EA045857B1 - NICOTINE CHEWING GUM AND METHOD OF ITS MANUFACTURE (VARIANTS), AS WELL AS ITS APPLICATION - Google Patents

Description

Scope of the invention

This invention relates to nicotine chewing gum providing immediate release and absorption of nicotine and sustained release and absorption of nicotine, and also provides a description of suitable methods for making such chewing gum formulations and the use of said chewing gum for the treatment of a person suffering from tobacco addiction and/or dependence from an electronic nicotine delivery device.

Prerequisites for creating the invention

According to WHO, about six million people die every year from smoking-related diseases, even though products (medicines) are available on the market to help smokers quit; for example, products such as nicotine gums, lozenges, sprays and transdermal patches.

The standard method for producing nicotine chewing gum is to complex nicotine with a cation exchange resin and add this complex to the chewing gum composition.

Such chewing gums have been available on the market for many years and are sold, for example, under the brand name Nicorette®. However, there are consumers who are looking for nicotine products (medicines) that could provide a faster reduction in smoking cravings, closer to reducing the cravings for smoking cigarettes, and thus there is still the possibility of developing a new nicotine chewing gum that could cater to this group of people who use tobacco and/or electronic nicotine delivery.

One product on the market that provides rapid smoking craving reduction is Nicorette™ QuickMist™, which is an oral spray designed to be applied to the mucous membrane from which the nicotine compound is easily absorbed into the bloodstream to provide rapid smoking craving reduction. .

WO 2006124366 describes a chewing gum containing at least a nicotine resin core, at least one inner polymer film coating applied thereto, and at least one outer hard coating. The formed chewing gum has long-lasting flavoring properties and provides a sustained release of nicotine when subjects chew the gum.

WO 2010044736 discloses a multi-portion lozenge dosage form in which at least one portion is rapidly disintegrating and at least one portion is slowly disintegrating, without mentioning anything about chewing gum. There are long lists of active pharmaceutical agents that may be suitable and lists of diseases.

The problem to be solved by this invention is to provide a product that can provide rapid absorption of nicotine as well as sustained release of nicotine to help a person quit smoking. To be able to achieve this effect, it is important to include the nicotine as well as a buffer in a format that will result in rapid absorption of the nicotine, in addition to the sustained/extended release characteristics already typically found in medicinal nicotine chewing gums.

However, there are consumers who could benefit from products that could provide both immediate and longer-lasting reduction in smoking cravings within the same product.

Summary of the invention

The authors of the invention studied the possibility of creating chewing gum that provokes immediate as well as prolonged release and absorption of nicotine, which at the same time would have a good taste. To provide immediate release and absorption of nicotine from the finished chewing gum, the inventors' approach has been to use nicotine in a more accessible nicotine salt form, such as nicotine bitartrate or nicotine ditartrate dihydrate, contained in at least one outer portion/layer fused to the outside of the nicotine gum. hard-coated chewing gum.

The PKa for nicotine is approximately 7.8. It is well known that nicotine in its uncharged form (free base form) can more easily and quickly penetrate biological membranes, such as the oral mucosa, in order to obtain rapid systemic absorption compared to nicotine in its positively charged acid form.

Thus, if an acidic drug salt, such as nicotine bitartrate, is included in the product, then the product also contains some readily available and quickly released buffer(s), which is also present outside the nicotinic acid. hard-coated chewing gum. This buffer(s) can quickly and briefly increase the pH of the solvent (in this case saliva) in order to convert nicotine to its free base form, resulting in relatively faster absorption of nicotine present at less at least in one area/layer outside the hard-coated chewing gum core.

- 1 045857

The average pH of human saliva is typically around 6-7.5.

By selecting and adding some easily and rapidly releasing buffer(s) to the portion outside the gum core, a rapid increase in salivary pH level to approximately one pH unit above the pKa of nicotine (thus within the pH range) can be achieved. 9 or higher). This will cause approximately 90% of the nicotine in at least one site/layer to be converted to its free base form after at least one site/layer is broken down and dissolved in saliva for easy absorption into the systemic circulation to provide faster craving reduction to smoking.

The free base form of nicotine is not suitable for direct preparation of semi-solid or solid dosage forms because the base form of nicotine is in the form of a highly volatile liquid under normal conditions.

To provide a short-term and suitable increase in pH, it is advantageous to use a buffer system, for example one or more different buffers (buffer types). In general, buffer systems do not taste good, so they must be carefully selected and their taste must be masked, for example, with sweeteners and flavorings. In addition, the buffering capacity of one buffer (buffer type) may not be sufficient.

To provide sustained release of nicotine from the nicotine gum core, the use of resin-bound nicotine, such as nicotine polacrilex, is suitable. Nicotine polacrilex is typically used in medicinal chewing gum available on the market. This medicinal chewing gum will provide a sustained release over time up to about 20-45 minutes depending on use. However, release and absorption from these chewing gums is somewhat limited during the first 5-10 minutes of use.

The nicotine chewing gum of the invention provides new features in the same product compared to other currently commercially available medicinal nicotine products.

Nicotine gum may also be an attractive product for consumers or patients who prefer the nicotine gum format itself.

In a first aspect, this invention relates to nicotine chewing gum containing:

i) a gum core containing nicotine, ii) a polymer-based film coating containing at least one flavor and at least one sweetener applied to the chewing gum core, iii) at least one polyol-based hard coating applied to the film a chewing gum coating containing at least one sugar alcohol or mixtures of sugar alcohols, iv) at least one portion/layer fused to the outer side of the polyol-based hard coating, said portion/layer comprising a nicotine salt and at least one sugar alcohol, or mixture of sugar alcohols,

v) at least one portion/layer fused to the outer side of the polyol-based hard coating, said portion/layer containing one or more buffers in an amount of from about 3 to about 7.5 mg and at least one sugar alcohol or mixture sugar alcohols, and wherein the release of nicotine from at least one outer portion/layer (iv) is immediate, and the release of nicotine from the core (i) is prolonged, and wherein the buffer(s) (v) located on the outside of the gum with hard coating, promote(s) rapid absorption of nicotine from (iv) through the oral mucosa, and wherein one or more buffer(s) is selected from the group consisting of sodium carbonate, sodium bicarbonate, trometamol base (Tris base) or the corresponding trometamol conjugate acid, such as trometamol hydrochloride (Tris-HCl), sodium hydrogenorthophosphate, or mixtures thereof.

