A lumiperone orodissolving film-taste-masking composition, preparation method and application thereof

Abstract

The present invention belongs to the field of medical technology, and relates to a lumiperone orodispersible film taste-masking composition, a preparation method and application thereof. The composition of the present invention comprises: an active ingredient, an alkaline excipient and an inclusion compound; the active ingredient comprises one or more of lumiperone and a pharmaceutically acceptable salt of lumiperone; the composition further comprises: one or more of a film-forming material, a plasticizer, a sweetener, a disintegrant and a colorant. The lumiperone orodispersible film obtained by the present invention has good taste, good instant solubility and high stability, and can effectively improve the problems of poor medication compliance, drug hiding and drug vomiting in patients with mental illness, and has high clinical application value.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines and relates to a lumiperone orodispersible film-dissolving taste-masking composition, a preparation method and application thereof. Background Art

[0002] Lumaperone (Lmateperone tosylate) is a novel mechanism of action for schizophrenia that can simultaneously regulate key neurotransmitters associated with severe mental illness: dopamine, serotonin, and glutamate. Specifically, Lumaperone is a dopamine receptor phosphoprotein modulator (DPPM) that selectively regulates D2 receptors with partial presynaptic agonism and postsynaptic antagonism. This novel action can reduce the release of presynaptic dopamine and block the activity of postsynaptic dopamine, thereby significantly reducing dopamine signaling. In addition, Lumaperone is also an antagonist of the serotonin 5-HT2A receptor, with an affinity for the 5-HT2A receptor that is 60 times higher than that of the D2 receptor. It is also an inhibitor of the serotonin reuptake transporter (SERT), producing an antidepressant effect and alleviating the negative symptoms of schizophrenia. Lumaperone can also regulate glutamatergic activity by increasing the phosphorylation of the NMDA receptor GluN2B subunit, thereby enhancing glutamatergic NMDA function. Since NMDA receptor activity is deficient in patients with schizophrenia, this enhancement of NMDA receptors may contribute to the antipsychotic and antidepressant effects of the drug. Compared with other antipsychotic drugs, lumepirone does not interact with muscarinic and histamine receptors and has fewer adverse reactions.

[0003] Lumiperone is a bitter and tongue-numbing drug that is highly irritating to the oral mucosa. It causes discomfort to the user when exposed in the oral cavity, especially to the tongue surface. Even after rinsing the mouth, this irritation lasts for half a day or even longer. This will affect the compliance of the medication and limit the application of oral preparations that are exposed in the oral cavity. Currently, most drugs for the treatment of mental illnesses are in common dosage forms such as tablets and capsules. For patients with mental illnesses, such dosage forms have problems such as difficulty swallowing and poor compliance, and are prone to hiding and vomiting drugs, which is not conducive to the patient's maintenance treatment.

[0004] Chinese invention patent application CN118557536A discloses a lumeperone orodisintegrating tablet composition and its preparation method and application. The lumeperone orodisintegrating tablet composition comprises: lumeperone tosylate, a hydrophilic diluent, an alkaline diluent, a disintegrant, a flavoring agent, a glidant and a lubricant. The lumeperone orodisintegrating tablet composition has good patient compliance and masks the bitterness and irritation of lumeperone to a certain extent. However, the oral irritation of lumeperone raw materials is strong, and it is difficult to achieve the taste masking effect by simply adding flavoring agents, bitterness inhibitors, etc. Summary of the invention

[0005] In view of the problems existing in the prior art, the present invention provides an improved new drug, lumepirone orodispersible film, which is used to treat mental diseases such as schizophrenia. The inclusion technology is used to block the contact between taste buds and drug molecules, thereby masking or reducing the bitterness of lumepirone or its pharmaceutically acceptable salts. At the same time, specific alkaline excipients, sweeteners, etc. are combined to improve the oral environment and block the transmission of bitter signals to the brain, thereby effectively masking the bitterness of the drug. In addition, the preparation method of the orodispersible film composition is simple, the active ingredients can be quickly dissolved, and the preparation stability is high.

