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NICOTINE POUCH COMPOSITION

20220151292 · 2022-05-19

    Inventors

    Cpc classification

    International classification

    Abstract

    A pouch composition is disclosed, the pouch composition includes a nicotine-ion exchange resin combination, water in an amount of at least 15% by weight of the pouch composition, and inorganic divalent cations. Also, an oral pouched nicotine product can include a saliva-permeable pouch and the pouch composition in said pouch.

    Claims

    1. A pouch composition comprising a nicotine-ion exchange resin combination, water in an amount of at least 15% by weight of the pouch composition, and inorganic divalent cations.

    2. The pouch composition according to claim 1, wherein the inorganic divalent cations are in a molar ratio of at least 0.1 relative to amount of nicotine in the nicotine-ion exchange resin combination.

    3. The pouch composition according to claim 1, wherein the composition comprises inorganic divalent cations in a molar ratio of at most 5 relative to amount of nicotine in the nicotine-ion exchange resin combination.

    4. The pouch composition according to claim 1, wherein the inorganic divalent cations are selected from the group consisting of divalent cations of calcium, magnesium, iron, zinc, and any combination thereof.

    5. The pouch composition according to claim 1, wherein the inorganic divalent cations are selected from the group consisting of divalent cations of calcium and magnesium.

    6. The pouch composition according to claim 1, wherein the inorganic divalent cations are provided as a salt comprising anions selected from the group consisting of carboxylates, organic sulfonate, organic sulfate, organic phosphate, chloride, bromide, nitrate, sulfate, hydrogen phosphate, oxide, and any combination thereof.

    7. (canceled)

    8. The pouch composition according to claim 1, wherein the inorganic divalent cations are provided as a salt in an amount of between 0.1 and 15.0% by weight of the composition.

    9. The pouch composition according to claim 1, wherein the inorganic divalent cations are provided as an inorganic salt comprising inorganic anions selected from the group consisting of chloride, bromide, nitrate, sulfate, hydrogen carbonate, hydrogen phosphate, oxide, hydroxide, and any combination thereof.

    10-13. (canceled)

    14. The pouch composition according to claim 1, wherein the divalent cations are provided as a water-soluble salt having a water-solubility of at least 5 gram per 100 mL of water measured at 25 degrees Celsius, atmospheric pressure and pH 7.0.

    15. The pouch composition according to claim 1, wherein the pouch composition comprises nicotine in an amount of at least 0.1% by weight.

    16. The pouch composition according to claim 1, wherein the pouch composition comprises the nicotine-ion exchange combination in an amount of 0.1 to 20% by weight of the pouch composition.

    17-19. (canceled)

    20. The pouch composition according to claim 1, wherein the ion exchange resin comprises polacrilex resin.

    21. (canceled)

    22. The pouch composition according to claim 1, wherein the nicotine-ion exchange resin combination comprises nicotine complexed with ion exchange resin.

    23. (canceled)

    24. The pouch composition according to claim 1, wherein the nicotine-ion exchange resin combination comprises free-base nicotine mixed with ion exchange resin.

    25. (canceled)

    26. The pouch composition according to claim 1, wherein the pouch composition comprises at least one sugar alcohol.

    27. The pouch composition according to claim 26, wherein the at least one sugar alcohol is selected from xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and mixtures thereof.

    28-30. (canceled)

    31. The pouch composition according to claim 1, wherein the pouch composition comprises at least one water-insoluble fiber.

    32-33. (canceled)

    34. The pouch composition according to claim 31, wherein the water-insoluble fiber is selected from wheat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, cellulose fibers, bran fibers, bamboo fibers, powdered cellulose, and combinations thereof.

    35-36. (canceled)

    37. The pouch composition according to claim 1, wherein the pouch composition comprises a pH regulating agent.

    38-50. (canceled)

    51. An oral pouched nicotine product comprising a saliva-permeable pouch and the pouch composition of claim 1 enclosed in said pouch.

    52-58. (canceled)

    Description

    DETAILED DESCRIPTION OF THE INVENTION

    [0229] As used herein the term “pouch composition” refers to the composition for use in an oral pouch, i.e. in pouches for oral use. Also, the terms “pouch composition” and “nicotine pouch composition” is used interchangeably.

    [0230] As used herein the term “nicotine” refers to nicotine used as a refined/isolated substance. Particularly, nicotine does not refer to tobacco materials having a content of nicotine. Thus, when referring to nicotine amounts also to be understood as the nicotine dose, the amounts refers to the amount of pure nicotine.

    [0231] Nicotine also covers nicotine not obtained from tobacco, often referred to as synthetic nicotine.

    [0232] As used herein, a molar ratio refers to the ratio of the molar content of the first component divided by the molar content of the second component.

    [0233] The relative content between the first component and the second component may also be presented as equivalents of the first component relative to the second component.

    [0234] Thus, a pouch comprising divalent cations in a molar ratio of 0.1 relative to the amount of nicotine in the nicotine-ion exchange resin combination, may also be presented as a pouch comprising 0.1 eq. of divalent cations relative to the amount of nicotine in the nicotine-ion exchange resin combination, i.e. a pouch comprising 0.1 eq. of divalent cations and 1 eq. of nicotine in the nicotine-ion exchange resin combination.

    [0235] As used herein the term “free-base nicotine” refers to non-protonated form of nicotine, and therefore does not include nicotine salts or nicotine provided as a complex between nicotine and an ion exchange resin. Nevertheless, the free-base nicotine may be mixed with an amount of ion exchange resin or water-soluble compositions such as sugar alcohols or water-soluble fibers. While free-base nicotine includes both free-base nicotine extracted from tobacco as well as synthetically manufactured free-base nicotine, the free-base nicotine is not provided in the form of tobacco or powdered tobacco. Typically, free-base nicotine is provided as a liquid.

    [0236] As used herein the term “pouch” is intended to mean a container typically formed by a web of a fibrous material enclosing a cavity. The pouch is pouch designed for administration of an active ingredient in the oral cavity, and thus it is adapted for oral use, it is non-toxic and not water-soluble. The fibrous material may e.g. form a woven or non-woven web or fabric. The pouch may for example be sealed by bonding two corresponding pieces of web or fabric to each other along their edges to form a cavity for the nicotine and the non-water-soluble composition. In order to release the nicotine, the pouch is made water-permeable so as to allow saliva from the oral cavity to penetrate the pouch and enter the cavity, where the saliva can come into contact with the nicotine, whereby the nicotine are released from the oral pouch.

    [0237] As used herein, the term “nicotine-ion exchange resin combination” refer to a combination comprising nicotine complexed with ion exchange resin and/or free-base nicotine mixed with ion exchange resin.

    [0238] As used herein, the term “nicotine complexed with ion-exchange resin” refers to nicotine bound to an ion exchange resin.

    [0239] In the present context, the term “free-base nicotine mixed with ion exchange resin” refers to a mixture comprising free-base nicotine and ion exchange resin. It is noted that even if some embodiments comprise a combination of nicotine complexed with ion exchange resin and nicotine in its free-base form mixed with ion exchange resin, the term “free-base nicotine mixed with ion exchange resin” requires the presence of nicotine in its free-base form. In some embodiments, the mixture is an aqueous mixture. Free-base nicotine and water is mixed with ion-exchange resin, whereby a mixture comprising both free-base nicotine and ion exchange resin is obtained. Free-base nicotine mixed with ion exchange resin is referred to as “premix” in the examples.

    [0240] As used herein the term “powder composition” refers to composition in the form of powder, i.e. as a particulate material having a relatively small particle size, for example between 1 and 1200 micrometer. Particularly, by powder composition is not meant a powdered tobacco.