In a second aspect, the invention relates to nicotine chewing gum containing:

i) a gum core containing nicotine, ii) at least one film coating applied to the gum core containing at least two buffers and at least one film-forming polymer, iii) at least one polyol-based hard coating applied over on at least one film coating, wherein the polyol-based hard coating contains at least one sugar alcohol or mixtures of sugar alcohols, iv) at least one area/layer fused to the outer side of the polyol-based hard coating, wherein said area/layer contains a 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 core (i) is prolonged and the buffers (ii) are at least one film coating located outside the core promotes rapid absorption of nicotine from (iv) through the oral mucosa and wherein one or more buffer(s) is selected from the group consisting of sodium carbonate, sodium bicarbonate, trometamol base (Tris base) or the corresponding trometamol conjugate acid,

- 2 045857 such as trometamol hydrochloride (Tris-HCl), sodium hydrogen orthophosphate, or mixtures thereof.

In another aspect, the invention relates to a method for making chewing gum, comprising the steps of:

i) providing a chewing gum center containing nicotine, ii) providing a polymer-based film coating composition containing at least one flavor and at least one sweetener, iii) applying a polymer-based film composition to the chewing gum center, iv) producing a chewing gum polymer-based film-coated rubber bands,

v) providing a polyol-based hard coating composition containing at least one sugar alcohol or mixtures of sugar alcohols, vi) applying said polyol-based hard coating composition to said chewing gum, vii) producing a polyol-based hard-coating chewing gum, viii) producing a composition comprising a nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, ix) fusing said composition of viii) onto the outer side of a hard-coated chewing gum in the form of at least one section/layer to obtain a hard-coated chewing gum with at least at least one area/layer containing nicotine salt,

x) preparing a composition containing one or more buffers in an amount of from about 3 to about 7.5 mg and at least one sugar alcohol or mixture of sugar alcohols, xi) fusing said composition of x) onto the outside of a hard-coated chewing gum in the form of at least one portion/layer and xii) providing a hard-coated nicotine chewing gum with at least one portion/layer containing one or more buffers, and wherein the release of nicotine from the at least one outer portion/layer (ix) is immediate , and the release of nicotine from the core (i) is prolonged and wherein one or more buffers in at least one film coating (xi) located on the outside of the hard coated gum promote rapid absorption of nicotine through the oral mucosa (see, e.g. , Fig. 1).

In another aspect, the invention relates to a method for making chewing gum, comprising the steps of:

i) providing a chewing gum center containing nicotine, ii) providing a polymer-based film coating composition containing at least two buffers, at least one sweetener and at least one flavoring agent, iii) applying said film composition to said chewing gum center polymer-based coating, iv) providing a film-coated chewing gum containing at least two buffers, at least one sweetener and at least one flavoring agent,

v) providing a polyol-based hard coating composition containing at least one sugar alcohol or mixtures of sugar alcohols, vi) applying said polyol-based hard coating composition to said film-coated chewing gum, vii) producing a hard-coated chewing gum, viii) producing a composition containing a nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, ix) fusing said composition of viii) onto the outer part of a hard-coated chewing gum in the form of at least one section/layer, x. producing a hard-coated nicotine chewing gum with at least one portion/layer containing a nicotine salt, wherein the release of nicotine from the outer portion/layer (ix) is immediate and the release of nicotine from the core (i) is sustained and at the same time at least two buffers in the film coating (iv), located outside the gum core, promote rapid absorption of nicotine through the oral mucosa (see, for example, Fig. 2).

In another aspect, the invention relates to a method for making chewing gum, comprising the steps of:

i) providing a chewing gum core containing nicotine, ii) providing a polymer-based film composition containing at least two buffers, iii) applying said polymer-based film composition to said chewing gum core, iv) producing a film-coated chewing gum, wherein the film coating contains at least two buffers,

v) providing a polymer-based film composition containing at least one sweetener and at least one flavoring agent, vi) applying said poly-based film composition to said chewing gum.

- 3 045857 measure, vii) obtaining chewing gum coated with a polymer-based film coating;

viii) providing a polyol-based hard coating composition containing at least one sugar alcohol or mixtures of sugar alcohols, ix) applying said polyol-based hard coating composition to said film-coated chewing gum,

x) producing a hard-coated chewing gum, xi) producing a composition comprising a nicotine salt and at least one sugar alcohol or mixture of sugar alcohols, xii) fusing said composition from xi) onto the outside of the hard-coated chewing gum in at least one section /layer to produce a hard-coated chewing gum with at least one portion/layer containing a nicotine salt, xiii) producing a hard-coated nicotine chewing gum, wherein the release of nicotine from the outer portion/layer (xii) is immediate, and the release of nicotine from the core (i) is prolonged and at the same time at least two buffers (iv) in the film coating, located outside the gum core, contribute to the rapid absorption of nicotine through the oral mucosa (see, for example, Fig. 3).

The stages described above can be in any order. In one example, the step of producing a polymer film composition containing at least two buffers, at least one sweetener and at least one flavoring agent replaces the two steps of producing at least one buffer in one polymer film composition in one step and providing at least one sweetener and at least one flavoring agent in one polymer-based film composition in another step.

In a final aspect, the invention relates to the use of the chewing gums described above for the treatment of a person suffering from addiction to tobacco and/or dependence on an electronic nicotine delivery device, i.e. to help a person quit smoking, vaping, snus or chewing tobacco.

Brief description of graphic materials

The drawings are not to scale and are intended to illustrate the invention.

In fig. 1 illustrates one embodiment of a nicotine chewing gum in accordance with the invention.

