Buccal tablet and preparation method thereof

Abstract

The invention belongs to the technical field of buccal tablets, and particularly relates to a buccal tablet and a preparation method thereof. The buccal tablet comprises a first supporting layer, an oil absorption layer and a second supporting layer which are sequentially arranged in a stacked mode, at least one of the first supporting layer and the second supporting layer is a water permeable layer, the oil absorption layer comprises an oil absorption base body and oily liquid, and the oily liquid comprises oily base liquid and active substances and / or flavor substances dissolved in the oily base liquid. The oil absorption base body strongly adsorbs and locks the oily liquid through the capillary action, and leakage of the oily liquid is prevented. The oil absorption layer continuously supplies the active substances during the buccal period, the first supporting layer can also control the seepage rate of the active substances, and the synergistic effect of the two ensures the release stability of the active substances.

Description

Technical Field

[0001] This application belongs to the field of oral lozenge technology, specifically relating to an oral lozenge and its preparation method. Background Technology

[0002] In related technologies, lozenges primarily use coated composite films or powder compression tablets as dosage forms, with the core function being the release of active or flavorful functional substances through the oral mucosa. Currently, lozenges suffer from the following drawbacks: coated composite films rely on matrix dissolution or swelling to release active substances, resulting in a rapid initial release rate followed by a slower rate, leading to large concentration fluctuations and an inability to sustainably alleviate withdrawal symptoms; the matrix has poor encapsulation properties, making it prone to disintegration during use, thus affecting the stability of active substance release.

[0003] Therefore, developing a new type of lozenge with a novel structure has become an urgent technical problem to be solved. Summary of the Invention

[0004] This application aims to provide a lozenge and its preparation method to solve the problems of poor stability of active substance release, onset speed, and shape stability of existing lozenges.

[0005] To address the aforementioned technical problems, this application provides a lozenge comprising: a first support layer, an oil-absorbing layer, and a second support layer stacked sequentially, wherein at least one of the first support layer and the second support layer is a water-permeable layer; the oil-absorbing layer comprises an oil-absorbing matrix and an oily liquid, wherein the oily liquid comprises an oily base liquid and active substances and / or flavoring substances dissolved in the oily base liquid; wherein the oil absorption ratio of the oil-absorbing matrix is ​​greater than that of the first support layer and the second support layer.

[0006] In one embodiment, the lozenge further includes at least one absorbent layer disposed between the oil-absorbing layer and the water-permeable layer; wherein the absorbent layer includes an absorbent matrix, and the oil absorption ratio of the absorbent matrix is ​​less than the oil absorption ratio of the oil-absorbing matrix.

[0007] In one embodiment, the thickness of the absorbent layer is 0.1 mm to 0.3 mm; and / or, the absorbent substrate is medical absorbent cotton.

[0008] In one embodiment, the active substance includes at least one of nicotine and nicotine derivatives; and / or, the flavor substance includes at least one of flavoring, sweetener, cooling agent, salting agent, and acidulant; and / or, the oily liquid further includes at least one of antioxidant and preservative; and / or, the oily base liquid includes vegetable oil, wherein the mass fraction of the vegetable oil in the oily liquid is not less than 20%; and / or, the oily liquid further includes water, wherein the water content of the oily liquid is not less than 10%.

[0009] In one embodiment, the first support layer and / or the second support layer are nonwoven fabric layers; and / or, the thickness of the first support layer and / or the second support layer is 0.14mm~0.25mm; and / or, the thickness of the oil-absorbing layer is 0.2mm~0.4mm; and / or, the oil absorption ratio of the oil-absorbing substrate is 30g / g~85g / g; and / or, the oil retention rate of the oil-absorbing substrate is 95%~100%; and / or, the moisture content of both the first support layer and the second support layer does not exceed 3%; and / or, the material of the first support layer and / or the second support layer is viscose fiber; and / or, the material of the oil-absorbing substrate is modified polypropylene fiber nonwoven fabric.

[0010] In one embodiment, the oil-absorbing layer comprises at least two layers of the oil-absorbing substrate.

[0011] In one embodiment, an isolation layer is provided between at least one pair of adjacent oil-absorbing substrates.

[0012] In one embodiment, the mouthpiece further includes a fixing structure formed on the periphery of the mouthpiece.

[0013] This application also provides a method for preparing a lozenge, the method comprising: stacking a first support layer, an oil-absorbing layer, and a second support layer sequentially, and obtaining the lozenge by pressing; wherein, the oil-absorbing layer comprises an oil-absorbing matrix adsorbing an oily liquid, the oily liquid comprising an oily base liquid and active substances and / or flavoring substances dissolved in the oily base liquid, and the oil absorption ratio of the oil-absorbing matrix is ​​greater than that of the first support layer and the second support layer, respectively.

