Buccal tablet and preparation method thereof

Abstract

The invention discloses a buccal tablet and a preparation method thereof, the buccal tablet sequentially comprises a first support layer, a functional layer, a seasoning layer and a second support layer, the functional layer contains active substances, and the seasoning layer contains a flavoring agent. The buccal tablet disclosed by the invention comprises a multi-layer structure, and the first supporting layer and the second supporting layer can provide supporting and protecting effects for the internal functional layer and the seasoning layer; the functional layer can provide active substances for a user to use; the seasoning layer can provide a flavoring agent to improve the taste; the active substances and the flavoring agents are located in the functional layer and the flavoring layer respectively, and intermolecular interference of the active substances and the flavoring agents can be reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of oral products, in particular to an oral tablet and a preparation method thereof. BACKGROUND

[0002] An oral product, such as an oral nicotine product, is a product containing a nicotine active ingredient (nicotine or its derivative), usually in the form of a powder, tablet, sachet, etc., which is placed in the oral cavity, then dissolves and releases the nicotine active ingredient, and is absorbed through the oral mucosa, thereby relieving nicotine withdrawal symptoms during smoking cessation.

[0003] An oral tablet is a tablet-shaped or film-shaped product, usually made of soluble material, containing a certain amount of active substance, and usually also containing a flavoring agent to improve taste. When used, the oral tablet is placed in the oral cavity and contacted with saliva, and the oral tablet can disintegrate or swell and release the active substance and the flavoring agent.

[0004] However, the active substance and the flavoring agent of the current oral tablet are usually mixed together and processed to obtain the tablet, and competition adsorption or mutual interference between molecules is prone to occur, affecting the taste. SUMMARY

[0005] The present application provides an oral tablet and a preparation method thereof, which are used to solve the problem that the active substance and the flavoring agent of the current oral tablet are usually mixed together and processed to obtain the tablet, and competition adsorption or mutual interference between molecules is prone to occur.

[0006] The present application discloses an oral tablet, which comprises a first support layer, a functional layer, a flavoring layer, and a second support layer in sequence, wherein the functional layer contains an active substance, and the flavoring layer contains a flavoring agent.

[0007] In one implementation of the present application, the oral tablet further comprises an isolation layer, and the isolation layer is arranged between the functional layer and the flavoring layer.

[0008] In one implementation of the present application, the functional layer comprises a first functional layer and a second functional layer, and the oral tablet further comprises an isolation layer, and the isolation layer is arranged between the first functional layer and the second functional layer.

[0009] In one implementation of the present application, the first support layer and the second support layer have water permeability, and the water permeability of the first support layer is different from that of the second support layer.

[0010] In one implementation of the present application, the first support layer and the second support layer are porous structures, wherein the buccal tablet satisfies at least one of (I) to (V): (I) the first support layer is provided with at least one of a microporous structure and a macroporous structure; (II) the second support layer is provided with at least one of a microporous structure and a macroporous structure; (III) the first support layer and / or the second support layer includes a temperature-sensitive auxiliary agent, and the temperature-sensitive auxiliary agent is used to adjust water permeability based on temperature changes; (IV) the porosity of the first support layer is 5% to 30%; (V) the porosity of the second support layer is 5% to 30%.

[0011] In one implementation of the present application, the active substance includes at least one of nicotine and nicotine derivatives; and / or the flavoring includes at least one of a sweetener, an aromatic, and a cooling agent; and / or the first supporting layer includes at least one of the following: a thermoplastic resin porous membrane, a natural fiber non-woven fabric, a synthetic fiber non-woven fabric, or a woven fabric; and / or the second supporting layer includes at least one of the following: polypropylene, a thermoplastic resin porous membrane, a natural fiber non-woven fabric, a synthetic fiber non-woven fabric, or a woven fabric.

[0012] In one implementation of the present application, the first supporting layer and / or the second supporting layer includes a temperature-sensitive auxiliary agent, and the temperature-sensitive auxiliary agent includes poly (N-isopropylacrylamide).

[0013] In one implementation of the present application, the functional layer further comprises at least one of the following: a film-forming agent, a sustained-release agent, a thickener, a plasticizer, a pH additive, and an antioxidant; the flavoring layer further comprises at least one of the following: a film-forming agent, a sustained-release agent, a thickener, a plasticizer, a pH additive, and an antioxidant.

[0014] In one implementation of the present application, the film-forming agent includes at least one of hydroxypropyl methylcellulose, polyvinyl alcohol, pullulan, gelatin, chitosan, polyvinyl pyrrolidone, and sodium carboxymethyl cellulose; and / or the sustained-release agent includes at least one of sodium alginate, carrageenan (κ type), and mesoporous silica; and / or the thickener includes at least one of a polycarboxyl polymer, a starch ether derivative, and a sodium hyaluronate-chitosan polyelectrolyte complex; and / or the plasticizer includes at least one of glycerol, sorbitol, propylene glycol, polyethylene glycol, and xylitol.

[0015] The present application also discloses a method for preparing a buccal tablet, comprising: obtaining a first supporting layer, an isolation layer, a second supporting layer, a first film-forming liquid comprising an active substance, and a second film-forming liquid comprising a flavoring agent, wherein the isolation layer has a first surface and a second surface arranged opposite to each other; applying the first film-forming liquid on the first surface of the isolation layer to form a functional layer on the first surface; applying the second film-forming liquid on the second surface of the isolation layer to form a flavoring layer on the second surface; covering the first supporting layer on a side of the functional layer facing away from the flavoring layer, and covering the second supporting layer on a side of the flavoring layer facing away from the functional layer, to obtain a buccal tablet, wherein the buccal tablet comprises the first supporting layer, the functional layer, the flavoring layer, and the second supporting layer arranged in sequence.

