dosage in the instructions for use of this product, the minimum dose of this product is 0.25 mg, but there is no low dose of 0.25 mg for oral solid medication on the market.

[0006] In order to improve the medication compliance of patients with mental illness, patent document CN101632651A discloses an oral fast-dissolving film of risperidone, which contains risperidone, water-soluble pharmaceutical polymer excipients, additives (flavoring agents, colorants, sunscreens, plasticizers, preservatives, pH regulators and disintegrants) and water. However, the invention ignores a property of the risperidone raw material itself, that is, the risperidone raw material has a strong bitter taste. Although the prescription contains flavoring agents, it is not enough to cover the strong bitter taste of risperidone. Moreover, when taking the medicine, the drug will directly contact the oral taste buds and maintain for a period of time, so the bitter taste will greatly affect the compliance of patients with mental illness when taking the medicine, and will further affect its clinical application to a certain extent.

[0007] Patent document CN103349657A discloses a risperidone film preparation. In order to mask the bitter taste of risperidone itself, multiple composite film strips are invented, including acidic strip film strips and alkaline strip film strips. When taken, the composite film forms an effervescent film when it meets water, generating a large number of bubbles, paralyzing the sense of smell and masking the taste. However, the invention requires the preparation of multiple film strips during production, and the production process is complicated, the cost is high, and it is not suitable for industrial production.

[0008] Patent document CN108685876A discloses an oral film-like pharmaceutical composition containing risperidone. Risperidone has low solubility in water, exists in granular form, and tastes bitter. The invention dissolves risperidone by adding an acidic substance, and then adds povidone for taste masking, but the product prepared by this method has poor stability.

[0009] Patent document CN104546806A discloses an oral fast-dissolving film containing risperidone and a preparation method. The invention achieves a taste-masking effect by cyclodextrin inclusion, and the auxiliary materials include cyclodextrin, film-forming material, plasticizer and flavoring agent. In the preparation process, a saturated aqueous solution-ultrasonic cell crushing method is used to prepare the risperidone inclusion compound. After the cyclodextrin and risperidone solution are mixed, ultrasonic action is performed 100 times, refrigerated in a 4°C refrigerator for 24 hours, filtered under reduced pressure, dried at 40°C for 4 hours to constant weight and then ground. This preparation process is cumbersome, inefficient, and not highly automated. It is not easy to industrialize production, and the invention does not clearly control the inclusion rate and does not have a step for removing free drugs. If the inclusion rate is low, there is unincluded risperidone, and the prepared oral fast-dissolving film will still have the problem of bitter taste.

[0010] Patent document CN113842376A discloses an oral fast-dissolving film containing risperidone and a preparation method thereof. The raw material drug and Eudragit are used as coating liquids, fluidized and coated on the surface of mannitol, and then the Eudragit coating liquid is further coated to obtain an intermediate containing the raw material drug. This coating method can form a dense coating film, which wraps risperidone therein, and can completely cover up the bitter taste of risperidone, which is more acceptable to patients. In addition, after coating, risperidone can be isolated from oxygen and certain excipients incompatible with risperidone, which can effectively reduce the generation of oxidized impurities and other impurities, and the preparation stability is excellent. However, the process is complicated, the operation is difficult, which is not conducive to production, and Eudragit is expensive and the cost is high.

[0011] Patent document CN107028917B is to increase compliance and thus prepare an orally dissolving film, but high concentration ethanol is added as a solvent, which has high production requirements, is dangerous during operation, and causes pollution to the environment.

[0012] In summary, there is an urgent need to develop a new dosage form containing risperidone that has good taste, wide dosage coverage, is easily accepted by patients, has good stability, fast dissolution, low production cost, and / or is suitable for industrial production. Summary of the invention

[0013] The invention provides a risperidone solid oral film. Each dosage unit of the risperidone solid oral film comprises: 0.10% to 8.00% of risperidone, 5.00% to 40.00% of a flavoring agent, 5.00% to 40.00% of a stabilizer, 2.00% to 15.00% of a plasticizer, 0% to 45.00% of a filler, 2.00% to 8.00% of a colorant and 25.00% to 70.00% of a film-forming material, wherein the percentage refers to the percentage of the mass of each component to the total mass of the risperidone solid oral film; and the risperidone solid oral film does not contain polyvinyl pyrrolidone and a coating material.

[0014] According to an embodiment of the present invention, each dosage unit of the risperidone solid oral film comprises 0.1 mg to 3 mg of risperidone, such as 0.25 mg, 1 mg or 2 mg of risperidone.

[0015] According to an embodiment of the present invention, the coating material refers to a conventional coating material in the art, such as Eudragit®.

[0016] According to an embodiment of the present invention, the content of risperidone is preferably 0.10% to 8.00%, further preferably 0.40% to 7.00%, for example 6.50%, 6.00%, 5.56%, 5.41%, 5.13%, 5.00%, 4.88%, 4.51%, 4.44%, 4.29%, 4.00%, 3.50%, 3.00%, 2.50%, 2.01%, 1.50%, 1.00%, 0.56%, 0.54%, 0.50% or 0.45%, and the percentage refers to the percentage of the mass of risperidone to the total mass of risperidone solid oral film.

[0017] According to an embodiment of the present invention, the flavoring agent is a substance that plays a flavoring role in the film, and is selected from one or more of sucrose, mannitol, dextran, sucralose, aspartame, menthol and sodium chloride.

[0018] In some embodiments, the flavoring agent is selected from one or more of sucralose, menthol, and sodium chloride.

[0019] In one embodiment, the flavoring agent consists of sucralose, menthol, and sodium chloride, or consists of sucralose and sodium chloride.

