Nicotine micropellet composition, nicotine micropellet oral pouch, and method for preparing same

Abstract

The present invention relates to a nicotine micropellet composition, a nicotine micropellet oral pouch, and a method for preparing same. The nicotine micropellet composition comprises: nicotine, a blank pellet core, a binder, a sweetener, a pH regulator, cellulose and a cellulose derivative, a macromolecular coating material, a lubricant, an essence perfume, and a solvent. Nicotine is loaded on the blank pellet core, and the macromolecular coating material forms a single-layer or multi-layer drug-loading part or coating on the blank pellet core. When the macromolecular coating material forms a multi-layer drug-loading part or coating, the macromolecular coating material comprises an isolation layer, a drug-containing layer, a protective layer, and a drug-loading layer sequentially from inside to outside. The nicotine micropellet composition and the nicotine micropellet oral pouch, according to the present invention, feature good fluidity, stable nicotine release, and stable fragrance release, and can thus be used for smoking cessation or treatment of nicotine dependence.

Description

Nicotine micropellet composition, nicotine micropellet oral bag and preparation method thereof Technical Field

[0001] The present invention relates to the technical field of nicotine compositions, and in particular to a nicotine pellet composition, a nicotine pellet oral bag, and a preparation method thereof. Background Art

[0002] Tobacco-free oral nicotine products, packaged in pouches, are increasingly popular with consumers due to their proven harm reduction benefits, ease of use, and novel flavors. These products allow users to enjoy nicotine without the need for tobacco. Nicotine snus, such as nicotine pouches, are typically placed between the upper and lower gums and lips for a period of time, allowing for direct absorption of nicotine through the mucous membranes. They avoid the harmful effects of nitrosamines, smoke, and various carcinogens associated with traditional tobacco products and are often used to help with smoking cessation or nicotine dependence treatment.

[0003] Existing nicotine pouches typically mix nicotine with some excipients to form granules, which are then packaged into small non-woven bags. However, nicotine granules tend to aggregate and adhere to the surface of the container or packaging, especially as the nicotine granules decrease in size. This increases the tendency and strength of the granules to aggregate. Furthermore, the varying shapes and sizes of the granules lead to unstable nicotine release rates. Furthermore, the fluidity of these nicotine granules is affected by flavors and fragrances, as well as moisture, resulting in poor fluidity. Furthermore, nicotine hydrolysis releases nicotine base, which can overwhelm the flavor and produce an unpleasant odor. Furthermore, product stability is poor, shortening shelf life.

[0004] Chinese patent CN107259634A (publication date: October 20, 2017) discloses an oral product comprising a body that can be entirely contained in the oral cavity. The body comprises: an extruded, mouth-stable polymer matrix comprising at least 10% by weight of one or more mouth-stable polymers selected from polyurethane, polyacrylate, polyethylene, SEBS, SBS, or a combination thereof; at least 10% by weight of cellulose fibers embedded in the mouth-stable polymer matrix, together forming a cellulose-polymer matrix; and nicotine or a derivative thereof dispersed and adsorbed within the cellulose-polymer matrix, such that the nicotine or derivative thereof is released from the body when the body is contained within the oral cavity and exposed to saliva. The body has a compressibility of between 45% and 90% at 250 N and a percent elasticity of between 75% and 90%. This patent utilizes an extrusion-spheronization process to prepare nicotine compositions, including spherical nicotine compositions. The patent does not disclose nicotine micropellet compositions made from blank pellet cores, nicotine, and excipients.

[0005] Chinese patent CN114521669A (publication date: May 24, 2022) discloses: a nicotine-stabilized oral tobacco product, comprising a binder, a nicotine source, a pH regulator, core material particles, and a filler. Its preparation method comprises the following steps: (1) preparing a nicotine-stabilized mixed solution: dissolving a polymer material in anhydrous ethanol, stirring evenly, and then adding the nicotine source and the pH regulator; (2) mixing the filler with the solution in (1): mixing a sweetener, a flavoring substance, and a moisturizer with the solution obtained in (1) and stirring evenly; (3) adding the solution obtained in (2) to the core material particles, stirring and absorbing them, and drying them overnight to obtain flavored nicotine-stabilized oral tobacco particles. This patented preparation method obviously cannot guarantee that the nicotine content on each core material particle is uniform.

