Lurasidone hydrochloride sublingual or buccal membrane agent as well as preparation method and application thereof

Abstract

The invention discloses a lurasidone hydrochloride sublingual or buccal membrane as well as a preparation method and application thereof. The lurasidone hydrochloride sublingual or buccal membrane agent comprises lurasidone hydrochloride with the particle size of less than or equal to 10 microns, a membrane forming material, a plasticizer and a flavoring agent, the film forming material comprises one or more of polyoxyethylene, polyvinyl alcohol, hydroxypropyl methyl cellulose, hydroxy propyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, ethyl cellulose and copovidone; the lurasidone hydrochloride with the particle size of less than or equal to 10 microns is prepared by a homogenizing method. The film agent is absorbed through a near-end mucous membrane, the problems of first-pass metabolism and gastrointestinal tracts are avoided, and the film agent is rapidly absorbed to take effect. The preparation is high in dissolution rate, uniform and stable in medicine content and capable of being dissolved in the oral cavity without drinking water, and the compliance of a patient is improved. The lurasidone hydrochloride raw material prepared by the preparation method of the film agent has a particle size of less than 10 [mu] m, is simple in production process, is environment-friendly and safe, and is convenient for commercial production and application.

Description

Technical Field

[0001] This invention relates to a lurasidone hydrochloride sublingual or buccal film preparation, its preparation method, and its application. Background Technology

[0002] Schizophrenia, or schizophrenia for short, is a clinical syndrome composed of a group of symptoms. It is a multifactorial disease that often has a slow or subacute onset in young adults. Clinically, it often manifests as a syndrome with diverse symptoms, involving disturbances in perception, thinking, emotion, and behavior, as well as incoordination of mental activity. According to WHO statistics, approximately 23 million people worldwide suffer from schizophrenia, and 60 million suffer from bipolar disorder. The latest national epidemiological survey data shows that the number of people with mental disorders in China exceeds 180 million, with as many as 4.8 million registered mental disorder patients nationwide, indicating a huge market demand.

[0003] Lurasidone hydrochloride is an atypical (second-generation) antipsychotic drug developed by Sumitomo Pharmaceuticals. It was approved by the U.S. Food and Drug Administration (FDA) on October 28, 2010, under the brand name Latuda, for the treatment of schizophrenia. Sumitomo Pharmaceuticals (Suzhou) Co., Ltd., a Chinese subsidiary of Sumitomo Pharmaceuticals, submitted its application to the China National Medical Products Administration (NMPA) in December 2015. On January 24, 2019, Sumitomo's atypical antipsychotic drug was submitted for an import license application. Lurasidone hydrochloride tablets have received import drug registration approval from the National Medical Products Administration (NMPA) for the treatment of schizophrenia in adults. Besides the original drug, six generic versions have been approved in China and are considered to have passed the evaluation. Additionally, Hunan Kelun Pharmaceutical's Class 2.2 new drug, lurasidone orally disintegrating tablets, has received clinical trial approval (implicit approval) for the treatment of schizophrenia.

[0004] The recommended starting dose of lurasidone hydrochloride tablets is 40 mg / day, with an effective dose range of 40–120 mg / day and a maximum recommended dose of 80 mg / day. Lurasidone hydrochloride should be taken with food. Currently available formulations of lurasidone hydrochloride include ordinary tablets, orally disintegrating tablets, injections, and oral solutions, with oral solid dosage forms being the most prevalent. Due to the specific needs of the patient population, patients often have difficulty swallowing solid oral dosage forms. Tablets and capsules have poor dissolution in the gastrointestinal tract, low bioavailability, and are not suitable for swallowing. Furthermore, some psychiatric patients may conceal tablets under their tongues and spit them out after medical personnel have left, resulting in "false medication" and significantly impacting the effectiveness of drug treatment.

[0005] Lurasidone hydrochloride is a BCS class II compound with poor water solubility and almost no solubility in gastric acid. After oral administration, only 9% to 19% is absorbed through the gastrointestinal tract, resulting in low bioavailability.

[0006] Patent WO2023078366A1 discloses a lurasidone orally disintegrating film composition, which contains basic components such as active ingredients, film-forming materials, plasticizers and flavoring agents. Under normal circumstances, the drug carried by the orally disintegrating film is partially absorbed in the oral cavity, but most of it is absorbed in the gastrointestinal tract.