[0016] The beneficial effects of this application are:

[0017] The buccal tablet of the present application includes a multi-layer structure, wherein the first supporting layer and the second supporting layer located in the outer layer can provide support and protection for the internal functional layer and flavoring layer; the functional layer can provide active substances for users to use; the flavoring layer can provide flavoring to improve the taste; the active substances and flavorings are respectively located in the functional layer and the flavoring layer, which can reduce the intermolecular interference between the active substances and the flavorings. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 A schematic structural diagram of a buccal tablet according to a specific embodiment of the present application is shown.

[0019] Figure 2 A schematic structural diagram of a buccal tablet according to another embodiment of the present application is shown.

[0020] Figure 3 A schematic structural diagram of a buccal tablet according to another embodiment of the present application is shown.

[0021] Figure 4 This is the nicotine release curve of the buccal tablets with different formulations involved in the examples of this application. DETAILED DESCRIPTION

[0022] The present invention is further described in detail below by specific embodiments in conjunction with the accompanying drawings. In the following embodiments, many detailed descriptions are intended to enable the present application to be better understood. However, those skilled in the art can readily appreciate that some of the features may be omitted in different circumstances, or may be replaced by other materials or methods. In some cases, some operations related to the present application are not shown or described in the specification. This is to avoid the core of the present application being overwhelmed by excessive descriptions, and for those skilled in the art, it is not necessary to describe these related operations in detail. They can fully understand the related operations based on the description in the specification and the general technical knowledge in the art.

[0023] In addition, the features, operations, or characteristics described in the specification may be combined in any appropriate manner to form various embodiments. Furthermore, the steps or actions in the method description may be reordered or adjusted in a manner readily apparent to those skilled in the art. Therefore, the various sequences in the specification and drawings are provided solely for the purpose of clearly describing a particular embodiment and are not intended to be mandatory, unless otherwise specified.

[0024] The serial numbers assigned to the components in this document, such as "first", "second", etc., are only used to distinguish the objects described and do not have any order or technical meaning.

[0025] At present, there are obvious deficiencies in the material selection and structural design of buccal tablets. It is difficult to accurately control the release rate of active substances while taking into account a good taste experience and stable structural performance. Innovative technical solutions are needed to break through these technical bottlenecks. In addition, the active substances and flavorings of current buccal tablets are usually mixed together and processed to obtain tablets. Molecules are prone to competitive adsorption or mutual interference, affecting the taste. In addition, the existing single-layer structure buccal tablets are prone to adhesion of the membrane to the oral cavity during use, causing discomfort, or residual fragments are left in the oral cavity after use, which are difficult to remove, reducing the user experience.

[0026] The present application provides a buccal tablet and a preparation method thereof, which have at least one of the following advantages: the active substance and the flavoring agent are not located in the same film layer, which can reduce competitive adsorption or mutual interference between molecules; the release rate of the active substance can be accurately controlled by the porous support layer; when the buccal tablet is used, the film is not easy to adhere to the oral cavity, and the residual fragments can be easily removed after use.

[0027] Figure 1 FIG. 1 shows a structural diagram of a buccal tablet 100 according to a specific embodiment of the present application. Figure 1 In order to conveniently display the structures of different layers, the layers are displayed separately. In actual situations, the layers are arranged to be in contact with each other.

[0028] In an embodiment, the lozenge 100 has a multi-layer structure.

[0029] In an embodiment, the lozenge 100 can include a support layer. The support layer can be water-insoluble. The support layer can be a porous structure. The support layer can have water permeability. The support layer can have through-holes for saliva to pass through the support layer. It should be noted that the support layer can serve the functions of support and protection, as well as allowing saliva to pass through and enter other film layers, and in addition, after use, by removing the support layer, undissolved film debris can be taken out together, reducing the foreign body sensation caused by residues, and improving the user experience.

[0030] In an embodiment, the support layer can include at least one of a thermoplastic resin porous film, a natural fiber non-woven fabric, a synthetic fiber non-woven fabric, and a woven fabric. It should be noted that the natural fiber non-woven fabric, the synthetic fiber non-woven fabric, and the woven fabric have good hydrophilicity, which can make the support layer have good hydrophilicity, and be conducive to saliva passing through the support layer and entering the internal other structure layers.

[0031] In an embodiment, the thermoplastic resin can include, but is not limited to, PP (polypropylene), PET (polyethylene terephthalate), PA (polyamide, also known as nylon), and PLA (polylactic acid).

[0032] In an embodiment, the support layer can be a thermoplastic resin porous film. For example, the support layer can be a porous polypropylene film.

[0033] In an embodiment, the pore size of the support layer can be 5 μm to 50 μm. For example, the pore size of the support layer can be 5 μm, 10 μm, 25 μm, 40 μm, or 50 μm.

[0034] In an embodiment, the porosity of the support layer can be 5% to 30%. For example, the porosity of the support layer can be 5%, 10%, 15%, 20%, 25%, or 30%.

[0035] In an embodiment, the number of support layers can be multiple.

[0036] In an embodiment, at least two support layers can be located on two surfaces of the lozenge 100, respectively. As shown in FIG. 1, in an embodiment, the support layer can include a first support layer 10 and a second support layer 50. Figure 1

[0037] In an embodiment, the support layer can contain a temperature-sensitive auxiliary agent. The temperature-sensitive auxiliary agent can be used to adjust the water permeability of the support layer based on temperature changes. The temperature-sensitive auxiliary agent can increase the porosity of the support layer when the temperature increases.

[0038] ​In one embodiment, the temperature-sensitive assistant can change its morphology when heated or cooled. When heated, the temperature-sensitive assistant can expand and increase the porosity of the support layer. When cooled, the temperature-sensitive assistant can contract and decrease the porosity of the support layer. In this case, the lozenge 100 can have a function of slow release of the active ingredients (including the active substance and the flavoring agent) at low temperature, and fast release of the active ingredients at high temperature.

[0039] In one embodiment, the first support layer 10 can contain a temperature-sensitive assistant.