[0006] The prior art fails to provide a nicotine product with good fluidity, stable nicotine release and stable aroma release.

[0007] Therefore, the existing technology needs to be improved. Summary of the Invention

[0008] The prior art fails to provide a nicotine product with good fluidity, stable nicotine release, and stable aroma release. Therefore, the present invention provides a nicotine micropellet composition, a nicotine micropellet oral bag, and a preparation method thereof to solve the above problems.

[0009] To achieve the above objectives, in a first aspect, the present invention provides a nicotine micropellet composition, comprising nicotine, a blank pellet core, a binder, a sweetener, a pH adjuster, cellulose and cellulose derivatives, a polymer coating material, a lubricant, flavors and fragrances, and a solvent. The blank pellet core is loaded with nicotine, and the polymer coating material forms a single or multiple layer drug carrier or coating on the blank pellet core.

[0010] In one implementation, when the polymer coating material forms a multi-layer drug-carrying or coating, it includes, from the inside to the outside, an isolation layer, a drug-containing layer, a protective layer, and a drug-carrying layer.

[0011] In one embodiment, the nicotine comprises any one or more of free base nicotine, nicotine salts, nicotine in a matrix or organometallic complex, a nicotine-ion exchange resin combination, a nicotine inclusion complex or any non-covalently bound nicotine, nicotine lactate, nicotine malate, nicotine salicylate, nicotine resin complex, nicotine cyclodextrin inclusion complex, nicotine hydrochloride, nicotine dihydrochloride, nicotine tartrate, nicotine tartrate dihydrate, nicotine sulfate, nicotine zinc chloride and nicotine benzoate.

[0012] In one embodiment, the blank pellet core includes a hydrophilic sugar-based pellet core and / or a hydrophobic cellulose pellet core, wherein the hydrophilic sugar-based pellet core is a pellet core composed of a water-soluble saccharide material, and the hydrophobic cellulose pellet core is a pellet core composed of a water-insoluble cellulose material.

[0013] In one implementation, the binder includes any one or more of povidone, cellulose derivatives, pregelatinized starch, sugar alcohol, gelatin, gum arabic, sodium alginate, and polyethylene glycol.

[0014] In one implementation, the sweetener includes any one or more of acesulfame potassium, cyclamate, saccharin, saccharin sodium, sucralose, neotame, sodium cyclamate, aspartame, stevia, licorice, disodium glycyrrhizate, tripotassium and trisodium glycyrrhizate, glucose, fructose, sucrose, maltose, starch sugar and lactose, sorbitol, maltitol, isomalt, xylitol, lactitol, mannitol and erythritol.

[0015] In one embodiment, the pH adjuster includes any one or more of acetate, alkali metal or ammonium carbonate, lactate, glycinate, gluconate, borate, glycerophosphate or citrate, phosphate, metal hydroxide, and mixtures thereof.

[0016] In one implementation, the cellulose and cellulose derivatives include any one or more of wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, bran fiber, bamboo fiber, pandan fiber, powdered cellulose and high molecular polymer materials.

[0017] In one implementation, the polymer coating material includes a sugar material or a polymer material, the sugar material includes any one or more of syrup, colored syrup, mucilage, talc and white wax, and the polymer material includes any one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, methacrylic acid copolymer, methacrylate copolymer, cellulose acetate phthalate, polyvinyl pyrrolidone, polyvinyl pyrrolidine and polyethylene glycol.

[0018] In one embodiment, the lubricant includes a hydrophobic lubricant and a hydrophilic lubricant, the hydrophobic lubricant includes any one or more of stearic acid, magnesium stearate, calcium stearate, glyceryl behenate, micropowdered silica gel, talc, vegetable oil, polyethylene glycols and sodium lauryl sulfate, and the hydrophilic lubricant includes sodium stearyl fumarate.

