Oral tablet suitable for active pharmaceutical ingredients

Abstract

The invention relates to an oral delivery tablet suitable for active pharmaceutical ingredients comprising a population of particles, the population of particles comprising a) directly compressible (DC) sugar alcohol particles, b) non-directly compressible (non-DC) sugar alcohol particles and c) particles comprising gum base, the non-DC particles providing the tablet with a plurality of discrete non-DC areas, and the non-DC areas resulting in induced saliva generation upon mastication of the tablet, wherein the tablet is designed to be masticated into a coherent residual containing water-insoluble components.

Claims

1. An oral delivery chewing gum tablet suitable for active pharmaceutical ingredients comprising a population of particles, the population of particles comprising a) directly compressible (DC) sugar alcohol particles, b) non-directly compressible (non-DC) sugar alcohol particles that have not been granulated prior to tableting, and c) particles comprising gum base, wherein a first module of the tablet comprises a) and b), a second module of the tablet comprises c), the non-DC sugar alcohol particles provide the first module of the tablet with a plurality of discrete non-DC areas embedded in a matrix comprising the DC sugar alcohol particles, the non-DC sugar alcohol particles have average particle size at least 50 μm larger than average particle size of the DC sugar alcohol particles, and the tablet comprises at least 20% by weight of gum base.

2. The oral delivery chewing gum tablet according to claim 1, wherein the non-DC sugar alcohol particles are non-DC particles of erythritol, or non-DC particles of maltitol, or non-DC particles of xylitol, or combinations thereof.

3. The oral delivery chewing gum tablet according to claim 1, wherein the tablet comprises said non-DC sugar alcohol particles in an amount of at least 10% by weight of the tablet.

4. The oral delivery chewing gum tablet according to claim 1, wherein the tablet further comprises an oral care agent in the amount of at least 0.1% by weight of the tablet.

5. The oral delivery chewing gum tablet according to claim 1, wherein the tablet further comprises tooth paste in the amount of at least 0.1% by weight of the tablet.

6. The oral delivery chewing gum tablet according to claim 1, wherein the non-DC areas are evenly distributed in the first module of the tablet.

7. The oral delivery chewing gum tablet according to claim 1, wherein a series of at least 10 of said tablets each comprises a gum base free module, and wherein the gum base free module comprises said non-DC sugar alcohol particles in an amount varying with a relative standard deviation (RSD) below 10%.

8. The oral delivery chewing gum tablet according to claim 1, wherein the tablet has a weight ratio between said non-DC sugar alcohol particles and said DC sugar alcohol particles that is between 0.3 and 1.2.

9. The oral delivery chewing gum tablet according to claim 1, wherein saliva generation upon mastication of the first module of the tablet is induced compared to a first module of the tablet where the discrete areas are based on DC sugar alcohol particles.

10. The oral delivery chewing gum tablet according to claim 1, wherein the tablet generates more than 1.0 mL saliva per 10 seconds within 30 seconds from onset of mastication.

11. The oral delivery chewing gum tablet according to claim 1, wherein the tablet further comprises an active pharmaceutical ingredient.

12. The oral delivery chewing gum tablet according to claim 1, wherein the first module of the tablet comprises said non-DC sugar alcohol particles in an amount of at least 10% by weight of the first module of the tablet.

13. The oral delivery chewing gum tablet according to claim 1, wherein the first module of the tablet comprises said DC sugar alcohol particles in an amount of at least 10% by weight of the first module of the tablet.

14. An oral delivery chewing gum tablet suitable for active pharmaceutical ingredients comprising a population of particles, the population of particles comprising a) directly compressible (DC) sugar alcohol particles, b) non-directly compressible (non-DC) sugar alcohol particles that have not been granulated prior to tableting, and c) particles comprising gum base, wherein said population of particles is tableted into a first module of the tablet, and a second population of particles is comprised in a second module of the tablet, the non-DC sugar alcohol particles provide the first module of the tablet with a plurality of discrete non-DC areas embedded in a matrix comprising the DC sugar alcohol particles, the non-DC sugar alcohol particles have average particle size at least 50 μm larger than average particle size of the DC sugar alcohol particles, and the tablet comprises at least 20% by weight of gum base.