[0020] According to an embodiment of the present invention, the content of the flavoring agent is preferably 5.00% to 40.00%, further preferably 6.00 to 35.00%, for example 32.00%, 30.00%, 27.02%, 25.64%, 25.00%, 24.99%, 24.39%, 22.54%, 22.23%, 21.62%, 21.46%, 20.00%, 15.00%, 10.00%, 8.03%, 7.50%, 7.00% or 6.50%, wherein the percentage refers to the percentage of the mass of the flavoring agent to the total mass of the risperidone solid oral film.

[0021] According to an embodiment of the present invention, the stabilizer refers to a substance that keeps the finished product stable, selected from one or more of citric acid (e.g., anhydrous citric acid or citric acid monohydrate) and / or sodium citrate, tartaric acid, hydrochloric acid and malic acid. In some embodiments, the stabilizer is selected from citric acid.

[0022] According to an embodiment of the present invention, the content of the stabilizer is preferably 5.00% to 40.00%, further preferably 5.00% to 35.00%, for example 5.41%, 5.56%, 6.63%, 9.86%, 10.26%, 10.81%, 14.16%, 14.63%, 15.00%, 17.50%, 20.00%, 22.22%, 25.00%, 30.00% or 32.00%, wherein the percentage refers to the mass of the stabilizer as a percentage of the total mass of the risperidone solid oral film.

[0023] According to an embodiment of the present invention, the plasticizer is a substance used to reduce the glass transition temperature of the film, increase plasticity and toughness, and improve elongation, and is selected from one or more of glycerol, propylene glycol, sorbitol, and polyethylene glycol. In some embodiments, the plasticizer is glycerol.

[0024] According to an embodiment of the present invention, the content of the plasticizer is preferably 2.00% to 15.00%, further preferably 2.00% to 13.00%, for example 2.70%, 3.50%, 4.00%, 4.29%, 4.44%, 4.51%, 4.88%, 5.13%, 5.41%, 5.56%, 6.00%, 7.00%, 8.00%, 9.00%, 10.04%, 11.00% or 12.00%, wherein the percentage refers to the percentage of the mass of the plasticizer to the total mass of the risperidone solid oral film.

[0025] According to an embodiment of the present invention, the filler refers to a solid substance added to a material to improve the material properties, or to increase the volume, increase the weight, and reduce the cost of the material, and is selected from one or more of microcrystalline cellulose (MCC), mannitol, starch, pregelatinized starch, maltodextrin, sucrose, lactose, sorbitol, and glucose. In some embodiments, the filler is microcrystalline cellulose.

[0026] According to an embodiment of the present invention, the content of the filler is preferably 0-45.00%, for example 43.00%, 42.00%, 41.00%, 40.16%, 35.00%, 30.00%, 25.00%, 20.00%, 15.21%, 15.00%, 14.48%, 11.27%, 10.73%, 10.00%, 5.00% or 0, and the percentage refers to the percentage of the mass of the filler to the total mass of the risperidone solid oral film.

[0027] According to an embodiment of the present invention, the colorant refers to a substance that can improve the appearance color of the preparation, can be used to identify the concentration of the preparation, distinguish the application method and reduce the patient's aversion to taking the medicine, and is selected from titanium dioxide.

[0028] According to an embodiment of the present invention, the content of the colorant is preferably 2.00% to 8.00%, further preferably 2.00% to 7.00%, for example 2.00%, 2.15%, 2.23%, 2.25%, 2.44%, 2.56%, 2.70%, 2.77%, 3.01%, 3.50%, 4.00%, 4.50%, 5.00%, 5.41%, 5.50%, 6.00% or 6.50%, wherein the percentage refers to the mass of the colorant as a percentage of the total mass of the risperidone solid oral film.

[0029] According to an embodiment of the present invention, the film-forming material is a drug carrier selected from hydroxypropyl methylcellulose (HMPC, such as hydroxypropyl methylcellulose E15) and / or polyvinyl alcohol.

[0030] According to an embodiment of the present invention, the content of the film-forming material is preferably 25.00% to 70.00%, 25.00% to 65.00%, for example 60.00%, 55.56%, 55.00%, 54.05%, 51.28%, 50.00%, 48.78%, 45.07%, 44.44%, 42.92%, 40.00%, 35.00%, 30.12%, 28.00% or 26.00%, wherein the percentage refers to the percentage of the mass of the film-forming material to the total mass of the risperidone solid oral film.

[0031] According to one embodiment of the present invention, the risperidone solid oral film, each dosage unit of the oral film comprises or is mainly composed of the following components:

[0032] 1.00% to 3.00% of risperidone, 5.00% to 10.00% of flavoring agent, 5.00% to 10.00% of stabilizer, 7.00% to 13.00% of plasticizer, 35.00% to 45.00% of filler, 2.00% to 5.00% of colorant and 25.00% to 40.00% of film-forming material; the percentage refers to the percentage of the mass of each component to the total mass of risperidone solid oral film; the risperidone solid oral film does not contain polyvinyl pyrrolidone and coating material;

[0033] Preferably, the flavoring agent is composed of sucralose and sodium chloride, for example, the mass ratio of sucralose to sodium chloride is 1:(1-3), for example, 1:1, 1:1.5, 1:1.6, 1:1.7, 1:2 or 1:2.5;

[0034] The stabilizer is citric acid, the plasticizer is glycerin, the filler is microcrystalline cellulose, the colorant is titanium dioxide, and the film-forming material is hypromellose.

