Buccal tablet and preparation method thereof

Abstract

The invention belongs to the technical field of food or medicine, and particularly relates to a buccal tablet and a preparation method thereof. The buccal tablet comprises a first supporting layer, a functional layer and a second supporting layer which are sequentially laminated, wherein the functional layer comprises an active substance, and the first supporting layer and the second supporting layer are both exocrine dissolving layers. The supporting layer in the buccal tablet is the exocrine dissolving layer and has a dissolving characteristic in saliva, so that the problem that the buccal tablet needs to be spitted after oral administration is solved, and the supporting layer also has an edible characteristic, so that discomfort and harm cannot be generated after unintentional swallowing.

Description

Technical Field

[0001] This application belongs to the field of food or pharmaceutical technology, specifically relating to a lozenge and its preparation method. Background Technology

[0002] The core functions of a lozenge are to encapsulate the contents, control the release rate, and prevent leakage. Therefore, the outer membrane must be made of materials that are saliva-resistant, tear-resistant, and insoluble in the oral environment. Consequently, it needs to be discarded after use. Furthermore, the contents of a lozenge are generally water-soluble, resulting in a rapid onset of action during oral administration. Since the outer layer is insoluble, it is prone to bursting when the contents dissolve to a certain extent, thus increasing oral waste. Summary of the Invention

[0003] This application aims to provide a lozenge and its preparation method to solve the problems of the need to discard the outer film of traditional lozenges and fiber residue.

[0004] To address the aforementioned technical problems, this application provides a lozenge comprising: a first support layer, a functional layer, and a second support layer stacked sequentially; wherein the functional layer comprises an active substance, and both the first and second support layers are exocrine fluid dissolving layers; at least one of the first and second support layers is permeable to saliva.

[0005] In one embodiment, at least one of the first support layer and the second support layer is provided with a through hole; and / or, at least one of the first support layer and the second support layer is a porous layer.

[0006] In one embodiment, the diameter of the through hole is 0.08 mm to 0.15 mm; and / or, the distribution density of the through hole is 30 holes / cm² to 50 holes / cm²; and / or, the porosity of the porous layer is 28% to 35%.

[0007] In one embodiment, the exocrine fluid dissolving layer comprises a skeleton material and a first auxiliary material; wherein the first auxiliary material comprises at least one of a solubility regulator, viscosity regulator, lubricant, crosslinking agent, first flavoring agent, bioadhesive, and pH regulator.

[0008] In one embodiment, the exocrine fluid dissolving layer comprises, by weight, the following components: 45-55 parts of a skeleton material, 20-28 parts of a solubility modifier, 12-18 parts of a viscosity modifier, 0.2-0.4 parts of a lubricant, 0.2-0.4 parts of a crosslinking agent, 0.1-0.3 parts of a bioadhesive, 0.4-0.9 parts of a first flavoring agent, and 0.3-0.6 parts of a pH adjuster.

[0009] In one embodiment, the skeleton material comprises at least one of the following: hydroxypropyl starch, pullulan, hydroxypropyl methylcellulose, sodium alginate; and / or, the solubility regulator comprises at least one of the following: trehalose, mannitol, lactose, maltodextrin; and / or, the viscosity regulator comprises at least one of the following: a mixture of polydextrose and pectin, xanthan gum, carrageenan, guar gum; and / or, the lubricant comprises at least one of the following: sodium hyaluronate, magnesium stearate, microcrystalline cellulose, talc; and / or, the crosslinking agent comprises... The first flavoring agent comprises at least one of the following: citrate, polyvinyl alcohol, povidone K30, or povidone K90; and / or the bioadhesive comprises at least one of the following: chitosan oligosaccharide, carbomer, or hydroxyethyl cellulose; and / or the first flavoring agent comprises at least one of a first flavoring, a first sweetener, a first cooling agent, a first salting agent, or a first acidifying agent; and / or the first flavoring agent is a flavor microcapsule; and / or the pH adjuster comprises at least one of the following: a mixture of disodium hydrogen phosphate and citric acid, or sodium bicarbonate.

[0010] In one embodiment, the functional layer includes a film-forming agent and a second excipient; wherein the second excipient includes at least one of an active substance, a hydrophilic regulator, a second flavoring agent, and a smoothing agent.

[0011] In one embodiment, the thickness of the exocrine fluid dissolving layer is 0.04 mm to 0.07 mm; and / or, the surface roughness of the exocrine fluid dissolving layer is ≤0.2 μm; and / or, the thickness of the functional layer is 0.03 mm to 0.05 mm; and / or, the water content of the lozenge is ≤2%; and / or, the area ratio of the exocrine fluid dissolving layer to the functional layer is 1.2 to 1.5:1.

[0012] In one embodiment, the length ratio of the exocrine fluid dissolving layer to the functional layer is (1.10~1.22):1; and / or, the width ratio of the exocrine fluid dissolving layer to the functional layer is (1.10~1.22):1.

[0013] This application also provides a method for preparing a lozenge, the method comprising: preparing a first support layer, a second support layer, and a functional layer; stacking the first support layer, the functional layer, and the second support layer in sequence, and obtaining a lozenge blank through a composite process; and obtaining the lozenge by low-temperature drying of the lozenge blank; wherein, the functional layer comprises an active substance, and the first support layer and the second support layer are both exocrine fluid dissolving layers; at least one of the first support layer and the second support layer is permeable to saliva.

[0014] This application provides a lozenge comprising: a first support layer and a second support layer consisting of a functional layer stacked sequentially; wherein both the first and second support layers are exocrine fluid-dissolving layers. The support layer in this lozenge is an exocrine fluid-dissolving layer, possessing saliva-dissolving properties, thus solving the problem of needing to spit it out after oral administration. Furthermore, this support layer is edible, so it will not cause discomfort or harm if accidentally swallowed.

[0015] Additional aspects and advantages of this application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of this application. Attached Figure Description

[0016] The above and / or additional aspects and advantages of this application will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which: Figure 1 This is a flowchart of the method for preparing lozenges in the embodiments of this application. Detailed Implementation

[0017] The embodiments of this application will now be described in detail. Examples of these embodiments are illustrated in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain this application, and should not be construed as limiting this application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0018] The terms "first" and "second" in the specification and claims of this application may explicitly or implicitly include one or more of the features. In the description of this application, unless otherwise stated, "multiple" means two or more. Furthermore, "and / or" in the specification and claims indicates at least one of the connected objects, and the character " / " generally indicates that the preceding and following objects are in an "or" relationship.