In fig. 2 illustrates one embodiment of a nicotine chewing gum in accordance with the invention.

In fig. 3 illustrates one embodiment of a nicotine chewing gum in accordance with the invention.

Detailed Description of Embodiments of the Invention

Definitions

For the purposes of this application and the invention, the following definitions apply.

The term nicotine refers to the amount (mg) of nicotine in any salt form or nicotine bound to any carrier, based on the amount of the corresponding free base.

The term core or gum core is intended to refer to the gum-based delivery system used to carry the gum base, sweeteners, flavors, fillers, and any other substances when chewing gum and inflatable gum. It provides all the basic structural and chewing properties of gum.

The term portion/layer is intended to refer to a portion that is bonded to or attached to the outer portion of the hard-coated chewing gum at any location. It can be of any shape, including a round section (point element), a square section, a conical section, a triangular section, etc. The specified area may be presented in the form of a trademark, and may also have a color. This area may also be a layer present on the outside of the hard cover of the gum, for example 40% of the surface of the gum for one layer, for example on one side, or on both sides of the gum.

The term buffer(s) refers to two different types of buffer forms, also differentiating the corresponding acid-base pair of the buffer system.

As used herein, the term extended release (RTR) refers to formulations that are characterized by the release of nicotine present in the gum core over an extended chewing period, typically 20-45 minutes when chewed (used) by the consumer or patient of the gum. rubber bands. 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 Drug Chewing Gums, Apparatus B).

As used herein, the term immediate release (IR) is intended to denote the release of nicotine contained in the polyol (sugar) based portion(s)/layer(s).

- 4 045857 alcohol) on the outside of chewing gum with a hard coating designed for rapid absorption through the oral mucosa. The rate of nicotine release is not prolonged by a controlled release matrix or other similar means, but is dependent on the disintegration and dissolution of the portion(s)/layer(s) or film coatings and the water solubility of the polyol and nicotine salt. As described herein, the immediate release component is released shortly after the sugar alcohol and nicotine mixture breaks down and dissolves (in saliva), which occurs shortly after the gum is inserted and chewing begins.

The amount of nicotine present in the gum center is calculated and most often expressed as the amount of the corresponding nicotine free base form.

The term deposited on, as used herein, is intended to be used interchangeably with attached to, fused to, bonded to, deposited on, coated on, adhered to, or melted on, or printed on.

Chewing gum

In one embodiment, the invention relates to nicotine chewing gum containing:

i) a gum core containing nicotine, ii) a polymer-based film coating containing at least one flavor and at least one sweetener applied to the chewing gum core, iii) at least one polyol-based hard coating applied to the film a chewing gum coating containing at least one sugar alcohol or mixtures of sugar alcohols, iv) at least one portion/layer fused to the outer side of the polyol-based hard coating, said portion/layer comprising a nicotine salt and at least one sugar alcohol, or mixture of sugar alcohols,

v) at least one portion/layer fused to the outer side of the polyol-based hard coating, said portion/layer containing one or more buffers in an amount of from about 3 to about 7.5 mg and at least one sugar alcohol or mixture sugar alcohols, wherein the release of nicotine from the outer portion/layer (iv) is immediate and the release of nicotine from the core (i) is sustained, and wherein the buffer(s) (v) are located on the outside of the hard-coated chewing gum core , promote(s) the rapid absorption of nicotine from (iv) through the oral mucosa (see, for example, Fig. 1) and wherein one or more buffers is selected from the group consisting of sodium carbonate, sodium bicarbonate, base trometamol (Tris base) or a corresponding trometamol conjugate acid such as trometamol hydrochloride (Tris-HCl), sodium hydrogenorthophosphate, or mixtures thereof.

The sugar alcohol present in the polyol-based portion(s) or layer(s) on the outside of the hard coating contains erythritol.

In another embodiment, the invention relates to nicotine chewing gum containing:

i) a gum core containing nicotine, ii) at least one film coating applied to the gum core containing at least two buffers and at least one film-forming polymer, iii) at least one polyol-based hard coating applied over on at least one film coating, wherein the polyol-based hard coating contains at least one sugar alcohol or mixtures of sugar alcohols, iv) at least one area/layer fused to the outer side of the polyol-based hard coating, wherein said area/layer contains a nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, and the release of nicotine from the outer portion/layer (iv) is immediate, and the release of nicotine from the core (i) of the gum is prolonged, and the buffers (ii) located in at least one film coating on the outside of the gum core, promote rapid absorption of nicotine from (iv) through the oral mucosa (see, for example, FIG. 2 and 3) and wherein one or more buffer(s) is selected from the group consisting of sodium carbonate, sodium bicarbonate, trometamol base (Tris-base) or a corresponding trometamol conjugate acid such as trometamol hydrochloride (Tris-HCl), hydrogen orthophosphate sodium, or mixtures thereof.

The sugar alcohol present in the polyol-based portion(s) or layer(s) on the outside of the hard-coated gum core contains erythritol.

In one embodiment of the invention, one film coating contains at least two buffers, at least one sweetener and at least one flavor.

In another embodiment of the invention, two different polymer-based film coatings are applied, with the first film coating being in contact with the gum core and the second film coating being located outside the first film coating. At least two buffers are present in one of the film coatings and at least one sweetener and at least one flavor are present in the other film coating. In one example, buffers are present

- 5 045857 in the first film coating and at least one sweetener and at least one flavoring agent in the second film coating. In another example, at least one sweetener and at least one flavor are present in the first film coating, and at least two buffers are present in the second film coating.

Those skilled in the art are well aware of how to prepare conventional chewing gum.

One example is the method described in US 3,877,468. Coated chewing gums are described in WO 2006/124366, which describes hard coatings based on a polyol in combination with an internal polymer coating containing one or more sweeteners and/or flavoring agents to improve taste and organoleptic perception of chewing gum.

