COATED GRANULES, SOLID DISPERSION AND PREPARATION CONTAINING VORTIOXETINE HYDROBROMIDE ORAL TASTE MASKING

Abstract

A coated granule, a solid dispersion, a composition, and an oral taste masking preparation that enhance the taste masking effect of vortioxetine hydrobromide and improve patient adherence and compliance.

Description

COATED GRANULE, SOLID DISPERSION AND PREPARATION CONTAINING VORTIOXETINE HYDROBROMIDE ORAL FLAVOR MASKER FIELD OF THE INVENTION The present invention relates to the technical field of pharmaceutical preparations, in particular to a coated granule, solid dispersion, combination and oral taste masking composition. BACKGROUND OF THE INVENTION Vortioxetine is a multitarget antidepressant with 5-HT3 receptor antagonism and 5-HTia receptor agonism, and is used for the treatment of major depressive disorder. Currently, vortioxetine hydrobromide is used clinically as its active ingredient, which was jointly developed by Takeda and H. Lundbeck. It was approved by the EDA on September 30, 2013 for marketing under the trade name Brintellix. The four approved strengths are 5 mg, 10 mg, 15 mg, and 20 mg, and the dosage form is film-coated tablets. The chemical name of vortioxetine hydrobromide is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]-perazine hydrobromide. Its English name is vortioxetine hydrobromide with the formula C18H22N2S HBr. Furthermore, patent US9562024B2 discloses the vortioxetine hemihydrobromide compound, that is, each two molecules of vortioxetine share one molecule of hydrobromic acid, and the molecular formula is CisH22N2S-1 / 2HBr. The structural formulas of CisH22N2S-HBr and CisH22N2S-1 / 2HBr are as follows: Depressive disorder is a common illness, with strong clinical demand. However, during the onset of depression, patients often refuse or do not cooperate with treatment, spitting out pills they have taken when medical staff and home nursing staff are not paying attention. Ordinary tablets and capsules are whole grain tablets, so it is still dangerous for mental patients, the elderly, and long-term bedridden patients (tablets get stuck in the esophagus) to take them. Therefore, there is a clinical need for more appropriate dosage forms to improve patients' adherence or compliance with medication. The oral dispersion drug product allows the drug to exist in the oral cavity in the state of particulate compositions (such as granules, powders, suspensions, dry suspensions) or liquid compositions (such as oral suspensions), or to be able to change rapidly in the cavity orally to a particulate state or a liquid state (e.g., orally disintegrating tablets, orally dispersible tablets). The orally dispersed dosage form is the most appropriate technical means to improve compliance in patients with depression. Among them, orally disintegrating tablet is the best dosage form due to its convenient use, convenient carrying, convenient transportation and stable quality, such as alprazolam orally disintegrating tablets, olanzapine orally disintegrating tablets and risperidone and so on. Due to the physical and chemical properties and clinical compliance of vortioxetine active pharmaceutical ingredients (APIs), very few other dosage forms have been marketed so far. Both vortioxetine hydrobromide and vortioxetine lactate marketed in Europe are very irritating to the oral mucosa, and will cause discomfort to the user when exposed to the mouth, especially on the surface of the tongue, even after rinsing, this irritation still lasted half a day or even more. This will affect drug compliance and limit the application of compositions exposed to the oral cavity. Therefore, it is necessary to prepare orally dispersible dosage forms other than film-coated tablets to overcome the problem of mucosal irritation. Two methods are generally used to overcome the unpleasant taste of drugs. The first method is to reduce the solubility of the drug to reduce the exposure of the drug in the oral cavity. The other method is to change the drug's ability to interact with taste receptors, affecting taste-related receptors, which will have potentially unknown side effects. Therefore, the first method is safer for patients. To reduce the irritation of the drug in the oral cavity, it is necessary to reduce the exposure of the drug in the oral cavity and reduce the dissolution of the drug. However, while reducing the dissolution of the drug, it will also slow down the absorption of the drug, thereby affecting the absorption and metabolism of the immediate-release dosage form and affecting the efficacy and safety of the drug. This technical contradiction is also the main technical obstacle to the product being marketed without an immediate-release oral dosage form that masks the taste. Especially when the patient's condition improves and he is willing to cooperate with the drug and switch to ordinary immediate-release coated tablets, the two dosage forms have different metabolism dissolution and absorption rates, leading to possible physiological and pathological problems afterwards. of the patient's medication change. The use of flavoring agents to adjust the taste is also a method to adjust the unfavorable taste such as bitterness and astringency of the API, but the effect of the flavoring agent on improving the irritation of vortioxetine is very bad. The approved oral solution of vortioxetine lactate has not been accepted on the market for many years due to its strong irritation. Therefore, there is an urgent need to develop new oral exposure type immediate release compositions with taste masking suitable for depressed patients to meet personalized clinical medicine. BRIEF DESCRIPTION OF THE INVENTION In view of the problems of vortioxetine on the oral mucosa and tongue surface irritation and bad taste, one or more embodiments of the present invention provide taste masking immediate release dosage compositions of vortioxetine, which can improve adherence and compliance through the use of appropriate excipients and preparation methods. One or more embodiments of the present invention provide orally dispersible compositions of vortioxetine hemihydrobromide, comprising vortioxetine hemihydrobromide and 5 pharmaceutically acceptable excipients. In one or more embodiments of the present invention, the orally dispersible compositions of the present application are tablets, granules, capsules, powders, suspensions, dry suspensions or solutions. In one or more embodiments of the present invention, the tablets are orally disintegrating tablets or dispersible tablets. One or more embodiments of the present invention provide an orally dispersed sador masking composition of vortioxetine hemihydrodromide or vortioxetine hydrodromide, comprising vortioxetine hemihydrodromide or vortioxetine hydrodromide and pharmaceutically acceptable sador masking excipients. In one or more embodiments of the present invention, and in the orally dispersed sador masking composition of the present invention, vortioxetine hemihydrodromide or vortioxetine hydrodromide are combined with sador masking excipients to form coated granules. In one or more embodiments of the present invention, the flavor masking excipients in the coated granules are cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, methacrylic acid copolymer, chitosan, copovidone or polyvinyl alcohol. In one or more embodiments of the present invention, the flavor masking excipients in the coated granule include alkaline excipients. In one or more embodiments of the present invention, wherein the coated granules comprise an anti-caking agent. In one or more embodiments of the present invention, the vortioxetine hemihydrodromide or vortioxetine hydrodromide in the orally dispersed sador masking composition is dispersed in the sador masking excipient to form a solid dispersion. In one or more embodiments of the present invention, the sador masking excipients in the solid dispersions are cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, methacrylic acid copolymer, chitosan, copovidone, povidone, polyvinyl alcohol or polyethylene glycol. In one or more embodiments of the present invention, the flavor masking excipients in the mentioned solid dispersions include alkaline excipients. In one or more embodiments of the present invention, the vortioxetine hemihydrobromide or vortioxetine hydrobromide in the solid dispersions are mixed with alkaline excipients. In one or more embodiments of the present invention, the vortioxetine hemihydrobromide or vortioxetine hydrobromide in the solid dispersions are mixed with at least one of trisodium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, potassium carbonate, sodium carbonate, bicarbonate sodium, potassium citrate, sodium acetate, calcium hydroxide, sodium hydroxide, potassium hydroxide or meglumine to form a composition. One or more embodiments of the present invention provide flavor masking coated granules of vortioxetine hemihydrobromide or vortioxetine hydrobromide, wherein the excipients of the flavor masking coating of the flavor masking coated granules are cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, copolymer of methacrylic acid, chitosan, copovidone, or polyvinyl alcohol. In one or more embodiments of the present invention, wherein the flavor masking coating excipients comprise alkaline excipients. In one or more embodiments of the present invention, wherein the flavor masking coating excipients comprise anti-caking agents. One or more embodiments of the present invention provide a solid dispersion of vortioxetine hemihydrobromide or vortioxetine hydrobromide, wherein the excipients of the flavor masking coating are cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, methacrylic acid copolymer, chitosan, copovidone, povidone, polyvinyl alcohol or polyethylene glycol. . In one or more embodiments of the present invention, wherein the flavor masking excipients comprise alkaline excipients. One or more embodiments of the present invention provide a vortioxetine hemihydrobromide or vortioxetine hydrobromide flavor masking composition, comprising vortioxetine hemihydrobromide or vortioxetine hydrobromide and alkaline excipients. In one or more embodiments of the present invention, wherein the alkaline excipients in the flavor masking composition are at least one of trisodium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, potassium carbonate, sodium carbonate, sodium bicarbonate, citrate potassium, sodium acetate, calcium hydroxide, sodium hydroxide, potassium hydroxide or meglumine. In one or more embodiments of the present invention, the methacrylic acid copolymers in the orally dispersible flavor masking composition, the flavor masking coated granule, or the solid flavor masking dispersion are polyacrylic resins. In one or more embodiments of the present invention, the polyacrylic resin in the orally dispersible flavor masking composition, the flavor masking coated granule or the solid flavor masking dispersion is polyacrylic resin II or polyacrylic resin IV. 3$ In one or more embodiments of the present invention, the vortioxetine hemihydrobromide or vortioxetine hydrobromide in the orally dispersible flavor masking composition or the flavor masking coated granule is coated with flavor masking excipients to form a coated granule , and wherein said coated granule is further dispersed in the flavor masking excipients to form a solid dispersion; Furthermore, the solid dispersion formed can be further mixed with alkaline excipients. In one or more embodiments of the present invention, said vortioxetine hemihydrobromide or said vortioxetine hydrobromide in the orally dispersible flavor masking composition or solid dispersion is dispersed in flavor masking excipients to form a solid dispersion, wherein the solid dispersion is further coated with excipients to form a coated granule; Furthermore, the formed coated granule can be further mixed with alkaline excipients. In one or more embodiments of the present invention, the vortioxetine hemihydrobromide or vortioxetine hydrobromide in the orally dispersed flavor masking composition or the flavor masking coated granule is coated with flavor masking excipients to form a coated granule, wherein the coated granule can be further mixed with alkaline excipients. In one or more embodiments of the present invention, said vortioxetine hemihydrobromide or said vortioxetine hydrobromide in the orally dispersible flavor masking composition or solid dispersion is dispersed in flavor masking excipients to form a solid dispersion, wherein the solid dispersion It is also mixed with alkaline excipients. In one or more embodiments of the present invention, the flavor masking coated excipients in the orally dispersible flavor masking composition or the flavor masking coated granule are cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, methacrylic acid copolymer, chitosan, copovidone or polyvinyl alcohol. In one or more embodiments of the present invention, the flavor masking excipients in the orally dispersible flavor masking composition or the solid flavor masking dispersion are cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, methacrylic acid copolymer, chitosan, copovidone, povidone, polyvinyl alcohol or polyethylene glycols. In one or more embodiments of the present invention, the alkaline excipients in the orally dispersible flavor masking composition or the flavor masking composition are at least one of trisodium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium citrate, sodium acetate, calcium hydroxide, sodium hydroxide, potassium hydroxide or meglumine. In one or more embodiments of the present invention, the weight proportion of vortioxetine hemihydrobromide or vortioxetine hydrobromide in the orally dispersible flavor masking composition, the flavor masking coated granule, the solid flavor masking dispersion or the composition flavor masking agent with the pharmaceutically acceptable flavor masking excipient used to form coatings or solid dispersions is 1:0.1-1:5. For example, 1:0.3-1:3, 1:0.5-1:1.5 and for example, 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7 , 1:0.8, 1:0.9, 1:1, 1:2, 1:3,1:4 or 1:5. In one or more embodiments of the present invention, the weight ratio of vortioxetine hemihydrobromide or vortioxetine hydrobromide to pharmaceutically acceptable alkaline excipient is amorphous 1:0.01-1:1.1. For example, 1:0.01 -1:1 and for example, 1:0.01,1:0.02,1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09 , 1:0.1, 1:0.5, 1:1,1:1.1. In one or more embodiments of the present invention, the orally dispersible flavor masking composition, flavor masking coated granule, flavor masking solid dispersion, or flavor masking composition of the present invention is a crystalline or amorphous substance. . In one or more embodiments of the present invention, the orally dispersible flavor masking composition, the flavor masking coated granule, the solid flavor masking dispersion or the flavor masking composition of the present invention also comprises a filler, a flavoring, a release regulating agent, a plasticizer, an anti-caking agent and / or a disintegrating agent. In one or more embodiments of the present invention, the anti-caking agent is talc, which represents 5% to 25% of the total weight of the coated flavor masking granule, for example, 10% to 20% and, for example, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% or 20%. In one or more embodiments of the present invention, the flavoring agent is Neotame, which represents 0.05%-0.5% of the total weight of the orally dispersible flavor masking composition, for example, 0.1%, 0.2% or 0.3%. 1§ In one or more embodiments of the present invention, the release regulating agent is polyethylene glycol or alkaline excipient. In one or more embodiments of the present invention, the disintegrating agent is sodium starch glycolate, croscarmellose sodium, crospovidone and combinations thereof, representing 1% to 8% of the total weight of the orally dispersible flavor masking composition. , preferably, 2%15 6%. In one or more embodiments of the present invention, the orally dispersible flavor masking composition, the flavor masking coated granule, the solid flavor masking dispersion or the flavor masking combination is (or is prepared) as tablets, granules, capsules, powders, suspensions, dry suspensions, solutions. In one or more embodiments of the present invention, wherein the tablets are orally disintegrating tablets or dispersible tablets. In one or more embodiments of the present invention, the vortioxetine hemihydrobromide or vortioxetine hydrobromide in the orally dispersible flavor masking composition, the flavor masking coated granule, the solid flavor masking dispersion or the flavor masking combination is amorphous or crystalline. One or more embodiments of the present invention provide for the use of vortioxetine hemihydrobromide in the preparation of an orally dispersible composition, an orally dispersible flavor masking composition, a flavor masking coated granule, a solid flavor masking dispersion or a masking combination of flavor. In one or more embodiments of the present invention, the oral dispersions or dispersible flavor masking compositions are tablets, granules, capsules, powders, suspensions, dry suspensions and solutions. In one or more embodiments of the present invention, wherein the tablets are orally disintegrating tablets or dispersible tablets. One or more embodiments of the present invention provide for the use of vortioxetine hydrobromide in the preparation of an orally dispersible composition, an orally dispersible flavor masking composition, a flavor masking coated granule, a solid flavor masking dispersion or a flavor masking combination. In one or more embodiments of the present invention, the oral dispersions or dispersible flavor masking compositions are tablets, granules, capsules, powders, suspensions, dry suspensions and solutions. In one or more embodiments of frfrfrznn / zznz / E / Yi the present invention, wherein the tablets are orally disintegrating tablets or dispersible tablets. One or more embodiments of the present invention provide a method for preparing flavor masking coated granules of vortioxetine hemihydrobromide or 5-vortioxetine hydrobromide or compositions thereof, comprising: (1) grinding vortioxetine hemihydrobromide or vortioxetine hydrobromide to obtain vortioxetine hemihydrobromide or vortioxetine hydrobromide powder; (2a) disperse the flavor masking excipients in a solvent, coat the vortioxetine hemihydrobromide or the vortioxetine hydrobromide powder with the flavor masking excipients through a fluid bed and remove the solvent to obtain the vortioxetine hemihydrobromide or the hydrobromide of vortioxetine coated with flavor masking excipients; or (2b) add the vortioxetine hemihydrobromide or vortioxetine hydrobromide powder and the flavor masking excipients to a solvent to form a suspension, remove the solvent through a fluid bed, spray drying or evaporation, then obtain the vortioxetine hemihydrobromide or vortioxetine hydrobromide coated with the flavor masking excipients; (3) Optionally, the coated vortioxetine hemihydrobromide or vortioxetine hydrobromide is prepared as a composition. In one or more embodiments of the present invention, materials are screened through a 20-300 mesh screen after grinding, for example, 100, 150 or 200 mesh screen. In one or more embodiments of the present invention, disperse the flavor masking excipient and the release regulating agent in a solvent. In one or more embodiments of the present invention, wherein the release regulating agent is polyethylene glycol or alkaline excipient. In one or more embodiments of the present invention, wherein the solvent is water, ethanol or dichloromethane. Preferably, wherein the vortioxetine hemihydrobromide or vortioxetine hydrobromide, the flavor masking excipient, the release regulating agent and the plasticizer are added to the solvent to form a suspension of vortioxetine hemihydrobromide or vortioxetine hydrobromide; more preferably, wherein the plasticizer is polyethylene glycol or triethyl citrate; preferably, where the solvent is water, ethanol or dichloromethane. One or more embodiments of the present invention provide a method for preparing a solid dispersion of vortioxetine hemihydrobromide or vortioxetine hydrobromide or compositions thereof, comprising: (1) grinding vortioxetine hemihydrobromide or vortioxetine hydrobromide to obtain vortioxetine hemihydrobromide or vortioxetine hydrobromide powder; (2a) mix vortioxetine hemihydrobromide or vortioxetine hydrobromide powder with flavor masking excipients, heat to 50-150°C to soften or liquefy, cool to solidify and grind to obtain the powder; or (2b) dissolving the vortioxetine hemihydrobromide or vortioxetine hydrobromide powder and the flavor masking excipients in a solvent, and removing the solvent by distillation, fluid bed or spray drying to obtain a powder; (3) Optionally, the powder obtained in step (2a) or (2b) is prepared as a composition. In one or more embodiments of the present invention, materials are screened through a 20-300 mesh screen after grinding, for example, 100, 150 or 200 mesh screen. In one or more embodiments of the present invention, wherein the vortioxetine hemihydrobromide or vortioxetine hydrobromide powder, the flavor masking excipient and the release regulating agent are mixed. In one or more embodiments of the present invention, wherein the solvent is water, ethanol or dichloromethane. In one or more embodiments of the present invention, the flavor masking excipients are cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, methacrylic acid copolymer, chitosan, copovidone, povidone, polyvinyl alcohol or polyethylene glycols. In one or more embodiments of the present invention, wherein the methacrylic acid copolymer is a polyacrylic resin. In one or more embodiments of the present invention, the polyacrylic resin is polyacrylic resin II or polyacrylic resin IV. One or more embodiments of the present invention provide a method for preparing a flavor masking combination of vortioxetine hemihydrobromide or vortioxetine hydrobromide or compositions thereof, comprising: (1) grinding vortioxetine hemihydrobromide or vortioxetine hydrobromide to obtain vortioxetine hemihydrobromide or vortioxetine hydrobromide powder; (2) mixing vortioxetine hemihydrobromide or vortioxetine hydrobromide powder with the alkaline excipients to obtain a flavor masking combination; (3) Optionally, the flavor masking combination is prepared as a composition. Preferably, sieve the materials through