[0019] In one implementation, the flavors and fragrances include any one or more of bergamot flavor, eucalyptus flavor, citrus flavor, lemon flavor, peppermint flavor, mint flavor, menthol, licorice flavor, wintergreen flavor, tobacco flavor, coffee flavor, vanilla flavor, lime flavor, apple flavor, peach flavor, mango flavor, cherry flavor, blueberry flavor, strawberry flavor, cola flavor, cinnamon flavor and watermelon flavor.

[0020] In one embodiment, the solvent includes water and / or an organic solvent, and the organic solvent includes any one or more of aromatic hydrocarbons, aliphatic hydrocarbons, alicyclic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, ketones, glycol derivatives, and other types such as acetonitrile, pyridine, and phenol.

[0021] In a second aspect, the present invention further provides a nicotine micropellet oral pouch, comprising a non-woven fabric pouch and any one of the above-mentioned nicotine micropellet compositions contained in the non-woven fabric pouch.

[0022] In a third aspect, the present invention further provides a method for preparing a nicotine micropellet oral bag, which is used to prepare the above-mentioned nicotine micropellet oral bag, and specifically comprises the following steps:

[0023] S1. Weighing and preparation process: weighing materials; preparing polymer coating materials according to the prescription;

[0024] S2. Drug coating process: After the polymer coating material is prepared, it is placed in the spray gun hopper. The weighed solid materials are sequentially added into the solid hopper of the fluidized bed or centrifugal coating machine according to the prescription. The machine is turned on to perform fluidized bed coating or centrifugal coating process, and the material is evenly coated on the pellet core to form one or more material layers to obtain nicotine-loaded micropellets;

[0025] S3, drying process: placing the granulated nicotine pellets into a drying oven or fluidized bed for drying;

[0026] S4, filling process: the dried nicotine pellets are transferred to the powder hopper of the granule packaging machine, and the non-woven fabric roll is placed in the film roll hopper of the granule packaging machine. The granule packaging machine is started to perform the filling process, so that the formed nicotine pellets are filled into the non-woven fabric bag to obtain the nicotine pellet oral bag.

[0027] Beneficial effects: The nicotine pellet composition and the nicotine pellet oral bag provided by the present invention achieve the effects of rapid nicotine release and uniform and stable release respectively by forming a single layer or multiple layers of drug loading or coating on the blank pellet core, so that the nicotine content and release are relatively stable, and the aroma release is also stable; by forming a drug loading layer or a coating layer, the effects of moisture-proof, light-proof and air-insulated can be achieved, and the stability of the nicotine pellet composition can be increased; the preparation method provided by the present invention does not require the addition of a flow aid during filling, and the weight difference is smaller than that of powder or granule filling, and the interaction of the compound ingredients during the preparation process can be avoided, so that the prepared nicotine pellet composition and the nicotine pellet oral bag have better fluidity. The present invention provides a nicotine product with good fluidity, stable nicotine release and stable aroma release, which can be used for the treatment of smoking cessation or nicotine dependence. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] FIG1 is a flow chart of the steps of the method for preparing the nicotine micropellet oral bag provided by the present invention.

[0029] The purpose, features and advantages of the present invention will be further described with reference to the accompanying drawings and in conjunction with the embodiments. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention is further described in detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, the descriptions of the terms "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" described below mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the technical features involved in the various embodiments of the present invention can be combined with each other as long as they do not conflict with each other.

[0031] The present invention provides a nicotine micropill composition, which includes nicotine, a blank pellet core, a binder, a sweetener, a pH adjuster, cellulose and cellulose derivatives, a polymer coating material, a lubricant, flavors and fragrances, and a solvent. The blank pellet core is loaded with nicotine, and the polymer coating material forms a single or multiple layer of drug loading or coating on the blank pellet core. When the polymer coating material forms a multi-layer drug loading or coating, it includes, from the inside to the outside, an isolation layer, a drug-containing layer, a protective layer, and a drug loading layer. When the blank pellet core is coated with a single layer of non-functional coating material, the nicotine can be released quickly during use. When the blank pellet core is coated with multiple layers of functional coating material, the nicotine can be released evenly and slowly during use.