[0007] Patent CN107137364A discloses a method for preparing lurasidone sublingual tablets and their uses. A large amount of disintegrant is added to the formulation to ensure compatibility of the raw materials and excipients before tableting. The resulting sublingual tablets have a high drug content, rapid disintegration, and good transmembrane absorption, making them suitable for sublingual administration. The formulation process in this example uses wet granulation. Generally, granulated particles have a relatively high density, which is detrimental to dissolution, release, and compressibility, and is prone to over-granulation.

[0008] Patent CN113081983B discloses a lurasidone sublingual tablet and its preparation method, resulting in sublingual tablets with high solubility and strong stability. However, this patent uses a direct powder compression process, which results in poor content uniformity and a tendency for stratification between different raw materials and excipients during material transfer and tableting. Furthermore, the excipients sorbitol and crospovidone in this patent require 100-mesh sieve treatment before use, making the process cumbersome and unsuitable for industrial production. Summary of the Invention

[0009] To address the aforementioned problems, the present invention aims to provide a sublingual or buccal film of lurasidone hydrochloride, its preparation method, and its application. This film has an attractive appearance, excellent physical properties, and a pleasant taste. It is absorbed through the proximal mucosa, avoiding first-pass metabolism and gastrointestinal problems, and is rapidly absorbed and takes effect. The formulation exhibits a rapid dissolution rate, uniform and stable drug content, and solves the inconvenience of conventional oral formulations. It dissolves in the oral cavity without the need for drinking water, improving patient compliance. Furthermore, the present invention optimizes the production process of the film, resulting in lurasidone hydrochloride raw material with a particle size of less than 10 μm. The production process is simple, uses pure water as a solvent, is environmentally friendly and safe, and facilitates commercial production and application.

[0010] The objective of this invention is achieved through the following technical solutions.

[0011] In a first aspect, the present invention provides a lurasidone hydrochloride sublingual or buccal film, characterized in that it comprises lurasidone hydrochloride with a particle size ≤10μm, a film-forming material, a plasticizer, and a flavoring agent; the film-forming material comprises one or more of polyoxyethylene, polyvinyl alcohol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, and copovidone; the lurasidone hydrochloride with a particle size ≤10μm is prepared by homogenization.

[0012] Preferably, the lurasidone hydrochloride sublingual or buccal film preparation meets one or more of the following conditions:

[0013] a. The particle size is 0.1–10 μm;

[0014] b. The thickness of the lurasidone hydrochloride sublingual or buccal film is 0.1 mm to 0.4 mm, for example, 0.15 mm;

[0015] c. The size of the lurasidone hydrochloride sublingual or buccal film is 20mm*30mm.

[0016] Preferably, the lurasidone hydrochloride sublingual or buccal film preparation meets one or more of the following conditions:

[0017] a. The film-forming material is one or more of hydroxypropyl cellulose, copovidone, hydroxypropyl methylcellulose and polyethylene oxide. Preferably, the film-forming material is one or more of hydroxypropyl methylcellulose E5, hydroxypropyl methylcellulose E15, hydroxypropyl cellulose LM, polyethylene oxide N80 and copovidone K30.

[0018] b. The plasticizer includes one or more of glycerol, propylene glycol, polyethylene glycol and glycerin, such as polyethylene glycol 400 and / or glycerin;

[0019] c. The flavoring agent is one or more of acesulfame potassium, sodium saccharin, sucralose, acesulfame potassium, aspartame, neotame, steviol glycoside, mannitol, xylitol, sorbitol and flavoring, preferably one or more of sucralose, acesulfame potassium, neotame, flavoring and menthol.

[0020] Preferably, the lurasidone hydrochloride sublingual or buccal film also includes one or more of other excipients, such as antioxidants, preservatives, colorants, and saliva stimulants.

[0021] More preferably, the other excipients satisfy one or more of the following conditions:

[0022] a. The antioxidants include one or more of butylated hydroxytoluene, disodium edetate, vitamin C, sodium sulfite, sodium metabisulfite, sodium benzoate, methylparaben, and ethylparaben;

[0023] b. The preservative includes one or more of sodium benzoate, potassium sorbate and parabens;

[0024] c. The colorant includes one or more of titanium dioxide, silicon dioxide, zinc oxide, and natural colorants;

[0025] d. The saliva stimulant includes one or more of citric acid, malic acid and lactic acid.