    [0241] As used herein the term “humectant” is understood as a moistening agent used to keep pouches moist, i.e. a humectant is added to the pouch composition with the purpose of keeping the pouch moist. Hence, the term humectant does not refer to substances added for other purposes, hereunder also hygroscopic substances added for other purposes, such as sugar alcohols, water-insoluble fibers and glycerol associated with ion-exchange resin in nicotine-ion exchange resin combinations, such as nicotine polacrilex. Examples of humectants include alginate, propylene glycol, hydroxypropyl cellulose, and glycerol. It is noted that when glycerol is included as a humectant, the glycerol is added as free glycerol and therefore liquid at room temperature. Further examples of humectants include triacetin, modified starch, pectin, xanthan gum, etc. The term humectant does not refer to sugar alcohols comprising 4 or more carbons. Also, the term humectant does not refer to fibers, such as water-insoluble fiber, such as wheat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, cellulose fibers, bran fibers, bamboo fibers, powdered cellulose, and combinations thereof. Also, the term humectant does not include e.g. NaCl.

    [0242] As used herein the term “water-soluble” refers to a relatively high water-solubility, for example a water-solubility of more than 5 gram of water-soluble composition or substance per 100 mL of water measured at 25 degrees Celsius, atmospheric pressure and pH of 7.0. When referring to a “soluble” composition or substance, water-soluble is meant, unless otherwise stated.

    [0243] As used herein the term “water-insoluble” refers to relatively low water-solubility, for example a water-solubility of less than 0.1 gram of composition or substance per 100 mL of water measured at 25 degrees Celsius, atmospheric pressure and pH of 7.0. When referring to “insoluble”, water-insoluble is meant unless otherwise stated. Therefore, compositions or substances having a water-solubility of between 0.1 and 5 gram per of composition or substance per 100 mL of water measured at 25 degrees Celsius, atmospheric pressure and pH of 7.0 are considered neither water-soluble nor water-insoluble, but having an intermediate water-solubility.

    [0244] The pouches of the invention provide a nicotine release into the oral cavity. A release profile of nicotine may be obtained which both comprises a fast release period and a sustained release period.

    [0245] As used herein the term “fast release” or “fast release period” may refer to the initial 2 minutes of the nicotine release profile, whereas the term “sustained release period refers” to the subsequent period of the release profile until end of experiment or end of use.

    [0246] As used herein the term “fast release rate” refers to the released nicotine per minute within the initial 2 minutes.

    [0247] As used herein the term “effective release” refers to the total release of nicotine over the release period of the experiment or the use period.

    [0248] As used herein, the term “dissolve” is the process where a solid substance enters a solvent (such as oral saliva or water within the pouch) to yield a solution.

    [0249] Typically, the pouches comprise openings, where the characteristic opening dimension is adapted to a characteristic dimension of the matrix composition so as to retain the matrix composition inside the pouch before use and/or to retain a part of the matrix composition, such as an water-insoluble composition, inside the pouch during use.

    [0250] In order to obtain a pouch having suitable opening dimensions in view of the matrix composition to be used, the material for the pouch may be selected accordingly, e.g. comprising e.g. woven and/or non-woven fabric.

    [0251] In other words, according to the various embodiments, the pouch forms a membrane allowing passage of saliva and prevents or inhibits passage of said matrix composition. The membrane of the pouch may be of any suitable material e.g. woven or non-woven fabric (e.g. cotton, fleece etc.), heat sealable non-woven cellulose or other polymeric materials such as a synthetic, semi-synthetic or natural polymeric material. An example of suitable pouch material is paper made of pulp and a small amount of wet strength agent. A material suitable for use must provide a semi-permeable membrane layer to prevent the powder or composition from leaving the bag or pouch during use. Suitable materials are also those that do not have a significant impact on the release of nicotine from the pouch.

    [0252] The pouch composition is filled into pouches and is maintained in the pouch by a sealing. An ideal pouch is chemically and physically stable, it is pharmaceutically acceptable, it is insoluble in water, it is easy to fill with powder and seal, and it provides a semi-permeable membrane layer which prevent the powder from leaving the bag, but permit saliva and therein dissolved or sufficiently small suspended components from the pouch composition in the pouch, such as nicotine, to pass through said pouch.

    [0253] The pouch may be placed in the oral cavity by the user. Saliva then enters into the pouch, and the nicotine and other components, which are soluble in saliva, start to dissolve and are transported with the saliva out of the pouch into the oral cavity, where the nicotine may be absorbed.

    [0254] According to an embodiment of the invention, the pouch composition may further comprise one or more additives.

    [0255] In an embodiment of the invention, said additives are selected from the group consisting of bile salts, cetomacrogols, chelating agents, citrates, cyclodextrins, detergents, enamine derivatives, fatty acids, labrasol, lecithins, phospholipids, synthetic and natural surfactants, nonionic surfactants, cell envelope disordering compounds, solvents, steroidal detergents, chelators, solubilization agents, charge modifying agents, pH regulating agents, degradative enzyme inhibitors, mucolytic or mucus clearing agents, membrane penetration-enhancing agents, modulatory agents of epithelial junction physiology, vasodilator agents, selective transport-enhancing agents, or any combination thereof. pH regulating agents include buffers.

    [0256] In an embodiment of the invention, said additives are selected from the group consisting of cetylpyridinium chloride (CPC), benzalkonium chloride, sodium lauryl sulfate, polysorbate 80, Polysorbate 20, cetyltrimethylammonium bromide, laureth 9, sodium salicylate, sodium EDTA, EDTA, aprotinin, sodium taurocholate, saponins, bile salt derivatives, fatty acids, sucrose esters, azone emulsion, dextran sulphate, linoleic acid, labrafil, transcutol, urea, azone, nonionic surfactants, sulfoxides, sauric acid/PG, POE 23 lauryl ether, methoxysalicylate, dextran sulfate, methanol, ethanol, sodium cholate, Sodium taurocholate, Lysophosphatidyl choline, Alkylglycosides, polysorbates, Sorbitan esters, Poloxamer block copolymers, PEG-35 castor oil, PEG-hydrogenated castor oil, Caprocaproyl macrogol-8 glycerides, PEG-8 caprylic/capric, glycerides, Dioctyl sulfosuccinate, Polyethylene lauryl ether, Ethoxydiglycol, Propylene glycol, mono-di-caprylate, Glycerol monocaprylate, Glyceryl fatty acids (C.sub.8-C.sub.18) ethoxylated Oleic acid, Linoleic acid, Glyceryl caprylate/caprate, Glyceryl monooleate, Glyceryl monolaurate, Capryliccapric triglycerides, Ethoxylated nonylphenols, PEG-(8-50) stearates, Olive oil PEG-6, esters, Triolein PEG-6 esters, Lecithin, d-alpha tocopherol polyethylene glycol 1,000 succinate, Citric acid, Sodium citrate, BRIJ, Sodium laurate, 5-methoxysalicylic acid, Bile salts, Acetyl salicylate, ZOT, Docosahexaenoic acid, Alkylglycosides, Sodium glycocholate (GC-Na), Sodium taurocholate (TC-Na), EDTA, Choline salicylate, Sodium caprate (Cap-Na), N-lauryl-beta-D-maltopyranoside (LM), Diethyl maleate, Labrasol, Sodium salicylate, Mentol, Alkali metal alkyl sulphate, Sodium lauryl sulphate, Glycerin, Bile acid, Lecithin, phosphatidylcholine, phosphatidylserine, sphingomyelin, phosphatidylethanolamine, cephalin, lysolecithin, Hyaluronic acid: alkalimetal salts, sodium, alkaline earth and aluminum, Octylphenoxypolyethoxyethanol, Glycolic acid, Lactic acid, Chamomile extract, Cucumber extract, Borage oil, Evening primrose oil, Polyglycerin, Lysine, Polylysine, Triolein, Monoolein, Monooleates, Monolaurates, Polydocanol alkyl ethers, Chenodeoxycholate, Deoxycholate, Glycocholic acid, Taurocholic acid, Glycodeoxycholic acid, Taurodeoxycholic acid, Sodium glycocholate, Phosphatidylcholine, Phosphatidylserine, Sphingomyelin, Phosphatidylethanolamine, Cephalin, Lysolecithin, Alkali metal hyaluronates, Chitosan, Poly-L-arginine, Alkyl glucoside, Saccharide alkyl ester, Fusidic acid derivatives, Sodium taurdihydrofusidate (STDHF), L-α-phosphatidylcholine Didecanoyl (DDPC), Nitroglycerine, nitropruside, NOC5 [3-(2-hydroxy-l-(methyl-ethyl)-2-nitrosohydrazino)-l-propanamine], NOC12 [iV-ethyl-2-(l-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine, SNAP [S-nitroso-N-acetyl-DL-penicillamine, NORI, NOR4, deacylmethyl sulfoxide, azone, salicylamide, glyceryl-l,3-diacetoacetate, l,2-isopropylideneglycerine-3-acetoacetate), Amino acids, Amino acid salts, monoaminocarboxlic acids, Glycine, alanine, phenylalanine, proline, hydroxyproline, hydroxyamino acids, serine, acidic amino acids, aspartic acid, Glutamic acid, Basic amino acids, Lysine, N-acetylamino acids, N-acetylalanine, N-acetylphenylalanine, TM-acetylserine, N-acetylglycine, N-acetyllysine, N-acetylglutamic acid, N-acetylproline, N-acetylhydroxyproline, lactic acid, malic acid and citric acid and alkali metal salts thereof, pyrrolidonecarboxylic acids, alkylpyrrolidonecarboxylic acid esters, N-alkylpyrrolidones, proline acyl esters, sodium lauryl phosphate, sodium lauryl sulphate, sodium oleyl phosphate, sodium myristyl sulphate, polyoxyethylene alkyl ethers, polyoxyethylene alkyl esters, and caproic acid, alkylsaccharide, fusidic acid, polyethylene glycol, cetyl alcohol, polyvinylpyrolidone, Polyvinyl alcohol, Lanolin alcohol, Sorbitan monooleate, Ethylene glycol tetraacetic acid, Bile acid conjugate with taurine, Cholanic acid and salts, Cyclodextran, Cyclodextrin, Cyclodextrin (beta), Hydroxypropyl-β-cyclodextran, Sulfobutylether-β-cyclodextran, Methyl-β-cyclodextrin, Chitosan glutamate, Chitosan acetate, Chitosan hydrochloride, Chitosan hydrolactate, 1-O-alkyl-2-hydroxy-sn-glycero-3-phosphocholine, 3-O-alkyl-2-acetoyl-sn-glycero-1-phosphocholine, 1-O-alkyl-2-O-acetyl-sn-glycero-3-phospho(N,N,N-trimethyl)hexanolamine, Propylene glycol, Tetradecylmaltoside (TDM), Sucrose dedecanoate.