a 50-300 mesh sieve after grinding, more preferably, 100-200 mesh sieve. Preferably, wherein the alkaline excipients are trisodium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium citrate, sodium acetate, calcium hydroxide, sodium hydroxide, potassium hydroxide or meglumine. In one or more embodiments of the present invention, wherein the powder can be prepared in a conventional composition using conventional methods in the field. In one or more embodiments of the present invention, the weight ratio of vortioxetine hemihydrobromide or vortioxetine hydrobromide to pharmaceutically acceptable flavor masking excipient is 1:0.1-1:5, for example, 1:0.5-1:1.5, 1 :0.3-1:1.5, 1:0.3-1:1.3 and, for example, , 35 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1 :0.8, 1:0.9, 1:1, 1:2, 1:3, 1:4, or 1:5; The weight ratio of vortioxetine hemihydrobromide or vortioxetine hydrobromide to pharmaceutically acceptable alkaline excipient is 1:0.01-1:1.1, preferably 1:0.01-1:1. One or more embodiments of the present invention provide a solid dispersion comprising vortioxetine hemihydrobromide and polyacrylic resin IV, wherein the weight ratio of vortioxetine hemihydrobromide to polyacrylic resin IV is 1:0.1 -1:5, for example, 1: 0.3-1:2,1:0.5-1:1.5, and for example, 1:0.1,1:0.2,1:0.3,1:0.4, 1:0.5,1:0.6,1:0.7,1:0.8, 1:0.9,1:1,1:2, 1:3, 1:4, or 1:5. One or more embodiments of the present invention provide a solid dispersion comprising vortioxetine hydrobromide and polyacrylic resin IV, wherein the weight ratio of vortioxetine hemihydrobromide to polyacrylic resin IV is 1:0.1-1:5, for example, 1 :0.3-1:2, 1:0.5-1:1.5, and for example, 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8 , 1:0.9, 1:1, 1:2, 1:3, 1:4, or 1:5. In one or more embodiments of the present invention, the solid dispersion comprising vortioxetine hemihydrobromide and polyacrylic resin IV has characteristic peaks as shown in Figure 20. In one or more embodiments of the present invention, the solid dispersion comprising vortioxetine hydrobromide and polyacrylic resin IV has characteristic peaks as shown in Figure 22. In one or more embodiments of the present invention, for the solid dispersion comprising vortioxetine hemihydrobromide and polyacrylic resin IV, or the solid dispersion formed by vortioxetine hydrobromide and polyacrylic resin IV, using Cu-Κα radiation, the diffraction pattern of Powder In one or more embodiments of the present invention, for the solid dispersion comprising vortioxetine hemihydrobromide and polyacrylic resin IV, or the solid dispersion formed by vortioxetine hydrobromide and polyacrylic resin IV, using Cu-Κα radiation, the diffraction pattern of Powder 22.6±0.2°, 24.4+0.2°, 26.0±0.2°, 28.2±0.2°, and 29.0±0.2°.. In one or more embodiments of the present invention, the solid dispersion comprising vortioxetine hemihydrobromide and polyacrylic resin IV, or the solid dispersion formed by vortioxetine hydrobromide and polyacrylic resin IV, also includes at least one of PEG 4000, PEG 6000 and PEG 8000. one or more embodiments of the present invention, wherein the weight ratio of polyacrylic resin IV to at least one of PEG 4000, PEG 6000 and PEG 8000 is 1:0.05-1:2, for example, 1:0.05 , 1:0.1, 1:0.5, 1:1, 1:1.5, or 1:2. One or more embodiments of the present invention provide for the use of vortioxetine hemihydrobromide or orally dispersed taste masking composition of vortioxetine hydrobromide, taste masking coated granule, taste masking solid dispersion and taste masking combination in the preparation of a drug antidepressant. One or more embodiments of the present invention provide orally dispersible flavor masking composition of vortioxetine hemihydrobromide or vortioxetine hydrobromide, flavor masking coated granules, flavor masking solid dispersion and flavor masking combination, which are used for the treatment of depressive disorder or the preparation of antidepressant drugs. One or more embodiments of the present invention provide a method for the treatment of depressive disorder, the method comprising administering the orally dispersible taste masking composition of vortioxetine hemihydrobromide or vortioxetine hydrobromide, taste masking coated granule, solid taste masking dispersion flavor or flavor masking combination to 5 a subject who needs it. DETAILED DESCRIPTION OF THE INVENTION In one or more embodiments of the present invention, orally dispersible compositions allow the drug to exist in the oral cavity in the state of particulate compositions (e.g., granules, powders, suspensions, dry suspensions) or liquid compositions (e.g. e.g., oral suspensions), or may be rapidly transformed to the particulate or liquid state (e.g., orally disintegrating tablets, orally dispersible tablets) in the oral cavity. In one or more embodiments of the present invention, coating the vortioxetine hydrobromide powder with suitable polymeric flavor masking excipients to obtain coated granules, then preparing orally dispersible compositions according to the known method of oral compositions. In one or more embodiments of the present invention, the orally dispersible composition of vortioxetine hydrobromide comprises vortioxetine hydrobromide, one of the polymers selected from taste masking polymers, chitosan and deacetylated chitosan, and other excipients. The weight ratio is vortioxetine hydrobromide: polymer containing dimethylaminoethyl units, chitosan or deacetylated chitosan = 1:0.1-1:5, for example: 0.3-1:3. In one or more embodiments of the present invention, the orally dispersible composition of vortioxetine hydrobromide also comprises an anti-caking agent to prevent adhesion during the preparation of the flavor masking coated granules, and the proportion (representing the total weight of the flavor masking granules) is 5%-25%. The anti-caking agent can be talc. In one or more embodiments of the present invention, the orally dispersible composition of vortioxetine hydrobromide also comprises a flavoring agent, and the proportion (the proportion of the total weight of the composition) is 0.05%-0.5%. The flavoring agent may be Neotame. The second solution provided by one or more embodiments of the present invention converts vortioxetine hydrobromide and suitable polymeric excipients into a crystalline or amorphous solid dispersion, and then prepares orally dispersible compositions according to the known method of oral compositions. In one or more embodiments of the present invention, the vortioxetine hydrobromide orally dispersible flavor masking composition comprises vortioxetine hydrobromide, one of polymers selected from flavor masking polymer, chitosan and deacetylated chitosan, and other excipients. The weight ratio is vortioxetine hydrobromide: polymer containing dimethylaminoethyl units, chitosan or deacetylated chitosan = 1:0.3-1:5. In one or more embodiments of the present invention, the vortioxetine hydrobromide orally dispersible frfrfrznn / zznz / E / Yii flavor masking composition also comprises a flavoring agent, and the proportion (the proportion of the total weight of the composition) is 0.05%-0.5%. The flavoring agent may be Neotame. The third solution provided by one or more embodiments of the present invention uses weak alkaline excipients to temporarily change the pH environment in which the drug is dispersed in the oral cavity, causing the drug to dissolve in the oral cavity below the stimulation threshold and then return to an acidic pH environment in the gastric juice, while solving the problems of oral exposure and dissolution and absorption metabolism in the gastrointestinal tract. In one or more embodiments of the present invention, the vortioxetine hydrobromide orally dispersible flavor masking composition comprises vortioxetine hydrobromide, alkaline or weak alkaline flavor masking agent, and flavoring agent. The weight ratio is vortioxetine hydrobromide (CisH22N2S1 / 2HBr or Ci8H22N2S-HBr): alkaline or weak alkaline flavor masking agent and flavoring agent = 1: (0.0001 -0.01), for example, 1: (0.0009 - 0.009). In one or more embodiments of the present invention, the flavor masking excipients in the orally dispersible flavor masking composition of vortioxetine hydrobromide are alkaline pharmaceutical excipients, including, but not limited to, trisodium phosphate, disodium hydrogen phosphate, hydrogen phosphate dipotassium, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium citrate, sodium acetate, calcium hydroxide, sodium hydroxide, potassium hydroxide or meglumine. In one or more embodiments of the present invention, the flavoring agent in the orally dispersible flavor masking composition of vortioxetine hydrobromide is a pharmaceutically acceptable flavoring agent, including, but not limited to, Neotame. In one or more embodiments of the present invention, the coated taste-masking particles or solid taste-masking dispersion of vortioxetine hydrobromide can be prepared as an oral composition of vortioxetine hydrobromide for oral dispersion. In one or more embodiments of the present invention, oral dispersion or display compositions of flavor-masking coated granules or taste-masking solid dispersions of vortioxetine hydrobromide include, but are not limited to, compositions that may exist in particulate compositions (e.g. , granules, powders, suspensions, dry suspensions) or solution compositions (e.g., oral solutions) in the oral cavity, or can be rapidly transformed into a particulate or solution state in the oral cavity (e.g., tablets that disintegrate by orally, orally dispersible tablets). One or more embodiments of the present invention provide methods for preparing vortioxetine hydrobromide flavor masking compositions, including at least three methods of preparation. Preparation method 1 (1) grind vortioxetine hydrobromide to obtain vortioxetine hydrobromide powder; preferably, sieving the material through a 20-300 mesh sieve after grinding, more preferably, hbh7nn / 77n7 / E / Yl· 100-200 mesh sieve; (2a) dispersing the flavor masking excipients in a solvent, coating the vortioxetine hydrobromide powder with the flavor masking excipients through a fluid bed and removing the solvent to obtain the vortioxetine hydrobromide coated with the flavor masking excipients; preferably, dispersing the flavor masking excipients and the release regulating agent in a solvent; more preferably, wherein the release regulating agent is polyethylene glycol or alkaline excipients; preferably, where the solvent is water, ethanol or dichloromethane; or (2b) add the vortioxetine hydrobromide powder and the flavor masking excipients to a solvent to form a suspension, remove the solvent through a fluid bed, spray drying or evaporation, then obtain the vortioxetine hydrobromide coated with the flavor masking excipients; preferably, wherein the vortioxetine hydrobromide, the flavor masking excipient, the release regulating agent and the plasticizer are added to the solvent to form a suspension of vortioxetine hydrobromide; preferably, wherein the plasticizer is polyethylene glycol or triethyl citrate; preferably, where the solvent is water, ethanol or dichloromethane; (3) Optionally, the coated vortioxetine hydrobromide is prepared as a composition. Preparation method 2: (1) grinding vortioxetine hydrobromide to obtain vortioxetine hydrobromide powder; preferably, sieving the material through a 20-300 mesh sieve after grinding, more preferably, 100-200 mesh sieve; (2a) mix the vortioxetine hydrobromide powder with the flavor masking excipients, heat to 50-150°C to soften or liquefy, cool to solidify and grind to obtain the powder; preferably, wherein the vortioxetine hydrobromide powder, the flavor masking excipient and the release regulating agent are mixed; or (2b) dissolving the vortioxetine hydrobromide powder and the flavor masking excipients in a solvent, and removing the solvent by distillation, fluid bed or spray drying to obtain a powder; preferably, where the solvent is water, ethanol or dichloromethane; (3) Optionally, the powder obtained in step (2a) or (2b) is prepared as a composition. Preparation method 3: (1) grind vortioxetine hemihydrobromide or vortioxetine hydrobromide to obtain powder; preferably, sieving the material through a 50-300 mesh sieve after grinding, more preferably, 100-200 mesh sieve; (2) mixing vortioxetine hemihydrobromide or vortioxetine hydrobromide powder with alkaline excipients to obtain a flavor masking composition; preferably, wherein the alkaline excipients are trisodium phosphate, disodium hydrogen phosphate, sodium carbonate, sodium bicarbonate, potassium citrate, sodium acetate, calcium hydroxide or meglumine; (3) Optionally, the flavor masking combination is prepared as a composition. In one or more embodiments of the present invention, in the methods mentioned above, vortioxetine hemihydrobromide or vortioxetine hydrobromide may be used, and an amorphous or crystalline vortioxetine hemihydrobromide or vortioxetine hydrobromide may be used. In one or more embodiments of the present invention, the three preparation methods mentioned above can be implemented independently or in combination with each other, or implemented in combination according to a known preparation process. In one or more embodiments of the present invention, the release regulating agent in the above preparation methods includes, among others, mannitol, sorbitol, xylitol, polyethylene glycol, hydroxypropyl cellulose and / or hydroxypropylmethyl cellulose. In one or more embodiments of the present invention, the plasticizer in the above preparation methods includes, but is not limited to, polyethylene glycol and / or triethyl citrate. In one or more embodiments of the present invention, the methods of preparing the orally dispersible taste masking composition of vortioxetine hydrobromide adopt one or more pharmaceutically acceptable resins and vortioxetine hydrobromide to be co-dissolved in one or more pharmaceutically acceptable solvents. to obtain a true solution; after removing the solvent by rotary evaporation, spray drying or fluid bed granulation, the solid dispersion of microcrystalline vortioxetine hydrobromide is obtained in the confined space of the polymer; According to the conventional preparation process, adding other known excipients in the prescribed amount, and then using the alkaline small molecule taste masking material, the oral exposure type vortioxetine hydrobromide oral dispersion and the composition can also be prepared. flavor masking. In one or more embodiments of the present invention, the polyacrylic resin IV and vortioxetine hemihydrobromide or vortioxetine hydrobromide are dissolved in solvent, and the weight ratio of vortioxetine hemihydrobromide or vortioxetine hydrobromide to polyacrylic resin IV is 1:0.125 1:5, preferably, 1:0.3-1:2, more preferably, 1:0.5-1:1.5. Then remove the solvent to obtain a solid dispersion and the characteristic peaks of the X-ray powder diffraction pattern: 4.2±0.2°, 14.5±0.2°, 17.4±0.2°, 19.2±0.2° and 22.6±0.2°; in addition, the characteristic peaks of the powder 24.4+0.2°, 26.0±0.2°, 28.2±0.2°, and 29.0+0.2°. The solid dispersion has been shown to be stable in solution, stable in impurities and stable in crystalline state through stability studies. In one or more embodiments of the present invention, the methods of preparing the orally dispersible taste masking composition of vortioxetine hydrobromide adopt one or more pharmaceutically acceptable resins and vortioxetine hydrobromide to co-dissolve in one or more pharmaceutically acceptable solvents and then reduce the solubility of the solution or eliminate the solvent, vortioxetine and the resin form a solid dispersion and its granule; according to the conventional preparation process, adding other known excipients in the prescribed amount can prepare an orally dispersible flavor masking composition of vortioxetine hydrobromide; wherein vortioxetine exists in the resin in the state of ions or molecules, and interacts with the functional groups of the resin, bbb7nn / 77n7 / E / Yl· so that the dissociation slows down in the oral environment, and after passing to Through the gastric juice environment, it can be rapidly dissociated into vortioxetine in the gastrointestinal tract. In one or more embodiments of the present invention, the methods of preparing the orally dispersible taste masking composition of vortioxetine hydrobromide adopt one or more pharmaceutically acceptable resins and vortioxetine hemihydrobromide or vortioxetine hydrobromide to codissolve in one or more pharmaceutically acceptable solvents and then reduce the solubility (for example, add poor solvents, or lower the temperature) of the solution or remove the solvent, obtain an amorphous solid dispersion of vortioxetine hydrobromide; According to the conventional preparation process, add other known excipients in the prescribed amount, selectively add alkaline excipients to external excipients. Alkaline excipients can change the microenvironment of receptors in the mucosa and taste buds and reduce irritation; wherein vortioxetine hydrobromide exists in an amorphous aggregate state. In one or more embodiments of the present invention, the resins include, but are not limited to, these linear polymeric materials: polyacrylic resins (type L, S or type II, III, IV), methacrylic acid containing -NH2 functional groups , NR2, -COOH, -COO-, -SO3H, or -SO3-, divinylbenzene resins and polystyrene resins. In one or more embodiments of the present invention, the methods of preparing the orally dispersible flavor masking compositions of vortioxetine hydrobromide, mix one or more pharmaceutically acceptable flavor masking excipients, one or more pharmaceutical release regulating agents acceptable with vortioxetine hydrobromide, after preparing the solid dispersion by hot melt granulation and hot melt extrusion processes, according to the conventional preparation process, add other known excipients in the prescribed amount, then the solid dispersion It can be mixed with alkaline flavor-masking excipients or additionally coated with flavor-masking excipients. The orally dispersible taste masking composition of vortioxetine hydrobromide is released slowly or not at all in the oral environment, and can be rapidly dissociated into vortioxetine hydrobromide in the gastrointestinal tract after passing through the gastric juice environment, which is absorbed through the gastrointestinal tract. In one or more embodiments of the present invention, alkaline linear polymeric materials include, but are not limited to, polyacrylic resins (e.g., type II or IV), chitosan or amino sugar polymers. In one or more embodiments of the present invention, wherein the release regulating agent includes, among others, mannitol, sorbitol, xylitol, polyethylene glycol, hydroxypropylcellulose or hydroxypropylmethylcellulose. The inventor unexpectedly discovered that vortioxetine hemihydrobromide (Ci8H22N2S-1 / 2HBr) is significantly less irritating than vortioxetine hydrobromide (CisH22N2S-HBr), even if converted to the same amount of C18H22N2S. There is little difference in solubility between the two salts in sodium acetate medium that simulates the oral environment pH 6.8 (using the USP method, the solubility of vortioxetine hydrobromide is 0.15 mg / ml and the solubility of vortioxetine hemihydrobromide is 0.14 mg / ml), but the irritation of vortioxetine hemihydrobromide is significantly reduced. Because vortioxetine hemihydrobromide has less oral and tongue irritation, it can be prepared in a solid dosage form with polymeric excipients, which greatly improves the dissolution rate and total dissolution rate of vortioxetine in the 5 gastrointestinal tract, without causing oral irritation. The disintegration rate is an important clinical indicator of orally disintegrating tablets, and the pharmacopoeias of several countries recommend that it be less than 1 minute. In clinical practice, faster is better, especially for medications with patient compliance issues. Freeze-dried orally disintegrating tablets can adopt lyophilization technology, where the active ingredients of the drug are uniformly dispersed in the skeleton material solution in the state of micropowder or solution, and the dispersed mixture is quantitatively packaged for each dose, and then From freeze-drying, the finished formulation can disintegrate within 5 seconds; but the process is complex and difficult to industrialize. The compressed orally disintegrating tablet is prepared using a general tablet preparation technology and can also achieve a disintegration time of 1 minute by using a highly efficient disintegrating agent and reducing the pressure of the tablet. However, reducing the pressure of the tablet pressing will greatly affect the strength of the tablets, and there will be many inconveniences due to wear during production, transportation and use. Researchers use a variety of disintegrants to obtain a compound disintegrant. It has been able to ensure that the finished product 20 is within the normal strength range of the tablet and that the disintegration is controlled within 10 seconds. In one or more embodiments of the present invention, compound disintegrants include, but are not limited to, carboxymethylstarch sodium, croscarmellose sodium and crospovidone. In one or more embodiments of the present invention, the weight ratio of sodium carboxymethyl starch, croscarmellose sodium and crospovidone is 1:1:1, and the weight ratio in the composition is 1%-8% respectively, for example, 2 %- 6%. In one or more embodiments of the present invention, this invention uses polymers recognized as safe. The currently known molded products of this type of polymer mainly include type II polyacrylic resin and type IV polyacrylic resin (Eudragit E), among which Eudragit E is the English trade name, and the general name is Amino Methacrylate Copolymer. It is included in the USP40-NF35 edition of the United States Pharmacopeia. The FDA has specified that the maximum daily dose of the polymer is 214.28mg when used in taste-masking orally disintegrating tablets, which can meet the needs of vortioxetine hydrobromide taste-masking. Its E100 analogues have the same chemical structure, physical and chemical properties and quality standards, and can also meet the preparation needs. In one or more embodiments of the present invention, the flavor is further improved by the selective addition of flavoring agent, while providing a variety of flavor portions. One of the flavoring agents used in this technology is Neotame, which has been included in the USP40NF35 edition of the United States Pharmacopeia. Neotame has been widely used