A directionally released nicotine oral film and oral chewing article

Abstract

This patent provides a directional release nicotine oral film and a mouthpiece. The nicotine oral film includes a nicotine release layer, a hydrophobic base layer, and an oleophilic adhesive layer. The nicotine oral film is a multi-layered composite film. During use, the nicotine release layer is located as the inner layer, the oleophilic adhesive layer as the outer layer, and the hydrophobic base layer as the middle layer between the nicotine release layer and the oleophilic adhesive layer. Nicotine in the nicotine release layer is released away from the hydrophobic base layer. The hydrophobic base layer not only provides directional barrier function, but its tensile strength also ensures that it maintains structural integrity throughout use and does not disintegrate. Together with the outer oleophilic adhesive layer, it forms a stable supporting framework. After the nicotine release is complete, it can be easily and completely removed from the mouth, eliminating the risk of accidental swallowing of fragments that may occur with traditional oral films, and significantly enhancing safety.

Description

Technical Field

[0001] This patent relates to the field of oral products technology, specifically to a directional release nicotine oral film and oral products. Background Technology

[0002] Tobacco dependence is a significant public health problem worldwide. Nicotine replacement therapy, as an effective smoking cessation aid, focuses on delivering nicotine to users through non-combustion methods to alleviate withdrawal symptoms and improve the success rate of quitting smoking.

[0003] To achieve this goal, various dosage forms have been developed on the market, such as chewing gum, transdermal patches, lozenges, and nasal sprays. However, these traditional formulations still have significant limitations in terms of release control, ease of use, and user experience.

[0004] Nicotine chewing gum was one of the earliest and most widely used dosage forms. It requires users to chew to release nicotine from the base. However, frequent chewing can lead to fatigue of the jaw muscles, and the release of nicotine is highly dependent on saliva flow rate and swallowing frequency, resulting in a short effective duration and large fluctuations in blood drug concentration. Users need to switch gums frequently to maintain the effect, which challenges compliance.

[0005] More importantly, this release method cannot achieve targeted and sustained drug action on the oral mucosa. A large amount of nicotine enters the digestive tract with saliva, undergoes the first-pass effect of the liver and is metabolized, resulting in low bioavailability. It may also cause side effects such as gastrointestinal irritation.

[0006] Nicotine transdermal patches offer another route of continuous administration, allowing for systemic absorption of nicotine through skin penetration. While this formulation avoids gastrointestinal side effects, its onset of action is extremely slow, typically requiring several hours to reach an effective nicotine concentration in the plasma, thus failing to provide timely relief for sudden withdrawal symptoms.

[0007] In addition, factors such as the thickness of the stratum corneum, local blood circulation, and environmental temperature and humidity can significantly affect the drug penetration rate, resulting in huge differences in release rates between individuals and even within an individual. This makes it difficult to achieve precise dosage control and flexibly adapt to the personalized needs of users for nicotine dosage at different stages of smoking cessation.

[0008] To overcome the shortcomings of the aforementioned dosage forms, orally dissolving film technology has been introduced into the field of nicotine delivery. Orally dissolving films can be rapidly wetted, adhered to, and dissolved or eroded in the oral cavity, allowing the drug to be absorbed through the oral mucosa, thereby avoiding the first-pass effect and theoretically improving bioavailability and accelerating onset of action.

[0009] However, most existing nicotine oral dissolving films use a single-layer homogeneous structure. When placed in the mouth, the entire film comes into contact with saliva, and nicotine diffuses freely in all directions. This not only reduces the local drug concentration in the target mucosal area, affecting absorption efficiency, but also causes a large amount of drug to diffuse throughout the oral cavity and be swallowed, repeating the problems of low bioavailability and gastrointestinal irritation.

[0010] In addition, single-layer membranes may break into fragments after dissolution, posing a risk of accidental ingestion, and their mechanical strength is often insufficient to maintain structural integrity and positional stability in the dynamic oral environment.

[0011] In the pharmaceutical field, multilayer composite membrane structures have been used to solve the problem of targeted drug release. For example, the Yike Patch for treating oral ulcers adopts a composite design of drug-containing layer and protective layer, which realizes targeted adhesion and local sustained release of ulcer lesions in a moist oral environment.

[0012] This technological insight suggests that by designing a composite architecture with different functional layers, the direction and rate of drug release can be effectively controlled. However, applying this approach to nicotine delivery systems presents entirely new challenges: the physicochemical properties of nicotine, the required release kinetics, and the extreme ease of use and comfort required for consumer-grade health products are all fundamentally different from those of hormonal preparations used to treat oral ulcers.

[0013] Therefore, there is a need for a targeted-release nicotine oral film and lozenge that can comprehensively address a range of issues, including rapid onset of action, long-lasting effect, targeted delivery, precise dosage, ease of use, and high comfort, in order to meet the diverse needs of modern smokers trying to quit. Summary of the Invention

[0014] This invention aims to solve the technical problems of existing nicotine replacement formulations, such as uncontrollable release, slow onset of action, low bioavailability, inconvenience of use, and poor comfort. This patent provides the following technical solution: In a first aspect, a directional release nicotine oral dissolving membrane is provided, comprising: a nicotine release layer that directly contacts and releases nicotine onto the oral mucosa; a hydrophobic base layer for isolating saliva and directionally releasing nicotine; and an oleophilic adhesive layer for absorbing the nicotine oral dissolving membrane. The nicotine oral dissolving membrane is a multilayer composite membrane. In use, the nicotine release layer is located in the inner layer and contacts the oral mucosa, the oleophilic adhesive layer is located in the outer layer, and the hydrophobic base layer is located in the middle layer between the nicotine release layer and the oleophilic adhesive layer. The nicotine in the nicotine release layer is released in a direction away from the hydrophobic base layer. The nicotine oral dissolving membrane has at least three layers.

[0015] Furthermore, the thickness of the nicotine oral solution membrane is 0.13~0.18mm, 0.18~0.23mm, or 0.23~0.28mm; the shape of the nicotine oral solution membrane is one of the following: circular, quadrilateral, triangular, pentagonal, hexagonal, star-shaped, heart-shaped, or elliptical; if the shape of the nicotine oral solution membrane is circular, the radius of the nicotine oral solution membrane is 0.3~0.7cm; the interlayer bonding strength of the nicotine oral solution membrane is ≥2N / cm².

[0016] Furthermore, the nicotine oral solution membrane has three layers: the thickness of the nicotine oral solution membrane is 0.13~0.18mm; the thickness of the nicotine release layer is 0.05~0.07mm; the thickness of the hydrophobic base layer is 0.06~0.08mm; and the thickness of the oleophilic adhesive layer is 0.02~0.03mm.