15. An oral delivery chewing gum tablet suitable for active pharmaceutical ingredients comprising a population of particles, the population of particles comprising: a) directly compressible (DC) sugar alcohol particles, b) non-directly compressible (non-DC) sugar alcohol particles that have not been granulated prior to tableting, and c) particles comprising gum base, wherein a) and b) are comprised in a first module of the tablet, c) is comprised in a second module of the tablet, and the non-DC sugar alcohol particles have average particle size at least 50 μm larger than average particle size of the DC sugar alcohol particles.

16. An oral delivery chewing gum tablet suitable for active pharmaceutical ingredients comprising a first module having a plurality of directly compressible (DC) sugar alcohol particles and a plurality of non-directly compressible (non-DC) sugar alcohol particles that have not been granulated prior to tableting, said non-DC sugar particles forming a plurality of discrete non-DC areas embedded in a matrix comprising the DC sugar alcohol particles, and a second module having a plurality of particles comprising gum base, wherein the tablet has a weight ratio between said non-DC sugar alcohol particles and said DC sugar alcohol particles that is between 0.3 and 1.2, and the non-DC sugar alcohol particles have average particle size at least 50 μm larger than average particle size of the DC sugar alcohol particles.

17. The oral delivery tablet according to claim 15, wherein the first module of the tablet is free of gum base.

18. The oral delivery chewing gum tablet according to claim 15, wherein the tablet has a weight ratio between said non-DC sugar alcohol particles and said DC sugar alcohol particles that is between 0.3 and 1.2.

19. The oral delivery chewing gum tablet according to claim 16, wherein the first module of the tablet comprises said non-DC sugar alcohol particles in an amount of at least 10% by weight of the first module of the tablet and the first module of the tablet comprises said DC sugar alcohol particles in an amount of at least 10% by weight of the first module of the tablet.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The invention will now be described with reference to the drawings where

(2) FIGS. 1a and 1 b shows an embodiment of the invention,

(3) FIGS. 2a and 2b shows a two-module version of an embodiment of the invention,

(4) FIGS. 3a and 3b shows a three-module version of an embodiment of the invention,

(5) FIGS. 4 and 5 illustrates embodiments of the invention and where

(6) FIG. 6 illustrates a two-module version of an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

(7) As used herein the term “oral delivery tablet” is considered as a tablet for oral use. The oral delivery tablet is considered as formed by tableting, i.e. compression of a particle composition, comprising the mentioned population of particles. The oral delivery tablet is a delivery tablet in the sense that it is suitable for active ingredients or active pharmaceutical ingredients. Attractive ingredients include compounds for oral care or nutraceuticals. Nevertheless, the oral delivery tablet may or may not comprise such active ingredients or active pharmaceutical ingredients. Typically, the oral delivery tablet may also be referred to as an oral tablet or merely a tablet.

(8) Water-insoluble components in the present context typically refer to elastomer, natural or synthetic resins or other water-insoluble components such as water-insoluble softener or inorganic fillers.

(9) As used herein, the phrase “tablet” refers to a tablet made by tabletting in a tabletting machine by pressing the tablet material to form the tablet. For example, the tablet material may be exposed to a punching means in a tableting machine, pressing e.g. granules and/or powder to a gathered mass of pressed material.

(10) In the present context the phrase “population of particles” refers to a statistical population of particles. The population of particles may be characterized by a number of different parameters, e.g. statistical parameters such as distribution of particles, average particle size, particle size distribution width, etc. The population of particles may have subpopulations, such as DC sugar alcohol particles, non-DC sugar alcohol particles, or in some embodiments particles comprising gum base. The phrasing “population of particles” may in an embodiment of the invention be provided as a plurality of tableted particles and where the population of particles are tableted in one module or it may refer to a population of particles where some of the particles are tableted into one module and other particles are tableted into another module.