[0035] According to an embodiment of the present invention, the risperidone solid oral film of the present invention can be any of the following prescriptions:

[0036] Prescription 1: 5.56% risperidone, 8.33% sucralose, 2.77% menthol, 13.89% sodium chloride, 5.56% anhydrous citric acid, 5.56% glycerol, 2.77% titanium dioxide and 55.56% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0037] Prescription 2: 5.41% risperidone, 8.11% sucralose, 13.51% sodium chloride, 10.81% anhydrous citric acid, 5.41% glycerol, 2.70% titanium dioxide and 54.05% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0038] Prescription 3: 5.41% risperidone, 8.10% sucralose, 5.41% menthol, 13.51% sodium chloride, 5.41% anhydrous citric acid, 2.70% glycerol, 5.41% titanium dioxide and 54.05% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0039] Prescription 4: 5.41% risperidone, 8.10% sucralose, 5.41% menthol, 13.51% sodium chloride, 5.41% anhydrous citric acid, 2.70% glycerol, 5.41% titanium dioxide and 54.05% polyvinyl alcohol, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0040] Prescription 5: 5.41% risperidone, 8.10% sucralose, 5.41% menthol, 13.51% sodium chloride, 5.41% citric acid, 5.41% glycerol, 2.70% titanium dioxide and 54.05% hypromellose, the percentages being the mass of each component relative to the total mass of the risperidone solid oral film;

[0041] Prescription 6: 5.13% risperidone, 7.69% sucralose, 5.13% menthol, 12.82% sodium chloride, 10.26% citric acid, 5.13% glycerol, 2.56% titanium dioxide and 51.28% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0042] Prescription 7: 4.88% risperidone, 7.32% sucralose, 4.88% menthol, 12.19% sodium chloride, 14.63% citric acid, 4.88% glycerol, 2.44% titanium dioxide and 48.78% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0043] Prescription 8: 4.44% risperidone, 6.67% sucralose, 4.44% menthol, 11.12% sodium chloride, 22.22% citric acid, 4.44% glycerol, 2.23% titanium dioxide and 44.44% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0044] Prescription 9: 4.00% risperidone, 6.00% sucralose, 4.00% menthol, 10.00% sodium chloride, 30.00% anhydrous citric acid, 4.00% glycerol, 2.00% titanium dioxide and 40.00% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0045] Prescription 10-12: 2.01% risperidone, 3.01% sucralose, 40.16% microcrystalline cellulose, 5.02% sodium chloride, 6.63% citric acid monohydrate, 10.04% glycerol, 3.01% titanium dioxide and 30.12% hypromellose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0046] Prescription 13: 0.56% risperidone, 6.76% sucralose, 4.51% menthol, 11.27% sodium chloride, 9.86% citric acid monohydrate, 4.51% glycerol, 15.21% microcrystalline cellulose, 2.25% titanium dioxide and 45.07% hypromellose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0047] Prescription 14: 4.51% risperidone, 6.76% sucralose, 4.51% menthol, 11.27% sodium chloride, 9.86% citric acid monohydrate, 4.51% glycerol, 11.26% microcrystalline cellulose, 2.25% titanium dioxide and 45.07% hypromellose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0048] Prescription 15: 0.54% risperidone, 6.44% sucralose, 4.29% menthol, 10.73% sodium chloride, 14.16% citric acid monohydrate, 4.29% glycerol, 14.48% microcrystalline cellulose, 2.15% titanium dioxide and 42.92% hypromellose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film;

[0049] Prescription 16: 4.29% risperidone, 6.44% sucralose, 4.29% menthol, 10.73% sodium chloride, 14.16% citric acid monohydrate, 4.29% glycerol, 10.73% microcrystalline cellulose, 2.15% titanium dioxide and 42.92% hypromellose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film.

[0050] The present invention also provides a method for preparing the risperidone solid oral film, comprising the following steps:

[0051] Step 1: Mix two, more or all of the prescribed amount of solvent, flavoring agent, stabilizer, plasticizer, colorant, filler and film-forming material, stir electrically or emulsify evenly, and vacuum degas to obtain drug-containing glue;

[0052] Step 2: Add the drug-containing glue obtained in step 1 into a film-making machine, apply film, and dry to obtain a dry film intermediate;

[0053] Step 3: cutting and packaging the dry film intermediate obtained in step 2 to obtain the risperidone solid oral film.

[0054] According to an embodiment of the present invention, in step 2, the drying temperature is preferably 60±10° C.; and the drying time is preferably 20 min.

[0055] According to an embodiment of the present invention, the risperidone solid oral film may be a risperidone fast-dissolving and / or fast-releasing solid oral film for administration via the gastrointestinal tract.

[0056] According to an embodiment of the present invention, the dry film thickness of the risperidone solid oral film is 10 μm to 200 μm, for example, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm or 100 μm.

[0057] The present invention also provides the use of the risperidone solid oral film in the preparation of medicines for treating and / or preventing neuropsychiatric diseases and / or mental disorders.

[0058] According to an embodiment of the present invention, the neuropsychiatric disease and mental disorder are selected from schizophrenia, psychotic disorder, Alzheimer's disease, frontotemporal dementia, vascular dementia, Lewy body dementia, senile dementia, mild cognitive impairment, benign amnesia, closed head trauma, autism spectrum disorder, Asperger's syndrome, fragile X syndrome, attention deficit hyperactivity disorder, attention deficit disorder, obsessive-compulsive disorder, tic disorder, childhood learning disabilities, premenstrual syndrome, depression, major depressive disorder, anhedonia, suicidal ideation and / or behavior, A cluster consisting of bipolar disorder, anxiety disorders, panic disorder, post-traumatic stress disorder, chronic mild and unpredictable stress, eating disorders, addiction disorders, personality disorders, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, ataxia, Friedreich's ataxia, Tourette's syndrome, nocturnal enuresis, non-epileptic seizures, blepharospasm, Duchenne muscular dystrophy, stroke, chronic pain, neuropathic pain, hyperalgesia, allodynia, diabetic polyneuropathy, seizures, and epilepsy.

[0059] The present invention also provides the use of the risperidone solid oral film in the preparation of a pharmaceutical preparation.

[0060] According to an embodiment of the present invention, the pharmaceutical preparation is a pharmaceutical preparation for treating and / or preventing neuropsychiatric diseases and / or mental disorders. Preferably, the neuropsychiatric diseases and mental disorders have the definitions shown above.

[0061] According to an embodiment of the present invention, the pharmaceutical preparation may be a risperidone fast-dissolving and / or fast-releasing solid oral film for administration via the gastrointestinal tract.

