Pharmaceutical composition containing lurasidone hydrochloride

Abstract

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a lurasidone hydrochloride-containing pharmaceutical composition and a preparation method thereof, the pharmaceutical composition further comprises a film-forming material and a plasticizer, and the film-forming material comprises polyvinyl alcohol. The pharmaceutical composition and the lurasidone hydrochloride oral instant film prepared from the pharmaceutical composition provided by the invention have in-vivo bioavailability equivalent to that of commercially available tablets, can be quickly disintegrated in the oral cavity without water, have good taste and bring convenience to clinical use. In addition, the device also has good stability and is convenient for production management. In addition, the lurasidone hydrochloride oral instant film provided by the invention is high in drug loading capacity, thin in thickness, small in tablet weight, excellent in mechanical property, convenient to produce and transport, beneficial to improving the specification of the film agent and good in social benefit.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical preparations, and particularly relates to a pharmaceutical composition containing lurasidone hydrochloride, and more particularly to an orally disintegrating film of lurasidone hydrochloride and a preparation method thereof. Background Art

[0002] Schizophrenia is a group of chronic diseases with unknown etiology, mostly occurring slowly or subacutely in young and middle-aged people, accompanied by disorders in multiple aspects such as perception, thinking, emotion and behavior, as well as disharmony of mental activities. The course of the disease is generally protracted, showing a trend of repeated attacks, aggravation or deterioration. Some patients experience mental activity decline and varying degrees of social function impairment, accounting for more than half of the inpatients in the department of psychiatry, bringing a serious burden to society, patients and their families.

[0003] Lurasidone hydrochloride is a second-generation antipsychotic drug and a first-line drug recommended by the World Federation of Societies of Biological Psychiatry (WFSBP) Schizophrenia Biological Treatment Guidelines. Compared with other existing antipsychotic drugs, lurasidone hydrochloride has a unique chemical structure, and has antagonistic effects on dopamine D2 receptor, 5-hydroxytryptamine (5-HT2A) receptor and 5-hydroxytryptamine (5-HT7) receptor. Its efficacy is comparable to that of the same kind, and the effect of improving cognitive function is better than that of quetiapine, and it has almost no effect on metabolism such as body weight, blood lipid, blood sugar and QT interval, having a safety advantage.

[0004] Currently, the clinical dosage form of lurasidone hydrochloride is ordinary tablets, but the disintegration speed of ordinary tablets is slow, and they need to be swallowed with water, resulting in inapplicability to children and elderly patients, and it is not convenient for patients to take without water.

[0005] In addition, ordinary tablets of antipsychotic drugs can cause esophageal motility disorders and aspiration, thus triggering aspiration pneumonia, which is a common cause of death in elderly patients, especially those with Alzheimer's disease. During the acute phase of schizophrenia patients, they often refuse to take medicine, hide medicine and spit out medicine in the mouth, and the problem of medication compliance is widespread. Therefore, dosage forms such as tablets and capsules often cannot play a role in schizophrenia patients, and it is necessary to consider providing a dosage form that is easy to use. In view of this, it is necessary to provide a new preparation that is convenient to use, has good compliance and stable quality to solve the above problems.

[0006] Oral disintegrating films are thin films prepared by loading effective ingredients of a certain dose of chemical drugs or traditional Chinese medicine extracts into a film-forming material. After being placed on the tongue, they can quickly dissolve and release the drug without the need to drink water. Since the oral disintegrating film can quickly dissolve on the tongue, there is no need to worry about choking or inhalation when patients take the medicine, nor about patients hiding or spitting out the medicine, which greatly improves the medication compliance and convenience of patients. It is especially suitable for children and the elderly, and can effectively reduce the clinical nursing cost.

[0007] Chinese patent application CN202110062769.6 discloses a lurasidone hydrochloride oral disintegrating film, which contains lurasidone hydrochloride, a highly water-soluble film-forming material, a plasticizer, a surfactant, a stabilizer, a flavoring agent, and a light-blocking agent. This patent application provides an orally disintegrating film that can quickly disintegrate in the oral cavity without water. However, this patent application only studied the in vitro dissolution of the drug, and did not further test the bioavailability in the human body. In addition, the prescription disclosed in this patent application contains a light-blocking agent, a stabilizer, and a surfactant, and the prescription components are relatively complex, which is not conducive to actual production management.

[0008] Although there are currently studies on new dosage forms of lurasidone hydrochloride, they still cannot be said to be sufficient, and there is still room for development of oral preparations of lurasidone hydrochloride. Summary of the Invention

[0009] Problems to be Solved by the Invention

[0010] Lurasidone hydrochloride belongs to BCS class II drugs, which are poorly soluble and highly permeable drugs, with obvious bitterness. Moreover, the specific surface area of the raw material after being crushed is large, the volume is large, and the hydrophobicity is strong. In addition, lurasidone hydrochloride, as an active pharmaceutical ingredient (API), has a relatively large specification in the preparation, which results in the dosage form used clinically being tablets and the tablet weight being relatively large. However, the disintegration speed of tablets is slow and the onset time is relatively long. Schizophrenia patients generally have problems such as refusal to take medicine, hiding medicine under the tongue, and spitting out medicine, with poor compliance, and it is difficult to achieve the therapeutic effect of the drug by taking ordinary tablets. These reasons all limit its wide clinical use. If it is developed into a dosage form suitable for schizophrenia patients to take clinically, not only the problems of low in vitro dissolution rate, low drug loading, and poor taste after rapid disintegration in the oral cavity need to be solved, but also its bioavailability in the human body needs to be improved, which has great technical difficulties.

[0011] Currently, the prior art has studied different types of tablets of lurasidone hydrochloride, but it still cannot be said to be sufficient. For example:

[0012] Existing ordinary tablets still need to be swallowed with water. They have a slow disintegration speed and a long onset time. Moreover, schizophrenic patients generally have problems such as refusing to take medicine, hiding medicine under the tongue, and spitting out medicine, which makes it difficult to achieve the therapeutic effect of drugs in schizophrenic patients with poor compliance. In addition, ordinary tablets can cause esophageal motility disorders and aspiration, posing certain risks.