    [0257] As used herein, the term “pH regulating agent” refers to agents, which active adjust and regulates the pH value of the solution to which they have been added or are to be added. Thus, pH regulating agents may be acids and bases, including acidic buffering agents and alkaline buffering agents. On the other hand, pH regulating agents does not including substances and compositions that can only affect the pH by

    dilution. Furthermore, pH regulating agents does not include e.g. flavoring, fillers, etc.

    [0258] In an embodiment of the invention, said pH-regulating agents are selected from the group consisting of Acetic acid, Adipic acid, Citric acid, Fumaric acid, Glucono-δ-lactone, Gluconic acid, Lactic acid, Malic acid, Maleic acid, Tartaric acid, Succinic acid, Propionic acid, Ascorbic acid, Phosphoric acid, Sodium orthophosphate, Potassium orthophosphate, Calcium orthophosphate, Sodium diphosphate, Potassium diphosphate, Calcium diphosphate, Pentasodium triphosphate, Pentapotassium triphosphate, Sodium polyphosphate, Potassium polyphosphate, Carbonic acid, Sodium carbonate, Sodium bicarbonate, Potassium carbonate, Calcium carbonate, Magnesium carbonate, Magnesium oxide, or any combination thereof.

    [0259] According to various embodiments of the invention, one or more sugar alcohols may be included in the pouch as part of the pouch composition, e.g. as a carrier or part thereof, or as a sweetener. Suitable sugar alcohols include sugar alcohols selected from the group of sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, hydrogenated starch hydrolyzates, isomalt, or any combination thereof.

    [0260] In an embodiment of the invention the pouch composition comprises high intensity sweetener.

    [0261] Preferred high intensity sweeteners include, but are not limited to sucralose, aspartame, salts of acesulfame, such as acesulfame potassium, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, stevioside and the like, alone or in combination.

    [0262] In an embodiment of the invention, the pouch composition comprises bulk sweeteners including sugar and/or sugarless components.

    [0263] In an embodiment of the invention, the pouch composition comprises bulk sweetener in the amount of 1.0 to about 80% by weight of the pouch composition, more typically constitute 5 to about 70% by weight of the pouch composition, and more commonly 10 to 60% by weight of the pouch composition or 10-50% by weight of the pouch composition. Bulk sweeteners may function both as a sweetener and also as a humectant. In some embodiments, inclusion of certain ingredients may limit the about amounts of bulk sweetener further.

    [0264] The sweeteners may often support the flavor profile of the pouch composition.

    [0265] Sugar sweeteners generally include, but are not limited to saccharide-containing components commonly known in the art of pouches, such as sucrose, dextrose, maltose, saccharose, lactose, sorbose, dextrin, trehalose, D-tagatose, dried invert sugar, fructose, levulose, galactose, corn syrup solids, glucose syrup, hydrogenated glucose syrup, and the like, alone or in combination.

    [0266] The sweetener can be used in combination with sugarless sweeteners. Generally, sugarless sweeteners include components with sweetening characteristics but which are devoid of the commonly known sugars and comprise, but are not limited to, sugar alcohols, such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolyzates, maltitol, isomalt, erythritol, lactitol and the like, alone or in combination.

    [0267] As used herein the term “flavor” is understood as having its ordinary meaning within the art. Flavor includes liquid and powdered flavors. Thus, flavors do of course not include sweeteners (such as sugar, sugar alcohols and high intensity sweeteners), or acids providing pure acidity/sourness, nor compounds providing pure saltiness (e.g. NaCl) or pure bitterness. Flavor enhancers include substances that only provide saltiness, bitterness or sourness. Flavor enhancers thus include e.g. NaCl, Citric acid, ammonium chloride etc.

    [0268] The flavors can be natural or synthetic flavors.

    [0269] In an embodiment of the invention the pouch composition comprises flavor. Flavor may typically be present in amounts between 0.01 and 15% by weight of the total composition of the pouch, such as between 0.01 and 5% by weight of the total composition.

    [0270] Non-exhaustive examples of flavors suitable in embodiments of the present invention are coconut, coffee, chocolate, vanilla, grape fruit, orange, lime, menthol, liquorice, caramel aroma, honey aroma, peanut, walnut, cashew, hazelnut, almonds, pineapple, strawberry, raspberry, tropical fruits, cherries, cinnamon, peppermint, wintergreen, spearmint, eucalyptus, and mint, fruit essence such as from apple, pear, peach, strawberry, apricot, raspberry, cherry, pineapple, and plum essence. The essential oils include peppermint, spearmint, menthol, eucalyptus, clove oil, bay oil, anise, thyme, cedar leaf oil, nutmeg, and oils of the fruits mentioned above.

    [0271] In various embodiments of the invention, the pouch composition comprises composition modifier. The composition modifier may be added to engineer the properties of the pouch composition and/or parts thereof, such as flowability, texture, homogeneity etc.

    [0272] The composition modifiers may, according to various embodiments, be selected group consisting of metallic stearates, modified calcium carbonate, hydrogenated vegetable oils, partially hydrogenated vegetable oils, polyethylene glycols, polyoxyethylene monostearates, animal fats, silicates, silicates dioxide, talc, magnesium stearates, calcium stearates, fumed silica, powdered hydrogenated cottonseed oils, hydrogenated vegetable oils, hydrogenated soya oil, emulsifiers, triglycerides, and mixtures thereof. Particularly, metallic stearates, such as magnesium stearate, may be advantageous.

    [0273] The composition modifiers may be added to the pouch composition in various ways.

    [0274] For example, the composition modifiers may be added by full powder mixture during the last few minutes of the final mixing.