The gum core contains nicotine, for example nicotine bound to ion exchange resins, for example nicotine polacrilex, nicotine bound to zeolites and/or nicotine bound to betacyclodextrins, preferably nicotine in the form of nicotine polacrilex. The nicotine present in the gum center (on a free base basis) may be from about 1.0 to about 6.0 mg, from about 2.0 to about 4.0 mg, for example, 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, 5.0, 5.5 or 6.0 in terms of chewing gum. Nicotine is released from the gum core when the user chews the gum, and the release occurs over an extended period of time, typically up to about 30-45 minutes, which is the average time a user or patient chews nicotine gum.

At least two buffers may be present in at least one film coating located on the outside of the gum core, or one or more buffers may be present in at least one portion/layer fused to the outside of the hard-coated gum. The buffer(s) are selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol base (Tris base) or the corresponding trometamol conjugate acid, e.g. trometamol hydrochloride (Tris-HCl), trisodium phosphate, sodium hydrogen orthophosphate, sodium dihydrogen phosphate, tripotassium phosphate, potassium hydrogen orthophosphate, potassium dihydrogen phosphate and mixtures thereof.

In some examples, the buffer(s) may be present in at least one film coating or in at least one portion/layer on the outside of the hard coated gum and is selected from the group consisting of sodium carbonate, sodium bicarbonate, trometamol base (tribase ) or the corresponding trometamol conjugate acid, for example trometamol hydrochloride (Tris-HCl) and mixtures thereof.

Acid nicotine salt and alkaline buffers are not suitable for being present in the same or adjacent polymer-based film coating or in the same area/layer on the outside of a hard-coated gum. The interaction during the drying and/or cooling process can result in the conversion of nicotine to the free base form, which is a volatile and unstable liquid, resulting in loss of nicotine or a chemically unstable product.

The buffer(s) in the film coating may be present in a total amount of from about 1.0 to about 7.5 mg (based on chewing gum), for example, from about 1.0 to about 6.0, for example, from about 2.0 to about 6.0, or about 2.0 to about 5.0 mg, or about 3.0 to about 6.0, or about 3.0 to about 5.0, for example 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 from 0.5 mg to about 3.5 mg, such as from 0.5 mg to 2.5 mg, such as from 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 trometamol conjugate acid, e.g. trometamol hydrochloride (Tris-HCl), may be present in an amount of from 1.5 mg to 5.0 mg, for example 2.0 to 5.0 mg, 3.0 mg to 5.0 mg or 1.5, 2.0, 2.5, 3.0, 3, 5, 4.0, 4.5 or 5.0 mg.

The gum core is coated with an outer hard polyol-based coating and may further include one or more polymer-based coatings.

The individual film coatings may have a thickness of from about 20 to about 200 microns, for example from 20 to about 100 microns, for example from 20 to 60 microns, for example 30 microns.

The film-forming polymers can be selected from hydroxypropyl methylcellulose (HPMC), methylhydroxyethylcellulose (MHEC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), methacrylic acid copolymer type C, sodium carboxymethylcellulose, hydroxypropyl methylcellulose phthalate, (HPMCP), ethylhydroxyethylcellulose (EHEC) and other film-forming polymers eg polydextrose, polyethylene glycols, acrylate polymers, polyvinyl alcohol-polyethylene glycol graft copolymers, polyvinylpyrrolidone (PVP) complex, eg povidone, polyvinyl alcohol (PVOH or PVA), microcrystalline cellulose, carrageenan, pregelatinized starch, polyethylene glycol and combinations thereof.

In one embodiment of the invention, the film-forming polymers are selected from hydroxypropyl methylcellulose (HPMC), methylhydroxyethylcellulose (MHEC), hydroxypropylcellulose

- 6 045857 (HPC), hydroxyethylcellulose (HEC), ethylhydroxyethylcellulose (ENEC) and polyvinyl alcohol (PVOH or PVA).

If two polymer-based film coatings are applied, then both the same and different polymers and their mixtures can be used in separate coatings. Examples include, for example, both layers of hydroxypropyl methylcellulose (HPMC) film, or one layer based on hydroxypropyl methylcellulose (HPMC) and the other layer based on another film-forming polymer, such as polyvinyl alcohol (PVOH or PVA). Film-forming polymers may have slightly different characteristics. For example, PVA is believed to be more resistant to elevated pH and thus may be suitable for use in a buffered film coating when the goal is to achieve a high pH.

HPMC, when applied to hard-coated nicotine chewing gum, provides a pleasant palatability and can also provide a long-lasting flavor and sweetener boost.

The polyol-based solid coating on the outside of the film coating contains at least one sugar alcohol or mixtures thereof. The sugar alcohol may be erythritol, maltitol, xylitol, lactitol, isomalt, mannitol, arabitol, isomalt and sorbitol or mixtures thereof. The polyol-based hardcoat may have a thickness of from about 350 to about 750 microns, such as 500 microns. In one embodiment of the invention, the polyol-based solid coating is a mixture of xylitol and maltitol or contains only xylitol.

Examples of flavorings/flavors include fruit and berry flavors, for example, lime, orange, lemon, blackcurrant, orange blossom, cranberry, cloudberry, goji berries, raspberry, strawberry, strawberry, sea buckthorn, cherry, melon, kiwi, papaya, pineapple , passion fruit, coconut and other flavors such as honey, herbs, anise, mustard, lemongrass, cooling agent, ginger, coffee, eucalyptus, mangosteen, peppermint, spearmint, wintergreen, tutti-frutti, cinnamon, cocoa, vanilla, liqueur , salt, pepper, chili, menthol, anise seed or mixtures thereof. Flavoring additives/flavors can be either natural extracts or synthetic and semi-synthetic derivatives, as well as flavor mixtures. The flavoring agents may be the same or different and may be present in the gum core, film coating(s), polyol-based hard coating, and outer portion(s)/layer(s). Suitable examples of flavoring agents include mint flavors, fruit flavors, and berry flavors.

In addition, the chewing gum may contain at least one artificial sweetener. At least one artificial sweetener may be present in the gum core, film coating(s) or polyol-based hard coating and/or outer portion(s)/layer(s). Examples of artificial sweeteners are saccharin, sodium saccharin, aspartame, acesulfame K, neotame, thaumatin, glycyrrhizin, sucralose, cyclamate, dihydrochalcone, elite, miraculin and monellin, and mixtures thereof.

