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CN-121987598-A - Directional release nicotine oral dissolving film, preparation method thereof and buccal product

CN121987598ACN 121987598 ACN121987598 ACN 121987598ACN-121987598-A

Abstract

The patent provides a directional release nicotine oral-dissolving film, a preparation method thereof and a buccal product, wherein the preparation method comprises the steps of S1, respectively preparing a first layer film, a second layer coating liquid and a third layer coating liquid, S2, coating the second layer coating liquid on the first layer film, drying in vacuum to obtain a double-layer composite film, and S3, coating the third layer coating liquid on the double-layer composite film, and drying to obtain the three-layer composite film. The three-layer composite structure uses the hydrophobic basal layer as a physical barrier to strictly limit the release path of nicotine in a single direction facing the oral mucosa, the directional release mechanism greatly improves the utilization efficiency of the drug, so that the nicotine can be quickly absorbed into systemic circulation through the capillaries of the oral mucosa, thereby realizing the effect taking speed exceeding that of the traditional transdermal patch, and aiming at the inherent strong bitter taste of the nicotine, the compound taste correction system in the nicotine release layer can effectively mask bad mouthfeel, thereby improving the sensory experience in the initial entrance.

Inventors

  • LI RUOXI
  • Xiong zhe
  • ZHANG YIMING
  • XIAO QIAN

Assignees

  • 湖北中烟工业有限责任公司

Dates

Publication Date
20260508
Application Date
20260304

Claims (10)

  1. 1. A method for preparing a directional release nicotine oral film, which is characterized by comprising the following steps: Step S1, preparing a first layer film, a second layer coating liquid and a third layer coating liquid respectively; step S2, coating the second layer coating liquid on the first layer film, and vacuum drying to obtain a double-layer composite film; And step S3, coating the third layer of coating liquid on the double-layer composite film and drying to obtain the three-layer composite film.
  2. 2. The method according to claim 1, wherein in the step S1, the first film preparing step includes: a1, respectively preparing a first matrix solution and a second matrix solution, and then mixing to obtain a uniform matrix solution; a2, sequentially adding a plasticizer, a compound flavoring agent and nicotine into the uniform matrix solution, and stirring at constant temperature to obtain a first layer of coating liquid; And A3, coating the first layer coating liquid on a bearing film, drying and demolding to obtain the first layer film.
  3. 3. The method according to claim 2, wherein in the step A1, the first matrix solution is obtained by mixing polyvinyl alcohol with deionized water and stirring at a constant temperature; the first matrix solution is kept at a constant temperature through a water bath, and the temperature of the water bath is 75-85 ℃; the stirring time is 25-35 min; the stirring rotating speed is 750-850 r/min; The second matrix solution is obtained by mixing hydroxypropyl methyl cellulose with the deionized water and stirring at constant temperature; The second matrix solution is kept at a constant temperature through a water bath, and the temperature of the water bath is 45-55 ℃; the stirring time is 25-35 min; the stirring speed is 750-850 r/min.
  4. 4. A method of preparation according to claim 3, wherein in step A2 the plasticizer comprises polyethylene glycol 400; the compound flavoring agent comprises aspartame and/or a cooling agent; The constant-temperature stirring temperature is 45-55 ℃; The stirring time after the plasticizer is added is 12-18 min; The stirring time after adding the compound flavoring agent is 17-23 min; the stirring time after the nicotine is added is 12-18 min; in the step S3, the carrier film is a polytetrafluoroethylene carrier film; the drying temperature of the first layer coating liquid is 45-55 ℃; the drying time is 40-80 min; the coating thickness of the first layer coating liquid is 160-200 mu m.
  5. 5. The method according to claim 1, wherein in the step S1, the second layer coating liquid is obtained by mixing and stirring the raw materials of the second layer film at constant temperature and filtering the mixed raw materials; the raw materials of the second layer of film comprise ethyl cellulose and absolute ethyl alcohol; The raw materials of the second layer of film are mixed and then kept at a constant temperature through a water bath, the water bath is kept at a constant temperature, and the temperature of the water bath is 40-50 ℃; the stirring time is 25-35 min; the stirring rotating speed is 200-300 r/min; the number of the filtered meshes is 80-120 meshes.
  6. 6. The method according to claim 1, wherein in the step S1, the third layer coating liquid is obtained by mixing the raw materials of the third layer film, stirring at room temperature, and filtering; The raw materials of the third layer film comprise modified polyacrylate and ethyl acetate; the stirring speed is 250-350 r/min; the stirring time is 20-30 min; the mesh number of the filtering is 100-140 meshes.
  7. 7. The method according to claim 1, wherein in the step S2, the second layer coating solution is coated on the first layer film to a thickness of 450 to 550 μm; the second layer coating liquid is sent into a vacuum drying box for vacuum drying after being coated on the first layer film; the temperature of the vacuum drying oven is 35-45 ℃; The vacuum degree of the vacuum drying oven is-0.05 to-0.11 MPa; And the drying time of the vacuum drying oven is 13-23 min.
  8. 8. The method according to claim 1, wherein in the step S3, the thickness of the third layer coating solution applied to the double-layer composite film is 25 to 35 μm; The drying time is 8-16 min; The drying temperature is 30-40 ℃.
  9. 9. A directional release nicotine oral soluble film is characterized in that, the nicotine oral film is prepared by the preparation method of any one of claims 1 to 8, comprising: a nicotine release layer that directly contacts the oral mucosa and releases nicotine to the oral mucosa; a hydrophobic substrate layer for sequestering saliva and releasing the nicotine in a targeted manner; a lipophilic attachable layer for accessing the nicotine oral film; The nicotine oral dissolving film is a three-layer composite film, when the nicotine oral dissolving film is used, the nicotine release layer is positioned on the inner layer and contacts with the oral mucosa, the oleophilic adhesive layer is positioned on the outer layer, the hydrophobic substrate layer is positioned on the nicotine release layer and the middle layer of the oleophilic adhesive layer, and the nicotine in the nicotine release layer is released in the direction away from the hydrophobic substrate layer.
  10. 10. A buccal product of a directional release nicotine oral film, characterized in that it comprises a nicotine oral film as claimed in claim 9; The nicotine oral dissolving film is subjected to blanking, screening and packaging to obtain the buccal product; the blanking pressure is 0.3-0.7 MPa; After screening, qualified products are obtained, and the reject ratio is less than 3%; The packaging material is an aluminum plastic bubble cap, and the nicotine mouth dissolving film is packaged by a single film; The temperature of the package is 20-24 ℃; the relative humidity of the package is 45-55%; the leak rate is less than or equal to 0.1 percent after the packaging is detected by adopting a negative pressure method; After being packaged, the materials are stored in a warehouse, and the storage temperature is 15-25%; The humidity of the storage is less than or equal to 60 percent.