    [0275] Alternatively, the composition modifiers may be added after granulation steps on a granulation premix.

    [0276] The composition modifier, such as magnesium stearate, may have a sealing effect and can be used to control the release of the nicotine and the solubility of the pouch.

    [0277] According to an embodiment of the invention, the pouch composition comprises polyvinylpyrrolidone (PVP). The pouch composition may also be free of PVP.

    [0278] One advantage of the above embodiment may be that a more uniform composition may be obtained.

    EXAMPLES

    Example 1A—Preparation of Pouches Designed for Administration of Nicotine

    [0279] The material of the pouches is heat sealable non-woven cellulose, such as long fiber paper. Pouches that are not in form of non-woven cellulose fabric may also be used according to the invention.

    [0280] The powder is filled into pouches and is maintained in the pouch by a sealing.

    Example 1B—Preparation of Pouches Designed for Administration of Nicotine

    [0281] The material of the pouches is manufactured using rayon fibers, such as viscose rayon staple fibers. The pouch membrane is heat sealed along its edges except for an opening in one end into an inner cavity formed by the pouch membrane.

    [0282] The powder is filled into pouches and is maintained in the pouch by a sealing.

    Example 2: Preparation of Nicotine Premixes

    [0283] A 60 liter planetary Bear Varimixer mixer was charged with water, and nicotine was weighed and added. The mixer was stirred at low speed for 1 minute at ambient temperature. Then ion exchange resin Amberlite® IRP64 was weighed and added to the mixer. The mixer was closed, stirred at high speed for 5 minutes, opened and scraped down, if necessary. Finally the mixer was stirred for further 5 minutes at high speed. The total process time was 20 minutes.

    [0284] Thereby, mixtures of nicotine and cation exchange resin were produced from the constituents stated in the below tables.

    [0285] Premix I:

    TABLE-US-00001 TABLE 1 Ingredients used to manufacture nicotine premix I (5.7% nicotine). % water in obtained nicotine-resin composition: 71.4 Constituent Amount (kg) Amount (%) Nicotine 1.0 5.7 Water 12.5 71.4 Resin 4.0 22.9 Total 17.5 100.0

    [0286] Premix II:

    TABLE-US-00002 TABLE 2 Ingredients used to manufacture nicotine premix II (13.2% nicotine). % water in obtained nicotine-resin composition: 34.1. Constituent Amount (kg) Amount (%) Nicotine 1.08 13.2 Water 2.80 34.1 Resin 4.32 52.7 Total 8.20 100.0

    [0287] Premix III:

    TABLE-US-00003 TABLE 3 Ingredients used to manufacture nicotine premix III (18.5% nicotine). % water in obtained nicotine-resin composition: 7.5. Constituent Amount (kg) Amount (%) Nicotine 1.08 18.5 Water 0.44 7.5 Resin 4.32 74.0 Total 5.84 100.0

    [0288] Premix IV:

    TABLE-US-00004 TABLE 4 Ingredients used to manufacture nicotine premix IV (10% nicotine). % water in obtained nicotine-resin composition: 50.0. Constituent Amount (kg) Amount (%) Nicotine 1.08 10.0 Water 5.40 50.0 Resin 4.32 40.0 Total 10.8 100.0

    [0289] Premix V:

    TABLE-US-00005 TABLE 5 Ingredients used to manufacture nicotine premix V (20% nicotine). % water in obtained nicotine-resin composition: 31.5. Constituent Amount (kg) Amount (%) Nicotine 1.78 20.0 Water 2.80 31.5 Resin 4.32 48.5 Total 8.90 100.0

    [0290] Premix VI:

    TABLE-US-00006 TABLE 6 Ingredients used to manufacture nicotine premix VI (30% nicotine). % water in obtained nicotine-resin composition: 27.5. Constituent Amount (kg) Amount (%) Nicotine 3.05 30.0 Water 2.80 27.5 Resin 4.32 42.5 Total 10.17 100.0

    [0291] Premix VII

    TABLE-US-00007 TABLE 7 Ingredients used to manufacture nicotine premix VII (35% nicotine). % water in obtained nicotine-resin composition: 25.6. Constituent Amount (kg) Amount (%) Nicotine 3.83 35.0 Water 2.80 25.6 Resin 4.32 39.4 Total 10.95 100.0

    [0292] Premix VIII:

    TABLE-US-00008 TABLE 8 Ingredients used to manufacture nicotine premix VIII (42% nicotine). % water in obtained nicotine-resin composition: 22.8. Constituent Amount (kg) Amount (%) Nicotine 5.15 42.0 Water 2.80 22.8 Resin 4.32 35.2 Total 12.27 100.0

    Example 3: Preparation of Pouch Compositions

    [0293] Pouches are prepared comprising powdered compositions as outlined in table 9-21. The pouches are made as follows.

    [0294] Fibers and water are mixed using a planetary Bear Varimixer mixer for 5 minutes. Then, the following ingredients were added subsequently under continuous mixing: first the nicotine-ion exchange combination (NPR or premix) (mixed for 2 minutes), then the remaining ingredients except liquid flavor and glidant if any (mixed for 2 minutes), then liquid flavor if any (mixed for 1 minute), then glidant if any (mixed for 1 minute). The total mixing time is 9-11 minutes.

    Example 4: Preparation of Filled Pouches

    [0295] The final pouch composition is filled into pouches (target fill weight 500 mg powder per pouch). The pouch material of example 1A or 1B may be used. The powder is filled into pouches and is maintained in the pouch by a sealing.

    Example 5A: Pouches

    [0296] The pouch compositions are prepared from the ingredients in table 9 using preparation method described in example 3.

    [0297] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00009 TABLE 9 Pouch compositions. Pouches P01 P02 P03 P04 P05 P06 P07 P08 C1 Amount of 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg nicotine Water 25 25 25 25 25 25 25 25 25 content [wt %] Inorganic 0.5 0.75 1 1.5 2 3 4 7.5 — divalent cations [eq]* Raw material Content in weight percent NPR (16%) 12.1 12.1 12.1 12.1 12.1 12.1 12.1 12.1 12.1 CaCl.sub.2** 0.7 1.0 1.3 2.0 2.6 3.9 5.2 10.0 — Xylitol 18.2 17.9 17.6 16.9 16.3 15.0 13.7 8.9 18.9 Purified 25 25 25 25 25 25 25 25 25 water Wheat 25 25 25 25 25 25 25 25 25 fiber Sodium 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 alginate Sodium 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 carbonate Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 High 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 intensity sweetener Potassium 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 sorbate Silicon 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 dioxide Total 100 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt.

    [0298] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0299] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0300] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0301] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0302] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0303] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0304] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0305] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5B

    [0306] The pouch compositions are prepared from the ingredients in table 10 using preparation method described in example 3.

    [0307] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00010 TABLE 10 Pouch compositions. Pouches P11 P12 P13 P14 P15 P16 P17 P18 C2 C3 Amount of 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg nicotine Water content 15 25 30 35 30 30 30 10 25 25 [wt %] Inorganic 1.0 1.0 1.0 1.0 1.0 1.5 2.0 1.0 — — divalent cations [eq]* Raw material Content in weight percent NPR (16%) 12.1 12.1 12.1 12.1 12.1 12.1 12.1 12.1 12.1 12.1 CaCl.sub.2** 1.3 1.3 1.3 1.3 — — — 1.3 — — MgCl.sub.2** — — — — 1.1 1.7 2.2 — — — Xylitol 37.6 17.6 7.6 2.6 12.8 12.2 11.7 32.6 12.0 18.2 Purified water 15 25 30 35 30 30 30 10 25 25 Wheat fiber 15 25 30 30 25 25 25 25 25 25 Sodium 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 alginate Sodium 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 carbonate Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 NaCl — — — — — — — — 6.9**** 0.7*** High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 sorbate Silicon 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 dioxide Total 100 100 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt. ***Corresponds to 1 eq of NaCl relative to nicotine in nicotine ion-exchange combination. ****Corresponds to 10 eq of NaCl relative to nicotine in nicotine ion-exchange combination.