[0017] Furthermore, the nicotine-releasing layer includes a matrix, nicotine, plasticizers, and compound flavoring agents; the matrix includes polyvinyl alcohol and hydroxypropyl methylcellulose; the mass ratio of polyvinyl alcohol to hydroxypropyl methylcellulose is 1:5 to 3:10; the plasticizer includes polyethylene glycol 400; the amount of plasticizer added accounts for 15 to 20% of the mass of the matrix; the compound flavoring agents include aspartame and a cooling agent; the amount of aspartame added accounts for 0.5 to 1% of the mass of the matrix; the amount of cooling agent added accounts for 0.3 to 0.8% of the mass of the matrix; the cooling agent includes WS-23 and WS-3, and the mass ratio of WS-23 to WS-3 is 4:5 to 6:5.

[0018] Furthermore, the elongation at break of the nicotine release layer is ≥150%; the pore size distribution of the nicotine release layer is 50~200nm; the nicotine loading in the nicotine release layer is 0.5~1.0mg / tablet; and the disintegration time of the nicotine release layer is at least 30min.

[0019] Furthermore, the raw material for the hydrophobic substrate is ethyl cellulose, with a purity of ≥99%; the water contact angle of the hydrophobic substrate is ≥90°; the tensile strength of the hydrophobic substrate is ≥15N / cm²; and the water permeability of the hydrophobic substrate is ≤0.1mg / cm² / h.

[0020] Furthermore, the oleophilic adhesive layer includes an oleophilic film that adheres to the finger surface via van der Waals forces; the surface energy of the oleophilic film is ≤30mN / m; the oleophilic film is a modified polyacrylate film; and the adhesion force of the oleophilic adhesive layer to the finger surface is 1~3N / cm².

[0021] Furthermore, the oral mucosal contact angle of the nicotine oral solution film is ≤30°; the adhesion force of the nicotine oral solution film is 5~10mN / cm²; the nicotine oral solution film is formed by gradient coating method.

[0022] Secondly, an oral product containing a directionally releasing nicotine oral film, the oral product comprising the aforementioned nicotine oral film; the oral product is obtained by punching, screening and packaging the nicotine oral film.

[0023] Furthermore, the punching pressure is 0.3~0.7MPa; after screening, qualified products are retained, and the defective product rate is less than 3%; the packaging material is aluminum-plastic blister pack, nicotine blister single-layer encapsulation; the packaging temperature is 20~24℃; the relative humidity of the packaging is 45~55%; after packaging, the sealing test is carried out using the negative pressure method, and the leakage rate is ≤0.1%; after packaging, the product is stored in the warehouse at a temperature of 15~25% and a humidity of ≤60%.

[0024] This patent has the following beneficial effects: 1. A directional release nicotine oral film and oral product are provided. The nicotine oral film includes a nicotine release layer, a hydrophobic base layer, and an oleophilic adhesive layer. The nicotine oral film is a multilayer composite film. In use, the nicotine release layer is located in the inner layer, the oleophilic adhesive layer is located in the outer layer, and the hydrophobic base layer is located in the middle layer between the nicotine release layer and the oleophilic adhesive layer. The nicotine in the nicotine release layer is released in a direction away from the hydrophobic base layer.

[0025] 2. In this patent, the nicotine orally dissolving membrane achieves directional and controllable release of nicotine into the oral mucosa. The hydrophobic base layer, acting as a key physical barrier, possesses strong hydrophobic properties with a water contact angle greater than or equal to 90 degrees, effectively blocking the penetration of saliva and thus strictly limiting the nicotine release pathway to a single direction. Nicotine does not need to undergo slow skin penetration or complex gastrointestinal absorption; instead, it directly enters the systemic circulation rapidly through the rich capillary network of the oral mucosa, allowing users to experience craving relief in a significantly shortened time and promptly address sudden withdrawal symptoms during smoking cessation. Because the drug release is directed to the absorption site and diffusion to other areas of the oral cavity and subsequent swallowing are minimized, metabolic losses caused by the first-pass effect of the liver are avoided. This allows an equivalent amount of nicotine to exert a stronger physiological effect, providing room for reducing the single-dose load and minimizing potential side effects. Furthermore, by optimizing the matrix material ratio and microporous structure of the nicotine release layer, combined with the isolation effect of the hydrophobic base layer, it is possible to achieve precise control of the drug dissolution rate, providing a stable and continuous release for tens of minutes, meeting the user's need for long-term maintenance, avoiding drastic fluctuations in blood drug concentration, significantly extending the effective time of a single use, reducing the need for frequent drug replenishment, and greatly improving the convenience of use and long-term user compliance.

[0026] 3. The hydrophobic base layer not only provides functional directional barrier but also possesses inherent tensile strength, ensuring structural integrity throughout use and preventing disintegration. Together with the outer oleophilic adhesive layer, it forms a stable support framework. After nicotine release, it can be easily and completely removed from the mouth, eliminating the risk of accidental swallowing of fragments that may occur with traditional oral films, thus significantly enhancing safety. Simultaneously, the strong bond formed between the layers through processes such as gradient coating ensures the film maintains structural integrity in the dynamic oral environment, preventing delamination or displacement and guaranteeing the stable execution of the directional release mechanism and reliable adhesion.

[0027] 4. To address the strong unpleasant taste of nicotine, the carefully formulated flavoring system in the nicotine release layer includes a high-efficiency sweetener and a cooling agent that provides a refreshing sensation. This effectively masks the bitterness and irritation, resulting in a pleasant initial taste. The cooling agent can also relieve the dry mouth discomfort commonly experienced during smoking cessation.

[0028] 5. The oleophilic and adhesive design is highly practical. Its low surface energy allows it to adhere appropriately to the skin and fingers through van der Waals forces, enabling precise and convenient application even with wet fingers. This solves the problems of traditional films being inconvenient to use and prone to sticking. Furthermore, the film's excellent overall flexibility and small contact angle with the oral mucosa ensure comfortable application to various areas such as the cheeks and gums without noticeable foreign body sensation, maintaining stability in various postures throughout daily life. The convenient application and removal characteristics of the oleophilic and adhesive layer make this product particularly suitable for use in situations where hands are limited or attention is distracted, such as during sports, driving, or work. Combined with the independent, well-sealed aluminum-plastic blister packaging, it is not only easy to carry and store, ensuring medication stability, but its compact and discreet appearance also caters to the user's privacy needs in social or public settings. Attached Figure Description

[0029] To more clearly illustrate the technical solutions of the embodiments of this patent, the drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this patent and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained from these drawings without creative effort.

[0030] Figure 1 This is an exploded view of the nicotine oral solution film in this patent.