[0013] Although existing technologies such as the above-mentioned patent application CN202110062769.6 provide a more convenient-to-use orally disintegrating film dosage form, they only explore the in vitro dissolution of drugs and do not further verify the bioavailability in the human body. The inventors of the present application believe that existing technologies improve the dissolution of drugs by adding surfactants. However, the bioavailability of drugs in the human body is related not only to dissolution but also to permeability, etc. The addition of surfactants may also lead to a decrease in permeability. Therefore, simply increasing dissolution by adding surfactants may instead result in a lower in vivo bioavailability. At the same time, the addition of a large amount of surfactants is also likely to increase gastrointestinal reactions when taking the orally disintegrating film of lurasidone hydrochloride. Moreover, in the film agent provided in this literature, the average particle size of the lurasidone hydrochloride raw material is controlled below 100 μm, and it may be difficult to obtain the desired rapid dissolution. The above problems may all lead to the fact that the orally disintegrating film provided by this existing technology cannot achieve the desired high bioavailability. In addition, light-shielding agents, stabilizers, and surfactants are added to the existing orally disintegrating film formulations, resulting in complex prescription components and being unfavorable for production management. Whether the above several components must be added remains to be further studied.

[0014] Aiming at the problems existing in the above-mentioned existing technologies, the present invention aims to develop an oral preparation of lurasidone hydrochloride that can clinically replace the administration of ordinary tablets, has a bioavailability in the body equivalent to or higher than that of commercially available tablets, can rapidly disintegrate in the oral cavity without water, and improves the compliance of schizophrenic patients.

[0015] Solutions for Solving the Problems

[0016] [1]. A pharmaceutical composition, which comprises lurasidone hydrochloride, a film-forming material, and a plasticizer, wherein the film-forming material comprises polyvinyl alcohol.

[0017] [2]. The pharmaceutical composition according to [1], wherein the film-forming material further comprises at least one of a polyvinyl alcohol-polyethylene glycol copolymer, hypromellose, polyvinylpyrrolidone, hydroxypropyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, and ethyl cellulose.

[0018] [3]. The pharmaceutical composition according to [1] or [2], wherein the particle size D of the lurasidone hydrochloride 90 ≤10 μm; and / or, the pharmaceutical composition does not contain a surfactant.

[0019] [4]. The pharmaceutical composition according to any one of [1] to [3], wherein, by mass percentage, the content of the film-forming material in the pharmaceutical composition is 25% to 50%.

[0020] [5]. The pharmaceutical composition according to any one of [2] to [4], wherein, by mass percentage, the content of the polyvinyl alcohol in the film-forming material is 30% to 100%.

[0021] [6]. The pharmaceutical composition according to any one of [1] to [5], wherein the plasticizer comprises at least one of dihydric alcohols, polyhydric alcohols, fatty acids, fatty acid glycerides and phthalates.

[0022] [7]. The pharmaceutical composition according to any one of [1] to [6], wherein the plasticizer comprises at least one of glycerol, polyethylene glycol, sorbitol, polysorbate, xylitol, maltitol, propylene glycol, diethyl phthalate, dimethyl phthalate and dibutyl phthalate.

[0023] [8]. The pharmaceutical composition according to any one of [1] to [7], wherein the plasticizer is any one or a combination of more than one of glycerol, polyethylene glycol, sorbitol, polysorbate, xylitol, maltitol and propylene glycol.

[0024] [9]. The pharmaceutical composition according to any one of [1] to [8], wherein, by mass percentage, the content of the plasticizer in the pharmaceutical composition is 10% to 20%.

[0025]

[10] . The pharmaceutical composition according to any one of [1] to [9], wherein the plasticizer comprises polyethylene glycol and glycerol.

[0026]

[11] . The pharmaceutical composition according to

[10] , wherein the mass ratio of the polyethylene glycol to the glycerol is (1.5 to 5):1.

[0027]

[12] . The pharmaceutical composition according to any one of [1] to

[11] , wherein the pharmaceutical composition further comprises a flavoring agent.

[0028]

[13] . The pharmaceutical composition according to

[12] , wherein the flavoring agent comprises at least one of a sweetening agent, an acidifying agent and a fragrance.

[0029]

[14] . The pharmaceutical composition according to

[12] or

[13] , wherein the flavoring agent comprises at least one of sucralose, menthol, sucrose, sodium saccharin, stevioside, aspartame, mint essence, cherry essence, strawberry essence, milk essence, chocolate essence, grape essence, sweet orange essence, mixed berry essence, citric acid and tartaric acid.

[0030]

[15] . The pharmaceutical composition according to any one of

[12] to

[14] , wherein, by mass percentage, the content of the flavoring agent in the pharmaceutical composition is 0.5% to 3%.

[0031]

[16] . The pharmaceutical composition according to any one of [1] to

[15] , wherein the pharmaceutical composition does not contain a stabilizer and a light-shielding agent.

[0032]

[17] . An orally disintegrating film of lurasidone hydrochloride, wherein the orally disintegrating film of lurasidone hydrochloride is prepared from the pharmaceutical composition according to any one of [1] to

[16] .

[0033]

[18] . The orally disintegrating film of lurasidone hydrochloride according to

[17] , wherein the drug loading of the orally disintegrating film of lurasidone hydrochloride is greater than 40%, and the tablet weight is less than 100 mg.

[0034]

[19] . The preparation method of the orally disintegrating film of lurasidone hydrochloride according to

[17] or

[18] , wherein the method comprises the following steps: adding a plasticizer and an optional flavoring agent into a solvent, mixing evenly, adding lurasidone hydrochloride and a film-forming material, mixing evenly, exhausting, and drying to obtain; wherein the solvent is an aqueous solution of a volatile organic solvent.

[0035]

[20] . The preparation method according to

[19] , wherein the volatile organic solvent comprises ethanol.

[0036]

[21] . Use of the pharmaceutical composition according to any one of [1] to

[16] or the orally disintegrating film of lurasidone hydrochloride according to

[17] or

[18] in the preparation of a drug for treating schizophrenia.

[0037] Effects of the Invention

[0038] By implementing the above technical solutions, the present invention has achieved the following beneficial effects:

[0039] First of all, the present invention provides a pharmaceutical composition and a orally disintegrating film of lurasidone hydrochloride prepared therefrom, which simultaneously achieve the equivalent in vivo bioavailability to the commercially available tablets, can rapidly disintegrate in the oral cavity without water, and have a good taste and other effects. When the orally disintegrating film of lurasidone hydrochloride provided by the present invention is clinically used, there is no need to worry about the problem of patients' dysphagia, nor worry about the schizophrenia patients hiding or spitting out the medicine, which greatly improves the compliance of patients' medication and the effectiveness of treatment, and is particularly suitable for pediatric and geriatric patients' medication, reducing the clinical nursing cost.