At least one section/layer is fused onto the polyol-based hard coating. At least one section contains a nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols. This region may also include at least one sweetener and/or at least one flavoring agent, such as those mentioned above. The nicotine salt in at least one portion/layer is designed to include nicotine in a readily soluble form.

In one embodiment, the other at least one portion/layer contains at least one buffer and at least one sugar alcohol or mixture of sugar alcohols, wherein the buffer(s) in an amount of from about 3 to about 7.5 mg is deposited. on hard-coated chewing gum. The at least one section/layer may also include at least one sweetener and/or at least one flavoring agent, such as those mentioned above.

The at least one portion/layers may be the same size and weight, or different sizes and weights, and may be placed on top of each other, adjacent to each other, or on different sides of the chewing gum. At least one portion/layer containing nicotine or buffer(s) may be placed on top of each other, adjacent to each other if at least one portion/layer is completely dry and cured, or on opposite sides of the chewing gum.

The above at least one section/layer may contain a mixture of erythritol and xylitol in a proportional amount of about 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 to xylitol). In another embodiment of the invention, said region contains at least erythritol.

Nicotine is uniformly distributed in the nicotine-containing at least one portion/layer on the outside of the hard-coated gum. In those embodiments in which there is at least one portion/layer on the outside of the hard-coated gum containing buffer(s), said buffer(s) are uniformly distributed in at least one portion/layer.

The nicotine salts in at least one portion/layer on the outer side of the hard-coated chewing gum may be present in an amount of from about 0.25 to about 2.5 mg, such as from 0.5 to about 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 mass

- 7 045857 area(s)/layer(s) is about 2-10%, for example 2-5% of the total mass of the chewing gum.

In another embodiment of the invention, at least one portion/layer containing one or more buffer(s) may include a combination of erythritol and xylitol or erythritol. Such portion(s)/layer(s) may have a total weight of the portion(s) or layer(s) of up to 10% or even up to 15% of the total weight of the chewing gum.

In the event that buffer(s) are present in the portion/layer on the outside of the hard-coated gum, the buffer(s) may be present in a total amount of from about 3 to about 7.5 mg for each chewing gum , for example about 3 to about 5 mg, for example 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, 7.5 or 7.5 mg.

In another embodiment, the invention relates to a novel chewing gum comprising at least a gum core containing nicotine polycrylex, at least one first film coating containing polyvinyl alcohol (PVA), which contains at least two buffers, wherein one buffer represents is sodium carbonate or sodium bicarbonate, and the other is trometamol base (Tris base) and/or trometamol conjugate acid, for example trometamol hydrochloride (Tris conjugated acid), and a second film coating containing LMPC and at least one flavoring agent and at least one sweetener, at least one outer polyol hard coating applied to film coatings containing at least xylitol, and at least one portion/layer fused to the outer polyol hard coating, wherein said at least one portion /layer is based on erythritol and contains a nicotine salt, for example, nicotine bitartrate or nicotine ditartrate dihydrate (may also be called nicotine hydrogen tartrate (NHT) or nicotine bitartrate).

At least one outer polyol-based portion/layer may be colored. Colorants include pigments and dyes approved as food additives, and examples of colorants are artificial colors or natural colors. One example is the area defined above, which may be a point similar to the points on a ladybug.

Examples of artificial colors approved for use in the EU include E104: Quinoline Yellow, E122: Carmoisine, E124: Ponceau 4R, E131: Patent Blue V and E142: Green S. In the US, seven artificial colors are generally allowed in foods. dyes: FD&C Blue No. 1 brilliant blue FCF, E133 (blue tint), FD&C Blue No. 2 - indigotine, E132 (indigo tint), FD&C Green No. 3 - permanent green FCF, E143 (turquoise tint), FD&C Red No. 3 - erythrosine , E127 (pink shade, often used in glazed cherries), FD&C Red No. 40 - charming red AC, E129 (red shade), FD&C Yellow No. 5 - tartrazine, E102 (yellow shade), FD&C Yellow No. 6 - sunset yellow FCF , E110 (orange tint) or iron oxide.

Examples of natural colors include: garotenoids (E160, E161, E164), chlorophyllin (E140, E141), anthocyanins (E163) and betanin (E162), annatto (E16Ob), reddish-orange color derived from achiote seeds, caramel color (E150a -d), obtained from caramelized sugar, carmine (E120), red color obtained from Mexican cochineal, Dactylopius coccus, black elderberry juice (E163), lycopene (E160d), paprika (E160c) and turmeric (E100), dioxide titanium or iron oxide.

In addition, the chewing gum may contain at least one artificial sweetener. At least one artificial sweetener may be present in the gum core, in the film coating(s), in the polyol-based hard coating, and/or on the outside of one or more portions/layers. Examples of artificial sweeteners are saccharin, sodium saccharin, aspartame, acesulfame K, neotame, thaumatin, glycyrrhizin, sucralose, cyclamate, dihydrochalcone, alitame, miraculin and monellin, and mixtures thereof.

The at least one outer portion/layer may have a total weight of about 1-10% of the total weight of the elastic, for example 2-10%, for example 2-3%, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0% or even up to 15% or even up to 20% of the total weight of the chewing gum.

The nicotine polacrilex present in the gum core may be in an amount of from about 1.0 to about 6.0 mg, from about 2.0 to about 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, based on the free base, and the nicotine salt present on the outside of at least one region/layer may be in an amount of from about 0.25 to about 2.5 mg, for example, 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, for example 0.25 to 1.0 mg, or 0.25 to 1.5, or from 0.25 to about 2.5 mg (based on free base).

The relative amount of nicotine salt relative to the buffer(s) located outside the gum core or located outside the hard-coated gum is important because the buffer(s) convert the nicotine salt to its free form. reasons to promote rapid absorption of nicotine.