[0006] To achieve the above object, the present invention provides a lumepirone orodispersible film-forming taste-masking composition, the composition comprising: an active ingredient, an alkaline excipient and an inclusion compound; the active ingredient comprises one or more of lumepirone and a pharmaceutically acceptable salt of lumepirone.

[0007] In some embodiments of the present invention, the composition has the following options:

[0008] (1) Lumiperone, basic excipients and inclusion compounds;

[0009] or (2) one or more pharmaceutically acceptable salts, basic excipients and inclusion compounds of lumepirone;

[0010] or (3) lumepirone, one or more pharmaceutically acceptable salts of lumepirone, alkaline excipients and inclusion compounds.

[0011] Furthermore, the alkaline auxiliary material is selected from one or more of meglumine, calcium phosphate, sodium hydroxide and sodium carbonate.

[0012] Preferably, the alkaline auxiliary material is selected from meglumine.

[0013] Furthermore, the inclusion compound is selected from one or more of starch, cyclodextrin and their derivatives.

[0014] Preferably, the inclusion compound is selected from cyclodextrin and its derivatives.

[0015] Furthermore, the molar ratio of the active ingredient to the alkaline auxiliary material is 1:(0.3-2.5); preferably 1:(0.5-2.0).

[0016] Furthermore, the molar ratio of the active ingredient to the inclusion compound is 1:(0.2-0.6); preferably 1:(0.2-0.5).

[0017] In the present invention, the active ingredient is enclosed by inclusion compound, the main purpose of which is to block the contact between taste buds and drug molecules, thereby masking or reducing the bitter taste.

[0018] Furthermore, the starch is selected from one or more of corn starch, potato starch or soybean starch; the cyclodextrin and its derivatives are selected from one or more of α-cyclodextrin, β-cyclodextrin, hydroxypropyl-β-cyclodextrin and sulfobutyl-β-cyclodextrin.

[0019] Furthermore, the starch accounts for 1-30% of the total mass of the composition; and the cyclodextrin and its derivatives account for 10-64.5% of the total mass of the composition.

[0020] Furthermore, the active ingredient accounts for 15-68.5% of the total mass of the composition; the alkaline auxiliary material accounts for 5.0-20.0% of the total mass of the composition.

[0021] In some embodiments of the present invention, the composition further comprises: one or more of a film-forming material, a plasticizer, a sweetener, a disintegrant and a colorant.

[0022] Furthermore, the film-forming material is selected from one or more of hydroxypropyl methylcellulose, polyvinyl alcohol, maltodextrin, sodium alginate and gelatin.

[0023] Furthermore, the plasticizer is selected from one or more of glycerol, polyethylene glycol 400, propylene glycol and sorbitol.

[0024] Furthermore, the sweetener is selected from one or more of sucralose, sodium chloride, menthol and aspartame.

[0025] Furthermore, the disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, microcrystalline cellulose and pregelatinized starch.

[0026] Furthermore, the colorant is selected from one or more of titanium dioxide, iron oxide and lake.

[0027] Among them, the alkaline excipient of the present invention, as a taste-masking material, can change the pH environment of the drug dispersed in the local oral cavity in a short time, causing the active ingredient to be dissolved in the oral cavity below the stimulation threshold, reducing the irritation of the active ingredient to the oral cavity, and restoring the acidic pH environment in the gastric juice, without affecting the dissolution and absorption metabolism in the gastrointestinal tract; at the same time, the sweetener plays a further taste-correcting role in the orodispersible film, binds to the G protein on the taste receptor, blocks the transmission of bitter signals to the brain, and thus effectively masks the bitter taste of the drug.