[0014] In one embodiment, the oil-absorbing layer includes an oil-absorbing matrix that adsorbs oily liquid, comprising: injecting a measured amount of the oily liquid into the oil-absorbing matrix to obtain the oil-absorbing layer.

[0015] This application provides a lozenge comprising: a first support layer, an oil-absorbing layer, and a second support layer stacked sequentially. At least one of the first and second support layers is a water-permeable layer. The oil-absorbing layer includes an oil-absorbing matrix and an oily liquid, the oily liquid comprising an oily base liquid and active substances and / or flavoring substances dissolved in the oily base liquid. The oil-absorbing matrix strongly adsorbs and locks in the oily liquid through capillary action, preventing leakage. During sublingual administration, the oil-absorbing layer continuously supplies the active substances, and the support layer can also control the exudation rate of the active substances. The synergistic effect of the two ensures the stability of the release of the active substances. At the same time, the second support layer, as the bottom controlled-release membrane and structural support, together with the first support layer, forms a symmetrical controlled-release structure, ensuring the consistency of release behavior on both sides during sublingual administration, guaranteeing the reliability and appearance stability of the lozenge during use, and preventing it from disintegrating in the mouth.

[0016] 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. Detailed Implementation

[0017] 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.

[0018] 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.

[0019] This application provides a lozenge, which includes: a first support layer, an oil-absorbing layer, and a second support layer stacked sequentially, wherein at least one of the first support layer and the second support layer is a water-permeable layer, the oil-absorbing layer includes an oil-absorbing matrix and an oily liquid, the oily liquid includes an oily base liquid and active substances and / or flavor substances dissolved in the oily base liquid; the oil absorption ratio of the oil-absorbing matrix is ​​greater than that of the first support layer and the second support layer.

[0020] This design employs a sandwich structure consisting of a first support layer, an oil-absorbing layer, and a second support layer. The oil absorption rate of the middle oil-absorbing layer is greater than that of the first and second support layers, effectively locking in oily liquids and preventing leakage. At least one of the first and second support layers is a water-permeable layer, which not only provides a channel for the active substance but also regulates its release rate. The synergistic effect of both layers ensures the stability of nicotine release.

[0021] In one embodiment, the first support layer and the second support layer are designed to be the same, both being water-permeable layers. The second support layer serves as the bottom controlled-release membrane and structural support, and together with the first support layer, they form a symmetrical controlled-release structure, ensuring the consistency of release behavior on both sides when taken orally. This guarantees the reliability and appearance stability of the lozenge during use, and prevents it from easily disintegrating in the mouth.

[0022] In one embodiment, one of the first support layer and the second support layer is a water-permeable layer and the other is a water-impermeable layer. In this case, saliva in the mouth will slowly permeate into the oil-absorbing layer in the middle through the water-permeable layer, causing the oil-absorbing matrix to swell and release the oily liquid adsorbed therein. Since the other support layer is water-impermeable, saliva cannot permeate from this side. When a user takes this type of lozenge orally, they can choose to place the water-impermeable layer on the surface of the gums. In this way, the oily liquid in the oil-absorbing layer can only be released unidirectionally to the side of the water-permeable layer (away from the gums), avoiding the components from dispersing towards the gums and avoiding the active substances and other components in the oily liquid from directly irritating the gums, thereby helping to protect the gums.

[0023] If the active ingredient in the oily liquid is a gum-protecting component, when taking this type of lozenge orally, the user can place it with the waterproof layer facing outwards towards the outside of the mouth / tongue. This prevents the oily liquid released from the absorbent layer from flowing outwards and also prevents saliva from diluting the absorbent layer from the outside. This allows the oily liquid to form a thin oil film between the waterproof layer and the gums, firmly adhering to the gingival mucosa surface. The oily base itself is hydrophobic and has good biocompatibility with the gingival mucosa biofilm, forming a continuous oil film on the gingival surface. This prevents the gum-protecting component from being quickly washed away by saliva, extending the duration of action from a few minutes with ordinary lozenges to tens of minutes, achieving long-lasting gum protection.

[0024] In one embodiment, the oil absorption ratio of the oil-absorbing matrix is ​​30 g / g to 85 g / g, where g / g represents the maximum mass of oily liquid that 1 gram of dry oil-absorbing matrix can absorb and retain. If the oil absorption ratio is too low, the matrix cannot lock in the oily liquid for a long time, resulting in the rapid release of the active substance and a shortened usage time. If the oil absorption ratio is too high, the matrix's binding force on the oily liquid is too strong, making it difficult for saliva to fully dissolve the active substance, reducing the absorption efficiency of the active substance by the oral mucosa and failing to achieve the expected physiological satisfaction effect. Therefore, the oil absorption ratio of the oil-absorbing matrix is ​​30 g / g to 85 g / g.

