PRODUCT AND METHOD FOR MANUFACTURING A RUBBER.

Abstract

This invention relates to a nicotine chewing gum that provides immediate nicotine release and uptake, as well as prolonged nicotine release and uptake, and also to describing suitable manufacturing processes for such chewing gum formulations and the use of the chewing gum for the treatment of a human suffering from cravings due to tobacco dependence and / or electronic cigarette dependence.

Description

PRODUCT AND METHOD FOR MANUFACTURING A RUBBER FIELD OF INVENTION This invention relates to a nicotine chewing gum that provides immediate nicotine release and uptake, as well as prolonged nicotine release and uptake, and also to describing suitable manufacturing processes for such chewing gum formulations and the use of the chewing gum for the treatment of a human suffering from cravings due to tobacco dependence and / or electronic cigarette dependence. BACKGROUND OF THE INVENTION According to the QMS, approximately six million people die from smoking-related diseases each year, despite the fact that there are products (medicines) on the market to help a smoker quit smoking; products such as e.g. nicotine comprising chewing gum, lozenges, sprays and transdermal patches. A traditional way to produce nicotine chewing gum is to create a nicotine complex with a cation exchange resin and add this complex to a chewing gum formulation. Such chewing gums have been available on the market for many years and are sold, for example, under the registered trademark Nicorette®. However, there are consumers who seek nicotine products (medicines) that could provide faster craving relief, closer to the craving relief of a cigarette, and therefore there is still an opportunity to develop new nicotine chewing gums that could satisfy this population that uses tobacco and / or electronic cigarettes. One product on the market that provides faster craving relief is Nicorette™ QuickMist™, which is an oral spray applied to the oral mucosa from which the nicotine compound is easily absorbed into the bloodstream to provide faster craving relief. WO2006124366 describes a chewing gum comprising at least one nicotine resin within a core, wherein at least one internal polymeric film coating is applied thereto and at least one external hard coating. The resulting gum exhibits a long-lasting flavoring effect and provides a sustained release of nicotine when subjects are chewing the gum. WO2010044736 describes a multi-portion intraoral lozenge dosage form, wherein at least one portion disintegrates rapidly and at least one portion disintegrates slowly, and makes no mention of chewing gum. Extensive lists of potentially suitable active pharmaceutical agents and disease lists exist. The problem this invention aims to solve is to provide a product that offers both rapid nicotine uptake and sustained nicotine release to help people quit smoking. To achieve this, it is essential to include nicotine and a regulator in a form that allows for both rapid nicotine uptake and the sustained / extended release commonly found in medicated nicotine chewing gum. However, there are consumers who could benefit from products that could provide both quick and longer-lasting relief from cravings for one or the same product. BRIEF DESCRIPTION OF THE INVENTION The inventors have been exploring the possibility of creating a chewing gum that results in both immediate and prolonged nicotine release and rapid nicotine uptake while still maintaining good taste and palatability. To provide immediate release and uptake in a nicotine gum product, the inventors' method has been to apply nicotine in a readily available nicotine salt form, such as nicotine bitartrate or nicotine ditartrate dihydrate, comprising at least one outer portion / layer fused to the exterior of a hard-coated nicotine chewing gum. The pKa for nicotine is approximately 7.8. It is known that the uncharged (free base form of nicotine) compared to nicotine in its positively charged acid form could enter biological membranes, such as the oral mucosa, more easily and quickly for rapid systemic uptake. Therefore, if a salt of the acid drug such as nicotine bitartrate is co-formulated in a product such that the product also contains some readily available and fast-release regulator(s), which are also present outside the core of nicotine chewing gum, these regulators could rapidly and transiently increase the pH of the solvent (in this case saliva) to convert the nicotine salt into its freebase form, resulting in a relatively faster absorption of the nicotine present in at least one portion / layer outside of a hard-coated chewing gum. The average pH of human saliva is normally approximately 6-7.5. By selecting and adding some quick-release regulators to at least one film coating outside the gum core, a rapid increase in salivary pH of approximately one pH unit above the pKa of nicotine can be achieved (hence, onn / zznz / E / YiAi in the range of or above pH 9). This would cause approximately 90% of the nicotine in at least one portion / layer to be converted into its freebase form when it disintegrates and dissolves in saliva, readily absorbed into the systemic circulation to provide faster craving relief. The freebase form of nicotine is not suitable for direct formulation into semi-solid or solid dosage forms because the nicotine base form is in a highly volatile liquid form under normal conditions. In order to provide a transient and adequate increase in pH, it is beneficial to use a regulatory system, such as at least two regulators (regulating species). Regulatory systems typically have an unpleasant taste and therefore need to be carefully selected and their flavor masked, for example, by sweeteners and flavorings. Furthermore, the regulatory capacity of a given regulator (regulatory species) may not be sufficient. To provide prolonged nicotine release from a traditional nicotine gum core, nicotine bound to a resin, such as nicotine polacrilex, is suitable. Nicotine polacrilex is commonly used in commercially available medicated chewing gums. Such medicated gum provides prolonged release for up to approximately 20 to 45 minutes, depending on usage. However, the release and absorption of these gums during the first 5–10 minutes of use is somewhat limited. The invented nicotine chewing gum provides new features in one and the same product, compared to other medicinal nicotine products currently on the market. Nicotine chewing gum could also become an attractive product for consumers or patients who prefer nicotine chewing gum as a format. In one aspect, the invention relates to a nicotine chewing gum comprising, (i) a gum core comprising nicotine, (ii) at least one film coating outside the gum core comprising at least two regulators, at least one sweetener, at least one