[0019] In the description of this application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc., indicating the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, 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, and therefore should not be construed as a limitation of this application.

[0020] In the description of this application, it should be noted that, unless otherwise expressly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection between two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0021] This application provides a lozenge, which includes: a first support layer, a functional layer, and a second support layer stacked sequentially; wherein the functional layer includes an active substance, and both the first support layer and the second support layer are exocrine fluid dissolving layers, and at least one of the first support layer and the second support layer is permeable to saliva.

[0022] The support layer of this lozenge is an exocrine fluid-dissolving layer, which has dissolving properties in saliva, solving the problem of needing to spit it out after oral administration. Moreover, this support layer is also edible, so it will not cause discomfort or harm if accidentally swallowed.

[0023] In one embodiment, at least one of the first and second support layers is a porous layer. For example, the pores can be micropores inherent in the material itself, through-holes, or a combination of both. When the pores are through-holes, they can further improve the dissolution rate of the support layer, making the dissolution rates of the support layer and the functional layer closer, thus avoiding the problem of the lozenge suddenly breaking open.

[0024] In one embodiment, the diameter of the through hole is 0.08 mm to 0.15 mm. This diameter range can ensure the number of through holes on the support layer, thereby ensuring the dissolution rate of the support layer.

[0025] Specifically, the diameter of the through hole is 0.08mm, 0.1mm, 0.12mm, 0.14mm, 0.15mm or any value within the above range.

[0026] In one embodiment, the distribution density of the through holes is 30 to 50 per cm². This distribution density not only ensures the stability of the support layer but also ensures the number of through holes.

[0027] Specifically, the distribution density of the through holes is 30 holes / cm², 40 holes / cm², 50 holes / cm², or any value within the above range.

[0028] In one embodiment, the porosity of the porous layer is 28% to 35%, which ensures the dissolution rate of the support layer.

[0029] Specifically, the porosity of the porous layer is 28%, 30%, 32%, 35%, or any value within the above range.

[0030] In one embodiment, the exocrine fluid dissolving layer includes a framework material and a first auxiliary material; wherein the first auxiliary material includes at least one selected from a solubility regulator, viscosity regulator, lubricant, crosslinking agent, first flavoring agent, bioadhesive, and pH adjuster. The formulation of this exocrine fluid dissolving layer ensures both the solubility of the support layer and the uniformity of the film formation within the support layer.

[0031] In one embodiment, the exocrine fluid dissolving layer, by weight, comprises the following components: 45-55 parts of a skeleton material, 20-28 parts of a solubility modifier, 12-18 parts of a viscosity modifier, 0.2-0.4 parts of a lubricant, 0.2-0.4 parts of a crosslinking agent, 0.1-0.3 parts of a bioadhesive, 0.4-0.9 parts of a first flavoring agent, and 0.3-0.6 parts of a pH adjuster. This composition and content of the exocrine fluid dissolving layer not only forms a protective film layer but also exhibits mild solubility.

[0032] The skeleton material includes at least one of the following: hydroxypropyl starch, pullulan, hydroxypropyl methylcellulose, and sodium alginate. These materials provide good film-forming properties and water solubility, ensuring the basic solubility of the support layer.

[0033] The solubility regulators include at least one of the following: trehalose, mannitol, lactose, and maltodextrin. They can not only regulate the dissolution rate of the support layer, but also reduce the glass transition temperature (Tg) of the support layer (e.g., Tg drops to 28~32℃), thereby improving the flexibility in low-temperature environments.

[0034] The viscosity modifiers include at least one of the following: a mixture of polydextrose and pectin, xanthan gum, carrageenan, and guar gum. These can optimize the mechanical properties of the support layer; for example, pectin improves the adhesion between the support layer and the functional layer, while polydextrose enhances the refreshing sensation in the mouth after dissolution.

[0035] The lubricant includes at least one of the following: sodium hyaluronate, magnesium stearate, microcrystalline cellulose, and talc. These components increase the lubricity of the support layer surface, preventing abrasion of the oral mucosa and gums caused by the roughness of traditional nonwoven fibers, thus improving its suitability for sensitive individuals.

[0036] The crosslinking agent includes at least one of the following: citrate, polyvinyl alcohol, povidone K30, or povidone K90. These can improve the tensile strength of the support layer, preventing breakage during sublingual administration, without affecting the dissolution rate of the support layer.

[0037] Among them, the bioadhesives include at least one of the following: chitosan oligosaccharides, carbomer, and hydroxyethyl cellulose. They can improve the compatibility between the support layer and the oral mucosa, reduce the coefficient of friction between the support layer and the oral mucosa, and reduce irritation in sensitive individuals.

[0038] The first flavoring agent includes at least one of the following: first flavoring, first sweetener, first cooling agent, first saltiness agent, and first acidity agent.

[0039] In one embodiment, the first flavoring agent is a first flavor microcapsule, such as gum arabic coated with spearmint essential oil. The microcapsule has a particle size of 5μm to 10μm and an encapsulation rate of ≥92%. Gum arabic provides excellent initial flavor through its rapid release characteristics, and its high encapsulation rate and small particle size ensure a delicate taste and stable flavor, ultimately achieving the product's core experiential advantage of "instant refreshing and long-lasting fragrance".

[0040] Specifically, the particle size of the first flavor microcapsules is 5 μm, 8 μm, 10 μm or any value within the above range; the encapsulation efficiency is 92%, 95%, 98% or any value within the above range.

[0041] The first flavoring is an edible flavoring, which may include at least one of the following: bergamot flavoring, eucalyptus flavoring, citrus flavoring, lemon flavoring, peppermint flavoring, peppermint flavoring, menthol, licorice flavoring, wintergreen flavoring, tobacco flavoring, coffee flavoring, vanilla flavoring, lime flavoring, apple flavoring, peach flavoring, mango flavoring, cherry flavoring, blueberry flavoring, strawberry flavoring, cola flavoring, cinnamon flavoring, pandan flavoring, and watermelon flavoring.

[0042] The first sweetener may include at least one of xylitol, sorbitol, mannitol, iodine, lactitol, maltitol, isomaltitol, hydrogenated starch hydrolysate, erythritol, maltotriol, aspartame, acesulfame potassium, sodium saccharin, sucralose, neotame, cyclamate, alitane, steviol glycosides, arabinitol, and monk fruit sweetener.