[0025] Specifically, the oil absorption ratio of the oil-absorbing matrix is ​​30g / g, 50g / g, 70g / g, 85g / g, or any value within the above range.

[0026] In one embodiment, the oil retention rate of the oil-absorbing matrix is ​​95% to 100%. This range ensures that the oily liquid is firmly locked after adsorption, with minimal loss during use, thus guaranteeing the stability of the active material and the user experience.

[0027] Specifically, the oil retention rate of the oil-absorbing matrix is ​​95%, 96%, 98%, 100%, or any value within the above range.

[0028] In one embodiment, the lozenge further includes at least one absorbent layer disposed between the oil-absorbing layer and the water-permeable layer. The absorbent layer includes an absorbent matrix, the oil absorption ratio of which is less than that of the oil-absorbing matrix.

[0029] The absorbency ratio of the water-absorbing matrix is ​​lower than that of the oil-absorbing matrix to ensure that the oily liquid is stored in the oil-absorbing matrix to the greatest extent. Simultaneously, the water-absorbing matrix has the characteristic of rapid water absorption, so it can quickly absorb saliva and establish a water channel from the oil-absorbing matrix to the oral mucosa during sublingual administration, thereby accelerating the onset of action of the active substance. Furthermore, the water-absorbing matrix also enhances the adsorption and diffusion of the active substance, thus increasing the absorption rate of the active substance through the oral mucosa.

[0030] In one embodiment, the thickness of the absorbent layer is 0.1 mm to 0.3 mm. This thickness can better promote the adsorption and diffusion of the active substance at the moment of ingestion.

[0031] Specifically, the thickness of the absorbent layer is 0.1 mm, 0.2 mm, 0.3 mm, or any value within the above range.

[0032] In one embodiment, the absorbent substrate is medical absorbent cotton. The high hydrophilicity and gentle skin-fitting properties of absorbent cotton meet the water-permeable controlled-release requirements of lozenges. At the same time, absorbent cotton is inexpensive and has safety properties, making it more conducive to industrialization.

[0033] In one embodiment, the oily liquid includes, in addition to the oily base liquid, active substance, and flavoring substance, at least one of antioxidant and preservative.

[0034] In one embodiment, the oily base liquid includes vegetable oil, and the mass fraction of vegetable oil in the oily liquid is not less than 20%. Dissolving the active substance in vegetable oil, combined with antioxidants and flavoring agents, can form a stable oily liquid that can both prevent the active substance nicotine from directly contacting the mucous membrane and reduce evaporation loss.

[0035] In one embodiment, the oily liquid also includes water, with a water mass fraction of not less than 10%. Although water is immiscible with oil, it can form a fine dispersion under high-speed stirring or homogenization. When the water-containing oily liquid is adsorbed by the oil-absorbing matrix, the water in saliva will more easily "connect" with the water in the oily liquid, quickly establishing a channel for the release of active substances from the oil phase to the saliva, thereby significantly accelerating the initial release rate of the active substances and solving the problem of slow onset of action in traditional oil-based formulations.

[0036] In one embodiment, the oily liquid, by weight parts, comprises: 5 to 15 parts of active ingredient, 0.1 to 0.2 parts of preservative, 30 to 55.8 parts of vegetable oil, 0.2 to 0.5 parts of antioxidant, 11 to 17 parts of flavoring agent, and 15 to 30 parts of water. This formulation of the oily liquid satisfies both safety and user experience requirements.

[0037] Specifically, the active ingredient is present in the following quantities: 5 parts by mass, 8 parts by mass, 12 parts by mass, 15 parts by mass, or any value within the above range; the preservative is present in the following quantities: 0.1 parts by mass, 0.15 parts by mass, 0.2 parts by mass, or any value within the above range; the vegetable oil is present in the following quantities: 30 parts by mass, 35 parts by mass, 40 parts by mass, 45 parts by mass, 50 parts by mass, 55.8 parts by mass, or any value within the above range; the antioxidant is present in the following quantities: 0.2 parts by mass, 0.3 parts by mass, 0.45 parts by mass, 0.5 parts by mass, or any value within the above range; the flavoring agent is present in the following quantities: 11 parts by mass, 13 parts by mass, 15 parts by mass, 17 parts by mass, or any value within the above range; and the water is present in the following quantities: 15 parts by mass, 20 parts by mass, 25 parts by mass, 30 parts by mass, or any value within the above range.