as a food additive. In one or more embodiments of the present invention, the use of alkaline excipients as taste masking agents can significantly reduce tongue irritation, and the irritation can be reduced to a level acceptable for clinical medication. In one or more embodiments of the present invention, the flavor masking agent used is a pharmaceutically acceptable excipient. The composition provided by one or more embodiments of the present invention can improve patient adherence and compliance, improve the dissolution of vortioxetine hydrobromide, potentially improve the bioavailability of the drug and resolve the deficiencies of the 1$ vortioxetine oral composition in the prior art that the dosage form is unique and does not respond to the needs of clinical differentiation and individualized administration. The inventor of the present invention has carried out research on commercially available vortioxetine hydrobromide film-coated tablets: after a single dose of 20 mg, 10 mg and 5 mg, there was obvious bitterness and strong long-term delayed irritation 15 after oral dispersion. Oral irritation limits the development and clinical application of oral compositions other than film-coated tablets. DESCRIPTION OF THE FIGURES Figure 1: X-ray powder diffraction pattern of vortioxetine hemihydrobromide. Figure 2: X-ray powder diffraction pattern of form a of vortioxetine hydrobromide. Figure 3: Powder X-ray diffraction pattern of the β form of vortioxetine hydrobromide. Figure 4: Powder X-ray diffraction pattern of UreleaseElOO: PEG 6000 = 1:0.23 after spray drying. Figure 5: Powder X-ray diffraction pattern of flavor masking powder (vortioxetine hemihydrobromide: UreleaseElOO: PEG 6000 = 1:0.3:0.07). Figure 6: Powder X-ray diffraction pattern of flavor masking powder (vortioxetine hydrobromide form a: UreleaseElOO: PEG 6000 = 1:0.3:0.07). Figure 7: Powder X-ray diffraction pattern of flavor masking powder (vortioxetine hydrobromide β form: UreleaseElOO:PEG 6000 = 1:0.3:0.07). Figure 8: UV spectrum of vortioxetine hydrobromide in 0.1 N hydrochloric acid. Figure 9: UV spectrum of Eudragit E PO in 0.1 N hydrochloric acid. Figure 10: UV spectrum of mixed powder (vortioxetine hydrobromide: Eudragit E PO=1:0.5) in 0.1 N hydrochloric acid. Figure 11: UV spectrum of mixed hot melt powder (vortioxetine hydrobromide: Eudragit E PO=1:0.5) in 0.1 N hydrochloric acid. Figure 12: UV spectrum of vortioxetine hemihydrobromide in 0.1 N hydrochloric acid. Figure 13: UV spectrum of directly mixed powder (vortioxetine hemihydrobromide: Eudragit E PO=1:1.5) in 0.1 N hydrochloric acid. Figure 14: UV spectrum of hot melt powder (vortioxetine hemihydrobromide: Eudragit E PO=1:1.5) in 0.1 N hydrochloric acid. Figure 15: UV spectrum of directly mixed powder (vortioxetine hemihydrobromide: Eudragit E PO=1:5) in 0.1 N hydrochloric acid. Figure 16: UV spectrum of hot melt powder (vortioxetine hemihydrobromide: Eudragit E PO=1:5) in 0.1 N hydrochloric acid. Figure 17: UV spectrum of polyacrylic resin IV in 0.1 N hydrochloric acid. 1§ Figure 18: UV spectrum of directly mixed powder (vortioxetine hydrobromide: polyacrylic resin IV =1:1.5) in 0.1 N hydrochloric acid. Figure 19: UV spectrum of hot melt powder (vortioxetine hydrobromide: polyacrylic resin IV =1:1.5) in 0.1 N hydrochloric acid. Figure 20: Powder X-ray diffraction pattern of vortioxetine IV hemihydrobromide polyacrylic resin 15 solid dispersion. Figure 21: Powder X-ray diffraction pattern of polyacrylic resin IV after spray drying. Figure 22: Powder X-ray diffraction pattern of solid dispersion of vortioxetine hydrobromide-polyacrylic resin IV. Figure 23: Vortioxetine hydrobromide: solid dispersion powder X-ray diffraction pattern of polyacrylic resin 11 = 1:1.5. Figure 24: X-ray diffraction pattern of polyacrylic resin II powder (by distilling the ethanol solvent). Figure 25: Vortioxetine hemihydrobromide: powder X-ray diffraction pattern of solid dispersion of polyacrylic resin 11 = 1:1.5. EXAMPLES Embodiments of the invention are described below in detail with reference to specific examples, but those skilled in the art should understand that the examples are only used to illustrate the invention and should not be considered as limiting the scope of the invention. If no specific conditions are indicated in the examples, it will be carried out in accordance with conventional conditions and conditions recommended by the manufacturer or supplier. Those reagents or instruments that do not indicate the specific manufacturer and model are all conventional products that can be purchased commercially. The polyacrylic resin II in this invention is called methylmethacrylic acid methacrylate copolymer (1:1) in the European Pharmacopeia and type A methacrylic acid copolymer in the American Pharmacopeia, and polyacrylic resin II in the Chinese Pharmacopeia. For example, it can be purchased from the supplier Evonik Rohm GmbH Company (for example, the trade name is Eudragit L, Eudragit L100 and Eudragit L PO) or Anhui Shanhe Pharmaceutical Excipients Co., Ltd. (for example, the product name is polyacrylic resin II). The polyacrylic resin IV in this invention is called amino methacrylate copolymer in the American Pharmacopeia, and it is called polyacrylic resin IV in the Chinese Pharmacopeia. For example, 5 can be purchased from the supplier Evonik Rohm GmbH Company (for example, the trade name is Eudragit E100, Eudragit E PO), Guangzhou Maofeng Pharmaceutical Excipients Co., Ltd. (for example, the product name is Urelease E, Urelease E100) or Anhui Shanhe Pharmaceutical Excipients Co. , Ltd. (for example, the product name is polyacrylic resin IV). Other polyacrylic resins can be purchased, for example, from Evonik Rohm GmbH 1§ Corporation, for example, under the trade names Eudragit RL100, Eudragit L100, Eudragit RS PO and Eudragit S100. The excipients used in the examples are not associated with this invention, while in preparing compositions using this invention, other known common and functional pharmaceutical excipients may be used depending on the dosage form, stability of the composition and the needs of clinical use. In the examples, vortioxetine hydrobromide does not indicate the specific crystal form used, meaning that the α, β or y crystal form is acceptable. Instruments used in the experiment: X-ray powder diffraction (XPRD): The instrument is D / max2200 / pc equipped with Θ-2Θ RINT2000 goniometer Vertical goniometer, MO monochromator and 20 scintillation counter detector. The acquisition software is XG operation. The instrument is calibrated with the monocrystalline silicon standard that comes with the instrument. Detection conditions: 2Θ angle scanning range: 3-40° or 3-50°, step size: 0.02°, speed: 6° / min. Detection process: use of a Cu target with a Ka X-ray wavelength of 1.54nm, under operating conditions of 40 kV and 20mA. The samples are tested at room temperature and the required samples are placed on the non-reflective Si P plate 25. The samples are sieved before testing. Ultraviolet Visible Spectrophotometer: UV-2600, Shimadzu, Japan. Analytical balance: AUW120D, SHIMADZU. Rotary evaporator: R205, Taizhou Xinli Electronic Equipment Co., Ltd. Hot air circulation oven: DHG-9070A, Shanghai Yiheng Scientific Instrument Co., 3S Ltd. Vertex mixer: Vortex-2, Shanghai Huxi Industrial Co., Ltd. Multifunctional fluid bed: BWF-1G, Chongqing Enger Granulation Coating Technology Co., Ltd. Vacuum freeze dryer: FD-2D, Beijing Boyikang Experimental Instrument Co., Ltd. 35 Rotary tablet press: ZP8, Shanghai Xinyuan Pharmaceutical Machinery Co., Ltd. High Efficiency Coating Machine: Labcoating IV, Shenzhen Xinyite Technology Co., Ltd. Dry granulator: GL-5B, Zhejiang Future Machinery Co., Ltd. Granulator: P100, Shenzhen Xinyite Technology Co., Ltd. Portable pH meter: STARTER 300. Lyophilizer: SCIENT2-30F, Ningbo Scientz Biotechnology Co., Ltd. Flat Blister Packing Machine: Zhejiang Future Machinery Co., Ltd. Related data collection methods: Test method for pH and exposure (calculated as vortioxetine): Take one tablet of this product (or powder equivalent to 20mg of vortioxetine), add 5.0 g of purified water, incubate for 5 minutes at 36±2°C with airtight shaking and disperse, then cool to room temperature and check the pH of the suspension. Filter through a 0.22 um microporous membrane, take 2.0mL of the filtrate and dilute to 10mL with purified water as a test solution, and take the solution quantitatively diluted with purified water to 10 ug / mL (based on vortioxetine) as a solution. For reference, the UV method detects the absorption value at a wavelength of 226 nm respectively and calculates the concentration and relative dissolution of vortioxetine. Relative dissolution. frfrfrznn / zznz / E / Yii UV absorbance of sample 100% Titration test method for determining bromine assay in vortioxetine hydrobromide: First prepare 0.1 mol / L silver nitrate titrant and then prepare 5 mg / mL eosin Y test solution. Dissolve 0.3 g of sample in 60 mL of methanol. Add 20mL of water, 20mL of glacial acetic acid and 8 drops of eosin Y TS. Titrate with 0.1 N SV silver nitrate to a pink endpoint. Carry out a blank degree. Calculation formula: (Vs-Vb)xNx7,990 Br%=—ú—- / ---2----rx1 θθ% 0.1 xWx(1 - % water) Where, Vs vb Volume of 0.1 mol / mL of silver nitrate consumed for the sample, mL Volume of 0.1 N silver nitrate consumed for blank, mL Normality of volumetric solution of silver nitrate sample weight, mg % water sample water 7,990 Each 7,990 mg of Br is equivalent to 1 mL of 0.1 mol / mL silver nitrate. In the examples, the taste masking effects of the test samples were evaluated by the subject's perception of bitterness and irritation of the oral cavity and tongue. Taste and irritation rating tested by subjects: Instantaneous irritation of 0-1 minute Delayed irritation Bitterness + + + Strong irritation, intolerable Delayed 1-15 minutes Acceptable + + Irritant, tolerable Delayed 15-30 minutes + Almost no irritation Delayed more than 30 minutes Unacceptable Tested by 5-10 subjects and taking the average value hbh7nn / 77n7 / E / Yl· Preparation Example 1: Preparation of Vortioxetine Free Base Vortioxetine was synthesized with reference to the preparation method of Example 24 in Patent Document WO2007 / 144005A1. Detailed process: 40.76 g of NaOBu', 0.33 g of Pddba2 and 0.68 g of rac-BINAP were stirred with 200 mL of toluene. 19.54g of 2,4-dimethylthiophenol was added and the white precipitate appeared. Then, 42.00 g of 2-bromo-iodobenzene were added. The suspension was heated to reflux and reflux continued for 5 hours. The reaction mixture was cooled to room temperature and filtered through an auxiliary filter. The filtrate was added to a mixture of 40.76 g of NaOBu', 42.2 g of piperazine, 0.33 g of Pddba? and 0.68 g of rac-BINAP and heated at reflux for 2 hours. The reaction mixture was cooled to room temperature. 100mL of water was added and the aqueous phase was separated. The organic phase was filtered through an auxiliary filter and then the filtrate was washed with 3x80mL of brine. The organic phase was heated to 70°C and then 16.50mL of 48% by weight HBr (145.9 mmol) and 8.3mL of water were added. The mixture was stirred for approximately 30 minutes, then cooled to room temperature and kept at room temperature for 2 hours. The final product (1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-perazine hydrobromide) was collected by filtration and washed with toluene, dried at 50°C for 10 hours, producing 40.18 g of white powder with a molar yield of 75%. The 40.18 g of vortioxetine hydrobromide (obtained in the previous step) were dissolved in 200 mL of water. 200 mL of dichloromethane was added, the pH was adjusted to 9-10 with 15% aqueous sodium hydroxide solution, then the solution was kept for 30 minutes. The solution was kept still and the aqueous phase was separated. The aqueous phase was extracted once with 100 mL of dichloromethane. The combined organic phase was washed with 10OmL of water and the separated organic phases were added with 5 g of anhydrous sodium sulfate to dry. The organic phase was filtered and then concentrated to obtain 29.7 g of whitish crystals of 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine hydrobromide, which was the free base of vortioxetine, in a yield molar of 94.0%. Preparation Example 2: Preparation of vortioxetine hemihydrobromide Vortioxetine hemihydrobromide was synthesized with reference to the preparation method of example 1 in patent document US9562024B2. Detailed process: 8.00 g (26.8 mmol) of vortioxetine was dissolved in 122 mL of ethanol by sonication in a 250 ml round bottom flask; 2.70 g of hydrobromic acid (40% w / w, 13.3 mmol) were dissolved in 16 mL of ethanol by sonication; with stirring, the hydrobromic acid solution was slowly added dropwise to the vortioxetine solution; the solids precipitated during the dropwise addition process; the solvent was removed by rotary evaporation at 40°C; After drying under vacuum at 40°C for 24 h, 8.91 g (13.1 mmol) of white solids of vortioxetine hemihydrobromide were obtained. The performance percentage was 98.5%. The bromine assay measured by the titration method was 11.60%. Preparation Example 3: Preparation of vortioxetine hydrobromide in form a The a form of vortioxetine hydrobromide was synthesized with reference to the preparation method of example 4a in patent document WO2007 / 144005A1. Detailed process: 2.0 g of 1 [2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]-piperazine was dissolved in hot 30 mL of ethyl acetate and 0.73 mL of HBr at 48% by weight (aq.) were added. . This addition caused the formation of a thick suspension and 10mL of ethyl acetate was added to achieve adequate agitation. The suspension was stirred at room temperature for one hour. Filtration and drying under vacuum (20°C) overnight afforded 2.0 g of the product as a white solid (80% yield). The product was the a crystal form of vortioxetine hydrobromide. The bromine assay measured by the titration method was 20.76%. Preparation example 4: Preparation of vortioxetine hydrobromide in β form The a form of vortioxetine hydrobromide was synthesized with reference to the preparation method of example 4c in patent document WO2007 / 144005A1. Detailed process: 49.5 g of 1 [2-(2,4-d i metí I -fe n ¡Isu Ifan i I)-f in ¡l]-piperazine were dissolved in 500 mL of ethyl acetate and 18.5 mL of 48 were added % by weight of HBr (aq.). This addition caused the formation of a thick suspension which was stirred overnight at room temperature. Filtration and drying under vacuum (50°C) overnight afforded the product at 29.6 g as a white solid (yield 47%). The product was the β crystalline form of vortioxetine hydrobromide. The bromine assay measured by the titration method was 20.69%. Preparation Example 5: Preparation of Vortioxetine Hydrobromide in γ Form The γ form of vortioxetine hydrobromide was synthesized with reference to the preparation method of example 4e in patent document WO2007 / 144005A1. Detailed process: 1 g of 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine hydrobromide was dissolved in 20 mL of water and heated to 85°C. . The solution was almost transparent. Addition of 1 drop of HBr cleared it up. HBr was added until the cloud point was observed. The solution was cooled to room temperature and dried. The product was the shape of glass 3^ γ vortioxetine hydrobromide. The bromine assay measured by the titration method was 20.73%. Example 1: Preparation of Vortioxetine Hydrobromide Taste Masking Powder + Coating Material 1a) Vortioxetine hemihydrobromide: UreleaseEI 00: PEG6000-1:0.3:0.07 preparation of 35 flavor masking powder 30.00 g of UreleaseEI 00 and 7.00 g of PEG6000 were added to 470.02 g of medicinal ethanol, stirred to dissolve and separated. 100.00 g of vortioxetine hemihydrobromide of 100-200 mesh and 10.00 g of hbh7nn / 77n7 / E / Yl talc with particle size less than 325 mesh were added to the BWF-1G multifunctional fluid bed installed in the spray coating mode. lower. The air inlet volume and height of the guide tube were adjusted so that the materials were in a fluidized state, and the air inlet temperature was set at 50-55°C, the peristaltic pump speed was 5 rpm. and the spray pressure was 1.0-1.5 5 atm. The prepared special coating liquid was sprayed into the fluid bed. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected and the powder with 60-150 mesh particle size was collected by sieving. 125.79 g of flavor masking powder were obtained with a yield of 85.57%. The assay (calculated as vortioxetine) of powder was 60.14%. If the materials were bonded during the preparation process, an appropriate amount of talcum powder could be added after stopping the machine to ensure that the materials were in a fluidized state. Flavor masking powder equivalent to 20mg vortioxetine and vortioxetine hemihydrobromide 100 15 mesh powder equivalent to 20mg vortioxetine were tested and compared by 5 subjects. Improved irritation from taste masking powder. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes 20 after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 1: hbh7nn / 77n7 / E / Yl· Table 1 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + ++ 1- 15 15-30 acceptable acceptable N / A N / A Subject 5 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A The powder The powder X-ray diffraction pattern of Urelease E100:PEG 6000=1:0.23 powder after spray drying is shown in Figure 4. 1b) Preparation of flavor masking powder of form a of vortioxetine hydrobromide: UreleaseE100: PEG6000=1:0.3:0.07 30.09 g of UreleaseEI 00 and 7.05 g of PEG6000 were added to 470.20 g of medicinal ethanol, stirred to dissolve and set aside. 100.02 g of 100-200 mesh vortioxetine hydrobromide in form a and 10.05 g of talc with particle size less than 325 mesh were added to the BWF-1G multifunctional fluid bed installed in the bottom spray coating mode. The air inlet volume and height of the guide tube were adjusted so that the materials were in a fluidized state, and the air inlet temperature was set at 50-55°C, the peristaltic pump speed was 5 rpm. and the spray pressure was 1.0-1.5 atm. The coating liquid prepared by Urelease was sprayed into the fluid bed. After the 1st spray, the materials continued to be fluidized for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected and the powder with 60-150 mesh particle size was collected by sieving. 127.81 g of flavor masking powder were obtained with a yield of 86.82%. The assay (calculated as vortioxetine) of powder was 52.77%. If the materials were bonded during the preparation process, an appropriate amount of talcum powder could be added after stopping the machine to ensure that the materials were in a fluidized state. Flavor masking powder equivalent to 20 mg vortioxetine and 100 mesh powder vortioxetine hydrobromide equivalent to 20 mg vortioxetine were tested and compared by 5 subjects. Improved irritation from taste masking powder. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 2: hbh7nn / 77n7 / E / Yl· Table 2 Flavor comparison test of vortioxetine hydrobromide taste masking powder in form a Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 ++ + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A The powder X-ray diffraction pattern of vortioxetine hydrobromide form a: Urelease E100 flavor masking powder: PEG 6000=1:0.3:0.07 is shown in Figure 6. The powder X-ray diffraction pattern of Urelease E100: PEG 6000=1:0.23 powder after spray drying is shown in Figure 4. 1c) Preparation of taste masking powder of the β form of 5-vortioxetine hydrobromide: Urelease E100:PEG6000=1:0.3:0.07 30.00 g of Urelease E100 and 7.00 g of PEG6000 were added to 470.20 g of medicinal ethanol, stirred to dissolve and separated. 100.00 g of 100-200 mesh vortioxetine hydrobromide in β form and 10.00 g of talc with particle size less than 325 mesh were added to the BWF-1G multifunctional fluid bed installed in the bottom spray coating mode. The air inlet volume and height of the guide tube were adjusted so that the materials were in a fluidized state, and the air inlet temperature was set at 50-55°C, the peristaltic pump speed was 5 rpm. and the spray pressure was 1.0-1.5 atm. The coating liquid prepared by Urelease was sprayed into the fluid bed. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected and the powder with 60-150 mesh particle size was collected by sieving. 126.78 g of flavor masking powder were obtained with a yield of 86.24%. The assay (calculated as vortioxetine) of powder was 53.15%. If the materials were bonded during the preparation process, an appropriate amount of talcum powder could be added after stopping the machine to ensure that the materials were in a fluidized state. Flavor masking powder equivalent to 20mg vortioxetine and vortioxetine hydrobromide 100 mesh powder in β form equivalent to 20mg vortioxetine were tested and compared by 5 subjects. Improved irritation from taste masking powder. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 3: Table 3 Flavor comparison test of β-form vortioxetine hydrobromide taste masking powder Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 ++ + ++ 1-15 >30 acceptable unacceptable N / A N / A | Subject5 | ++ | +++ | 1-15 | >30 | acceptable | unacceptable | N / A | N / A ~| The powder X-ray diffraction pattern of the β form of vortioxetine hydrobromide: Urelease E100: PEG 6000=1:0.3:0.07 is shown in Figure 7. 6000=1:0.23 after spraying drying is shown in Figure 4. 1d) Preparation of vortioxetine hemihydrobromide flavor masking powder: ethylcellulose N10: PEG 6000=1:3:0.07 150.00 g of N10 ethylcellulose and 3.50 g of PEG 6000 were added to 1500.00 g of medicinal ethanol, stirred to dissolve and set aside. 50.00 g of vortioxetine hemihydrobromide of 100-200 mesh and 25.00 g of talc with particle size less than 325 mesh were added to the BWF-1G multifunctional fluid bed installed in the bottom spray coating mode. The air inlet volume and height of the guide tube were adjusted so that the materials were in a fluidized state, and the air inlet temperature was set at 50-55°C, the speed of the peristaltic pump was 5 rpm. and the spray pressure was 1.0-1.5 atm. The coating liquid prepared by Urelease was sprayed into the fluid bed. After spraying, the materials continued to be fluidized for 30 minutes to remove residual ethanol, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected and the powder with 60-150 mesh particle size was collected by sieving. 