    [0308] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0309] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0310] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0311] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0312] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0313] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0314] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0315] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5C

    [0316] The pouch compositions are prepared from the ingredients in table 11 using preparation method described in example 3.

    [0317] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00011 TABLE 11 Pouch compositions. Pouches P20 P21 P22 P23 P24 P25 P26 P27 P28 P29 Amount of 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 4.8 mg 7.2 mg 12.0 mg nicotine Water 28 28 28 28 28 28 28 28 28 28 content [wt %] Inorganic 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 cations [eq]* Raw material Content in weight percent NPR (16%) 12.1 12.1 12.1 12.1 12.1 12.1 12.1 6.1 9.0 15.1 CaCl.sub.2** — — — — — — — 0.7 1.0 1.6 Calcium 1.9 — — — — — — — — — acetate** Magnesium — 1.7 — — — — — — — — acetate** Calcium — — 2.6 — — — — — — — lactate** Magnesium — — — 2.4 — — — — — — lactate** FeCl.sub.2** — — — — 1.5 — — — — — ZnCl.sub.2** — — — — — 1.6 — — — — AlCl.sub.3** — — — — — — 1.6 — — — Xylitol 11.0 11.2 10.3 10.5 11.4 11.3 11.3 18.2 15.0 8.3 Purified 28 28 28 28 28 28 28 28 28 28 water Wheat fiber 28 28 28 28 28 28 28 28 28 28 Sodium 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 alginate Sodium 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 carbonate Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 sorbate Silicon 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 dioxide Total 100 100 100 100 100 100 100 100 100 100 *The inorganic cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Multivalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt.

    [0318] Pouch content: 500 mg total.

    [0319] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0320] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0321] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0322] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0323] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0324] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0325] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5D

    [0326] The pouch compositions are prepared from the ingredients in table 12 using preparation method described in example 3.

    [0327] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00012 TABLE 12 Pouch compositions. Pouches P30 P31 P32 P33 P34 P35 P36 P37 P38 P39 Amount of nicotine 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 4.8 mg 7.2 mg 12.0 mg Water content 28 28 28 28 28 28 28 28 28 28 [wt %] Inorganic cations 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 [eq]* Raw material Content in weight percent Premix VI 6.4 6.4 6.4 6.4 6.4 6.4 6.4 3.2 4.8 8.0 CaCl.sub.2** — — — — — — — 0.7 1.0 1.6 Calcium acetate** 1.9 — — — — — — — — — Magnesium — 1.7 — — — — — — — — acetate** Calcium lactate** — — 2.6 — — — — — — — Magnesium — — — 2.4 — — — — — — lactate** FeCl.sub.2** — — — — 1.5 — — — — — ZnCl.sub.2** — — — — — 1.6 — — — — AlCl.sub.3** — — — — — — 1.6 — — — Xylitol 18.7 18.9 18.0 18.2 19.1 19.0 19.0 21.9 20.5 17.6 Purified water 26 26 26 26 26 26 26 27.2 26.7 25.8 Wheat fiber 28 28 28 28 28 28 28 28 28 28 Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Sodium carbonate 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium sorbate 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Total 100 100 100 100 100 100 100 100 100 100 *The inorganic cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Multivalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt.

    [0328] Pouch content: 500 mg total.

    [0329] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0330] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0331] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0332] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0333] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0334] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0335] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5E

    [0336] The pouch compositions are prepared from the ingredients in table 13 using preparation method described in example 3.

    [0337] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00013 TABLE 13 Pouch compositions. Pouches P40 P41 P42 P43 P44 P45 C4 C5 Amount of nicotine 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg Water content 30 30 30 30 30 30 30 30 [wt %] Inorganic divalent 0.75 1.0 1.5 0.75 1.0 1.5 — — cations [eq]* Raw material Content in weight percent Premix II 14.6 14.6 14.6 — — — 14.6 — Premix VI — — 6.4 6.4 6.4 — 6.4 CaCl.sub.2** 1.0 1.3 2.0 1.0 1.3 2.0 — — Xylitol 10.4 10.1 9.4 15.6 15.3 14.6 9.4 14.6 Purified water 25 25 25 28 28 28 25 28 Wheat fiber 30 30 30 30 30 30 30 30 Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Sodium carbonate 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 NaCl — — — — — — 2.0 2.0 Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium sorbate 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Total 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt.

    [0338] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0339] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0340] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0341] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0342] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0343] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0344] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0345] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5F

    [0346] The pouch compositions are prepared from the ingredients in table 14 using preparation method described in example 3.

    [0347] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00014 TABLE 14 Pouch compositions. Pouches P50 P51 P52 P53 P54 P55 C6 C7 Amount of 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg nicotine Water content 15 25 40 30 30 10 30 30 [wt %] Inorganic divalent 1.0 1.0 1.0 1.0 1.0 1.0 — — cations [eq]* Raw material Content in weight percent Premix VI 6.4 6.4 6.4 — — 6.4 — — Premix VII — — — 5.5 — — 5.5 — Premix VIII — — — — 4.6 — 4.6 CaCl.sub.2** 1.3 1.3 1.3 1.3 1.3 1.3 — — Xylitol 45.3 25.3 4.3 15.6 16.1 49.3 21.9 17.4 Purified water 13 23 38 28.6 29 9 28.6 29 Wheat fiber 15 25 31 30 30 15 25 30 Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Sodium 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 carbonate Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 sorbate Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Total 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non- hydrated salt.

    [0348] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0349] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0350] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0351] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0352] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0353] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0354] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0355] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5G

    [0356] The pouch compositions are prepared from the ingredients in table 15 using preparation method described in example 3.

    [0357] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00015 TABLE 15 Pouch compositions. Pouches P60 P61 P62 P63 P64 P65 P66 P67 C8 C9 Amount of 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg nicotine Water content 27 27 27 27 27 27 35 30 30 30 [wt %] Inorganic divalent 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 — — cations [eq]* Raw material Content in weight percent Premix VI 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 CaCl.sub.2** 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 — — Xylitol 5.0 — — — — 7.0 5.0 5.0 5.0 Isomalt — 21.3 — — — — — — — Sorbitol — — 21.3 — — — — — — Mannitol — — — 21.3 — — — — — Maltitol — — — — 21.3 — — — — Erythritol 16.3 — — — — 14.3 14.2 23.5 18.5 Purified water 25 25 25 25 25 25 33 28 28 28 Wheat fiber 27 27 27 27 27 27 40.3 30 15 15 Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Sodium 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 carbonate Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 5.0 7.0 7.0 NaCl — — — — — — — — 5.0 10.0 High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 sorbate Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Total 100 100 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt.

    [0358] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0359] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0360] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0361] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0362] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0363] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0364] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0365] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5H

    [0366] The pouch compositions are prepared from the ingredients in table 16 using preparation method described in example 3.

    [0367] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00016 TABLE 16 Pouch compositions. Pouches P70 P71 P72 P73 P74 P75 P76 P77 Amount of nicotine 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg Water content [wt %] 27 27 27 20 20 35 20 35 Inorganic divalent cations 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 [eq]* Raw material Content in weight percent Premix VI 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 CaCl.sub.2** 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 Xylitol 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 Erythritol 18.2 18.2 18.2 42.2 22.2 17.2 22.2 17.2 Purified water 25 25 25 18 18 33 18 33 Wheat fiber — — — 10 30 20 — — Oat fiber 27 — — — — — 30 20 Pea Fiber — 27 — — — — — — Powdered Cellulose — — 27 — — — — — Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Sodium carbonate 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 Flavor 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 High intensity sweetener 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Potassium sorbate 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Total 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non- hydrated salt.

    [0368] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0369] Wheat fiber, trade name “Vitacel 600 WF plus” or “Vitacel 200WF”.

    [0370] Powdered cellulose, trade name “Vitacel L00” or “Vitacel L700G”.

    [0371] Oat fiber, trade name “Vitacel HF 600”.

    [0372] Pea fiber, trade name “Vitacel EF150”.

    [0373] Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, powdered cellulose, cellulose fibers, apple fibers, cocoa fibers, bamboo fibers, bran fibers, and cellulose fiber.