[0040] In one embodiment, the second support layer 50 can contain a temperature-sensitive assistant.

[0041] In one embodiment, the temperature-sensitive assistant can include poly-N-isopropyl acrylamide (PNIPAM).

[0042] In one embodiment, the temperature-sensitive assistant can be attached to the pores of the support layer by immersing the support layer in an impregnation solution.

[0043] In one embodiment, the impregnation solution can further include a porogen. The porogen can include at least one of microcrystalline cellulose, polyvinylpyrrolidone. The porogen can be attached to the pores of the support layer by impregnation, and then indirectly increase the pores of the support layer by a "swelling-leaching" mechanism, thereby increasing the porosity.

[0044] In one embodiment, the support layer can contain an antistatic agent. The antistatic agent can include at least one of quaternary ammonium salt, glycerol monostearate, polyethylene glycol. The antistatic agent can be attached to the support layer by impregnation.

[0045] In one embodiment, the support layer can contain a lubricant. The lubricant can include at least one of magnesium stearate, micronized silicon dioxide. The lubricant can be attached to the support layer by impregnation.

[0046] In one embodiment, the first support layer 10 and the second support layer 50 can have the same porosity. In one embodiment, the second support layer 50 can have a higher porosity than the first support layer 10. In this case, water can enter the flavor layer 40 (described later in detail) more quickly, and the flavoring agent in the flavor layer 40 can be released more quickly to mask the odor of the active substance and improve the taste. In some embodiments, the release rate of the active substance in the functional layer 20 (described later in detail) can be controlled by the porosity of the first support layer. In one embodiment, the second support layer 50 can have a lower porosity than the first support layer 10. In this case, the active substance can have a relatively faster release rate to meet the needs of the user.

[0047] In a specific embodiment, the thickness of the first supporting layer 10 may be 0.1 mm to 0.2 mm. For example, the thickness of the first supporting layer 10 may be 0.1 mm, 0.13 mm, 0.15 mm, 0.17 mm, or 0.2 mm.

[0048] In a specific embodiment, the thickness of the second supporting layer 50 may be 0.1 mm to 0.2 mm. For example, the thickness of the second supporting layer 50 may be 0.1 mm, 0.13 mm, 0.15 mm, 0.17 mm, or 0.2 mm.

[0049] In a specific embodiment, the buccal tablet 100 may include a functional layer 20. The functional layer 20 may include an active substance.

[0050] In a specific embodiment, the active substance may include at least one of nicotine and a nicotine derivative, for providing a sense of satisfaction.

[0051] In a specific embodiment, nicotine may include natural nicotine or synthetic nicotine. Nicotine derivatives may include one or more of nicotine salts, nicotine in a matrix such as a sugar matrix or an organometallic complex, a nicotine-resin combination, a nicotine inclusion complex, and non-covalently bound nicotine. Non-covalently bound nicotine includes nicotine lactate, nicotine malate, nicotine salicylate, nicotine cyclodextrin inclusion complex, nicotine hydrochloride, nicotine dihydrochloride, nicotine tartrate, nicotine tartrate dihydrate, nicotine sulfate, nicotine zinc chloride, nicotine benzoate, and the like. Nicotine derivatives also include nicotine containing substituents, such as hexamethyl nicotine, hexamethyl nicotine lactate, hexamethyl nicotine malate, hexamethyl nicotine salicylate, hexamethyl nicotine cyclodextrin embedded complex, hexamethyl nicotine hydrochloride, hexamethyl nicotine dihydrochloride, hexamethyl nicotine tartrate, hexamethyl nicotine tartrate dihydrate, hexamethyl nicotine sulfate, hexamethyl nicotine zinc chloride, and hexamethyl nicotine benzoate. One or more mixtures thereof.

[0052] In a specific embodiment, the active substance may also be selected from other substances with medical or other specific uses, such as vitamins, capsaicin, caffeine, etc., to meet the needs of different users.

[0053] In a specific embodiment, the active substance can also be selected from other alkaloids or amino acids, for example, alkaloids such as tobacco, coffee, and tea.

[0054] In one embodiment, the functional layer 20 may be located in the inner layer of the buccal tablet 100. In one embodiment, the support layer may be located in the outer layer, and the functional layer 20 may be located in the inner layer, thereby protecting the functional layer through the support layer.

[0055] like Figure 1 As shown, in a specific embodiment, the buccal tablet 100 may include a flavoring layer 40. The flavoring layer 40 may include a flavoring agent. The flavoring agent may include at least one of a sweetener, an aromatic, and a cooling agent.

[0056] In one specific embodiment, functional layer 20 may contain an active substance but no flavoring agent. Flavoring layer 40 may contain a flavoring agent but no active substance. This allows the active substance and flavoring agent to be loaded into separate layers, reducing competitive adsorption or interference between their molecules. In some examples, functional layer 20 may also contain a flavoring agent, but the flavoring agent content in functional layer 20 is lower than that in flavoring layer 40. In some embodiments, functional layer 20 may contain a sweetener and a cooling agent but no fragrance, while the flavoring layer may contain a fragrance.

[0057] In a specific embodiment, the sweetener may include at least one of xylitol, sorbitol, mannitol, iglesia, lactitol, maltitol, isomalt, hydrogenated starch hydrolysate, erythritol, maltotriitol, aspartame, acesulfame potassium, saccharin sodium, sucralose, neotame, cyclamate, alitame, steviol glycosides, arabitol, and monk fruit sweetener. The sweetener may also be selected from other edible-grade substances, which will not be detailed here.

[0058] In a specific embodiment, the fragrance may include at least one of essence, natural essential oil, and natural extract. The essence is an edible essence, which may include at least one of bergamot essence, eucalyptus essence, citrus essence, lemon essence, peppermint essence, mint essence, menthol, licorice essence, wintergreen essence, tobacco essence, coffee essence, vanilla essence, lime essence, apple essence, peach essence, mango essence, cherry essence, blueberry essence, strawberry essence, cola essence, cinnamon essence, vanilla essence, and watermelon essence. The fragrance may also be other types of edible essences, which will not be detailed here.