[0032] The nicotine herein includes any one or more of free base nicotine, nicotine salts, nicotine in a matrix or organometallic complex, nicotine-ion exchange resin combinations, nicotine inclusion complexes, or any non-covalently bound nicotine, nicotine lactate, nicotine malate, nicotine salicylate, nicotine resin complexes, nicotine cyclodextrin inclusion complexes, nicotine hydrochloride, nicotine dihydrochloride, nicotine tartrate, nicotine tartrate dihydrate, nicotine sulfate, nicotine zinc chloride, and nicotine benzoate. The nicotine also refers to synthetic nicotine and nicotine extracted from natural tobacco.

[0033] The blank pellet core refers to the masterbatch necessary for preparing the skeleton-type micropellets. The blank pellet core includes a hydrophilic sugar-based pellet core and / or a hydrophobic cellulose pellet core, which is a spherical or quasi-spherical solid with a diameter of less than 2.5 mm. The hydrophilic sugar-based pellet core is a pellet core composed of a water-soluble saccharide material, and the hydrophobic cellulose pellet core is a pellet core composed of a water-insoluble cellulose material. Furthermore, the hydrophilic sugar-based pellet core includes a sucrose blank pellet core or a starch blank pellet core, and the hydrophobic cellulose pellet core includes a microcrystalline cellulose blank pellet core.

[0034] The binder is a pharmaceutically acceptable binder, including any one or more of povidone, cellulose derivatives, pregelatinized starch, sugar alcohol, gelatin, gum arabic, sodium alginate, and polyethylene glycol.

[0035] The sweeteners herein refer to artificially synthesized and / or naturally extracted sweeteners. The sweeteners include any one or more of acesulfame potassium, cyclamate, saccharin, saccharin sodium, sucralose, neotame, sodium cyclamate, aspartame, stevia, licorice, disodium glycyrrhizate, tripotassium and trisodium glycyrrhizate, glucose, fructose, sucrose, maltose, starch sugar and lactose, sorbitol, maltitol, isomalt (isomaltitol, palatinitol), xylitol, lactitol, mannitol, and erythritol.

[0036] The pH regulator includes any one or more of acetate, alkali metal or ammonium carbonate, lactate, glycine, gluconate, borate, glycerophosphate or citrate, phosphate, metal hydroxide and mixtures thereof.

[0037] The cellulose and cellulose derivatives herein refer to pharmaceutically acceptable substances used as diluents, lubricants, sustained-release agents, binders, disintegrants, glidants, stabilizers, or excipients, and are insoluble in water. Furthermore, the cellulose and cellulose derivatives include any one or more of wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, bran fiber, bamboo fiber, pandan fiber, powdered cellulose, and polymer materials. The cellulose and cellulose derivatives and / or polymer materials are permeable to saliva and partially or completely dissolve in the nicotine micropellet composition.

[0038] The polymer coating material includes a sugar material or a polymer material, wherein the sugar material includes any one or more of syrup, colored syrup, glue, talc, and white wax, and the polymer material includes any one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methylcellulose, methacrylic acid copolymer, methacrylate copolymer, cellulose acetate phthalate, polyvinyl pyrrolidone, polyvinyl pyrrolidine, and polyethylene glycol. The polymer coating material is coated on a solid surface to form one or more multifunctional protective layers of varying thickness and elasticity that are tightly adhered to the surface and are saliva-soluble.

[0039] The lubricant includes a hydrophobic lubricant and a hydrophilic lubricant. The hydrophobic lubricant includes any one or more of stearic acid, magnesium stearate, calcium stearate, glyceryl behenate, micro-powdered silica gel, talc, vegetable oil, polyethylene glycol and sodium lauryl sulfate, and the hydrophilic lubricant includes sodium stearyl fumarate. The lubricant is used to effectively reduce the mutual friction between particles or powder particles to enhance their fluidity, lubricity or anti-stickiness.