    [0374] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0375] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0376] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0377] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0378] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0379] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5I

    [0380] The pouch compositions are prepared from the ingredients in table 17 using preparation method described in example 3.

    [0381] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00017 TABLE 17 Pouch compositions. Pouches P80 P81 P82 P83 P84 P85 P86 P87 P88 Amount of 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg nicotine Water content 28 28 28 28 28 35 28 28 28 [wt %] Inorganic divalent 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 — cations [eq]* Raw material Content in weight percent NPR (16%) 12.1 12.1 12.1 12.1 12.1 12.1 12.1 12.1 12.1 CaCl.sub.2** 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 Xylitol 5.0 — — — — — 5.0 5.0 5.0 Isomalt — 13.5 — — — — — — — Sorbitol — — 13.5 — — — — — — Mannitol — — — 13.5 — — — — — Maltitol — — — — 13.5 — — — — Erythritol 8.5 — — — — — 8.5 8.5 8.5 Purified water 28 28 28 28 28 35 28 28 28 Wheat fiber 28 28 28 28 28 34.5 — — — Oat fiber — — — — — — 28 — — Pea Fiber — — — — — — — 28 — Powdered — — — — — — — — 28 Cellulose Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Sodium 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 carbonate Flavor 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 sorbate Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Total 100 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt.

    [0382] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0383] Wheat fiber, trade name “Vitacel 600 WF plus” or “Vitacel 200WF”.

    [0384] Powdered cellulose, trade name “Vitacel L00” or “Vitacel L700G”.

    [0385] Oat fiber, trade name “Vitacel HF 600”.

    [0386] Pea fiber, trade name “Vitacel EF150”.

    [0387] Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, powdered cellulose, cellulose fibers, apple fibers, cocoa fibers, bamboo fibers, bran fibers, and cellulose fiber.

    [0388] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0389] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0390] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0391] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0392] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0393] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5J

    [0394] The pouch compositions are prepared from the ingredients in table 18 using preparation method described in example 3.

    [0395] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00018 TABLE 18 Pouch compositions. Pouches P90 P91 P92 P93 P94 P95 P96 P97 P98 Amount of 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg nicotine Water content 30 30 27 27 27 30 30 30 30 [wt %] Inorganic 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 divalent cations [eq]* Raw material Content in weight percent NPR (16%) 7.0 12.1 12.1 12.1 12.1 12.1 12.1 12.1 12.1 NBT 2.3 — — — — — — — — CaCl.sub.2** 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 Xylitol 10.4 10.1 8.6 11.6 11.6 12.6 7.6 7.6 11.5 Purified water 30 30 27 27 27 30 30 30 30 Wheat fiber 30 30 27 27 27 30 30 30 30 Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 — — — Glycerol — — — — — — 2.0 — — Hydroxypropyl — — — — — — — 2.0 — cellulose Sodium 5.0 2.5 10.0 3.5 — — 5.0 5.0 5.0 carbonate Sodium — — — 3.5 — — — — — hydrogen- carbonate Trometamol — — — — 7.0 — — — — Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 7.0 High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 sorbate Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Total 100 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt.

    [0396] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0397] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0398] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0399] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0400] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0401] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0402] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0403] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5K

    [0404] The pouch compositions are prepared from the ingredients in table 19 using preparation method described in example 3.

    [0405] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00019 TABLE 19 Pouch compositions. Pouches P100 P101 P102 P103 P104 P105 P106 P107 P108 Amount of 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg nicotine Water content 30 30 27 27 27 30 30 30 30 [wt %] Inorganic divalent 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 cations [eq]* Raw material Content in weight percent Premix VI 3.7 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 NBT 2.3 — — — — — — — — CaCl.sub.2** 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 Xylitol 14.7 17.8 13.3 16.3 16.3 20.3 15.3 15.3 17.3 Purified water 29 28 25 25 25 28 28 28 28 Wheat fiber 30 30 30 30 30 30 30 30 30 Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 — — — Glycerol — — — — — — 2.0 — — Hydroxypropyl — — — — — — — 2.0 — cellulose Sodium 5.0 2.5 10.0 3.5 — — 5.0 5.0 5.0 carbonate Sodium — — — 3.5 — — — — — hydrogencarbonate Trometamol — — — — 7.0 — — — — Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 sorbate Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Total 100 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt.

    [0406] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0407] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0408] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0409] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0410] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0411] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0412] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0413] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5L

    [0414] The pouch compositions are prepared from the ingredients in table 20 using preparation method described in example 3.

    [0415] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00020 TABLE 20 Pouch compositions. Pouches P110 P111 P112 P113 P114 P115 C10 C11 Amount of 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg nicotine Water content 30 30 30 30 30 30 30 30 [wt %] Inorganic divalent 0.75 1.0 1.5 0.75 1.0 1.5 — — cations [eq]* Raw material Content in weight percent Premix II 14.6 14.6 14.6 — — — 14.6 — Premix VI — — — 6.4 6.4 6.4 — 6.4 CaCl.sub.2** 1.0 1.3 2.0 1.0 1.3 2.0 — — Xylitol 12.4 12.1 11.4 17.6 17.3 16.6 13.4 18.6 Purified water 25 25 25 28 28 28 25 28 Wheat fiber 30 30 30 30 30 30 30 30 Sodium 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 carbonate Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 sorbate Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Total 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt.

    [0416] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0417] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0418] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0419] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0420] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0421] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0422] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 5M

    [0423] The pouch compositions are prepared from the ingredients in table 21 using preparation method described in example 3.

    [0424] The pouch compositions are filled into pouches as described in example 4 (pouch material of examples 1A was used, but 1B could also have been applied).

    TABLE-US-00021 TABLE 21 Pouch compositions. Pouches P120 P121 P122 P123 P124 P125 P126 P127 Amount of 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg 9.6 mg nicotine Water content 30 30 30 30 30 30 27 27 [wt %] Inorganic 2.0 3.0 4.0 2.0 3.0 4.0 7.5 7.5 divalent cations [eq]* Raw material Content in weight percent Premix II 14.6 14.6 14.6 — — — 14.6 — Premix VI — — 6.4 6.4 6.4 — 6.4 CaCl.sub.2** 2.6 3.9 5.2 2.6 3.9 5.2 10.0 10.0 Xylitol 8.8 7.5 6.2 14.0 12.7 11.4 7.4 12.6 Purified water 25 25 25 28 28 28 22 25 Wheat fiber 30 30 30 30 30 30 27 27 Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Sodium 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 carbonate Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 High intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 sweetener Potassium 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 sorbate Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Total 100 100 100 100 100 100 100 100 *The inorganic divalent cations are presented as equivalents relative to nicotine in nicotine ion-exchange combination. **Divalent cations may be provided as a hydrated salt, such as dihydrate, tetrahydrate, hexahydrate etc. The weight % in the table are based on the non-hydrated salt.

    [0425] Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.

    [0426] Wheat fiber, trade name “Vitacel 600 WF plus”. Other fibers may be used as well, such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered cellulose, bran fibers, bamboo fibers, and cellulose fiber.

    [0427] Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may also be used in combination with sodium alginate, glycerol or HPC or as an alternative.

    [0428] Sodium carbonate is used as an alkaline buffering agent. Other buffering agents as described herein may also be used in combination with sodium carbonate or an alternative.

    [0429] Flavor example, a mixture of e.g. menthol and peppermint may be used. Of course, other flavors as described herein may be use as well, in combination with menthol and/or peppermint or replacing these. The flavor may be liquid or flavored or a combination, i.e. a liquid flavor and a powdered flavor is added.

    [0430] Acesulfame potassium and/or sucralose may as an example be used as high intensity sweeteners. Other usable high intensity sweeteners described herein may be used in combination with or instead of acesulfame potassium and/or sucralose.

    [0431] Potassium sorbate is used as a preservative. Other preservatives as described herein may also be used in combination with or instead of potassium sorbate.

    [0432] Silicon dioxide is used as a glidant. Other possible glidants include e.g. magnesium stearate, starch and talc.