[0038] In one embodiment, the active substance includes 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.

[0039] 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.

[0040] In some embodiments, the active substance may also include other substances with specific active or medicinal properties, such as at least one of caffeine, tea polyphenols, theophylline, vitamins, etc.

[0041] In one embodiment, the vegetable oil includes at least one of the following: olive oil and sunflower seed oil. These can increase the solubility of nicotine, thereby reducing irritation.

[0042] In one embodiment, the preservative includes at least one of the following: ethylparaben, methylparaben, sodium benzoate, and potassium sorbate. These preservatives inhibit the growth and reproduction of microorganisms by disrupting their cell structure or metabolic processes, thereby preventing microbial proliferation.

[0043] In one embodiment, the antioxidant includes at least one of the following: vitamin E, ascorbate palmitate, tert-butyl-p-hydroxyanisole, and di-tert-butyl-p-cresol. These antioxidants scavenge free radicals in the system by donating hydrogen atoms or electrons, thereby preventing nicotine oxidation.

[0044] In one embodiment, the flavoring agent includes at least one of flavoring, sweetener, cooling agent, salting agent, and acidulant. These can mask residual off-flavors, thereby improving the taste.

[0045] In one embodiment, the flavoring includes 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.

[0046] In one embodiment, the sweetener includes at least one of the following: 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.

[0047] In one embodiment, the cooling agent includes at least one of the following: menthol, menthol derivatives, WS. 3 and WS twenty three.

[0048] In one embodiment, the saltiness agent includes at least one of the following: sodium chloride, monosodium glutamate, and amino acid salt.

[0049] In one embodiment, the acidulant includes at least one of the following: citric acid, malic acid, fumaric acid, and phosphoric acid.

[0050] In one embodiment, the first support layer and / or the second support layer are non-woven fabric layers, meaning that at least one of the first support layer and the second support layer is a non-woven fabric layer. The non-woven fabric layer is a water-permeable layer, which can effectively ensure the permeation effect of active substances and water, thereby facilitating the uniform release of active substances in the oral cavity.

[0051] The thickness of the first and second support layers should not be too large, as this will affect the user experience; conversely, the thickness of the first and second support layers should not be too small, otherwise it will be difficult to control the release rate of oily liquid in the oil-absorbing layer. In one embodiment, the thickness of the first and / or second support layers is 0.14 mm to 0.25 mm. For example, the thickness of both the first and / or second support layers may be 0.14 mm, 0.18 mm, 0.22 mm, 0.25 mm, or any value within the above range.

[0052] In one embodiment, the water content of both the first support layer and the second support layer is ≤3%. The low water content in the support layer ensures that when the lozenge is not used, the moisture will not form a water channel with the moisture in the oil-absorbing matrix, allowing the active substance to dissipate and ensuring the stability of the oily liquid.

[0053] Specifically, the water content of the first support layer and the second support layer is 1%, 2%, 3%, or any value within the above range.

[0054] In one embodiment, the thickness of the oil-absorbing layer is 0.2 mm to 0.4 mm. This thickness can lock in oily liquids, preventing leakage, and can also reduce the overall thickness of the lozenge, improving the user experience.

[0055] Specifically, the thickness of the oil-absorbing layer is 0.2 mm, 0.3 mm, 0.4 mm, or any value within the above range.

[0056] In one embodiment, the material of the first support layer and / or the second support layer is viscose fiber.

[0057] In one embodiment, the oil-absorbing substrate is made of modified polypropylene fiber nonwoven fabric. The modified polypropylene fiber nonwoven fabric includes meltblown microfiber polypropylene nonwoven fabric with an oleophilic and hydrophobic surface modification.

[0058] In one embodiment, the oil-absorbing layer comprises at least two oil-absorbing substrates. This oil-absorbing layer is composed of two or more oil-absorbing substrates with different properties, layered and stacked together. This multi-layered composite structure, through the complementary properties of different oil-absorbing substrates, enables precise loading of active components and flavor substances.

[0059] In order to eliminate interlayer performance interference, accurately control the component migration path, and enhance structural stability, an isolation layer is provided between at least one pair of adjacent oil-absorbing substrates.

[0060] In one embodiment, the lozenge further includes a fixing structure formed on the periphery of the lozenge, such as the edge of the lozenge or a region at a certain distance from the edge, and the fixing structure can ensure the adhesion between the layers of the lozenge.

[0061] This application also provides a method for preparing a lozenge, the method comprising: stacking a first support layer, an oil-absorbing layer and a second support layer in sequence, and obtaining a lozenge by pressing.