[0043] The first cooling agent may include menthol, menthol derivatives, and WS. 3 and WS At least one of 23.

[0044] The first salting agent may include at least one of sodium chloride, monosodium glutamate, and amino acid salts.

[0045] The first acidulant may include at least one of citric acid, malic acid, fumaric acid, and phosphoric acid.

[0046] pH adjusters may include at least one of the following: a mixture of disodium hydrogen phosphate and citric acid, citric acid, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, and magnesium carbonate. They can stabilize the pH of the substrate at 6.6–7.1, better matching the oral saliva environment and reducing acid-base irritation in the mouth.

[0047] Specifically, by weight, the exocrine fluid dissolving layer comprises the following components: 48-52 parts of skeleton material, 24-26 parts of dissolution regulator, 14-16 parts of viscosity regulator, 0.2-0.3 parts of lubricant, 0.3-0.4 parts of crosslinking agent, 0.2-0.3 parts of bioadhesive, 0.5-0.8 parts of primary flavoring agent, and 0.4-0.5 parts of pH adjuster.

[0048] In one embodiment, the functional layer further includes a film-forming agent and a second excipient; wherein the second excipient includes at least one of a hydrophilic regulator, a second flavoring agent, and a smoothing agent. This functional layer can better match the dissolution rate of the exocrine fluid-dissolving layer while also ensuring the optimal user experience of the lozenge.

[0049] The active substances include at least one of nicotine and nicotine derivatives. For example, nicotine includes natural nicotine and / or synthetic nicotine, and nicotine derivatives include one or more of nicotine salts, nicotine in a matrix such as a glycobase or an organometallic complex, nicotine-resin combinations, nicotine inclusion complexes, and non-covalently bound nicotine.

[0050] Non-covalently bonded nicotine includes nicotine lactate, nicotine malate, nicotine salicylate, nicotine cyclodextrin encapsulated complex, nicotine hydrochloride, nicotine dihydrochloride, nicotine tartrate, nicotine tartrate dihydrate, nicotine sulfate, nicotine zinc chloride, and nicotine benzoate. Nicotine derivatives also include nicotine with substituents, such as 6-methylnicotine, 6-methylnicotine lactate, 6-methylnicotine malate, 6-methylnicotine salicylate, 6-methylnicotine cyclodextrin encapsulated complex, 6-methylnicotine hydrochloride, 6-methylnicotine dihydrochloride, 6-methylnicotine tartrate, 6-methylnicotine tartrate dihydrate, 6-methylnicotine sulfate, 6-methylnicotine zinc chloride, and one or more mixtures of 6-methylnicotine benzoate.

[0051] The hydrophilic modifiers include at least one of the following: a mixture of polyethylene glycol 400 and povidone K30, a mixture of gelatin and pullulan, and a mixture of hydroxypropyl cellulose and mannitol. These are used to improve the solubility synchronization between the functional layer and the substrate, reducing the phenomenon of "inner solubility but outer insolubility".

[0052] The second flavoring agent includes at least one of the following: a second flavoring agent, a second sweetener, a second cooling agent, a second salting agent, and a second acidifying agent.

[0053] In one embodiment, the second flavoring agent is a second flavor microcapsule with a particle size of 5μm to 10μm and an encapsulation rate of ≥92%. The outer shell material of the flavor microcapsule is β-cyclodextrin. For example, the second flavor microcapsule is spearmint essential oil coated with β-cyclodextrin. β-cyclodextrin is used to reduce direct irritation and prolong the refreshing sensation.

[0054] It should be noted that in some embodiments, the different shell materials of the first and second flavor microcapsules are based on differentiated designs according to their functional positioning and release requirements, aiming to achieve a synergistic effect of rapid initial release and sustained sustained release of flavor. For example, the shell material of the first flavor microcapsule is gum arabic, which dissolves quickly and can rapidly release flavor in the initial stage of administration, providing a strong initial refreshing sensation, promptly masking any off-flavors of the active ingredient, and improving the user experience. The shell material of the second flavor microcapsule is β-cyclodextrin, which releases flavor slowly through molecular inclusion, forming a lasting flavor base, avoiding later taste decay, and significantly extending the duration of the refreshing sensation. Together, they constitute a "fast-slow" dual-stage release system, ensuring flavor intensity and persistence while enhancing taste complexity and product stability.

[0055] The second flavoring is an edible flavoring, which may include at least one of the following: bergamot flavoring, eucalyptus flavoring, citrus flavoring, lemon flavoring, peppermint flavoring, peppermint flavoring, menthol, licorice flavoring, wintergreen flavoring, tobacco flavoring, coffee flavoring, vanilla flavoring, lime flavoring, apple flavoring, peach flavoring, mango flavoring, cherry flavoring, blueberry flavoring, strawberry flavoring, cola flavoring, cinnamon flavoring, pandan flavoring, and watermelon flavoring.

[0056] The second sweetener may include at least one of xylitol, sorbitol, mannitol, iodine, lactitol, maltitol, isomaltitol, hydrogenated starch hydrolysate, erythritol, maltotriol, aspartame, acesulfame potassium, sodium saccharin, sucralose, neotame, cyclamate, alitane, steviol glycosides, arabinitol, and monk fruit sweetener.

[0057] The second cooling agent may include menthol, menthol derivatives, and WS. 3 and WS At least one of 23.

[0058] The second salting agent may include at least one of sodium chloride, monosodium glutamate, and amino acid salts.

[0059] The second acidulant may include at least one of citric acid, malic acid, fumaric acid, and phosphoric acid.

[0060] Among them, film-forming agents such as polyvinyl alcohol are the main film-forming agents of the functional layer, which can ensure the rapid dissolution of the functional layer and ensure that the functional layer has good toughness.

[0061] Of course, the functional layer can also include functional ingredients. Functional ingredients include at least one of the following: vitamins, caffeine, tea polyphenols, capsaicin, etc. These can be customized according to specific needs, such as for soothing a sore throat or providing an energy boost.

[0062] Among these are lubricants such as silica. These are used to improve the smoothness of the surface of the exudate-dissolving layer, thereby reducing oral friction.