(11) In the present context, the term “non-DC areas” refers to small volumes or spaces formed during tableting from the non-DC particles of non-DC sugar alcohol. Moreover, each of the non-DC areas may be composed of a single non-DC sugar alcohol particle, or may comprise several non-DC sugar alcohol particles. When the non-DC areas are distinct, i.e. not diffuse, the non-DC areas may be evenly distributed in the tablet, or at least one module thereof when the tablet comprises two or more modules. In such embodiments, where the non-DC areas are evenly distributed in in the tablet, or at least one module thereof, the non-DC areas may thus facilitate an even saliva generation in the mouth upon mastication.

(12) The term “non-DC sugar alcohol particles” refer to particles of non-directly compressible (non-DC) sugar alcohol. It is noted that the terms “non-DC sugar alcohol particles” and “non-DC particles” are used interchangeably. In the present context, the non-DC sugar alcohol particles refer to particles which have not been preprocessed by granulation with e.g. other sugar alcohols or binders for the purpose of obtaining so-called direct compressible particles (DC). Thus, non-DC sugar alcohol particles are considered as particles consisting of non-DC sugar alcohol(s), often consisting of a single non-DC sugar alcohol.

(13) The term “DC sugar alcohol particles” refer to particles of direct compressible (DC) sugar alcohol. It is noted that the terms “DC sugar alcohol particles” and “DC particles” are used interchangeably. DC sugar alcohol particles may be obtained e.g. as particles of sugar alcohols having DC grade by nature, e.g. sorbitol, or by granulating non-DC sugar alcohol with e.g. other sugar alcohols or binders for the purpose of obtaining so-called direct compressible particles (DC).

(14) In the present context when the non-DC areas are referred to as “discrete” this signifies that the non-DC sugar alcohols are not continuously distributed, but present in the discrete areas corresponding to the discrete nature of the non-DC sugar alcohol particles.

(15) In the present context, the term “suitable for active pharmaceutical ingredients” refers to the tablet as a suitable vehicle for e.g. inclusion and delivery of active pharmaceutical ingredients. However, it is noted that the tablet does not necessarily include active pharmaceutical ingredients or active ingredients.

(16) The term “fast release” may in an embodiment refer to a large amount, such as at least 50% by weight of higher, of e.g. the active ingredient being released in a short time, such as within 20 seconds from onset of mastication, or shorter.

(17) When referring to induced saliva generation, it is noted that this induced saliva generation exceeds any saliva generation without the use of the tablet of the invention. Particularly, in an embodiment the induced saliva generation exceeds saliva generation when using conventional tablets without non-DC areas. Then, induced saliva generation is increased over any saliva generation associated with conventional products, e.g. by comparing with a tablet without non-DC sugar alcohol particles, or with a tablet where the discrete areas are based on DC sugar alcohol particles.

(18) When referring to induced saliva generation, the saliva generation may be tested using the following method.

(19) Test subjects abstain from eating and drinking at least 30 minutes before initiation of any test. Immediately before introducing of the tablet into the oral cavity, the test subject swallows. The test subject refrains from swallowing during the test. Immediately after introducing of the tablet into the oral cavity, the test subject starts masticating the tablet at a frequency of 1 chew per second for 30 seconds. 30 seconds after starting the test, the test subject discards saliva into a plastic cup, which is weighted. The test subject keeps the coherent residue in the mouth and continues chewing immediately after each discarding of saliva. Saliva is discarded also at 90 seconds after onset of mastication, at 180 seconds after onset of mastication, at 300 seconds after onset of mastication, at 420 seconds after onset of mastication, and at 600 seconds after onset of mastication. Saliva generation is noted as average amount of saliva per 10 seconds within the given time period.

(20) As used herein, the term “particle size” refers to the average particle size as determined according to European Pharmacopoeia 9.1 when using test method 2.9.38 particle size distribution estimation by analytical sieving, unless otherwise specifically is mentioned.

(21) In the present context, the term “taste masking” refers broadly to masking of any sensations perceived as unpleasant or other off-note tastes, but not necessarily confined to the classical five basic tastes. A typical example of off-note taste includes bitter taste. Also, metallic taste is another example of as an off-note taste.