If too little buffer(s) are available against the nicotine salt, the conversion of nicotine to its free base form will be affected, which may result in relatively more

- 8 045857 high proportion of nicotine in its acidic form, which will lead to a decrease in the proportion of nicotine absorbed by the oral mucosa, and instead nicotine will be transported to the gastrointestinal tract and the so-called first-pass metabolism. This may result in a comparatively slower and reduced absorption of nicotine, affecting the concentration of nicotine in the systemic circulation, as well as a comparatively slower (and lower) reduction in smoking cravings.

In some embodiments, at least one outer portion/layer on the hard-coated gum contains nicotine bitartrate or nicotine ditartrate dihydrate in an amount of 0.25 to 2.5 mg of nicotine (based on free base), as well as one or more buffers which are located in another portion/layer on the outside of the hard-coated gum or in a film coating on the outside of the gum core, the buffer(s) containing sodium carbonate and/or sodium bicarbonate in an amount of 0.5 to 3.5 mg and the basic form of trometamol, as above, in an amount of 1.5 to 5.0 mg.

Making nicotine chewing gum.

The invention also relates to a method of making chewing gum using the steps of, for example, mixing, rolling and cutting, applying film and hard coating and depositing/fusing one or more polyol-based areas onto the surface of the gum by screen printing, melt layering, ink printing, pipetting or 3D printing, the following steps may be used.

Step A: Preparation of a chewing gum center containing nicotine, for example, nicotine polacrylex, wherein the chewing gum may be prepared as shown in the methods and examples described in US Pat. No. 3,877,468.

Step B: Prepare a polymer-based film coating composition containing sweeteners and flavors and apply the film coating to a chewing gum center using, for example, commercially available film coating equipment suitable for aqueous formulations, allowing the coating to dry on the chewing gum using, for example, air, eg temperature-controlled dry air, to produce film-coated chewing gum.

Step C: Providing a polymer-based film composition containing at least two buffers and optionally also at least one sweetener and at least one flavoring agent, applying a film coating to said chewing gum using, for example, commercially available film coating equipment. a coating suitable for aqueous formulations, allowing the coating to dry on the chewing gum using, for example, temperature-controlled dry air, and providing a film-coated chewing gum.

Stage B can be omitted if stage C is present.

Stage C can be omitted if stage G is included. Stage B and stage C can go in any order if they are included.

Step E: Providing a polyol-based hard coating composition containing at least one sugar or a sugar alcohol mixture as defined above, and applying the polyol-based hard coating composition to the chewing gum and producing an outer coated chewing gum using, for example, one available in selling hard coating equipment suitable for aqueous formulations, allowing the coating to dry on the chewing gum using, for example, air, such as temperature controlled dry air, to produce a hard coated chewing gum.

Step F. Preparation of a composition containing a nicotine salt, for example nicotine monotartrate, bitartrate, citrate, malate, hydrochloride, nicotine bitartrate or nicotine bitartrate dihydrate, nicotine salt and at least one sugar alcohol or mixture of sugar alcohols, for example erythritol, maltitol, xylitol, lactitol , isomalt, mannitol, arabitol, isomalt and sorbitol, or mixtures thereof, and fusing said composition onto said hard-coated chewing gum in the form of one or more sections or layers located on the outside of the hard-coated chewing gum, and producing an outer-coated chewing gum i) nicotine area(s) or layer(s) using screen printing, melt deposition, ink printing, pipetting or 3-D printing.

Step G. Providing a composition containing one or more buffers and at least one sugar alcohol or a mixture of sugar alcohols, and fusing said composition onto said chewing gum in one or more sections or layers using screen printing, melt layering, ink printing, pipetting or 3-D printing to produce a hard-coated gum containing one or more regions or layers containing a nicotine salt, and with one or more regions or layers containing one or more buffers.

The various components and ingredients that must be included in the process can be found above.

Finally, the invention relates to the use of chewing gums as defined above for

- 9 045857 treatment of a person suffering from addiction to tobacco and/or dependence on an electronic nicotine delivery device.

Examples

Specific embodiments of the present invention are illustrated by the examples below. The present invention is not limited by the limitations set forth in these examples.

The amounts of ingredients are expressed differently in the examples and do not correspond to what will result in the finished chewing gum. However, it will be obvious to one skilled in the art how to redesign and develop chewing gum in accordance with the present invention.

Example 1 Chewing Gum with One Polymer Film Coating with One or More Buffers

The gum base was obtained from a commercial gum base manufacturer, and the preparation of nicotine polacrilex chewing gums was performed in accordance with one or more of the methods/examples disclosed in US 3,877,468. WO 2006/124366 discloses a method for formulating and manufacturing polymer-based nicotine gums contained within a solid polyol-based coating.

To obtain the film coating in this example, the following film-forming compositions were used. The compositions are presented as mg per chewing gum.

Examples 1 2 3 4 5 6 7 8 9 10 eleven 12 13 14 15 16 17 18 19 20 Hydroxypropyl methylcellulose (HPMC) 7.5 9 7.5 13 15 9 9 9 eleven eleven 9 eleven 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 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 Bicarbonate of soda 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 water ¹ ' Ven. Qty. IN Ven. Qty. IN Ven. Qty. IN Ven. Qty. IN Ven. Qty. IN Ven. QUANTITY Ven. Qty. IN Ven. QUANTITY Ven. Qty. IN Ven. QUANTITY Ven. Qty. IN Ven. Qty. IN Ven. QUANTITY Ven. Qty. IN Ven. Qty. IN Ven. Qty. IN Ven. QTY Ven. Qty. IN Ven. QTY Ven. QTY Hydrochloric acid (10%) or NaOH (0.1 M) ²⁾ UP TO pH 9.5 UP TO pH 9.5 up to pH 10 UP TO pH 10.5 BEFORE pH 10.5 UP TO pH 9.5 up to pH 10 UP TO pH 9 up to pH 10 up to pH 9 UP TO pH 9 UP TO pH 10.5 BEFORE pH up to pH 10 BEFORE pH UP TO pH 10.5 UP TO pH 10 UP TO pH 10.5 up to pH 10 UP TO pH 10.5

1) During the film coating process, most of the purified water is removed.