[0062] Existing processes require mold changes and powder ratio adjustments to achieve different dosages, resulting in long switchover cycles and high costs, and are not suitable for quickly adapting to individuals with mild, moderate, or severe nicotine dependence. Therefore, one embodiment utilizes a fully automated injection system to inject oily liquid into the oil-absorbing layer. Different dosages can be achieved simply by adjusting the injection volume, without requiring equipment replacement. The specific method is as follows: S1. The first support layer, the oil-absorbing layer, and the second support layer are stacked in sequence and pressed into a composite sheet using an ultrasonic welding machine. The pressing parameters of the ultrasonic welding machine include: power of 250W~350W, frequency of 18kHz~22kHz, and time of 0.4s~0.6s.

[0063] Ultrasonic welding achieves extremely high interlayer bonding strength, meaning that the structure remains a solid whole during the use of the lozenge, without delamination or disintegration. In contrast, traditional products have poor interlayer bonding strength, leading not only to burst release but also physical irritation. Lozenges in the mouth often shed powder, become fuzzy, or delaminate due to friction and saliva. These fine particles adhere to the oral mucosa, directly causing a foreign body sensation and discomfort, severely reducing the taste. In contrast, the lozenge in this embodiment does not delaminate, shed particles, or generate dust during use, maintaining a smooth surface and dense structure. This physical integrity ensures that users do not experience the roughness caused by carrier breakage, greatly improving the comfort of use.

[0064] Specifically, the power is 250W, 300W, 350W or any value within the above range; the frequency is 18kHz, 20kHz, 22kHz or any value within the above range; and the time is 0.4s, 0.5s, 0.6s or any value within the above range.

[0065] The composite sheet is a circular sheet with a diameter of 20 mm and a height of 1 mm.

[0066] In one embodiment, a water-absorbing layer may also be provided between the first support layer and the oil-absorbing layer in this step. The water-absorbing matrix in the water-absorbing layer has the characteristic of rapid water absorption, so it can quickly absorb saliva and establish a water channel from the oil-absorbing matrix to the oral mucosa when taken sublingually, thereby accelerating the onset of action of the active substance.

[0067] In one embodiment, the oil-absorbing layer may include at least two oil-absorbing substrates. This multi-layer composite structure can achieve precise loading of active components and flavor substances by complementing the properties of different oil-absorbing substrates.

[0068] To eliminate interlayer performance interference, precisely control component migration paths, and enhance structural stability, an isolation layer can be set between adjacent oil-absorbing matrix layers.

[0069] S2, Preparation of oily liquids.

[0070] Add vegetable oil to a sterile mixing tank and heat to a first temperature of 35℃~45℃, maintaining a constant temperature. Then add the antioxidant and stir at 400rpm~600rpm for 8min~12min (i.e., the first stirring) until completely dissolved. Then cool the solution to a second temperature of 20℃~30℃, and add the active ingredient, preservative, active substance, and water in sequence. Then stir at 250rpm~350rpm for 15min~25min (i.e., the second stirring) until a homogeneous and stable dispersion system, i.e., an oily liquid, is formed. Immediately transfer to a light-proof container for storage until use.

[0071] Specifically, the first temperature is 35℃, 40℃, 45℃ or any value within the above range; the first stirring speed is 400rpm, 500rpm, 600rpm or any value within the above range; the first stirring time is 8min, 10min, 12min or any value within the above range; the second temperature is 20℃, 25℃, 30℃ or any value within the above range; the first stirring speed is 250rpm, 300rpm, 350rpm or any value within the above range; and the first stirring time is 15min, 20min, 25min or any value within the above range.

[0072] S3. Place the composite sheet into the loading tray of the fully automatic injection molding machine to ensure that the oily liquid is injected into the oil-absorbing layer and does not penetrate to the surface of the support layer.

[0073] The dosage of the oily liquid is 50mg to 167mg per tablet. Specifically, the dosage of the oily liquid is 50mg / tablet, 80mg / tablet, 120mg / tablet, 140mg / tablet, 167mg / tablet, or any value within the above range.

[0074] S4. After injecting the oily liquid, the composite sheet is sent into a hot air circulating oven for drying and conditioning.

[0075] The drying parameters include: temperature of 30℃~40℃, time of 8min~12min, and wind speed of 0.5m / s~1.5m / s. This drying process ensures that the moisture content of the first and second support layers is ≤3%, preventing moisture from affecting the stability of nicotine.

[0076] Specifically, the drying temperature is 30℃, 35℃, 40℃ or any value within the above range; the time is 8min, 10min, 12min or any value within the above range; and the wind speed is 0.5m / s, 1m / s, 1.5m / s or any value within the above range.