[0062] The present invention also provides a method for treating and / or preventing neuropsychiatric diseases and / or mental disorders, comprising providing a therapeutically effective amount of the risperidone solid oral film to a patient in need.

[0063] According to an embodiment of the present invention, the neuropsychiatric diseases and mental disorders have the meanings as indicated above.

[0064] In one embodiment, the neuropsychiatric disease and / or psychotic disorder is schizophrenia.

[0065] The reagents and raw materials used in the present invention are commercially available.

[0066] Beneficial effects of the present invention:

[0067] The inventors found that risperidone is a low-solubility, high-permeability drug. Due to its low solubility and slow dissolution in the gastrointestinal tract, the absorption of the drug is limited; the strong bitter taste of risperidone is not easy to be masked, and patients have poor oral drug compliance. The risperidone solid oral film for gastrointestinal administration provided by the present invention has at least one of the following advantages:

[0068] First, the oral film is fast-dissolving and / or fast-release, dissolving quickly, and completely dissolving in four dissolution media: water, 0.1 mol / L hydrochloric acid solution, pH 4.5 acetic acid-sodium acetate buffer, and pH 6.8 phosphate buffer within 10 minutes, with a high solubility;

[0069] Second, the oral film has a good taste and good patient compliance;

[0070] Thirdly, the oral film has good stability, such as good stability under high temperature, high humidity, light avoidance, accelerated and long-term conditions;

[0071] Fourthly, the preparation method is simple to operate, has good reproducibility, and is suitable for industrial production.

[0072] Definition and explanation of terms

[0073] The term "oral film per dosage unit" refers to an oral film of unit dose, i.e., an oral film containing the above-mentioned percentages of risperidone, flavoring agent, stabilizer, plasticizer, filler, colorant and film-forming material loaded into one unit package.

[0074] The term "plurality" refers to more than two, for example, two, three or more.

[0075] The term "mainly composed of..." means that the sum of the masses of these components accounts for no less than 85% of the total mass of the risperidone solid oral film dosage form, for example no less than 90%, exemplified by 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

[0076] The term "patient" refers to any animal including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses or primates, and most preferably humans.

[0077] The term "therapeutically effective amount" refers to that amount of an active compound or drug that will elicit the biological or medical response that is being sought by a researcher, veterinarian, medical doctor or other clinician in a tissue, system, animal, individual or human. BRIEF DESCRIPTION OF THE DRAWINGS

[0078] Figure 1 A diagram showing the main impurities of prescriptions 5-7 in Example 3;

[0079] in, It indicates the impurity content line when the tablet is placed at 50°C with a citric acid dosage of 2 mg / g; It indicates the impurity content line when the tablet is placed at 50°C with a citric acid dosage of 4 mg / g; It indicates the impurity content line when the tablet is placed at 50°C and the dosage of citric acid is 6 mg / g. DETAILED DESCRIPTION

[0080] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0081] Unless otherwise specified, the raw materials and reagents used in the following examples are all commercially available, or can be prepared by known methods, or selected according to commercial specifications.

[0082] The API content detection method is as follows:

[0083] Determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition, Part IV, General Rules 0512).

[0084] Chromatographic conditions: Use octadecylsilane bonded silica gel as filler (it is recommended to use Zhongpu Technology RD-C18, 4.6mm×150mm, 5μm or chromatographic column with equivalent performance); use ammonium acetate buffer (take 5g of ammonium acetate, add 1000ml of water to dissolve)-methanol (40:60) as mobile phase; flow rate is 1.0ml per minute; column temperature is 30℃; detection wavelength is 275nm; injection volume is 10μl, and running time is 10 minutes.

[0085] The relevant substance detection methods are as follows:

[0086] Determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition, Part IV, General Rules 0512).

[0087] Chromatographic conditions: Use octadecylsilane bonded silica gel as filler (Waters XSelect HSSC18, 4.6mm×250mm, 3.5μm or chromatographic column with equivalent performance is recommended); ammonium acetate buffer (take 5g of ammonium acetate, add 1000ml of water to dissolve)-acetonitrile (70:30) as mobile phase A; methanol as mobile phase B; gradient elution according to the table below, detection wavelength is 260nm; flow rate is 1.0ml per minute; column temperature is 30℃; injection volume is 30μl.

[0088]

[0089]

[0090] Example 1

[0091] Table 1 Prescription Summary Table of Example 1

[0092]

[0093] *Purified water is removed after the membrane is dried.

[0094] Preparation methods of prescription 1 and prescription 2:

[0095] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, colorant, raw material drug, and film-forming material in the prescribed amount shown in Table 1, electrically stirring or vacuum emulsifying evenly, and vacuum degassing to obtain the drug-containing glue solution;

[0096] Step 2: Add the drug-containing glue obtained in step 1 to a film-making machine for film coating and drying at a drying parameter of 60±10°C / 20min to obtain a dry film intermediate;

[0097] Step 3: cutting and packaging the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0098] Example 2

[0099] The prescription table is as follows:

[0100] Table 2 Prescription Summary Table of Example 2

[0101]

[0102]

[0103] *Purified water is removed after the membrane is dried.

[0104] Preparation methods of prescriptions 3 and 4:

[0105] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, colorant, raw material drug, and film-forming material in the prescribed amount shown in Table 2, electrically stirring or vacuum emulsifying evenly, and vacuum degassing to obtain the drug-containing glue solution;

[0106] Step 2: Add the drug-containing glue obtained in step 1 to a film-making machine for film coating and drying at a drying parameter of 60±10°C / 20min to obtain a dry film intermediate;

[0107] Step 3: cutting and packaging the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0108] The obtained oral film samples were placed at a high temperature of 50°C for stability testing, and were taken out after 5, 10, and 30 days to examine the content of related substances. The summary data is shown in Table 3:

[0109] Table 3 Summary of the formula stability of Example 2

[0110]

[0111]

[0112] Note: “ / ” means not detected.