2) Preparation of the coating involves adjusting the pH with hydrochloric (10%) acid or NaOH (0.1 M) to the target pH level

For the polymer application process, the dry matter content of the coating formulation may vary between 20-50% w/w to facilitate the inclusion of varying amounts of buffering agents. Adapting the dry formulation with different amounts of buffering agent will facilitate the preparation of the coating without salting out the polymer.

Example 2 Chewing gum with two polymer film coatings, one containing two or more buffers and the other containing flavorings and sweeteners

The gum base was obtained from a gum base manufacturer, and the preparation of nicotine polacrilex gum cores was performed in accordance with one or more of the methods/examples disclosed in US 5,976,581. WO 2006/124366 discloses 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. The compositions are presented as mg per chewing gum.

Examples 1 2 3 4 5 6 7 8 9 10 Polymer 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 Bicarbonate of soda 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 water ¹ - ¹ Ven. QTY Ven. QTY Ven. QTY Ven. QTY Ven. QTY Ven. QTY Ven. QTY Ven. QTY Ven. QTY Ven. QTY Hydrochloric acid (10%) ²⁾ up to pH 9.5 up to pH 9.5 up to pH 10.5 up to pH 9 up to pH 10.5 up to pH 10.5 pH 10.7 up to pH 10.5 pH 10.7 up to 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 water ¹ - ¹ Delivery, quantity Delivery, quantity Delivery, quantity Delivery, quantity Delivery, quantity Delivery, quantity Delivery, quantity Delivery, quantity Delivery, quantity Delivery, quantity

1) During the film coating process, most of the purified water is removed

2) Preparation of the coating involves adjusting the pH with hydrochloric (10%) acid or NaOH (0.1 M) to the target pH level

The dry matter content of the coating formulation can be varied between 20-50% w/w to facilitate the inclusion of varying amounts of buffering agents.

Claims (15)