[0028] In addition, plasticizers can reduce the glass transition temperature of the film, increase the plasticity and toughness of the orally soluble film, and improve the elongation rate. Disintegrants promote rapid disintegration of the preparation, thereby allowing the active ingredient to dissolve quickly. In addition, the appearance of the active ingredient is white to off-white powder. The present invention improves the appearance color of the preparation by using a colorant, thereby improving the patient's compliance with medication.

[0029] Furthermore, the film-forming material accounts for 3.00-70.0% of the total mass of the composition.

[0030] Furthermore, the plasticizer accounts for 5.0-30.0% of the total mass of the composition.

[0031] Furthermore, the sweetener accounts for 0.5-2.0% of the total mass of the composition.

[0032] Furthermore, the disintegrant accounts for 0.5-5.0% of the total mass of the composition.

[0033] Furthermore, the colorant accounts for 0.5-1.0% of the total mass of the composition.

[0034] The present invention also provides a method for preparing any of the above-mentioned lumiperone orosoluble film-dissolving taste-masking compositions, comprising the following steps:

[0035] (1) mixing the active ingredient and the alkaline excipient uniformly to obtain a mixture 1;

[0036] (2) adding mixture 1 to the inclusion compound aqueous solution and mixing homogeneously to obtain solution A;

[0037] (3) adding a plasticizer, a sweetener, a disintegrant and a colorant to solution A, stirring and mixing to obtain solution B;

[0038] (4) adding the film-forming material to solution B, stirring and mixing after sufficient swelling, and defoaming to obtain solution C;

[0039] (5) Apply solution C and dry it.

[0040] Furthermore, the inclusion complex concentration in the inclusion complex aqueous solution is 5-40% (w / v).

[0041] The present invention also provides any of the above-mentioned lumetirone orodispersible film taste-masking compositions, and use of the lumetirone orodispersible film taste-masking composition prepared by any of the above-mentioned preparation methods in the preparation of anti-psychotic drugs.

[0042] Furthermore, the mental illness includes any one of schizophrenia, bipolar disorder type I or type II.

[0043] Compared with the prior art, the present invention has the following beneficial effects:

[0044] The present invention provides a new dosage form of an antipsychotic drug containing lumepirone - an orodispersible film. No water is needed when taking the drug. The drug film can be quickly dispersed and dissolved in the oral cavity, has a quick onset of action, is more convenient to take, and can significantly improve the medication compliance of special groups such as the elderly, patients with dysphagia, and patients with limited water intake. The orodispersible film of the present invention dissolves immediately in the mouth, sticks to the administration site and is not easy to spit out, which can reduce the frequency of patients' non-compliance with medication, and the drug treatment effect (effectiveness and safety) is more precise, meeting clinical needs.

[0045] Since the drug is rapidly released in the oral cavity after being prepared into an orodispersible film, the irritation to the oral cavity is enhanced. The present invention mainly uses inclusion technology and cooperates with suitable auxiliary materials to mask the taste. On the one hand, the inclusion technology is used to block the contact between taste buds and drug molecules, thereby masking or reducing the bitterness; on the other hand, the local pH environment of the oral cavity is changed by alkaline auxiliary materials to adjust the stimulation threshold, and at the same time, specific sweeteners block the transmission of bitter signals to the brain, thereby effectively masking the bitterness of the drug.

[0046] In addition, the process for preparing the lumepirone orodispersible film composition of the present invention is simple; and the combination of alkaline excipients and inclusion compounds can not only produce better oral solubility, so that the preparation has instant dissolution characteristics, but also improve the stability of the preparation. DETAILED DESCRIPTION

[0047] The embodiments of the present invention will be described in detail below in conjunction with the examples, but those skilled in the art will appreciate that the following examples are only used to illustrate the present invention and should not be construed as limiting the scope of the present invention. The reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.