flavoring, and at least one film-forming polymer, or at least two film coatings outside the gum core, wherein one film coating comprises at least two regulators and at least one film-forming polymer and the other film coating comprises at least one sweetener, at least one flavoring, and at least one film-forming polymer, (iii) at least one polyol-based hard coating outside at least one film coating, wherein the polyol-based hard coating comprises at least one sugar alcohol or mixtures of sugar alcohols, (iv) at least one portion / layer fused to the outside of the polyol-based hard coating, wherein the portion comprises nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols and where the release of nicotine from at least one outer portion / layer (iv) is immediate and the release of nicotine from the core (i) is extended and wherein the at least two regulators (ii) located in at least one film coating located outside the core, promote rapid uptake of nicotine from (iv) through the oral mucosa (see, for example, Figures 1 and 2). In another aspect, the invention relates to a method for making chewing gum, comprising the steps of i. providing a chewing gum core comprising nicotine, ii. providing a polymer-based film coating formulation comprising at least two regulators, at least one sweetener, and at least one flavoring, iii. coating the chewing gum core with the polymer-based film coating formulation, iv. obtaining a film-coated chewing gum comprising at least two regulators, at least one sweetener, and at least one flavoring, v. providing a polyol-based hard coating formulation comprising at least one sugar alcohol or mixtures of sugar alcohols, vi. coating the film-coated chewing gum with the polyol-based hard coating formulation, vii. obtaining a hard-coated chewing gum, viii. providing a formulation comprising nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, ix. fusing the composition of viii) to the exterior of the hard-coated chewing gum as at least one portion / layer, x. obtaining a hard-coated nicotine chewing gum with at least one portion / layer outside the hard-coated chewing gum, wherein the release of nicotine from at least one outer portion / layer (ix) is immediate and the release of nicotine from the core (i) is extended and ic / on / οηη / ζζηζ / Ε / γίΛΐ where at least two regulators (iv) located outside the gum core promote rapid uptake of nicotine through the oral mucosa (see, for example, Figure 1). In another aspect, the invention relates to a method for making chewing gum, comprising the steps of; i. providing a chewing gum core comprising nicotine, ii. providing a polymer-based film formulation comprising at least two regulators, iii. coating the chewing gum core with the polymer-based film formulation, iv. obtaining a film-coated chewing gum with a film coating comprising at least two regulators, v. providing a polymer-based film formulation comprising at least one sweetener and at least one flavoring, vi. coating the chewing gum with a polymer-based film formulation, vii. obtaining a chewing gum coated with two polymer-based film coatings, a film coating comprising at least two regulators, and a film coating comprising at least one sweetener and at least one flavoring, viii. providing a polyol-based hard coating formulation comprising at least one sugar alcohol or mixtures of sugar alcohols, ix. coating the film-coated chewing gum with the polyol-based hard coating formulation, x. obtaining a hard-coated chewing gum, xi. providing a composition comprising nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, xii. fusing the composition of xi) to the outside of the hard-coated chewing gum as at least one portion / layer, and xiii. obtaining a hard-coated nicotine chewing gum with at least one portion / layer containing nicotine salt wherein the release of nicotine from the outer portion / layer (xiii) is immediate and the release of nicotine from the core (i) is extended and ic / onn / zznz / E / YiAi where at least two regulators (vil) located outside the gum core promote rapid uptake of nicotine through the oral mucosa (see, for example, Figure 2). The steps mentioned above could be in different orders. For example, a step of providing a polymer-based film formulation comprising at least two regulators, at least one sweetener, and at least one flavoring replaces the two steps of providing at least one regulator in a polymer-based film formulation in one step and providing at least one sweetener and at least one flavoring in a polymer-based film formulation in another step. The order of addition of the polymer films could be reversed; that is, the first film comprises at least one sweetener and at least one flavoring, and the second film comprises at least two regulators. In a final aspect, the invention relates to the use of the chewing gums described above for the treatment of a human being suffering from cravings due to dependence on tobacco and / or electronic cigarette dependence, i.e., to help a person quit smoking, smoking electronic cigarettes, using snus tobacco or chewing tobacco. BRIEF DESCRIPTION OF THE FIGURES There is no scale in the figures, and they are there to illustrate the invention. Figure 1 shows a modality of a nicotine chewing gum according to the invention. Figure 2 shows a modality of a nicotine chewing gum according to the invention. DETAILED DESCRIPTION OF THE MODALITIES OF THE INVENTION Definitions In the context of this application and invention, the following definitions apply: The term nicotine refers to the amount (mg) of nicotine in any salt form or attached to any carrier calculated as the corresponding amount of freebase per piece of gum. The term core or gum core is intended to mean a gum-based delivery system used to carry gum base, sweeteners, flavorings, fillers, and any other substances in chewing gum and gum paste. It provides all the basic textural and chewing properties of the gum. / p / onn / zznz / E / YiAi The term portion / layer is intended to mean a part that is fused or attached to the hard-coated exterior of the chewing gum anywhere. It can be any shape, including a round portion (dot), a square portion, a conical portion, a triangle, etc. The portion may be in the shape of a trademark and may also be colored. The portion may also be a layer present outside the hard coating of the gum, such as 40% of the gum's surface area for a layer, such as one side or both sides of the gum. The term regulator(s) refers to two different types of regulatory species that also differentiate the corresponding acid-base pair of a regulatory system. As used in this description, the term prolonged release (PR) refers to formulations characterized by the fact that the nicotine present in the chewing gum core will be released over a prolonged period of chewing, typically 