Synthetic nicotine composition and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and particularly discloses a synthetic nicotine composition and a preparation method thereof. The nicotine buccal film agent disclosed by the invention is prepared from the following components in parts by weight: 2 to 4 parts of nicotine clathrate compound powder, 0.2 to 0.6 part of phosphatidic acid, 0.1 to 0.3 part of tannic acid, 0.1 to 0.2 part of sodium ascorbate, 0.04 to 0.06 part of tocopherol, 0.01 to 0.02 part of ethylene diamine tetraacetic acid, 2 to 4 parts of povidone and 40 to 80 parts of absolute ethyl alcohol. The synthesized nicotine composition prepared by the invention can effectively relieve the phenomenon that the faster the nicotine is released, the stronger the bitter taste is. Meanwhile, in a high-temperature and high-humidity environment, the stability of nicotine can be effectively maintained, and the oxidation half-life period of nicotine is prolonged.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, and more specifically, to a synthetic nicotine composition and its preparation method. Background Technology

[0002] According to statistics from the World Health Organization, approximately 8 million people die globally each year from tobacco-related diseases. Nicotine replacement therapy (NRT), as a first-line method for smoking cessation, can effectively alleviate withdrawal symptoms. However, traditional NRT preparations (such as chewing gum and patches) have significant limitations. Chewing gum requires frequent chewing, which can easily lead to temporomandibular joint strain, is inconvenient to use in public, and 30% of users report stomach discomfort; transdermal patches, on the other hand, have a slow onset of action and cannot quickly suppress acute cravings.

[0003] Oral dissolving films have become an ideal dosage form for nicotine replacement therapy due to their non-chewing, portability, and discreet nature. However, existing nicotine films still face three major technological bottlenecks:

[0004] (1) Bitterness masking contradicts taste: Nicotine free base has an extremely low bitterness threshold (0.008ppm), and commercially available film agents (such as...) Relying on high amounts of sweeteners leads to a decrease in oral pH, which stimulates saliva secretion and accelerates the release of bitterness. Conventional taste-masking technologies such as ion exchange resins and lipid coatings reduce solubility and cannot meet the "rapid onset" needs of smokers quitting.

[0005] (2) Defects in stability and dosage form integrity: Nicotine is easily oxidized and degraded. Existing technologies use BHT as a single antioxidant, which has a sharp drop in efficiency under high temperature conditions. HPMC single-component membranes are prone to local gelation in the high humidity environment of the oral cavity, resulting in uneven drug release.

[0006] (3) Bottlenecks in industrial production: Low-dose nicotine (1-4 mg / tablet) is not evenly dispersed in the slurry. The content uniformity RSD of the traditional solvent casting method is greater than 6%, which exceeds the pharmacopoeia limit. The hot air drying process causes the "surface skin-internal bubbles" defect, resulting in an increase in the die-cutting scrap rate. Summary of the Invention

[0007] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a synthetic nicotine composition and a method for preparing the same.

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] A synthetic nicotine composition, comprising, by weight, 2-4 parts of nicotine inclusion complex powder, 0.2-0.6 parts of phosphatidic acid, 0.1-0.3 parts of tannic acid, 0.1-0.2 parts of sodium ascorbate, 0.04-0.06 parts of tocopherol, 0.01-0.02 parts of disodium EDTA, 2-4 parts of povidone, and 40-80 parts of anhydrous ethanol.

[0010] Furthermore, the nicotine inclusion complex powder is made by coating nicotine base with hydroxypropyl-β-cyclodextrin.

[0011] Furthermore, the nicotine inclusion complex powder has a particle size of 10–50 μm and a drug loading of 15%–25% w / w.

[0012] Furthermore, the method for preparing the nicotine inclusion complex powder includes the following steps:

[0013] S1. Mix nicotine base and hydroxypropyl-β-cyclodextrin at a molar ratio of 1:2 to 4, dissolve in an aqueous ethanol solution, and stir until homogeneous to obtain a mixture.

[0014] S2. Add 10%–15% sodium carbonate solution by mass to the mixture to adjust the pH to 8.5–9.5, stir at 40–60°C for 2–4 hours, then spray dry and cool at room temperature to obtain nicotine inclusion complex powder.