    Example 6A: Release Experiment and Varying Salts

    [0433] The release experiment was performed by adding an amount of NPR (16%) and varying equivalent of CaCl.sub.2 to 900 mL of water corresponding to a nicotine concentration of 28 mg/L. The equivalents of CaCl.sub.2 are relative to nicotine. The temperature of the water was 25 degrees Celsius throughout the experiment and stirring of 100 rpm was applied throughout the experiment. pH was measured at experiment start and end. The pH was in all experiments below 7.0 at both the start and end of the experiment.

    [0434] A relative low nicotine concentration is used in order to reduce the impact of equilibrium on both the release rate and effective release of nicotine from the ion-exchange resin.

    [0435] Samples were taken out at varying timepoints and analyzed for nicotine content using standard HPLC. The results are presented as percentage of nicotine released.

    TABLE-US-00022 TABLE 22 Release of nicotine over time in the presence of varying salts and varying equivalents of cations. Salt No 1 eq 10 eq 1 eq 10 eq Salt NaCl NaCl CaCl.sub.2 CaCl.sub.2 Minutes Released nicotine (%) 1 12.4 — — 46.3 — 2 15.9 24.4 43.8 — 80.3 3 — — — 58.4 — 4 18.1 — — — — 8 20.2 — — 69.2 — 11 20.9 — — 72.6 — 13 — 28.1 51.9 89.9 14 21.8 — — 75.0 — 17 22.4 — — 76.5 — 20 23.1 — — 78.2 — 23 — 29.9 52.9 — 25 24.0 — — — 30 24.8 — — — 33 — 30.1 54.5 90.4 35 25.7 — — — 40 26.5 — — — 45 27.2 — — 81.1 — 60 28.8 — — 82.0 —

    [0436] Evaluation: the result shows that the presence of CaCl.sub.2 significantly increases the release of nicotine from NPR. Increasing the amount of CaCl.sub.2 result in an increased release of nicotine. The presence of CaCl.sub.2 increases both the initial release rate and seems to also increase the effective release of nicotine.

    [0437] Furthermore, the results show that NaCl has a much lower effect on the release of nicotine, thus high amount of NaCl are needed in order to achieve comparable release of nicotine in the presence of for example 1 eq. of CaCl.sub.2.

    Example 6B: Release Experiment Using NPR and Varying Equivalents of CaCl.SUB.2

    [0438] The release experiment was performed by adding NPR (16%) and varying equivalent of CaCl.sub.2 to a volume of water corresponding to a nicotine concentration of 28 mg/L. The equivalents of CaCl.sub.2 are relative to nicotine. The temperature of the water was 25 degrees Celsius throughout the experiment and stirring of 100 rpm was applied throughout the experiment. pH was measured at experiment start and end. The pH was in all experiments below 7.0 at both the start and end of the experiment.

    [0439] A relative low nicotine concentration is used in order to reduce the impact of equilibrium on both the release rate and effective release of nicotine from the ion-exchange resin.

    [0440] Samples were taken out at varying timepoints and analyzed for nicotine content using standard HPLC. The result is presented as percentage of nicotine released.

    TABLE-US-00023 TABLE 23 Shows the percentage of nicotine released from NPR at different timepoints in the presence of varying equivalent of CaCl.sub.2. CaCl.sub.2 0 eq 0.1 eq 0.25 eq 0.5 eq 0.75 eq 1 eq 4 eq Minutes Released nicotine (%) 1 12.4 17.7 25.0 30.5 38.5 46.3 59.1 2 15.9 22.0 — 39.7 — — — 3 — — 33.9 — 51.7 58.4 71.8 4 18.1 24.3 — 46.1 — — — 5 — — 38.6 — 59.3 — 76.8 7 — — 42.4 — 64.0 — — 8 20.2 26.6 — 53.3 — 69.2 79.9 9 — — 43.3 — 66.7 — — 11 20.9 27.8 44.1 56.4 68.9 72.6 82.4 13 — — 46.0 — 71.0 — — 14 21.8 28.7 — 58.9 — 75.0 83.9 15 — — 45.9 — 73.0 — — 17 22.4 29.3 — 61.0 74.4 76.5 84.7 18 — — 47.2 — — — — 20 23.1 30.3 47.5 62.4 76.3 78.2 85.0 25 24.0 31.1 — 64.4 — — — 30 24.8 31.8 49.3 65.8 — — — 35 25.7 32.6 — 66.8 — — — 40 26.5 33.2 — 67.8 — — — 45 27.2 33.8 50.6 69.2 80.2 81.1 87.3 60 28.8 35.0 51.7 69.2 81.1 82.0 88.1

    [0441] Evaluation: the result shows that the presence of CaCl.sub.2 significantly increases the release of nicotine from NPR. Increasing the amount of CaCl.sub.2 result in an increased release of nicotine. The presence of CaCl.sub.2 increases both the initial release rate and seems to also increase the effective release of nicotine.

    Example 6C: Release Experiment Using NPR and Varying Equivalents of MgCl.SUB.2

    [0442] The release experiment was performed by adding NPR (16%) and varying equivalents of MgCl.sub.2 to a volume of water corresponding to a nicotine concentration of 28 mg/L. The equivalents of MgCl.sub.2 are relative to nicotine. The temperature of the water was 25 degrees Celsius throughout the experiment and stirring of 100 rpm was applied throughout the experiment. pH was measured at experiment start and end. The pH was in all experiments below 7.0 at both the start and end of the experiment.

    [0443] A relative low nicotine concentration is used in order to reduce the impact of equilibrium on both the release rate and effective release of nicotine from the ion-exchange resin.

    [0444] Samples were taken out at varying timepoints and analyzed for nicotine content using standard HPLC. The result is presented as percentage of nicotine released.

    TABLE-US-00024 TABLE 24 Shows the percentage of nicotine released from NPR at different timepoints in the presence of varying equivalents of MgCl.sub.2. MgCl.sub.2 Min- 0 eq 0.1 eq 0.25 eq 0.5 eq 0.75 eq 1 eq 2 eq 4 eq utes Released nicotine (%) 1 12.4 16.8 23.2 33.7 40.6 42.3 53.7 63.0 3 — 22.9 32.2 44.1 52.2 55.3 66.5 73.6 5 — 25.8 37.0 49.9 58.1 62.4 72.2 79.4 7 — 27.6 39.9 54.0 62.4 66.7 74.8 81.3 9 — 28.4 41.6 56.7 64.8 69.3 76.5 83.2 11 20.9 29.1 43.0 58.6 67.5 71.7 78.2 83.9 13 — 29.9 44.5 60.2 70.1 73.0 79.7 85.1 15 — 30.5 44.8 61.6 71.2 74.2 80.4 87.0 20 23.1 31.5 47.2 64.5 72.8 76.5 82.1 87.5 25 24.0 32.5 47.7 65.7 75.8 77.7 83.8 87.9 30 24.8 33.2 48.8 68.1 78.2 — — 88.1

    [0445] Evaluation: the result shows that the presence of MgCl.sub.2 significantly increases the release of nicotine from NPR. Increasing the amount of MgCl.sub.2 result in an increased release of nicotine. The presence of MgCl.sub.2 increases both the initial release rate and seems to also increase the effective release of nicotine. The results are comparable to the result presented in example 6B.

    Example 6D: Release Experiment Using 1 Equivalent of CaCl.SUB.2 .and Nicotine Premix Having Varying Content of Nicotine

    [0446] The release experiment was performed by adding nicotine premix having varying content of nicotine and 1 equivalent of CaCl.sub.2 to a volume of water, whereby a corresponding nicotine concentration of 28 mg/L is obtained. The equivalent of CaCl.sub.2 is relative to nicotine. The temperature of the water was 25 degrees Celsius throughout the experiment and stirring of 150 rpm was applied throughout the experiment. pH was measured at experiment start and end. The pH was in all experiments below 7.0 at both the start and end of the experiment.

    [0447] A relative low nicotine concentration is used in order to reduce the impact of equilibrium on both the release rate and effective release of nicotine from the ion-exchange resin.

