Risperidone solid oral film, preparation method therefor and use thereof

Abstract

A risperidone solid oral film. Each dosage unit of the oral film comprises: 0.10%-8.00% of risperidone, 5.00%-40.00% of a flavoring agent, 5.00%-40.00% of a stabilizer, 2.00%-15.00% of a plasticizer, 0%-45.00% of a filler, 2.00%-8.00% of a coloring agent and 25.00%-70.00% of a film-forming material. The risperidone solid oral film does not contain polyvinylpyrrolidone and a coating material. The risperidone solid oral film is instant and / or quick-release, and thus achieves fast dissolution and a high dissolution rate, and the preparation method involves simple operation and good reproducibility and thus is suitable for industrial production.

Description

Risperidone solid oral film, preparation method and application thereof

[0001] This application claims priority to 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, its preparation method and application”. Technical Field

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

[0003] Risperidone is a serotonin / dopamine antagonist with a uniquely balanced mechanism. It is effective for both positive and negative symptoms of schizophrenia, improves cognitive function, and facilitates social reintegration. As a new atypical antipsychotic, risperidone selectively inhibits the mesolimbic dopaminergic nervous system without the severe extrapyramidal effects of traditional antipsychotics. Its clinical efficacy is minimal, its safety is high, and its price is relatively low, making it one of the preferred antipsychotics for schizophrenia.

[0004] Currently, the main risperidone preparations used clinically in China 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 injections (25mg, 37.5mg, and 50mg). Risperidone tablets, manufactured by Xi'an Janssen Pharmaceutical Co., Ltd. under the trade name "Wei Si Tong," were the first risperidone tablets to be marketed in China, approved for marketing in 2001.

[0005] Ordinary tablets and capsules require water for administration, making them particularly inconvenient for children and elderly patients with dysphagia. Furthermore, psychiatric patients often refuse to take their medication or vomit it. While orally disintegrating tablets address these issues to some extent, they leave an unpleasant, gritty feeling in the mouth. Furthermore, orally disintegrating tablets are fragile during transportation, which can easily lead to inaccurate dosing and place high demands on production, packaging, and storage. Oral liquids require a special metering cup for administration, making them inconvenient to carry and hindering their widespread clinical application. The instructions for use and dosage for this product indicate that the minimum dose is 0.25 mg, but currently, no oral solid medications are available on the market at a dose as low as 0.25 mg.

[0006] To improve medication compliance among patients with mental illness, patent document CN101632651A discloses an oral fast-dissolving film formulation of risperidone, which contains risperidone, a water-soluble pharmaceutical polymer excipient, additives (flavoring, coloring, opacifying agent, plasticizer, preservative, pH adjuster, and disintegrant), and water. However, this invention overlooks a property of the risperidone raw material itself: its strong bitter taste. Although the formulation contains flavoring, it is insufficient to mask the strong bitterness of risperidone. Furthermore, the bitterness of risperidone, which comes into direct contact with oral taste buds for a period of time during medication administration, significantly affects the compliance of patients with mental illness, and thus, to a certain extent, affects its clinical application.

[0007] Patent document CN103349657A discloses a risperidone film preparation. To mask the bitter taste of risperidone, the invention employs multiple composite films, including acidic and alkaline film strips. Upon administration, the composite films form an effervescent film upon contact with water, producing numerous bubbles that numb the sense of smell and mask the taste. However, this invention requires the preparation of multiple film strips, resulting in a complex and costly production process and unsuitable 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 has a bitter taste. This invention dissolves risperidone in an acidic substance and then adds povidone for taste masking. However, the product produced 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 through cyclodextrin inclusion, and the excipients include cyclodextrin, a film-forming material, a plasticizer and a 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 solutions are mixed, ultrasonic action is performed 100 times, the solution is refrigerated at 4°C for 24 hours, and then filtered under reduced pressure and dried at 40°C for 4 hours to constant weight and then ground. This preparation process is cumbersome, inefficient, and not very automated. It is not easy to industrialize. In addition, 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 and there is unincluded risperidone, the prepared oral fast-dissolving film will still have the problem of bitter taste.