20–45 minutes, the time the consumer or patient is chewing (using) the gum. The release profile can be assessed by in vitro dissolution using techniques known to those skilled in the art (European Pharmacopoeia 9.0, General Chapters, Method of Analysis, 2.9.25 Dissolution for chewing gums as medicaments, Apparatus B). The term immediate release (IR), as used herein, is intended to mean the release of nicotine contained in the polyol (sugar alcohol)-based portion(s) / layer(s) located on the exterior of the hard-coated gum, intended to be available for rapid oromucosal absorption. The rate of nicotine release is not prolonged by a controlled-release matrix or other similar means, but rather depends on the disintegration and dissolution of the portion(s) / layer(s) and the water solubility of the polyol and nicotine salt. As described herein, an immediate-release component is released shortly after the sugar alcohol and nicotine mixture disintegrate and dissolve (in saliva), which occurs soon after the gum is administered and chewing begins. The amount of nicotine present in chewing gum is calculated and most frequently expressed as the amount of the corresponding freebase form of nicotine per portion of gum. The term fused to used throughout the application is intended to be interchangeable with attached to, fused to, glued to, deposited on, adhered to, melted on or printed on. Chewing gum In a first embodiment, the invention relates to a chewing gum comprising, (i) a gum core comprising nicotine, (ii) at least one film coating outside the gum core comprising at least two regulators, at least one sweetener, at least one flavor, and at least one film-forming polymer, or at least two film coatings outside the gum core, wherein one film coating comprises at least two regulators and at least one film-forming polymer and the other film coating comprises at least one sweetener, at least one flavor, and at least one film-forming polymer, (iii) at least one polyol-based hard coating outside at least one film coating, wherein the polyol-based hard coating comprises at least one sugar alcohol or mixtures of sugar alcohols, (iv) at least one portion / layer fused to the outside of the polyol-based hard coating, wherein the portion comprises nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols And where the release of nicotine from at least one outer portion / layer (iv) is immediate and the release of nicotine from the core (i) is extended and wherein at least two regulators (ii) in at least one film coating located outside the gum core promote rapid uptake of nicotine from (iv) through the oral mucosa (see, for example, Figures 1 and 2). In another embodiment, two film coatings based on different polymers are applied. The first coating is in contact with the rubber core, and the second film coating is applied over the first film coating. At least two regulators are present in one of the film coatings, and at least one sweetener and at least one flavoring are present in the other film coating. In one example, the regulators are present in the first film coating, and the at least one sweetener and at least one flavoring are present in the second film coating. In another example, the at least one sweetener and at least one flavoring are present in the first film coating, and the at least two regulators are present in the second film coating. A person skilled in the art knows how to produce traditional chewing gum. One example is the process described in US 3,877,468. Coated chewing gums have been described in WO2006 / 124366, where hard polyol-based coatings in combination with an internal polymer coating comprising one or more sweeteners and / or flavorings were described to improve the taste and sensory acceptability of the chewing gum. The gum core comprises nicotine, such as nicotine bound to ion-exchange resins, such as nicotine polacrilex, nicotine bound to zeolites, and / or nicotine bound to beta-cyclodextrins, preferably in the form of nicotine polacrilex. The nicotine present in the chewing gum core (calculated as the freebase) can be from approximately 1.0 to approximately 6.0 mg. 1^1 ΟΩΠ / 77Ω7 / B / YILI approximately 2.0 to approximately 4.0 mg, such as 1.25, 1.5, 1.75, 2.0, 2.25, 2.5, 2.75, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 5.0, 5.5, or 6.0, calculated per piece of gum. Nicotine will be released from the gum core when the user is chewing the gum, and the release will occur over an extended period of time, typically up to approximately 30–45 minutes, which is the average time a consumer or patient chews a nicotine gum. At least two buffers are present in at least one film coating. The buffer(s) is / are selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol base (Tris base), or the corresponding conjugate acid of trometamol, such as trometamol hydrochloride (Tris HCl), trisodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, and mixtures thereof. In some examples, the regulator(s) present in at least one film coating are selected from the group consisting of sodium carbonate, sodium bicarbonate, trometamol base (Tris base) or the corresponding conjugate acid of trometamol, such as trometamol hydrochloride (Tris HCI), and mixtures of these. Nicotine acid salts and alkaline regulators are not suitable for use in the same or adjacent polymer-based film coating. Interaction during the drying and cooling process could lead to the transformation of nicotine into its freebase form, which is a volatile and unstable liquid, resulting in nicotine loss or a chemically unstable product. The regulator(s) located in at least one film coating outside the rubber core may be present in a total amount of approximately 1.0 to approximately 7.5 mg (calculated per piece of rubber), such as approximately 1.0 to approximately 6.0 mg, or approximately 2.0 to approximately 6.0 mg, or approximately 2.0 to approximately 5.0 mg, or approximately 3.0 to approximately 6.0 mg, or approximately 3.0 to approximately 5.0 mg, such as 1.0, 1.25, 1.5, 1.75, 2.0, 2.25, 2.5, 2.75, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.25, 5.5, 5.75, 6.0, 6.25, 6.5, 6.75, 7.0, 7.25, or 7.5 mg. In one example, sodium carbonate or sodium bicarbonate may be present in an amount of 0.5 mg to approximately 3.5 mg, such as 0.5 mg to 2.5 mg, such as 0.5 mg to 1.0 mg or 0.5, 1.0, 1.5, 2.0 or 2.5 mg and trometamol base (Tris base), or the corresponding conjugate acid of trometamol, such as trometamol hydrochloride (Tris HCl), may be present in an amount of 1.0 mg to 5.0 mg, such as 2.0 to 5.0, 3.0 mg to 5.0, or 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5 or 5.0 mg. The rubber core is coated with an external hard polyol-based coating and may also include one or more internal polymer-based film coatings. onn / zznz / E / YiAi Individual film coatings