Description

Directional release nicotine oral dissolving film, preparation method thereof and buccal product Technical Field The patent relates to the technical field of buccal products, in particular to a nicotine oral solution film capable of being released in a directional manner, a preparation method thereof and a buccal product. Background Tobacco dependence is an important public health problem worldwide, and nicotine replacement therapy is used as an effective smoking cessation assisting means, and is characterized in that nicotine is provided for users in a non-combustion mode so as to relieve withdrawal symptoms and improve smoking cessation success rate. To achieve this, various dosage forms have been developed on the market, such as chewing gums, transdermal patches, lozenges, nasal sprays, etc., but these conventional formulations still have significant limitations in terms of release control, ease of use and user experience. Nicotine chewing gum is one of the earliest widely used dosage forms that requires the user to promote release of nicotine from the matrix by chewing action. However, frequent chewing is prone to mandibular muscle fatigue, and nicotine release is severely dependent on saliva flow rate and swallowing frequency, resulting in short effective time, large blood concentration fluctuations, repeated changes required by the user to maintain the effect, compliance is challenged. More importantly, the release mode can not realize the directional and continuous action of the drug on the oral mucosa, a large amount of nicotine enters the digestive tract along with saliva and is metabolized by the first pass effect of the liver, the bioavailability is low, and meanwhile, the side effects such as gastrointestinal tract irritation and the like can be possibly caused. Transdermal nicotine patches provide another sustained route of administration that achieves systemic absorption of nicotine through skin permeation. Although the dosage form avoids the side effects of the gastrointestinal tract, the dosage form has extremely slow effect, and usually takes a few hours to enable the nicotine concentration in the blood plasma to reach the effective level, so that the sudden withdrawal symptoms cannot be relieved in time. In addition, factors such as the thickness of the skin stratum corneum, the local blood circulation condition, the environmental temperature and humidity can obviously influence the permeation rate of the medicine, so that the release rate difference among individuals and even among the individuals is huge, accurate dosage control is difficult to realize, and the individual requirement of a user on nicotine dosage in different smoking stopping stages cannot be flexibly adapted. To overcome the deficiencies of the above-described dosage forms, orolytic techniques were introduced into the field of nicotine delivery. The oral dissolving film can be quickly wetted, adhered, dissolved or eroded in the oral cavity, so that the medicine is absorbed through the oral mucosa, thereby avoiding the first pass effect, theoretically improving the bioavailability and accelerating the effect. However, the existing nicotine oral soluble film products mostly adopt a single-layer homogeneous structure. When placed in the mouth, the film is in contact with saliva as a whole, nicotine can freely diffuse in all directions, which not only results in reduced local drug concentration acting on the target mucosal area, affecting absorption efficiency, but also causes large amounts of drug to diffuse throughout the mouth and be swallowed, follow bioavailability is low and gastrointestinal irritation is a switch. In addition, single layer films may generate fragments after dissolution, present a risk of endocytosis, and their mechanical strength tends to be difficult to maintain structural integrity and positional stability in a dynamic oral environment. In the field of medicine, a multilayer composite film structure has been used for solving the problem of drug positioning and release, for example, the purpose of treating canker sore can be achieved by adopting a design of compounding a drug-containing layer and a protective layer, and the targeted adhesion and local slow release of ulcer focus in a moist oral environment are realized. This shows that the release direction and rate of the drug can be effectively controlled by designing the composite architecture of different functional layers. However, the application of this concept to nicotine delivery systems presents entirely new challenges in terms of physicochemical properties of nicotine, the desired release kinetics, and the extreme ease of use and comfort requirements necessary as consumer grade health products, all in essence differing from hormone formulations for the treatment of canker sores. Therefore, an innovative nicotine oral solution film capable of being released in a directional manner, a preparation method thereof and a buccal product are neede