[0026] More preferably, the lurasidone hydrochloride sublingual or buccal film, by weight percentage, meets one or more of the following conditions:

[0027] ① The content of lurasidone hydrochloride is 30-60%, preferably 40-60%;

[0028] ②The film-forming material comprises 25-51%, preferably 25-47%;

[0029] ③ The plasticizer is 7-10%, preferably 7-9%;

[0030] ④ The flavoring agent is 5-12%;

[0031] ⑤ The other excipients are 0.01-5%, preferably 1-5%.

[0032] In some preferred embodiments, the lurasidone hydrochloride sublingual or buccal film preparation comprises, by weight percentage: 40-60% lurasidone hydrochloride, 25-47% film-forming material, 7-9% plasticizer, 5-12% flavoring agent, and other excipients including colorant, preferably 1-5% colorant.

[0033] In some preferred embodiments, the film-forming material is polyoxyethylene N80 and / or hydroxypropyl methylcellulose LM, the plasticizer is polyethylene glycol 400, the flavoring agent is neotame, and the colorant is titanium dioxide.

[0034] In some specific embodiments, the lurasidone hydrochloride sublingual or buccal film comprises: 40% lurasidone hydrochloride, 47% polyoxyethylene N80 and hydroxypropyl methylcellulose LM, 7% polyethylene glycol 400, 5% neotame, and 1% titanium dioxide.

[0035] Secondly, the present invention also provides a method for preparing the above-described lurasidone hydrochloride sublingual or buccal film, comprising the following steps:

[0036] S1: The raw material lurasidone hydrochloride is homogenized to form a lurasidone hydrochloride suspension with a particle size ≤10μm;

[0037] S2: Mix the lurasidone hydrochloride suspension with the other components of the lurasidone hydrochloride sublingual or buccal film preparation evenly;

[0038] S3: Apply the coating liquid.

[0039] Preferably, in step S1, the homogenization time is 20-60 minutes, for example, 30 minutes.

[0040] Preferably, in step S2, the mixing method is stirring, and preferably, the stirring time is 1 to 2 hours.

[0041] Preferably, in step S2, after mixing, a vacuum degassing step is also included to obtain the coating liquid.

[0042] Preferably, in step S3, the coating thickness is 0.3 mm to 0.6 mm, for example, 0.5 mm.

[0043] Preferably, step S3 is followed by drying and cutting steps; preferably, the drying temperature is 60-120°C, for example 80°C.

[0044] Thirdly, the present invention also provides the use of the lurasidone hydrochloride sublingual or buccal film as described above in the preparation of sublingual or buccal film pharmaceutical formulations.

[0045] Based on common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0046] The reagents and raw materials used in this invention are all commercially available.

[0047] The positive and progressive effects of this invention are as follows:

[0048] (1) The lurasidone hydrochloride sublingual or buccal film of the present invention has a thickness between 0.1 mm and 0.4 mm, a uniform and delicate appearance, and no gritty feeling when taken orally. It is not only easy to carry and take, but also particularly suitable for clinical use in patients with schizophrenia. The film can rapidly disintegrate in the oral cavity within 2 minutes and the dissolution rate can reach more than 90% within 5 minutes, showing extremely rapid dissolution and absorption capabilities.

[0049] (2) The lurasidone hydrochloride sublingual or buccal film of the present invention exhibits excellent stability, with low impurity content even after long-term storage. Furthermore, the film has a rapid onset of action, high bioavailability, and can significantly reduce individual differences in drug efficacy.

[0050] (3) The preparation method of the lurasidone hydrochloride sublingual or buccal film of the present invention achieves the expected effect by means of homogenization emulsification without reducing the particle size of lurasidone hydrochloride to the nanoscale, to below 10 μm, so that it is uniformly and stably distributed in the coating solution. This not only greatly improves the drug loading capacity, but also significantly enhances the storage stability of the coating solution, and avoids the sedimentation and agglomeration of lurasidone hydrochloride in mass production.

[0051] (4) The preparation method of lurasidone hydrochloride sublingual or buccal film preparation of the present invention effectively improves the content uniformity, solubility and dissolution rate of the preparation, ensuring that the preparation can quickly disintegrate and dissolve and be absorbed by the oral mucosa. The entire preparation process is simple, with little environmental pollution, and is easy to scale up for industrial production. Attached Figure Description

[0052] Figure 1 The dissolution curves are for the sublingual or buccal films of lurasidone hydrochloride in Example 4 and Comparative Example 1. Detailed Implementation

[0053] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0054] The sources of the raw materials used in the following embodiments are shown in the table below:

[0055] Table 1

[0056]

[0057] In the following examples, the homogenizer is a vacuum homogenizer / emulsifier, sourced from Becomes GmbH, Germany, model RW 60CD.