[0113] From the 50°C 30-day data of Prescription 3 and Prescription 4, it can be seen that when the film-forming material is hydroxypropyl methylcellulose, both the single impurity and the total impurity are relatively small and the stability is high.

[0114] Example 3

[0115] The prescription is summarized as follows:

[0116] Table 4 Prescription Summary Table of Example 3

[0117]

[0118]

[0119] *Purified water is removed after the membrane is dried.

[0120] Preparation methods of prescriptions 5 to 9:

[0121] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, colorant, raw material drug, and film-forming material in the prescribed amount shown in Table 4, electrically stirring or vacuum emulsifying evenly, and vacuum degassing to obtain the drug-containing glue solution;

[0122] Step 2: Add the drug-containing glue obtained in step 1 to a film-making machine for film coating and drying at a drying parameter of 60±10°C / 20min to obtain a dry film intermediate;

[0123] Step 3: Cut and package the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0124] The oral film samples obtained from prescriptions 5 to 7 were placed at a high temperature of 50°C for stability testing, and were taken out after 5, 10, and 30 days to examine the content of related substances. The summary data is shown in Table 5:

[0125] Table 5 Summary of stability data of prescriptions 5 to 7

[0126]

[0127]

[0128] The content of the main impurity RRT1.14 is shown in Figure 1 .

[0129] Example 4

[0130] The prescription tables of three specifications of risperidone solid oral film, 0.25 mg, 1 mg and 2 mg, are as follows:

[0131] Table 6 Prescription 10-12

[0132]

[0133] *Purified water is removed after the membrane is dried;

[0134] **Citric acid is calculated on anhydrous basis. The content of anhydrous citric acid in 2mg risperidone solid oral film is 6mg / tablet.

[0135] Preparation method of prescriptions 10 to 12:

[0136] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, API, colorant, filler, and film-forming material in the prescribed amount shown in Table 6, stir by electric stirring or vacuum emulsification evenly, and vacuum degassing to obtain a drug-containing glue solution;

[0137] Step 2: Add the drug-containing glue obtained in step 1 to a film-making machine for film coating and drying at a drying parameter of 60±10°C / 20min to obtain a dry film intermediate;

[0138] Step 3: cutting and packaging the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0139] At the same time, the dissolution of risperidone solid oral film with prescriptions 10-12 was investigated in four dissolution media: water, 0.1 mol / L hydrochloric acid solution, pH 4.5 acetic acid-sodium acetate buffer, and pH 6.8 phosphate buffer. The dissolution test conditions were in accordance with the second method-paddle method of 0931 of the fourth general rule of the 2020 edition of the Chinese Pharmacopoeia, with precipitation blue added: the volume of the dissolution medium was 500 ml and the rotation speed was 50 revolutions per minute. The sampling time was 5, 10, 15, 30, and 60 minutes, and the samples were injected and measured separately by HPLC. The dissolution results are summarized in Table 7:

[0140] Table 7 Summary of dissolution of prescription 10 (specification: 0.25 mg) in four media

[0141]

[0142] Table 8 Summary of dissolution of prescription 11 (specification: 1 mg) in 4 media

[0143]

[0144] Table 9 Summary of dissolution of prescription 12 (specification: 2 mg) in 4 media

[0145]

[0146]

[0147] From the above dissolution data, it can be seen that prescriptions of different strengths are rapidly dissolved in the four media, which can effectively improve the oral absorption of this type of drug.

[0148] Example 5

[0149] The dosage of citric acid was 4 mg and 6 mg. The pH value changes of risperidone aqueous solutions with different concentrations are shown in Table 10.

[0150] Table 10 Summary of pH values ​​of risperidone aqueous solutions

[0151]

[0152] From the above data, it can be seen that in the same citric acid dosage system, the pH value of risperidone aqueous solution with different concentrations will fluctuate.

[0153] Table 11 Summary of prescriptions 13-16

[0154]

[0155] *Purified water is removed after film drying

[0156] Exemplary preparation methods of prescriptions 13 to 16:

[0157] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, API, colorant, filler, and film-forming material in the prescribed amount shown in Table 11, stir by electric stirring or vacuum emulsification evenly, and vacuum degassing to obtain the drug-containing glue solution;

[0158] Step 2: Add the drug-containing glue obtained in step 1 to a film-making machine for film coating and drying at a drying parameter of 60±10°C / 20min to obtain a dry film intermediate;

[0159] Step 3: cutting and packaging the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0160] The risperidone solid oral film samples of prescriptions 13 to 16 were placed at a high temperature of 50°C for stability testing, and were taken out after 10 days to examine the content of related substances. The summary data is shown in Table 12:

[0161] Table 12 Summary of stability of prescription 13-1650℃

[0162]

[0163] The data show that when the citric acid content is 4 mg / tablet, both specifications of the finished products are very stable and the relevant substances meet the quality standards for raw material finished products.

[0164] In summary, the risperidone solid oral film provided by the present invention has good taste, is easily accepted by patients, has good pharmaceutical stability, has low production cost, is suitable for industrial production, and has little environmental pollution.

[0165] Comparative Example 1

[0166] Table 13 Summary of Prescription A

[0167]

[0168]

[0169] *Purified water is removed after the membrane is dried.

[0170] Preparation method of prescription A:

[0171] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, API, colorant, and film-forming material in the prescribed amount shown in Table 13, stir them electrically or emulsify them in vacuum, and then degas them in vacuum to obtain a drug-containing gel solution;

[0172] Step 2: Add the drug-containing glue obtained in step 1 into a film-making machine, apply film, and dry (drying parameters are 60±10°C / 20min) to obtain a dry film intermediate;

[0173] Step 3: cutting and packaging the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0174] After tasting the obtained product, it was found that it had a severe bitter taste that could not be masked by flavoring agents.