[0077] The oral lozenges of this application exhibit high drug release stability, meaning that the active substances and / or flavor substances are continuously and uniformly released in the oral cavity, with a stable hourly release rate and a linear release curve, without phenomena such as "sudden release" or "sudden drop." Simultaneously, the lozenges offer high comfort, as the composite layer formed by the first support layer, oil-absorbing layer, and second support layer provides excellent coverage, preventing the active substances from directly contacting the oral mucosa, effectively eliminating bitterness and burning sensations, and eliminating dust adhesion issues. Furthermore, the lozenges demonstrate high storage safety; the oil-absorbing layer locks in the active components, while the support layer isolates them, forming a double protection that significantly reduces the oxidation and volatilization rate of the active substances, ensuring long-term storage. The production of the lozenges is highly flexible; no mold changes or raw material ratio adjustments are required, and different dosages of lozenges can be rapidly produced simply by adjusting the injection volume of the fully automated injection system.

[0078] To better explain this application, embodiments and comparative examples are also provided below.

[0079] Example 1 The preparation of lozenges includes: 1. Stack the first support layer, water-absorbing layer, oil-absorbing layer and second support layer in sequence, and press them into a composite sheet using an ultrasonic welding machine.

[0080] 2. Add olive oil to a sterile mixing tank and heat to 40°C, maintaining a constant temperature. Then add vitamin E and stir at 500 rpm for 10 minutes (first stirring) until completely dissolved. Next, cool the mixture to 25°C and add nicotine, ethylparaben, sucralose, menthol, flavoring, and water in sequence. Then stir at 300 rpm for 20 minutes (second stirring) until a homogeneous and stable dispersion is formed, i.e., an oily liquid.

[0081] 3. Place the composite sheet into the feed tray of the fully automatic injection molding machine to ensure that the oily liquid is injected into the oil-absorbing layer and does not penetrate to the surface of the nonwoven fabric.

[0082] 4. After the composite tablets are injected with oily liquid, they are sent into a hot air circulating oven for drying and stabilization to obtain lozenges.

[0083] The ultrasonic welding machine pressing parameters include: power of 300W, frequency of 20kHz, and time of 0.5s; the injection volume of oily liquid is 100mg / tablet; the drying parameters include: temperature of 35℃, time of 10min, and wind speed of 1m / s. The first and second support layers are made of viscose fiber; the absorbent layer is made of medical degreased cotton; and the oil-absorbing layer is made of meltblown microfiber polypropylene nonwoven fabric with an oleophilic and hydrophobic surface modification.

[0084] The oily liquids include: 10% nicotine, 0.1% ethylparaben, 45% olive oil, 0.3% vitamin E, 1% sucralose, 0.5% menthol, 14% lemon flavoring, and 29.1% water.

[0085] The thickness of the first and second support layers is 0.2 mm; the thickness of the water-absorbing layer is 0.2 mm; and the thickness of the oil-absorbing layer is 0.3 mm.

[0086] The first and second support layers each have a water content of 1%; the oil absorption ratio of the meltblown microfiber polypropylene nonwoven fabric modified with an oleophilic and hydrophobic surface is 50 g / g; and the oil retention rate of the meltblown microfiber polypropylene nonwoven fabric modified with an oleophilic and hydrophobic surface is 97%.

[0087] Example 2 The difference from Example 1 is that the oily liquid includes: 5% nicotine, 0.1% ethylparaben, 55.8% olive oil, 0.2% vitamin E, 0.5% sucralose, 0.5% menthol, 10% lemon flavoring, and 27.9% water.

[0088] Example 3 The difference from Example 1 is that the oily liquid includes: 15% nicotine, 0.2% ethylparaben, 38% olive oil, 0.5% vitamin E, 1% sucralose, 1% menthol, 15% lemon flavoring, and 29.3% water.

[0089] Example 4 The difference from Example 1 is that the thickness of both the first support layer and the second support layer is 0.14 mm.

[0090] Example 5 The difference from Example 1 is that the thickness of both the first support layer and the second support layer is 0.25 mm.

[0091] Example 6 The difference from Example 1 is that the thickness of the absorbent layer is 0.1 mm.

[0092] Example 7 The difference from Example 1 is that the thickness of the absorbent layer is 0.3 mm.

[0093] Example 8 The difference from Example 1 is that the thickness of the oil-absorbing layer is 0.2 mm.

[0094] Example 9 The difference from Example 1 is that the thickness of the oil-absorbing layer is 0.4 mm.

[0095] Example 10 The difference from Example 1 is that there is no absorbent layer. Example 11 The difference from Example 1 is that the oil-absorbing layer consists of two layers of oleophilic and hydrophobic modified meltblown polypropylene nonwoven fabric, with a layer of porous polyethylene membrane sandwiched in between.