can have a thickness of approximately 10 pm to approximately 200 pm, such as 20 pm to approximately 100 pm, such as 20 pm to 60 pm, such as 30 pm. Film-forming polymers may be selected from hydroxypropyl methylcellulose (HPMC), methyl hydroxyethylcellulose (MHEC), hydroxypropyl cellulose (HPC), hydroxyethylcellulose (HEC), methacrylic acid type C copolymer, sodium carboxymethylcellulose, hydroxypropyl methylcellulose phthalate (HPMCP), ethyl hydroxyethylcellulose (EHEC), and other film-forming polymers such as polydextrose, polyethylene glycols, acrylate polymers, polyethylene glycol-polyvinyl alcohol graft copolymers, polyvinylpyrrolidone complex (PVP) such as povidone, polyvinyl alcohol (PVOH or PVA), microcrystalline cellulose, carrageenan, pregelatinized starch, polyethylene glycol, and combinations thereof of these. In one embodiment, the film-forming polymers are selected from hydroxypropyl methylcellulose (HPMC), methyl hydroxyethylcellulose (MHEC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), ethyl hydroxyethylcellulose (EHEC), and polyvinyl alcohol (PVOH or PVA). If two polymer-based film coatings are applied, the same or different polymers and blends of polymers could be used in the separate coatings. Examples include when both film layers are based on hydroxypropyl methylcellulose (HPMC), or when one is based on HPMC and the other on a different film-forming polymer, such as polyvinyl alcohol (PVOH or PVA). Film-forming polymers can exhibit somewhat different characteristics. For example, PVA is considered more resistant to high pH and might therefore be suitable for use in a film coating containing a buffer when a high pH is a target. HPMC provides a pleasant palatability, as well as the ability to provide a prolonged increase in flavor and sweetness when applied to a hard-coated nicotine chewing gum. The polyol-based hard coating applied over one or more film coatings comprises at least one sugar alcohol or mixtures thereof. The sugar alcohol may be erythritol, maltitol, xylitol, lactitol, isomalt, mannitol, arabitol, isomalt, sorbitol, or mixtures thereof. The polyol-based hard coating may have a thickness of approximately 350 µm to approximately 750 µm, such as 500 µm. In one embodiment, the polyol-based hard coating is a mixture of xylitol and maltitol or contains only xylitol. Examples of flavoring agents include fruit and berry flavors such as lime, orange, lemon, blackcurrant, blood orange, blueberry, cherimoya, goji berry, raspberry, strawberry, wild strawberry, sea buckthorn, cherry, melon, kiwi, papaya, pineapple, passion fruit, coconut, and other flavors such as honey, herbs, anise, luziola, lemongrass, cooling agent, ginger, coffee, eucalyptus, mangosteen, mint, spearmint, wintergreen, tutti-frutti, cinnamon, cocoa, vanilla, licorice, salt, pepper, chili, menthol, aniseed, or mixtures thereof. Flavoring agents may be natural extracts, as well as synthetic and semi-synthetic versions, and flavor blends. The flavors may be the same or different and may be present in the gum core, film coating(s), external polyol-based hard coating, as well as in the outer portion(s) / layer(s).Suitable examples of flavorings are flavors from the mint family, fruit flavors, and berry flavors. In addition, chewing gum may contain at least one artificial sweetener. This at least one artificial sweetener may be present in the gum core, film coating(s), or external polyol-based hard coating, and / or in the outer portion(s) / layer(s). Examples of artificial sweeteners include saccharin, sodium saccharin, aspartame, acesulfame K, neotame, thaumatin, glycyrrhizin, sucralose, cyclamate, dihydrochalcone, alitame, miraculin, and monelin, and mixtures thereof. Fused onto the hard polyol-based coating is at least one portion / layer. This at least one portion / layer comprises a nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols. The portion may also comprise at least one sweetener and / or at least one flavoring, as mentioned above. The nicotine salt in the portion comprises nicotine in an easily soluble form. The at least one portion / layer may be the same size and weight or different sizes and weights, placed on top of each other, side by side, or on different sides of the chewing gum. The at least one portion / layer comprising the nicotine or regulator(s) may be placed on top of each other, side by side if the at least one portion / layer dries and solidifies completely, or on opposite sides of the chewing gum. The portion / layer mentioned above may comprise a mixture of erythritol and xylitol in a proportional amount of approximately 90:10, 91:9, 92:8, 93:7, 96:4, 95:5, 96:4, 97:3, 98:2, 99:1, or 100:0 (% w / w erythritol / xylitol). In another embodiment, the portion comprises at least erythritol. The nicotine is evenly distributed in the nicotine that contains at least one portion / layer outside the hard-coated gum. Nicotine salts in at least one portion / layer on the outside of the hard-coated chewing gum may be present in an amount of approximately 0.25 to approximately 2.5 mg, such as 0.5 to approximately 1 mg or 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.25, or 2.5 mg. In addition, the total weight of the portion(s) / layer(s) is approximately 2–10%, such as 2–5% of the total weight of the chewing gum. In another embodiment, the invention relates to a novel chewing gum comprising at least a gum core comprising nicotine polacrilex, at least a first film coating comprising polyvinyl alcohol (PVA) comprising at least two regulators wherein one regulator is sodium carbonate or sodium bicarbonate and the other is trometamol base acid (Tris base) and / or trometamol conjugated as trometamol hydrochloride (Tris conjugated acid), and a second film coating comprising HMPC and at least one flavoring and at least one sweetener, at least one outer hard polyol coating outside the film coatings comprising at least xylitol, and a melted portion / layer on the outer hard polyol coating, wherein the portion / layer is erythritol-based and comprises a nicotine salt.such as nicotine bitartrate or nicotine ditartrate dihydrate (it could also be called nicotine hydrogen tartrate (NHT) or nicotine bitartrate). The polyol-based outer layer / portion can be colored. Coloring agents include lakes and dyes approved as food additives, and examples of coloring agents are artificial or natural colors. An example of a coloring portion, as defined above, can be a dot, like the spots on a ladybug. Examples of artificial colors approved for food use in the EU include: E104: Quinoline Yellow, E122: Carmoisine, E124: Ponceau 4R, E131: Patent Blue V, and E142: Green S. In the US, the following seven artificial colors are generally permitted in food: FD&C Blue No. 1 - Brilliant Blue FCF, E133 (blue hue), FD&C Blue No. 2 - Indigotine, E132 (indigo hue), FD&C Green No. 3 - Fast Green FCF, E143 (turquoise hue), FD&C Red No. 3 - Erythrosine, E127 (pink hue, commonly used in glacé cherries), FD&C Red No. 40 - Allura Red AC, E129 (red hue), FD&C Yellow No. 5 - tartrazine, E102 (yellow tint), FD&C yellow no. 6 - sunset yellow FCF, E110 (orange tint) or iron oxide. Examples of natural colors include: carotenoids (E160, E161, E164), chlorophyllin (E140, E141), anthocyanins (E163), and betanin (E162), annatto (E160b), a reddish-orange dye made from the annatto seed, caramel color (E150a-d), made from caramelized sugar, carmine (E120), a red dye derived from the cochineal insect, Dactytopius coccus, elderberry juice (E163), lycopene (E160d), paprika (E160c), turmeric (E100), titanium dioxide or iron oxide. In addition, chewing gum may contain at least one artificial sweetener. This at least one artificial sweetener may be present in the gum core, film coating(s), polyol-based hard coating, and / or in one or more outer portions / layers. Examples of artificial sweeteners include saccharin, sodium saccharin, aspartame, acesulfame K, neotame, thaumatin, glycyrrhizin, sucralose, cyclamate, dihydrochalcone, alitame, miraculin, and monelin, and mixtures thereof. The at least one outer portion / layer may have a total weight of approximately 1.5-10% of the total weight of the gum, such as 2-10%, 2-3%, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0% or even up to 15% of the total weight of the chewing gum. jqj οηη / ζζηζ / Ε / γίΛΐ The nicotine polacrilex present in the gum core may be in an amount of approximately 1.0 to approximately 6.0 mg, from approximately 2.0 to approximately 4.0 mg, such as 1.0, 1.25, 1.5, 1.75, 2.0, 2.25, 2.5, 2.75, 3.0, 3.25, 3.5, 3.75, 4.0, 4.5, 5.0, 5.5 or 6.0, calculated as the freebase per piece of gum, and the nicotine salt present in the outer portion / coating may be in an amount of approximately 0.25 to approximately 2.5 mg, such as 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1.0, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, 1.95, 2.0, 2.05, 2.1, 2.15, 2.2, 2.25, 2.3, 2.35, 2.4, 2.45 or 2.5 mg, such as about 0.25 to 1.0 mg or about 0.25 to 1.5 or about 0.25 2.5 mg (calculated as the free base). The relative amount of nicotine salt in at least one portion / layer in relation to the regulator(s) located in at least one film coating outside the gum core is important because the regulator(s) will allow a conversion of the nicotine salt into its freebase form to promote rapid nicotine uptake. If very little regulator(s) is available relative to the nicotine salt, the conversion of nicotine to its freebase form will be impaired, which can lead to a relatively higher proportion of nicotine in its acidic form. This results in a smaller fraction of nicotine being adsorbed onto the oral mucosa; instead, it will be subject to transport to the gastrointestinal tract and exposure to what is known as first-pass metabolism. This could lead to comparatively slower and reduced nicotine absorption, affecting nicotine concentrations in the systemic circulation and comparatively slower (and lesser) craving relief. In some embodiments, at least one outer portion / layer in the hard-coated gum comprises nicotine bitartrate or nicotine ditartrate dihydrate in an amount of 0.25 mg to 2.5 mg of nicotine (calculated as freebase), and the at least one film coating comprises at least two regulators outside the gum core but within the hard-coated chewing gum, wherein the at least two regulators comprise sodium carbonate and / or sodium bicarbonate in an amount of 0.5 mg to 3.5 mg and trometamol base form as mentioned above, in an amount of 1.5 mg to 5.0 mg. Manufacturing a nicotine chewing gum The invention also relates to a method for manufacturing chewing gum by using steps such as mixing, rolling and cutting, hard coating and filming, and deposition / fusion of one or more polyol-based portions onto the surface of the gum by stencil printing, melt lamination, ink printing, pipetting, or 3-D printing, where the following steps could be used. irt οηη / ζζηζ / Ε / γίΛΐ Step A. Providing a chewing gum core comprising nicotine, such as nicotine polacrilex, wherein the chewing gum can be manufactured as shown by the processes and examples described in 3,877,468. Step B. Provide a polymer-based film coating formulation comprising sweeteners and flavorings and apply the film coating to the chewing gum core using, for example, commercially available film coating equipment suitable for aqueous formulations, allowing the coating to dry onto the chewing gum using, for example, air, such as dry air and controlled temperature to obtain a film-coated chewing gum. Step C. Providing a polymer-based film formulation comprising at least two regulators and, optionally, furthermore, at least one sweetener and at least one flavoring, coating said chewing gum with the film using, for example, commercially available film coating equipment suitable for aqueous formulations, enabling the coating to dry onto the chewing gum using, for example, air, such as temperature-controlled dry air, and obtaining a film-coated chewing gum. STAGE B may be omitted when there is a STAGE C comprising at least one sweetener and at least one flavoring. Stage B and Stage C may appear in any order if included. Eapa D. Providing a polyol-based hard coating formulation comprising at least one sugar or sugar alcohol mixture as defined above, coating the gum with a polyol-based hard coating formulation and obtaining an externally coated chewing gum using, for example, commercially available hard coating equipment suitable for aqueous formulations, to allow the coating to dry onto the chewing gum using, for example, air, such as temperature-controlled dry air and temperature control, and to obtain a hard coated chewing gum. Step E. Providing a composition comprising nicotine salt, such as monotartrate salt, hydrogen tartrate, citrate, malate, hydrochloride, nicotine bitartrate or nicotine bitartrate dihydrate and at least one sugar alcohol or a mixture of sugar alcohols, such as erythritol, maltitol, xylitol, lactitol, isomalt, mannitol, arabitol, isomalt and sorbitol or mixtures thereof, and fusing said composition onto said hard-coated chewing gum as one or more portions or layers located outside the hard-coated gum, and obtaining chewing gum with one or more external portions or layers of nicotine, by stencil printing, fused lamination, ink printing, pipetting or 3-D printing. The different components and ingredients that will be included in the manufacturing process could be found above. οηη / ζζηζ / Ε / γίΛΐ Finally, the invention relates to the use of the chewing gum defined above for the treatment of human beings suffering from cravings due to tobacco dependence and / or electronic cigarette