(22) As used herein the term “active ingredient” refers to a substance that is biologically active and has a physiological effect on the human body for the benefit of the human body or part thereof. Active ingredients include active pharmaceutical ingredients, but also other active substances such as nutraceuticals.

(23) In the present context, the term “disintegrate” refers to is a process where a part or module of the tablet falls apart or disintegrates in to smaller aggregates and as defined by European Pharmacopeia 2.9.1 “Disintegration of tablets and capsules”. The time period of obtaining the desired disintegration, here less than 20 seconds.

(24) In the present context the term “release” refers to the released substance being liberated from the water-soluble matrix. In some embodiments, the process of releasing a substance corresponds to the substance being dissolved in saliva.

(25) As used herein the term “buccal absorption” refers to a substance diffusing across the oral mucosa from the oral cavity to enter the bloodstream.

(26) As used herein the term “oral mucosa” refers to the mucous membrane in the oral cavity, i.e. in the mouth.

(27) As used herein the term “gastrointestinal tract” refers to the part of the digestive system starting with the stomach and ending with the rectum, including the intestines. Thus, the mouth and esophagus are not considered part of the gastrointestinal tract for the purposes of the present application.

(28) As used herein the term “throat” is considered front part of the neck, positioned in front of the vertebra, and including the pharynx and larynx.

(29) The tabletting may be performed at a certain pressure, e.g. typically defined as compression force. Different types of tabletting machines are known within the art, such as a rotary press device available by Fette.

(30) As used herein, the phrase “granules” refers to entities made e.g. by granulation, and may typically contain a plurality of particles adhered together.

(31) By the phrase “texture” is meant a qualitative measure of the visco-elastic properties of the tablet and of the overall mouth-feel experienced by the user during the mastication process. Thus, the term “texture” encompasses measurable quantities such as hardness and elasticity as well as more subjective parameters related to the chew-feel experienced by a user.

(32) In some embodiments of the present invention, the gum base components comprise for example elastomer in the range of 1-15% by weight of the tablet, natural and/or synthetic resin in the range of 5-35% by weight of the tablet, and further other gum base components in the range of 5-30% by weight of the tablet.

(33) It is evident, that the overall total amount of these above gum base components must be mutually adjusted in order to fit requirements with respect to tablet content of calcium carbonate, sweetener, flavor, etc.

(34) In some embodiments of the present invention, the tablet comprises natural resins in an amount of 0.1 to 30%, such as 1 to 25%, such as 3 to 25% or 5 to 25%, by weight of the tablet.

(35) In some embodiments of the present invention, the tablet comprises natural resins in an amount of at least 10% by weight of the tablet.

(36) In some embodiments of the present invention, the tablet is free of natural resins.

(37) In embodiments of the present invention, the tablet comprises synthetic resins in an amount of 0.1 to 30%, such as 1 to 25%, such as 3 to 25% or 5 to 25%, by weight of the tablet.

(38) In embodiments of the present invention, the tablet comprises elastomer in an amount of at least 2% by weight of the tablet, such as at least 4% by weight of the tablet.

(39) In embodiments of the present invention, the tablet comprises elastomer in an amount of less than 35% by weight of the tablet, such as less than about 25% by weight of the tablet, such as less than 20%, 15% or 10% by weight of the tablet.

(40) In embodiments of the present invention, the tablet comprises one or more flavoring agents, preferably in powdered form, selected from the group consisting of essential oils, essences, extracts, powders, acids, coconut, coffee, chocolate, vanilla, grape fruit, orange, lime, menthol, liquorice, caramel aroma, honey aroma, peanut, walnut, cashew, hazelnut, almonds, pineapple, strawberry, raspberry, apple, pear, peach, apricot, blackberry, cherry, pineapple, plum essence, clove oil, bay oil, anise, thyme, cedar leaf oil, nutmeg, cinnamon, peppermint, wintergreen, spearmint, eucalyptus, mint, or any combination thereof.