[0040] Secondly, in the pharmaceutical composition provided by the present invention and the orally disintegrating film of lurasidone hydrochloride prepared therefrom, the particle size D of lurasidone hydrochloride 90 ≤10 μm. Due to the relatively fine particle size, the film agent provided by the present invention has both a faster in vitro dissolution and a bioavailability equivalent to that of the commercially available tablets.

[0041] Moreover, in the pharmaceutical composition provided by the present invention and the orally disintegrating film of lurasidone hydrochloride prepared therefrom, without adding surfactants, stabilizers and light-shielding agents, it can achieve a rapid in vitro dissolution and an in vivo bioavailability equivalent to that of the commercially available tablets, and can obtain good stability, be suitable for long-term storage, and be convenient for production management. And after the patients take it, it is not easy to produce side effects such as nausea and vomiting.

[0042] In addition, the orally disintegrating film of lurasidone hydrochloride provided by the present invention has a high drug loading (the proportion of API can reach more than 40%, even up to about 60%), a thin thickness (can be lower than 100 μm, even lower than 80 μm, such as about 78 μm), a small tablet weight (can be lower than 100 mg, even can be lower than 70 mg, such as about 67 mg), is small, light and portable, is not easy to be brittle, has excellent mechanical properties, is convenient for transportation during the production process, increases the production batch so as to further reduce the production cost. At the same time, the single-piece independent packaging and anti-folding property are more convenient for patients to carry around, providing great convenience for patients in use. At the same time, it is beneficial to improve the film agent specifications and has good social benefits.

[0043] Meanwhile, the present invention also provides a preparation method of the above-mentioned orally disintegrating film of lurasidone hydrochloride, which has simple operation and is easy to scale up production. Description of the Drawings

[0044] Figure 1 It is the dissolution curves of Example 7, Comparative Example 7 and commercially available tablets in the dissolution medium (hydrochloric acid solution with pH 1.2).

[0045] Figure 2 It is the dissolution curves of Example 7, Comparative Example 7 and commercially available tablets in the dissolution medium (citric acid-phosphate buffer solution with pH 4.0).

[0046] Figure 3Dissolution curves of Example 7, Comparative Example 7, and commercially available tablets in a dissolution medium (phosphate buffer solution at pH 6.8 + 0.1 wt% SDS).

[0047] Figure 4 Dissolution curves of Example 7, Comparative Example 7, and commercially available tablets in a dissolution medium (water + 0.2 wt% SDS). Detailed implementation manners

[0048] The following describes the implementation manners of the present invention, but the present invention is not limited thereto. The present invention is not limited to the various components described below. Various changes can be made within the scope claimed in the invention. Embodiment modes and embodiments obtained by appropriately combining the technical means respectively disclosed in different embodiment modes and embodiments are also included in the technical scope of the present invention.

[0049] In the present invention, a numerical range represented by "numerical value A to numerical value B" or "numerical value A - numerical value B" refers to a range including the end point numerical values A and B.

[0050] In the present invention, the meaning represented by "may" includes both the meaning of performing a certain process and the meaning of not performing a certain process.

[0051] In the present invention, "optional" or "optionally" means that the subsequent described event or situation may or may not occur, and this description includes the situation where the event occurs and the situation where the event does not occur.

[0052] In the present invention, the term "a" or "an" or "the" may mean "one", or may also mean "one or more", "at least one", and "one or more than one".

[0053] In the present invention, the terms "comprising", "having", "including", or "containing" may mean inclusive or open-ended, and do not exclude additional, unrecited elements or method steps. At the same time, "comprising", "having", "including", or "containing" may also mean closed-ended, excluding additional, unrecited elements or method steps.

[0054] In the present invention, the term "about" may mean: a value includes the standard error or standard deviation of the device or method used to measure the value. The numerical ranges and parameters defining the present invention are all approximate numerical values, and the relevant numerical values in the specific embodiments have been presented as precisely as possible here. However, any numerical value inevitably contains the standard deviation caused by the aforementioned test device or method. Therefore, unless otherwise clearly stated, it should be understood that all ranges, quantities, numerical values, and percentages used in the present invention are modified by "about". Here, "about" generally means that the actual numerical value is within ±5%, ±3%, ±1%, or ±0.5% of a certain specific numerical value or range.

[0055] In the present invention, the "water" includes any feasible water that can be used in the art, such as deionized water, distilled water, ion-exchanged water, double-distilled water, high-purity water, purified water, water for injection, etc.

[0056] In addition, unless otherwise defined, other technical and scientific terms used in the present invention have the same meanings as those commonly understood by those of ordinary skill in the technical field to which the present invention pertains.

[0057] The technical solutions of the present invention are further specifically described as follows:

[0058] Drug Composition and Oral Disintegrating Film of Lurasidone Hydrochloride Prepared therefrom

[0059] First, the present invention provides a pharmaceutical composition, which comprises lurasidone hydrochloride, a film-forming material, and a plasticizer. At the same time, the present invention also provides an orally disintegrating film of lurasidone hydrochloride prepared from the above pharmaceutical composition.

[0060] In order to form a good orally disintegrating film of lurasidone hydrochloride, the present invention has studied the film-forming material in the pharmaceutical composition.

[0061] In some embodiments, the film-forming material comprises polyvinyl alcohol; optionally, the film-forming material further comprises at least one of a polyvinyl alcohol-polyethylene glycol copolymer, hypromellose, povidone, hydroxypropyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, and ethyl cellulose.

[0062] In some specific embodiments, the film-forming material is a combination of polyvinyl alcohol, a combination of polyvinyl alcohol and a polyvinyl alcohol-polyethylene glycol copolymer, a combination of polyvinyl alcohol and hypromellose, a combination of polyvinyl alcohol and povidone, a combination of polyvinyl alcohol and hydroxypropyl cellulose, a combination of polyvinyl alcohol and sodium carboxymethyl cellulose, a combination of polyvinyl alcohol and methyl cellulose, or a combination of polyvinyl alcohol and ethyl cellulose.

[0063] In some preferred embodiments, the film-forming material is polyvinyl alcohol, a combination of polyvinyl alcohol and a polyvinyl alcohol-polyethylene glycol copolymer, a combination of polyvinyl alcohol and hypromellose, or a combination of polyvinyl alcohol and povidone.