dependence. Examples The specific embodiments of the present invention are illustrated by the following examples. This invention is not restricted to the specific limitations stipulated in those examples. The ingredient quantities are expressed differently in the examples and are not entirely consistent with the final chewing gum. However, for someone skilled in the technique, it is obvious how to recalculate and develop the chewing gum according to the description. Example 1. Chewing gum with a polymeric film coating with one or more regulators The chewing gum base was obtained from a commercial chewing gum base producer and the preparation of polacrilex nicotine chewing gum was done in accordance with the process described in US 3,877,468. WO2006 / 124366 describes the process for formulating and manufacturing polymer-based film nicotine gums containing within a hard polyol-based coating. The following film-forming compositions were used to obtain a film coating in this example. The compositions are presented in mg per piece of rubber. / r / onn / zznz / E / YiAi Examples 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Hydroxypropyl methylcellulose (HPMC) 7.5 9 7.5 13 15 9 9 9 11 11 9 11 13 26 7.5 9 Polyvinyl alcohol (PVA) 7.5 8 8 8 Polysorbate 80 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 1.0 0.5 0.5 Sucralose 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 10 5 2.5 Flavoring 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 18 9 10 Sodium Carbonate 1 1.25 3.5 1 0.5 0.25 0.5 0.25 1 1 1.5 1.25 3 1 1 Sodium Bicarbonate 1 1 1.25 1 0.5 0.5 1 0.75 1.75 3 0.25 1.5 2.75 4 Trometamol Base 2 3 3 1 1 3 5 5 5 5 5 5 3 1.75 Purified Water1' qs ... (0.1 M)2' for pH 9.5 for pH 9.5 for pH 10 for pH 10.5 for pH 10.5 for pH 9.5 for pH 10 for pH9 for pH 10 for pH9 for pH9 for pH 10.5 for pH9 for pH 10 for pH 9.5 for PH 10.5 for pH 10 for pH 10.5 for pH 10 for pH 10.5 1) Most of the purified water is removed during the film coating process. 2) The coating preparation is adjusted to pH with hydrochloric acid (10%) and NaOH (0.1 M) to a target pH. MO / ZW / CHILI For the polymer coating process, the dry content of the coating preparation can be varied between 20-50% w / w to facilitate the incorporation of varying amounts of buffering agents. Adjusting the dry content with different amounts of buffering agents will facilitate coating preparation without salting the polymer. Example 2. Chewing gum with two polymer film coatings, one with two or more regulators and one with flavorings and sweeteners The chewing gum base was obtained from a chewing gum base producer 10, and the preparation of polacrilex nicotine chewing gum cores was done according to one or more of the processes / examples described in US 5,976,581. WO2006 / 124366 describes a polymer-based film coating within a polyol-based hard coating. The chewing gums were coated with two different polymer-based film coatings as shown in the table below. Compositions are presented in mg per piece of gum. Examples 1 2 3 4 5 6 7 8 9 10 Polymeric Coating A Polyvinyl alcohol (PVA) 7.5 8 8 8 8 9 10 8 10 9 Sodium carbonate 1 2.5 1.5 2.5 1.5 2.5 Sodium bicarbonate 1 1 0.5 0.5 2.5 1.5 2.5 1.0 2.5 Sodium hydrogen phosphate 0.5 1 5 5 2 Trometamol 3 5 5 5 5 7 5 Purified water1) q.s. ... 10.7 for pH 10.5 Polymer Coating B Hydroxypropyl methylcellulose (HPMC) 7.5 8 9 7.5 7.5 9 9 8 10 10 Polysorbate 80 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Sucralose 4 5 5 4 4 4.9 5 5 5.3 5.2 Flavoring 9 8 9 7 9 9 9 8 9.3 9.2 Purified Water1) qs ... 1) Most of the purified water is removed during the film coating process. 2) The coating preparation is adjusted to pH with hydrochloric acid (10%) or NaOH (0.1 M) to target pH. The dry content of the coating preparation can vary between 20-50% w / w to facilitate the incorporation of various amounts of regulating agents. Example 3. Formulation of nicotine salt compositions for portions (fes) or caps) external) ic ι οηη / ζζηζ / E / γίΛΐ Preparation of different portions containing nicotine and excipients. Examples of portions that contain nicotine Examples 1 2 3 4 5 6 7 8 9 Amounts expressed in % w / w for each component e.g. API Nicotine bitartrate dihydrate 15.39 15.4 14.3 14.3 14.3 14.3 14.3 7.13 15.35 Excipients Xylitol 82.8 80.4 82.4 20.0 3.9 Isomalt 84.61 Erythritol 3.3 83.7 65.7 79.8 92.7 84.65 Dye q.s. ... Manufacturing: All starting materials, polyols or mixtures of several polyols, nicotine source and dye, seeding agent or sweetener, if applicable, were mixed in a beaker. The mixture was heated until melted under stirring of all components except titanium dioxide. 20 to 40 mg of the melt was deposited onto the chewing gum using a micropipette. The drop was occasionally flattened with a heated tool immediately after deposition to reduce the thickness of the deposited drop. The use of xylitol as the primary polyol resulted in solidification times that were too long for commercial manufacturing. The use of seeding agents (mannitol 25 μm or titanium dioxide) did not reduce the solidification time. Isomalt had a very rapid solidification time but a very high melting point (153 °C), which is undesirable from a stability and safety perspective. Erythritol exhibited rapid solidification and a much lower melting point (121.5 °C). Example 4. Formulation of compositions for portion(s) or external layers that include regulators) ic / onn / zznz / E / YiAi 1 2 3 4 5 Amounts expressed in (g) per excipient for example Erythritol (g) 29.25 28.875 28.5 27.00 26.75 Trometamol (g) 0.75 1.125 1.5 3.00 3.75 Na2CO3 (g) 0.75 0.75 0.75 0.75 0.75 Total (g) 30.75 30.75 30.75 30.75 30.75 All formulations in example 1 to 5 resulted in a clear solution after gentle manual mixing and melting at 125 °C, with no residual particles remaining upon visual inspection. The solidification time after deposition of portions onto the chewing gum was prolonged with increasing trometamol concentration, but remained within manufacturing capacity limits. Manufacturing: All starting materials, polyol, and regulator(s) were mixed in a beaker. The mixture was heated until melted under stirring of all components. 20–40 mg of the melted mass was deposited onto the chewing gum using a micropipette. The drop was occasionally flattened with a heated tool immediately after depositing to reduce the thickness of the deposited drop. The following list of modalities forms part of the description. 