[0059] In a specific embodiment, the cooling agent may include at least one of menthol, a menthol derivative, WS-3, and WS-23.

[0060] Figure 2 FIG2 shows a structural schematic diagram of a buccal tablet 100 according to another specific embodiment of the present application.

[0061] In a particular embodiment, the buccal tablet 100 may include an isolation layer 30 .

[0062] In one embodiment, the isolation layer 30 may be a hydrophobic or water-repellent film. The isolation layer 30 may be water-impermeable. The isolation layer 30 is hydrophobic and can block, control, or slow the passage of water.

[0063] In one embodiment, the isolation layer 30 can separate the functional layer 20 from the flavoring layer 40. That is, the functional layer 20 can be located between the first support layer 10 and the isolation layer 30. The flavoring layer 40 can be located between the isolation layer 30 and the second support layer 50.

[0064] In a specific embodiment, the buccal tablet 100 may include a first supporting layer 10, a functional layer 20, an isolation layer 30, a flavoring layer 40, and a second supporting layer 50 in sequence.

[0065] In one specific embodiment, the isolation layer 30 can be at least one of a polytetrafluoroethylene film, a polyethylene film, a polyvinylidene fluoride film, a polyurethane film, a silicone rubber film, and a silicone-coated fabric. It should be noted that the isolation layer 30 can block and regulate the ingress of moisture from both layers of the buccal tablet 100 into the functional layer 20 or the flavoring layer 40, thereby preventing the buccal tablet 100 from dissolving too quickly in the mouth. Furthermore, the hydrophobic film 30 can advantageously serve as a coating substrate, allowing the functional layer 20 and the flavoring layer 40 to be directly coated onto the surface of the hydrophobic film 30.

[0066] In a specific embodiment, the thickness of the isolation layer 30 may be 50 μm to 100 μm. For example, the thickness of the isolation layer 30 may be 50 μm, 75 μm, or 100 μm.

[0067] In one embodiment, the first supporting layer 10, the isolation layer 30, and the second supporting layer 50 can be fixedly connected to each other. Thus, after using the buccal tablet 100, the first supporting layer 10, the isolation layer 30, and the second supporting layer 50 can be removed together, reducing the difficulty of removing the first supporting layer 10, the isolation layer 30, and the second supporting layer 50 due to delamination or displacement.

[0068] In one specific embodiment, when the buccal tablet 100 is in use, the first supporting layer 10 may be positioned on the side closest to the oral mucosa or lips, while the second supporting layer 50 may be positioned on the side closest to the gums or tongue. This facilitates greater absorption of the active substances in the functional layer 20 through the oral mucosa or labial mucosa, reducing the amount of active substances entering the mouth and stomach through saliva, thereby reducing stomach irritation. Furthermore, the flavoring agent in the flavoring layer 40 can enter the mouth through saliva, enhancing the flavor and masking the odor of the active substances, thereby improving the user experience.

[0069] In a specific embodiment, when the buccal tablet 100 is in use, the second supporting layer 50 may be on the side close to the oral mucosa or lips, and the first supporting layer 10 may be on the side close to the gums or tongue.

[0070] In one embodiment, the functional layer 20 contains an active substance and the flavoring layer 40 contains a flavoring agent. During use, moisture in saliva causes the functional layer 20 and the flavoring layer 40 to dissolve or swell, thereby releasing the active substance or flavoring agent.

[0071] In one specific embodiment, the swelling rate of the flavoring layer 40 can be higher than that of the functional layer 20. For example, by using a film-forming material with a faster swelling rate, the flavoring in the flavoring layer 40 can be released earlier and / or faster than the active substance in the functional layer 20. Alternatively, the functional layer 20 can contain a sustained-release agent with a better sustained-release effect or a larger amount to slow the release of the active substance in the functional layer 20. This can enhance flavor, mask the unpleasant taste of nicotine, and improve user experience. This can also improve user acceptance, such as for first-time users. In other examples, the swelling rate of the flavoring layer 40 can be lower than that of the functional layer 20, resulting in a more balanced mouthfeel for the lozenge 100.

[0072] In one embodiment, the release rate of the active substance in the flavoring layer 40 can be higher than the release rate of the active substance in the functional layer 20. This allows the buccal tablet 100 to release the flavoring faster, enhancing the flavor, masking the unpleasant taste of nicotine, and improving the user experience. In other examples, the release rate of the active substance in the flavoring layer 40 can also be lower than the release rate of the active substance in the functional layer 20.

[0073] In a specific embodiment, the thickness of the functional layer 20 may be 50 μm to 200 μm. For example, the thickness of the functional layer 20 may be 50 μm, 100 μm, 150 μm, or 200 μm.

[0074] In a specific embodiment, the thickness of the flavoring layer 40 may be 50 μm to 1000 μm. For example, the thickness of the flavoring layer 40 may be 50 μm, 100 μm, 250 μm, 500 μm, 750 μm, or 1000 μm.

[0075] Figure 3 FIG2 shows a structural diagram of a buccal tablet 100 according to another embodiment of the present application.

[0076] In a specific embodiment, the functional layer 20 may include a first functional layer 21 and a second functional layer 22. The first functional layer 21 and the second functional layer 22 contain active materials.

[0077] In a specific embodiment, the first functional layer 21 and the second functional layer 22 may be located on both sides of the isolation layer 30 , respectively.

[0078] In one embodiment, the first functional layer 21 and the second functional layer 22 may be the same.

[0079] In one embodiment, the first functional layer 21 and the second functional layer 22 may be different. For example, the first functional layer 21 and the second functional layer 22 may contain different active substances, or contain the same active substance but different concentrations or other components (such as film-forming agents).