[0064] The present invention does not particularly limit the molecular weights of polymers such as polyvinyl alcohol, polyvinyl alcohol - polyethylene glycol copolymer, and povidone, and those skilled in the art can select according to actual needs. In some specific embodiments, polyvinyl alcohol with a molecular weight of 20,000 Da to 220,000 Da can be selected, such as 20,000 Da, 25,000 Da, 30,000 Da, 35,000 Da, 120,000 Da, 130,000 Da, 140,000 Da, 200,000 Da, 210,000 Da, 220,000 Da, and polyvinyl alcohol with a molecular weight of 20,000 Da to 35,000 Da is preferably used. In some specific embodiments, polyvinyl alcohol - polyethylene glycol copolymer with a molecular weight of 40,000 Da to 50,000 Da can be selected, such as 40,000 Da, 45,000 Da, 50,000 Da. In some specific embodiments, povidone with a molecular weight of 25,000 Da to 1,500,000 Da can be selected, such as 25,000 Da, 28,000 Da, 30,000 Da, 34,000 Da, 50,000 Da, 400,000 Da, 1,000,000 Da, and povidone with a molecular weight of 28,000 Da to 34,000 Da is preferably used.

[0065] In some embodiments, by mass percentage, the content of the film - forming material in the pharmaceutical composition or the orally disintegrating film of lurasidone hydrochloride prepared therefrom is 25% to 50%, such as about 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49% or 50%, etc.; preferably 25% to 45%.

[0066] In some embodiments, by mass percentage, the content of the polyvinyl alcohol in the film - forming material is 30% to 100%. Such as about 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100%, etc.; preferably 40% to 100%.

[0067] Polyvinyl alcohol has good film-forming properties. The film agents prepared by using it alone as a film-forming material or in combination with at least one of polyvinyl alcohol-polyethylene glycol copolymer, hypromellose, povidone, hydroxypropyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, and ethyl cellulose (wherein polyvinyl alcohol accounts for 30% - 100% of the total mass of the film-forming material) all have good disintegration properties and toughness. However, when any one of polyvinyl alcohol-polyethylene glycol copolymer, hypromellose, povidone, hydroxypropyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, and ethyl cellulose is used alone, the resulting film agent has poor toughness and is difficult to form a film.

[0068] Furthermore, the present invention has found through research that in existing orally disintegrating films of lurasidone hydrochloride, surfactants are usually added to improve the in vitro dissolution rate of the drug. However, the surfactants simultaneously lead to a decrease in the drug permeability, ultimately resulting in a relatively low bioavailability of the drug in vivo. To address this problem, the present invention has conducted extensive research and found that:

[0069] Since lurasidone hydrochloride is a poorly soluble drug, particle size has a significant impact on its in vitro dissolution, further affecting its dissolution rate in the human body and ultimately its bioavailability in the human body. Through the investigation of the dissolution curves of the film agents prepared from raw materials with different particle sizes in the present invention, it is found that when the particle size D of the raw material 90 ≤10 μm, the dissolution degree of the resulting film agent at 15 min > 85%, belonging to very rapid dissolution. Therefore, in some embodiments, in the pharmaceutical composition provided by the present invention and the orally disintegrating film of lurasidone hydrochloride prepared therefrom, the particle size D of the lurasidone hydrochloride 90 ≤10 μm.

[0070] The pharmaceutical composition provided by the present invention and the orally disintegrating film of lurasidone hydrochloride prepared therefrom do not contain surfactants. While achieving rapid in vitro dissolution of the drug, it has an in vivo bioavailability comparable to that of commercially available tablets. Comparing the pharmacokinetic parameters of the orally disintegrating film of lurasidone hydrochloride provided by the present invention with those of commercially available tablets, the experimental data show that the geometric means and their 90% confidence intervals of C max , AUC 0-t and AUC 0-∞ of the orally disintegrating film of lurasidone hydrochloride provided by the present invention and commercially available tablets are all between 80% - 125%. Its bioavailability is consistent with that of commercially available preparations, and the two have bioequivalence.

[0071] Furthermore, in order to provide an orally disintegrating film of lurasidone hydrochloride with more excellent performance, the present invention has studied other components in the pharmaceutical composition.

[0072] Plasticizers can lower the glass transition temperature of the film agent and increase the elongation rate of the film agent when used in combination with the film-forming material, thereby improving the mechanical properties of the film agent. Therefore, the pharmaceutical composition provided by the present invention and the orally disintegrating film of lurasidone hydrochloride prepared therefrom contain plasticizers.

[0073] In some embodiments, the plasticizer comprises at least one of dihydric alcohols, polyhydric alcohols, fatty acids, fatty acid glycerides, and phthalates.

[0074] In some specific embodiments, the plasticizer comprises at least one of glycerol, polyethylene glycol, sorbitol, polysorbate, xylitol, maltitol, propylene glycol, diethyl phthalate, dimethyl phthalate, and dibutyl phthalate.

[0075] In some preferred embodiments, the plasticizer is any one or a combination of more than one of glycerol, polyethylene glycol, sorbitol, polysorbate, xylitol, maltitol, and propylene glycol.

[0076] In some embodiments, by mass percentage, the content of the plasticizer in the pharmaceutical composition or the orally disintegrating film of lurasidone hydrochloride prepared therefrom is 10% - 20%, such as about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%, etc.; preferably 10% - 16%.

[0077] Since lurasidone hydrochloride belongs to BCS class II drugs, only a very small part of the drug is dissolved and absorbed in the human body, resulting in low bioavailability. Therefore, while meeting rapid dissolution, it is also necessary to promote the penetration of lurasidone hydrochloride to a greater extent as much as possible, thereby improving its bioavailability in vivo. Therefore, in some preferred embodiments, the present invention selects dihydric alcohols and / or polyhydric alcohols (such as any one or a combination of more than one of glycerol, polyethylene glycol, sorbitol, polysorbate, xylitol, maltitol, and propylene glycol) that have good penetration-promoting effects as plasticizers to improve the absorption of the pharmaceutical composition of the present invention and the orally disintegrating film of lurasidone hydrochloride prepared therefrom in the intestine and improve bioavailability.

[0078] In some preferred embodiments, the plasticizer comprises polyethylene glycol and glycerol; preferably, the plasticizer is a combination of polyethylene glycol and glycerol. The present invention does not make a special limitation on the molecular weight of polyethylene glycol, and those skilled in the art can select according to actual needs. In some specific embodiments, polyethylene glycol with a molecular weight of 400 - 4000 can be selected, such as PEG400, PEG1000, PEG2000, and PEG4000. In some specific embodiments, PEG1000 can be selected.