[0010] Patent document CN113842376A discloses a kind of oral fast-dissolving film containing risperidone and its preparation method. The raw material drug and Eudragit are used as coating liquid, fluidized coating is applied to 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, can completely mask the bitter taste of risperidone, and is more easily accepted by patients. In addition, after coating, risperidone can be isolated from oxygen and certain excipients incompatible with risperidone, which can effectively reduce the generation of its oxidative impurities and other impurities, and the preparation stability is excellent. However, this process is complicated and difficult to operate, which is not conducive to production, and Eudragit is expensive and costly.

[0011] Patent document CN107028917B aims to increase compliance and thus prepare an orally dissolving film, but the use of high-concentration ethanol as a solvent places high demands on production, is dangerous during operation, and causes environmental pollution.

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

[0013] Summary of the Invention

[0014] The present 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. The percentages refer to the percentages 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 or a coating material.

[0015] 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.

[0016] According to an embodiment of the present invention, the coating material refers to a conventional coating material in the art, such as Eudragit®.

[0017] 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%, where the percentage refers to the mass of risperidone as a percentage of the total mass of risperidone solid oral film.

[0018] 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.

[0019] In some embodiments, the flavoring agent is selected from one or more of sucralose, menthol, and sodium chloride.

[0020] In one embodiment, the flavoring agent consists of sucralose, menthol, and sodium chloride, or consists of sucralose and sodium chloride.

[0021] According to an embodiment of the present invention, the content of the flavoring agent is preferably 5.00% to 40.00%, more 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%, where the percentage refers to the mass of the flavoring agent as a percentage of the total mass of the risperidone solid oral film.

[0022] According to an embodiment of the present invention, the stabilizer refers to a substance that stabilizes the finished product and is 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.

[0023] 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%, where the percentage refers to the mass of the stabilizer as a percentage of the total mass of the risperidone solid oral film.

[0024] According to an embodiment of the present invention, the plasticizer is a substance used to lower 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.

[0025] 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%, where the percentage refers to the mass of the plasticizer as a percentage of the total mass of the risperidone solid oral film.

[0026] According to an embodiment of the present invention, the filler refers to a solid substance added to a material to improve material properties, increase volume, increase weight, or reduce material costs, 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.

[0027] 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.

[0028] According to an embodiment of the present invention, the colorant refers to a substance that can improve the appearance color of the preparation and 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.

[0029] 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%, where the percentage refers to the mass of the colorant as a percentage of the total mass of the risperidone solid oral film.

[0030] According to an embodiment of the present invention, the film-forming material is a drug carrier selected from hypromellose (HMPC, such as hypromellose E15) and / or polyvinyl alcohol.

[0031] 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%, where the percentage refers to the percentage of the mass of the film-forming material to the total mass of the risperidone solid oral film.

[0032] 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:

[0033] 1.00% to 3.00% of risperidone, 5.00% to 10.00% of a flavoring agent, 5.00% to 10.00% of a stabilizer, 7.00% to 13.00% of a plasticizer, 35.00% to 45.00% of a filler, 2.00% to 5.00% of a colorant, and 25.00% to 40.00% of a film-forming material; the percentages refer to the mass percentage of each component to the total mass of the risperidone solid oral film; the risperidone solid oral film does not contain polyvinyl pyrrolidone or a coating material;

[0034] Preferably, the flavoring agent consists of sucralose and sodium chloride, for example, the mass ratio of sucralose to sodium chloride is 1:(1-3), such as 1:1, 1:1.5, 1:1.6, 1:1.7, 1:2 or 1:2.5;

[0035] 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.

[0036] According to an embodiment of the present invention, the risperidone solid oral film of the present invention can be any of the following formulations:

[0037] Prescription 1: 5.56% risperidone, 8.33% sucralose, 2.77% menthol, 13.89% sodium chloride, 5.56% anhydrous citric acid, 5.56% glycerin, 2.77% titanium dioxide and 55.56% hypromellose, where the percentages refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film;

[0038] 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% hypromellose. The percentages mentioned refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film.

[0039] Prescription 3: 5.41% risperidone, 8.10% sucralose, 5.41% menthol, 13.51% sodium chloride, 5.41% anhydrous citric acid, 2.70% glycerin, 5.41% titanium dioxide, and 54.05% hypromellose. The percentages mentioned refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film.

[0040] 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 mentioned refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film.