[0015] Furthermore, the mass fraction of the ethanol aqueous solution in step S1 is 30% to 70%.

[0016] Furthermore, in step S2, the mass fraction of the sodium carbonate solution is 10% to 15%, and the spray drying conditions are an inlet air temperature of 100 to 120°C, an outlet air temperature of 50 to 65°C, and an atomization pressure of 0.2 to 0.5 MPa.

[0017] Furthermore, the method for preparing the synthetic nicotine composition is characterized by comprising the following steps:

[0018] (1) Weigh each component raw material according to the weight proportions;

[0019] (2) Add nicotine inclusion complex powder, phosphatidic acid, tannic acid, sodium ascorbate, and disodium EDTA to a wet mixing granulator and cut at a speed of 100-200 rpm for 10-15 min to obtain premixed powder;

[0020] (3) Add povidone to anhydrous ethanol, stir evenly, add tocopherol, and place in a high-speed shear homogenizer to process at 2000-3000 rpm for 2-3 minutes to obtain a drug-containing adhesive solution.

[0021] (4) Add the medicated adhesive solution to the premixed powder that is being stirred at low speed by spraying, and stir at 200-400 rpm for 2-4 minutes to obtain a moist soft material.

[0022] (5) The moist soft material is passed through a 14-16 mesh screen of a swing pellet mill to make wet granules, and then transferred to a fluidized bed dryer to dry for 6-10 minutes. After cooling at room temperature, it is passed through an 18-20 mesh screen to obtain a synthetic nicotine composition with uniform particle size.

[0023] Furthermore, the spraying conditions in step (4) are a spraying speed of 5-10 ml / min and an atomization pressure of 0.8-1.2 bar.

[0024] Furthermore, the drying conditions in step (5) are an air inlet temperature of 38–42°C.

[0025] In summary, this application includes at least the following beneficial effects:

[0026] (1) The present invention provides a synthetic nicotine composition in which nicotine molecules are encapsulated in a hydrophobic cavity of cyclodextrin. Phosphatidic acid is embedded in the outer wall of the cyclodextrin cavity through a hydrophobic tail chain and is released as the inclusion complex dissolves. The phosphate groups on the phosphatidic acid can preferentially occupy the T2R bitter taste receptors on the tongue surface, cover the receptors before nicotine exposure, and inhibit the activation of bitter taste receptors. The oral film agent, through the molecular-level spatial synergy of the nicotine-hydroxypropyl-β-cyclodextrin inclusion complex and the phosphatidic acid bitter taste blocker, blocks the bitter taste signal transmission while increasing the dissolution rate, thereby alleviating the phenomenon that the faster the nicotine is released, the stronger the bitter taste.

[0027] (2) This invention constructs a water / lipid biphasic antioxidant network by synergistically blocking the oxidation chain reaction of sodium ascorbate, tocopherol, and disodium EDTA, maintaining the stability of nicotine under high temperature and high humidity conditions and prolonging the nicotine oxidation half-life. Ascorbic acid reduces and regenerates tocopherol free radicals, maintaining a slightly acidic environment and inhibiting nicotine oxidation. The hydrophobic chain of tocopherol is anchored in the hydrophobic region of hydroxypropyl methylcellulose, protecting the inclusion complex interface and accepting electrons from ascorbic acid, thus achieving recycling. Disodium EDTA chelates metal ions, interrupts the oxidation catalytic chain, and synergistically prevents the metal ion-catalyzed auto-oxidation of ascorbic acid. Detailed Implementation

[0028] It should be noted that, where there is no conflict, the embodiments and features described in this application can be combined with each other. The present invention will now be described in detail with reference to the embodiments.

[0029] It should be noted that, unless otherwise specified, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0030] This invention provides a method for preparing a synthetic nicotine composition, comprising the following steps:

[0031] (1) Mix nicotine base and hydroxypropyl-β-cyclodextrin at a molar ratio of 1:2 to 4, dissolve them in an aqueous ethanol solution with a mass fraction of 30% to 70%, and stir until homogeneous to obtain a mixture.