1. A chewing gum comprising, i. a rubber core comprising nicotine, ii. at least one film coating outside the rubber core comprising at least two regulators, at least one sweetener, at least one flavoring, and at least one film-forming polymer or at least two film coatings outside the rubber core, wherein one film coating comprises at least two regulators and at least one film-forming polymer and another film coating comprises at least one sweetener, at least one flavoring, and at least one film-forming polymer, iii. at least one polyol-based hard coating outside the at least one film coating, wherein the polyol-based hard coating comprises at least one sugar alcohol or mixtures of sugar alcohols, iv.at least one portion / layer fused to the outside of the polyol-based hard coating, wherein the at least one portion / layer comprises nicotine salt, and at least one sugar alcohol or a mixture of sugar alcohols, and. where the release of nicotine from the outer portion / layer (iv) is immediate and the release of nicotine from the gum core (i) is prolonged and where the regulators (i) at least one film coating outside the gum core promote rapid uptake of nicotine from (iv) through the oral mucosa. 2. Chewing gum according to modality 1, wherein the polymers in the film coating are selected from the group consisting of hydroxypropyl methylcellulose (HPMC), methyl hydroxyethylcellulose (MHEC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), ethylhydroxyethylcellulose (EHEC) and polyvinyl alcohol (PVOH or PVA) or a mixture thereof. 3. Chewing gum according to modality 2, wherein one of the two film coatings comprises PVA and at least two regulators and the other film coating comprises HPMC and at least one sweetener and at least one flavoring. 4. Chewing gum according to modalities 1-3, wherein at least two regulators are selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol base (Tris base) or the corresponding conjugate acid of trometamol such as trometamol hydrochloride (Tris HCI), trisodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, and mixtures thereof. 5. Chewing gum according to modality 4, wherein at least two regulators are selected from the group consisting of sodium carbonate, sodium bicarbonate, trometamol base (Tris base) or the corresponding conjugate acid of trometamol such as trometamol hydrochloride (Tris HCI), or mixtures thereof. 6. Chewing gum in accordance with any of the above modalities wherein the regulators in at least one film coating outside the core of the gum are present in an amount of approximately 1.0 to approximately 6.0 mg / gum. 7. Chewing gum according to modalities 1-6, wherein the nicotine in the core of the gum is nicotine polacrilex and the nicotine in at least one portion / layer fused to the outside of the polyol-based hard coating is nicotine bitartrate or nicotine ditartrate dihydrate. 8. Chewing gum according to any of the above forms, wherein the sugar alcohol in the outer portion(s) comprises xylitol. 9. Chewing gum according to any of the above embodiments, wherein the gum core comprises nicotine polacrilex in an amount of approximately 1.0 mg to approximately 7.5 mg (calculated as the free base) and at least one portion / layer fused to the outside of the polyol-based hard coating comprising nicotine salt present in an amount of approximately 0.25 mg to approximately 2.5 mg (calculated as the free base). 10. Chewing gum in accordance with any of the above forms, comprising: i. nicotine bitartrate or nicotine ditartrate dihydrate in an amount of 0.25 mg to 2.5 mg in a portion / layer fused to the outside of a hard polyol-based coating (calculated as the free base), ii. sodium carbonate and / or sodium bicarbonate in an amount of 0.5 mg to 3.5 mg and iii. trometamol base or the corresponding conjugate acid of trometamol such as trometamol hydrochloride (Tris HCI) in an amount of 1.5 mg to 5.0 mg wherein i) and iii) at least one film coating located outside the core of the gum is present. 11. A method for manufacturing chewing gum, comprising the steps of: i. providing a chewing gum core comprising nicotine, ii. providing a polymer-based film coating formulation comprising at least two regulators, at least one sweetener and at least one flavoring, iii. coating the chewing gum core with the polymer-based film coating formulation, iv. obtaining a film-coated chewing gum comprising at least two regulators and at least one sweetener and at least one flavoring, v. providing a polyol-based hard coating formulation comprising at least one sugar alcohol or mixtures of sugar alcohols, vi. coating the film-coated chewing gum with the polyol-based hard coating formulation, vii. obtaining a hard-coated chewing gum, viii. providing a formulation comprising nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, ix. fusing the composition of viii) to the exterior of the hard-coated chewing gum as at least one portion / layer, x. obtaining a hard-coated nicotine chewing gum with at least one portion / layer outside the hard-coated chewing gum, οηη / ζζηζ / E / γίΛΐ wherein the release of nicotine from the at least one outer portion / layer (ix) is immediate and the release of nicotine from the gum core (i) is extended and where the at least two regulators (iv) located outside the core of the gum promote rapid uptake of nicotine through the oral mucosa. 12. A method for manufacturing chewing gum, comprising the steps of: i. providing a chewing gum core comprising nicotine, ii. providing a polymer-based film formulation comprising at least two regulators, iii. coating the chewing gum core with the polymer-based film formulation, iv. obtaining a film-coated chewing gum with a film coating comprising at least two regulators, v. provide a polymer-based film formulation comprising at least one sweetener and at least one flavoring, v. coating the chewing gum with the polymer-based film formulation comprising at least one sweetener and at least one flavoring, vii. obtaining a chewing gum coated with two polymer-based film coatings, a film coating comprising at least two regulators, and a film coating comprising at least one sweetener and at least one flavoring, viii. providing a polyol-based hard coating formulation comprising at least one sugar alcohol or mixtures of sugar alcohols, ix. coating the film-coated chewing gum with the polyol-based hard coating formulation, x. obtaining a hard-coated chewing gum, xii. providing a composition comprising nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, xii. fusing the composition of xii) to the outside of the hard-coated chewing gum as at least one portion / layer, and xiii. obtaining a hard-coated nicotine chewing gum with at least one portion / layer containing nicotine salt wherein the release of nicotine from the outer portion / layer (xiii) is immediate and the release of nicotine from the core of the gum (i) is extended. where the at least two regulators (iv) located outside the core of the gum promote rapid uptake of nicotine through the oral mucosa. 13. Use of chewing gum in accordance with any of the modalities 1-10 for the treatment of a human being suffering from cravings due to tobacco dependence and / or electronic cigarette dependence.