[0058] In the following examples, the particle size of lurasidone hydrochloride was measured using a Neopatek laser particle size analyzer from Neopatek GmbH, Germany.

[0059] Example 1

[0060] The recipe is as follows:

[0061]

[0062] The method for preparing lurasidone hydrochloride sublingual or buccal film using the components of the above formulation is as follows:

[0063] (1) After mixing the lurasidone hydrochloride raw material with purified water, homogenize it at high speed for 0.5 h using a homogenizer at a speed of 20 m / s. This yields a lurasidone hydrochloride suspension with a particle size of less than 10 μm.

[0064] (2) Add flavoring agent, other excipients, film-forming material and plasticizer, and stir thoroughly for 1-2 hours to obtain a uniform drug-containing viscous liquid;

[0065] (3) After vacuum degassing, the coating liquid is obtained;

[0066] (4) Pour the coating solution onto an inert carrier and use a coating dryer to coat a thickness of 0.5 mm at a drying temperature of 80°C to obtain a 0.15 mm thick lurasidone hydrochloride coating. Cut it into 20 mm * 30 mm pieces and seal it in a package to obtain a lurasidone hydrochloride sublingual or buccal film.

[0067] Example 2

[0068] The recipe is as follows:

[0069]

[0070]

[0071] The method for preparing lurasidone hydrochloride sublingual or buccal film using the components of the above formulation is the same as in Example 1.

[0072] Example 3

[0073] The recipe is as follows:

[0074]

[0075] The method for preparing lurasidone hydrochloride sublingual or buccal film using the components of the above formulation is the same as in Example 1.

[0076] Example 4

[0077] The recipe is as follows:

[0078]

[0079] The method for preparing lurasidone hydrochloride sublingual or buccal film using the components of the above formulation is the same as in Example 1.

[0080] Example 5

[0081] The recipe is as follows:

[0082]

[0083] The method for preparing lurasidone hydrochloride sublingual or buccal film using the components of the above formulation is the same as in Example 1.

[0084] Example 6

[0085] The recipe is as follows:

[0086]

[0087] The method for preparing lurasidone hydrochloride sublingual or buccal film using the components of the above formulation is the same as in Example 1.

[0088] Example 7

[0089] The recipe is as follows:

[0090]

[0091]

[0092] The method for preparing lurasidone hydrochloride sublingual or buccal film using the components of the above formulation is the same as in Example 1.

[0093] Example 8

[0094] The recipe is as follows:

[0095]

[0096] The method for preparing lurasidone hydrochloride sublingual or buccal film using the components of the above formulation is the same as in Example 1.

[0097] Example 9

[0098] The recipe is as follows:

[0099]

[0100]

[0101] The method for preparing lurasidone hydrochloride sublingual or buccal film using the components of the above formulation is the same as in Example 1.

[0102] Comparative Example 1

[0103] The recipe is as follows:

[0104]

[0105] The method for preparing lurasidone hydrochloride sublingual or buccal film preparation using the components of the above formulation differs from that in Example 1 only in that: high-speed homogenization is performed using a homogenizer for 15 minutes to obtain a lurasidone hydrochloride suspension with a particle size of 30-500 μm.

[0106] Effect Example

[0107] I. Collapse Time Limit Test

[0108] Disintegration time is a crucial indicator affecting the quality and medication adherence of film-forming products. It is generally believed that the shorter the disintegration time, the better the taste. Disintegration within 1 minute is generally considered good. In the disintegration time test, six tablets each of lurasidone hydrochloride sublingual or buccal films from Examples 1-9 and Comparative Example 1 were taken, cut into films of the same size, clamped with paperclips, and held in place using two layers of stainless steel wire mesh with an inner diameter of 2.0 mm. The disintegration time was tested according to the method described under the tablet disintegration test, and the time it took for the film to completely melt and pass through the sieve was observed and recorded. The relevant results are shown in Table 2 below. Comparative Example 1 had a longer disintegration time due to its larger raw material particle size, while Examples 1-9 had a shorter disintegration time and better results.