[0079] From the perspective of improving the peelability and mechanical properties during the preparation of the orally disintegrating film of lurasidone hydrochloride, the mass ratio of the polyethylene glycol to the glycerol is (1.5 to 5):1, such as about 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1 or 5:1, etc.; preferably (1.5 to 4.5):1; more preferably (2 to 4):1; even more preferably (2.5 to 3.5):1.

[0080] The orally disintegrating film of lurasidone hydrochloride provided by the present invention can rapidly disintegrate in the oral cavity without drinking water, while lurasidone hydrochloride itself has an obvious bitter taste. In order to improve the poor taste after the rapid disintegration of the film in the oral cavity, in some embodiments, the pharmaceutical composition of the present invention and the orally disintegrating film of lurasidone hydrochloride prepared therefrom further contain a flavoring agent.

[0081] In some embodiments, the flavoring agent includes at least one of a sweetening agent, an acidifying agent, and a flavor.

[0082] In some specific embodiments, the flavoring agent includes at least one of sucralose, menthol, sucrose, sodium saccharin, stevioside, aspartame, mint flavor, cherry flavor, strawberry flavor, milk flavor, chocolate flavor, grape flavor, sweet orange flavor, mixed berry flavor, citric acid, and tartaric acid.

[0083] In some preferred embodiments, the flavoring agent is a combination of sucralose and menthol.

[0084] In some embodiments, by mass percentage, the content of the flavoring agent in the pharmaceutical composition or the orally disintegrating film of lurasidone hydrochloride prepared therefrom is 0.5% to 3%, such as about 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9% or 3.0%, etc.; preferably 1.0% to 2.5%. When the content of the flavoring agent is within the above range, the orally disintegrating film of lurasidone hydrochloride provided by the present invention has an excellent taste and is easy to accept.

[0085] In addition, in some embodiments, the pharmaceutical composition of the present invention and the orally disintegrating film of lurasidone hydrochloride prepared therefrom do not contain a stabilizer and a light-shielding agent, and good stability can be obtained, which can be stored for a long time, is convenient for production management, and at the same time, side effects such as nausea and vomiting are not easily generated after the patient takes it.

[0086] The existing orally disintegrating films of lurasidone hydrochloride have a tablet weight design of approximately 100 mg at the API specification of 40 mg. However, for the orally disintegrating films of lurasidone hydrochloride provided by the present invention, at the same specification, the use of pharmaceutical excipients is reduced. For example, by selecting film-forming materials and plasticizers with good performance, and without adding surfactants, stabilizers, light-shielding agents, etc., the drug loading is higher, the thickness is thinner, and the tablet weight is smaller. In some embodiments, the drug loading of the orally disintegrating film of lurasidone hydrochloride is greater than 40%, and can even reach approximately 60%. In some embodiments, the tablet weight of the orally disintegrating film of lurasidone hydrochloride is less than 100 mg, preferably less than 70 mg, such as approximately 67 mg. In some embodiments, the thickness of the orally disintegrating film of lurasidone hydrochloride is less than 100 μm, preferably less than 80 μm, such as approximately 78 μm.

[0087] Preparation Method of Oral Disintegrating Film of Lurasidone Hydrochloride

[0088] The present invention provides a method for preparing the above-mentioned orally disintegrating film of lurasidone hydrochloride, which comprises the following steps: adding a plasticizer and an optional flavoring agent to a solvent, mixing evenly, adding lurasidone hydrochloride and a film-forming material, mixing evenly, exhausting air, and drying to obtain the product.

[0089] In some specific embodiments, the method comprises the following steps: adding a plasticizer and a flavoring agent to a solvent, mixing evenly, adding lurasidone hydrochloride with a controlled particle size D 90 ≤10 μm and a film-forming material, mixing evenly, slowly exhausting air until the bubbles dissipate to obtain a slurry; coating the slurry on a pharmaceutical polyester film and drying to obtain the product.

[0090] The present invention does not particularly limit the means for controlling the particle size of lurasidone hydrochloride, and those skilled in the art can adjust it according to actual needs. For example, equipment such as a jet mill can be used for particle size control.

[0091] In order to better dissolve or disperse the various components of the orally disintegrating film of lurasidone hydrochloride, in some embodiments, the solvent is an aqueous solution of a volatile organic solvent; preferably, the volatile organic solvent includes ethanol.

[0092] In some embodiments, the addition of lurasidone hydrochloride with a controlled particle size D 90 ≤10 μm and a film-forming material is the addition of lurasidone hydrochloride with a controlled particle size D 90 ≤10 μm, polyvinyl alcohol, and an optional other film-forming material.

[0093] In order to avoid film-forming difficulties caused by the generation of bubbles, in some embodiments, the time for exhausting air can be controlled to be 2 - 3 h.

[0094] For the convenience of subsequent use of the lurasidone hydrochloride orally disintegrating film, in some embodiments, after the drying step, there are also steps of peeling and cutting.

[0095] Medical Use

[0096] In some embodiments, the pharmaceutical composition or the lurasidone hydrochloride orally disintegrating film provided by the present invention can be prepared into a drug for treating schizophrenia.

[0097] In some embodiments, the pharmaceutical composition or the lurasidone hydrochloride orally disintegrating film provided by the present invention can be used to treat schizophrenia.

[0098] In some embodiments, the present invention provides a method for treating schizophrenia, the method comprising administering a therapeutically effective amount of the pharmaceutical composition or the lurasidone hydrochloride orally disintegrating film to a patient.

[0099] The lurasidone hydrochloride orally disintegrating film provided by the present invention can rapidly disintegrate in the oral cavity without water, and has a good taste. There is no need to worry about schizophrenic patients hiding or spitting out the medicine, which greatly improves the patient's medication compliance and treatment effectiveness. It is especially suitable for children and the elderly, reducing the clinical nursing cost. At the same time, the lurasidone hydrochloride orally disintegrating film provided by the present invention does not contain various complex raw materials such as surfactants, stabilizers, and light-shielding agents, and it is not easy for patients to have side effects such as nausea and vomiting after taking it.

[0100] To more clearly describe the technical solutions of the present invention, the following further illustrates with specific examples and comparative examples, but it cannot be used to limit the present invention. These are only partial examples of the present invention. Any simple improvement to the present invention under the premise of the technical solutions of the present invention belongs to the protection scope of the present invention. Unless otherwise specified, the instruments, reagents, materials, experimental animals, etc. used in the present invention can be obtained through conventional commercial means. For those not specified in the examples, they are carried out according to conventional conditions or the conditions recommended by the manufacturer.