[0063] In one embodiment, the functional layer comprises, by weight, the following components: 20-28 parts of film-forming agent, 8-12 parts of hydrophilic modifier, 3-5 parts of active substance, 2-5 parts of functional ingredient, 3.2-5.6 parts of second flavoring agent, and 0.05-0.1 parts of smoothing agent.

[0064] Specifically, by weight, the functional layer comprises the following components: 23-25 ​​parts of film-forming agent, 9-11 parts of hydrophilic regulator, 4-5 parts of active substance, 3-4 parts of functional ingredient, 4-5.2 parts of secondary flavoring agent, and 0.06-0.08 parts of smoothing agent.

[0065] It should also be noted that the functional layer can be a two-layer or multi-layer structure. Each layer can be configured with the same components, or different components can be configured according to requirements such as release rate and flavor.

[0066] When the functional layer is a two-layer or multi-layer structure, in some embodiments, in order to avoid mutual interference between two adjacent sub-functional layers in the functional layer, an isolation layer can be set between them, such as an exocrine fluid dissolving layer.

[0067] In one embodiment, the thickness of the exocrine fluid dissolving layer is 0.04 mm to 0.07 mm. This thickness ensures both the film-forming properties of the support layer and the release rate of the functional layer.

[0068] Specifically, the thickness of the exocrine fluid dissolution layer is 0.04 mm, 0.05 mm, 0.06 mm, 0.07 mm, or any value within the above range.

[0069] In one embodiment, the surface roughness of the exocrine fluid dissolving layer is ≤0.2μm, which can reduce the abrasive sensation during oral administration.

[0070] Specifically, the surface roughness of the exocrine fluid dissolution layer is 0.1 μm, 0.2 μm, or any value within the above range.

[0071] In one embodiment, the viscosity of the solution after the exocrine fluid dissolution layer is completely dissolved is ≤5 mPa. The viscosity of this dissolving solution ensures that there is no foreign body sensation after oral administration, avoiding or facilitating the disposal of the solution.

[0072] Specifically, the viscosity of the solution after the exocrine fluid dissolution layer is completely dissolved is 1 mPa. s, 3mPa s, 5mPa s or any value within the above range.

[0073] In one embodiment, the thickness of the functional layer is 0.03mm to 0.05mm, which is sufficient to support the material of the functional layer while ensuring the overall thickness of the lozenge.

[0074] Specifically, the thickness of the functional layer is 0.03mm, 0.04mm, 0.05mm or any value within the above range.

[0075] In one embodiment, the irritation index of the lozenge is ≤0.5, which is a non-irritating level, thus not only improving the experience but also making it suitable for sensitive individuals.

[0076] Specifically, the stimulation index of the lozenge is 0.1, 0.3, 0.5 or any value within the above range.

[0077] In one embodiment, the moisture content of the lozenge is ≤2%, which ensures both the stability of the lozenge's shape and the stability of the functional layer components.

[0078] Specifically, the moisture content of the lozenges is 0.5%, 1%, 2%, or any value within the above range.

[0079] In one embodiment, the time difference between the dissolution of the exocrine fluid dissolving layer and the functional layer is ≤3 min. This time difference can completely prevent the disintegration of the lozenge caused by "external dissolution but internal insolution".

[0080] Specifically, the time difference between the dissolution of the exocrine fluid dissolution layer and the functional layer is 1 min, 2 min, 3 min, or any value within the above range.

[0081] In one embodiment, the area ratio of the exocrine fluid dissolving layer to the functional layer is 1.2 to 1.5:1. Since the exocrine fluid dissolving layer comes into contact with saliva first, this area ratio can ensure that the exocrine fluid dissolving layer can wrap the functional layer when it dissolves, while avoiding the direct and rapid exposure of the functional layer, which would lead to the instantaneous release of the active ingredients.

[0082] Specifically, the area ratio of the exocrine fluid dissolving layer to the functional layer is 1.2:1, 1.4:1, 1.5:1, or any value within the above range.

[0083] In one embodiment, the length ratio of the exocrine fluid dissolving layer to the functional layer is (1.10~1.22):1, and the width ratio of the exocrine fluid dissolving layer to the functional layer is (1.10~1.22):1. By adjusting the length ratio and the width ratio, the area ratio of the exocrine fluid dissolving layer to the functional layer can be 1.2~1.5:1.

[0084] Specifically, the length ratio of the exocrine fluid dissolving layer to the functional layer is 1.10:1, 1.15:1, 1.22:1 or any value within the above range; the width ratio of the exocrine fluid dissolving layer to the functional layer is 1.10:1, 1.15:1, 1.22:1 or any value within the above range.

[0085] This application also provides a method for preparing a lozenge, such as... Figure 1 As shown, the method includes: S1. Prepare a first support layer, a second support layer, and a functional layer. Both the first and second support layers are exocrine fluid dissolving layers.

[0086] Step S1 specifically includes: S11. Preparation of the exocrine fluid dissolving layer, including: S111. Add the skeleton material, solubility regulator, and viscosity regulator to water, and stir for the first time at 55℃~60℃ to obtain a premixed solution.

[0087] The parameters for the first stirring process include: a stirring speed of 300 rpm to 500 rpm and a stirring time of 30 minutes to 40 minutes. These stirring parameters ensure both the uniformity of the premixed liquid and the appropriate stirring time.

[0088] Specifically, the stirring rate of the first stirrer is 300 rpm, 400 rpm, 500 rpm or any value within the above range; the stirring time of the first stirrer is 30 minutes, 35 minutes, 40 minutes or any value within the above range.

[0089] S112. Cool to 40℃~45℃, add lubricant, crosslinking agent, bio-adhesive, first flavoring agent and pH adjuster to the premixed liquid, and obtain a mixed liquid by second stirring.

[0090] Preferably, the temperature is lowered to 40℃~45℃, and lubricant, crosslinking agent, bioadhesive and pH adjuster are added to the premix. After stirring at 300rpm~500rpm for 15 minutes~20 minutes, the first flavoring agent is slowly added, and stirring is continued for 8 minutes~12 minutes to obtain the mixture. The purpose is to avoid microcapsule rupture.

[0091] The parameters for the second stirring process include: a stirring speed of 300 rpm to 500 rpm and a stirring time of 10 minutes to 30 minutes. These stirring parameters ensure both the uniformity of the mixture and the appropriate stirring time.