[0040] The flavors and fragrances herein refer to substances with a certain aroma and fragrance composed of hydrocarbons, alcohols, acids, esters, lactones, ethers, aldehydes, ketones, acetals, ketals, phenols, macrocyclic rings, polycyclic rings, heterocyclic rings containing nitrogen, oxygen, and sulfur elements, as well as halides or nitriles. Furthermore, the flavors and fragrances include any one or more of bergamot essence, eucalyptus essence, citrus essence, lemon essence, peppermint essence, mint essence, menthol, licorice essence, wintergreen essence, tobacco essence, coffee essence, vanilla essence, lime essence, apple essence, peach essence, mango essence, cherry essence, blueberry essence, strawberry essence, cola essence, cinnamon essence, and watermelon essence.

[0041] The solvent includes water and / or an organic solvent, and the organic solvent includes any one or more of aromatic hydrocarbons, aliphatic hydrocarbons, alicyclic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, ketones, glycol derivatives, and other types such as acetonitrile, pyridine, and phenol.

[0042] 1 is a flowchart of the steps of the method for preparing a nicotine micropellet oral bag provided by the present invention. The present invention also provides a nicotine micropellet oral bag, which includes a non-woven fabric pouch and any of the above-mentioned nicotine micropellet compositions contained in the non-woven fabric pouch.

[0043] The present invention also provides a method for preparing a nicotine micro-pellet oral bag, which is used to prepare the above-mentioned nicotine micro-pellet oral bag, and specifically comprises the following steps:

[0044] S1. Weighing and preparation process: weighing materials; preparing polymer coating materials according to the prescription;

[0045] S2. Drug coating process: After the polymer coating material is prepared, it is placed in the spray gun hopper. The weighed solid materials are sequentially added into the solid hopper of the fluidized bed or centrifugal coating machine according to the prescription. The machine is turned on to perform fluidized bed coating or centrifugal coating process, and the material is evenly coated on the pellet core to form one or more material layers to obtain nicotine-loaded micropellets;

[0046] S3, drying process: placing the granulated nicotine pellets into a drying oven or fluidized bed for drying;

[0047] S4, filling process: the dried nicotine pellets are transferred to the powder hopper of the granule packaging machine, and the non-woven fabric roll is placed in the film roll hopper of the granule packaging machine. The granule packaging machine is started to perform the filling process, so that the formed nicotine pellets are filled into the non-woven fabric bag to obtain the nicotine pellet oral bag.

[0048] The present invention provides the following examples to illustrate the technical solutions of the present invention.

[0049] Example 1. Preparation of a nicotine micropellet oral bag for rapid nicotine release and its preparation process, as well as in vitro dissolution data.

[0050] Weigh the required materials according to the formula in Table 1.

[0051] Table 1. Formula of the nicotine pellet composition in Example 1:

[0052] .

[0053] The materials of Table 1 were prepared as follows:

[0054] Step 1. Prepare the drug-containing coating solution: Heat 100g of 95% ethanol to 50°C, then add nicotine ditartaric acid dihydrate. Disperse the mixture using an emulsifier for 5 minutes until clear. Cool to 30°C, then add povidone and dissolve it using an emulsifier for 5 minutes until completely dissolved. Next, add neotame and dissolve it using an emulsifier for 5 minutes until completely dissolved. Add the cooling agent and dissolve it using an emulsifier for 5 minutes until completely dissolved. Finally, add the flavoring and dissolve it using an emulsifier for 10-15 minutes until completely dissolved.

[0055] Step 2, drug coating process: put the blank sucrose pellets into the material bin of the centrifugal granulation coating machine, put the drug-containing coating liquid prepared in step 1 into the spray gun material bin, set the machine parameters according to the parameters in Table 2, start the machine for centrifugal coating process, and perform the centrifugal coating process for 60 minutes to evenly coat the sucrose pellets with the drug-containing coating liquid to form a drug-containing layer.

[0056] Table 2, preparation process parameters in Example 1:

[0057] .

[0058] Step 3: Drying: Place the pellets obtained in step 2 in a drying oven at 45°C for 4-6 hours.

[0059] Step 4, filling process: transfer the dried nicotine pellets obtained in step 3 into the powder hopper of the granule packaging machine, and place the non-woven fabric roll into the film roll hopper of the granule packaging machine; start the granule packaging machine to start the filling process.