162.91 g of flavor masking powder were obtained with a yield of 71.30%. The assay (calculated as vortioxetine) of powder was 19.57%. If the materials were bonded during the preparation process, an appropriate amount of talcum powder could be added after stopping the machine to ensure that the materials were in a fluidized state. Flavor masking powder equivalent to 20mg vortioxetine and vortioxetine hemihydrobromide 100 mesh powder equivalent to 20mg vortioxetine were tested and compared by 5 subjects. Improved irritation from taste masking powder. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 4: hbh7nn / 77n7 / E / Yl· Table 4 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + ++ 1-15 15-30 acceptable acceptable N / A N / A Subject 5 + +++ 1-15 >30 acceptable unacceptable N / A N / A e> Preparation of vortioxetine hemihydrobromide taste masking powder: Eudragit RL100: meglumine = 1:3:0.07 150.00 g of Eudragit RL100 and 3.50 g of meglumine were added to 1500.00 g of medicinal ethanol, stirred to dissolve and set aside. 50.00 g of vortioxetine hemihydrobromide of 100-200 mesh and 25.00 g of talc with particle size less than 325 mesh were added to the BWF-1G multifunctional fluid bed installed in the bottom spray coating mode. The air inlet volume and height of the guide tube were adjusted so that the materials were in a fluidized state, and the air inlet temperature was set at 50-55°C, the speed of the peristaltic pump was 5 rpm. and the spray pressure was 1.0-1.5 atm. The coating liquid prepared by Urelease was sprayed into the fluid bed. After spraying, the materials continued to be fluidized for 30 minutes to remove residual ethanol, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected and the powder with 60-150 mesh particle size was collected by sieving. The flavor masking powder was obtained. If the materials were bonded during the preparation process, an appropriate amount of talcum powder could be added after stopping the machine to ensure that the materials were in a fluidized state. Flavor masking powder equivalent to 20mg vortioxetine and vortioxetine hemihydrobromide 100 mesh powder equivalent to 20mg vortioxetine were tested and compared by 5 subjects. Improved irritation from taste masking powder. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 5: Table 5 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + ++ 1-15 15-30 acceptable acceptable N / A N / A Subject 5 + +++ 1-15 >30 acceptable unacceptable N / A N / A Example 2: Preparation of Vortioxetine Hydrobromide Flavor Masking Powder + Coating Material 2a) Preparation of vortioxetine hemihydrobromide taste masking powder: Urelease E100 = 1:0.7 7.73 g of UreleaseE100 was added to 77.20 g of medicinal ethanol, stirred to dissolve and set aside. 10.02 g of 200 mesh vortioxetine hemihydrobromide was added to the solution prepared above, stirred to disperse. After sieving through a 100 mesh stainless steel sieve, the materials were collected and continued agitation to prevent sedimentation. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The prepared suspension material was sprayed into the fluid bed and the state of the material was observed at any time. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by sieving. 7.81 g of flavor masking powder were obtained with a yield of 43.98%. The assay (calculated as vortioxetine) of powder was 48.63%. The remaining materials were lightly ground and then sieved to collect powder with particle size less than 80 mesh. 6.23 g of flavor masking powder were obtained with a yield of 35.08%. The assay (calculated as vortioxetine) of powder was 49.38%. Five subjects tested and compared the two types of flavor masking powder equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine. Irritation from taste masking powders improved significantly. After mixing the two types of taste masking powder, 5 subjects tested the mixed taste masking powder equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine, which showed that the irritation of the treated vortioxetine taste masking powders was significantly improved. Self-made sample 1: Instant irritation +, disappeared within 1 -15 minutes after delayed irritation, and the bitterness was acceptable. Self-made sample 2: Instant irritation +, disappeared within 1 to 15 minutes after delayed irritation, and the bitterness was acceptable. Mixed self-brewed sample: Instant + irritation, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 6: Table 6 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Mixed own-made sample Reference sample Mixed own-made sample Reference sample Mixed own-made sample Reference sample Mixed own-made sample Reference sample Subject 1 + +++ 1- 15 >30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + +++ 1-15 1-15 acceptable unacceptable N / A N / A Subject 4 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 15-30 acceptable unacceptable N / A N / A 2b) Preparation of vortioxetine hydrobromide taste masking powder:15UreleaseEI 00:PEG6000 = 1:0.77 7.70 g of UreleaseEI 00 was added to 77.10 g of medicinal ethanol, stirred to dissolve and set aside. 10.00 g of 200 mesh vortioxetine hydrobromide was added to the solution prepared above, stirred to disperse. After sieving through a 20 100 mesh stainless steel sieve, the materials were collected and continued stirring to prevent sedimentation. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The prepared suspension material was sprayed into the fluid bed and the state of the material was observed at any time. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by sieving. 6.98 g of flavor masking powder were obtained with a yield of 39.44%. The assay (calculated as vortioxetine) of powder was 44.63%. 3^ The remaining materials were lightly ground and then sieved to collect powder with particle size less than 80 mesh. 5.93 g of flavor masking powder were obtained with a yield of 33.50%. The assay (calculated as vortioxetine) of powder was 45.38%. Five subjects tested and compared the two types of flavor masking powder equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine. Irritation from taste masking powders improved significantly. After mixing the two types of flavor masking powder, 5 subjects tested and compared the mixed flavor masking powder equivalent to 20mg of vortioxetine and the 100 mesh vortioxetine hemihydrobromide powder equivalent to 20mg of vortioxetine. Irritation from taste masking powders improved significantly. Self-made sample 1: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and the bitterness was acceptable. Self-made sample 2: Instant irritation +, disappeared within 1 to 15 5 minutes after delayed irritation, and the bitterness was acceptable. Mixed self-made sample: Instant + irritation, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 7: Table 7 Flavor comparison test of flavor masking powder with vortioxetine hydrobromide Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Mixed own-made sample Reference sample Mixed own-made sample Reference sample Mixed own-made sample Reference sample Mixed own-made sample Reference sample Subject 1 + +++ 1- 15 >30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + + + 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 >30 acceptable unacceptable N / A N / A 2c) Preparation of vortioxetine hemihydrobromide flavor masking powder: cellulose acetate: PEG 6000 =1:0.7:0.07 7.00 g of cellulose acetate and 0.70 g of PEG 6000 were added to 70.20 g of medicinal ethanol, stirred to dissolve and set aside. 10.00 g of 200 mesh vortioxetine hemihydrobromide was added to the solution prepared above, stirred to disperse. After sieving through a 100 mesh stainless steel sieve, the materials were collected and continued agitation to prevent sedimentation. The BWF-1G multifunctional fluid bed was installed according to the granulation mode by 3S top spray, and the air volume was set at 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was 8 rpm and the spray pressure was 1.0-1.5 atm. The prepared suspension material was sprayed into the fluid bed and the state of the material was observed at any time. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The 35 materials were collected, and the powder with particle size less than 80 meshes was collected by sieving. 6.97 g of flavor masking powder were obtained with a yield of 40.76%. The assay (calculated as vortioxetine) of powder was 47.93%. The remaining materials were lightly ground and then sieved to collect powder with particle size less than 80 mesh. 6.00 g of flavor masking powder were obtained with a yield of 33.90%. The assay (calculated as vortioxetine) of powder was 48.98%. Five subjects tested and compared the two types of flavor masking powder equivalent to 20 mg of vortioxetine and the 100 mesh vortioxetine hemihydrobromide powder equivalent to 5 mg of vortioxetine. Irritation from taste masking powders improved significantly. After mixing the two types of taste masking powder, 5 subjects tested the mixed taste masking powder equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine, which showed that the irritation of the treated vortioxetine taste masking powders was significantly improved. 1§ Self-made sample 1: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and the bitterness was acceptable. Self-made sample 2: Instant irritation +, disappeared within 1 to 15 minutes after delayed irritation, and the bitterness was acceptable. Mixed self-made sample: Instant irritation +, disappeared within 1-15 15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 8: Table 8 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Mixed own-made sample Reference sample Mixed own-made sample Reference sample Mixed own-made sample Reference sample Mixed own-made sample Reference sample Subject 1 + +++ 1- 15 >30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 ++ +++ 1-15 1-15 acceptable unacceptable N / A N / A Subject 4 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 15-30 acceptable unacceptable N / A N / A 3^ 2d) Preparation of vortioxetine hemihydrobromide flavor masking powder: polyvinyl alcohol (low viscosity) = 1:0.7 7.00 g of polyvinyl alcohol (low viscosity) was added to 100.00 g of purified water, stirred in a 90°C water bath to dissolve, cooled to room temperature, 0.07 g of potassium citrate was added , stirred to dissolve, set aside. 10.00 g of 200 mesh vortioxetine hemihydrobromide was added to the solution prepared above, stirred to disperse. After sieving through a 100 mesh stainless steel sieve, the materials were collected and continued agitation to prevent sedimentation. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set at 30-33 m3, the inlet temperature was 60-55°C, the pump speed peristaltic pressure was 8 rpm and the spray pressure was 1.0-1.5 atm. The prepared suspension material was sprayed into the fluid bed and the state of the material was observed at any time. After spraying, the materials continued to fluidize for 30 minutes, then heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by sieving. 12.79 g of flavor masking powder were obtained with a yield of 75.24%. The assay (calculated as vortioxetine) of powder was 50.99%. Flavor masking powder equivalent to 20mg vortioxetine and vortioxetine hemihydrobromide 100 mesh powder equivalent to 20mg vortioxetine were tested and compared by 5 subjects. The irritation of the taste masking powder was significantly improved. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes 15 after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 9: Table 9 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 ++ +++ 1-15 1-15 acceptable unacceptable N / A N / A Subject 4 + ++ 1- 15 >30 acceptable unacceptable N / A N / A Subject 5 ++ ++ 1-15 15-30 acceptable unacceptable N / A N / A Example 3: Preparation of Vortioxetine Hemihydrobromide Flavor Masking Powder: Coating Material = 1:1 3a) Preparation of vortioxetine hemihydrobromide flavor masking powder: 30Eudragit E100: PEG 6000 =1:1:0.07 10.00 g of Eudragit E100 and 0.70 g of PEG 6000 were added to 70.00 g of medicinal ethanol, stirred to dissolve and set aside. 10.01 g of 200 mesh vortioxetine hemihydrobromide was added to the solution prepared above, stirred to disperse. After sieving through a 100 mesh stainless steel sieve, the materials were collected and continued agitation to prevent sedimentation. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The prepared suspension material was sprayed into the fluid bed and the state of the material was observed at any time. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The 5 materials were collected, and the powder with particle size less than 80 meshes was collected by sieving. 13.78 g of flavor masking powder were obtained with a yield of 66.54%. The assay (calculated as vortioxetine) of powder was 41.79%. Flavor masking powder equivalent to 20mg vortioxetine and vortioxetine hemihydrobromide 100 mesh powder equivalent to 20mg vortioxetine were tested and compared by 1§ 5 subjects. The irritation of the taste masking powder was significantly improved. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 10: Table 10 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1-15 1-15 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 1-15 acceptable unacceptable N / A N / A 3b) Preparation of vortioxetine hemihydrobromide flavor masking powder: Eudragit L100: PEG 6000 =1:1:0.07 10.00 g of Eudragit L100 and 0.70 g of PEG 6000 were added to 70.00 g of medicinal ethanol, stirred to dissolve and set aside. 10.00 g of 200 mesh vortioxetine hemihydrobromide was added to the solution prepared above, stirred to disperse. After sieving through a 100 mesh stainless steel sieve, the materials were collected and continued stirring to prevent sedimentation. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The prepared suspension material was sprayed into the fluid bed and the state of the material was observed at any time. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected and the powder with particle size less than 80 mesh was collected by sieving. 14.14 g of flavor masking powder were obtained with a yield of 68.31%. The assay (calculated as vortioxetine) of powder was 42.01%. Flavor masking powder equivalent to 20mg vortioxetine and vortioxetine hemihydrobromide 100 mesh powder equivalent to 20mg vortioxetine were tested and compared by 5 subjects. The irritation of the taste masking powders was significantly improved and almost non-irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 11: Table 11 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1-15 1-15 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 1-15 acceptable unacceptable N / A N / A 3c) Preparation of vortioxetine hemihydrobromide taste masking powder: copovidone AV64=1:1 10.00 g of copovidone AV64 was added to 70.00 g of medicinal ethanol, stirred to dissolve and set aside. 10.00 g of 200 mesh vortioxetine hemihydrobromide was added to the solution prepared above, stirred to disperse. After sieving through a 100 mesh stainless steel sieve, the materials were collected and continued stirring to prevent sedimentation. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The prepared suspension material was sprayed into the fluid bed and the state of the material was observed at any time. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected and the powder with particle size less than 80 mesh was collected by sieving. 14.16 g of flavor masking powder were obtained with a yield of 70.80%. The assay (calculated as vortioxetine) of powder was 42.78%. Flavor masking powder equivalent to 20mg vortioxetine and vortioxetine hemihydrobromide 100 mesh powder equivalent to 20mg vortioxetine were tested and compared by 5 subjects. The irritation of the taste masking powder was significantly improved. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 12: Table 12 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 ++ ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1 -15 >30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 >30 acceptable unacceptable N / A N / A Example 4: Preparation of Vortioxetine Hydrobromide Mixture: Eudragit = 1:0.5 4a) Preparation of the vortioxetine hemihydrobromide mixture: Eudragit E PO = 1:0.5 5.00 g of vortioxetine hemihydrobromide that had passed through a 200 mesh stainless steel sieve and 2.50 g of Eudragit E PO were placed in a clean, dry 50 ml screw cap glass reagent bottle. The mixture was mixed with a Vortex-2 vortex mixer for 5 minutes. After passing through a 100 mesh stainless steel sieve, mixing the mixture was continued with a Vortex-2 vortex mixer for 5 minutes. 0.50 g of the sample was taken for the test. The remaining materials were collected and stacked in a 75 mm diameter stainless steel tray, and the stainless steel tray was placed in a DHG-9070A hot air circulation oven at 120-130°C. After heating for 30 minutes, the material converted to a semi-fluid state. After taking it out and letting it cool, it was ground through a 100 mesh stainless steel sieve with a BJ-300A multifunctional pulverizer several times to obtain a 1:0.5 powder mixture. The powder mixture equivalent to 20mg vortioxetine and the 100 mesh vortioxetine hemihydrobromide powder equivalent to 20mg vortioxetine were tested and compared by 5 subjects. Improved irritation from powder mixture. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 13: Table 13 Taste comparison test of solid dispersion of vortioxetine hemihydrobromide Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 ++ ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 ++ ++ + 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 15-30 acceptable unacceptable N / A N / A 4b) Preparation of vortioxetine hydrobromide mixture: Eudragit E PO = 1:0.5 5.00 g of vortioxetine hydrobromide that had been passed through a 200 mesh stainless steel sieve and 2.50 g of Eudragit E PO were placed in a clean, dry 50 ml screw cap glass reagent bottle. The mixture was mixed with a Vortex-2 vortex mixer for 5 minutes. After passing through a 100 mesh stainless steel sieve, mixing the mixture was continued with a Vortex-2 vortex mixer for 5 minutes. 0.50 g of the sample was taken for the test. The remaining materials were collected and stacked in a 75 mm diameter stainless steel tray, and the stainless steel tray was placed in a DHG-9070A hot air circulation oven at 120-130°C. After heating for 30 minutes, the material converted to a semi-fluid state. After taking it out and letting it cool, it was ground through a 100 mesh stainless steel sieve with a BJ-300A multifunctional pulverizer several times to obtain a 1:0.5 powder mixture. The powder mixture equivalent to 20mg of vortioxetine and the 100 mesh powder of vortioxetine hydrobromide equivalent to 20mg of vortioxetine were tested and compared by 5 subjects. Improved irritation from powder mixture. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 14: Table 14 Vortioxetine Hydrobromide Solid Dispersion Taste Comparison Test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 ++ +++ >30 >30 acceptable unacceptable N / A N / A Subject 4 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 +++ +++ 1-15 >30 acceptable unacceptable N / A N / A UV scanning showed that the maximum absorption wavelength and maximum intensity of the vortioxetine-treated material did not change significantly. The results are shown in Figure 8, Figure 9, Figure 10 and Figure 11. 4c) Preparation of vortioxetine hydrobromide mixture: Eudragit RS PO = 1:0.5 5.00 g of vortioxetine hydrobromide that had been passed through a 200 mesh stainless steel sieve and 2.50 g of Eudragit RS PO were placed in a clean, dry 50 ml screw cap glass reagent bottle. The mixture was mixed with a Vortex-2 vortex mixer for 5 minutes. After passing through a 100 mesh stainless steel sieve, mixing the mixture was continued with a Vortex-2 vortex mixer for 5 minutes. 0.50 g of the sample was taken for the test. The remaining materials were collected and stacked in a 75 mm diameter stainless steel tray, and the stainless steel tray was placed in a DHG-9070A hot air circulation oven at 120-130°C. After heating for 30 minutes, the material converted to a semi-fluid state. After taking it out and letting it cool, it was ground through a 100 mesh stainless steel sieve with a BJ-300A multifunctional pulverizer several times to obtain a 1:0.5 powder mixture. The powder mixture equivalent to 20mg of vortioxetine and the 100 mesh powder of vortioxetine hydrobromide equivalent to 20mg of vortioxetine were tested and compared by 5 subjects. Improved irritation from powder mixture. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 15: Table 15 Vortioxetine Hydrobromide Solid Dispersion Taste Comparison Test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 ++ +++ >30 >30 acceptable unacceptable N / A N / A Subject 4 ++ ++ + 1-15 >30 acceptable unacceptable N / A N / A Subject 5 +++ +++ 1-15 >30 acceptable unacceptable N / A N / A Example 5: Preparation of vortioxetine hemihydrobromide mixture: Eudragit E PO=1:1.5 5.00 g of vortioxetine hemihydrobromide that had passed through a 200 mesh stainless steel sieve and 7.50 g of Eudragit E PO were placed in a clean, dry 50 ml screw cap glass reagent bottle. The mixture was mixed with a Vortex-2 vortex mixer for 5 minutes. After passing through a 100 mesh stainless steel sieve, mixing the mixture was continued with a Vortex-2 vortex mixer for 5 minutes. 0.50 g of the sample was taken for the test. The remaining materials were collected and stacked in a 75 mm diameter stainless steel tray, and the stainless steel tray was placed in a DHG-9070A 5 hot air circulation oven at 120-130°C. After heating for 30 minutes, the material converted to a semi-fluid state. After taking it out and letting it cool, it was ground through a 100 mesh stainless steel sieve with a BJ-300A multifunctional pulverizer several times to obtain a 1:1.5 powder mixture. The 1:1.5 powder mixture equivalent to 20mg vortioxetine and the 100 mesh vortioxetine hemihydrobromide powder equivalent to 20mg vortioxetine were tested and compared by 5 1§ subjects. The irritation of the powder mixture improved significantly. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 16: Table 16 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 4 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 15-30 acceptable unacceptable N / A N / A UV scanning showed that the maximum absorption wavelength and maximum intensity of the vortioxetine-treated material did not change significantly. The results are shown in Figure 9, Figure 12, Figure 13 and Figure 14. Example 6: Preparation of vortioxetine hemihydrobromide mixture: Eudragit E PO=1:5 5.00 g of vortioxetine hemihydrobromide that had been passed through a 200 mesh stainless steel sieve and 25.00 g of Eudragit E PO were placed in a clean, dry 100 ml screw cap glass reagent bottle. The mixture was mixed with a Vortex-2 vortex mixer for 5 minutes. After passing through a 100 mesh stainless steel sieve, mixing the mixture was continued with a Vortex-2 vortex mixer for 5 minutes. 