[0041] 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 mentioned refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film.

[0042] 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% hypromellose. The percentages mentioned refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film.

[0043] Prescription 7: 4.88% risperidone, 7.32% sucralose, 4.88% menthol, 12.19% sodium chloride, 14.63% citric acid, 4.88% glycerin, 2.44% titanium dioxide, and 48.78% hypromellose. The percentages mentioned refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film.

[0044] 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% hypromellose. The percentages mentioned refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film.

[0045] Prescription 9: 4.00% risperidone, 6.00% sucralose, 4.00% menthol, 10.00% sodium chloride, 30.00% anhydrous citric acid, 4.00% glycerin, 2.00% titanium dioxide, and 40.00% hypromellose. The percentages mentioned refer to the mass of each component relative to the total mass of the risperidone solid oral film.

[0046] Prescriptions 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 mentioned refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film.

[0047] Prescription 13: 0.56% risperidone, 6.76% sucralose, 4.51% menthol, 11.27% sodium chloride, 9.86% citric acid monohydrate, 4.51% glycerin, 15.21% microcrystalline cellulose, 2.25% titanium dioxide and 45.07% hypromellose. The percentages mentioned refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film.

[0048] Prescription 14: 4.51% risperidone, 6.76% sucralose, 4.51% menthol, 11.27% sodium chloride, 9.86% citric acid monohydrate, 4.51% glycerin, 11.26% microcrystalline cellulose, 2.25% titanium dioxide and 45.07% hypromellose. The percentages mentioned refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film.

[0049] Prescription 15: 0.54% risperidone, 6.44% sucralose, 4.29% menthol, 10.73% sodium chloride, 14.16% citric acid monohydrate, 4.29% glycerin, 14.48% microcrystalline cellulose, 2.15% titanium dioxide and 42.92% hypromellose, where the percentages refer to the mass of each component as a percentage of the total mass of the risperidone solid oral film;

[0050] 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 the risperidone solid oral film.

[0051] The present invention also provides a method for preparing the risperidone solid oral film, comprising the following steps:

[0052] 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 uniformly, and vacuum degas to obtain drug-containing glue;

[0053] Step 2: Add the drug-containing glue obtained in step 1 to a film-making machine, apply film, and dry to obtain a dry film intermediate;

[0054] Step 3: cutting and packaging the dry film intermediate obtained in step 2 to obtain the risperidone solid oral film.

[0055] 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 minutes.

[0056] According to an embodiment of the present invention, the risperidone solid oral film dosage form may be a risperidone fast-dissolving and / or fast-releasing solid oral film dosage form for administration through the gastrointestinal tract.

[0057] According to an embodiment of the present invention, the dry film thickness of the risperidone solid oral film dosage form 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.

[0058] The present invention also provides the use of the risperidone solid oral film in the preparation of drugs for treating and / or preventing neuropsychiatric diseases and / or mental disorders.

[0059] According to an embodiment of the present invention, 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, 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, addictive disorders, personality disorders, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, ataxia, Friedreich's ataxia, Tourette syndrome, nocturnal enuresis, non-epileptic seizures, blepharospasm, Duchenne muscular dystrophy, stroke, chronic pain, neuropathic pain, hyperalgesia, allodynia, diabetic polyneuropathy, seizures, and epilepsy.

[0060] The present invention also provides the use of the risperidone solid oral film in the preparation of pharmaceutical preparations.

[0061] 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.

[0062] 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.

[0063] 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.

[0064] According to an embodiment of the present invention, the neuropsychiatric diseases and mental disorders have the meanings as shown above.

[0065] In one embodiment, the neuropsychiatric disease and / or psychiatric disorder is schizophrenia.

[0066] The reagents and raw materials used in the present invention are commercially available.

[0067] Beneficial effects of the present invention:

[0068] The inventors discovered that risperidone is a low-solubility, high-permeability drug. Due to its low solubility and slow dissolution in the gastrointestinal tract, its absorption is limited. Risperidone's strong bitter taste is difficult to mask, leading to poor oral medication compliance in patients. The risperidone solid oral film for gastrointestinal administration provided by the present invention has at least one of the following advantages:

[0069] First, the oral film is fast-dissolving and / or quick-release, dissolving quickly. It completely dissolved within 10 minutes 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, demonstrating a high solubility.