[0080] In a specific embodiment, the active substances in the first functional layer 21 and the second functional layer 22 may have different release rates. For example, the release rate of the active substance in the first functional layer 21 is lower than the release rate of the active substance in the second functional layer 22; or, the release rate of the active substance in the first functional layer 21 is higher than the release rate of the active substance in the second functional layer 22. It should be noted that most of the current buccal tablet products adopt a single functional layer design, and the release rate of the active substance is single. For example, it is a fast release type with a fast release rate, which cannot meet the demand for long-term release. By providing multiple functional layers 20, and the release rates of the active ingredients in the multiple functional layers 20 are different, it can be helpful to better meet user needs, such as taking into account the dual needs of rapid release and sustained release.

[0081] In a specific embodiment, the release rate of the active substance in the first functional layer 21 and the second functional layer 22 can be regulated by at least one of the following: the water permeability of the first support layer 10 and / or the second support layer 50 (the porosity of the first support layer 10 and / or the second support layer 50), the formulation in the first functional layer 21 and / or the second functional layer 22 (for example, the amount of sustained-release agent, the use of different film-forming agents or different amounts of film-forming agents, etc.).

[0082] In a specific embodiment, the buccal tablet 100 may include a first supporting layer 10, a first functional layer 21, an isolation layer 30, a second functional layer 22, a flavoring layer 40, and a second supporting layer 50 in sequence.

[0083] In a specific embodiment, the functional layer 20 may include a first film-forming agent.

[0084] In one embodiment, the flavored layer 40 may include a second film-forming agent.

[0085] In a specific embodiment, the first film-forming agent may include at least one of hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol, pullulan, gelatin, chitosan, polyvinyl pyrrolidone, and sodium carboxymethyl cellulose.

[0086] In a specific embodiment, the second film-forming agent may include at least one of hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), pullulan, gelatin, chitosan, polyvinyl pyrrolidone, and sodium carboxymethyl cellulose.

[0087] In a specific embodiment, the HPMC can be low-viscosity HPMC, for example, at least one of HPMC E3, HPMC E4, and HPMC E5.

[0088] In a specific embodiment, the functional layer 20 may further include a first sustained-release agent. The first sustained-release agent is used to slow down the release of the active substance.

[0089] In a specific embodiment, the flavoring layer 40 may further include a second sustained-release agent. The first sustained-release agent is used to slow down the release of the flavoring agent.

[0090] In a specific embodiment, the first sustained-release agent includes at least one of sodium alginate, carrageenan (κ type), and mesoporous silica.

[0091] In a specific embodiment, the second sustained-release agent includes at least one of sodium alginate, carrageenan (κ type), and mesoporous silica.

[0092] In a specific embodiment, the functional layer 20 may further include a thickener. The thickener is used to increase the viscosity, which is beneficial to the sustained release effect and the interlayer bonding strength.

[0093] In one embodiment, the flavoring layer 40 may further include a thickener, which is used to increase viscosity, facilitate sustained release, and enhance interlayer bonding strength.

[0094] In a specific embodiment, the thickener may include at least one of a polycarboxyl high molecular polymer, a starch ether derivative, and a sodium hyaluronate-chitosan polyelectrolyte complex.

[0095] In a specific embodiment, the functional layer 20 may further include a plasticizer.

[0096] In one embodiment, the flavoring layer 40 may further include a plasticizer.

[0097] In a specific embodiment, the plasticizer may include at least one of glycerol, sorbitol, propylene glycol, polyethylene glycol, and xylitol. The plasticizer may be used to improve the toughness of the membrane and prevent the membrane from being too brittle.

[0098] In one embodiment, the functional layer 20 may further include a pH adjuster.

[0099] In one embodiment, the flavoring layer 40 may further include a pH adjuster.

[0100] In a specific embodiment, the pH adjuster may include at least one of citric acid, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, and magnesium carbonate.

[0101] In one embodiment, the functional layer 20 may further include an antioxidant.

[0102] In one embodiment, the flavoring layer 40 may further include an antioxidant.

[0103] In a specific embodiment, the antioxidant may include at least one of ethylparaben, ascorbic acid, vitamin E, butylated hydroxytoluene, and butylated hydroxyanisole.

[0104] In a specific embodiment, the functional layer 20 may further include a solubilizer.

[0105] In a specific embodiment, the flavoring layer 40 may further include a solubilizer.

[0106] In a specific embodiment, the solubilizing agent may include at least one of the following: polyethylene glycol (e.g., PEG-200, PEG-400, PEG-600, etc.), Tween (e.g., Tween-20, Tween-80, etc.), and poloxamer to improve the solubility of the raw material.

[0107] In a specific embodiment, the functional layer 20 may include 10 to 80 parts by weight of the first film-forming agent. For example, the functional layer 20 may include 10, 20, 30, 40, 50, 60, 70, or 80 parts by weight of the first film-forming agent.

[0108] In a specific embodiment, the functional layer 20 may include 2 to 6 parts of active material by weight. For example, the functional layer 20 may include 2, 3, 4, 5, or 6 parts of active material by weight.

[0109] In a specific embodiment, the functional layer 20 may include 0 to 10 parts by weight of a thickener. For example, the functional layer 20 may include 0, 2, 4, 6, 8, or 10 parts by weight of a thickener.

[0110] In a specific embodiment, the functional layer 20 may include 2 to 15 parts by weight of a plasticizer. For example, the functional layer 20 may include 2 parts, 5 parts, 7.5 parts, 10 parts, 12.5 parts, or 15 parts by weight of a plasticizer.

[0111] In a specific embodiment, the functional layer 20 may include 0 to 1 part by weight of a pH adjuster. For example, the functional layer 20 may include 0 part, 0.05 part, 0.1 part, 0.5 part, or 1 part by weight of a pH adjuster.

[0112] In a specific embodiment, the functional layer 20 may include 0 to 0.5 parts by weight of an antioxidant. For example, the functional layer 20 may include 0, 0.1, 0.2, 0.3, 0.4, or 0.5 parts by weight of an antioxidant.