[0101] The quality evaluation methods used in the experimental examples of the present invention are as follows:

[0102] 1. Disintegration time limit

[0103] Using a vibrating water bath device, place the sample in a petri dish containing 20 ml of pH 6.8 PBS at a temperature of (37 ± 0.5) °C, with a shaking speed of 70 r / min, and record the time when the sample completely disintegrates as the disintegration time limit, and record the longest disintegration time.

[0104] 2. Dissolution curve

[0105] Perform a dissolution test on the preparation prepared by the present invention, and the dissolution method is as follows:

[0106] Dissolution method: The second method (paddle method) in the Chinese Pharmacopoeia (2020 Edition);

[0107] Rotation speed: 50 rpm;

[0108] Media: Hydrochloric acid solution with pH 1.2, citrate - phosphate buffer with pH 4.0, phosphate buffer with pH 6.8 + 0.1 wt% SDS, water + 0.2 wt% SDS;

[0109] Volume of media: 900 ml;

[0110] Sampling time (min): 5, 10, 15, 20, 30, 45, 60.

[0111] 3. Mechanical properties

[0112] The following method is used to determine the toughness, tensile strength, and percentage elongation of the film - agent prepared by the present invention.

[0113] (1) Toughness: After folding the film - agent, place it on a polyethylene plate, add a 500 - g metal weight on it and keep it for 2 s, fold it repeatedly for many times until it breaks, record the number of folds (if it does not break after 10 folds, no more folding is carried out). The level is divided into 3 options. Poor toughness: Easy to be brittle and break when folded in half twice; Good toughness: Can be folded in half 3 times and break when folded in half 4 times; Excellent toughness: Can be folded in half more than 5 times without breaking.

[0114] (2) Tensile strength: It is measured using a universal material testing machine. Clamp the film with 2 clips and keep it in a vertical state, stretch it at a speed of 300 mm / min, record the external stress (load) borne by the pharmaceutical film when it breaks. Tensile strength = external stress (load) / cross - sectional area of the pharmaceutical film.

[0115] (3) Percentage elongation: It is measured using a universal material testing machine. Clamp the film with 2 clips and keep it in a vertical state, record the length of the pharmaceutical film between the 2 clips at this time (original length), stretch it at a speed of 300 mm / min, record the displacement length (increase in length) of the 2 clips when the pharmaceutical film breaks. Percentage elongation = increase in length / original length × 100%.

[0116] 4. Taste evaluation

[0117] Take the film agent prepared by the present invention. After the subject rinses the mouth with an appropriate amount of water, place 1 tablet of this product on the tongue. There is no need to drink water, chew, or swallow. Wait until the film agent is completely softened or dissolved by saliva, then spit it out, rinse the mouth, and record the disintegration time limit in the oral cavity and the taste. Use the presence or absence of bitterness and astringency, the presence or absence of sweetness, the presence or absence of a gritty feeling, the disintegration time limit, and the overall taste evaluation as the investigation indicators. In the overall taste evaluation, it is divided into four options: very good (≥90 points), better (≥75 points and <90 points), average (≥60 points and <75 points), and poor (<60 points).

[0118] 5. Peelability

[0119] Peelability refers to the ease of peeling the medicinal film from the carrier film. Appropriate peelability can ensure the smoothness of the cutting and packaging process in the next process and ensure that the medicinal film can be smoothly peeled from the carrier film. Use the ease of manually peeling the medicinal film from the carrier film as the evaluation standard for the peelability of this variety, which is divided into difficult to peel: the film agent is very difficult to tear off from the PET film and may even be torn, and the adhesion between the film agent and the PET film is very large; moderate peelability: the film agent can be completely peeled from the PET film, and the adhesion is moderate; easy to peel: the film agent is very easy to tear off from the PET film and may even peel off from the PET film by itself, and the adhesion is small.

[0120] Examples 1 to 4:

[0121] Table 1 Prescriptions of Examples 1 to 4

[0122]

[0123] Note: [1-2] Purified water and ethanol are solvents used in the process and finally removed.

[0124] Preparation processes of Examples 1 to 4: Take ziprasidone hydrochloride and pulverize it with an air-flow pulverizer, and control the D 90 of ziprasidone hydrochloride after pulverization ≤10 μm; stir and mix purified water and ethanol evenly, add glycerol, polyethylene glycol, sucralose, and menthol, stir and homogenize until evenly dispersed, then add ziprasidone hydrochloride, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol copolymer, or hydroxypropyl methylcellulose, or polyvinylpyrrolidone, stir and homogenize to make it evenly dispersed, and then slowly stir for 2 - 3 h to dissipate the bubbles to obtain a slurry; coat the prepared slurry on a medicinal polyester film with a coating frame, dry it in an oven, then peel the medicinal film from the polyester film, and cut it into a size of 3×2 cm 2 to obtain.

[0125] Comparative Examples 1 to 3:

[0126] Table 2 Prescriptions of Comparative Examples 1 to 3

[0127]

[0128] Note:[1-2] Purified water and ethanol are solvents used in the process and finally removed.

[0129] Preparation processes of Comparative Examples 1 - 3: The same as the prescription process in Table 1.

[0130] Experimental Example 1:

[0131] Appearance, mechanical properties, and disintegration time limit of the samples of Examples 1 - 4 and Comparative Examples 1 - 3 were studied, and the data are shown in the following table:

[0132] Table 3 Comparison results of appearance, mechanical properties, and disintegration time limit of the samples of Examples 1 - 4 and Comparative Examples 1 - 3

[0133]

[0134] The above experimental results show that the orally disintegrating films prepared by using polyvinyl alcohol alone as the film - forming material or in combination with polyvinyl alcohol - polyethylene glycol copolymer, hypromellose, and povidone have good appearance and mechanical properties, and can completely disintegrate within 60 s; however, when using polyvinyl alcohol - polyethylene glycol copolymer, hypromellose, and povidone alone, the prepared orally disintegrating films have poor toughness and are difficult to form films.

[0135] Examples 5 - 6 and Comparative Examples 4 - 5:

[0136] Table 4 Prescriptions of Examples 5 - 6 and Comparative Examples 4 - 5

[0137]

[0138] Note: [1-2] Purified water and ethanol are solvents used in the process and finally removed.