Example 3 Formulation of Nicotine Salt Compositions for Outer Section(s) or Layer(s) Preparation of Various Sections Containing Nicotine Salt and Excipients Examples 1 2 3 4 5 6 7 8 9 Amounts expressed as % w/w. for each component in each example API Nicotine bitartrate dihydrate 15.39 15.4 14.3 14.3 14.3 14.3 14.3 7.13 15.35 You are excipient 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 Dost, quantity Dost, quantity Dost, quantity Dost, quantity Dost, quantity Dost, quantity Dost, quantity Dost, quantity Dost, quantity Mannitol 25 mk 3.3 Sodium carbonate Neotame 0.15 Titanium dioxide 1.8 2.0 2.0 2 Preparation: All starting materials, polyols or mixtures of multiple polyols, nicotine source and colorant, crystallization seed or sweetener, if applicable, were mixed in a glass beaker. The mixture was heated until melted and all components were mixed, with the exception of titanium dioxide. From 20 to 40 mg of the molten mass was applied to the chewing gum using a micropipette. The drop was periodically flattened with a heated tool immediately after application to reduce the thickness of the applied drop. The use of xylitol as the primary polyol resulted in a cure time that was too long to be used for commercialization. The use of crystallization seeds (mannitol 25 c or titanium dioxide) does not reduce the solidification time. Isomalt had a very fast hardening time, but a very high melting point (153°C), which is undesirable from the point of view of stability and safety. Erythritol showed rapid solidification and a much lower melting point (121.5°C). Example 4 Formulation of Compositions for Outer Section(s) or Layer(s) Including Buffers 1 2 3 4 5 Erythritol (g) 29.25 28,875 28.5 27.00 26.75 Tromethamine (g) 0.75 1.125 1.5 3.00 3.75 Na ₂ CO ₃ (g) 0.75 0.75 0.75 0.75 0.75 Total (g) 30.75 30.75 30.75 30.75 30.75 From all compositions of examples 1-5, a clear solution was obtained with gentle manual stirring and melting at 125°C, not containing any residual particles when visually inspected. The hardening time for deposition of patches onto chewing gum increased with increasing concentration of trometamol, but was within production feasibility. Preparation: All starting materials, polyol and buffer(s) were mixed in a glass beaker. The mixture was heated until melted while all components were stirred. From 20 to 40 mg of the molten mass was fused onto the chewing gum using a micropipette. The drop was periodically flattened with a heated tool immediately after application to reduce the thickness of the applied drop. CLAIM 1. Nicotine chewing gum containing: i) a gum core containing nicotine, ii) a polymer-based film coating containing at least one flavor and at least one sweetener applied to the chewing gum core, iii) at least one polyol-based hard coating applied to the film a chewing gum coating containing at least one sugar alcohol or mixtures of sugar alcohols, iv) at least one portion/layer fused to the outer side of the polyol-based hard coating, said portion/layer comprising a nicotine salt and at least one sugar alcohol, or mixture of sugar alcohols, v) at least one portion/layer fused to the outer side of the polyol-based hard coating, said portion/layer containing one or more buffers in an amount of from about 3 to about 7.5 mg and at least one sugar alcohol or mixture sugar alcohols, and the release of nicotine from the outer portion/layer (iv) is immediate, and the release - 11 045857 release of nicotine from the core (i) of the gum is prolonged and the buffer(s) (v) outside the core facilitates the rapid absorption of nicotine from (iv) through the mucous membrane of the oral cavity, characterized in that one or more buffers selected from the group consisting of sodium carbonate, sodium bicarbonate, trometamol base (Tris base) or a corresponding conjugate trometamol acid such as trometamol hydrochloride (Tris-HCl), sodium hydrogenorthophosphate, or mixtures thereof. 2. Chewing gum according to claim 1, characterized in that at least one sugar alcohol in the section(s)/layer(s) is erythritol. 3. Nicotine chewing gum containing: i) a gum core containing nicotine, ii) at least one film coating applied to the gum core containing at least two buffers and at least one film-forming polymer, iii) at least one polyol-based hard coating applied over on at least one film coating, wherein the polyol-based hard coating contains at least one sugar alcohol or mixtures of sugar alcohols, iv) at least one area/layer fused to the outer side of the polyol-based hard coating, wherein said area/layer contains a 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 core (i) of the gum is prolonged and the buffers (ii) are at least at least one film coating on the outside of the gum core promotes rapid absorption of nicotine from (iv) through the oral mucosa, characterized in that one or more buffer(s) is selected from the group consisting of sodium carbonate, sodium bicarbonate, trometamol base (Tris base ) or a corresponding trometamol conjugate acid, such as trometamol hydrochloride (Tris-HCl), sodium hydrogenorthophosphate, or mixtures thereof. 4. Chewing gum according to claim 3, wherein the at least one film coating on the outside of the gum core contains at least two buffers, at least one sweetener, at least one flavoring agent and at least one film-forming polymer. 5. Chewing gum according to claim 3, containing at least two film coatings on the outside of the gum core, wherein one film coating contains at least two buffers and at least one film-forming polymer, and the other film coating contains at least one sweetener, at least one flavoring agent and at least one film-forming polymer. 6. Chewing gum according to any one of claims 1 to 5, 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 (PVA) or mixtures thereof. 7. Chewing gum according to claim 6, wherein one of the two polymer coatings contains PVA and at least two buffers, and the other polymer coating contains HPMC, at least one sweetener and at least one flavor. 8. Chewing gum according to any one of claims 3 to 7, characterized in that at least one sugar alcohol in the outer portion(s)/layer(s) is erythritol. 9. The chewing gum of any one of the preceding claims, wherein the buffer(s) in the at least one film coating on the outside of the gum core is present in an amount of from about 1.0 to about 7.5 mg. 10. Chewing gum according to any one of claims 1 to 9, characterized in that the nicotine in the gum core is nicotine polacrylex, and the nicotine in the outer section(s)/layer(s) is nicotine bitartrate or nicotine ditartrate dihydrate . 11. Chewing gum according to any one of the preceding claims, characterized in that the gum core contains nicotine polacrylex in an amount of from about 1.0 to about 7.5 mg (based on free base), and at least one area/layer fused on the outside of the polyol-based solid coating, contains a nicotine salt present in an amount of from about 0.25 to about 2.5 mg (based on the free base). 12. Chewing gum according to any of the preceding claims, containing: i) nicotine bitartrate or nicotine ditartrate dihydrate in an amount of from 0.25 g to 2.5 mg in the area/layer fused to the outside of the polyol-based hard coating (based on the free base), ii) sodium carbonate and/or bicarbonate sodium in an amount from 0.5 g to 3.5 mg and iii) trometamol base or a corresponding trometamol conjugate acid, for example trometamol hydrochloride (Tris-HCl) in an amount from 1.5 g to 5.0 mg, wherein ii) and iii) present in the film coating on the outside of the gum core or in the outer portion/layer fused to the polyol-based hard coating. - 12 045857 13. A method for producing chewing gum according to any one of claims 1-12, including the stages: i) providing a chewing gum center containing nicotine, ii) providing a polymer film coating composition containing at least one flavor and at least one sweetener, iii) applying said polymer film coating composition to the chewing gum center, iv) producing chewing gum with a film coating based on a polymer, v) providing a polyol-based hard coating composition containing at least one sugar alcohol or mixtures of sugar alcohols, vi) applying said polyol-based hard coating composition to said chewing gum, vii) producing a polyol-based hard-coating chewing gum, viii) producing a composition comprising a nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, ix) fusing said composition of viii) onto the outer side of a hard-coated chewing gum in the form of at least one section/layer to obtain a hard-coated chewing gum with at least at least one area/layer containing nicotine salt, x) preparing a composition containing one or more buffers in an amount of from about 3 to about 7.5 mg and at least one sugar alcohol or mixture of sugar alcohols, xi) fusing said composition of x) onto the outside of a hard-coated chewing gum in the form of at least one section/layer and xii) producing a hard-coated nicotine chewing gum, wherein the release of nicotine from the outer section(s)/layer(s) (ix) is immediate and the release of nicotine from the core (i) is prolonged and at the same time one or more buffers located on the outside of the hard-coated chewing gum (xi) promote rapid absorption of nicotine through the oral mucosa. 14. A method for producing chewing gum according to any one of claims 1-12, including the stages: i) providing a chewing gum center containing nicotine, ii) providing a polymer-based film coating composition containing at least two buffers, at least one sweetener and at least one flavoring agent, iii) applying said film composition to said chewing gum center polymer-based coatings, iv) producing film-coated chewing gum, v) providing a polyol-based hard coating composition containing at least one sugar alcohol or mixtures of sugar alcohols, vi) applying said polyol-based hard coating composition to said film-coated chewing gum, vii) producing a hard-coated chewing gum, viii) producing a composition containing a nicotine salt and at least one sugar alcohol or a mixture of sugar alcohols, ix) fusing said composition of viii) onto the outer part of a hard-coated chewing gum in the form of at least one section/layer, x) producing a hard-coated nicotine chewing gum, wherein the release of nicotine from at least one region/layer (ix) is immediate, and the release of nicotine from the core (i) is sustained, and wherein at least two buffers (iv) are present on the outside Gum cores promote rapid absorption of nicotine through the oral mucosa. 15. A method for producing chewing gum according to any one of claims 1-12, including the stages: i) providing a chewing gum core containing nicotine, ii) providing a polymer-based film composition containing at least two buffers, iii) applying said polymer-based film composition to said chewing gum core, iv) producing a film-coated chewing gum, having a first film coating, v) providing a polymer-based film composition containing at least one sweetener and at least one flavoring agent, vi) applying a second polymer-based film composition to said chewing gum, vii) providing a chewing gum coated with two polymer-based film coatings, viii) providing a polyol-based hard coating composition containing at least one sugar alcohol or mixtures of sugar alcohols, ix) applying said composition to said film-coated chewing gum -