[0113] In one embodiment, the flavoring layer 40 may include 10 to 80 parts by weight of the second film-forming agent. For example, the flavoring layer 40 may include 10, 20, 30, 40, 50, 60, 70, or 80 parts by weight of the second film-forming agent.

[0114] In a specific embodiment, the flavoring layer 40 may include 5 to 15 parts of flavoring agent by weight. For example, the flavoring layer 40 may include 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 parts of flavoring agent by weight.

[0115] In a specific embodiment, the flavoring layer 40 may include 2 to 7 parts of a cooling agent by weight. For example, the cooling agent may be 2, 3, 4, 5, 6, or 7 parts. The flavoring layer 40 may include 5 to 10 parts of a sweetener by weight. For example, the sweetener may be 5, 6, 7, 8, 9, or 10 parts. The flavoring layer 40 may include 0 to 5 parts of a fragrance by weight. For example, the fragrance may be 0, 1, 2, 3, 4, or 5 parts.

[0116] In a specific embodiment, the flavoring layer 40 may include 0 to 10 parts by weight of a thickener. For example, the flavoring layer 40 may include 0, 2, 4, 6, 8, or 10 parts by weight of a thickener.

[0117] In a specific embodiment, the flavoring layer 40 may include 2 to 15 parts by weight of a plasticizer. For example, the flavoring layer 40 may include 2 parts, 5 parts, 7.5 parts, 10 parts, 12.5 parts, or 15 parts by weight of a plasticizer.

[0118] In a specific embodiment, the flavoring layer 40 may include 0 to 1 part of a pH adjuster by weight. For example, the flavoring layer 40 may include 0 part, 0.05 part, 0.1 part, 0.5 part, or 1 part of a pH adjuster by weight.

[0119] In one embodiment, the flavoring layer 40 contains 0 to 0.5 parts by weight of an antioxidant. For example, the flavoring layer 40 may contain 0, 0.1, 0.2, 0.3, 0.4, or 0.5 parts by weight of an antioxidant.

[0120] The present application provides a method for preparing a buccal tablet 100 (hereinafter sometimes referred to as "preparation method"). It should be noted that the ingredients, dosages, etc. involved in the preparation method can be referred to the aforementioned description of the buccal tablet 100.

[0121] In a specific embodiment, the preparation method may include the following steps: obtaining a first supporting layer 10, an isolation layer 30, a second supporting layer 50, a first film-forming liquid comprising an active substance, and a second film-forming liquid comprising a flavoring agent, wherein the isolation layer 30 has a first surface and a second surface disposed opposite each other; applying the first film-forming liquid on the first surface of the isolation layer 30 to form a functional layer 20 on the first surface; applying the second film-forming liquid on the second surface of the isolation layer 30 to form a flavoring layer 40 on the second surface; covering the first supporting layer 10 on a side of the functional layer 20 facing away from the flavoring layer 40, and covering the second supporting layer 50 on a side of the flavoring layer 40 facing away from the functional layer 20, to obtain a buccal tablet 100. The buccal tablet 100 includes the first supporting layer 10, the functional layer 20, the flavoring layer 40, and the second supporting layer 50 disposed in sequence.

[0122] A first supporting layer 10, an isolation layer 30, and a second supporting layer 50 are obtained; a first film-forming liquid is obtained, and the first film-forming liquid is applied to form a functional layer 20; a second film-forming liquid is obtained, and the second film-forming liquid is applied to form a flavoring layer 40; the first supporting layer 10, the functional layer 20, the isolation layer 30, the flavoring layer 40, and the second supporting layer 50 are stacked in sequence to obtain a composite film, and then a lozenge 100 is obtained.

[0123] In a specific embodiment, the preparation method may include the following steps: applying a first film-forming liquid on the surface of the isolation layer 30 to obtain a functional layer 20; applying a second film-forming liquid on the other surface of the isolation layer to obtain a flavoring layer 40; superimposing a first support layer 10 and a second support layer 20 on both sides of the isolation layer to obtain a composite film; and subjecting the composite film to a hot press-cold roller alternating process to obtain a lozenge 100.

[0124] In one embodiment, the buccal tablet 100 is prepared by the above-mentioned preparation method.

[0125] The present invention is further described in detail below by specific experimental process and experimental data examples. The following examples are only used to further illustrate the present invention and should not be construed as limiting the present invention. In the present embodiment, unless otherwise specified, the reagents and instruments used are all commercially available, and the experimental operations are all carried out in accordance with the product specifications and conventional experimental specifications.

[0126] 1. Preparation process:

[0127] Buccal tablet A:

[0128] (1) Preparation of support layer:

[0129] Obtain porous nonwoven fabric made from polypropylene.

[0130] Use ultraviolet laser to perform secondary processing on porous non-woven fabrics with an energy density of 0.5-2J / cm 2 , pulse frequency 10-50kHz, scanning speed 100-500mm / s, forming 5μm to 50μm holes on the surface of porous non-woven fabric.

[0131] The first support layer adopts a porous non-woven fabric with a low-density macroporous design (pore size 30μm~50μm, porosity 25%-30%), and the second support layer adopts a high-density microporous design (pore size 5μm~20μm, porosity 5%-10%).

[0132] (2) Preparation of functional layer:

[0133] Weigh polyvinyl alcohol (PVA) according to the formula, add an appropriate amount of solvent (water or ethanol), and stir to dissolve at 45°C to form a uniform colloidal solution. Add nicotine raw material and continue stirring for 45 minutes to ensure that nicotine is completely dissolved and evenly dispersed in the colloidal solution. Add glycerol and polyethylene glycol (PEG) as sustained-release aids and stir for 20 minutes to fully mix the solution. Filter the solution with a 100-200 mesh filter to remove possible impurities to obtain a functional layer film-forming liquid. Centrifuge the film-forming liquid at 600rpm for 15 minutes to remove bubbles in the liquid. The formula is shown in the following table:

[0134] Function raw material Mass parts (parts) Film-forming materials PVA 80 Active substances nicotine 5 solvent water 15

[0135] (3) Coating of functional layer:

[0136] Lay a PTFE film (0.01mm thick) flat on the coating machine and evenly apply the functional layer film-forming liquid to the PTFE film surface using a scraper or roller. The coating is uniform and there are no gaps, ensuring a consistent film thickness.