(41) In embodiments of the present invention, the tablet is provided with a coating.

(42) In embodiments of the present invention, the tablet has a weight in the range of 0.1 to 10 grams, such as in the range of 0.5 to 4 grams or such as in the range of 1.5 to 2.5 grams.

(43) According to an embodiment of the invention, the tablet may comprise filler. In embodiments of the present invention, the tablet comprises an additional filler in an amount of 0.1 to 40% by weight of the tablet.

(44) Elastomers provide the rubbery, cohesive nature to the tablet, which varies depending on this ingredient's chemical structure and how it may be compounded with other ingredients. Elastomers suitable for use in the tablet of the present invention may include natural or synthetic types.

(45) Elastomer plasticizers vary the firmness of the gum base components. Their specificity on elastomer inter-molecular interaction (plasticizing) along with their varying softening points cause varying degrees of finished tablet firmness and compatibility with other ingredients. This may be important when one wants to provide more elastomeric chain exposure to the alkane chains of the waxes. The elastomer plasticizers may typically resins, such as synthetic resins and/or natural resins.

(46) The elastomers employed in the tablet may vary depending upon various factors such as the desired texture of the coherent residual (i.e. the tablet after mastication) and the other components used in the formulation to make the tablet. The elastomer may be any water-insoluble polymer known in the art. Illustrative examples of suitable polymers in the tablet include both natural and synthetic elastomers. For example, those polymers which are suitable in the tablet include, without limitation, natural substances (of vegetable origin) such as chicle gum, natural rubber, crown gum, nispero, rosidinha, jelutong, perillo, niger gutta, tunu, balata, guttapercha, lechi capsi, sorva, gutta kay, and the like, and mixtures thereof. Examples of synthetic elastomers include, without limitation, styrene-butadiene copolymers (SBR), polyisobutylene, isobutylene-isoprene copolymers, polyethylene, and the like, and mixtures thereof.

(47) Natural resins may be used according to the invention and may be natural rosin esters (also known as ester gums), including as examples glycerol esters of partially hydrogenated rosins, glycerol esters of polymerized rosins, glycerol esters of partially dimerized rosins, glycerol esters of tally oil rosins, pentaerythritol esters of partially hydrogenated rosins, methyl esters of rosins, partially hydrogenated methyl esters of rosins, pentaerythritol esters of rosins, synthetic resins such as terpene resins derived from alpha-pinene, beta-pinene, and/or d-limonene, and natural terpene resins.

(48) In an embodiment of the invention a synthetic resin may include polyvinyl acetate (PVA) and/or vinyl acetate-vinyl laurate (VA-VL) copolymers.

(49) In an embodiment of the invention, the tablet may comprise one or more components selected from the group consisting of bulk sweeteners, flavors, dry-binders, tabletting aids, anti-caking agents, emulsifiers, antioxidants, enhancers, absorption enhancers, high intensity sweeteners, softeners, colors, or any combination thereof.

(50) In an embodiment of the invention, the tablet comprises, apart from the DC and non-DC sugar alcohol particles, sweeteners, such as bulk sweeteners, sugar sweeteners, sugar substitute sweeteners, artificial sweeteners, high-intensity sweeteners, or any combination thereof.

(51) Suitable bulk sweeteners include both sugar and non-sugar sweetening components.

(52) Bulk sweeteners typically constitute from about 5 to about 95% by weight of the tablet, more typically about 20 to about 80% by weight such as 30 to 70% or 30 to 60% by weight of the tablet.

(53) Useful sugar sweeteners are saccharide-containing components commonly known in the tablet art including, but not limited to, sucrose, dextrose, maltose, lactose, dextrins, trehalose, D-tagatose, dried invert sugar, fructose, levulose, galactose, corn syrup solids, and the like, alone or in combination.

(54) As an example, sorbitol can be used as a non-sugar sweetener. Other useful non-sugar sweeteners include, but are not limited to, other sugar alcohols such as mannitol, xylitol, maltitol, isomalt, erythritol, lactitol and the like, alone or in combination.