[0092] Specifically, the stirring rate of the second stirrer is 300 rpm, 400 rpm, 500 rpm or any value within the above range; the stirring time of the second stirrer is 10 minutes, 20 minutes, 30 minutes or any value within the above range.

[0093] S113. The mixture is subjected to a first coating treatment and a first drying treatment to obtain an initial substrate.

[0094] The parameters for the first coating process include: a coating speed of 1.2 m / min to 1.5 m / min and a coating thickness of 0.08 mm to 0.12 mm. These parameters ensure the basic properties of the substrate while reducing the coating process time.

[0095] Specifically, the coating speed of the first coating process is 1.2 m / min, 1.4 m / min, 1.5 m / min or any value within the above range; the coating thickness is 0.08 mm, 0.1 mm, 0.12 mm or any value within the above range.

[0096] The parameters for the first drying process include: a drying temperature of 65℃~70℃ and a drying time of 25 minutes~30 minutes. These parameters meet the drying requirements of the substrate while saving time in the drying process.

[0097] Specifically, the drying temperature of the first drying process is 65℃, 68℃, 70℃ or any value within the above range; the drying time is 25 minutes, 28 minutes, 30 minutes or any value within the above range.

[0098] S114. After forming through holes on the initial substrate, an exudate dissolving layer is obtained.

[0099] S12. Fabrication of the functional layer, including: S121. Add the film-forming agent and hydrophilic regulator to water, and after a third stirring at 70℃~75℃, obtain the stirred solution.

[0100] The parameters for the third stirring step include: a stirring speed of 600 rpm to 800 rpm and a stirring time of 40 to 50 minutes. These stirring parameters ensure both the homogeneity of the solution after stirring and the appropriate stirring time.

[0101] Specifically, the stirring rate of the third stirring is 600 rpm, 700 rpm, 800 rpm or any value within the above range; the stirring time is 40 minutes, 45 minutes, 50 minutes or any value within the above range.

[0102] S122. Cool the temperature to 45℃~55℃, add the active substance, second flavoring agent and smoothing agent to the stirred solution, and obtain the film-forming solution by stirring.

[0103] Specifically, the process includes: cooling the solution to 45℃~55℃, adding active substances and a lubricant to the stirred solution, and obtaining an initial film-forming solution through a fourth stirring; adding a second flavoring agent to the initial film-forming solution, and obtaining a film-forming solution through a fifth stirring.

[0104] The parameters for the fourth stirring step include: stirring speed of 600 rpm to 800 rpm and stirring time of 10 minutes to 15 minutes.

[0105] Specifically, the stirring rate of the fourth stirring is 600 rpm, 700 rpm, 800 rpm or any value within the above range, and the stirring time is 10 minutes, 12 minutes, 15 minutes or any value within the above range.

[0106] The parameters for the fifth stirring process include: stirring speed of 300 rpm to 400 rpm and stirring time of 5 minutes to 10 minutes.

[0107] Specifically, the stirring rate of the fourth stirring is 300 rpm, 350 rpm, 400 rpm or any value within the above range, and the stirring time is 5 minutes, 8 minutes, 10 minutes or any value within the above range.

[0108] S123. Perform a second coating treatment and a second drying treatment on the film-forming liquid to obtain a functional layer.

[0109] Specifically, the film-forming solution is filtered through a 100-120 mesh filter, degassed under a vacuum of -0.08MPa to -0.09MPa for 10-20 minutes, and then subjected to a second coating process and a second drying process to obtain a functional layer.

[0110] The filter screen is 100 mesh, 110 mesh, 120 mesh or any value within the above range; the vacuum pressure is -0.08MPa, -0.085MPa, -0.09MPa or any value within the above range; the degassing time is 10 minutes, 15 minutes, 20 minutes or any value within the above range.

[0111] The parameters for the second coating process include: a coating speed of 1.0 m / min to 1.2 m / min and a coating thickness of 0.06 mm to 0.08 mm. Specifically, the coating speed for the second coating process is 1.0 m / min, 1.1 m / min, 1.2 m / min, or any value within the above range; the coating thickness for the second coating process is 0.06 mm to 0.08 mm, or any value within the above range.

[0112] The parameters for the second drying process include: a drying temperature of 55℃~60℃ and a drying time of 20 minutes~25 minutes. Specifically, the drying temperature for the second drying process is 55℃, 58℃, 60℃ or any value within the above range; the drying time is 20 minutes, 23 minutes, 25 minutes or any value within the above range.

[0113] S2. The first support layer, the functional layer and the second support layer are stacked in the order of stacking, and the oral lozenge blank is obtained through composite processing.

[0114] Step S2 specifically includes: S21. Stack the first support layer, the functional layer and the second support layer in that order, and align them according to the area ratio of the substrate to the functional layer of 1.2~1.5:1, and then place them in the upper and lower molds of the radio frequency ultrasonic composite machine.

[0115] S22. A composite membrane is obtained through composite processing.

[0116] The parameters for the composite process include: composite temperature of 38℃~48℃, radio frequency power of 100W~150W, ultrasonic frequency of 20kHz~25kHz, composite pressure of 0.08MPa~0.12MPa, and composite time of 8 seconds~12 seconds. This composite technology improves the adhesion of the substrate through radio frequency preheating and achieves precise local composite through ultrasound, avoiding the compaction and clumping of the substrate.

[0117] Specifically, the composite temperature is 38℃, 40℃, 45℃, 48℃ or any value within the above range; the radio frequency power is 100W, 130W, 150W or any value within the above range; the ultrasonic frequency is 20kHz, 23kHz, 25kHz or any value within the above range; the composite pressure is 0.08MPa, 0.01MPa, 0.12MPa or any value within the above range; and the composite time is 8 seconds, 10 seconds, 12 seconds or any value within the above range.

[0118] S23. Use a CNC cutting machine to cut the composite film into pre-set specifications (such as 15mm×20mm) of oral tablet blanks.

[0119] S3. The oral lozenge blank is dried at low temperature to obtain oral lozenges.

[0120] The parameters for low-temperature drying include: temperature of 35℃~40℃, humidity of 30%RH~35%RH, and time of 15 minutes~20 minutes. This drying process ensures that the moisture content of the oral product is ≤2%, allowing for long-term storage.

[0121] Specifically, the temperature for low-temperature drying is 35℃, 37℃, 40℃ or any value within the above range; the humidity for low-temperature drying is 30%RH, 33%RH, 35%RH or any value within the above range; and the drying time is 15 minutes, 18 minutes, 20 minutes or any value within the above range.