[0137] (4) Drying:

[0138] Place the coated wet film in a tunnel oven and dry it in a vacuum nitrogen oven at 40–50°C until the film feels dry to the touch and the residual moisture content is less than 5%. Drying time: 30 minutes.

[0139] (5) Preparation of seasoning layer:

[0140] Prepare the film-forming liquid for the seasoning layer according to the following formula:

[0141] Function raw material Mass parts (parts) Film-forming materials Hydroxypropyl methylcellulose 50 Film-forming materials polyvinyl alcohol 25 flavoring Menthol 5 flavoring Natural sweetener (erythritol) 7.5 Cementitious materials Xanthan gum 2.5 moisturizer Propylene glycol 10

[0142] (6) Flavoring layer coating: Turn the polytetrafluoroethylene film coated with the functional layer to the other side up, coat the film-forming solution of the flavoring layer through the coating equipment, and the coating film thickness is 1 mm. After the flavoring layer is coated, the second support layer is covered on the flavoring layer. Dry at a temperature of 35-40°C, vacuum dry, and the drying time is 20 minutes.

[0143] (7) Pressing: Cover the functional layer with the first support layer, and perform hot pressing-cold roller compounding on the six-layer mold.

[0144] (8) Packaging: Cut the six-layer film into independent dosage pieces according to the specifications. Use a packaging machine and a sealing hot pressing device to place each piece of the buccal tablet in an aluminum foil bag, vacuum or nitrogen seal the package, and place it in a low-humidity sealed bag.

[0145] Buccal tablet B:

[0146] The difference between buccal tablet B and buccal tablet A is that the support layer and the functional layer are different. In buccal tablet B, by adjusting the spray-melting process parameters, a polypropylene non-woven fabric with a porosity of 15%-20% is prepared, and the first support layer and the second support layer are both polypropylene non-woven fabric with a porosity of 15%-20%. The film-forming solution formula of the functional layer of buccal tablet B is shown in the following table:

[0147] Function raw material Mass parts (parts) Film-forming materials Hydroxypropyl methylcellulose 65 Film-forming materials polyvinyl alcohol 5 Active substances nicotine 5 plasticizers glycerin 2 solvent water 23

[0148] Buccal tablet C:

[0149] The difference between buccal tablet C and buccal tablet A is that the support layer, the functional layer and the flavoring layer are different. In buccal tablet C, the same polypropylene porous non-woven fabric as in buccal tablet A is subjected to post-treatment immersion process. The non-woven fabric is soaked in an immersion solution containing temperature-sensitive additives (poly N-isopropyl acrylamide, PNIPAM) and pore-forming agents, so that the additives are attached to the inside of the non-woven fabric pores, forming a temperature-responsive structure with a porosity of 20%-25%. The ratio of the immersion solution is shown in the following table:

[0150] Function raw material Mass parts (parts) antistatic agent Glyceryl monostearate 1.5 lubricant magnesium stearate 1.5 Temperature sensitive additives Poly (N-isopropylacrylamide) 3 Porosity enhancer microcrystalline cellulose 4 solvent water Adjust volume to 100ml

[0151] The film-forming solution formula of the functional layer of buccal tablet C is shown in the following table:

[0152] Function raw material Mass parts (parts) Film-forming materials PVA 70 sustained-release tablets Sodium alginate 14 Active substances nicotine 5 plasticizers glycerin 11

[0153] The film-forming solution formula of the flavoring layer of buccal tablet C is shown in the following table:

[0154] Function raw material Mass parts (parts) Film-forming materials gelatin 72 flavoring Menthol 5 flavoring Natural sweetener (xylitol) 7 Cementitious materials agar 3 Moisturizing ingredients Propylene glycol 13

[0155] II. Performance test

[0156] Porosity testing, dissolution experiments, and breaking strength tests were conducted on buccal tablets A, B, and C to verify the characteristics of different formulations in terms of pore structure, nicotine release performance, and structural strength, providing data support for formulation optimization and product performance evaluation.

[0157] (1) Porosity test

[0158] The FX3300 air permeability tester produced by Germany's TEXTEST company is used. The instrument complies with international standards such as ISO 9237 and ASTM D737. The test range is 0.2-12000 mm / s and the accuracy is ±2%.

[0159] Three circular samples with a diameter of 5 cm were cut from the first and second supporting layers of each group of oral tablets and placed in the sample cell of the gas permeability tester. The temperature during the test was 25°C ± 1°C (standard room temperature conditions). The nitrogen pressure was set to 0.1 MPa. After stabilizing the airflow, the gas flow rate passing through the sample per unit time was recorded. Three parallel groups of samples were tested. The porosity was calculated according to the gas permeability formula: ε = QμL / AΔP, where Q is the gas flow rate, μ is the gas viscosity, L is the sample thickness, A is the sample area, and ΔP is the pressure difference.

[0160] The test results of buccal tablet A are shown in the table below:

[0161]

[0162] The test results of buccal tablet B are shown in the table below:

[0163]

[0164] The test results of buccal tablet C are shown in the table below:

[0165]

[0166] (2) Nicotine dissolution test

[0167] Dissolution apparatus: The RCZ-8M intelligent drug dissolution apparatus produced by Tianjin Tianda Tianfa Technology Co., Ltd. is used. The instrument has 8 independent dissolution cups and can accurately control the speed and temperature. The speed range is 25-200rpm and the temperature control accuracy is ±0.5℃.