(55) Applicable but non-limiting non-DC sugar alcohols to be used within the scope of the invention includes: Non DC Xylitol: Xivia C from Dupont Non DC Isomalt: Isomalt GS from Beneo Paltinit Non DC Mannitol: Pearlitol from Roquette Non DC Maltitol: Maltisorb. P200 from Roquette Non DC Erythritol: Zerose 16952 from Cargill

(56) High intensity artificial sweetening agents can also be used alone or in combination with the above sweeteners. For example, high intensity sweeteners include, but are not limited to sucralose, aspartame, salts of acesulfame, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, stevioside (natural intensity sweetener) and the like, alone or in combination. In order to provide longer lasting sweetness and flavor perception, it may be desirable to encapsulate or otherwise control the release of at least a portion of the artificial sweeteners. Techniques such as wet granulation, wax granulation, spray drying, spray chilling, fluid bed coating, conservation, encapsulation in yeast cells and fiber extrusion may be used to achieve desired release characteristics. Encapsulation of sweetening agents can also be provided.

(57) Usage level of the artificial sweetener will vary considerably and will depend on factors such as potency of the sweetener, rate of release, desired sweetness of the product, level and type of flavor used and cost considerations. Thus, the active level of artificial sweetener may vary from about 0.001 to about 8% by weight (such as from about 0.02 to about 8% by weight). When carriers used for encapsulation are included, the usage level of the encapsulated sweetener will be proportionately higher. Combinations of sugar and/or non-sugar sweeteners may be used in the tablet formulation.

(58) A tablet according to the invention may, if desired, include one or more fillers/texturisers including as examples, magnesium, sodium sulphate, ground limestone, silicate compounds such as magnesium and aluminum silicate, kaolin and clay, aluminum oxide, silicium oxide, talc, titanium oxide, mono-, di- and tri-calcium phosphates, cellulose polymers, such as wood or microcrystalline cellulose (MCC), and combinations thereof.

(59) A number of further tablet materials well known within the art may be applied within the scope of the present invention. Such components comprise but are not limited to waxes, fats, softeners, fillers, flavors, antioxidants, emulsifiers, colouring agents, binding agents and acidulants

(60) The granules or some of the granules may for example consist or largely comprise of gum base components and such granules may be manufactured by means of extrusion and under-water pelletizing.

(61) According to the invention it is also possible to produce granules comprising gum base with different average diameters by making granules with one diameter, and subsequently mix the granules with different average diameters in desired proportions.

(62) Although the openings of a die of an extruder device may have cross-sections of any desired shape, e.g. circular, oval, square etc., it is in some embodiments preferred that the die device comprises openings with substantially circular cross-section and diameters in the range of 0.1 to 1.3 mm. A first set of openings can e.g. have a first diameter in the range of 0.07 to 0.7 mm, such as in the range of 0.15 to 0.6 mm, and suitably in the range of 0.2 to 0.5 mm. A second set of openings can have a second diameter larger than said first diameter. The second diameter is conveniently in the range of 0.4 to 1.3 mm, such as in the range of 0.7 to 1.2 mm.

(63) In some embodiments the tablet granulating system further comprises a drying device. Powder sweetener or talk may be added to the granules in a final drying step. The drying device can be a conventional centrifugal dryer or another suitable dryer e.g. a fluid bed dryer. The drying device can, for example, include a mixer. The powder sweetener may in an embodiment be sorbitol, which is mixed to the dried or partially dried granules. Minor amounts of residual moisture on the surface of the granules, e.g. 2% Wt. based on the total weight of the granules, may contribute to the adherence of the sorbitol powder to the surface of the granules. It is possible to use a conventional anti-agglomerating agent as e.g. talc, but sorbitol powder can function as an anti-agglomerating agent, and at the same time serves as sweetener. Although sorbitol is found to be most suitable, other bulk sweeteners based on polyols may also be suitable, e.g. mannitol, xylitol, hexa-resorcinol, maltitol, isomalt, erythriol, and lactitol.