[0175] Comparative Example 2

[0176] Prepared according to the method of Example 1 of CN107028917A, the prescription is as follows:

[0177] Table 14 Summary of Prescription B

[0178]

[0179] The recipe was prepared by referring to the preparation method in CN107028917A. The obtained product was tasted and found to have severe bitterness which could not be covered by the flavoring agent.

[0180] Comparative Example 3

[0181] Prepared with reference to the exemplary method of CN108685876A (Example 3), the prescription is as follows:

[0182] Table 15 Summary of Prescription C

[0183] prescription Prescription C Risperidone g 0.8 Purified water ml 20 L-Tartaric acid g 3 Sucrose g 0.2 Sweet orange flavor 0.2 Titanium dioxide g 0.3 Edetate disodium g 0.02 Povidone K30g 1.5 Hydroxypropyl methylcellulose E3 g 2 Hydroxypropyl methylcellulose E15g 1 Glycerol g 0.098 Taste The bitter taste is so severe that sweeteners cannot cover it up

[0184] With reference to the preparation method in CN108685876A, a prescription was prepared and the obtained product was tasted and found to have a severe bitter taste which could not be covered by the flavoring agent.

[0185] Moreover, according to the record in paragraph 0006 of the CN113842376A specification, the stability of this prescription is poor when placed under high temperature conditions of 60°C for 10 days, and the unknown single impurity exceeds the limit (actually measured 0.59% in 5 days, 0.94% in 10 days, and the limit is 0.2%), which will affect the patient's medication safety to a certain extent.

[0186] Example 6

[0187] With reference to the Technical Guidelines for the Design and Evaluation of the Taste of Children's Drugs (Draft for Public Comments) and the literature Li Pan, Han Xue, Lin Junzhi, Jiang Hong, Yang Ming, Zhang Dingkun, Han Li. Application and Development of Volunteer Sensory Tests in Drug Taste Evaluation [J]. Chinese Journal of Pharmaceutical Sciences, 2017, 52(22): 1971-1975, the bitterness rating method and the multi-factor survey evaluation method were used to evaluate the palatability of prescriptions A, B, C and prescriptions 10 to 16.

[0188] According to the quality attributes of orodispersible films, the palatability is evaluated from the aspects of appearance, bitterness, sweetness, numbness, and foreign body sensation in the mouth. Bitterness, numbness, and foreign body sensation in the mouth are the main scoring items, and appearance and sweetness are bonus items. The grades, scoring ranges, and evaluation results are as follows:

[0189] Table 16 Taste Evaluation Table

[0190]

[0191]

[0192]

[0193]

[0194] The above prescriptions were evaluated for taste. Compared with prescriptions A, B, and C, the bitterness was not removed and the taste needed to be improved. However, the prescriptions 10 to 16 of the present invention had an acceptable taste without bitterness, which was very outstanding.

[0195] Example 7 Stability Test of Prescriptions 11 and 12

[0196] The samples with inner packaging (polyester / aluminum / cast polyethylene pharmaceutical composite film) were placed under high temperature (50°C) and high humidity (90% RH±5% RH) conditions, and samples were taken for testing at 0, 5, 10, and 30 days; the samples without packaging were placed under high temperature (50°C) and samples were taken for testing at 0, 5, 10, and 30 days; at the same time, the samples without packaging boxes and inner packaging were placed under light conditions (total illumination ≥1.2×10 6 lux·hr, total UV amplitude ≥200W·hr / m 2 ) and samples were taken for testing at 10 days. Samples with inner packaging (polyester / aluminum / cast polyethylene pharmaceutical composite film) were sampled and tested at 0, 1, 3, and 6 months under accelerated conditions (40°C ± 2°C, 75% RH ± 5% RH). Samples with inner packaging (polyester / aluminum / cast polyethylene pharmaceutical composite film) were sampled and tested at 0, 3, and 6 months under long-term conditions (25°C ± 2°C, 60% RH ± 5% RH).

[0197] 1. Stability test of influencing factors

[0198]

[0199]

[0200]

[0201]

[0202]

[0203]

[0204]

[0205]

[0206]

[0207] Table 20 Summary of accelerated stability data of prescription 12 (2 mg)

[0208]

[0209]

[0210] Prescription 12 (2 mg specification) was placed at 40°C ± 2°C, 75% RH ± 5% RH under the proposed packaging conditions (polyester / aluminum / cast polyethylene pharmaceutical composite film (inner packaging)) for 6 months. Compared with 0 months, there were no significant differences in the various inspection indicators and all were within the acceptable standards.

[0211] 3. Long-term stability test

[0212] Table 21 Summary of long-term stability data of formulation 11 (1 mg)

[0213]

[0214]

[0215] Prescription 11 (1 mg specification) was placed at 25°C ± 2°C, 60% RH ± 5% RH under the proposed packaging conditions (polyester / aluminum / cast polyethylene pharmaceutical composite film (inner packaging)) for 6 months. Compared with 0 months, there were no significant differences in the various inspection indicators and all were within the acceptable standards.

[0216] Table 22 Summary of long-term stability data of formulation 12 (2 mg)

[0217]

[0218]

[0219] Prescription 12 (2 mg specification) was placed at 25°C ± 2°C, 60% RH ± 5% RH under the proposed packaging conditions (polyester / aluminum / cast polyethylene pharmaceutical composite film (inner packaging)) for 6 months. Compared with 0 months, there were no significant differences in the various inspection indicators and all were within the acceptable standards.

[0220] Example 8 Mechanical Strength and Disintegration Time Test of Formulations 11 and 12

[0221] Tensile strength test:

[0222] Mechanical properties: After powering on, install the tensile test module, perform force calibration and height calibration, and set the height to 2mm.

[0223] Use a thickness gauge and a ruler to measure the thickness and width of the orodispersible film, and calculate the cross-sectional area of ​​the orodispersible film (mm 2 ), 6 replicates were tested in parallel.