[0031] The reference numerals in the attached figures are explained as follows: 100: Nicotine release layer; 200: Hydrophobic substrate; 300: Oleophilic and adhesive. Detailed Implementation

[0032] The detailed features and advantages of this application are described below in the specific embodiments. The content of this description is sufficient to enable any person skilled in the art to understand the technical content of this application and implement it accordingly. Based on the specification, claims and drawings disclosed in this specification, a person skilled in the art can easily understand the related objectives and advantages of this application.

[0033] The invention will now be described with reference to the accompanying drawings, in which similar reference numerals denote similar elements. While specific structures and arrangements are discussed, it should be understood that this is done merely for illustrative purposes. Those skilled in the art will recognize that other structures and arrangements can be used without departing from the spirit and scope of the invention. It will be apparent to those skilled in the art that the invention can also be used in a variety of other applications.

[0034] In this specification and claims, several terms will be used, and unless otherwise indicated, these terms will be defined to have the following meanings: The singular forms “a” and “the” include their corresponding plural forms. “At least one” means one or more, and “more” means two or more. “At least one of the following” or similar expressions refer to any combination of these items, including any combination of single or plural items. For example, at least one of a, b, or c can be expressed as: a, b, c, ab, ac, bc, or abc, where a, b, and c can be single or multiple.

[0035] All figures used to represent component amounts, properties (e.g., molecular weight), reaction conditions, etc., should be considered to be modified in all cases by the terms "within the unavoidable margin of error" or "about". Therefore, the numerical values ​​set forth herein are approximate and may vary depending on the desired properties sought to be obtained by the present invention. The principles of equivalents, which are applied to a minimum and not intended to limit the scope of the claims, should be applied, for example, each value should be interpreted at least according to the reported significant digits and by applying conventional rounding techniques.

[0036] It should be understood that the term "and / or" in this article is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, or B existing alone. A and B can be singular or plural. Additionally, the character " / " in this article generally indicates an "or" relationship between the preceding and following related objects, but it can also represent an "and / or" relationship. Please refer to the context for a more accurate understanding.

[0037] In the description of this embodiment, it should be noted that the terms "upper", "lower", "inner", "bottom", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship in which the product is usually placed during use. They are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application.

[0038] Unless otherwise indicated, the following abbreviations have the following meanings, and any other abbreviations used herein but not defined have their generally accepted standard meanings: All other terms used herein for special definition are intended to have the general meaning understood by one of ordinary skill in the art, and in particular, meaning that one of ordinary skill in the art, upon reading the claims, specification and drawings of this patent, can directly and without doubt determine how the technical solution of this patent can be implemented.

[0039] Even if there are incomplete descriptions, omissions, or ambiguities in the grammar, words, punctuation, graphics, symbols, etc. of the claims, specification, and drawings of this patent, a person skilled in the art can still arrive at the only correct understanding by reading the claims, specification, and drawings as a whole without extensive reasoning or experimentation, and effectively exclude various incorrect interpretations that are not aimed at achieving the purpose of this patent.

[0040] Those skilled in the art would first choose to read the claims, specification, and drawings of this patent to reasonably interpret the terms; secondly, they would choose to refer to the relevant definitions in other documents published by the applicant before the filing date to reasonably interpret the terms; thirdly, they would choose the references cited in this patent to reasonably interpret the terms; and finally, they would choose to combine the technical dictionaries, technical manuals, reference books, textbooks, national or industry technical standards, etc., commonly used by those skilled in the art to reasonably interpret the terms.

[0041] To make the objectives, technical solutions, and advantages of this application clearer, the following will describe in detail its implementation methods in conjunction with the specific structure and working process of the device of the present invention.

[0042] Please refer to Figure 1 A directional nicotine oral solution membrane, comprising: a nicotine release layer 100, a hydrophobic base layer 200, and an oleophilic adhesive layer 300, wherein the nicotine oral solution membrane is a multilayer composite membrane, wherein in use, the nicotine release layer 100 is located in the inner layer, the oleophilic adhesive layer 300 is located in the outer layer, and the hydrophobic base layer 200 is located in the middle layer between the nicotine release layer 100 and the oleophilic adhesive layer 300, wherein the nicotine in the nicotine release layer 100 is released in a direction away from the hydrophobic base layer 200.

[0043] Specifically, the nicotine oral coating has at least three layers.

[0044] The nicotine release layer 100 directly contacts the oral mucosa and releases nicotine into it; the hydrophobic base layer 200 is used to isolate saliva and release nicotine in a directional manner; and the finger can pick up the nicotine oral film through the oleophilic adhesive layer 300.

[0045] The thickness of the nicotine oral film is 0.13~0.18mm, 0.18~0.23mm or 0.23~0.28mm, preferably 0.13~0.18mm.

[0046] The shape of the nicotine oral fusion membrane can be one of the following: circular, quadrilateral, triangular, pentagonal, hexagonal, star-shaped, heart-shaped, or elliptical; if the shape of the nicotine oral fusion membrane is circular, the radius of the nicotine oral fusion membrane is 0.3~0.7cm.

[0047] In particular, the layers of the nicotine oral solution film are tightly connected and difficult to peel off, and the interlayer bonding strength of the nicotine oral solution film is ≥2N / cm².

[0048] When using, apply the oleophilic adhesive layer 300 to your finger and then transfer the nicotine oral solution film into your mouth. Position the nicotine release layer 100 towards the oral mucosa and adhere it. The oral mucosa contact angle of the nicotine oral solution film should be ≤30°. The adhesion force of the nicotine oral solution film is 5~10mN / cm².

[0049] In addition to the oral mucosa, nicotine oral dissolving films can also be applied to the gums.

[0050] In some embodiments, the nicotine oral solution film preferably has 3 layers, adopting an "inner layer-middle layer-outer layer" sandwich composite structure, and the thickness of the nicotine oral solution film is 0.13~0.18mm.

[0051] The inner layer is a nicotine-releasing layer 100, which directly contacts the oral mucosa to deliver the drug; the middle layer is a hydrophobic base layer 200, which provides structural support and directional barrier function; and the outer layer is an oleophilic adhesive layer 300, which mainly enables convenient pick-up and drop operations.

[0052] Specifically, the nicotine release layer 100 includes a matrix, nicotine, plasticizers, and compound flavoring agents.

[0053] The matrix comprises polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC); the mass ratio of PVA to HPMC is 1:5 to 3:10, preferably 1:4.

[0054] Among them, PVA provides excellent film-forming properties and biocompatibility, creating a stable matrix for nicotine loading; HPMC, with its excellent water solubility and thickening properties, precisely regulates the film dissolution rate and nicotine release rhythm.

[0055] The plasticizer includes polyethylene glycol 400 (PEG400), and the amount of plasticizer added accounts for 15~20% of the mass of the matrix. This can optimize the flexibility of the film to adapt to the dynamic oral environment, improve the extensibility of the film by reducing the intermolecular forces of the matrix, and achieve an elongation at break of ≥150%.