[0096] Example 12 The difference from Example 1 is that the water content of both the first and second support layers is 3%.

[0097] Example 13 The difference from Example 1 is that the oil absorption ratio of the meltblown microfiber polypropylene nonwoven fabric modified with oleophilic and hydrophobic surfaces is 30 g / g; and the oil retention rate of the meltblown microfiber polypropylene nonwoven fabric modified with oleophilic and hydrophobic surfaces is 95%.

[0098] Example 14 The difference from Example 1 is that the oil absorption ratio of the meltblown microfiber polypropylene nonwoven fabric modified with oleophilic and hydrophobic surfaces is 85 g / g; and the oil retention rate of the meltblown microfiber polypropylene nonwoven fabric modified with oleophilic and hydrophobic surfaces is 99%.

[0099] Comparative Example 1 Traditional coated lozenges have a three-layer structure, with the top and bottom layers being hydrophilic nonwoven fabric and the middle layer being hydrophobic nonwoven fabric. The middle layer consists of the following components: 10% nicotine, 2% hydroxypropyl cellulose, 1% hydroxypropyl methylcellulose, 2% menthol, 2% sucralose, and the remainder being an ethanol / water mixture.

[0100] The oral tablets in the above embodiments and comparative examples were subjected to the following tests, and the test data are shown in Table 1.

[0101] 1. Nicotine dissolution test.

[0102] Take appropriate amounts of the oral tablets from the examples and comparative examples as samples. The nicotine content in the examples and comparative examples is the same, which is 10 mg.

[0103] Preheat 500 mL of simulated saliva to 37°C and add it to the dissolution vessel. Secure the lozenges from the examples above to the bottom of the dissolution apparatus paddle and start the dissolution apparatus. Take 5 mL samples at the following time points and replenish the solution simultaneously: 1, 5, 10, 15, 30, 60, and 120 minutes.

[0104] Samples at each time point were filtered through a 0.22 μm filter membrane, and the nicotine concentration was determined by HPLC.

[0105] The nicotine release curve is simulated based on the nicotine content at each time point, and it is determined whether the release curve conforms to the zero-order release kinetic curve. If it does, it means that the release rate remains constant during the test time and the release amount per unit time is uniform.

[0106] The cumulative nicotine release is determined based on the nicotine concentration at 120 minutes, and then the nicotine utilization rate is judged based on the cumulative nicotine release.

[0107] 2. Stability test of oral lozenge structure.

[0108] The lozenges from the examples and comparative examples were cut into 20mm×30mm test strips, with 30 strips in each group.

[0109] Drying environment test: Fix the sample strip on the test machine fixture and peel it at a rate of 100 mm / min at 90°. Record the maximum force value during the separation process of non-woven fabric and oil-absorbing layer. Divide the maximum force value by the sample width to obtain the peel strength.

[0110] Humidity environment test: Immerse the sample strip in simulated artificial saliva (pH=6.8) at 37℃ for 2 hours to simulate the oral environment. After removal, gently blot dry the surface droplets with filter paper and immediately perform the peel strength test as described above.

[0111] The artificial saliva formula is as follows: sodium chloride 8.0 g / L, potassium chloride 1.2 g / L, calcium chloride 0.18 g / L, sodium bicarbonate 0.35 g / L, and sodium dihydrogen phosphate 0.08 g / L.

[0112] 3. Stability test of lozenges.

[0113] Take appropriate amounts of the oral tablets from the examples and comparative examples as samples. The nicotine content in the examples and comparative examples is the same, which is 100 mg.

[0114] Accelerated testing: The samples were placed in a constant temperature and humidity chamber at 40℃ and 75% relative humidity. Samples were taken and tested at the end of 0, 1, 2, 3, and 6 months.

[0115] Long-term test: The samples were placed in a stability test chamber at 25℃ and 60% relative humidity. Samples were taken and tested at the end of 0, 3, 6, 9, 12, 18 and 24 months respectively.

[0116] The nicotine content in the samples at the above time points was tested by HPLC, and the nicotine retention rate was obtained by (measured content / initial content) × 100%.

[0117] Observe the surface of the lozenges under natural light to see if there is discoloration, spots, cracks, deformation, etc., and record and photograph the results for comparison.

[0118] Table 1. Test data of lozenges for the examples and comparative examples.

[0119] As shown in Table 1, the release curve of the lozenges in the examples conforms more to zero-order release kinetics, indicating that the release rate remains constant during the test time and the release amount per unit time is uniform. In contrast, the release curve of the lozenges in the comparative examples conforms to first-order release kinetics, with the release rate being proportional to the remaining drug amount. The initial rate is high, but it rapidly decreases as the drug concentration decreases, which is a typical "burst release-rapid decline" characteristic.