[0109] Table 2

[0110] Serial Number Disintegration time / s Example 1 57 Example 2 52 Example 3 49 Example 4 55 Example 5 50 Example 6 42 Example 7 56 Example 8 58 Example 9 53 Comparative Example 1 69

[0111] II. Taste Evaluation

[0112] Unpleasant taste not only affects medication adherence, thus impacting treatment duration and efficacy, but also increases the risk of adverse drug behavior; therefore, improving taste is particularly important. The taste evaluation of the lurasidone hydrochloride sublingual or buccal films prepared in each example and comparative example is shown in Table 3 below:

[0113] Table 3

[0114]

[0115]

[0116] The main difference between Example 1 and Comparative Example 1 is the particle size of the raw materials. The type and amount of sweetener added are the same, so the taste is basically the same. The sweetener used in Examples 2-9 is neotame, and the taste is optimal when the amount added is 5%.

[0117] III. Dissolution Test

[0118] The dissolution profiles of the lurasidone hydrochloride sublingual film formulations prepared according to the formulations of Example 4 and Comparative Example 1 were determined using the following methods:

[0119] Test medium: water (37℃±0.5℃);

[0120] Dissolution method: Chinese Pharmacopoeia 2020 Edition 0931 Dissolution and release determination, second stage (paddle method), rotation speed 50 rpm;

[0121] Sampling time: 5 min, 10 min, 15 min

[0122] Take 6 tablets of lurasidone hydrochloride sublingual film preparation and determine the dissolution curve using the method described above. The dissolution curve is as follows: Figure 1 The results are shown in Table 4 below:

[0123] Table 4

[0124]

[0125] Dissolution test data from the examples and comparative examples show that the lurasidone hydrochloride sublingual or buccal film preparation obtained in Example 4 of this invention achieves a dissolution rate of over 90% in the oral cavity within 5 minutes and over 96% within 15 minutes. In contrast, Comparative Example 1, due to the homogenization process resulting in particle sizes of 30–500 μm, exhibits a dissolution rate of only 80.3% in the oral cavity within 5 minutes and less than 90% within 15 minutes, at only 87.6%. Therefore, the present invention's method of homogenizing a lurasidone hydrochloride suspension with a particle size ≤10 μm before mixing it with excipients promotes drug dissolution, increases drug dissolution rate and dissolution rate, thereby improving drug bioavailability.

[0126] IV. Related Substances Testing

[0127] The RP-HPLC method was used to determine the anaerobic rurasidone hydrochloride sublingual or buccal membrane formulation prepared according to the formulation of Example 4. Welch Ultimat C 18 The chromatographic column (150mm*4.6mm, 5μm) and mobile phase A were 0.005mol / L dipotassium hydrogen phosphate solution (adjusted to pH 7.0 with phosphoric acid) - acetonitrile (4:1).

[0128] 1) Mobile phase B was acetonitrile, gradient elution was used, the detection wavelength was 230 nm, the column temperature was 25 °C, and the flow rate was 0.7 mL / min. The results are shown in Table 5 below. The sample obtained in Example 4 had relatively low maximum unknown single impurity and total impurity content.

[0129] Table 5

[0130] Sample Information Maximum unknown single hybrid General Miscellaneous Lurasidone hydrochloride sublingual membrane 0.04％ 0.06％

[0131] While specific embodiments of the present invention have been described above, those skilled in the art should understand that these are merely illustrative examples, and the scope of protection of the present invention is defined by the appended claims. Those skilled in the art can make various changes or modifications to these embodiments without departing from the principles and essence of the present invention, but all such changes and modifications fall within the scope of protection of the present invention.

Claims

1. A lurasidone hydrochloride sublingual or buccal film preparation, characterized in that, It comprises lurasidone hydrochloride with a particle size ≤10μm, a film-forming material, a plasticizer, and a flavoring agent; the film-forming material includes one or more of polyoxyethylene, polyvinyl alcohol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, and copovidone; the lurasidone hydrochloride with a particle size ≤10μm is prepared by homogenization.

2. The lurasidone hydrochloride sublingual or buccal film as described in claim 1, characterized in that, The lurasidone hydrochloride sublingual or buccal film preparation meets one or more of the following conditions: a. The particle size is 0.1–10 μm; b. The thickness of the lurasidone hydrochloride sublingual or buccal film is 0.1 mm to 0.4 mm, for example, 0.15 mm; c. The size of the lurasidone hydrochloride sublingual or buccal film is 20mm*30mm.