[0056] To address the inherent bitterness of nicotine, a compound flavoring system was developed: the compound flavoring agents include aspartame and a cooling agent.

[0057] Specifically, aspartame is added at a rate of 0.5-1% of the matrix. Aspartame is 180-200 times sweeter than sucrose and can effectively mask bitterness.

[0058] The amount of cooling agent added is 0.3~0.8% of the base mass. The cooling agent not only provides a fresh and cool taste, but also relieves the common symptoms of dry mouth and discomfort during smoking cessation.

[0059] The cooling agent includes WS-23 and WS-3, with the mass ratio of WS-23 to WS-3 being 4:5 to 6:5, preferably 1:1.

[0060] The thickness of the nicotine release layer 100 is 0.05~0.07mm. At this thickness, the matrix can form a uniform porous network through intermolecular hydrogen bonds, with a pore size distribution of 50~200nm, providing a precise diffusion channel for the controlled release of nicotine. The nicotine loading is controlled at 0.5~1.0mg per tablet.

[0061] The raw material for the hydrophobic substrate 200 is ethyl cellulose, with a purity of ≥99%. The large number of ethyl groups in the molecular structure of ethyl cellulose endow it with strong hydrophobicity, making the water contact angle of the hydrophobic substrate 200 ≥90°, thereby constructing a hydrophobic support framework that is insoluble in water and saliva.

[0062] The thickness of the hydrophobic substrate 200 is 0.06~0.08mm. At this thickness, the tensile strength of the hydrophobic substrate 200 is ≥15N / cm², which can withstand dynamic external forces such as chewing and swallowing without damage.

[0063] The hydrophobic substrate 200 forms a dense hydrophobic film structure through a coating process. The water permeability of the hydrophobic substrate 200 is ≤0.1mg / cm² / h. It can effectively prevent nicotine from diffusing to the oral cavity and resist structural collapse caused by saliva infiltration, providing a stable physical support environment for the release of the inner layer.

[0064] The oleophilic adhesive layer 300 includes an oleophilic film, which is a modified polyacrylate film with a surface energy ≤30mN / m.

[0065] In particular, the hydrophobic groups on the oleophilic film molecular chain can form van der Waals forces with the natural fatty acid glycerides on the finger surface to adhere to the finger surface, thus enabling precise picking and placing with a single fingertip without material residue. The adhesion force of the oleophilic adhesive layer 300 on the finger surface is 1~3 N / cm².

[0066] The thickness of the oleophilic adhesive layer 300 is 0.02~0.03mm. This thickness ensures the flexibility and ease of peeling of the oleophilic adhesive layer 300, which can not only meet the packaging folding requirements, but also be easily removed together with the nicotine release layer 100 after use, avoiding secondary contamination.

[0067] In particular, the nicotine oral solution film is formed by a gradient coating method.

[0068] The prepared nicotine soluble film is cut, screened and packaged to obtain oral products.

[0069] Specifically, the dried three-layer composite film blank is peeled off from the carrier film and cut into a circular film with a radius of 0.5cm using a circular die, with a cutting pressure of 0.5MPa, to ensure that the edges are flat and burr-free.

[0070] After punching, each piece is inspected with a thickness tester to select qualified products with a total thickness of 0.15±0.02mm, and the defective product rate is controlled within 3%.

[0071] The qualified film agent was packaged in aluminum-plastic blister packs, with each blister individually sealed. The packaging environment was controlled to a cleanliness level of Class 10000, a temperature of 22℃, and a relative humidity of 50%. After sealing, a negative pressure method was used to test the seal, and the leakage rate was ≤0.1%.

[0072] After packaging, the product is stored in a cool, dry place at a temperature of 15-25°C and a relative humidity of ≤60%, thus obtaining the finished oral product.

[0073] Table 1 lists the names of the raw materials and their suppliers used in the following examples, comparative examples, and experimental cases.

[0074] Table 1. Names of Raw Materials and Suppliers

[0075] Example 1

[0076] 1. Preparation of nicotine release layer

[0077] Weigh the following raw materials for the nicotine release layer according to the following mass percentages: PVA 15 parts, HPMC 60 parts, PEG400 20 parts, aspartame 0.4 parts, WS-23 0.2 parts, WS-3 0.2 parts, nicotine 1 part, and deionized water 500 parts.

[0078] PVA was added to deionized water and placed in an 80°C constant temperature water bath. The mixture was stirred at 800 rpm for 30 minutes until it was completely dissolved to form a homogeneous and transparent first matrix solution.

[0079] HPMC is added to deionized water and placed in a 50°C constant temperature water bath. It is stirred at 800 rpm for 30 minutes until it is completely dissolved to form a homogeneous and transparent second matrix solution. The PVA and HPMC solutions are then mixed to obtain a homogeneous matrix solution.

[0080] PEG400 (stir for 15 min), aspartame and cooling agent (stir for 20 min), and nicotine (stir for 15 min) were added sequentially to a homogeneous matrix solution. The temperature was kept constant at 50°C throughout the process to prepare a uniform nicotine coating solution.

[0081] The coating liquid was evenly coated onto the polytetrafluoroethylene carrier film using a doctor blade coater, with a coating thickness of 180 μm. After drying on a 50°C heating plate for 1 hour, a 70 μm nicotine layer pre-film was obtained after demolding and set aside for later use.

[0082] 2. Preparation of hydrophobic substrate layer

[0083] Weigh 80 parts of ethyl cellulose and 400 parts of anhydrous ethanol. Add the ethyl cellulose to the anhydrous ethanol and place it in a constant temperature water bath at 45°C. Stir at 250 r / min for 30 min until completely dissolved. Filter the solution through a 100-mesh filter cloth to remove impurities and obtain the hydrophobic substrate coating solution.

[0084] The nicotine release layer pre-film is fixed on the worktable of the coating machine, and the hydrophobic substrate coating liquid is evenly coated on the surface of the nicotine release layer with a coating thickness of 400μm. Then it is sent into a 40℃ vacuum drying oven with a vacuum degree of -0.08MPa and dried for 18min to ensure that the ethanol is completely evaporated, forming a bilayer composite film of nicotine release layer-hydrophobic substrate layer, which is ready for use.

[0085] 3. Preparation of oleophilic adhesive layers

[0086] Weigh 30 parts of modified polyacrylate and 300 parts of ethyl acetate, stir at 300 r / min for 25 min at room temperature (25℃) until the materials are completely dissolved, and then filter through a 120 mesh filter cloth to obtain an oleophilic and adhesive coating solution.