[0032] (2) Add 10% to 15% sodium carbonate solution to the mixture to adjust the pH to 8.5 to 9.5, stir at 40 to 60°C for 2 to 4 hours, and then spray dry under the conditions of 100 to 120°C inlet air temperature, 50 to 65°C outlet air temperature and 0.2 to 0.5 MPa atomization pressure. Cool at room temperature to obtain nicotine inclusion complex powder with a particle size of 10 to 50 μm and a drug loading of 15% to 25% w / w.

[0033] (3) Weigh the following components by weight: 2-4 parts of nicotine inclusion complex powder, 0.2-0.6 parts of phosphatidic acid, 0.1-0.3 parts of tannic acid, 0.1-0.2 parts of sodium ascorbate, 0.04-0.06 parts of tocopherol, 0.01-0.02 parts of disodium ethylenediaminetetraacetate, 2-4 parts of povidone, and 40-80 parts of anhydrous ethanol.

[0034] (4) Add nicotine inclusion complex powder, phosphatidic acid, tannic acid, sodium ascorbate, and disodium EDTA to a wet mixing granulator and cut at a speed of 100-200 rpm for 10-15 minutes to obtain premixed powder.

[0035] (5) Add povidone to anhydrous ethanol, stir evenly, add tocopherol, and place in a high-speed shear homogenizer to process at 2000-3000 rpm for 2-3 minutes to obtain a drug-containing adhesive solution.

[0036] (6) The medicated adhesive is added to the premixed powder being stirred at low speed by spraying at a solution spraying speed of 5-10 ml / min and atomization pressure of 0.8-1.2 bar. The mixture is then stirred at a speed of 200-400 rpm for 2-4 min to obtain a moist soft material.

[0037] (7) The moist soft material is passed through a 14-16 mesh screen of a swing pellet mill to make wet granules, and then transferred to a fluidized bed dryer to dry for 6-10 minutes at an inlet air temperature of 38-42℃. After cooling at room temperature, it is passed through an 18-20 mesh screen to obtain a synthetic nicotine composition with uniform particle size.

[0038] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0039] Example 1

[0040] The method for preparing the nicotine lozenge in this embodiment includes the following steps:

[0041] (1) Nicotine base and hydroxypropyl-β-cyclodextrin are mixed at a molar ratio of 1:2 and then dissolved in a 30% ethanol aqueous solution. The mixture is stirred until homogeneous to obtain a mixed solution.

[0042] (2) Add 10% sodium carbonate solution to the mixture to adjust the pH to 8.5, stir at 40°C for 2 hours, and then spray dry under the conditions of 100°C inlet air temperature, 50°C outlet air temperature and 0.2MPa atomization pressure. Cool at room temperature to obtain nicotine inclusion complex powder with a particle size of 10μm and a drug loading of 15% w / w.

[0043] (3) Weigh the following components by weight: 2 parts of nicotine inclusion complex powder, 0.2 parts of phosphatidic acid, 0.1 parts of tannic acid, 0.1 parts of sodium ascorbate, 0.04 parts of tocopherol, 0.01 parts of disodium EDTA, 2 parts of povidone, and 40 parts of anhydrous ethanol.

[0044] (4) Add nicotine inclusion complex powder, phosphatidic acid, tannic acid, sodium ascorbate, and disodium EDTA to a wet mixing granulator and cut at 100 rpm for 10 min to obtain premixed powder.

[0045] (5) Add povidone to anhydrous ethanol, stir evenly, add tocopherol, and place in a high-speed shear homogenizer to process at 2000 rpm for 2 min to obtain a drug-containing adhesive solution.

[0046] (6) The medicated adhesive is added to the premixed powder being stirred at low speed by spraying at a solution spraying speed of 5 ml / min and atomization pressure of 0.8 bar. The mixture is then stirred at 200 rpm for 2 min to obtain a moist soft material.

[0047] (7) The moist soft material is passed through a 14-mesh sieve by a swing pellet mill to make wet granules, and then transferred to a fluidized bed dryer to dry for 6 minutes at an inlet air temperature of 38°C. After cooling at room temperature, it is passed through an 18-mesh sieve to obtain a synthetic nicotine composition with uniform particle size.

[0048] Example 2

[0049] This embodiment describes a method for preparing a synthetic nicotine composition, comprising the following steps:

[0050] (1) Nicotine base and hydroxypropyl-β-cyclodextrin are mixed at a molar ratio of 1:3 and then dissolved in a 50% ethanol aqueous solution. The mixture is stirred until homogeneous to obtain a mixed solution.