[0122] To prevent moisture absorption and deterioration, in one embodiment, aluminum-plastic blister packaging is used to package the lozenge blank (packaging film barrier properties: oxygen permeability ≤ 0.5cc / 24h). m², water vapor transmission rate ≤0.3g / 24h m²), each individually packaged.

[0123] To better explain this solution, embodiments and comparative examples are also provided below.

[0124] Example 1 The preparation of lozenges includes: Step 1: Prepare the exocrine fluid dissolution layer.

[0125] (1) Add 50 parts of hydroxypropyl starch, 25 parts of trehalose, 15 parts of polydextrose and pectin to 4 parts of purified water and stir at 58°C and 400 rpm for 35 minutes to form a uniform premix.

[0126] (2) Cool down to 43°C, add 0.3 parts of sodium hyaluronate, 0.3 parts of citrate, 0.2 parts of chitosan oligosaccharide, 0.5 parts of disodium hydrogen phosphate and citric acid to form a mixture, stir for 18 minutes, then slowly add 0.6 parts of gum arabic coated spearmint essential oil, continue stirring for 10 minutes to obtain a mixture.

[0127] (3) Pour the mixture into the casting machine (coating speed is 1.4m / min, coating thickness is 0.1mm), and dry it in a hot air drying oven at 68℃ for 28 minutes to obtain an initial substrate of 0.05mm.

[0128] (4) A UV laser perforation machine (wavelength 355nm, power 7W) was used to perforate the initial substrate. The hole diameter was 0.1mm and the hole density was 40 holes / cm².

[0129] Step 2: Prepare the functional layer.

[0130] (1) Add 25 parts of polyvinyl alcohol, 10 parts of polyethylene glycol 400 and povidone K30 to 43 parts of purified water, stir at 73°C and 700 rpm for 45 minutes, cool to 50°C and add 4 parts of nicotine, 3 parts of vitamin, 0.2 parts of sucralose, 0.2 parts of Ws-23, 4 parts of β-cyclodextrin-coated spearmint oil and 0.08 parts of silica, stir for 20 minutes to obtain film-forming solution.

[0131] (2) The film-forming liquid was filtered through a 110-mesh filter and then degassed under vacuum (-0.08MPa~-0.09MPa, 15 minutes). It was then formed on a casting machine (coating speed 1.1m / min, coating thickness 0.07mm) and dried in a 56℃ drying oven for 23 minutes to obtain a 0.04mm functional layer.

[0132] Step 3: Radiofrequency-assisted cryogenic ultrasonic composite molding.

[0133] (1) Stack the first support layer (exocrine fluid dissolving layer), the functional layer and the second support layer (exocrine fluid dissolving layer) in the order of the first support layer (exocrine fluid dissolving layer), and align them according to the area ratio of the substrate to the functional layer of 1.4:1, and then place them in the upper and lower molds of the radio frequency ultrasound composite machine.

[0134] (2) The composite membrane was obtained by completing the composite under the conditions of 45℃ temperature, 130W radio frequency power, 23kHz ultrasonic frequency, 0.1MPa pressure and 10 seconds composite time.

[0135] (3) Use a CNC cutting machine to cut the composite film into 15mm×20mm oral tablet blanks.

[0136] Step 4: Finished product processing and packaging.

[0137] (1) The oral lozenge blank was placed in a constant temperature and humidity chamber at 40℃ and 35%RH for 18 minutes to dry, and the final moisture content was 2%.

[0138] (2) Aluminum-plastic blister packaging is used, and each piece is individually packaged to avoid moisture absorption and deterioration.

[0139] Example 2 The difference from Example 1 is that the raw materials for preparing the exocrine fluid dissolving layer in step 1 are changed, specifically: 25 parts pullulan, 25 parts hydroxypropyl methylcellulose, 12.5 parts mannitol, 12.5 parts maltodextrin, 7.5 parts xanthan gum, 7.5 parts carrageenan, 0.3 parts magnesium stearate, 0.3 parts polyvinyl alcohol, 0.1 parts carbomer, 0.5 parts a mixture of disodium hydrogen phosphate and citric acid, 0.3 parts peppermint flavoring, 0.3 parts WS-23 cooling agent, and 4 parts purified water.

[0140] Example 3 The difference from Example 1 is that the content of raw materials for preparing the exocrine fluid dissolving layer in step 1 is changed, specifically: 45 parts of hydroxypropyl starch, 20 parts of trehalose, 12 parts of a mixture of polydextrose and pectin, 0.2 parts of sodium hyaluronate, 0.2 parts of citrate, 0.1 parts of chitosan oligosaccharide, 0.3 parts of a mixture of disodium hydrogen phosphate and citric acid, 0.4 parts of gum arabic coated spearmint essential oil, and 3 parts of purified water.

[0141] Example 4 The difference from Example 1 is that the content of raw materials for preparing the exocrine fluid dissolving layer in step 1 is changed, specifically: 55 parts of hydroxypropyl starch, 28 parts of trehalose, 18 parts of a mixture of polydextrose and pectin, 0.4 parts of sodium hyaluronate, 0.4 parts of citrate, 0.3 parts of chitosan oligosaccharide, 0.6 parts of a mixture of disodium hydrogen phosphate and citric acid, 0.9 parts of gum arabic coated spearmint essential oil, and 5 parts of purified water.

[0142] Example 5 The difference from Example 1 is that the raw materials for preparing the functional layer in step 2 are changed, specifically: 12.5 parts sodium alginate, 12.5 parts pullulan, 10 parts a mixture of gelatin and pullulan, 4 parts nicotine tartrate, 3 parts vitamins, 0.2 parts sucralose, 0.2 parts Ws-23, 4 parts an equal mass of a mixture of licorice flavoring and xylitol, 0.08 parts talc, and 43 parts purified water.

[0143] Example 6 The difference from Example 1 is that the content of raw materials for preparing the functional layer in step 2 is changed, specifically: 20 parts of polyvinyl alcohol, 8 parts of a mixture of polyethylene glycol 400 and povidone K30, 3 parts of nicotine, 2 parts of vitamins, 0.1 parts of sucralose, 0.1 parts of Ws-23, 3 parts of β-cyclodextrin-coated spearmint oil, 0.05 parts of silica, and 40 parts of purified water.