[0087] The hydrophobic substrate layer of the bilayer composite membrane of nicotine release layer-hydrophobic substrate layer is fixed with the hydrophobic substrate layer facing upward. The oleophilic adhesive coating liquid is coated on the surface of the hydrophobic substrate layer with a coating thickness of 30 μm. The membrane is then dried in a ventilated drying room at 35℃ for 12 min to allow the ethyl acetate to fully evaporate, resulting in a three-layer composite membrane blank of nicotine release layer-hydrophobic substrate layer-oleophilic adhesive layer. This three-layer composite membrane is a nicotine oral solution membrane.

[0088] Example 2

[0089] 1. Preparation of nicotine release layer

[0090] Weigh the following raw materials for the nicotine release layer according to the following mass percentages: PVA 20 parts, HPMC 55 parts, PEG400 20 parts, aspartame 0.4 parts, WS-23 0.2 parts, WS-3 0.2 parts, nicotine 1 part, and deionized water 500 parts.

[0091] PVA was added to deionized water and placed in an 80°C constant temperature water bath. The mixture was stirred at 800 rpm for 30 minutes until it was completely dissolved to form a homogeneous and transparent first matrix solution.

[0092] HPMC is added to deionized water and placed in a 50°C constant temperature water bath. It is stirred at 800 rpm for 30 minutes until it is completely dissolved to form a homogeneous and transparent second matrix solution. The PVA and HPMC solutions are then mixed to obtain a homogeneous matrix solution.

[0093] PEG400 (stir for 15 min), aspartame and cooling agent (stir for 20 min), and nicotine (stir for 15 min) were added sequentially to a homogeneous matrix solution. The temperature was kept constant at 50°C throughout the process to prepare a uniform nicotine coating solution.

[0094] The coating liquid was evenly coated onto the polytetrafluoroethylene carrier film using a doctor blade coater, with a coating thickness of 180 μm. After drying on a 50°C heating plate for 1 hour, a 70 μm nicotine layer pre-film was obtained after demolding and set aside for later use.

[0095] 2. Preparation of hydrophobic substrate layer

[0096] Weigh 80 parts of ethyl cellulose and 400 parts of anhydrous ethanol. Add the ethyl cellulose to the anhydrous ethanol and place it in a constant temperature water bath at 45°C. Stir at 250 r / min for 30 min until completely dissolved. Filter the solution through a 100-mesh filter cloth to remove impurities and obtain the hydrophobic substrate coating solution.

[0097] The nicotine release layer pre-film is fixed on the worktable of the coating machine, and the hydrophobic substrate coating liquid is evenly coated on the surface of the nicotine release layer with a coating thickness of 400μm. Then it is sent into a 40℃ vacuum drying oven with a vacuum degree of -0.08MPa and dried for 18min to ensure that the ethanol is completely evaporated, forming a bilayer composite film of nicotine release layer-hydrophobic substrate layer, which is ready for use.

[0098] 3. Preparation of oleophilic adhesive layers

[0099] Weigh 30 parts of modified polyacrylate and 300 parts of ethyl acetate, stir at 300 r / min for 25 min at room temperature (25℃) until the materials are completely dissolved, and then filter through a 120 mesh filter cloth to obtain an oleophilic and adhesive coating solution.

[0100] The hydrophobic substrate layer of the bilayer composite membrane of nicotine release layer-hydrophobic substrate layer is fixed with the hydrophobic substrate layer facing upward. The oleophilic adhesive coating liquid is coated on the surface of the hydrophobic substrate layer with a coating thickness of 30 μm. The membrane is then dried in a ventilated drying room at 35℃ for 12 min to allow the ethyl acetate to fully evaporate, resulting in a three-layer composite membrane blank of nicotine release layer-hydrophobic substrate layer-oleophilic adhesive layer. This three-layer composite membrane is a nicotine oral solution membrane.

[0101] Example 3

[0102] 1. Preparation of nicotine release layer

[0103] Weigh the following raw materials for the nicotine release layer according to the following mass percentages: PVA 15 parts, HPMC 60 parts, PEG400 15 parts, glycerin 5 parts, aspartame 0.4 parts, WS-23 0.2 parts, WS-3 0.2 parts, nicotine 1 part, and deionized water 500 parts.

[0104] PVA was added to deionized water and placed in an 80°C constant temperature water bath. The mixture was stirred at 800 rpm for 30 minutes until it was completely dissolved to form a homogeneous and transparent first matrix solution.

[0105] HPMC is added to deionized water and placed in a 50°C constant temperature water bath. It is stirred at 800 rpm for 30 minutes until it is completely dissolved to form a homogeneous and transparent second matrix solution. The PVA and HPMC solutions are then mixed to obtain a homogeneous matrix solution.

[0106] PEG400 (stir for 15 min), aspartame and cooling agent (stir for 20 min), and nicotine (stir for 15 min) were added sequentially to a homogeneous matrix solution. The temperature was kept constant at 50°C throughout the process to prepare a uniform nicotine coating solution.

[0107] The coating liquid was evenly coated onto the polytetrafluoroethylene carrier film using a doctor blade coater, with a coating thickness of 180 μm. After drying on a 50°C heating plate for 1 hour, a 70 μm nicotine layer pre-film was obtained after demolding and set aside for later use.

[0108] 2. Preparation of hydrophobic substrate layer

[0109] Weigh 80 parts of ethyl cellulose and 400 parts of anhydrous ethanol. Add the ethyl cellulose to the anhydrous ethanol and place it in a constant temperature water bath at 45°C. Stir at 250 r / min for 30 min until completely dissolved. Filter the solution through a 100-mesh filter cloth to remove impurities and obtain the hydrophobic substrate coating solution.

[0110] The nicotine release layer pre-film is fixed on the worktable of the coating machine, and the hydrophobic substrate coating liquid is evenly coated on the surface of the nicotine release layer with a coating thickness of 400μm. Then it is sent into a 40℃ vacuum drying oven with a vacuum degree of -0.08MPa and dried for 18min to ensure that the ethanol is completely evaporated, forming a bilayer composite film of nicotine release layer-hydrophobic substrate layer, which is ready for use.

[0111] 3. Preparation of oleophilic adhesive layers

[0112] Weigh 30 parts of modified polyacrylate and 300 parts of ethyl acetate, stir at 300 r / min for 25 min at room temperature (25℃) until the materials are completely dissolved, and then filter through a 120 mesh filter cloth to obtain an oleophilic and adhesive coating solution.

[0113] The hydrophobic substrate layer of the bilayer composite membrane of nicotine release layer-hydrophobic substrate layer is fixed with the hydrophobic substrate layer facing upward. The oleophilic adhesive coating liquid is coated on the surface of the hydrophobic substrate layer with a coating thickness of 30 μm. The membrane is then dried in a ventilated drying room at 35℃ for 12 min to allow the ethyl acetate to fully evaporate, resulting in a three-layer composite membrane blank of nicotine release layer-hydrophobic substrate layer-oleophilic adhesive layer. This three-layer composite membrane is a nicotine oral solution membrane.