[0060] The nicotine pellet composition oral bag prepared in Example 1 was subjected to an in vitro dissolution test. The experimental data are shown in Table 3.

[0061] Table 3. External dissolution data of nicotine micropellets for rapid nicotine release in oral bag of Example 1:

[0062] .

[0063] From Example 1, it can be seen that the nicotine micropellet oral bag prepared by the centrifugal granulation coating process and the micropellet coating method has the effect of rapidly releasing nicotine.

[0064] Example 2: Preparation of a nicotine micropellet oral bag for slow nicotine release, preparation process, and in vitro dissolution data.

[0065] Weigh the required materials according to the formula in Table 4.

[0066] Table 4, Nicotine pellet composition formula in Example 2:

[0067] .

[0068] The materials of Table 4 were prepared as follows:

[0069] A. Isolation layer coating process:

[0070] Step A1: Prepare the isolation layer coating solution: Dissolve the formulated amount of ethyl cellulose and magnesium stearate in 95% ethanol. Weigh the blank sucrose pellets according to the formulated amount.

[0071] Step A2, isolation layer coating process: The prepared ethyl cellulose and magnesium stearate alcohol solution is placed in the spray gun hopper, and the weighed blank sucrose pellets are placed in the fluidized bed solid hopper. The machine parameters are set according to the parameters in Table 5, and the machine is started to perform the fluidized bed coating process. At the same time, the fluidized bed is dried for 60 minutes to evenly coat the ethyl cellulose and magnesium stearate materials on the sucrose pellets and form an isolation layer.

[0072] Table 5, isolation layer coating process parameters:

[0073] .

[0074] Step A3: Drying process: The pellet drying process is completed simultaneously with the isolation layer coating.

[0075] B. Drug-containing layer coating process:

[0076] Step B1: Prepare the drug-containing coating solution: Dissolve the formulated amounts of nicotine ditartaric acid dihydrate, povidone, acesulfame potassium, magnesium stearate, flavoring agent, and sodium carbonate aqueous solution in 95% ethanol to obtain solution A. Weigh the sugar pills coated with the isolation layer according to the formulated amounts.

[0077] Step B2, drug-containing layer coating process: The prepared solution A was placed in the spray gun hopper, and the weighed sugar pills coated with the isolation layer were placed in the fluidized bed solid hopper. The machine parameters were set according to the parameters in Table 6, and the machine was started to perform the fluidized bed coating process. The fluidized bed drying was also performed for 45 minutes. The nicotine-containing composition was evenly coated on the sugar pills coated with the isolation layer.

[0078] Table 6, drug-containing layer coating process parameters:

[0079] .

[0080] Step B3: Drying process: The pellet drying process is completed simultaneously with the drug-containing layer coating.

[0081] C. Protective layer coating process:

[0082] Step C1: Prepare the protective layer coating solution: Dissolve the formulated amounts of povidone and magnesium stearate in 95% ethanol. Weigh the drug-coated nicotine pellets according to the formulated amounts.

[0083] Step C2, protective layer coating process: The prepared povidone and magnesium stearate alcohol solution was placed in the spray gun hopper, and the weighed nicotine micropellets coated with the drug-containing layer were placed in the fluidized bed solid hopper. The machine parameters were set according to the parameters in Table 7, and the machine was started to perform the fluidized bed coating process. The fluidized bed was dried simultaneously for 30 minutes to evenly coat the protective layer coating liquid on the nicotine micropellets coated with the drug-containing layer.

[0084] Table 7, protective layer coating process parameters:

[0085] .

[0086] Step C3: Drying process: The drying process is completed while the protective layer is being coated.

[0087] D. Drug-coating process:

[0088] Step D1: Prepare the drug-coating solution: Dissolve the formulated amounts of nicotine ditartaric acid dihydrate, methacrylic acid-ethyl acrylate copolymer, neotame, flavor, and sodium carbonate aqueous solution in 95% ethanol to obtain solution B. Weigh the protective layer-coated nicotine pellets according to the formulated amounts.