[0144] Example 7 The difference from Example 1 is that the content of raw materials for preparing the functional layer in step 2 is changed, specifically: 28 parts of polyvinyl alcohol, 12 parts of a mixture of polyethylene glycol 400 and povidone K30, 5 parts of nicotine, 5 parts of vitamins, 0.3 parts of sucralose, 0.3 parts of Ws-23, 5 parts of β-cyclodextrin-coated spearmint essential oil, 0.1 parts of silica, and 45 parts of purified water.

[0145] Example 8 The difference from Example 1 is that in step 3, the radio frequency power is 100W, the ultrasonic frequency is 20kHz, the pressure is 0.08MPa, and the composite time is 8 seconds.

[0146] Example 9 The difference from Example 1 is that in step 3, the radio frequency power is 150W, the ultrasonic frequency is 25kHz, the pressure is 0.12MPa, and the composite time is 12 seconds.

[0147] Comparative Example 1 The preparation of the oral pouch includes: 1. Under the condition of using purified water as a wetting agent, 4 parts nicotine, 15 parts hydroxypropyl methylcellulose, 80 parts sorbitol, 1.5 parts menthol, and 0.2 parts sucralose were subjected to high-speed shear granulation.

[0148] 2. The wet granules are dried in a fluidized bed at 60°C until the moisture content is 2% to obtain the dried granules.

[0149] 3. Mix the dried granules with 1 part magnesium stearate evenly, fill the mixture between two pieces of non-woven fabric, and seal the edges with heat to make a traditional mouth bag.

[0150] The following tests were performed on the oral products of the above embodiments and comparative examples.

[0151] I. Simulation experiment on disintegration time and oral dissolution behavior. The test results are shown in Table 1.

[0152] 1. Using a disintegration time limit test device, the basket was immersed in a constant temperature water bath at 37°C. The medium in the beaker was artificial saliva. The pH of the artificial saliva was 6.8, and the formula was: 0.844g sodium chloride, 1.200g potassium chloride, 0.260g sodium bicarbonate, 0.028g sodium dihydrogen phosphate, 0.010g sodium urate, 0.030g lactic acid, and 3.000g mucin in 1000mL purified water.

[0153] 2. Take the oral products from the examples and comparative examples as samples, and place the samples in the glass tube of the basket to activate the disintegration time limit test device. At the same time, place the samples in another undisturbed beaker containing an equal amount of artificial saliva and let the samples stand to observe the complete dissolution time.

[0154] 3. Remove the sample every 5 minutes, gently touch it with soft tweezers, observe its morphological changes, and record the entire process from initial expansion, the appearance of pores on the surface, to gradual disintegration and thinning. Also record the time it takes for the main structure to completely disintegrate and lose its sheet shape. For the disintegrated sample, use tweezers to check the basket for any insoluble residual substrate.

[0155] 4. Observe the static sample and record the time required for it to become clear that there are no visible residues after it has been placed in the solution.

[0156] Table 1. Simulation Experiment Data on Disintegration Time and Intraoral Dissolution Behavior of Lozenges

[0157] As shown in Table 1, the lozenges in the examples completely dissolve within 50-58 minutes, maintain their main structure for 25-33 minutes, enabling continuous nicotine release, and then rapidly dissolve completely without any insoluble residue, achieving the ultimate goal of "no need to spit it out." In the comparative example, although the functional layer dissolves rapidly, it always leaves an intact non-woven fabric substrate.

[0158] II. The experiment on the determination of nicotine dissolution rate is shown in Table 2.

[0159] 1. A dissolution tester was used. The rotation speed was set to 50 rpm, the dissolution medium was 500 mL of artificial saliva, and the temperature was maintained at 37℃.

[0160] 2. Take the oral products of the examples and comparative examples as samples, and put the samples into the dissolution cup. Automatically take 5 mL samples at 2, 5, 10, 15, 20, 30, 45 and 60 minutes respectively, and at the same time replenish fresh dissolution medium of the same temperature and volume.

[0161] 3. The sample was filtered through a 0.45 μm microporous membrane, and the nicotine content in the filtrate at each time point was determined by high performance liquid chromatography. The formula for the cumulative nicotine dissolution percentage is as follows: ; Where Pn represents the cumulative leaching percentage (%) of nicotine at the nth sampling time point; C n V0 represents the nicotine concentration (μg / mL) in the filtrate of the sample taken at the nth sampling time point; V0 represents the volume of the dissolution medium, 500 mL; C i V represents the nicotine concentration (μg / mL) in the filtrate of the sample taken at the i-th sampling time point; s W0 indicates a fixed automatic sampling volume of 5 mL each time; W0 indicates the labeled amount of nicotine in the lozenge sample is 4000 μg; D indicates the correction coefficient for the dosage unit and is 1.

[0162] The test parameters for high performance liquid chromatography were as follows: C18 column, mobile phase of acetonitrile-phosphate buffer (50:50, v / v) at pH 4.5, and detection wavelength of 260 nm.

[0163] Table 2. Experimental data for nicotine dissolution determination.

[0164] As shown in Table 2, compared to the comparative example, the dissolution percentage of the lozenge in the embodiment reached 79% after 30 minutes, indicating that the active ingredient could be continuously and stably released during the main period of sublingual administration. The dissolution percentage reached 98% after 60 minutes, indicating that the active ingredient was almost completely released, with high bioavailability and no waste. Therefore, the dissolution and disintegration behaviors of the lozenge in the embodiment are highly synergistic, enabling the continuous release of most of the nicotine within 30 minutes to meet usage needs, and complete release within 1 hour, further demonstrating the rationality of the product design.

[0165] III. Stability and moisture-proof adhesion test, the experimental data are shown in Table 3.

[0166] 1. Take the oral products of the completed aluminum-plastic blister packaging examples and comparative examples as samples, and divide the samples into two groups and place them in a constant temperature and humidity chamber.

[0167] 2. Place one lozenge in a high-temperature, high-humidity environment (40℃, 75%RH), and take samples for testing at the end of 0, 1, 2, and 3 months. Finally, characterize the moisture-proof performance of the lozenge based on the moisture absorption weight gain rate. The formula for the moisture absorption weight gain rate is: W g =(W t W0) / W0×100%.

[0168] Among them, W g Indicates the moisture absorption weight gain rate (%); W t W0 represents the mass (g) of the sample at test time t; W0 represents the initial mass (g) of the sample.