[0114] Example 4

[0115] Weigh the following raw materials for the nicotine release layer according to the following mass percentages: PVA 15 parts, HPMC 60 parts, PEG400 10 parts, glycerin 10 parts, aspartame 0.4 parts, WS-23 0.1 parts, WS-3 0.3 parts, nicotine 1 part, and deionized water 500 parts.

[0116] PVA was added to deionized water and placed in an 80°C constant temperature water bath. The mixture was stirred at 800 rpm for 30 minutes until it was completely dissolved to form a homogeneous and transparent first matrix solution.

[0117] HPMC is added to deionized water and placed in a 50°C constant temperature water bath. It is stirred at 800 rpm for 30 minutes until it is completely dissolved to form a homogeneous and transparent second matrix solution. The PVA and HPMC solutions are then mixed to obtain a homogeneous matrix solution.

[0118] PEG400 (stirred for 15 min), aspartame and cooling agent (stirred for 20 min), and nicotine (stirred for 15 min) were added sequentially to a homogeneous matrix solution. The temperature was kept constant at 50°C throughout the process to prepare a uniform coating solution. The coating solution was then uniformly coated onto a polytetrafluoroethylene carrier film using a doctor blade coater to a coating thickness of 700 μm. The film was then dried on a 50°C heating plate for 1 h to obtain a nicotine oral solution film.

[0119] Experimental Example 1

[0120] The nicotine oral dissolving film A1 prepared in Example 1 was made into a lozenge D1, and the specific process is as follows.

[0121] The dried three-layer composite film blank is peeled off from the carrier film and cut into circular film blanks with a radius of 0.5 cm using a circular die. The cutting pressure is 0.5 MPa to ensure that the edges are smooth and burr-free. After cutting, each blank is inspected with a thickness tester, and qualified products with a total thickness of 0.15 mm are selected. The defective product rate is controlled within 3%.

[0122] The qualified film agent is packaged in aluminum-plastic blister packs, with each blister individually sealed. The packaging environment is controlled to a cleanliness level of Class 10000, a temperature of 22℃, and a relative humidity of 50%. After sealing, a negative pressure method is used to test the seal, with a leakage rate of ≤0.1%. After packaging, the product is stored in a cool, dry place at a temperature of 15-25℃ and a relative humidity of ≤60%, thus obtaining oral product D1.

[0123] Experiment Example 2

[0124] The nicotine oral dissolving film prepared in Example 2 was made into oral product D2, and the specific process is as follows.

[0125] The dried three-layer composite film blank is peeled off from the carrier film and cut into circular film blanks with a radius of 0.5 cm using a circular die. The cutting pressure is 0.5 MPa to ensure that the edges are smooth and burr-free. After cutting, each blank is inspected with a thickness tester, and qualified products with a total thickness of 0.15 mm are selected. The defective product rate is controlled within 3%.

[0126] The qualified film agent is packaged in aluminum-plastic blister packs, with each blister individually sealed. The packaging environment is controlled at a cleanliness level of Class 10000, a temperature of 22℃, and a relative humidity of 50%. After sealing, a negative pressure method is used to test the seal, with a leakage rate of ≤0.1%. After packaging, the product is stored in a cool, dry place at a temperature of 15-25℃ and a relative humidity of ≤60%, thus obtaining oral product D2.

[0127] Experimental Example 3

[0128] The nicotine oral dissolving film prepared in Example 3 was used to make oral product D3. The specific process is as follows.

[0129] The dried three-layer composite film blank is peeled off from the carrier film and cut into circular film blanks with a radius of 0.5 cm using a circular die. The cutting pressure is 0.5 MPa to ensure that the edges are smooth and burr-free. After cutting, each blank is inspected with a thickness tester, and qualified products with a total thickness of 0.15 mm are selected. The defective product rate is controlled within 3%.

[0130] The qualified film agent is packaged in aluminum-plastic blister packs, with each blister individually sealed. The packaging environment is controlled to a cleanliness level of Class 10000, a temperature of 22℃, and a relative humidity of 50%. After sealing, a negative pressure method is used to test the seal, with a leakage rate of ≤0.1%. After packaging, the product is stored in a cool, dry place at a temperature of 15-25℃ and a relative humidity of ≤60%, thus obtaining oral product D3.

[0131] Comparative Example

[0132] The nicotine oral dissolving film prepared in Example 4 was made into a lozenge Z1, and the specific process is as follows.

[0133] After drying, the nicotine oral solution membrane was demolded to obtain a 290μm nicotine membrane, which was then cut into 2 pieces. Prepare a 2.5cm film sample for later use.

[0134] Roll feeding: The aluminum-plastic composite aluminum foil roll is fed into the fully automatic strip bag packaging machine, where it is folded into a bag shape by the forming device; Film filling and nitrogen filling: After the single-dose oral soluble film falls into the bag, the equipment automatically fills it with high-purity nitrogen (residual oxygen content ≤2%) to replace the air in the bag and inhibit nicotine oxidation; Heat sealing and cutting: The bag opening is sealed by longitudinal sealing (temperature 130-150℃) and transverse sealing (temperature 140-160℃), and then cut into individual strip bags. The heat sealing width of the bag opening is ≥8mm to ensure sealing strength.

[0135] Disintegration and release characteristic detection experiment

[0136] Experimental conditions: The solvent used was a solution simulating the oral cavity environment, artificial saliva, pH 6.8, containing electrolytes and enzymes. Nicotine oral dissolution films A1-A4 were immobilized in dissolution cups, and the temperature was maintained at 37℃ to simulate body temperature. The amount of nicotine released over time was measured using HPLC.

[0137] The experimental results are shown in Table 2: Table 2 Experimental results of Examples A1-A4

[0138] Conclusion: The disintegration test was conducted under strict conditions simulating the oral cavity environment. The results clearly show that the product of this invention achieves the controllable, long-lasting, and targeted release effect of traditional single-layer oral disintegration films.

[0139] Experimental data show that the nicotine release layer of the three-layer (A1-A3) membrane maintained a disintegration time of over forty minutes in artificial saliva. This is attributed to the core role of the hydrophobic base layer, composed of high-purity ethyl cellulose, which possesses extremely strong hydrophobic properties and effectively prevents saliva from seeping into the nicotine release layer from the dorsal side. Therefore, the nicotine release layer can only absorb water and gradually dissolve from the side in contact with the oral mucosa, with the release process proceeding from the surface inwards. The rate is effectively controlled, avoiding the "burst release" phenomenon caused by the rapid and indiscriminate disintegration of a single-layer membrane in saliva. In contrast, the disintegration time of the comparative single-layer membrane is not significantly different, but due to its structural defects, the direction and rate of disintegration cannot be controlled.