[0070] Second, the oral film has a good taste and good patient compliance;

[0071] Third, the oral film has good stability, such as good stability under high temperature, high humidity, light protection, accelerated, and long-term conditions;

[0072] Fourthly, the preparation method is simple to operate, has good reproducibility, and is suitable for industrial production.

[0073] Definitions and Explanations of Terms

[0074] The term "oral film per dosage unit" refers to a unit-dose oral film, i.e., an oral film comprising the above-mentioned percentages of risperidone, flavoring agent, stabilizer, plasticizer, filler, colorant and film-forming material loaded into one unit package.

[0075] The term "plurality" refers to two or more, for example, two, three or more.

[0076] The term "mainly composed of..." means that the sum of the masses of these components accounts for not less than 85% of the total mass of the risperidone solid oral film dosage form, for example not less than 90%, exemplified by 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

[0077] 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.

[0078] The term "therapeutically effective amount" refers to that amount of an active compound or drug that elicits the biological or medical response that is being sought in a tissue, system, animal, individual or human by a researcher, veterinarian, medical doctor or other clinician. BRIEF DESCRIPTION OF THE DRAWINGS

[0079] FIG1 shows a diagram of the main impurities of prescriptions 5-7 in Example 3;

[0080] in, The impurity content line indicates the impurity content when the tablet is placed at 50°C with a citric acid dosage of 2 mg / g; The impurity content line indicates the impurity content when the tablet is placed at 50°C with a citric acid dosage of 4 mg / g; The impurity content line indicates the impurity content when the tablet is placed at 50°C and the dosage of citric acid is 6 mg / g. DETAILED DESCRIPTION

[0081] The technical solutions of the present invention will be described in further detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative 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 encompassed within the scope of protection that the present invention is intended to protect.

[0082] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available, or can be prepared by known methods, or selected according to commercial specifications.

[0083] The API content detection method is as follows:

[0084] Determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 0512).

[0085] Chromatographic conditions: Use octadecylsilane bonded silica gel as the filler (it is recommended to use Zhongpu Technology RD-C18, 4.6mm×150mm, 5μm or a chromatographic column with equivalent performance); use ammonium acetate buffer (take 5g of ammonium acetate and dissolve it in 1000ml of water)-methanol (40:60) as the mobile phase; the flow rate is 1.0ml per minute; the column temperature is 30℃; the detection wavelength is 275nm; the injection volume is 10μl, and the running time is 10 minutes.

[0086] The detection methods for relevant substances are as follows:

[0087] Determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 0512).

[0088] Chromatographic conditions: Use octadecylsilane bonded silica gel as the filler (Waters XSelect HSS C18, 4.6 mm × 250 mm, 3.5 μm or equivalent performance column is recommended); ammonium acetate buffer (5 g of ammonium acetate is dissolved in 1000 ml of water)-acetonitrile (70:30) as mobile phase A; methanol as mobile phase B; gradient elution according to the table below, detection wavelength at 260 nm; flow rate of 1.0 ml per minute; column temperature of 30°C; injection volume of 30 μl.

[0089] Example 1

[0090] Table 1 Summary of prescriptions for Example 1 *Purified water is removed after the membrane is dried.

[0091] Preparation methods of Prescription 1 and Prescription 2:

[0092] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, colorant, API, and film-forming material in the prescribed amounts shown in Table 1, stir electrically or emulsify uniformly, and vacuum degas to obtain a drug-containing glue solution;

[0093] 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;

[0094] Step 3: Cut and package the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0095] Example 2

[0096] The prescription table is as follows:

[0097] Table 2 Prescription summary table of Example 2 *Purified water is removed after the membrane is dried.

[0098] Preparation methods of prescriptions 3 and 4:

[0099] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, colorant, API, and film-forming material in the prescribed amounts shown in Table 2, stir by electric stirring or vacuum emulsify evenly, and vacuum degas to obtain a drug-containing glue solution;

[0100] 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;

[0101] Step 3: Cut and package the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0102] 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:

[0103] Table 3 Summary of the stability of the formulation of Example 2 Note: “ / ” means not detected.