Claims

1. A chewing gum comprising, i. a gum core comprising nicotine, ii. at least one film coating outside the gum core comprising at least two regulators, at least one sweetener, at least one flavoring, and at least one film-forming polymer or at least two film coatings outside the gum core, characterized in that one film coating comprises at least two regulators and at least one film-forming polymer and another film coating comprises at least one sweetener, at least one flavoring, and at least one film-forming polymer, iii. at least one polyol-based hard coating outside the at least one film coating, wherein the polyol-based hard coating comprises at least one sugar alcohol or mixtures of sugar alcohols, iv.at least one portion / layer fused to the outside of the hard polyol-based coating, wherein the at least one portion / layer comprises nicotine salt, and at least one sugar alcohol or a mixture of sugar alcohols, and wherein the release of nicotine from the outer portion / layer (iv) is immediate and the release of nicotine from the rubber core (i) is extended, and wherein regulators (i) in the film coating outside the rubber core promote rapid uptake of nicotine from (iv) through the oral mucosa.

2. Chewing gum according to claim 1, characterized in that the polymers in the film coating are selected from the group consisting of hydroxypropyl methylcellulose (HPMC), methylhydroxyethylcellulose (MHEC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), ethylhydroxyethylcellulose (EHEC) and polyvinyl alcohol (PVOH or PVA) or a mixture thereof.

3. The chewing gum according to claim 2, characterized in that one of the two film coatings comprises PVA and at least two regulators and the other film coating comprises HPMC and at least one sweetener and at least one flavoring.

4. Chewing gum according to claims 1-3, characterized in that at least two regulators are selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol base (Tris base) or the corresponding conjugate acid of trometamol such as trometamol hydrochloride (Tris onn / zznz / E / YiAi HCI), trisodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, and mixtures thereof.

5. The chewing gum according to claim 4, characterized in that at least two regulators are selected from the group consisting of sodium carbonate, sodium bicarbonate, trometamol base (Tris base) or the corresponding conjugate acid of trometamol such as trometamol hydrochloride (Tris HCI) or mixtures thereof.

6. Chewing gum according to any of the preceding claims characterized in that the regulators in the at least one film coating outside the core of the gum are present in an amount of approximately 1.0 to approximately 6.0 mg / gum.

7. Chewing gum according to claims 1-6, characterized in that the nicotine in the core of the gum is nicotine polacrilex and the nicotine in the at least one portion / layer fused to the outside of the polyol-based hard coating is nicotine bitartrate or nicotine ditartrate dihydrate.

8. Chewing gum according to any of the preceding claims, characterized in that the sugar alcohol in the outer portion(s) / layer(s) comprises xylitol.

9. Chewing gum according to any of the preceding claims, characterized in that the gum core comprises nicotine polacrilex in an amount of approximately 1.0 mg to approximately 7.5 mg (calculated as the free base) and at least one portion / layer fused to the outside of the polyol-based hard coating comprises nicotine salt present in an amount of approximately 0.25 mg to approximately 2.5 mg (calculated as the free base).

10. Chewing gum according to any of the preceding claims, comprising: i. nicotine bitartrate or nicotine ditartrate dihydrate in an amount of 0.25 mg to 2.5 mg in a portion / layer fused to the outside of a hard polyol-based coating (calculated as the free base), ii. sodium carbonate and / or sodium bicarbonate in an amount of 0.5 mg to 3.5 mg, and iii. trometamol base or the corresponding conjugate acid of trometamol such as trometamol hydrochloride (Tris HCl) in an amount of 1.5 mg to 5.0 mg wherein i) and iii) at least one film coating located outside the gum core is present.

11. A method for manufacturing chewing gum, comprising the steps of: i. providing a chewing gum core comprising nicotine, ii. providing a polymer-based film coating formulation comprising at least two regulators, at least one sweetener, and at least one flavoring, iii. coating the chewing gum core with the polymer-based film coating formulation, iv. obtaining a film-coated chewing gum comprising at least two regulators, at least one sweetener, and at least one flavoring, v. providing a polyol-based hard coating formulation comprising at least one sugar alcohol or mixtures of sugar alcohols, vi. coating the film-coated chewing gum with the polyol-based hard coating formulation, vii. obtaining a hard-coated chewing gum, viii.providing a formulation comprising nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, ix. fusing the composition of viii) to the outside of the hard-coated chewing gum as at least one portion / layer, x. obtaining a hard-coated nicotine chewing gum with at least one portion / layer outside the hard-coated chewing gum, characterized in that the release of nicotine from the at least one outer portion / layer (ix) is immediate and the release of nicotine from the gum core (i) is extended and wherein the at least two regulators (iv) located outside the gum core promote rapid uptake of nicotine through the oral mucosa.

12. A method for manufacturing chewing gum, comprising the steps of: i. providing a chewing gum core comprising nicotine, ii. providing a polymer-based film formulation comprising at least two regulators, iii. coating the chewing gum core with the polymer-based film formulation, iv. obtaining a film-coated chewing gum with a film coating comprising at least two regulators, v. providing a polymer-based film formulation comprising at least one sweetener and at least one flavoring, vi. coating the chewing gum with the polymer-based film formulation comprising at least one sweetener and at least one flavoring, vii.obtaining a chewing gum coated with two polymer-based film coatings, a film coating comprising at least two regulators, and a film coating comprising at least one sweetener and at least one flavoring, viii. providing a polyol-based hard coating formulation comprising at least one sugar alcohol or mixtures of sugar alcohols, ix. coating the film-coated chewing gum with the polyol-based hard coating formulation, x. obtaining a hard-coated chewing gum, xi. providing a composition comprising nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, xii. fusing the composition of xi) to the exterior of the hard-coated chewing gum as at least one portion / layer, and xiii.obtaining a hard-coated nicotine chewing gum with at least one portion / layer containing nicotine salt characterized in that the release of nicotine from the outer portion / layer (xiii) is immediate and the release of nicotine from the gum core (i) is extended and wherein the at least two regulators (iv) located outside the gum core promote rapid uptake of nicotine through the oral mucosa.

13. A chewing gum according to any of claims 1-10 for use in the treatment of a human being suffering from cravings due to tobacco dependence and / or electronic cigarette dependence.