0.50 g of the sample was taken for the test. The remaining materials were collected and stacked in a 75 mm diameter stainless steel tray, and the stainless steel tray was placed in a DHG9070A hot air circulation oven at 120-130°C. After heating for 30 minutes, the material converted to a semi-fluid state. After taking it out and letting it cool, it was ground through a 100 mesh stainless steel sieve with a BJ-300A multifunctional pulverizer several times to obtain a powder mixture of 1:5 with assay (calculated as vortioxetine) 14.39%. The 1:5 powder mix equivalent to 20mg vortioxetine and the 100 mesh vortioxetine hemihydrobromide powder equivalent to 20mg vortioxetine were tested and compared by 5 subjects. The irritation of the powder mixture improved significantly. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 17: frfrfrznn / zznz / E / Yii Table 17 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 4 + +++ 1 -15 15-30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 >30 acceptable unacceptable N / A N / A UV scanning showed that the maximum absorption wavelength and maximum intensity of the vortioxetine-treated material did not change significantly. The results are shown in Figure 9, Figure 12, Figure 15 and Figure 16. Example 7: Preparation of mixture of vortioxetine hydrobromide: polyacrylic resin IV = 1:1.5 7a) Preparation of the mixture of vortioxetine hemihydrobromide: polyacrylic resin IV =251:1.5 5.00 g of vortioxetine hemihydrobromide that had been passed through a 200 mesh stainless steel sieve and 7.50 g of polyacrylic resin IV that had been passed through a 100 mesh stainless steel sieve were placed in a reagent bottle. clean and dry 100mL glass with screw cap. The mixture was mixed with a Vortex-2 vortex mixer for 5 minutes. After •3^ passing through a 100 mesh stainless steel sieve, mixing the mixture was continued with a Vortex-2 vortex mixer for 5 minutes. 0.50 g of the sample was taken for the test. The remaining materials were collected and stacked in a 75 mm diameter stainless steel tray, and the stainless steel tray was placed in a DHG-9070A hot air circulation oven at 120-130°C. After heating for 30 minutes, the material converted to a semi-fluid state. After taking it out 35 and letting it cool, it was ground through a 100 mesh stainless steel sieve with a BJ-300A multifunctional pulverizer several times to obtain 10.98g of the 1:1.5 powder mixture with a yield of 87.84% and assayed. (calculated as vortioxetine) of 35.71%. The 1:1.5 powder mixture equivalent to 20mg vortioxetine and the 100 mesh vortioxetine hemihydrobromide powder equivalent to 20mg vortioxetine were tested and compared by 5 subjects. The irritation of the powder mixture improved significantly. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes 5 after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 18: Table 18 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 ++ +++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 4 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 >30 acceptable unacceptable N / A N / A 7b) Preparation of the mixture of vortioxetine hydrobromide: polyacrylic resin IV = 1:1.5 5.00 g of vortioxetine hydrobromide that had been passed through a 200 mesh stainless steel sieve and 7.50 g of polyacrylic resin IV that had been passed through a 100 mesh stainless steel sieve were placed in a reagent bottle. clean and dry 100mL glass with screw cap. The mixture was mixed with a Vortex-2 vortex mixer for 5 minutes. After passing through a 100 mesh stainless steel sieve, mixing the mixture was continued with a Vortex-2 vortex mixer for 5 minutes. 0.50 g of the sample was taken for the test. The remaining materials were collected and stacked in a 75 mm diameter stainless steel tray, and the stainless steel tray was placed in a DHG-9070A hot air circulation oven at 120-130°C. After heating for 30 minutes, the material converted to a semi-fluid state. After taking it out and letting it cool, The 1:1.5 powder mixture equivalent to 20mg vortioxetine and the 100 mesh vortioxetine hydrobromide powder equivalent to 20mg vortioxetine were tested and compared by 5 subjects. The irritation of the powder mixture improved significantly. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is included in Table 19: Table 19 Vortioxetine Hydrobromide Solid Dispersion Taste Comparison Test Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 ++ +++ 1 -15 >30 acceptable unacceptable N / A N / A Subject 5 ++ ++ 1-15 >30 acceptable unacceptable N / A N / A UV scanning showed that the maximum absorption wavelength and maximum intensity of the vortioxetine-treated material did not change significantly. The results are shown in Figure 8, Figure 17, Figure 18 and Figure 19. Example 8: preparation of solid dispersion of vortioxetine hemihydrobromide: polyacrylic resin = 1:0.3 8a) Vortioxetine hemihydrobromide: polyacrylic resin IV=1:0.3 solid dispersion preparation 10.00 g of vortioxetine hemihydrobromide, 3.00 g of polyacrylic resin IV and 0.70 g of PEG 4000 were added to 300.00 g of medicinal ethanol, stirred until dissolved and set aside. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. 10.29 g of powder material were obtained with a yield of 75.11%. The assay (calculated as vortioxetine) of powder was 62.97%. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was obvious and could barely be tolerated, while the irritation of the treated solid vortioxetine dispersion was mild and could be tolerated. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 20: Table 20 Flavor comparison test of hbh7nn / 77n7 / E / Yl·vortioxetine hemihydrobromide flavor masking powder Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 ++ ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 15-30 acceptable unacceptable N / A N / A 8b) Preparation of solid dispersion of vortioxetine hemihydrobromide: polyacrylic resin 11=1:0.3 10.00 g of vortioxetine hemihydrobromide and 3.00 g of polyacrylic resin II were added to 300.00 g of medicinal ethanol, stirred until dissolved and separated. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was obvious and could barely be tolerated, while the irritation of the treated solid vortioxetine dispersion was mild and could be tolerated. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 21: Table 21 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 ++ ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 ++ ++ 1-15 15-30 acceptable unacceptable N / A N / A hbh7nn / 77n7 / E / Yl· Example 9: = Preparation of solid dispersion of vortioxetine hemihydrobromide: flavor masking excipient 1:0.7 9a) Preparation of solid dispersion of vortioxetine hemihydrobromide: polyacrylic resin IV=1:0.7 10.00 g vortioxetine hemihydrobromide, 7.70 g polyacrylic resin IV (Eudragit E100 or Eudragit E PO - purchased from supplier Evonik Rohm GmbH Company, or Urelease E or Urelease E100 purchased from supplier Guangzhou Maofeng Pharmaceutical Excipients Co., Ltd., or Resin polyacrylic IV (trade name) - purchased from Anhui Shanhe Pharmaceutical Excipients Co., Ltd.) were added to 170.00 g of medicinal ethanol, heated to 50-55°C, stirred to dissolve, set aside at 50-55°C. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by sieving. 12.69 g of powder material were obtained with a yield of 71.69%. The assay (calculated as vortioxetine) of powder was 49.47%. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the solid dispersion of treated vortioxetine was almost non-irritating. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 22: Table 22 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 15-30 acceptable unacceptable N / A N / A The powder X-ray diffraction pattern of the solid dispersion of vortioxetine hemihydrobromide: polyacrylic resin IV=1:0.7 is shown in Figure 20, and the powder by spraying is shown in Figure 21. The stability of the solid dispersion of Example 9a) was tested in accordance with the requirements of the 2015 Edition of the Pharmacopoeia of the People's Republic of China (accelerated for 6 months, 40±2°C, humidity 75%±5%), and stability was good. The dissolution rate of the solid dispersion in Example 9a) in 0.1 N hydrochloric acid and pH 4.5 acetate buffer (paddle method, 50 rpm) was fast with complete dissolution (30 minutes), the results are shown in Table 23. Table 23 Vortioxetine Hydrobromide Stability Test Table Time Identification Test Maximum single impurity (%) free base Br Dissolution rate in 0.1 N HCl (%) 10 minutes Dissolution rate in pH 4.5 acetate buffer (%) 10 minutes 30 minutes Initial + + 95 94 98 0.11 6 months + + 96 97 99 0.12 9b) Preparation of solid dispersion of vortioxetine hydrobromide: polyacrylic resin IV=1:0.77 10.00 g of vortioxetine hydrobromide, 7.70 g of polyacrylic resin IV (Eudragit E100 or Eudragit E PO - purchased from supplier Rohm Company, or Urelease E or Urelease E100 - purchased from supplier Guangzhou Maofeng Pharmaceutical Excipients Co., Ltd., or polyacrylic resin IV (trade name), purchased from Anhui Shanhe Pharmaceutical Excipients Co., Ltd.) were added to 300.00 g of medicinal ethanol, stirred to dissolve, and separated. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. 11.73 g of powder material were obtained with a yield of 66.27%. The assay (calculated as vortioxetine) of powder was 44.47%, and the assay (calculated as vortioxetine hydrobromide) of powder was 11.83%. The solid dispersion equivalent to 20mg of vortioxetine and the 100 mesh powder of vortioxetine hydrobromide equivalent to 20mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was obvious and could hardly be tolerated, while the solid dispersion of treated vortioxetine was slightly irritating. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 24: Table 24 Vortioxetine Hydrobromide Solid Dispersion Taste Comparison Test Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 ++ +++ 1 -15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 >30 acceptable unacceptable N / A N / A The powder X-ray diffraction pattern of the solid dispersion of vortioxetine hydrobromide: polyacrylic resin IV=1 Ό.77 shown in Figure 22, and the powder of spray drying is shown in Figure 21. The stability of the solid dispersion of Example 9b) was tested in accordance with the requirements of the 2015 Edition of the Pharmacopoeia of the People's Republic of China (accelerated for 6 months, 40±2° C, humidity 75%±5%), and the stability was good. The dissolution rate of the solid dispersion in Example 9b) in 0.1 N hydrochloric acid and pH 4.5 acetate buffer (paddle method, 50 rpm) was fast with complete dissolution (30 minutes), the results are shown in Table 25. Table 25 Vortioxetine Hydrobromide Stability Test Table Time Identification Test Maximum single impurity (%) Free base Br Dissolution rate in 0.1 N HCl (%) 10 minutes Dissolution rate in pH 4.5 acetate buffer (%) 10 minutes 30 minutes Initial + + 95 93 97 0.10 6 months + + 96 95 99 0.11 9c) Preparation of solid dispersion of vortioxetine hemihydrobromide: Eudragit RL100: PEG 6000 = 1:0.7:0.07 10.00 g of vortioxetine hemihydrobromide, 7.00 g of Eudragit RL100 and 0.70 g of PEG 6000 were added to 300.00 g of medicinal ethanol, stirred until dissolved and separated. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set at 33m3, the inlet temperature was 50-55°C, the peristaltic pump speed was 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time 5, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by sieving. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the solid dispersion of treated vortioxetine was almost non-irritating. Self-made sample: Instant irritation ++, disappeared within 1-15 minutes 15 after delayed irritation and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 26: 2g Table 26 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 ++ ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 ++ +++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 ++ ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 ++ ++ + 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 15-30 acceptable unacceptable N / A N / A 9d) Preparation of solid dispersion for vortioxetine hemihydrobromide: Eudragit S100 = 1:0.7 10.00 g of vortioxetine hemihydrobromide and 7.00 g of Eudragit S100 were added to 300.00 g of medicinal ethanol, stirred until dissolved and set aside. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. The solid dispersion equivalent to 20mg of vortioxetine and the 100 mesh powder of 5-vortioxetine hemihydrobromide equivalent to 20mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the solid dispersion of treated vortioxetine was almost non-irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 27: Table 27 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 ++ ++ 1-15 15-30 acceptable unacceptable N / A N / A 9e) Preparation of solid dispersion of vortioxetine hemihydrobromide: Eudragit L100 = 1:0.7 10.00 g of vortioxetine hemihydrobromide and 7.00 g of Eudragit L100 were added to 300.00 g of medicinal ethanol, stirred until dissolved and separated. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the solid dispersion of treated vortioxetine was almost non-irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes 5 after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 28: Table 28 Taste comparison test of solid dispersion of vortioxetine hemihydrobromide Subject Instant irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 ++ ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1- 15 >30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Example 10: Preparation of solid dispersion of vortioxetine hemihydrobromide:polyacrylic resin I V=1:1 10.00 g of vortioxetine hemihydrobromide, 10.00 g of polyacrylic resin IV and 0.70 g of PEG 6000 were added to 300.00 g of medicinal ethanol, stirred until dissolved and set aside. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. 13.31 g of material were obtained with a yield of 64.30%. The assay (calculated as vortioxetine) of powder was 43.38%. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was obvious and could hardly be tolerated, while the solid dispersion of treated vortioxetine was slightly irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 29: Table 29 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 4 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Example 11: Preparation of solid dispersion of vortioxetine hydrobromide: flavor masking excipient = 1:1.5 11a) Preparation of solid dispersion of vortioxetine hemihydrobromide: polyacrylic resin IV=1:1.5 10.00 g of vortioxetine hemihydrobromide and 15.00 g of polyacrylic resin IV were added to 300.00 g of medicinal ethanol, stirred until dissolved and set aside. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. 18.11 g of material were obtained with a yield of 72.44%. The assay (calculated as vortioxetine) of powder was 34.47%. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the solid dispersion of treated vortioxetine was almost non-irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 30: Table 30 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 4 + +++ 1- 15 15-30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 >30 acceptable unacceptable N / A N / A 11b) Preparation of solid dispersion of vortioxetine hydrobromide: polyacrylic resin IV=1:1.5 10.00 g of vortioxetine hydrobromide, 15.00 g of polyacrylic resin IV and 0.70 g of PEG 6000 were added to 300.00 g of medicinal ethanol, stirred until dissolved and set aside. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. 17.17 g of material were obtained with a yield of 66.81%. The assay (calculated as vortioxetine) of powder was 30.57%. The solid dispersion equivalent to 20mg of vortioxetine and the 100 mesh powder of vortioxetine hydrobromide equivalent to 20mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the solid dispersion of treated vortioxetine was almost non-irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 31: Table 31 Vortioxetine Hydrobromide Solid Dispersion Taste Comparison Test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 >30 acceptable unacceptable N / ANA hbh7nn / 77n7 / E / Yl· 11c) Preparation of solid dispersion of vortioxetine hydrobromide: ethylcellulose NI 0=1:1.5 5 10.00 g of vortioxetine hydrobromide and 15.00 g of ethylcellulose N10 were added to 300.00 g of medicinal ethanol, stirred until dissolved. Then 1.00 g of potassium citrate was added after passing through a 200 mesh sieve, stirred until dispersed to prevent sedimentation, set aside. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set at 33 m3, the inlet temperature was 50-55°C, the 10 speed of the peristaltic pump was 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The 15 materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. The solid dispersion equivalent to 20mg of vortioxetine and the 100 mesh powder of vortioxetine hydrobromide equivalent to 20mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the treated vortioxetine 2S solid dispersion was almost non-irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 32: Table 32 Vortioxetine Hydrobromide Solid Dispersion Taste Comparison Test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1- 15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 >30 acceptable unacceptable N / A N / A Example 12: Preparation of solid dispersion of vortioxetine hemihydrobromide: flavor masking excipient = 1:2 12a) Solid dispersion preparation of vortioxetine hemihydrobromide: polyacrylic resin IV=1:2 10.00 g of vortioxetine hemihydrobromide, 20.00 g of polyacrylic resin IV and 0.70 g of PEG 6000 were added to 300.00 g of medicinal ethanol, stirred until dissolved and set aside. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the 1§ heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. 20.20 g of material were obtained with a yield of 65.80%. The assay (calculated as vortioxetine) of powder was 27.99%. The solid dispersion equivalent to 20mg of vortioxetine and the 100 mesh powder of vortioxetine 15 hemihydrobromide equivalent to 20mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the solid dispersion of treated vortioxetine was almost non-irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 33: Table 33 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + ++ 1-15 15 -30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 >30 acceptable unacceptable N / A N / A 12b) Preparation of solid dispersion of vortioxetine hemihydrobromide: cellulose acetate = 1:2 10.00 g of vortioxetine hemihydrobromide, 20.00 g of cellulose acetate and 0.70 g of PEG 8000 were added to 300.00 g of medicinal ethanol, stirred until dissolved and set aside. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 1§ subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the solid dispersion of treated vortioxetine was almost non-irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes 15 after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 34: Table 34 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + ++ 1-15 15 -30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 >30 acceptable unacceptable N / A N / A Example 13: Preparation of solid dispersion of vortioxetine hemihydrobromide + flavor masking excipient 13a) Preparation of solid dispersion of vortioxetine hemihydrobromide: polyacrylic resin IV=1:5 10.00 g of vortioxetine hemihydrobromide and 50.00 g of polyacrylic resin IV were added to 500.00 g of medicinal ethanol, stirred until dissolved, and separated. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. 49.29 g of material were obtained with a yield of 82.15%. The assay (calculated as vortioxetine) of powder was 14.67%. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the solid dispersion of treated vortioxetine was almost non-irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes 1§ after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 35: Table 35 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 4 + +++ 1- 15 15-30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 >30 acceptable unacceptable N / A N / A 13b) Preparation of solid dispersion of vortloxetine hemihydrobromide:hydroxypropylcellulose LF = 1:3 10.00 g of vortioxetine hemihydrobromide, 30.00 g of hydroxypropylcellulose LF and 1 g of meglumine were added to 300.00 g of medicinal ethanol, stirred until dissolved and separated. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The solution prepared above was sprayed into the fluid bed, the material state was observed at any time, and the parameters were appropriately adjusted to ensure normal spraying and drying. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected, and the powder with particle size less than 80 mesh was collected by crushing and sieving. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 subjects. The irritation of the untreated material was evident and could hardly be tolerated, while the solid dispersion of treated vortioxetine was almost non-irritating. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 36: Table 36 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 4 + +++ 1- 15 15-30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 >30 acceptable unacceptable N / A N / A Example 14: Vortioxetine hydrobromide + solid dispersion preparation of polyacrylic resin 14a) Preparation of solid dispersion of vortioxetine hemihydrobromide: polyacrylic resin 11=1:5 10.00 g of vortioxetine hemihydrobromide and 50.00 g of polyacrylic resin II were added to 500.00 g of medicinal ethanol, stirred and dissolved in a water bath at 40-50°C, filtered with a 0.45 um microporous membrane. In the stirred state, the pH of the filtrate was adjusted with a 5% (g / g) sodium hydroxide solution until no more precipitates appeared in the material (the pH was 8.54 at that time), then the ethanol was removed with vacuum, rotary evaporator and the resulting solid was removed with the vacuum lyophilizer at 40-50°C, then the solid was passed through the 100 mesh stainless steel sieve. 50.54 g of solid dispersion containing vortioxetine with a performance of 84.23%. The assay (calculated as vortioxetine) of powder was 14.79%. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 subjects. The unique irritation of vortioxetine was not felt. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 37: Table 37 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 15-30 acceptable unacceptable N / A N / A 14b) Preparation of solid dispersion of vortioxetine hydrobromide: polyacrylic resin 11=1:1.5 10.00 g of vortioxetine hydrobromide and 15.00 g of polyacrylic resin II were added to 250.00 g of medicinal ethanol, stirred and dissolved in a water bath at 40-50°C, filtered with a 0.45 um microporous membrane. In the stirred state, the pH of the filtrate was adjusted with a 5% (g / g) sodium hydroxide solution until no more precipitates appeared in the material (the pH was 8.32 at that time), then the ethanol was removed with vacuum rotary evaporator and the resulting solid was removed with the vacuum lyophilizer at 40-50°C, then the solid was passed through the 100 mesh stainless steel sieve. 19.67 g of solid dispersion containing vortioxetine with a performance of 78.68%. The assay (calculated as vortioxetine) of powder was 29.97%. The solid dispersion equivalent to 20mg of vortioxetine and the 100 mesh powder of vortioxetine hydrobromide equivalent to 20mg of vortioxetine were tested and compared by 5 subjects. The unique irritation of vortioxetine was not felt. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation +++, disappears after more than 30 minutes after Delayed irritation, and bitterness was Unacceptable. Detailed information is shown in Table 38: Table 38 Vortioxetine Hydrobromide Solid Dispersion Taste Comparison Test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1 -15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 >30 acceptable unacceptable N / A N / A The powder X-ray diffraction pattern of the solid dispersion of vortioxetine hydrobromide: polyacrylic resin 11=1:1.5 is shown in Figure 23, and the powder of ethanol) is shown in Figure 24. Example 15: Preparation of solid dispersion of vortioxetine hemihydrobromide: polyacrylic resin 11=1:1.5 10.00 g of vortioxetine hemihydrobromide and 15.00 g of polyacrylic resin II were added to 5,250.00 g of medicinal ethanol, stirred and dissolved in a water bath at 40-50°C, filtered with a 0.45 um microporous membrane. In a stirred state, the pH of the filtrate was adjusted with 5% (g / g) sodium hydroxide solution until no more precipitates appeared in the material (pH at that time was 8.47), then the insoluble was separated and added to 400 g of purified water. After homogenizing through a 100 mesh sieve at 40-50°C, it was granulated by top spraying of BWF-1G multifunctional fluid bed. Then, the obtained powder was passed through the 100 mesh stainless steel sieve. 12.94 g of solid dispersion containing vortioxetine was obtained with a yield of 51.76%. The assay (calculated as vortioxetine) of powder was 35.77%. The solid dispersion equivalent to 20 mg of vortioxetine and the 100 mesh powder of vortioxetine hemihydrobromide equivalent to 20 mg of vortioxetine were tested and compared by 5 15 subjects. You cannot feel the unique irritation of vortioxetine. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 39: Table 39 Vortioxetine hemihydrobromide solid dispersion taste comparison test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + +++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + +++ 1- 15 1-15 acceptable unacceptable N / A N / A Subject 5 + ++ 1-15 >30 acceptable unacceptable N / A N / A The X-ray powder diffraction pattern of the solid dispersion of vortioxetine hemihydrobromide: polyacrylic resin 11=1:1.5 is shown in Figure 25, and the of ethanol) is shown in Figure 24. Example 16: Preparation of flavor masking granules with flavor masking coating powder 10.00 g of Eudragit RS100 was added to 150.00 g of ethanol, stirred to dissolve and set aside. 10.00 g of the powder prepared in Example 1d) was added to the solution prepared above, stirred until dispersed. After sieving through a 60 mesh stainless steel sieve, the materials were continued to agitate to prevent sedimentation. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode, and the air volume was set to 33 m3, the inlet temperature was 50-55°C, the peristaltic pump speed was of 8 rpm and the spray pressure was 1.0-1.5 atm. The prepared suspension material 5 was sprayed into the fluid bed and the state of the material was observed at any time. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The materials were collected and the powder with particle size less than 50 mesh was collected by crushing and sieving. 15.87 g of powder were obtained with a yield of 79.35%. The assay (calculated as vortioxetine) of powder was 25.47%. Five subjects tested and compared taste masking granules equivalent to 20 mg of vortioxetine and vortioxetine hemihydrobromide 100 mesh powder equivalent to 20 mg of vortioxetine. Irritation from the untreated material was evident and could hardly be tolerated, while the treated vortioxetine granules were mildly irritating and could be tolerated. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 40: Table 40 Taste comparison test of flavor masking granules with vortioxetine hemihydrobromide Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 15-30 acceptable unacceptable N / A N / A Example 17: Preparation of flavor masking powder with solid dispersion 5.00 g of chitosan (degree of deacetylation greater than or equal to 85%) was added to 100.00 g of purified water, stirred to dissolve and set aside. 10.00 g of the powder prepared in Example 9a) was added to the solution prepared above, stirred until dispersed. After sieving through a 60 mesh stainless steel sieve, the materials were continued to agitate to prevent sedimentation. The BWF-1G multifunctional fluid bed was installed according to the top spray granulation mode and the air volume was set at 33 m3, the inlet temperature was 60-65°C, the peristaltic pump speed was 8 rpm and the spray pressure was 1.0-1.5 atm. The prepared suspension material was sprayed into the fluid bed and the state of the material was observed at any time. After spraying, the materials continued to fluidize for 30 minutes, then the heating was stopped and waited until the temperature of the materials cooled to room temperature. The 5 materials were collected, and the powder with particle size less than 60 meshes was collected by crushing and sieving. 11.11 g of powder were obtained with a yield of 74.07%. The assay (calculated as vortioxetine) of powder was 35.17%. Taste masking granules equivalent to 20mg vortioxetine and vortioxetine hemihydrobromide 100 mesh powder equivalent to 20mg vortioxetine were tested and compared 1§ by 5 subjects, which showed that the irritation of the untreated material was obvious and could hardly tolerated, while vortioxetine treated powder was mildly irritating and could be tolerated. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Reference sample: Instant irritation ++, disappears after more than 30 minutes 15 after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 41: Table 41 Flavor comparison test of flavor masking powder with vortioxetine hemihydrobromide Subject Instant irritation Delayed irritation (min) Bitterness Harsh Self-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Own-made sample Reference sample Subject 1 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 2 + ++ 1-15 15-30 acceptable unacceptable N / A N / A Subject 3 + +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 + ++ 1-15 >30 acceptable unacceptable N / A N / A Subject 5 + +++ 1-15 15-30 acceptable unacceptable N / A N / A Example 18: Preparation of film-coated tablets of Vortioxetine Hydrobromide 10mg / tablet The formula of 100 tablets weighing 0.152 g each made with vortioxetine hydrobromide was as follows: Powder prepared from Example 9b 2.25 g (equal to 1.0 g of vortioxetine) Microcrystalline cellulose 4.15g Mannitol P100SD 8.00g Sodium starch glycolate 0.70g Magnesium stearate 0.10g Total stomach soluble coating material q.s. (0.456g) 15.20g Preparation process: (1) The prescribed amount of powder prepared from Example 9b, microcrystalline cellulose, mannitol P100SD, sodium starch glycolate and magnesium stearate was placed in a clean and dry 50mL screw cap glass reagent bottle. After mixing in a vortex mixer for five minutes, the mixture was extracted after passing through an 80 mesh sieve. After mixing for another five minutes, the mixture was extracted after passing through an 80 mesh sieve, and finally after mixing for another five minutes, the compressed premix was obtained; (2) The compressed premix was pressed using a ZP8 rotary tablet press with a mold diameter of 8.0 mm, controlling the tablet weight of 147-157 mg / tablet and hardness of 401§60 N, and obtaining the core from the tablet; (3) The stomach-soluble coating material was added to purified water to prepare a suspension with a solids content of about 10%, continued stirring, and separated; (4) Using the coating liquid prepared in step (3), the tablet core was coated with a high-efficiency coating machine and the actual weight gain of the tablet core is about 1%. Ten subjects tested and compared the commercially available product (10 mg / tablet) and the ground powder of the finished product in this invention. The irritation of the commercially available product was obvious and could hardly be tolerated, while the taste of the self-made product in this invention was acceptable. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Commercially available product: Instant irritation ++, disappears after more than 30 minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 42: t7bh7nn / 77n7 / E / YIAI Table 42 Taste Comparison Test of Vortioxetine Hydrobromide Film-Coated Tablets Subject Instantaneous irritation Delayed irritation (min) Bitterness Harsh Homemade sample Commercially available product Homemade sample Commercially available product Homemade sample Commercially available product Homemade sample Commercially available product Subject 1 +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 2 +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 3 +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 4 ++ +++ 1-15 > 30 acceptable unacceptable N / A N / A Subject 5 +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 6 4- +++ 1-15 >30 acceptable unacceptable N / A N / A Subject +++ 1- 15 >30 acceptable unacceptable N / A N / A 7 subject 8 ++ +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 9 +++ 1-15 >30 acceptable unacceptable N / A N / A Subject 10 +++ 1-15 >30 acceptable unacceptable N / ANA The self-made finished product of this invention was tested for preliminary stability in accordance with the requirements of the 2015 Edition of the Pharmacopoeia of the People's Republic of China. Compared with the commercially available product, the dissolution rate of the self-made finished product of this invention in 0.1 N hydrochloric acid and pH 4.5 acetate buffer (paddle method, 50 r / min) was significantly faster and the degree dissolution time (30 minutes) is significantly better. The results are shown in Table 43. Table 43 Vortioxetine Hydrobromide Preliminary Stability Test Table (Temperature: 50°C±2°C, Humidity: 75%±5%) 15 70 25 Time Source Identification Test Maximum unique impurity (%) free base Br Content uniformity Dissolution rate in 0.1 N HCl (%) 10 minutes Dissolution rate in pH 4.5 acetate buffer (%) 10 minutes 30 minutes Initial Commercially available + + Approves 81 68 78 0.12 Own preparation + + Approves 94 93 98 0.10 5 days Commercially available + + Approves 79 71 79 0.13 Own preparation + + Approves 98 97 99 0.11 10 days Commercially available + + Approves 84 65 81 0.14 Own preparation + + Pass 95 97 99 0.12 Example 19: Preparation of 20mg / tablet of orally disintegrating tablets (compressed tablet) 19a) The formula of 100 tablets of 0.088 g weight each made from vortioxetine hemihydrobromide was the following: Vortioxetine hemihydrobromide 2.28 g (equal to 2 g of vortioxetine) Mannitol P100SD 5.14 g Trisodium phosphate 0.228 g Crospovidone XL 0.352 g Croscarmellose Sodium 0.352 g Sodium starch glycolate 0.352 g Magnesium stearate 0.044 g Neotame Red Ferric Oxide Total 0.010g 0.044g 8.802g Preparation process: (1) Neotame and red iron oxide passed 200 mesh sieve, and other raw materials passed 100 mesh sieve, were reserved; (2) The prescribed amount of vortioxetine hemihydrobromide, trisodium phosphate, mannitol P100SD, crospovidone XL, croscarmellose sodium, sodium starch glycolate, magnesium stearate, Neotame, and red iron oxide was placed in a glass reagent bottle with a stopper. 50 mi thread, clean and dry. After mixing in a vortex mixer for five minutes, the mixture was extracted after passing through an 80 mesh sieve. After mixing for another five minutes, the mixture was extracted after passing through an 80 mesh sieve, and finally after mixing for another five minutes, the compressed premix was obtained; (3) The compressed premix was pressed using a ZP8 rotary tablet press with a shallow concave mold of 6.0 mm diameter, controlling the tablet weight of 86-90 mg / tablet and hardness of 0.7-1.5 kg, and getting the tablet. 19b: The formula of 100 tablets weighing 0.088 g each made with vortioxetine hydrobromide was as follows: Vortioxetine hydrobromide Mannitol P100SD Trisodium phosphate Crospovidone XL Croscarmellose Sodium Sodium starch glycolate Neotame Magnesium Stearate Red Ferric Oxide Total 2.54 g (equal to 2 g of vortioxetine) 4.88g 0.228g 0.352g 0.352g 0.352g 0.044g 0.010g 0.044g 8.802g Preparation process: (1) Neotame and red iron oxide passed 200 mesh sieve, and other raw materials passed 100 mesh sieve, were reserved; (2) The prescribed amount of vortioxetine hydrobromide, trisodium phosphate, mannitol P100SD, crospovidone XL, croscarmellose sodium, sodium starch glycolate, magnesium stearate, Neotame, and red iron oxide was placed in a glass reagent bottle with a stopper. 50 mi thread, clean and dry. After mixing in a vortex mixer for five minutes, the mixture was extracted after passing through an 80 mesh sieve. After mixing for another five minutes, the mixture was extracted after passing through an 80 mesh sieve, and finally after mixing for another five minutes, the compressed premix was obtained; (3) The compressed premix was pressed using a ZP8 rotary tablet press with a shallow concave mold of 6.0 mm diameter, controlling the tablet weight of 86-90 mg / tablet and hardness of 0.7-1.5 kg, and getting the tablet. After 10 subjects tested the taste, the two samples did not have a gritty sensation; With the sample made of vortioxetine hemihydrobromide, the irritation was hardly felt and the taste was better; while the sample made with vortioxetine hydrobromide was significantly more irritating than the samples with vortioxetine hemihydrobromide and showed mild discomfort. Self-made sample 19a: Instant irritation +, disappeared within 1 to 15 minutes after delayed irritation and bitterness was acceptable. 1§ Self-made sample 19b: Instant irritation ++, disappears after more than minutes after delayed irritation, and bitterness was unacceptable. Detailed information is shown in Table 44: Table 44 Vortioxetine Hemihydrobromide Orally Disintegrating Tablets Taste Comparison Test Subject Instantaneous irritation delayed irritation (min) Bitterness Rough vortioxetine hemihydrobromide samples vortioxetine hydrobromide samples vortioxetine hemihydrobromide samples vortioxetine wall vortioxetine hydrobromide samples vortioxetine hemihydrobromide samples vortioxetine hydrobromide samples vortioxetine hemihydrobromide samples hydrobromide samples vortioxetine Subject 1 + 1-15 15-30 acceptable acceptable No No Subject 2 ++ +++ 1-15 >30 acceptable unacceptable No No Subject 3 + + 1-15 15-30 acceptable unacceptable No No Subject 4 ++ ++ + 1-15 >30 acceptable unacceptable No No Subject 5 + ++ 1-15 15-30 acceptable unacceptable No No Subject 6 ++ +++ 1-15 15-30 acceptable unacceptable No No Subject 7 + ++ 1-15 15-30 acceptable acceptable No Not subject 8 + ++ 1-15 15-30 acceptable unacceptable No No Subject 9 ++ +++ 1-15 >30 acceptable unacceptable No No Subject 10 + + 1-15 1-15 acceptable acceptable No no Example 20: Preparation of 20 mg / tablet orally disintegrating tablets (compressed tablet) The formula of 100 tablets weighing 0.152 g each made from vortioxetine hemihydrobromide was as follows: Powder prepared from example 10 Mannitol P100SD Trisodium phosphate Crospovidone XL Croscarmellose Sodium Sodium starch glycolate Magnesium stearate Neotame 4.61 g (equal to 2.0 g of vortioxetine) 8.30g 0.304g 0.608g 0.608g 0.608g 0.076g 0.015g Red Ferric Oxide 0.076 g Total 15.205g Preparation process: (1) Neotame and red iron oxide passed 200 mesh sieve, and other raw materials 5 passed 100 mesh sieve, were reserved; (2) The prescribed amount of solid dispersion, trisodium phosphate, mannitol P100SD, crospovidone XL, croscarmellose sodium, sodium starch glycolate, magnesium stearate, Neotame and red iron oxide was placed in a glass reagent bottle with screw cap of 50mL clean and dry. After mixing in a vortex mixer for five minutes, the mixture was extracted after passing through an 80 mesh sieve. After mixing for another five minutes, the mixture was extracted after passing through an 80 mesh sieve, and finally after mixing for another five minutes, the compressed premix was obtained; (3) The compressed premix was pressed using a ZP8 rotary tablet press with a shallow concave mold of 8.0 mm in diameter, controlling the tablet weight of 145-149 mg / tablet and a hardness of 15-30N, and obtaining the tablet. The pH detection value and relative exposure: 8.92, 0.19% (7.5ug / ml). After 10 subjects tested the taste, the sample dissolved in the oral cavity within 10 seconds, there was no gritty sensation, there was almost no irritation, and the taste was good. Self-made sample: Instant irritation +, disappeared within 1-15 minutes 20 after delayed irritation, and bitterness was acceptable. Detailed information is shown in Table 45: Table 45 Taste Comparison Test of Vortioxetine Hemihydrobromide Solid Dispersion Orally Disintegrating Tablets Subject Instant irritation Delayed irritation (min) Bitterness Harsh Subject 1 + 1-15 acceptable No Subject 2 + 1-15 acceptable No Subject 3 + 1-15 acceptable No Subject 4 + 1-15 acceptable No Subject 5 + 1-15 acceptable No Subject 6 + 1-15 acceptable No Subject 7 + 1-15 acceptable No Subject 8 + 1-15 acceptable No Subject 9 + 1-15 acceptable No Subject 10 ++ 1-15 acceptable No Example 21: Preparation of 20 mg / tablet orally disintegrating tablets (lyophilized tablets) The formula: Vortioxetine hemihydrobromide Mannitol Sorbitol 0.912g 1,876g 2,000g 64 PEG 4000 1.030g Trisodium phosphate 0.248 g Gelatin Type B Medicinal Neotame Red Ferric Oxide Total 0.124 g 0.001 g 0.003 g 6.194g Purified water was added to 16 g to prepare 40 tablets, each of which was approximately 0.4 g and contained approximately 0.1548 g of solids. 1§ Preparation process: (1) Vortioxetine hemihydrobromide and red iron oxide passed through a 100 mesh sieve, set aside; (2) The prescribed amount of mannitol, sorbitol, PEG 4000, medicinal gelatin type B and Neotame was placed in a clean and dry 20 ml screw-cap glass reagent bottle, then 8 g of purified water was added and the lid was tightened. After stirring to dissolve at 50°C, the solution was cooled to room temperature, then the prescribed amount of vortioxetine hemihydrobromide, red iron oxide and anhydrous trisodium phosphate was added, stirring and dispersing, then purified water was added to the amount prescribed. After stirring and dispersing, the mixture was passed through an 80 mesh stainless steel sieve 3 times, the suspension was obtained for loading separately, and stirred continuously to prevent sedimentation; (3) The suspension to dispense was 0.4 g per hole in the mold hole, it was freeze-dried; (4) The Iophylized sample was heat sealed to obtain IiofiIized orally disintegrating tablets. The pH detection value and relative exposure: 10.42, 0.27% (10.7ug / ml). After being analyzed by 10 volunteer subjects, the sample disintegrated in 5 seconds in the oral cavity, with no sensation of grit and minimal irritation. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Detailed information is shown in Table 46: Table 46 Vortioxetine Hemihydrobromide Orally Disintegrating Tablets Taste Comparison Test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Subject 1 + 1-15 acceptable No Subject 2 + 1-15 acceptable No Subject 3 ++ 1-15 acceptable No Subject 4 + 1-15 acceptable No Subject 5 + 1-15 acceptable No Subject 6 + 1-15 acceptable No Subject 7 + 1-15 acceptable No Subject 8 ++ 1-15 acceptable No Subject 9 + 1-15 acceptable No Subject 10 + 1-15 acceptable No frfrfrznn / zznz / E / Yi Example 22: Preparation of 20 mg / tablet orally disintegrating tablets (compressed tablets, lyophilized tablets) 22a: The formula of 100 tablets weighing 0.152 g each manufactured from the micronized powder coated powder of vortioxetine hemihydrobromide was as follows: Powder prepared from Example 3a 4.79 g (equal to 2.0 g of vortioxetine) Mannitol P100SD 8.15 g Sodium bicarbonate 0.304 g Crospovidone XL 0.608 g Croscarmellose Sodium 0.608 g Sodium starch glycolate 0.608 g Magnesium stearate 0.076 g Neotame 0.015 g Red ferric oxide 0.076 g Total 15.20 5g Preparation process: (1) Neotame and red iron oxide passed 200 mesh sieve and other raw materials passed 80 mesh sieve, reserved; (2) The prescribed amount of powder prepared from Example 3a, sodium bicarbonate, mannitol P100SD, crospovidone XL, croscarmellose sodium, sodium starch glycolate, magnesium stearate, Neotame and red iron oxide was placed in a glass. with clean and dry screw cap of 20 mi. reagent bottle. After mixing in a vortex mixer for five minutes, the mixture was extracted after passing through an 80 mesh sieve. After mixing for another five minutes, the mixture was extracted after passing through an 80 mesh sieve, and finally after mixing for another five minutes, the compressed premix was obtained; (3) The compressed premix was pressed using a ZP8 rotary tablet press with a shallow concave mold of 8.0 mm in diameter, controlling the tablet weight of 145-149 mg / tablet and a hardness of 15-30N, and obtaining the tablet. 