[0048] 1. Investigation of alkaline excipients, inclusion compounds and sweeteners

[0049] Example 1

[0050] The composition of the present invention is shown in Table 1, and the preparation process is as follows:

[0051] (1) uniformly mixing the prescribed amount of lumepirone tosylate and meglumine to obtain a mixture 1;

[0052] (2) adding mixture 1 to a β-cyclodextrin aqueous solution (β-cyclodextrin concentration is 20% (w / v)), and homogenizing to obtain solution A;

[0053] (3) adding propylene glycol, sucralose, cross-linked polyvinylpyrrolidone and titanium dioxide to solution A and mixing well to obtain solution B;

[0054] (4) adding hydroxypropyl methylcellulose to solution B, mixing evenly after fully swelling, and defoaming to obtain solution C;

[0055] (5) Applying and drying the solution C, thereby obtaining the lumepirone orosoluble film.

[0056] Example 2

[0057] The composition of the present invention is shown in Table 1, and the preparation process is as follows:

[0058] (1) Add the prescribed amount of lumiperone tosylate to a β-cyclodextrin aqueous solution (β-cyclodextrin concentration is 20% (w / v)), and mix them homogeneously to obtain solution A;

[0059] (2) adding propylene glycol, sucralose, cross-linked polyvinylpyrrolidone and titanium dioxide to solution A and mixing well to obtain solution B;

[0060] (3) adding hydroxypropyl methylcellulose to solution B, mixing evenly after fully swelling, and defoaming to obtain solution C;

[0061] (4) Applying and drying the solution C to obtain the lumepirone orosoluble film.

[0062] Example 3

[0063] The composition of the present invention is shown in Table 1, and the preparation process is as follows:

[0064] (1) uniformly mixing the prescribed amounts of lumepirone tosylate and meglumine to obtain a mixture 1;

[0065] (2) adding mixture 1 into deionized water (the amount of deionized water is the same as that of the β-cyclodextrin aqueous solution in Example 1), and mixing homogeneously to obtain solution A;

[0066] (3) adding propylene glycol, sucralose, cross-linked polyvinylpyrrolidone and titanium dioxide to solution A and mixing well to obtain solution B;

[0067] (4) adding hydroxypropyl methylcellulose to solution B, and after sufficient swelling, defoaming to obtain solution C;

[0068] (5) Applying and drying the solution C, thereby obtaining the lumepirone orosoluble film.

[0069] Example 4

[0070] The composition of the present invention is shown in Table 1, and the preparation process is as follows:

[0071] (1) uniformly mixing the prescribed amount of lumepirone tosylate, sucralose, crospovidone and titanium dioxide to obtain a mixture 1;

[0072] (2) Add mixture 1 into deionized water (the amount of deionized water is the same as that of the β-cyclodextrin aqueous solution in Example 1), mix well, and obtain solution A;

[0073] (3) Adding hydroxypropyl methylcellulose to 90° C. purified water while stirring, and adding propylene glycol after cooling to prepare solution B;

[0074] (4) mixing solution A and solution B, allowing them to fully swell, and then defoaming to obtain solution C;

[0075] (5) Applying and drying the solution C, thereby obtaining the lumepirone orosoluble film.

[0076] Example 5

[0077] The composition of the present invention is shown in Table 1, and the preparation process is as follows:

[0078] (1) uniformly mixing the prescribed amount of lumepirone tosylate and meglumine to obtain a mixture 1;

[0079] (2) adding mixture 1 to a β-cyclodextrin aqueous solution (β-cyclodextrin concentration is 20% (w / v)), and homogenizing and mixing to obtain solution A;

[0080] (3) adding propylene glycol, cross-linked polyvinylpyrrolidone and titanium dioxide to solution A and mixing them evenly to obtain solution B;

[0081] (4) adding hydroxypropyl methylcellulose to solution B, mixing evenly after fully swelling, and defoaming to obtain solution C;

[0082] (5) Apply solution C and dry it to obtain the product.