[0051] (2) Add 12% sodium carbonate solution to the mixture to adjust the pH to 9, stir at 50°C for 3 hours, and then spray dry under the conditions of 110°C inlet air temperature, 58°C outlet air temperature and 0.4MPa atomization pressure. Cool at room temperature to obtain nicotine inclusion complex powder with a particle size of 30μm and a drug loading of 20% w / w.

[0052] (3) Weigh the following components by weight: 3 parts of nicotine inclusion complex powder, 0.4 parts of phosphatidic acid, 0.2 parts of tannic acid, 0.15 parts of sodium ascorbate, 0.05 parts of tocopherol, 0.015 parts of disodium EDTA, 3 parts of povidone, and 60 parts of anhydrous ethanol.

[0053] (4) Add nicotine inclusion complex powder, phosphatidic acid, tannic acid, sodium ascorbate, and disodium EDTA to a wet mixing granulator and cut at 150 rpm for 13 min to obtain premixed powder.

[0054] (5) Add povidone to anhydrous ethanol, stir evenly, add tocopherol, and place in a high-speed shear homogenizer to process at 2500 rpm for 2.5 min to obtain a drug-containing adhesive solution.

[0055] (6) The medicated adhesive is added to the premixed powder being stirred at low speed by spraying at a solution spraying speed of 7 ml / min and atomization pressure of 1 bar. The mixture is stirred at 300 rpm for 3 min to obtain a moist soft material.

[0056] (7) The moist soft material is passed through a 15-mesh sieve by a swing pellet mill to make wet granules, and then transferred to a fluidized bed dryer to dry for 8 minutes at an air inlet temperature of 40°C. After cooling at room temperature, it is passed through a 19-mesh sieve to obtain a synthetic nicotine composition with uniform particle size.

[0057] Example 3

[0058] This embodiment describes a method for preparing a synthetic nicotine composition, comprising the following steps:

[0059] (1) Nicotine base and hydroxypropyl-β-cyclodextrin are mixed at a molar ratio of 1:4 and then dissolved in a 70% ethanol aqueous solution. The mixture is stirred until homogeneous to obtain a solution.

[0060] (2) Add 15% sodium carbonate solution to the mixture to adjust the pH to 9.5, stir at 60°C for 4 hours, and then spray dry under the conditions of 120°C inlet air temperature, 65°C outlet air temperature and 0.5MPa atomization pressure. Cool at room temperature to obtain nicotine inclusion complex powder with a particle size of 50μm and a drug loading of 25% w / w.

[0061] (3) Weigh the following components by weight: 4 parts of nicotine inclusion complex powder, 0.6 parts of phosphatidic acid, 0.3 parts of tannic acid, 0.2 parts of sodium ascorbate, 0.06 parts of tocopherol, 0.02 parts of disodium ethylenediaminetetraacetate, 4 parts of povidone, and 80 parts of anhydrous ethanol.

[0062] (4) Add nicotine inclusion complex powder, phosphatidic acid, tannic acid, sodium ascorbate, and disodium EDTA to a wet mixing granulator and cut at 200 rpm for 15 min to obtain premixed powder.

[0063] (5) Add povidone to anhydrous ethanol, stir evenly, add tocopherol, and place in a high-speed shear homogenizer to process at 3000 rpm for 3 min to obtain a drug-containing adhesive solution.

[0064] (6) The medicated adhesive was added to the premixed powder being stirred at low speed by spraying at a solution spraying speed of 10 ml / min and atomization pressure of 1.2 bar. The mixture was stirred at 400 rpm for 4 min to obtain a moist soft material.

[0065] (7) The moist soft material is passed through a 16-mesh sieve by a swing pellet mill to make wet granules, and then transferred to a fluidized bed dryer to dry for 10 minutes at an inlet air temperature of 42°C. After cooling at room temperature, it is passed through a 20-mesh sieve to obtain a synthetic nicotine composition with uniform particle size.

[0066] Comparative Example 1

[0067] The preparation method of the nicotine lozenge in this comparative example is basically the same as that in Example 1, except that phosphatidic acid and tannic acid were not added in this comparative example.