[0120] In the example, the cumulative nicotine release rate of the lozenge at 120 minutes was higher than that of the comparative example, indicating that the nicotine utilization rate of the lozenge in the example was higher.

[0121] In the embodiment, the peel strength value of the lozenge is higher than that of the comparative example, regardless of whether it is in a dry or humid environment. This indicates that the four-layer structure of the lozenge in the embodiment is always a solid whole during the entire process of taking it, without delamination or disintegration. This ensures that nicotine can be released according to the preset path, and at the same time, it does not delaminate, shed, or generate dust during taking it, thus reducing discomfort.

[0122] In the example, at the end of the 6-month accelerated testing, the nicotine retention rate of the lozenges was greater than 97%, far exceeding that of the comparative example, and the appearance of the lozenges remained intact. Furthermore, at the end of the 24-month long-term testing, the nicotine retention rate of the lozenges in the example was greater than 94.3%, far exceeding that of the comparative example, and the appearance showed no discoloration, deformation, or cracking. All of the above demonstrates that the lozenges in the example possess excellent chemical and physical stability.

[0123] 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.

[0124] 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, an oil-absorbing layer, and a second support layer stacked sequentially, wherein at least one of the first support layer and the second support layer is a water-permeable layer, and the oil-absorbing layer comprises an oil-absorbing matrix and an oily liquid, wherein the oily liquid comprises an oily base liquid and active substances and / or flavoring substances dissolved in the oily base liquid; The oil absorption ratio of the oil-absorbing substrate is greater than that of the first support layer and the second support layer.

2. The lozenge according to claim 1, characterized in that, The lozenge further includes at least one absorbent layer, which is disposed between the oil-absorbing layer and the water-permeable layer; The absorbent layer includes an absorbent matrix, and the oil absorption ratio of the absorbent matrix is ​​less than that of the oil absorption matrix.

3. The lozenge according to claim 2, characterized in that, The thickness of the absorbent layer is 0.1mm~0.3mm; and / or, The absorbent substrate is medical absorbent cotton.

4. The lozenge according to claim 1, characterized in that, The active substance includes at least one of nicotine and nicotine derivatives; and / or, The flavoring substance includes at least one of flavoring, sweetener, cooling agent, saltiness agent, and acidifier; and / or, The oily liquid further includes at least one of an antioxidant and a preservative; and / or, The oily base liquid includes vegetable oil, wherein the vegetable oil has a mass fraction of not less than 20% in the oily liquid; and / or, The oily liquid also includes water, wherein the water content of the oily liquid is not less than 10%.

5. The lozenge according to any one of claims 1 to 4, characterized in that, The first support layer and / or the second support layer are non-woven fabric layers; and / or, The thickness of the first support layer and / or the second support layer is 0.14 mm to 0.25 mm; and / or, The thickness of the oil-absorbing layer is 0.2mm~0.4mm; and / or, The oil absorption ratio of the oil-absorbing matrix is ​​30g / g to 85g / g; and / or, The oil retention rate of the oil-absorbing matrix is ​​95%~100%; and / or, The moisture content of both the first support layer and the second support layer does not exceed 3%; and / or, The material of the first support layer and / or the second support layer is viscose fiber; and / or, The oil-absorbing substrate is made of modified polypropylene fiber nonwoven fabric.

6. The lozenge according to claim 1, characterized in that, The oil-absorbing layer comprises at least two layers of the oil-absorbing substrate.

7. The lozenge according to claim 6, characterized in that, An isolation layer is provided between at least one pair of adjacent oil-absorbing substrates.

8. The lozenge according to claim 1, characterized in that, The lozenge also includes a fixing structure formed on the periphery of the lozenge.

9. A method for preparing a lozenge, characterized in that, The method for preparing the lozenge as described in any one of claims 1 to 8 comprises: The first support layer, the oil-absorbing layer and the second support layer are stacked in sequence and then pressed to obtain the lozenge. The oil-absorbing layer includes an oil-absorbing substrate that adsorbs oily liquid. The oily liquid includes an oily base liquid and active substances and / or flavoring substances dissolved in the oily base liquid. The oil absorption ratio of the oil-absorbing substrate is greater than that of the first support layer and the second support layer, respectively.

10. The preparation method according to claim 9, characterized in that, The oil-absorbing layer includes an oil-absorbing matrix that adsorbs oily liquid, and includes injecting a measured amount of the oily liquid into the oil-absorbing matrix to obtain the oil-absorbing layer.

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