[0169] 3. Take 10 lozenges and place them in high temperature and high humidity (40℃, 75%RH) and room temperature (25℃, 60%RH) environments. Stack them together and apply a certain pressure (50g weight) for 1 minute. At the end of 0, 1, 2 and 3 months, use a texture analyzer to quantitatively determine their peel force to indicate whether the lozenges stick together.

[0170] 4. Place one piece of the oral medication under high temperature and high humidity (40℃, 75%RH) and room temperature (25℃, 60%RH) conditions. Samples are taken at the end of 0, 1, 2, and 3 months to test the peel strength between the substrate and the functional layer. This is used to characterize the composite strength between the substrate and the functional layer of the oral medication. Observe the surface under a magnifying glass for any signs of deliquescence, deformation, discoloration, etc. The initial composite strength between the substrate and the functional layer is 2.35 N.

[0171] Table 3. Experimental data on stability and moisture-proof adhesion.

[0172] As can be seen from Table 3, compared with the comparative example, even when the oral product of the embodiment was subjected to accelerated testing at 40°C and 75% RH, the moisture absorption weight gain rate at the end of 3 months was less than 2%, which is far lower than the common moisture absorption standard in the industry (usually >5% is considered unqualified). This is due to the efficient low-temperature drying process and the high-barrier aluminum-plastic packaging.

[0173] Furthermore, the oral tablets in the embodiment, after three months of accelerated testing at 40°C and 75%RH, only showed slight adhesion, with peel strength far below the standard that would cause difficulty in use. After three months of accelerated testing at 25°C and 60%RH, they showed no adhesion at all. This indicates that the product surface is smooth and the moisture content is extremely low, effectively preventing the oral tablets from sticking together due to moisture absorption.

[0174] In addition, the oral tablets of the embodiment were subjected to accelerated testing at 40°C and 75%RH or 25°C and 60%RH. After three months, there was no change in appearance, and the composite strength after three months remained above 90% of the initial composite strength. This proves the effectiveness of the radio frequency assisted low-temperature ultrasonic composite process and ensures that there is no risk of delamination throughout the product's entire life cycle.

[0175] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "illustrative embodiment," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0176] Although embodiments of this application have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of this application, the scope of which is defined by the claims and their equivalents.

Claims

1. A lozenge, characterized in that, The lozenge comprises: a first support layer, a functional layer, and a second support layer stacked sequentially; The functional layer includes an active substance, and both the first support layer and the second support layer are exocrine fluid dissolving layers; at least one of the first support layer and the second support layer is permeable to saliva.

2. The lozenge according to claim 1, characterized in that, At least one of the first support layer and the second support layer is provided with a through hole; And / or, at least one of the first support layer and the second support layer is a porous layer.

3. The lozenge according to claim 2, characterized in that, The diameter of the through hole is 0.08mm~0.15mm; And / or, the distribution density of the through holes is 30 holes / cm² to 50 holes / cm²; And / or, the porosity of the porous layer is 28% to 35%.

4. The lozenge according to claim 1, characterized in that, The exocrine fluid dissolving layer comprises a skeleton material and a first auxiliary material; The first auxiliary material includes at least one of a solubility modifier, viscosity modifier, lubricant, crosslinking agent, first flavoring agent, bioadhesive, and pH adjuster.

5. The lozenge according to claim 4, characterized in that, By weight, the exocrine fluid dissolving layer comprises the following components: 45-55 parts of skeleton material, 20-28 parts of dissolution regulator, 12-18 parts of viscosity regulator, 0.2-0.4 parts of lubricant, 0.2-0.4 parts of crosslinking agent, 0.1-0.3 parts of bioadhesive, 0.4-0.9 parts of first flavoring agent, and 0.3-0.6 parts of pH adjuster.

6. The lozenge according to claim 4, characterized in that, The skeleton material includes at least one of the following: hydroxypropyl starch, pullulan, hydroxypropyl methylcellulose, and sodium alginate; And / or, the solubility regulator includes at least one of the following: trehalose, mannitol, lactose, maltodextrin; And / or, the viscosity modifier comprises at least one of the following: a mixture of polydextrose and pectin, xanthan gum, carrageenan, or guar gum; And / or, the lubricant comprises at least one of the following: sodium hyaluronate, magnesium stearate, microcrystalline cellulose, talc; And / or, the crosslinking agent includes at least one of the following: citrate, polyvinyl alcohol, povidone K30, or povidone K90; And / or, the bioadhesive comprises at least one of the following: chitosan oligosaccharide, carbomer, hydroxyethyl cellulose; And / or, the first flavoring agent includes at least one of a first flavoring, a first sweetener, a first cooling agent, a first salting agent, and a first acidifier; And / or, the first flavoring agent is a flavor microcapsule; And / or, the pH adjuster includes at least one of the following: a mixture of disodium hydrogen phosphate and citric acid, or sodium bicarbonate.

7. The lozenge according to claim 1, characterized in that, The functional layer also includes a film-forming agent and a second excipient; The second excipient includes at least one of a hydrophilic regulator, a second flavoring agent, and a smoothing agent.

8. The lozenge according to any one of claims 1 to 7, characterized in that, The thickness of the exocrine fluid dissolution layer is 0.04 mm to 0.07 mm; And / or, the surface roughness of the exocrine fluid dissolving layer is ≤0.2μm; And / or, the thickness of the functional layer is 0.03mm~0.05mm; And / or, the moisture content of the lozenge is ≤2%; And / or, the area ratio of the exocrine fluid dissolving layer to the functional layer is 1.2~1.5:

1.

9. The lozenge according to claim 8, characterized in that, The length ratio of the exocrine fluid dissolving layer to the functional layer is (1.10~1.22):1; And / or, the width ratio of the exocrine fluid dissolving layer to the functional layer is (1.10~1.22):

1.

10. A method for preparing a lozenge, characterized in that, The method for preparing the lozenge as described in any one of claims 1 to 9 comprises: Fabricate a first support layer, a second support layer, and a functional layer; The first support layer, the functional layer and the second support layer are stacked in that order, and a composite process is performed to obtain a lozenge blank. The lozenge is obtained by low-temperature drying of the lozenge blank; The functional layer includes an active substance, and both the first support layer and the second support layer are exocrine fluid dissolving layers; at least one of the first support layer and the second support layer is permeable to saliva.

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