[0140] More importantly, the release rate test results showed that while achieving prolonged disintegration, the nicotine release rate of the film was high. This proves that while the hydrophobic base layer acts as a "directional valve," it does not hinder effective drug delivery. During the swelling process, the hydrophilic matrix in the nicotine release layer forms a regular nanoscale porous network through intermolecular hydrogen bonds. These micropores constitute dedicated channels for the outward diffusion of nicotine molecules. With the hydrophobic base layer blocking the reverse diffusion, nicotine is forcibly guided and penetrates the oral mucosa, achieving highly efficient directional absorption. This synergistic mechanism of "hydrophobic layer barrier and hydrophilic layer controlled release" can provide users with a continuous and stable supply of nicotine, meeting the need for long-term relief of cravings during smoking cessation.

[0141] In summary, the disintegration and release experiments strongly confirm that the three-layer composite structure of this invention successfully solves the problems of excessively rapid disintegration and disordered release in traditional orally disintegrating films. Through a dual approach of physical isolation and matrix regulation, directional and sustained-release delivery of nicotine to the mucosal side is achieved. This not only enables rapid onset of action and ensures a long-lasting effective effect with a single dose, but also represents a significant advancement in release behavior control.

[0142] Fit and suitability testing experiment

[0143] Experimental conditions: Simulated saliva: Commercially available artificial saliva (containing enzymes) was used, with the pH adjusted to 6.8±0.2 and the temperature controlled at 37±0.5℃.

[0144] Simulated chewing conditions: A reciprocating chewing simulation device was used, with a chewing frequency of 60 times / minute, a chewing pressure of 50±5g, and a chewing stroke of 10mm; Simulated saliva flushing conditions: Artificial saliva flushing was achieved through a constant flow pump, with a flow rate of 1mL / min and a flushing direction at a 30° angle to the mucosal surface.

[0145] Dynamic scene simulation: sports scene (simulating jogging, device vibration frequency 1.5Hz, amplitude 5mm), office scene (simulating hand tapping action, intermittent vibration, frequency 0.5Hz, amplitude 3mm, once every 30s), driving scene (simulating road bumps, continuous vibration frequency 1Hz, amplitude 4mm).

[0146] The experimental results are shown in Table 2: Table 3 Experimental results of Examples A1-A4

[0147] Conclusion: The effectiveness of the nicotine oral dissolving film described in this invention in practical applications largely depends on its stable adhesion performance in dynamic oral environments. Adhesion experiments, simulating various real-world usage conditions, systematically evaluated the initial adhesion and sustained adhesion stability of the film, and the results fully validated its superior performance in terms of adhesion and applicability.

[0148] The experiment first measured the initial contact angle and adhesion force between the film and the oral mucosa. The extremely low contact angle indicates that the nicotine-releasing layer surface has excellent hydrophilicity, allowing it to be rapidly wetted by the moist film on the oral mucosa surface, thus forming a tight interfacial contact in a short time. The moderate adhesion force ensures that the film can be easily and accurately adhered to predetermined sites such as the buccal mucosa and gums, and immediately generates sufficient adhesive strength to resist the effects of gravity and prevent detachment. This "easy-to-adhere and firmly attached" characteristic stems from the bioadhesive and flexible design of the nicotine-releasing layer material itself, allowing the film to adapt well to the irregular surface of the oral mucosa.

[0149] Continuous saliva secretion, periodic swallowing, speech, and potential chewing all exert scouring and shearing forces on the adhesive film. Experiments simulated these harsh conditions, and the results showed that the film exhibited extremely high adhesion stability thanks to the combined protection of the three-layer composite structure. The hydrophobic base layer forms the "skeleton" of the entire film, preventing structural collapse or breakage under saliva immersion and soft tissue compression. Simultaneously, the extremely low water permeability ensures dryness on the back side, maintaining the stability of the nicotine release layer matrix and thus preserving the source of adhesion. Although the oleophilic adhesive layer does not come into contact with the oral cavity during use, it acts as an outer protective layer, tightly bonding with the hydrophobic base layer to jointly maintain the integrity of the overall film structure and prevent interlayer delamination.

[0150] Of particular note is the stability of the film in tests simulating specific dynamic scenarios such as sports, office work, and driving. This demonstrates that its adhesion is not a fragile static adhesion, but rather a dynamic adhesion capable of withstanding a certain degree of vibration and intermittent impact. This allows the product to completely overcome the limitations of traditional oral medications in terms of usage posture and scenario, truly achieving the convenience of use anytime, anywhere. Stable adhesion not only ensures the physical basis for continuous and targeted drug release, but also reduces the risk of accidental swallowing due to film displacement or detachment, and avoids the foreign body sensation or discomfort that may be caused by a detached film sliding in the mouth, thus improving the user experience from both a safety and comfort perspective.

[0151] In the several embodiments provided in this application, it should be understood that the disclosed devices, apparatus and methods can be implemented in other ways.

[0152] For example, the device embodiments described above are merely illustrative. For instance, the division of units is only a logical functional division. In actual implementation, there may be other division methods. For example, multiple units or components may be combined or integrated into another device, or some features may be ignored or not executed.

[0153] The units described as separate components may or may not be physically separate. The components shown as units may or may not be physical units; that is, they may be located in one place or distributed across multiple network units. Some or all of the units can be selected to achieve the purpose of this embodiment according to actual needs.

[0154] In addition, the functional units in the various embodiments of this application can be integrated into one processing unit, or each unit can exist physically separately, or two or more units can be integrated into one unit.

[0155] In this specification, references to "an embodiment" or "a specific implementation" mean that a particular feature, structure, or characteristic described in connection with that embodiment / specific implementation is included in at least one embodiment / specific implementation of the invention. Therefore, the phrase "in one embodiment / specific implementation" appearing in various places in this specification does not necessarily refer to the same embodiment / setting, but rather to potentially different embodiments. Furthermore, specific features, structures, or characteristics may be combined in one or more embodiments / settings in any suitable manner, as will be apparent to those skilled in the art from this disclosure.

[0156] Similarly, it should be understood that in the above description of exemplary embodiments / specific implementations of the invention, various features of the invention are sometimes combined in a single embodiment / specific implementation or its figures and description, with the aim of simplifying the disclosure and aiding in the understanding of one or more of the various aspects of the invention. However, except for expressly stated instructions to the contrary or obvious technical contradictions or exclusions, the method of description in this patent should not be construed as reflecting an intention that the claimed features of the invention are more than those expressly stated in each claim.