[0224] The orodispersible film after thickness and width testing was fixed on the texture analyzer so that the tested cross section was perpendicular to the stretching direction of the device, and the maximum force and sample height were recorded.

[0225] Tensile strength (MPa) = maximum force (gf) ÷ 102 ÷ cross-sectional area (mm 2 );

[0226] Percent elongation = maximum force distance (mm) ÷ sample height (mm) × 100%.

[0227] Disintegration time test of a small amount of solvent: Place the sample in a culture dish containing 20 mL of pH 6.8 phosphate buffer solution at a temperature of (37±0.5)℃, and record the time when the sample is completely dissolved as the disintegration time.

[0228] The packaging in Table 23-24 refers to the inner packaging, polyester / aluminum / cast polyethylene pharmaceutical composite film.

[0229] Table 23 Summary of mechanical strength and small amount of solvent disintegration during the period of influencing factors of prescription 11

[0230]

[0231]

[0232] Table 24 Summary of mechanical strength and small amount of solvent disintegration during the period of influencing factors of prescription 12

[0233]

[0234] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A risperidone solid oral film, characterized in that: Each dosage unit of risperidone solid oral film comprises: 0.10% to 8.00% of risperidone, 5.00% to 40.00% of flavoring agent, 5.00% to 40.00% of stabilizer, 2.00% to 15.00% of plasticizer, 0 to 45.00% of filler, 2.00% to 8.00% of colorant and 25.00% to 70.00% of film-forming material, wherein the percentage refers to the percentage of the mass of each component to the total mass of the risperidone solid oral film; the risperidone solid oral film does not contain polyvinyl pyrrolidone and coating material.

2. The risperidone solid oral film according to claim 1, characterized in that: Each dosage unit of the risperidone solid oral film comprises 0.1 mg to 3 mg of risperidone, such as 0.25 mg, 1 mg or 2 mg of risperidone.

3. The risperidone solid oral film according to claim 1, characterized in that: The flavoring agent is selected from one or more of sucrose, mannitol, dextran, sucralose, aspartame, menthol and sodium chloride; and / or, The stabilizer is selected from one or more of citric acid and / or sodium citrate, tartaric acid, hydrochloric acid and malic acid; and / or, The plasticizer is selected from one or more of glycerol, propylene glycol, sorbitol and polyethylene glycol; and / or, The filler is selected from one or more of microcrystalline cellulose, mannitol, starch, pregelatinized starch, maltodextrin, sucrose, lactose, sorbitol and glucose; and / or, The colorant is selected from titanium dioxide; and / or, The film-forming material is selected from hydroxypropyl methylcellulose and / or polyvinyl alcohol.

4. The risperidone solid oral film according to claim 3, characterized in that: The content of the flavoring agent is 5.00% to 40.00%, preferably 6.00% to 35.00%, and the percentage refers to the percentage of the mass of the flavoring agent to the total mass of the risperidone solid oral film; and / or, The content of the stabilizer is 5.00% to 40.00%, preferably 5.00% to 35.00%, and the percentage refers to the percentage of the mass of the stabilizer to the total mass of the risperidone solid oral film; and / or, The content of the plasticizer is 2.00% to 15.00%, preferably 2.00% to 13.00%, and the percentage refers to the percentage of the mass of the plasticizer to the total mass of the risperidone solid oral film; and / or, The content of the filler is 0-45.00%, preferably 0-43.00%, and the percentage refers to the percentage of the mass of the filler to the total mass of the risperidone solid oral film; and / or, The content of the colorant is 2.00% to 8.00%, preferably 2.00% to 7.00%, and the percentage refers to the percentage of the mass of the colorant to the total mass of the risperidone solid oral film; and / or, The content of the film-forming material is 25.00% to 70.00%, preferably 25.00% to 65.00%, wherein the percentage refers to the percentage of the mass of the film-forming material to the total mass of the risperidone solid oral film; Preferably, the risperidone solid oral film, each dosage unit of the oral film comprises or is mainly composed of the following components: 1.00% to 3.00% of risperidone, 5.00% to 10.00% of flavoring agent, 5.00% to 10.00% of stabilizer, 7.00% to 13.00% of plasticizer, 35.00% to 45.00% of filler, 2.00% to 5.00% of colorant and 25.00% to 40.00% of film-forming material; the percentage refers to the percentage of the mass of each component to the total mass of risperidone solid oral film; the risperidone solid oral film does not contain polyvinyl pyrrolidone and coating material; Preferably, the flavoring agent consists of sucralose and sodium chloride, the stabilizer is citric acid, the plasticizer is glycerol, the filler is microcrystalline cellulose, the colorant is titanium dioxide, and the film-forming material is hypromellose.