22b: The formula of the micronized powder coated powder of vortioxetine hemihydrobromide converted into lyophilized orally disintegrating tablets was as follows: Powder prepared from Example 3a 1.914 g (equal to 0.8 g of vortioxetine) Mannitol 2,000 g Sorbitol 2,000 g PEG 4000 1,030 g Sodium bicarbonate 0.124 g Gelatin Type B Medicinal 0.124 g Neotame 0.001 g Red Ferric Oxide 0.003 g Total 7.196g hbhZnn / ZZnZ / E / YIAI Purified water was added to 16 g to prepare 40 tablets, each of which was approximately 0.4 g and contained approximately 0.1799 g of solids. Preparation process: (1) API passed through 100 mesh sieve, reserved; (2) The prescribed amount of mannitol, sorbitol, PEG 4000, medicinal gelatin type B and Neotame 10 was placed in a clean and dry 20 ml screw cap glass reagent bottle, then approximately 8 g of purified water was added and the lid was tightened. After stirring to dissolve at 50°C, the solution was cooled to room temperature, then the prescribed amount of powder prepared from Example 3a, red iron oxide and sodium bicarbonate was added, stirring and dispersing, then water was added. purified up to the prescribed amount. After stirring and dispersing, the mixture was passed through an 80 mesh stainless steel sieve 3 times, the suspension was obtained for loading separately, and stirred continuously to prevent sedimentation; (3) The suspension to dispense was 0.4 g per hole in the mold hole, freeze-dried; (4) The lyophilized sample was heat sealed to obtain orally disintegrating lyophilized tablets. The pH detection value and relative exposure: Own preparation sample 22a: pH 8.02, 0.21% (8.3 ug / ml); Own preparation sample 22b: pH 9.79, 0.25% (9.9 ug / ml). After testing by 10 volunteer subjects, sample 22a disintegrated in the oral cavity in 10 seconds, and sample 22b disintegrated in the oral cavity in 5 seconds, and there was no grittiness and minimal irritation. Self-made sample 22a: Instant irritation +, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Self-made sample 22b: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. 3$ Detailed information is shown in Table 47: Table 47 Comparison of taste of vortioxetine hemihydrobromide micropowder-coated orally dissolving tablets Subject Instant Delayed irritation (min) Bitterness Harsh Sample 22a Sample 22b Sample 22a Sample 22b Sample 22a Sample 22b Sample 22a Sample 22b Subject 1 + + 1-15 1-15 acceptable acceptable No No Subject 2 + + 1-15 1-15 acceptable acceptable No No Subject 3 + + 1-15 1-15 acceptable acceptable No No Subject 4 ++ ++ 1-15 1-15 acceptable acceptable No No Subject 5++ 1-15 1-15 acceptable acceptable No No Subject 6++ 1-15 1-15 acceptable acceptable No No Subject 7++ 1-15 1-15 acceptable acceptable No No Subject 8++ 1-15 15 -30 acceptable unacceptable No No Subject 9 + + 1-15 15-30 acceptable unacceptable No No Subject 10 + + 1-15 1-15 acceptable acceptable No No Example 23: Preparation of 20 mg / tablet orally disintegrating tablets (compressed tablets, lyophilized tablets) 23a: The formula of 100 tablets weighing 0.152 g each made from the micronized powder-coated powder of vortioxetine hemihydrobromide was as follows: Powder prepared from Example 7a Mannitol P100SD Anhydrous tripotassium phosphate Crospovidone XL Croscarmellose Sodium Sodium starch glycolate Magnesium stearate Neotame Red Ferric Oxide Total 5.60 g (equal to 2.0 g of vortioxetine) 7.31g 0.304g 0.608g 0.608g 0.608g 0.076g 0.015g 0.076g 15.205g Preparation process: (1) Neotame and red iron oxide passed 200 mesh sieve and other raw materials passed 80 mesh sieve, reserved; (2) The prescribed amount of powder prepared from Example 7a, anhydrous tripotassium phosphate, mannitol P100SD, crospovidone XL, croscarmellose sodium, sodium starch glycolate, magnesium stearate, Neotame and red iron oxide were placed in a container with a lid of clean and dry thread of 50 mi. glass reagent bottle. After mixing in a vortex mixer for five minutes, the mixture was extracted after passing through an 80 mesh sieve. After mixing for another five minutes, the mixture was extracted after passing through an 80 mesh sieve, and finally after mixing for another five minutes, the compressed premix was obtained; (3) The compressed premix was pressed using a ZP8 rotary tablet press with a shallow concave mold of 8.0 mm in diameter, controlling the tablet weight of 145-149 mg / tablet and a hardness of 15-30N, and obtaining the tablet. 23b: The formula of the micronized powder-coated powder of vortioxetine hemihydrobromide converted into lyophilized orally disintegrating tablets was as follows: Powder prepared from Example 7a 2,240 g (equal to 0.8 g of Vortioxetine) Mannitol 2,000 g Sorbitol 2,000 g PEG 4000 1.030g Anhydrous tripotassium phosphate 0.124 g Gelatin Type B Medicinal 0.124 g Neotame 0.001 g Red Ferric Oxide 0.003 g Total 7.522g Purified water was added to 16 g to prepare 40 tablets, each of which was approximately 0.4 g and contained approximately 0.1881 g of solids. Preparation process: 1§ (1) API passed through a 100 mesh sieve, reserved; (2) The prescribed amount of mannitol, sorbitol, PEG 4000, medicinal gelatin type B and Neotame was placed in a clean and dry 20mL screw-cap glass reagent bottle, then approximately 8 g of purified water was added and He tightened the lid. After stirring to dissolve at 50°C, the solution was cooled to room temperature, then the prescribed amount of powder prepared from Example 7a, red iron oxide and anhydrous tripotassium phosphate was added, stirring and dispersing, then added purified water according to prescription. After stirring and dispersing, the mixture was passed through a 100 mesh stainless steel sieve 3 times, the suspension was obtained for loading separately, and stirred continuously to prevent sedimentation; (3) The suspension to dispense was 0.4 g per hole in the mold hole, it was freeze-dried; (4) The Iophylized sample was heat sealed to obtain IiofiIized orally disintegrating tablets. The pH detection value and relative exposure: Own preparation sample 23a: pH 8.02, 0.21% (8.3 ug / ml); Own preparation sample 23b: pH 9.79, 0.25% (9.9 ug / ml). After testing by 10 volunteer subjects, sample 23a disintegrated in the oral cavity within 10 seconds, and sample 23b disintegrated in the oral cavity within 5 seconds, and there was no grittiness and minimal irritation. Self-made sample 23a: Instant irritation +, disappeared within 1 to 15 minutes after delayed irritation and bitterness was acceptable. Self-made sample 23b: Instant irritation +, disappeared within 1 to 15 minutes after delayed irritation and bitterness was acceptable. Detailed information is shown in Table 48: Table 48 Taste Comparison of Vortioxetine Hemihydrobromide Solid Dispersion Oral Dissolution Tablets Subject Instant Delayed irritation (min) Bitterness Harsh Sample 23a Sample 23b Sample 23a Sample 23b Sample 23a Sample 23b Sample 23a Sample 23b Subject 1 + + 1-15 1-15 acceptable acceptable No No Subject 2++ 1-15 1-15 acceptable acceptable No No Subject 3++ 1-15 1-15 acceptable acceptable No No Subject 4 +++ 1-15 1-15 acceptable acceptable No No Subject 5+++ 1- 15 1-15 acceptable acceptable No No Subject 6 + + 1-15 1-15 acceptable acceptable No No Subject 7 + + 1-15 1-15 acceptable acceptable No No Subject 8 + + 1-15 1-15 acceptable acceptable No No Subject 9 + + 1-15 1-15 acceptable acceptable No No Subject 10 + + 1-15 1-15 acceptable acceptable No No Example 24: Preparation of 20 mg / tablet orally disintegrating tablets (compressed tablets, lyophilized tablets) 24a: The formula of 100 tablets weighing 0.152 g each manufactured from the micronized powder coated powder of vortioxetine hemihydrobromide was as follows: Powder prepared from Example 11 at 5.80 g (equal to 2.0 g of vortioxetine) Mannitol P100SD 7.140 g Anhydrous disodium hydrogen phosphate 0.304 g Crospovidone XL 0.608 g Croscarmellose Sodium 0.608 g Sodium starch glycolate 0.608 g Magnesium stearate 0.07 6g Neotame 0.015 g Red Ferric Oxide 0.076 g Total 15.235g Preparation process: (1) Neotame and red iron oxide passed 200 mesh sieve and other raw materials passed 80 mesh sieve, reserved; (2) The prescribed amount of powder prepared from Example 11a, disodium hydrogen phosphate anhydrous, mannitol P100SD, crospovidone XL, croscarmellose sodium, sodium starch glycolate, magnesium stearate, Neotame and iron oxide red were placed in a screw 50mL clean and dry, top glass reagent bottle. After mixing in a vortex mixer for five minutes, the mixture was extracted after passing through an 80 mesh sieve. After mixing for another five minutes, the mixture was extracted after passing through an 80 mesh sieve, and finally after mixing for another five minutes, the compressed premix was obtained; (3) The compressed premix was pressed using a ZP8 rotary tablet press with a shallow concave mold of 8.0 mm in diameter, controlling the tablet weight of 147-157 mg / tablet and a hardness of 15-30N, and obtaining the tablet. 24b: The formula of the micronized powder coated powder of vortioxetine hemihydrobromide transformed into lyophilized orally disintegrating tablets was as follows: Powder prepared from Example 11 at 2.321 g (equal to 0.8 g of vortioxetine) ΊΟ Mannitol 2,000 g Sorbitol 2,000 g PEG 4000 1,030g Anhydrous disodium hydrogen phosphate 0.124 g Gelatin Type B Medicinal 0.124 g Neotame 0.001 g Red Ferric Oxide 0.003 g Total 7.603g hbh7nn / 77n7 / E / Yl· Purified water was added to 16 g to prepare 40 tablets, each of which had 1§ approximately 0.4 g and contained approximately 0.1901 g of solids. Preparation process: (1) Neotame and iron oxide were passed through 200 mesh and other raw materials were passed through 80 mesh sieve and separated; (2) The prescribed amount of mannitol, sorbitol, PEG 4000, medicinal gelatin type B and Neotame was placed in a clean and dry 20mL screw-cap glass reagent bottle, then approximately 8 g of purified water was added and He tightened the lid. After stirring to dissolve at 50°C, the solution was cooled to room temperature, then the prescribed amount of powder prepared from Example 11a, red iron oxide and anhydrous disodium hydrogen phosphate was added, stirred and dispersed, then Purified water was added according to the prescription amount. After stirring and dispersing, the mixture was passed 3 times through a 100 mesh stainless steel sieve, the suspension was obtained to be loaded separately and stirred continuously to prevent sedimentation; (3) The suspension to dispense was 0.4 g per hole in the mold hole, it was freeze-dried; (4) The lyophilized sample was heat sealed to obtain orally disintegrating lyophilized tablets. The pH detection value and relative exposure: Own preparation sample 24a: pH 7.98, 0.29% (11.5 ug / ml); Own preparation sample 24b: pH 9.79, 0.35% (13.9 ug / ml). After being tested by 10 volunteer subjects, sample 24a disintegrated in the oral cavity within 10 seconds, and sample 24b disintegrated in the oral cavity within 5 seconds, and there was no grittiness and minimal irritation. Self-made sample 24a: Instant irritation +, disappeared within 1 to 15 minutes after delayed irritation and bitterness was acceptable. Self-made sample 24b: Instant irritation +, disappeared within 1-15 minutes after delayed irritation and bitterness was acceptable. Detailed information is shown in Table 49: Table 49 Taste Comparison of Vortioxetine Hemihydrobromide frfrfrznn / zznz / E / YiAi Solid Dispersion Oral Dissolution Tablets Subject Instant Delayed irritation (min) Bitterness Harsh Sample 24a Sample 24b Sample 24a Sample 24b Sample 24a Sample 24b Sample 24a Sample 24 b Subject 1 + + 1-15 1-15 acceptable acceptable No No Subject 2 + + 1-15 1-15 acceptable acceptable No No Subject 3 + + 1-15 1-15 acceptable acceptable No No Subject 4 + + 1-15 1-15 acceptable acceptable No No Subject 5 + + 1-15 1-15 acceptable acceptable No No Subject 6 + + 1-15 1-15 acceptable acceptable No No Subject 7 + + 1-15 1-15 acceptable acceptable No No Subject 8 + + 1-15 1-15 acceptable acceptable No No Subject 9 + ++ 1-15 1-15 acceptable acceptable No No Subject 10 + + 1-15 1-15 acceptable acceptable No No Example 25: Preparation of 20 mg / tablet dispersible tablets The formula of 100 tablets with a weight of 0. Powder prepared from example 10 Microcrystalline cellulose Mannitol P100SD Calcium hydroxide Sodium starch glycolate Neotame Magnesium stearate Total grams each was as follows: 4.61 g (equal to 2.0 g of vortioxetine) 2.68g 7.35g 0.02g 0.60g 0.001g 0.05g 15.17g Preparation process: (1) The prescribed amount of powder prepared from Example 10, microcrystalline cellulose, mannitol P100SD, calcium hydroxide, sodium starch glycolate, Neotame and magnesium stearate were placed in a glass reagent bottle with screw cap. 50 mi, clean and dry. After mixing in a vortex mixer for five minutes, the mixture was extracted after passing through an 80 mesh sieve. After mixing for another five minutes, the mixture was extracted after passing through an 80 mesh sieve, and finally after mixing for another five minutes, the compressed premix was obtained; (2) The compressed premix was pressed using a ZP8 rotary tablet press with a shallow concave mold of 8.0 mm in diameter, controlling the tablet weight of 147-157 mg / tablet and a hardness of 50-80N, and obtaining the tablet. The pH detection value and relative exposure: pH 8.79, 0.45% (17.9 ug / ml). After converting the sample to powder, 10 subjects tested the powder equivalent to 20 mg of vortioxetine. The taste of the finished product was acceptable with mild irritation within 1 minute. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Detailed information is shown in Table 50: hbh7nn / 77n7 / E / Yl· Table 50 Taste Comparison Test of Vortioxetine Hemihydrobromide Solid Dispersion Dispersible Tablets Subject Instant irritation Delayed irritation (min) Bitterness Harsh Subject 1 + 1-15 acceptable No Subject 2 + 1-15 acceptable No Subject 3 + 1-15 acceptable No Subject 4 ++ 1-15 acceptable No Subject 5 + 1-15 acceptable No Subject 6 + 1-15 acceptable No Subject 7 ++ 1-15 acceptable No Subject 8 + 1-15 acceptable No Subject 9 + 1-15 acceptable No Subject 10 + 1-15 acceptable No Example 26: Preparation of 20 mg / tablet dispersible tablets The formula of 100 tablets weighing 0.152 g each was as follows: Powder prepared from example 17 Microcrystalline cellulose Mannitol P100SD Sodium starch glycolate Neotame Magnesium stearate Total 5.69 g (equal to 2.0 g of vortioxetine) 5.35g 3.50g 0.60g 0.01g 0.05g 15.20g Preparation process: (1) The prescribed amount of powder prepared from Example 17, microcrystalline cellulose, mannitol P100SD, sodium starch glycolate, Neotame and magnesium stearate were placed in a clean, 50 ml screw cap glass reagent bottle. dry. After mixing in a vortex mixer for five minutes, the mixture was extracted after passing through an 80 mesh sieve. After mixing for another five minutes, the mixture was extracted after passing through an 80 mesh sieve, and finally after mixing for another five minutes, the compressed premix was obtained; (2) The compressed premix was pressed using a ZP8 rotary tablet press with a shallow concave mold of 8.0 mm in diameter, controlling the tablet weight of 147-157 mg / tablet and a hardness of 50-80N, and obtaining the tablet. The pH detection value and relative exposure: 8.79, 0.45% (17.9 ug / ml). After converting the sample to powder, 10 subjects tested the powder equivalent to 20 mg of vortioxetine. The taste of the finished product was acceptable with mild irritation within 1 minute. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Detailed information is shown in Table 51: Table 51 Vortioxetine Hemihydrobromide Dispersible Tablets Flavor Comparison Test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Subject 1 + 1-15 acceptable No Subject 2 + 1-15 acceptable No Subject 3 + 1-15 acceptable No Subject 4 + 1-15 acceptable No Subject 5 + 1-15 acceptable No Subject 6 + 1-15 acceptable No Subject 7 + 1-15 acceptable No Subject 8 + 1-15 acceptable No Subject 9 + 1-15 acceptable No Subject 10 + 1-15 acceptable No Example 27: Preparation of granules or dry suspension (5 g per bag, containing 20 mg of vortioxetine) The formula for 100 bags of 5 g each was as follows: Vortioxetine hemihydrobromide 2.28 g (equal to 2.0 g of vortioxetine) 5 g 25 Magnesium stearate i g Total 500.28g Preparation process: (1) API and excipients were passed through the 100 mesh sieve, set aside; (2) The prescribed amount of vortioxetine hemihydrobromide, xylitol, mannitol P100SD, microcrystalline cellulose, colloidal silicon dioxide, sodium carboxymethylcellulose, tripotassium citrate, sodium starch glycolate, Neotame and magnesium stearate were placed in a stainless steel hopper of 2 liters clean and dry. The hopper was installed on the hopper mixing machine, mixed at 10 rpm for 10 minutes and taken out. After granulating with a rotary granulator and 0.5 mm stainless steel round hole mesh plate, mixing was continued with a hopper mixer for 10 minutes at 10 rpm to obtain the premix for granulation; (3) The premix for granulation was pressed into thin slices with a dry granulator and then granulated using a 1.5 mm stainless steel round mesh plate. After sieving with a 40 mesh stainless steel sieve, the fine powder was returned for regranulation. 461.34 grams of granules were obtained and the yield was 92.2%. (4) The prepared particles were packed into aluminum-plastic heat-sealed bags at 5 g / bag and then heat-sealed. A bag of samples was dispersed in 20 ml of purified water. After 10 subjects taste tested, the finished product tasted acceptable. Self-made sample: Instant irritation +, disappeared within 1-15 minutes after delayed irritation, and bitterness was acceptable. Detailed information is shown in Table 52: Table 52 Vortioxetine hemihydrobromide granules taste test Subject Instant irritation Delayed irritation (min) Bitterness Harsh Subject 1 + 1-15 acceptable No Subject 2 + 1-15 acceptable No Subject 3 + 1-15 acceptable No Subject 4 ++ 1-15 acceptable No Subject 5 + 1-15 acceptable No Subject 6 + 1-15 acceptable No Subject 7 + 1-15 acceptable No Subject 8 + 1-15 acceptable No Subject 9 + 1-15 acceptable No Subject 10 + 1-15 acceptable No Example 28: Preparation of oral suspension (5mL per bottle, containing 20mg of vortioxetine) The formula of the solid dispersion of vortioxetine hemihydrobromide made in 5 ml:20 mg oral suspension was as follows: Solid dispersion prepared from Example 13a 13.63 g (equal to 2.0 g of Vortioxetine) Xylitol50 g Sodium carboxymethylcellulose0.5 g Sodium acetate0.5 g Purified water was added to 50ml, Preparation process: (1) The prescribed amount of solid dispersion prepared from Example 13a, xylitol, sodium carboxymethylcellulose and sodium acetate was added to 400mL of purified water. The mixture was homogenized at 12,000 rpm for 2 minutes and continued stirring for later use; (2) After passing the suspension obtained in the previous step through a 100 mesh stainless steel sieve, the pH value was adjusted to 8.0-8.5 with 1N HCl or 1N NaOH solution, and the purified water was added. to the prescribed amount and shaken for use; (3) The suspension was divided into a 5mL vial per bottle, and capped. Detailed information is shown in Table 53: Table 53 Taste test of vortioxetine hemihydrobromide solid dispersion oral suspension Subject Instant irritation Delayed irritation (min) Bitterness Harsh Subject 1 + 1-15 acceptable No Subject 2 + 1-15 acceptable No Subject 3 + 1-15 acceptable No Subject 4 + 1-15 acceptable No Subject 5 + 1-15 acceptable No Subject 6 + 1-15 acceptable No Subject 7 + 1-15 acceptable No Subject 8 + 1-15 acceptable No Subject 9 + 1-15 acceptable No Subject 10 + 1-15 acceptable No Comparative Example 1: Comparison of the taste of different salts Vortioxetine lactate salt, vortioxetine hydrobromide and vortioxetine hemihydrobromide equivalent to 5 mg vortioxetine respectively in 100 mesh powders were placed directly in front of the top of the tongue for one minute. There were 10 subjects in each salt type group, and each subject randomly tested each salt type 3 times. After trying one type of salt taste, they rinsed their mouth and tried another type of salt after there was no irritation. After tasting the taste, the level of bitterness and irritation of the tongue was recorded, they spit out a few seconds later, rinsed their mouth, recorded the time for the irritation to subside, ate 1 -1.5 hours later and recorded the irritation again. The following table 54 shows the comparison of the taste of different vortioxetine salts in 30 trials of 10 subjects. Table 54 Comparison of the taste of different types of vortioxetine salt by 10 subjects in 30 trials (unit: times) Type of salt Number of subjects who felt different levels of bitterness Number of subjects who experienced different irritations Extremely bitter Slightly bitter Not bitter unbearable Slightly irritating, tolerable Basically no irritation lactate salt 29 1 0 27C) 3<2> 0 hydrobromate monosalt 28 2 0 28(1) 2<2) 0 hemihydrobromide 12 18 0 120) 17(2) 1 Note: (1) Because the irritation was so strong that it was almost unbearable and could not subside even after many mouth rinses. The decrease time was more than 1 hour, and the irritation could not decrease after eating. (2) There was no irritation after gargling. Comparative Example 2: Comparison of the taste of the solid dispersions in this invention and the commercially available pharmaceutical product The solid dispersion equivalent to 10 mg of vortioxetine prepared in Example 9b, the powder of vortioxetine hemihydrobromide equivalent to 10 mg of vortioxetine, and the powder pressed by the marketed pharmaceutical product of vortioxetine hydrobromide equivalent to 10 mg of vortioxetine hydrobromide were transferred to through a 100 mesh sieve, then placed directly in front of the top of the tongue for one minute. There were 20 subjects in each powder group. After trying one powder flavor, they rinsed their mouths and tried another powder after there was no irritation. After tasting the taste, the level of bitterness and irritation of the tongue were recorded, they spit out a few seconds more 1$ late, they rinsed their mouth, the time for the irritation to subside was recorded, they ate 1-1.5 hours later and the irritation was recorded again. Table 55 Comparison of taste of different vortioxetine powders by 20 subjects Powder Number of subjects who felt different levels of bitterness Number of subjects who experienced different irritations Extremely bitter Slightly bitter Not bitter unbearable Slightly irritating, tolerable Basically no irritation Vortioxetine hemihydrobromide powder 9 11 0 2(1) 12(2) 6 Solid dispersion prepared from Example 9b 2 18 0 1(1) 6(2) 13 Pressed powder of marketed pharmaceutical product 20 0 0 20 (1) 0 0 Note: (1) Because the irritation was so strong that it was almost unbearable and could not subside even after many mouth rinses. The decrease time was more than 2 hours, and the irritation could not decrease after eating. (2) There was no irritation after gargling.