[0083] Table 1

[0084]

[0085] Effect test:

[0086] 1. Irritation evaluation

[0087] In order to evaluate the irritation intensity of Lumiperone Orodispersible Film, a program was designed and a volunteer oral irritation experience test was conducted to properly evaluate its oral irritation inhibition effect, as follows:

[0088] Test plan: A total of 10 male and female volunteers aged 20-40 were selected to conduct a taste test on the 5 groups of examples, and the oral irritation sensation was scored based on the taste.

[0089] Scoring criteria:

[0090] 85-100 points: no irritation or almost no irritation;

[0091] 70-84.99 points: slight irritation, acceptable;

[0092] 55-69.99 points: irritating, but not strong, unacceptable;

[0093] <55 points: The irritation is strong and unacceptable.

[0094] The specific oral irritation test results of the above examples are shown in Table 2.

[0095] Table 2

[0096]

[0097] 2. Bitterness Evaluation

[0098] In order to evaluate the bitterness intensity of Lumiperone orodispersible film, a program was designed and a volunteer bitterness experience test was conducted to properly evaluate its bitterness suppression effect, as follows:

[0099] Test plan: A total of 10 male and female volunteers aged 20-40 were selected to conduct a taste test on the 5 groups of examples and score them based on the taste.

[0100] Scoring criteria:

[0101] 85-100 points: no bitterness or almost no bitterness;

[0102] 70-84.99 points: slightly bitter, acceptable;

[0103] 55-69.99 points: bitter, but not strong;

[0104] <55 points: The bitterness is strong and unacceptable.

[0105] The specific taste test results of the above examples are shown in Table 3.

[0106] Table 3

[0107]

[0108] 3. Oral dissolution test

[0109] A total of 10 male and female volunteers aged 20-40 were selected to conduct a test on the volunteers' oral dissolution time (unit: s).

[0110] The specific oral dissolution test results of the above examples are shown in Table 4.

[0111] Table 4

[0112]

[0113] The results in Tables 2-4 show that the present invention adopts alkaline excipients in combination with active ingredients, and under the inclusion action of the inclusion compound, the oral irritation and taste of the active ingredients can be significantly masked, and the average oral dissolution time is within 1 minute, which meets the oral dissolution property of the orodispersible film (compared with Examples 1-4); in addition, the use of sweeteners also brings about a certain taste masking effect (comparison between Example 1 and Example 5).

[0114] (IV) Stability test

[0115] The stability test was carried out on the examples, and the properties, content and dissolution were recorded. The results are shown in Table 5.

[0116] Table 5

[0117]

[0118] The results in Table 5 show that the properties of Examples 1 and 5 placed under high temperature 60°C and high humidity 75%RH for 30 days were normal compared with those on day 0, and both were off-white flaky films; the contents were between 90.0-110.0% compared with those on day 0, which met the requirements; the dissolution rate was greater than 85% in 15 minutes, indicating rapid dissolution. However, the properties of Examples 2-4 changed significantly after being placed under high temperature and high humidity conditions for 30 days, with the contents reduced to about 90%, and the dissolution rate tended to decrease compared with that on day 0. Therefore, when the preparation is prepared by combining alkaline excipients and inclusion agents, there is no significant change in properties, content, and dissolution during the stability period, and the preparation is more stable.

[0119] II. Investigation of alkaline excipients and inclusion compounds

[0120] Based on Example 1, the basic excipients and the types of inclusion compounds in the prescription were replaced, and the taste masking effect of the lumepirone orosoluble film of the present invention was investigated by taste evaluation.

[0121] Embodiment 6-7:

[0122] The prescription composition is shown in Table 6, and the preparation process is the same as Example 1.

[0123] Table 6

[0124]

[0125] The results of the oral irritation test, mouthfeel test, oral dissolution test and stability test of the lumiperone orodispersible films prepared in the above examples are respectively recorded in Tables 7-10.