[0068] Comparative Example 2

[0069] The preparation method of the nicotine lozenge in this comparative example is basically the same as that in Example 1. The difference is that the preparation method of this comparative example is to directly put all the powder raw materials into the mixer, mix for 30 minutes, dilute the tocopherol with a small amount of ethanol, spray it into the powder being mixed, and continue mixing for 10 minutes to obtain the product.

[0070] Experimental Example

[0071] Products from Examples 1-3 and Comparative Examples 1-2 were selected as raw materials to prepare oral film samples, and various performance tests were conducted, including:

[0072] Bitterness onset time: Based on the time point when the electronic tongue response value exceeds 200% of the baseline (sensor type: ZZ), the subject of the manual taste test must pass the taste threshold test (sucrose 0.5% w / v, quinine 0.0008% w / v).

[0073] Release rate test: USPIV flow cell was used at a flow rate of 8 mL / min (medium pH 6.8) and a sampling time of 0.5 min.

[0074] Degradation products: Accelerated conditions 40℃ / 75%RH, HPLC gradient elution program (trifluoroacetic acid-acetonitrile system).

[0075] Content uniformity: According to the content uniformity test method in Chinese Pharmacopoeia 0951, take 10 film-forming tablets, pulverize each tablet independently; accurately weigh (accuracy 0.0001g), and calculate the unit weight. Dissolve the sample in 50mL of methanol-water (50:50), filter through a 0.45μm filter membrane; determine nicotine by HPLC external standard method; calculate the actual content per tablet (μg / mg). Content uniformity = standard deviation / average content × 100%.

[0076] Mucosal irritation rating: Based on the modified Draize method (hamster cheek pouch model), the observation time point was 4 hours. The specific results are shown in Table 1.

[0077] Table 1: Performance Test Results of Oral Film Samples from Examples and Comparative Examples

[0078] project Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Bitterness onset time (s) 8.1 8.0 8.3 12.5 9.0 Nicotine release rate in 30 seconds (%) 82.3 85.5 83.4 84.1 65.3 Degradation products (%) at 40℃ for 3 months 0.38 0.32 0.37 0.45 1.85 Content uniformity (%) 2.1 2.0 2.2 3.4 7.0 Mucosal irritation score 1.2 1.0 1.5 1.9 3.5

[0079] A comparison of Example 1 and Comparative Example 1 in Table 1 shows that Comparative Example 1 lacks the presence of phosphatidic acid occupying bitter taste receptors, increasing the onset time of bitterness. Simultaneously, the trace amounts of free nicotine slightly increase the uniformity of degradation products and their content, leading to accelerated bitterness perception, ineffective bitterness control, and prolonged bitterness duration. Example 1, on the other hand, utilizes the hydrophobic tail chain of phosphatidic acid embedded in the outer wall of the cyclodextrin cavity and released during the dissolution of the inclusion complex. The phosphate groups on the phosphatidic acid preferentially occupy the T2R bitter taste receptors on the tongue, covering the receptors before nicotine exposure and inhibiting bitter taste receptor activation. Therefore, in the oral film prepared using the method of this invention, the nicotine-hydroxypropyl-β-cyclodextrin inclusion complex and the phosphatidic acid bitterness blocker work synergistically at the molecular level, increasing the dissolution rate while blocking bitterness signal transduction, thereby alleviating the phenomenon that the faster the nicotine release, the stronger the bitterness.

[0080] A comparison of Example 1 and Comparative Example 2 in Table 1 shows that, compared to the simple physical mixing of Example 1, the low-dose components in Comparative Example 2, especially nicotine, could not achieve uniform molecular-level dispersion in a large amount of excipients, resulting in a content uniformity exceeding the pharmacopoeia requirement of ≤6%. Furthermore, due to uneven distribution and high local nicotine concentrations, Comparative Example 2 exhibited increased mucosal irritation and a reduced palatability. Additionally, the exposure of some nicotine led to oxidative degradation and accelerated deterioration. In contrast, Example 1, through the synergistic blocking of the oxidation chain reaction of sodium ascorbate, tocopherol, and disodium EDTA, constructed a water / lipid biphasic antioxidant network, maintaining the stability of nicotine under high temperature and humidity conditions and prolonging the nicotine oxidation half-life. Ascorbic acid reduced and regenerated tocopherol free radicals, maintaining a slightly acidic environment and inhibiting nicotine oxidation. The hydrophobic chain of tocopherol is anchored in the hydrophobic region of hydroxypropyl methylcellulose, protecting the inclusion complex interface and accepting electrons from ascorbic acid, thus enabling recycling. Disodium EDTA chelates metal ions, breaks the oxidation catalytic chain, and works synergistically with antioxidants to prevent metal ions from catalyzing the auto-oxidation of ascorbic acid.