3. The lurasidone hydrochloride sublingual or buccal film as described in claim 1, characterized in that, Lurasidone hydrochloride sublingual or buccal film preparations meet one or more of the following conditions: a. The film-forming material is one or more of hydroxypropyl cellulose, copovidone, hydroxypropyl methylcellulose and polyethylene oxide, preferably one or more of hydroxypropyl methylcellulose E5, hydroxypropyl methylcellulose E15, hydroxypropyl cellulose LM, polyethylene oxide N80 and copovidone K30. b. The plasticizer includes one or more of glycerol, propylene glycol, polyethylene glycol and glycerin, such as polyethylene glycol 400 and / or glycerin; c. The flavoring agent is one or more of acesulfame potassium, sodium saccharin, sucralose, acesulfame potassium, aspartame, neotame, steviol glycoside, mannitol, xylitol, sorbitol and flavoring, preferably one or more of sucralose, acesulfame potassium, neotame, flavoring and menthol.

4. The lurasidone hydrochloride sublingual or buccal film as described in claim 1, characterized in that, The lurasidone hydrochloride sublingual or buccal film also includes one or more of the following excipients: antioxidants, preservatives, colorants, and saliva stimulants.

5. The lurasidone hydrochloride sublingual or buccal film as described in claim 4, characterized in that, The other excipients meet one or more of the following conditions: a. The antioxidants include one or more of butylated hydroxytoluene, disodium edetate, vitamin C, sodium sulfite, sodium metabisulfite, sodium benzoate, methylparaben, and ethylparaben; b. The preservative includes one or more of sodium benzoate, potassium sorbate and parabens; c. The colorant includes one or more of titanium dioxide, silicon dioxide, zinc oxide, and natural colorants; d. The saliva stimulant includes one or more of citric acid, malic acid and lactic acid.

6. The lurasidone hydrochloride sublingual or buccal film as described in any one of claims 1-5, characterized in that, By weight percentage, the lurasidone hydrochloride sublingual or buccal film preparation meets one or more of the following conditions: ① The content of lurasidone hydrochloride is 30-60%, preferably 40-60%; ②The film-forming material comprises 25-51%, preferably 25-47%; ③ The plasticizer is 7-10%, preferably 7-9%; ④ The flavoring agent is 5-12%; ⑤ The other excipients are 0.01-5%, preferably 1-5%.

7. The lurasidone hydrochloride sublingual or buccal film as described in claim 6, characterized in that, By weight percentage, the lurasidone hydrochloride sublingual or buccal film comprises: 40-60% lurasidone hydrochloride, 25-47% film-forming material, 7-9% plasticizer, 5-12% flavoring agent, and other excipients including colorant, preferably 1-5% colorant; Preferably, the film-forming material is polyoxyethylene N80 and / or hydroxypropyl methylcellulose LM, the plasticizer is polyethylene glycol 400, the flavoring agent is neotame, and the colorant is titanium dioxide; Preferably, the lurasidone hydrochloride sublingual or buccal film comprises: 40% lurasidone hydrochloride, 47% polyoxyethylene N80 and hydroxypropyl methylcellulose LM, 7% polyethylene glycol 400, 5% neotame, and 1% titanium dioxide.

8. A method for preparing a lurasidone hydrochloride sublingual or buccal film as described in any one of claims 1-7, characterized in that, Includes the following steps: S1: The raw material lurasidone hydrochloride is homogenized to form a lurasidone hydrochloride suspension with a particle size ≤10μm; S2: Mix the lurasidone hydrochloride suspension with the other components of the lurasidone hydrochloride sublingual or buccal film preparation evenly; S3: Apply the coating liquid.

9. The preparation method according to claim 8, characterized in that, In step S1, the homogenization time is 20-60 minutes, for example, 30 minutes; And / or, in step S2, the mixing method is stirring, preferably, the stirring time is 1 to 2 hours; And / or, in step S2, after mixing, a vacuum degassing step is further included to obtain the coating liquid; And / or, in step S3, the coating thickness is 0.3mm to 0.6mm, for example 0.5mm; And / or, after step S3, there are also steps of drying and cutting; preferably, the drying temperature is 60 to 120°C, for example 80°C.

10. The use of lurasidone hydrochloride sublingual or buccal film as described in any one of claims 1 to 7 in the preparation of sublingual or buccal film pharmaceutical formulations.

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