[0157] Conversely, the inventive aspect reflected in the claims lies in not all the features of a single foregoing disclosed embodiment / specification. Therefore, the claims following the detailed description are expressly incorporated herein, each claim existing independently as a separate embodiment / specification of the invention.

[0158] Furthermore, while some embodiments / specific implementations described herein include, but are not limited to, other features included in other embodiments / specific implementations, combinations of features from different embodiments / specific implementations are intended to be within the scope of the invention and form different embodiments / specific implementations, as will be understood by those skilled in the art. For example, in the following claims, embodiments / specific implementations of any claim can be used in any combination.

[0159] The terms and expressions used in this specification are for illustrative purposes and not for limitation. The use of these terms and expressions is not intended to exclude any equivalents of the features or portions thereof shown and described, but rather to allow for the understanding that various modifications may be made within the scope of the invention.

[0160] Therefore, it should be understood that although the invention has been specifically disclosed through preferred embodiments, exemplary embodiments and optional features, those skilled in the art may take variations or modifications of the concepts disclosed herein, and such variations and modifications are therefore considered to be within the scope of the invention as defined by the appended claims.

[0161] The specific embodiments given in this specification are examples of useful implementations of the present invention. It will be apparent to those skilled in the art that the present invention can be implemented using many variations of the devices, device components, and method steps disclosed in this specification.

[0162] The foregoing description of specific embodiments fully discloses the general features of the present invention, enabling others to easily modify and / or adapt such specific embodiments for various applications by applying knowledge within the scope of the art, without conducting excessive experimentation and without departing from the general concept of the present invention.

[0163] Therefore, based on the teachings and guidance provided herein, it is intended that such modifications and alterations be included within the meaning and scope of equivalents of the disclosed embodiments. It should be understood that the wording or terminology used herein is for descriptive purposes and is not intended to be limiting; thus, the wording or terminology in this specification will be interpreted by those skilled in the art based on the foregoing teachings and guidance.

[0164] Furthermore, the scope of the invention should not be limited to any of the exemplary embodiments described above, but is defined solely by the appended claims and their equivalents.

Claims

1. A directional release nicotine oral coating, characterized in that, The nicotine oral coating comprises: The nicotine release layer directly contacts the oral mucosa and releases nicotine into the oral mucosa. A hydrophobic base layer is used to isolate saliva and direct the release of the nicotine; An oleophilic adhesive layer is used for retrieving the nicotine oral solution membrane; The nicotine oral dissolving membrane is a multi-layer composite membrane. In use, the nicotine release layer is located in the inner layer and is used to contact the oral mucosa, the oleophilic adhesive layer is located in the outer layer, and the hydrophobic base layer is located in the middle layer between the nicotine release layer and the oleophilic adhesive layer. The nicotine in the nicotine release layer is released in a direction away from the hydrophobic base layer. The nicotine oral coating has at least three layers.

2. The nicotine oral dissolving film according to claim 1, characterized in that, The thickness of the nicotine oral film is 0.13~0.18mm, 0.18~0.23mm, or 0.23~0.28mm; The shape of the nicotine oral film is one of the following: circular, quadrilateral, triangular, pentagonal, hexagonal, star-shaped, heart-shaped, or elliptical. If the nicotine oral solution film is circular, the radius of the nicotine oral solution film is 0.3~0.7cm; The interlayer bonding strength of the nicotine oral solution film is ≥2N / cm².

3. The nicotine oral dissolving film according to claim 1, characterized in that, The nicotine oral solution film has 3 layers and a thickness of 0.13~0.18mm. The thickness of the nicotine-releasing layer is 0.05~0.07mm; The thickness of the hydrophobic substrate layer is 0.06~0.08 mm; The thickness of the oleophilic adhesive layer is 0.02~0.03mm.

4. The nicotine oral dissolving film according to claim 3, characterized in that, The nicotine-releasing layer includes a matrix, nicotine, plasticizers, and compound flavoring agents; The matrix comprises polyvinyl alcohol and hydroxypropyl methylcellulose; The mass ratio of the polyvinyl alcohol to the hydroxypropyl methylcellulose is 1:5 to 3:10; The plasticizer includes polyethylene glycol 400; The amount of plasticizer added is 15-20% of the mass of the matrix; The compound flavoring agent includes aspartame and a cooling agent; The amount of aspartame added is 0.5-1% of the mass of the matrix; The amount of the cooling agent added is 0.3-0.8% of the mass of the matrix; The cooling agent includes WS-23 and WS-3, and the mass ratio of WS-23 to WS-3 is 4:5 to 6:

5.

5. The nicotine oral dissolving film according to claim 4, characterized in that, The elongation at break of the nicotine release layer is ≥150%; The pore size distribution of the nicotine release layer is 50~200nm; The nicotine loading in the nicotine-releasing layer is 0.5~1.0 mg / tablet; The nicotine release layer has a disintegration time of at least 30 minutes.

6. The nicotine oral dissolving film according to claim 2, characterized in that, The hydrophobic substrate is made from ethyl cellulose, and the purity of the ethyl cellulose is ≥99%. The water contact angle of the hydrophobic substrate layer is ≥90°; The tensile strength of the hydrophobic substrate is ≥15 N / cm². The water permeability of the hydrophobic substrate is ≤0.1 mg / cm² / h.

7. The nicotine oral dissolving film according to claim 2, characterized in that, The oleophilic adhesive layer includes an oleophilic film that adheres to the surface of the finger by van der Waals forces; The surface energy of the oleophilic film is ≤30mN / m; The oleophilic film is a modified polyacrylate film; The adhesion force of the oleophilic adhesive layer to the finger surface is 1~3 N / cm².

8. The nicotine oral dissolving film according to claim 1, characterized in that, The oral mucosal contact angle of the nicotine oral solution film is ≤30°; The adhesion force of the nicotine oral solution film is 5~10mN / cm²; The nicotine oral solution film is formed by gradient coating.

9. A lozenge containing a targeted-release nicotine oral film, characterized in that, The oral product comprises a nicotine oral film as described in any one of claims 1 to 8; The nicotine oral dissolving film is cut, screened and packaged to obtain the oral product.

10. The oral article according to claim 9, characterized in that, The punching pressure is 0.3~0.7MPa; After the screening process, qualified products are retained, and the defective product rate is less than 3%. The packaging material is an aluminum-plastic blister pack, and the nicotine oral solution film is used for single-layer encapsulation. The temperature of the packaging is 20~24℃; The relative humidity of the packaging is 45-55%; The packaging was then subjected to a negative pressure test for airtightness, with a leakage rate ≤0.1%. After packaging, the product is stored in a warehouse at a temperature of 15-25%. The humidity of the stored material is ≤60%.

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