[0089] Step D2, drug-coating process: The prepared solution B was placed in the spray gun hopper, and the weighed nicotine pellets coated with the protective layer were placed in the fluidized bed solid hopper. The machine parameters were set according to the parameters in Table 8, and the machine was started to perform the fluidized bed coating process. The fluidized bed was dried simultaneously for 60 minutes to evenly coat the nicotine-containing composition on the sugar pellets coated with the isolation layer.

[0090] Table 8, drug-loaded layer coating process parameters:

[0091] .

[0092] Step D3, drying process: the pellet drying process is completed simultaneously with the drug-loaded layer coating.

[0093] Step D4, Filling Process: Transfer the dried nicotine pellets to the powder hopper of the granule packaging machine and place the non-woven fabric roll into the film roll hopper of the granule packaging machine. Start the granule packaging machine to start the filling process.

[0094] The nicotine pellet oral bag prepared in Example 2 was subjected to an in vitro dissolution test. The experimental data are shown in Table 9.

[0095] Table 9. External dissolution data of the nicotine micropellets slowly releasing nicotine in the oral bag of Example 2:

[0096] .

[0097] From Example 2, it can be seen that the nicotine pellet oral bag prepared by using the fluidized bed bottom spray coating and drying process and the pellet coating method has the effect of slowly releasing nicotine.

[0098] In summary, the nicotine pellet composition and nicotine pellet oral pouch provided by the present invention, through the preparation process, uniformly wrap the nicotine composition on the pellet core, and form a single or multiple layers of drug loading or coating on the blank pellet core to achieve the effects of rapid nicotine release and uniform and stable nicotine release, respectively, so that the nicotine content and release are relatively stable, and the aroma release is also stable; at the same time, after the nicotine and aroma are prepared into pellets, the mass and contents of each pellet are almost equal, and the drug release state is the same, so that the release of nicotine and the aroma are synchronized and can be maintained until the nicotine is completely released; by forming the drug loading or coating, the effects of moisture-proof, light-proof and air-proof can be achieved, and the stability of the nicotine pellet oral pouch can be increased; the preparation method provided by the present invention does not require the addition of a glidant during filling, and the weight difference is smaller than that of powder or granule filling. It can also avoid the interaction of the compound components during the preparation process, so that the prepared nicotine pellet composition and nicotine pellet oral pouch have good fluidity. The present invention provides a nicotine product with good fluidity, stable nicotine release and stable aroma release, which can be used for smoking cessation or nicotine dependence treatment.

[0099] The above description is only a preferred embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made by using the contents of the present invention description and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A nicotine pellet composition, characterized in that, It includes nicotine, blank pellets, binder, sweetener, pH regulator, cellulose and cellulose derivatives, polymer coating material, lubricant, essence and solvent. The blank pellets carry the nicotine, and the polymer coating material forms a single-layer or multi-layer drug-loading or coating on the blank pellets.

2. The nicotine pellet composition according to claim 1, characterized in that, When the polymer coating material forms a multi-layer drug-loading or coating, it sequentially includes a barrier layer, a drug-containing layer, a protective layer and a drug-loading layer from the inside to the outside.

3. The nicotine pellet composition according to claim 1, wherein The nicotine includes any one or more of free-base nicotine, nicotine salts, nicotine in a matrix or organometallic complex, nicotine-ion exchange resin combination, nicotine inclusion complex, or any non-covalently bound nicotine, nicotine lactate, nicotine malate, nicotine salicylate, nicotine resin complex, nicotine cyclodextrin inclusion complex, nicotine hydrochloride, nicotine dihydrochloride, nicotine tartrate, nicotine tartrate dihydrate, nicotine sulfate, nicotine zinc chloride and nicotine benzoate.

4. The nicotine pellet composition according to claim 1, characterized in that, The blank pellets include hydrophilic sugar-based pellets and / or hydrophobic cellulose pellets. The hydrophilic sugar-based pellets are pellets composed of water-soluble saccharide materials, and the hydrophobic cellulose pellets are pellets composed of water-insoluble cellulose materials.