[0126] Table 7

[0127]

[0128] Table 8

[0129]

[0130] The results in Tables 7-8 show that when the alkaline excipients are meglumine and β-cyclodextrin, the lumepirone orodispersible film has the least irritation to the oral cavity and the best taste; when the alkaline excipient is replaced by sodium acetate in Example 6, its oral irritation is significantly increased and the taste is reduced; when the inclusion compound is replaced by 18-crown (ether)-6 in Example 7, its oral irritation is increased and the taste is reduced. Therefore, in the present invention, when the alkaline excipient is preferably meglumine and the inclusion compound is preferably β-cyclodextrin, the oral irritation and taste are significantly improved, indicating that the selection of alkaline excipients and inclusion compounds has achieved unexpected technical effects.

[0131] Table 9

[0132]

[0133] The results in Table 9 show that when the alkaline excipient is meglumine and the inclusion compound is β-cyclodextrin, the average oral dissolution time of the lumepirone orodispersible film is within 1 minute, while when the alkaline excipient is sodium acetate and the inclusion compound is 18-crown-6, the average oral dissolution time is close to 1 minute, indicating that the selection of alkaline excipients and inclusion compounds also has a great influence on the dissolution effect of the orodispersible film.

[0134] Table 10

[0135]

[0136] The results in Table 10 show that when the alkaline excipient is meglumine and the inclusion compound is β-cyclodextrin, the properties of the films placed under high temperature 60°C and high humidity 75%RH for 30 days are normal compared with those on day 0, and are all off-white flaky films; the contents are between 90.0-110.0% compared with those on day 0, which meets the requirements; the dissolution rates in 15 min are all greater than 85%, indicating rapid dissolution; and when the alkaline excipient is replaced with sodium acetate and the inclusion compound is replaced with 18-crown-6, the properties change after the accelerated experiment, the off-white flaky films show patterns, the contents decrease, and the dissolution rates are comparable, indicating that the selection of the alkaline excipients and inclusion compounds of the present invention also has a significant impact on the stability of the orally dissolving film.

[0137] 3. Investigation on the ratio of active ingredients to alkaline excipients, and active ingredients to inclusion compounds

[0138] Embodiment 8-14:

[0139] The prescription composition is shown in Table 11, and the preparation process is the same as Example 1.

[0140] Table 11

[0141]

[0142] The results of the oral irritation test, mouthfeel test, oral dissolution test and stability test of the lumiperone orodispersible films prepared in the above examples are recorded in Tables 12-15, respectively.

[0143] Table 12

[0144]

[0145] Table 13

[0146]

[0147] Table 14

[0148]

[0149] Table 15

[0150]

[0151] The results in Tables 12-15 show that when Examples 8-11 are compared with Example 1, when the molar ratio of active ingredient / alkaline excipient is between 1:0.5-2.0, that is, Examples 1 and Examples 9-10, the oral irritation and taste evaluation results are greater than 85 points, with no bitterness or almost no bitterness; when the molar ratio of active ingredient / alkaline excipient is between 1:0.3 and 1:2.5, that is, Examples 8 and 11, the evaluation results are between 70-84.99 points, with slight irritation and slight bitterness, which are acceptable. The oral solubility results show that the oral solubility of Examples 1 and Examples 8-11 is within 1 minute, which meets the requirements. The stability results show that the properties of Example 11 change under high temperature and high humidity conditions, and the other examples meet the requirements.

[0152] When the molar ratio of active ingredient / inclusion compound of Examples 12-14 is between 1:0.2-0.6, that is, Examples 1 and 12-14, the results of the oral irritation test and the taste test are all greater than 85 points, with no bitterness or almost no bitterness. The results of the oral dissolution test are all within 1 minute, which meets the requirements. The stability results all meet the requirements.