[0139] Preparation processes of Examples 5 - 6 and Comparative Examples 4 - 5: Take lurasidone hydrochloride and crush it to obtain lurasidone hydrochloride with different particle sizes; stir and mix purified water and ethanol evenly, add glycerol, polyethylene glycol, sucralose, and menthol, stir and homogenize until evenly dispersed, then add lurasidone hydrochloride and polyvinyl alcohol, stir and homogenize to make it evenly dispersed, and then slowly stir for 2 - 3 h to dissipate bubbles to obtain a slurry; coat the prepared slurry on a medicinal polyester film using a coating frame, after drying in an oven, peel the drug film from the polyester film, and cut it into a size of 3×2 cm 2 That is how to obtain it.

[0140] Experimental Example 2:

[0141] Appearance and dissolution curves (the medium is citric acid - phosphate buffer solution with pH 4.0) of the samples of Examples 5 - 6 and Comparative Examples 4 - 5 were studied, and the data are shown in the following table:

[0142] Table 5 Comparison results of the appearance and dissolution curves of the samples in Examples 5-6 and Comparative Examples 4-5

[0143]

[0144] The above experimental results show that the appearance of the films prepared from raw materials with different particle sizes in Examples 5-6 and Comparative Examples 4-5 all meet the expectations. When the particle size of the raw material is selected as 99.781 μm as described in the reference patent application CN202110062769.6, the dissolution rate at 60 min is only 56.1%, and it is difficult to dissolve; while the dissolution rate of the films obtained in Examples 5-6 at 15 min > 85%. Therefore, the particle size of the raw material is controlled to D 90 ≤10 μm.

[0145] Examples 7-9 and Comparative Example 6:

[0146] Table 6 Formulations of Examples 7-9 and Comparative Example 6

[0147]

[0148] Note: [1-2] Purified water and ethanol are solvents used in the process and finally removed.

[0149] The preparation processes of Examples 7-9 and Comparative Example 6: The same as Example 5.

[0150] Experimental Example 3:

[0151] The appearance, mechanical properties, disintegration time limit, and peelability of the samples in Examples 7-9 and Comparative Example 6 were studied, and the data are shown in the following table:

[0152] Table 7 Comparison results of the appearance, mechanical properties, disintegration time limit, and peelability of the samples in Examples 7-9 and Comparative Example 6

[0153]

[0154] The above data indicate that when the ratio of polyethylene glycol to glycerol is 1.5:1 - 4.5:1, the obtained films have excellent appearance and mechanical properties and moderate peelability. However, when only glycerol is added to the formulation, the obtained films are difficult to peel.

[0155] Meanwhile, in the orally disintegrating films of lurasidone hydrochloride provided in Examples 7 to 9, the drug loading (the calculation formula is: drug loading (%) = weight of API in the film / weight of the film (excluding ethanol and purified water) × 100%) can reach about 60%. At high drug loadings, the tablet weight of the film is smaller, and when the film area is fixed, the thickness is also thinner, and the disintegration is faster. At the same time, the reduction in the amount of excipients effectively reduces the production cost. The maximum daily dose of lurasidone hydrochloride is 80 mg. At high drug loadings, the number of times patients take the medicine can be reduced, improving patient compliance. And at high drug loadings, the stability, tolerance, etc. of the film are all good, proving that the formulation provided by the present invention can tolerate a high proportion of API.

[0156] Comparative Example 7:

[0157] Reproduce the prescription process described in Example 3 of patent application CN202110062769.6 to prepare the orally disintegrating film of lurasidone hydrochloride (Comparative Example 4), and the prescription and preparation process are as follows.

[0158] Table 8 Prescription of Comparative Example 7

[0159]

[0160] Note: [1] Purified water is the solvent used in the process and finally removed.

[0161] Preparation process of Comparative Example 7: Crush lurasidone hydrochloride, control D 90 <100 μm, and set aside; disperse hypromellose in purified water at 70 - 90 °C, and cool to room temperature for later use; add lurasidone hydrochloride, glycerol, poloxamer, disodium edetate, sucralose, and titanium dioxide to the above hypromellose solution, stir and homogenize to obtain a light yellow emulsion; after ultrasonic defoaming of the above obtained light yellow emulsion, coat it on a medicinal polyester film using a coating frame, dry it in an oven, peel the drug film from the polyester film, and cut it into 3 × 2 cm 2 size to obtain the orally disintegrating film preparation of lurasidone hydrochloride.

[0162] Experimental Example 4:

[0163] Compare the orally disintegrating film of lurasidone hydrochloride prepared in Example 7 with the orally disintegrating film of lurasidone hydrochloride prepared in Comparative Example 7 and the commercially available tablets in terms of taste, disintegration time limit, dissolution curve, stability, and in vivo pharmacokinetics, etc., and the results are as follows.

[0164] Table 9 Comparison results of the physicochemical properties of Example 7, Comparative Example 7, and commercially available tablets

[0165]

[0166] As can be seen from the results in Table 9, the lurasidone hydrochloride orally disintegrating film provided by the present invention has the following advantages compared with the commercially available tablets: ① It can disintegrate rapidly and has an excellent taste. At the same time, it can avoid the problems of drug hiding, spitting by schizophrenia patients, and swallowing difficulties in children or elderly patients, greatly improving the compliance of clinical drug administration; ② It is small, light, and has excellent mechanical properties, making it easy for patients to carry around.

[0167] The comparison results of the dissolution curves of Example 7, Comparative Example 7, and the commercially available tablets are as Figures 1 to 4 shown. It can be seen that the dissolution curves of Example 7 and Comparative Example 7 in four dissolution media, namely hydrochloric acid solution at pH 1.2, citrate-phosphate buffer at pH 4.0, phosphate buffer at pH 6.8 + 0.1 wt% SDS, and water + 0.2 wt% SDS, are similar to those of the commercially available tablets or have a faster dissolution rate than the commercially available tablets.

[0168] The research method for the pharmacokinetics of the preparation in the human body is as follows:

[0169] A randomized, open-label, single-dose, three-sequence, three-period, three-way crossover trial design was adopted. A total of 12 healthy subjects aged 18 - 45 years were randomly divided into three groups, with 4 people in each group. They were respectively subjected to 3-cycle trials. After oral administration of Example 7 (without water), Comparative Example 7 (without water), and the commercially available tablets (with water) under postprandial conditions, samples were collected, and the washout period was 7 days.