[0104] From the 30-day data of Prescription 3 and Prescription 4 at 50°C, it can be seen that when the film-forming material is hydroxypropyl methylcellulose, both the single impurities and the total impurities are relatively small, and the stability is high.

[0105] Example 3

[0106] The prescription is summarized as follows:

[0107] Table 4 Summary of prescriptions for Example 3 *Purified water is removed after the membrane is dried.

[0108] Preparation methods of prescriptions 5 to 9:

[0109] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, colorant, API, and film-forming material in the prescribed amounts shown in Table 4, stir electrically or emulsify uniformly, and vacuum degas to obtain a drug-containing glue solution;

[0110] 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;

[0111] Step 3: Cut and package the dry film intermediate obtained in step 2 to obtain risperidone fast-acting solid oral film.

[0112] The oral film samples obtained from prescriptions 5 to 7 were placed at a high temperature of 50°C for stability testing. The samples were taken out after 5, 10, and 30 days to examine the content of related substances. The summary data is shown in Table 5:

[0113] Table 5 Summary of stability data of prescriptions 5 to 7

[0114] The content of the main impurity RRT1.14 is shown in Figure 1.

[0115] Example 4

[0116] The prescription tables for the three strengths of risperidone solid oral film, 0.25mg, 1mg, and 2mg, are as follows:

[0117] Table 6 Prescriptions 10-12 *Purified water is removed after film formation and drying. **Citric acid is calculated on anhydrous basis. The content of anhydrous citric acid in a 2mg risperidone solid oral film is 6mg / tablet.

[0118] Preparation method of prescriptions 10 to 12:

[0119] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, API, colorant, filler, and film-forming material in the prescribed amounts shown in Table 6, stir electrically or emulsify uniformly, and vacuum degas to obtain a drug-containing glue solution;

[0120] 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;

[0121] Step 3: Cut and package the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0122] At the same time, the dissolution of risperidone solid oral film with prescription 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 of the paddle method in 0931 of the fourth general rule of the 2020 edition of the Chinese Pharmacopoeia, with the addition of sedimentation blue: 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:

[0123] Table 7 Summary of dissolution of prescription 10 (strength: 0.25 mg) in four media

[0124] Table 8 Summary of dissolution of prescription 11 (strength: 1 mg) in four media

[0125] Table 9 Summary of dissolution of prescription 12 (strength: 2 mg) in four media

[0126] 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.

[0127] Example 5

[0128] The pH changes of risperidone aqueous solutions with different concentrations of citric acid at 4 mg and 6 mg are shown in Table 10.

[0129] Table 10 Summary of pH values ​​of risperidone aqueous solutions

[0130] 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.

[0131] Table 11 Summary of prescriptions 13-16 *Purified water is removed after film drying

[0132] Exemplary preparation methods of prescriptions 13 to 16:

[0133] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, API, colorant, filler, and film-forming material in the prescribed amounts shown in Table 11, stir electrically or emulsify uniformly, and vacuum degas to obtain a drug-containing glue solution;

[0134] 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;

[0135] Step 3: Cut and package the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0136] Risperidone solid oral film samples of formulations 13 to 16 were placed at a high temperature of 50°C for stability testing. The samples were taken out after 10 days to examine the content of related substances. The summary data is shown in Table 12:

[0137] Table 12 Summary of stability of formulations 13-16 at 50°C

[0138] 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 of the finished raw materials.

[0139] In summary, the risperidone solid oral film provided by the present invention has a good taste, is easily accepted by patients, has good pharmaceutical stability, is low in production cost, is suitable for industrial production, and has little environmental pollution.

[0140] Comparative Example 1

[0141] Table 13 Summary of Prescription A *Purified water is removed after the membrane is dried.

[0142] Preparation method of prescription A:

[0143] Step 1: After adding the solvent, flavoring agent, stabilizer, plasticizer, API, colorant, and film-forming material in the prescribed amounts shown in Table 13, stir them electrically or emulsify them in a vacuum, and then degas in a vacuum to obtain a drug-containing glue solution;

[0144] Step 2: Add the drug-containing glue obtained in step 1 to a film-making machine, apply film, and dry (drying parameters are 60±10℃ / 20min) to obtain a dry film intermediate;

[0145] Step 3: Cut and package the dry film intermediate obtained in step 2 to obtain a risperidone solid oral film.