[0168] Method: USPII paddle method, speed: 75 rpm, temperature: 37°C.

[0169] Dissolution medium: 900 mL PBS (pH 6.8) phosphate buffer (simulating saliva environment).

[0170] Sampling device: Equipped with an automatic sampler, it can automatically complete sampling, filtration and rehydration operations at the set time point to reduce human errors.

[0171] High Performance Liquid Chromatography (HPLC): An Agilent 1260 Infinity II HPLC equipped with a C18 column (4.6×250 mm, 5 μm) was used for accurate determination of nicotine content.

[0172] Sampling time points: sampling was performed at 30s, 1min, 2min, 3min, 5min, 10min, 15min, 20min, 30min, 45min, and 60min, respectively. 5mL of sample was taken each time (5mL of isothermal dissolution medium was added at the same time). The samples were filtered through a 0.45μm microporous membrane and then prepared for HPLC analysis.

[0173] In buccal tablets A / B / C, the nicotine content of each buccal tablet is 5%, and the specific nicotine content in the buccal tablet is 12 mg / g. Calculate the nicotine dissolution amount (unit: mg / g) at different time points for each formula. The results are Figure 4 And see the table below:

[0174]

[0175] As can be seen, the nicotine dissolution rate for buccal tablet A was the fastest, reaching a plateau after approximately 15 minutes. The nicotine dissolution rate for buccal tablet B was the slowest, but gradually stabilized after approximately 30 minutes. The nicotine dissolution rate for buccal tablet C was intermediate, with a moderate dissolution rate. This suggests that the porosity of the support layer and the formulation of the functional layer can synergistically control the release rate.

[0176] The above content is a further detailed description of the present application in conjunction with specific implementation methods, and the specific implementation of the present application cannot be considered to be limited to these descriptions. For ordinary technicians in the technical field to which the present application belongs, several simple deductions or substitutions can be made without departing from the concept of the present application.

Claims

1. A buccal tablet, characterized in that: The invention comprises a first supporting layer, a functional layer, a flavoring layer and a second supporting layer in sequence. The functional layer contains active substances, and the flavoring layer contains flavoring agents.

2. The buccal tablet according to claim 1, wherein The buccal tablet further includes an isolation layer, which is arranged between the functional layer and the flavoring layer.

3. The buccal tablet according to claim 1, wherein The functional layer includes a first functional layer and a second functional layer. The buccal tablet further includes an isolation layer, and the isolation layer is provided between the first functional layer and the second functional layer.

4. The buccal tablet according to claim 1, wherein The first supporting layer and the second supporting layer are water permeable, and the water permeability of the first supporting layer is different from the water permeability of the second supporting layer.

5. The buccal tablet according to claim 1, wherein The first supporting layer and the second supporting layer are porous structures, wherein the buccal tablet satisfies at least one of (I) to (V): (I) the first supporting layer is provided with at least one of a microporous structure and a macroporous structure; (II) the second supporting layer is provided with at least one of a microporous structure and a macroporous structure; (III) the first support layer and / or the second support layer comprises a temperature-sensitive auxiliary agent, wherein the temperature-sensitive auxiliary agent is used to adjust water permeability based on temperature changes; (IV) the porosity of the first supporting layer is 5% to 30%; (V) The porosity of the second supporting layer is 5% to 30%.

6. The buccal tablet according to claim 1, wherein The active substance includes at least one of nicotine and a nicotine derivative; and / or, the flavoring agent comprises at least one of a sweetener, an aromatic, and a cooling agent; and / or, the first supporting layer comprises at least one of the following: a thermoplastic resin porous membrane, a natural fiber nonwoven fabric, a synthetic fiber nonwoven fabric, and a woven fabric; And / or, the second supporting layer includes at least one of the following: polypropylene, a thermoplastic resin porous membrane, a natural fiber non-woven fabric, a synthetic fiber non-woven fabric, and a woven fabric.

7. The buccal tablet according to claim 1, wherein The first supporting layer and / or the second supporting layer includes a temperature-sensitive auxiliary agent, and the temperature-sensitive auxiliary agent includes poly (N-isopropylacrylamide).

8. The buccal tablet according to any one of claims 1 to 7, wherein The functional layer further comprises at least one of the following: a film former, a sustained-release agent, a thickener, a plasticizer, a pH additive, and an antioxidant; the flavoring layer further comprises at least one of the following: a film former, a sustained-release agent, a thickener, a plasticizer, a pH additive, and an antioxidant.

9. The buccal tablet according to claim 8, wherein The film-forming agent includes at least one of hydroxypropyl methylcellulose, polyvinyl alcohol, pullulan, gelatin, chitosan, polyvinyl pyrrolidone, and sodium carboxymethyl cellulose; And / or, the sustained-release agent includes at least one of sodium alginate, carrageenan (κ type), and mesoporous silica; And / or, the thickener comprises at least one of a polycarboxyl high molecular polymer, a starch ether derivative, and a sodium hyaluronate-chitosan polyelectrolyte complex; And / or, the plasticizer includes at least one of glycerol, sorbitol, propylene glycol, polyethylene glycol and xylitol.

10. A method for preparing a buccal tablet, characterized in that: include: Obtaining a first supporting layer, an isolation layer, a second supporting layer, a first film-forming liquid comprising an active substance, and a second film-forming liquid comprising a flavoring agent, wherein the isolation layer has a first surface and a second surface disposed opposite to each other; applying the first film-forming liquid on the first surface of the isolation layer to form a functional layer on the first surface; applying the second film-forming liquid on the second surface of the isolation layer to form a flavoring layer on the second surface; The first supporting layer is covered on a side of the functional layer facing away from the flavoring layer, and the second supporting layer is covered on a side of the flavoring layer facing away from the functional layer to obtain a buccal tablet, wherein the buccal tablet includes the first supporting layer, the functional layer, the flavoring layer and the second supporting layer arranged in sequence.

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