5. The nicotine pellet composition according to claim 1, wherein The binder includes any one or more of povidone, cellulose derivatives, pregelatinized starch, sugar alcohol, gelatin, gum arabic, sodium alginate and polyethylene glycol.

6. The nicotine pellet composition according to claim 1, characterized in that, The sweetener includes any one or more of acesulfame potassium, sodium cyclamate, saccharin, sodium saccharin, sucralose, neotame, sodium cyclohexylsulfamate, aspartame, stevia, licorice, disodium glycyrrhizinate, tripotassium and trisodium glycyrrhizinate, glucose, fructose, sucrose, maltose, starch sugar and lactose, sorbitol, maltitol, isomaltitol, xylitol, lactitol, mannitol and erythritol.

7. The nicotine pellet composition according to claim 1, wherein The pH regulator includes any one or more of acetates, carbonates of alkali metals or ammonium, lactates, glycine salts, gluconates, borates, glycerophosphates or citrates, phosphates, metal hydroxides and their mixtures.

8. The nicotine pellet composition according to claim 1, wherein The cellulose and cellulose derivatives include any one or more of wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, bran fiber, bamboo fiber, vanilla fiber, powdered cellulose and polymer materials.

9. The nicotine pellet composition according to claim 1, characterized in that, The polymer coating material includes sugar materials or polymer materials. The sugar materials include any one or more of syrup, colored syrup, mucilage, talcum powder and white wax. The polymer materials include any one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methylcellulose, methacrylic acid copolymer, methacrylate copolymer, cellulose acetate phthalate, polyvinylpyrrolidone, polyvinylpyrrole and polyethylene glycol.

10. The nicotine pellet composition according to claim 1, characterized in that, The lubricant includes a hydrophobic lubricant and a hydrophilic lubricant. The hydrophobic lubricant includes any one or more of stearic acid, magnesium stearate, calcium stearate, glyceryl behenate, colloidal silica, talc powder, vegetable oil, polyethylene glycols, and sodium lauryl sulfate. The hydrophilic lubricant includes sodium stearyl fumarate.

11. The nicotine pellet composition according to claim 1, characterized in that, The flavoring agent includes any one or more of bergamot essence, eucalyptus essence, citrus essence, lemon essence, peppermint essence, mint essence, menthol, licorice essence, wintergreen essence, tobacco essence, coffee essence, vanilla essence, lime essence, apple essence, peach essence, mango essence, cherry essence, blueberry essence, strawberry essence, cola essence, cinnamon essence, and watermelon essence.

12. The nicotine pellet composition according to claim 1, characterized in that, The solvent includes water and / or an organic solvent. The organic solvent includes any one or more of aromatic hydrocarbons, aliphatic hydrocarbons, alicyclic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, ketones, diol derivatives, and other types such as acetonitrile, pyridine, and phenol.

13. A nicotine pellet buccal pouch, characterized in that, It includes a non-woven fabric sachet and the nicotine pellet composition according to any one of claims 1 to 12 contained in the non-woven fabric sachet.

14. A preparation method of a nicotine pellet buccal pouch, characterized in that, For preparing the nicotine pellet buccal pouch according to claim 13, it specifically includes the following steps: S1. Weighing and formulation process: Weigh the materials; formulate the polymer coating material according to the prescription. S2. Drug-loading coating process: After formulating the polymer coating material, put it into the spray gun hopper. Put the weighed solid materials into the solid material hopper of the fluidized bed or centrifugal coater in sequence according to the prescription. Start the machine to carry out the fluidized bed coating or centrifugal coating process, and evenly coat the materials on the pill cores to form one or more layers of material layers, obtaining nicotine-loaded pellets. S3. Drying process: Put the granulated nicotine pellets into a drying oven or fluidized bed for drying. S4. Filling process: Transfer the dried nicotine pellets to the powder hopper of the granule packaging machine, and put the non-woven fabric roll into the film roll hopper of the granule packaging machine. Start the granule packaging machine to carry out the filling process, so that the formed nicotine pellets are filled into the non-woven fabric sachet, obtaining the nicotine pellet buccal pouch.

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