(64) In one embodiment the tablet granulating system according to the invention further comprises one or more sieves adapted for removing granules with an average diameter such as above 1.3 mm. The removal of larger granules improves a subsequent tabletting process.

(65) Examples of gum base components applicable for tablets of the present invention are described in the PCT/DK02/00461 and PCT/DK02/00462, hereby incorporated by reference.

(66) The composition of gum base components, which are admixed with tablet ingredients as defined below, can vary substantially depending on the particular product to be prepared and on the desired masticatory and other sensory characteristics of the final product. However, typical ranges (weight %) of the above gum base components are: elastomer in the range of 1-15% by weight of the tablet, natural and/or synthetic resin in the range of 5-35% by weight of the tablet, and further other gum base components in the range of 5-30% by weight of the tablet.

(67) It is evident, that the overall total amount of these above gum base components must be mutually adjusted in order to fit requirements with respect to tablet content of calcium carbonate, sweetener, flavor, etc.

(68) Granulates of gum base components may be manufactured according to conventional methods or e.g. those described in the PCT/DK02/00461 and PCT/DK02/00462, hereby incorporated by reference.

(69) According to embodiments of the invention, encapsulated flavors or active ingredients may be added to the final blend of raw materials prior to compression.

(70) Different methods of encapsulating flavors or active ingredients, which may both refer to flavors or active ingredients mixed into the raw materials to be compressed into the tablet may e.g. include spray drying, spray cooling, film coating, coascervation, Double emulsion method (Extrusion technology) or prilling.

(71) Materials to be used for the above-mentioned encapsulation methods may e.g. include Gelatine, Wheat protein, Soya protein, Sodium caseinate, Caseine, Gum arabic, Mod. starch, Hydrolyzed starches (maltodextrines), Alginates, Pectin, Carregeenan, Xanthan gum, Locus bean gum, Chitosan, Bees wax, Candelilla wax, Carnauba wax, Hydrogenated vegetable oils, Zein and/or Sucrose.

(72) Preferably, these ingredients should be added subsequent to any significant heating or mixing. In other words, the active ingredients should preferably be added immediately prior to the compression of the final tablet.

(73) In one embodiment, the adding of active ingredients may be cautiously blended with pre-mixed gum base granulates and further ingredients such as the ingredients stipulated by the present claims, immediately prior to the final compression of the tablet.

(74) For those active ingredients listed below, it should be noted that they are optional in the present invention unless specifically stated.

(75) In one embodiment the tablet according to the invention comprises a pharmaceutically, cosmetically or biologically active substance. Examples of such active substances, a comprehensive list of which is found e.g. in WO 00/25598, which is incorporated herein by reference, include drugs, dietary supplements, antiseptic agents, pH adjusting agents, anti-smoking agents and substances for the care or treatment of the oral cavity and the teeth such as hydrogen peroxide and compounds capable of releasing urea during chewing. Examples of useful active substances in the form of antiseptics include salts and derivatives of guanidine and biguanidine (for instance chlorhexidine diacetate) and the following types of substances with limited water-solubility: quaternary ammonium compounds (e.g. ceramine, chloroxylenol, crystal violet, chloramine), aldehydes (e.g. paraformaldehyde), derivatives of dequaline, polynoxyline, phenols (e.g. thymol, p-chlorophenol, cresol), hexachlorophene, salicylic anilide compounds, triclosan, halogenes (iodine, iodophores, chloroamine, dichlorocyanuric acid salts), alcohols (3,4 dichlorobenzyl alcohol, benzyl alcohol, phenoxyethanol, phenylethanol), cf. also Martindale, The Extra Pharmacopoeia, 28th edition, pages 547-578; metal salts, complexes and compounds with limited water-solubility, such as aluminum salts, (for instance aluminum potassium sulphate AlK(SO4)2, 12H2O) and salts, complexes and compounds of boron, barium, strontium, iron, calcium, zinc, (zinc acetate, zinc chloride, zinc gluconate), copper (copper chloride, copper sulphate), lead, silver, magnesium, sodium, potassium, lithium, molybdenum, vanadium should be included; other compositions for the care of mouth and teeth: for instance; salts, complexes and compounds containing fluorine (such as sodium fluoride, sodium monofluorophosphate, aminofluorides, stannous fluoride), phosphates, carbonates and selenium. Further active substances can be found in J. Dent. Res. Vol. 28 No. 2, pages 160-171, 1949.