5. The risperidone solid oral film according to claim 1, characterized in that: The risperidone solid oral film is selected from any of the following prescriptions: Prescription 1: 5.56% risperidone, 8.33% sucralose, 2.77% menthol, 13.89% sodium chloride, 5.56% anhydrous citric acid, 5.56% glycerol, 2.77% titanium dioxide and 55.56% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 2: 5.41% risperidone, 8.11% sucralose, 13.51% sodium chloride, 10.81% anhydrous citric acid, 5.41% glycerol, 2.70% titanium dioxide and 54.05% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 3: 5.41% risperidone, 8.10% sucralose, 5.41% menthol, 13.51% sodium chloride, 5.41% anhydrous citric acid, 2.70% glycerol, 5.41% titanium dioxide and 54.05% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 4: 5.41% risperidone, 8.10% sucralose, 5.41% menthol, 13.51% sodium chloride, 5.41% anhydrous citric acid, 2.70% glycerol, 5.41% titanium dioxide and 54.05% polyvinyl alcohol, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 5: 5.41% risperidone, 8.10% sucralose, 5.41% menthol, 13.51% sodium chloride, 5.41% anhydrous citric acid, 5.41% glycerol, 2.70% titanium dioxide and 54.05% hypromellose, the percentages being the mass of each component as a percentage of the total mass of risperidone solid oral film; Prescription 6: 5.13% risperidone, 7.69% sucralose, 5.13% menthol, 12.82% sodium chloride, 10.26% anhydrous citric acid, 5.13% glycerol, 2.56% titanium dioxide and 51.28% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 7: 4.88% risperidone, 7.32% sucralose, 4.88% menthol, 12.19% sodium chloride, 14.63% anhydrous citric acid, 4.88% glycerol, 2.44% titanium dioxide and 48.78% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 8: 4.44% risperidone, 6.67% sucralose, 4.44% menthol, 11.12% sodium chloride, 22.22% anhydrous citric acid, 4.44% glycerol, 2.23% titanium dioxide and 44.44% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 9: 4.00% risperidone, 6.00% sucralose, 4.00% menthol, 10.00% sodium chloride, 30.00% anhydrous citric acid, 4.00% glycerol, 2.00% titanium dioxide and 40.00% hydroxypropyl methylcellulose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 10-12: 2.01% risperidone, 3.01% sucralose, 40.16% microcrystalline cellulose, 5.02% sodium chloride, 6.63% citric acid monohydrate, 10.04% glycerol, 3.01% titanium dioxide and 30.12% hypromellose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 13: 0.56% risperidone, 6.76% sucralose, 4.51% menthol, 11.27% sodium chloride, 9.86% citric acid monohydrate, 4.51% glycerol, 15.21% microcrystalline cellulose, 2.25% titanium dioxide and 45.07% hypromellose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 14: 4.51% risperidone, 6.76% sucralose, 4.51% menthol, 11.27% sodium chloride, 9.86% citric acid monohydrate, 4.51% glycerol, 11.26% microcrystalline cellulose, 2.25% titanium dioxide and 45.07% hypromellose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 15: 0.54% risperidone, 6.44% sucralose, 4.29% menthol, 10.73% sodium chloride, 14.16% citric acid monohydrate, 4.29% glycerol, 14.48% microcrystalline cellulose, 2.15% titanium dioxide and 42.92% hypromellose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film; Prescription 16: 4.29% risperidone, 6.44% sucralose, 4.29% menthol, 10.73% sodium chloride, 14.16% citric acid monohydrate, 4.29% glycerol, 10.73% microcrystalline cellulose, 2.15% titanium dioxide and 42.92% hypromellose, the percentages refer to the percentage of the mass of each component to the total mass of risperidone solid oral film.

6. The risperidone solid oral film according to claim 1, characterized in that: The dry film thickness of the risperidone solid oral film is 10 μm to 200 μm.

7. The method for preparing the risperidone solid oral film according to any one of claims 1 to 6, characterized in that The following steps are involved: Step 1: Mix two or more of the prescribed amount of solvent, flavoring agent, stabilizer, plasticizer, colorant, filler and film-forming material, stir electrically or emulsify evenly, and vacuum degas to obtain a drug-containing glue solution; Step 2: Add the drug-containing glue obtained in step 1 into a film-making machine, apply film, and dry to obtain a dry film intermediate; Step 3: cutting and packaging the dry film intermediate obtained in step 2 to obtain the risperidone solid oral film.

8. Use of the risperidone solid oral film according to any one of claims 1 to 6 in the preparation of a drug for treating and / or preventing neuropsychiatric diseases and / or mental disorders; Preferably, the neuropsychiatric disease and mental disorder are selected from schizophrenia, psychotic disorder, Alzheimer's disease, frontotemporal dementia, vascular dementia, Lewy body dementia, senile dementia, mild cognitive impairment, benign amnesia, closed head trauma, autism spectrum disorder, Asperger's syndrome, fragile X syndrome, attention deficit hyperactivity disorder, attention deficit disorder, obsessive-compulsive disorder, tic disorder, childhood learning disabilities, premenstrual syndrome, depression, major depressive disorder, anhedonia, suicidal ideation and / or behavior, bipolar disorder, A group consisting of psychiatric disorders, anxiety disorders, panic disorders, post-traumatic stress disorder, chronic mild and unpredictable stress, eating disorders, addiction disorders, personality disorders, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, ataxia, Friedreich's ataxia, Tourette's syndrome, nocturnal enuresis, non-epileptic seizures, blepharospasm, Duchenne muscular dystrophy, stroke, chronic pain, neuropathic pain, hyperalgesia, allodynia, diabetic polyneuropathy, seizures, and epilepsy.

9. Use of the risperidone solid oral film according to any one of claims 1 to 6 in the preparation of a pharmaceutical preparation; Preferably, the pharmaceutical preparation is a pharmaceutical preparation for treating and / or preventing neuropsychiatric diseases and / or mental disorders; preferably, the neuropsychiatric diseases and mental disorders are selected from schizophrenia, psychotic disorders, Alzheimer's disease, frontotemporal dementia, vascular dementia, Lewy body dementia, senile dementia, mild cognitive impairment, benign amnesia, closed head trauma, autism spectrum disorder, Asperger's syndrome, fragile X syndrome, attention deficit hyperactivity disorder, attention deficit disorder, obsessive-compulsive disorder, tic disorder, childhood learning disabilities, premenstrual syndrome, depression, major depressive disorder, Cluster consisting of anhedonia, suicidal ideation and / or behavior, bipolar disorder, anxiety disorders, panic disorder, post-traumatic stress disorder, chronic mild and unpredictable stress, eating disorders, addiction disorders, personality disorders, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, ataxia, Friedreich's ataxia, Tourette's syndrome, nocturnal enuresis, non-epileptic seizures, blepharospasm, Duchenne muscular dystrophy, stroke, chronic pain, neuropathic pain, hyperalgesia, allodynia, diabetic polyneuropathy, seizures, and epilepsy.

10. The use according to claim 9, characterized in that: The pharmaceutical preparation is a risperidone fast-dissolving and / or fast-releasing solid oral film for administration through the gastrointestinal tract.

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