    [0448] Samples were taken out at varying timepoints and analyzed for nicotine content using standard HPLC. The result is presented as percentage of nicotine released.

    TABLE-US-00025 TABLE 25 Shows the percentage of nicotine released from nicotine premix at different timepoints in the presence of 1 equivalent of MgCl.sub.2. Ingredients Premix II II VI VI VII VII VIII VIII CaCl.sub.2 — 1 eq. — 1 eq. — 1 eq. — 1 eq. Min. Released nicotine (%) 1 2.1 9.1 37.2 56.3 43.8 55.7 58.3 69.6 2 3.0 14.7 44.9 66.9 53.4 66.0 66.2 78.7 3 4.0 19.9 48.9 71.4 57.4 73.4 70.1 82.6 4 4.9 24.7 51.8 76.8 60.1 77.8 72.0 85.9 5 5.7 29.8 53.7 79.5. 62.2 81.4 73.0 88.4 6 6.5 33.7 54.4 81.6 63.0 84.1 74.7 90.3 7 7.1 38.6 55.4 83.1 64.4 86.2 75.0 92.3 8 8.0 42.0 56.1 84.8 65.2 88.9 75.4 92.9 9 8.4 46.4 56.9 86.3 65.5 90.5 75.7 94.5 10 9.0 49.9 57.4 87.3 66.1 91.1 76.0 94.7 11 — 53.1 58.0 88.0 66.5 92.6 76.5 95.7 12 — 55.6 58.4 89.2 67.3 93.4 — 96.3 13 — 57.7 58.5 89.9 66.9 93.8 77.0 96.9 14 — 60.5 58.9 90.9 67.3 95.0 — 97.3 15 11.8  62.0 59.6 91.6 68.2 95.8 77.3 97.3

    [0449] Evaluation: the result shows that the presence of CaCl.sub.2 significantly increases the release of nicotine from premixes. The presence of CaCl.sub.2 increases both the initial release rate and seems to also increase the effective release of nicotine. Furthermore, the results demonstrate that increasing the nicotine content of the premixes also increases the nicotine release.

    Example 6E: Release Experiment Using 1 Equivalent of AlCl.SUB.3 .or 1 Equivalent of MgO

    [0450] The release experiment was performed by adding NPR (16%) and 1 equivalent of AlCl.sub.3 to a volume of water corresponding to a nicotine concentration of 28 mg/L. The equivalents are relative to nicotine. The temperature of the water was 25 degrees Celsius throughout the experiment and stirring of 150 rpm was applied throughout the experiment. pH was measured at experiment start and end. The pH was in all experiments below 7.0 at both the start and end of the experiment.

    [0451] A relative low nicotine concentration is used in order to reduce the impact of equilibrium on both the release rate and effective release of nicotine from the ion-exchange resin.

    [0452] Samples were taken out at varying timepoints and analyzed for nicotine content using standard HPLC. The result is presented as percentage of nicotine released.

    TABLE-US-00026 TABLE 24 Shows the percentage of nicotine released from NPR at different timepoints in the presence of 1 equivalent of AlCl.sub.3. Salt No Salt 1 eq AlCl.sub.3 Minutes Released nicotine (%) 1 11.1 39.9 3 14.5 49.4 5 16.1 55.4 8 18.2 60.9 11 19.7 64.4 15 20.0 68.4 20 21.1 71.4 25 21.5 74.0 30 22.4 75.4

    [0453] Evaluation: the results demonstrate that the presence of 1 equivalent of AlCl.sub.3 significantly increases the release of nicotine from NPR. The presence of AlCl.sub.3 increases both the initial release rate and seems to also increase the effective release of nicotine.

    Example 7A: Pouch Release Experiments (In Vitro)

    [0454] The release properties of the pouches were tested in an in vitro experiment.

    [0455] Reaction tubes having a diameter approx. 2 cm and containing 10 mL of 0.02 M potassium dihydrogen phosphate-buffer (pH adjusted to 7.4) were warmed to 37 degrees Celsius. One reaction tuber per timepoint was used.

    [0456] A pouch was submerged in the buffer of the first reaction tube using tweezers. After a specified time period, the pouch was captured with the tweezer and gently swirled in the buffer before being removed from the first reaction tube and added to the next reaction tube, representing the next time point. The procedure was repeated until the desired number of time points had been tested.

    [0457] The whole release experiment was performed at 37 degrees Celsius. No stirring or shaken was applied during the release experiment.

    [0458] The amount of release nicotine was determined by analyzing the buffer samples at the different timepoints using standard HPLC.

    Example 8A: Release Experiment on Pouches

    [0459] The release experiment was performed as described in example 7A.

    TABLE-US-00027 TABLE 27 Shows the percentage of nicotine released from nicotine pouches at different timepoints in the presence of varying equivalents of CaCl.sub.2. Pouch C4 P40 P42 C5 P43 P45 C10 P110 C11 P113 Premix II II II VI VI VI II II VI VI CaCl.sub.2 — 0.75 eq 1.5 eq — 0.75 eq 1.5 eq — 0.75 eq — 0.75 eq NaCl 2.9 eq — — 2.9 eq — — — — — — Min. Released nicotine (%) 2 13.8 12.9 32.4 20.8 24.0 39.3 16.2 29.5 26.9 38.7 5 25.7 26.0 49.6 39.8 42.9 62.5 28.6 50.9 47.4 58.2 10 37.5 40.3 66.0 59.0 61.7 78.8 42.0 64.8 66.0 74.8 30 60.4 62.3 79.9 79.4 82.6 90.3 59.2 78.7 79.5 92.2

    [0460] Evaluation: comparing P110 and P113 with C10 and C11 respectively, the result shows that the presence of CaCl.sub.2 increases the release of nicotine from pouches. The presence of CaCl.sub.2 increases both the initial release rate and seems to also increase the effective release of nicotine. Comparing P40 and P42, demonstrate that increasing the amount of CaCl.sub.2 in a pouch also increases the nicotine release from the pouch.

    [0461] Furthermore, the results demonstrate that increasing the nicotine content of the premixes also increases the nicotine release from the pouches, comparing P40 with P43, P42 with P45 and P110 with P113.

    [0462] Finally, it is noted that in order to obtain a release being comparable to the release obtained from pouches comprising only 0.75 eq CaCl.sub.2, a much higher amount of NaCl will be needed, here at least 2.9 eq NaCl required to obtain a release being comparable to 0.75 eq CaCl.sub.2 (see C4, C5, P40 and P43).

    Example 9A: User Evaluation

    [0463] The produced pouches of the invention were evaluated and found highly suitable as delivery vehicles of nicotine in that they provide a favorable release of nicotine and at the same time are pleasant to the user, e.g. with respect to a desirable mouthfeel such as a moist and moldable texture and a desirable taste.

    Example 9B: User Evaluation

    [0464] The pouch product P03 and P44 was evaluated with respect to perceived effect from nicotine and mouthfeel.

    [0465] Evaluation of perceived effect from nicotine and mouthfeel is performed as described in the following.

    [0466] Perceived effect from nicotine and mouthfeel was evaluated by a test panel of 4 trained assessors. Each assessor evaluates all samples twice. Average evaluations are estimated.

    [0467] The pouch product P03 and P44 were evaluated to have a fast onset of action and a high perceived effect from nicotine by all four assessors. Also, all four assessors evaluated the pouch products to have a desirable mouthfeel, i.e. the pouches were found to be moist and have a desirable taste.

    [0468] Similarly, the pouches, P08 and P127, were evaluated. These pouches were evaluated to have a fast onset of action and a high perceived effect from nicotine by all four assessors. However, the pouches were found to provide a less desirable mouthfeel, the pouches being perceived as somewhat dry, adhering to the oral mucosa and/or as having a poor taste or less desirable taste, i.e. too salty.

    [0469] It should be noted that the invention in its broader aspects is not limited to the specific details, representative compositions, methods, and processes, and illustrative examples described in connection with the preferred embodiments and preferred methods. Modifications and equivalents will be apparent to practitioners skilled in this art and are encompassed within the spirit and scope of the appended claims.