[0153] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A lumiperone orodispersible film-dissolving taste-masking composition, characterized in that: The composition comprises: an active ingredient, an alkaline excipient, an inclusion compound, a film-forming material, a plasticizer, a sweetener, a disintegrant and a colorant; the active ingredient comprises one or more of lumepirone and a pharmaceutically acceptable salt of lumepirone; the alkaline excipient is one or more of meglumine, calcium phosphate, sodium hydroxide and sodium carbonate; the inclusion compound is one or more of starch, cyclodextrin and derivatives thereof; the cyclodextrin and derivatives thereof are selected from one or more of α-cyclodextrin, β-cyclodextrin, hydroxypropyl-β-cyclodextrin and sulfobutyl-β-cyclodextrin; The molar ratio of the active ingredient to the alkaline auxiliary material is 1:(0.3-2.5), and the molar ratio of the active ingredient to the inclusion compound is 1:(0.2-0.6); The preparation method of the lumiperone orosoluble film-dissolving taste-masking composition comprises the following steps: (1) mixing the active ingredient and the alkaline excipient uniformly to obtain a mixture 1; (2) adding mixture 1 to the inclusion compound aqueous solution and mixing homogeneously to obtain solution A; (3) adding a plasticizer, a sweetener, a disintegrant and a colorant to solution A, stirring and mixing to obtain solution B; (4) adding the film-forming material to solution B, stirring and mixing after sufficient swelling, and defoaming to obtain solution C; (5) Apply solution C and dry it.

2. The lumiperone orosoluble film-dissolving taste-masking composition according to claim 1, characterized in that: The starch is selected from one or more of corn starch, potato starch and soybean starch.

3. The orodispersible film-dissolving taste-masking composition of lumepirone according to claim 2, characterized in that: The starch accounts for 1-30% of the total mass of the composition; the cyclodextrin and its derivatives account for 10-64.5% of the total mass of the composition.

4. The lumiperone orosoluble film-dissolving taste-masking composition according to claim 1, characterized in that: The active ingredient accounts for 15-68.5% of the total mass of the composition; the alkaline auxiliary material accounts for 5.0-20.0% of the total mass of the composition.

5. The orodispersible film-dissolving taste-masking composition of lumepirone according to claim 1, characterized in that: The film-forming material is selected from one or more of hydroxypropyl methylcellulose, polyvinyl alcohol, maltodextrin, sodium alginate and gelatin; the plasticizer is selected from one or more of glycerol, polyethylene glycol 400, propylene glycol and sorbitol; the sweetener is selected from one or more of sucralose and aspartame; the disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, microcrystalline cellulose and pregelatinized starch; the colorant is selected from one or more of titanium dioxide, iron oxide and lake.

6. The orodispersible film-dissolving taste-masking composition of lumepirone according to claim 1, characterized in that: The film-forming material accounts for 3.0-70.0% of the total mass of the composition; the plasticizer accounts for 5.0-30.0% of the total mass of the composition; the sweetener accounts for 0.5-2.0% of the total mass of the composition; the disintegrant accounts for 0.5-5.0% of the total mass of the composition; and the colorant accounts for 0.5-1.0% of the total mass of the composition.

7. The method for preparing the lumiperone orosoluble film-dissolving taste-masking composition according to any one of claims 1 to 6, characterized in that: The following steps are involved: (1) mixing the active ingredient and the alkaline excipient uniformly to obtain a mixture 1; (2) adding mixture 1 to the inclusion compound aqueous solution and mixing homogeneously to obtain solution A; (3) adding a plasticizer, a sweetener, a disintegrant and a colorant to solution A, stirring and mixing to obtain solution B; (4) adding the film-forming material to solution B, stirring and mixing after sufficient swelling, and defoaming to obtain solution C; (5) Apply solution C and dry it.

8. The preparation method according to claim 7, characterized in that: The inclusion compound concentration in the inclusion compound aqueous solution is 5-40% w / v.

9. Use of the lumidperone orodissolving film-taste-masking composition according to any one of claims 1 to 6 or the lumidperone orodissolving film-taste-masking composition prepared by the preparation method according to claim 7 or 8 in the preparation of antipsychotic drugs, characterized in that: The psychiatric disorder includes any of schizophrenia, bipolar disorder type I or type II.

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