Claims

CLAIMS Proposed Claim Amendments 5 1. An orally dispersible flavor masking composition of vortioxetine hemihydrobromide, which is a tablet, granule, capsule, powder, suspension, dry suspension or solution; wherein the orally dispersible flavor masking composition comprises vortioxetine hemihydrobromide and pharmaceutically acceptable flavor masking excipients.

2. The orally dispersible flavor-masking composition according to claim 1, further comprising granules in which the vortioxetine hemihydrobromide is coated with the flavor-masking excipients; preferably, the flavor-masking excipients are cellulose acetate, ethylcellulose, hydroxypropylcellulose, methacrylic acid copolymer, chitosan, copovidone, or polyvinyl alcohol; preferably wherein the methacrylic acid copolymer is polyacrylic resin II or polyacrylic resin IV; optionally, the coated granules comprise an anti-caking agent.

3. The orally dispersible flavor-masking composition according to claim 1, further comprising a solid dispersion wherein vortioxetine hemihydrobromide is dispersed in the flavor-masking excipients; preferably, the flavor-masking excipients are cellulose acetate, ethylcellulose, hydroxypropylcellulose, methacrylic acid copolymer, chitosan, copovidone, povidone, polyvinyl alcohol, or polyethylene glycol; preferably wherein the methacrylic acid copolymer is polyacrylic resin II or polyacrylic resin IV, wherein the polyethylene glycol includes at least one of PEG 4000, PEG 6000, and PEG 8000; preferably wherein the weight ratio of polyacrylic resin IV to at least one of PEG 4000, PEG 6000, and PEG 8000 is 1:0.05-1:

2.

4. The orally dispersible flavor masking composition according to claim 1, wherein the flavor masking excipients comprise alkaline excipients selected from the group consisting of trisodium phosphate, disodium hydrogen phosphate, disodium hydrogen phosphate, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium citrate, sodium acetate, calcium hydroxide, sodium hydroxide, potassium hydroxide, and meglumine.

5. The orally dispersible flavor masking composition according to claim 2, wherein the flavor masking excipients comprise alkaline excipients, the weight ratio of vortioxetine hemihydrobromide to flavor masking excipient is 1:0.1-1:5, and the weight ratio of vortioxetine hemihydrobromide to alkaline excipient is 1:0.01-1:1.

1.

6. The orally dispersible flavor masking composition according to claim 3, wherein the flavor masking excipients comprise alkaline excipients, the weight ratio of vortioxetine hemihydrobromide to the flavor masking excipient is 1:0.1-1:5, and the weight ratio of vortioxetine hemihydrobromide to the alkaline excipient is 1:0.01-1:1.

1.

7. The orally dispersible flavor masking composition according to claim 4, wherein the weight ratio of vortioxetine hemihydrobromide to the alkaline excipient is 1:0.01-1:1.

1.

8. The orally dispersible flavor-masking composition according to claim 5, further comprising a solid dispersion wherein the granules are dispersed in the flavor-masking excipients.

9. The orally dispersible flavor masking composition according to claim 6, further comprising granules wherein the solid dispersion is coated with the flavor masking excipient.

10. The orally dispersible flavor masking composition according to claim 1, wherein the orally dispersible flavor masking composition has a crystalline form 1§, and wherein the crystalline form has characteristic peaks at 4.2±0.2° and 17.4±0.2° when Cu-Kα radiation is used and the powder X-ray diffraction pattern is expressed at angles of 29.

11. The orally dispersible flavor masking composition according to any one of claims 1 to 3, further comprising a filler, a flavoring agent, a release regulator, a plasticizer, an anti-caking agent and / or a disintegrant; 15 preferably, the anti-caking agent is talc, representing from 5% to 25% of the total weight of the flavor-masking coated granule; wherein the disintegrant is sodium starch glycolate, croscarmellose sodium, crospovidone and combinations thereof, representing from 1% to 8% of the total weight of the orally dispersible flavor masking composition; preferably, wherein the flavoring agent is neotame, representing from 0.05% to 0.5% of the total weight of the orally dispersible flavor masking composition.

12. A method for preparing the orally dispersible flavor-masking composition according to claim 1, comprising: (a) dispersing the flavor-masking excipients in a solvent, coating the vortioxetine hemihydrobromide with the flavor-masking excipients in the solvent through a fluidized bed, thereby forming a mixture; and removing the solvent from the mixture, thereby obtaining vortioxetine hemihydrobromide coated with the flavor-masking excipients; preferably, dispersing the flavor-masking excipient and the release regulator in a solvent; more preferably, wherein the release regulator is polyethylene glycol or an alkaline excipient; preferably, wherein the solvent is water, ethanol, or dichloromethane; or (b) adding the vortioxetine hemihydrobromide and the flavor-masking excipients to a solvent to form a suspension;and removing the solvent from the suspension through a fluidized bed, spray drying or evaporation, thereby obtaining vortioxetine hemihydrobromide coated with the flavor-masking excipients; preferably, wherein the vortioxetine hemihydrobromide, the flavor-masking excipient, the release regulator and / or the plasticizer are added to the solvent to form a suspension; preferably, wherein the plasticizer is polyethylene glycol or triethyl citrate; preferably, wherein the solvent is water, ethanol or dichloromethane; thereby preparing a composition comprising the coated vortioxetine hemihydrobromide.

13. A method for preparing the orally dispersible flavor-masking composition according to claim 1, comprising: (a) mixing the vortioxetine hemihydrobromide with the flavor-masking excipients to form a combination; heating the combination to 50-150°C to form a soft or liquefied mixture; cooling the soft or liquefied mixture to form a solidified mixture; and milling the solidified mixture to obtain granules of vortioxetine hemihydrobromide; preferably wherein the vortioxetine hemihydrobromide, the flavor-masking excipient, and the release-regulating agent are mixed; or (b) dissolving the vortioxetine hemihydrobromide and the flavor-masking excipients in a solvent to form a solution;and removing the solvent from the solution by distillation, fluidized bed or spray drying, thereby obtaining granules of vortioxetine hemihydrobromide; preferably wherein the solvent is water, ethanol or dichloromethane; thereby obtaining a composition comprising granules of vortioxetine hemihydrobromide. 15; 14. A method for preparing the orally dispersible flavor-masking composition according to claim 1, wherein the flavor-masking excipients comprise alkaline excipients, comprising: (a) mixing vortioxetine hemihydrobromide with the alkaline excipients to obtain a flavor-masking combination; preferably wherein the alkaline excipients are trisodium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium citrate, sodium acetate, calcium hydroxide, sodium hydroxide, potassium hydroxide, or meglumine; and (b) preparing the flavor-masking combination as a composition.

15. The method of preparation according to any of claims 1225 14, wherein the flavor masking excipients comprise alkaline excipients, the weight ratio of vortioxetine hemihydrobromide to the flavor masking excipient to form a coating or solid dispersion is 1:0.1-1:5, and the weight ratio of vortioxetine hemihydrobromide to alkaline excipient is 1:0.01-1:1.

1.

16. The orally dispersible flavor masking composition according to claim 3, wherein the flavor masking excipients comprise polyacrylic resin IV, wherein the orally dispersible flavor masking composition has a crystalline form, and wherein the crystalline form has characteristic peaks at 4.2±0.2°, 14.5±0.2°, 17.4±0.2°, and 22.6+0.2° when Cu-Kα is used and the powder X-ray diffraction pattern is expressed in 2Θ angles.

17. An orally dispersible flavor masking composition comprising vortioxetine hydrobromide and alkaline excipients, wherein the weight ratio of vortioxetine hydrobromide to alkaline excipient is 1:0.01-1:1.1, wherein the orally dispersible flavor masking composition has a crystalline form, and wherein the crystalline form has characteristic peaks at 4.2±0.2° and 17.4±0.2° when Cu-Kα radiation is used and the powder X-ray diffraction pattern is expressed in 20° angles.

18. A method for treating a depressive disorder in a subject, comprising administering to the subject an effective amount of the orally dispersible flavor-masking composition according to claim 1 or claim 17.