[0170] Sampling design: Approximately 4 mL of venous blood was collected at 15 min, 30 min, 45 min, 1 h, 1.5 h, 2.0 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, and 24 h after drug administration, and the plasma was separated by centrifugation.

[0171] The postprandial pharmacokinetic results are shown in Table 10.

[0172] Table 10 Summary of plasma pharmacokinetic parameters in the postprandial trial

[0173] Group Commercially Available Tablets Example 7 Comparative Example 7 <![CDATA[t 1 / 2 (h)]]> 22.08±21.14 21.67±14.16 18.25±15.01 <![CDATA[T max (h)]]> 1.33(0.67，2.33) 1.33(0.67，2.33) 1.48(0.65，2.68) <![CDATA[C max (ng / ml)]]> 42.46±23.14 39.64±20.25 29.56±24.39 <![CDATA[AUC 0-t (h·ng / mL)]]> 141.74±73.74 137.57±67.29 131.21±79.27 <![CDATA[AUC 0-∞ (h·ng / mL)]]> 157.30±88.72 153.86±76.35 147.28±90.64

[0174] Table 11 Equivalence evaluation of the main pharmacokinetic parameters between Example 7 and the commercially available tablets in the postprandial trial

[0175]

[0176] Table 12 Equivalence evaluation of the main pharmacokinetic parameters between Comparative Example 7 and the commercially available tablets in the postprandial trial

[0177]

[0178] From the above results, it can be found that for Example 7 and the commercially available tablet C max , AUC 0-t and AUC 0-∞The geometric mean ratios of the three and their 90% confidence intervals all fall within 80% - 125% simultaneously, indicating that Example 7 and are bioequivalent. While for Comparative Example 7 and the commercially available tablet C max , AUC 0-t and AUC 0-∞ The geometric mean ratios of the three and their 90% confidence intervals do not all fall within 80% - 125% simultaneously, indicating that Comparative Example 7 and are not bioequivalent, and the bioavailability of Comparative Example 7 in the human body is relatively low. This shows that the orally disintegrating film of lurasidone hydrochloride provided by the present invention not only has a bioavailability equivalent to that of the commercially available tablet in vivo, but also rapidly disintegrates without water in the oral cavity, greatly improving the compliance of schizophrenia patients and being more convenient for clinical use.

[0179] The influencing factor tests were carried out on the naked samples of Example 7 and Comparative Example 7. They were placed at high temperature (60 °C) and high humidity (92.5% RH) for 10 days and 30 days respectively, and at light (4500 ± 500 Lx) for 11 days. Samples were taken to detect related substances, and the results are shown in the following table.

[0180] Table 13 Detection results of related substances of Comparative Example 7 for influencing factors

[0181]

[0182] Table 14 Detection results of related substances of Example 7 for influencing factors

[0183]

[0184] The above data show that when the naked samples of Example 7 and Comparative Example 7 were placed at light (4500 ± 500 Lx) for 11 days, the related substances increased slightly compared with those on day 0, and there was no obvious difference in the growth trends of the two. No impurities were detected in the remaining samples, indicating that the orally disintegrating film of lurasidone hydrochloride provided by the present invention can obtain good stability without adding light-shielding agents such as titanium dioxide and stabilizers such as disodium edetate.

Claims

1. A pharmaceutical composition comprising lurasidone hydrochloride, a film-forming material, and a plasticizer, characterized in that, the film-forming material comprises polyvinyl alcohol; Optionally, the film-forming material further comprises at least one of polyvinyl alcohol-polyethylene glycol copolymer, hypromellose, povidone, hydroxypropyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, and ethyl cellulose.

2. The pharmaceutical composition according to claim 1, characterized in that, The particle size D of said lurasidone hydrochloride 90 ≤ 10 μm; and / or, said pharmaceutical composition does not contain a surfactant.

3. The pharmaceutical composition according to claim 1 or 2, characterized in that, the plasticizer comprises at least one of dihydric alcohols, polyhydric alcohols, fatty acids, fatty acid glycerides, and phthalates; Preferably, the plasticizer comprises at least one of glycerol, polyethylene glycol, sorbitol, polysorbate, xylitol, maltitol, propylene glycol, diethyl phthalate, dimethyl phthalate, and dibutyl phthalate; More preferably, the plasticizer is any one or a combination of more than one of glycerol, polyethylene glycol, sorbitol, polysorbate, xylitol, maltitol, and propylene glycol.

4. The pharmaceutical composition according to any one of claims 1 to 3, characterized in that, the plasticizer comprises polyethylene glycol and glycerol; Preferably, the mass ratio of polyethylene glycol to glycerol is (1.5 - 5):

1.

5. The pharmaceutical composition according to any one of claims 1 to 4, characterized in that, the pharmaceutical composition further comprises a flavoring agent; Preferably, the flavoring agent comprises at least one of a sweetening agent, an acidifying agent, and a fragrance; More preferably, the flavoring agent comprises at least one of sucralose, menthol, sucrose, sodium saccharin, stevioside, aspartame, mint fragrance, cherry fragrance, strawberry fragrance, milk fragrance, chocolate fragrance, grape fragrance, sweet orange fragrance, mixed berry fragrance, citric acid, and tartaric acid.

6. The pharmaceutical composition according to any one of claims 1 to 5, characterized in that, the pharmaceutical composition does not contain a stabilizer and a light-shielding agent.

7. A lurasidone hydrochloride orally disintegrating film, characterized in that, the lurasidone hydrochloride orally disintegrating film is prepared from the pharmaceutical composition according to any one of claims 1 to 6.

8. The lurasidone hydrochloride orally disintegrating film according to claim 7, characterized in that, the drug loading of the lurasidone hydrochloride orally disintegrating film is greater than 40%, and the tablet weight is less than 100 mg.

9. The preparation method of the lurasidone hydrochloride orally disintegrating film according to claim 7 or 8, characterized in that, the preparation method comprises the following steps: adding a plasticizer and an optional flavoring agent to a solvent, mixing evenly, then adding lurasidone hydrochloride and a film-forming material, mixing evenly, exhausting, and drying to obtain; wherein, the solvent is an aqueous solution of a volatile organic solvent; Preferably, the volatile organic solvent includes ethanol.

10. Use of the pharmaceutical composition according to any one of claims 1 to 6 or the lurasidone hydrochloride orally disintegrating film according to claim 7 or 8 in the preparation of a drug for treating schizophrenia.

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