[0146] The product was tasted and found to have a severe bitter taste that could not be masked by flavoring agents.

[0147] Comparative Example 2

[0148] Prepared according to the method of Example 1 of CN107028917A, the prescription is as follows:

[0149] Table 14 Summary of Prescription B

[0150] The recipe was prepared by referring to the preparation method in CN107028917A. The obtained product was tasted and found to have a severe bitter taste that could not be masked by flavoring agents.

[0151] Comparative Example 3

[0152] Prepared with reference to the exemplary method of CN108685876A (Example 3), the prescription is as follows:

[0153] Table 15 Summary of Prescription C

[0154] The preparation method in CN108685876A was referred to and a prescription was prepared. After tasting the obtained product, it was found that the bitterness was severe and could not be masked by the flavoring agent.

[0155] Moreover, according to the record in paragraph 0006 of the CN113842376A specification, this prescription has poor stability when placed under high temperature conditions of 60°C for 10 days, and the unknown single impurity exceeds the limit (actually measured 0.59% after 5 days, 0.94% after 10 days, and the limit is 0.2%), which will affect the patient's medication safety to a certain extent.

[0156] Example 6

[0157] With reference to the Technical Guidelines for the Design and Evaluation of the Taste of Children's Medicines (Draft for Public Comment) 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 the Evaluation of Drug Taste [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.

[0158] Based on the quality attributes of orally dissolving films, palatability evaluation was conducted based on appearance, bitterness, sweetness, numbness, and foreign body sensation in the mouth. Bitterness, numbness, and foreign body sensation in the mouth were the main scoring items, while appearance and sweetness were bonus items. The grades, scoring ranges, and evaluation results were established as follows:

[0159] Table 16 Taste Evaluation Table

[0160] The above recipes were evaluated for taste. Compared with recipes A, B, and C, none of them had any bitter taste and the taste needed to be improved. However, recipes 10 to 16 of the present invention had an acceptable taste without bitterness and were very outstanding.

[0161] Example 7 Stability Test of Prescriptions 11 and 12

[0162] 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 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, 1, 3, and 6 months under long-term conditions (25°C ± 2°C, 60% RH ± 5% RH).

[0163] 1. Stability test of influencing factors

[0164] Table 20 Summary of accelerated stability data for Formulation 12 (2 mg)

[0165] Prescription 12 (2mg specification) was placed at 40℃±2℃, 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 was no significant difference in all the inspection indicators and all were within the acceptable standards.

[0166] 3. Long-term stability test

[0167] Table 21 Summary of long-term stability data of Formulation 11 (1 mg)

[0168] 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)). Compared with 0 months, there was no significant difference in all the inspection indicators, and all were within the acceptable standards.

[0169] Table 22 Summary of long-term stability data of Formulation 12 (2 mg)

[0170] Prescription 12 (2mg specification) was placed at 25℃±2℃, 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 was no significant difference in all the inspection indicators and all were within the acceptable standards.

[0171] Example 8 Mechanical Strength and Disintegration Time Test of Formulations 11 and 12

[0172] Tensile strength test:

[0173] Mechanical properties: After powering on, install the tensile test module, perform force calibration and height calibration, and set the height to 2mm.

[0174] Use a thickness gauge and a ruler to measure the thickness and width of the orally dissolving film and calculate the cross-sectional area of ​​the orally dissolving film (mm 2 ), 6 replicates were tested in parallel.

[0175] The orally disintegrating 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.

[0176] Tensile strength (MPa) = maximum force (gf) ÷ 102 ÷ cross-sectional area (mm 2 );

[0177] Percent elongation = maximum force distance (mm) ÷ sample height (mm) × 100%.

[0178] Disintegration time test in 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)°C. The time required for the sample to completely dissolve is recorded as the disintegration time.

[0179] The packaging in Table 23-24 refers to the inner packaging, polyester / aluminum / cast polyethylene pharmaceutical composite film.

[0180] Table 23 Summary of mechanical strength and small amount of solvent disintegration during the period of influencing factors of prescription 11

[0181] Table 24 Summary of mechanical strength and small amount of solvent disintegration during the period of influencing factors of prescription 12

[0182] The above describes the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the scope of protection 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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