[0081] Therefore, the synthetic nicotine composition provided by this invention can effectively maintain the stability of nicotine under high temperature and high humidity conditions, prolong the oxidative half-life of nicotine, alleviate the phenomenon that the faster the nicotine is released, the stronger the bitterness, and achieve the effect of instant dissolution and gentle release in the mouth, which has good medical prospects.

[0082] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. A synthetic nicotine composition, characterized in that, The raw materials, by weight, include: 2-4 parts of nicotine inclusion complex powder, 0.2-0.6 parts of phosphatidic acid, 0.1-0.3 parts of tannic acid, 0.1-0.2 parts of sodium ascorbate, 0.04-0.06 parts of tocopherol, 0.01-0.02 parts of disodium EDTA, 2-4 parts of povidone, and 40-80 parts of anhydrous ethanol.

2. The synthetic nicotine composition according to claim 1, characterized in that, The nicotine inclusion complex powder is made by coating nicotine base with hydroxypropyl-β-cyclodextrin.

3. The synthetic nicotine composition according to claim 1, characterized in that, The nicotine inclusion complex powder has a particle size of 10–50 μm and a drug loading of 15%–25% w / w.

4. The synthetic nicotine composition according to claim 1, characterized in that, The method for preparing the nicotine inclusion complex powder includes the following steps: S1. Mix nicotine base and hydroxypropyl-β-cyclodextrin at a molar ratio of 1:2 to 4, dissolve in an aqueous ethanol solution, and stir until homogeneous to obtain a mixture. S2. Add 10%–15% sodium carbonate solution by mass to the mixture to adjust the pH to 8.5–9.5, stir at 40–60°C for 2–4 hours, then spray dry and cool at room temperature to obtain nicotine inclusion complex powder.

5. A synthetic nicotine composition according to claim 4, characterized in that, The mass fraction of the ethanol aqueous solution in step S1 is 30% to 70%.

6. The synthetic nicotine composition according to claim 4, characterized in that, In step S2, the sodium carbonate solution has a mass fraction of 10% to 15%, and the spray drying conditions are an inlet air temperature of 100 to 120°C, an outlet air temperature of 50 to 65°C, and an atomization pressure of 0.2 to 0.5 MPa.

7. A method for preparing the synthetic nicotine composition according to any one of claims 1 to 6, characterized in that, Includes the following steps: (1) Weigh each component raw material according to the weight proportions; (2) Add nicotine inclusion complex powder, phosphatidic acid, tannic acid, sodium ascorbate, and disodium EDTA to a wet mixing granulator and cut at a speed of 100-200 rpm for 10-15 min to obtain premixed powder; (3) Add povidone to anhydrous ethanol, stir evenly, add tocopherol, and place in a high-speed shear homogenizer to process at 2000-3000 rpm for 2-3 minutes to obtain a drug-containing adhesive solution. (4) Add the medicated adhesive solution to the premixed powder that is being stirred at low speed by spraying, and stir at 200-400 rpm for 2-4 minutes to obtain a moist soft material. (5) The moist soft material is passed through a 14-16 mesh screen of a swing pellet mill to make wet granules, and then transferred to a fluidized bed dryer to dry for 6-10 minutes. After cooling at room temperature, it is passed through an 18-20 mesh screen to obtain a synthetic nicotine composition with uniform particle size.

8. The method for preparing a synthetic nicotine composition according to claim 7, characterized in that, The conditions for the spraying method in step (4) are a spraying speed of 5-10 ml / min and an atomization pressure of 0.8-1.2 bar.

9. The method for preparing a synthetic nicotine composition according to claim 7, characterized in that, The drying conditions in step (5) are an air inlet temperature of 38–42°C.