(76) Examples of active substances in the form of agents adjusting the pH in the oral cavity include: acids, such as adipic acid, succinic acid, fumaric acid, or salts thereof or salts of citric acid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoric acid and glutaric acid and acceptable bases, such as carbonates, hydrogen carbonates, phosphates, sulphates or oxides of sodium, potassium, ammonium, magnesium or calcium, especially magnesium and calcium.

(77) Active ingredients may comprise the below mentioned compounds or derivates thereof but are not limited thereto: Acetaminophen, Acetylsalicylic acid, Buprenorphine, Bromhexin, Celcoxib, Codeine, Diphenhydramin, Diclofenac, Etoricoxib, Ibuprofen, Indometacin, Ketoprofen, Lumiracoxib, Morphine, Naproxen, Oxycodon, Parecoxib, Piroxicam, Pseudoefedrin, Rofecoxib, Tenoxicam, Tramadol, Valdecoxib, Calciumcarbonat, Magaldrate, Disulfiram, Bupropion, Nicotine, Azithromycin, Clarithromycin, Clotrimazole, Erythromycin, Tetracycline, Granisetron, Ondansetron, Prometazin, Tropisetron, Brompheniramine, Ceterizin, leco-Ceterizin, Chlorcyclizine, Chlorpheniramin, Chlorpheniramin, Difenhydramine, Doxylamine, Fenofenadin, Guaifenesin, Loratidin, des-Loratidin, Phenyltoloxamine, Promethazin, Pyridamine, Terfenadin, Troxerutin, Methyldopa, Methylphenidate, Benzalcon. Chloride, Benzeth. Chloride, Cetylpyrid. Chloride, Chlorhexidine, Ecabet-sodium, Haloperidol, Allopurinol, Colchinine, Theophylline, Propanolol, Prednisolone, Prednisone, Fluoride, Urea, Actot, Glibenclamide, Glipizide, Metformin, Miglitol, Repaglinide, Rosiglitazone, Apomorfin, Cialis, Sildenafil, Vardenafil, Diphenoxylate, Simethicone, Cimetidine, Famotidine, Ranitidine, Ratinidine, cetrizin, Loratadine, Aspirin, Benzocaine, Dextrometorphan, Phenylpropanolamine, Pseudoephedrine, Cisapride, Domperidone, Metoclopramide, Acyclovir, Dioctylsulfosucc, Phenolphtalein, Almotriptan, Eletriptan, Ergotamine, Migea, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan, Aluminum salts, Calcium salts, Ferro salts, Ag-salts, Zinc-salts, Amphotericin B, Chlorhexidine, Miconazole, Triamcinolonacetonid, Melatonine, Phenobarbitol, Caffeine, Benzodiazepiner, Hydroxyzine, Meprobamate, Phenothiazine, Buclizine, Brometazine, Cinnarizine, Cyclizine, Difenhydramine, Dimenhydrinate, Buflomedil, Amphetamine, Caffeine, Ephedrine, Orlistat, Phenylephedrine, Phenylpropanolamin, Pseudoephedrine, Sibutramin, Ketoconazole, Nitroglycerin, Nystatin, Progesterone, Testosterone, Vitamin B12, Vitamin C, Vitamin A, Vitamin D, Vitamin E, Pilocarpin, Aluminumaminoacetat, Cimetidine, Esomeprazole, Famotidine, Lansoprazole, Magnesiumoxide, Nizatide and or Ratinidine.

(78) The invention is suitable for increased or accelerated release of active agents selected among the group of dietary supplements, oral and dental compositions, antiseptic agents, pH adjusting agents, anti-smoking agents, sweeteners, flavorings, aroma agents or drugs. Some of those will be described below.

(79) The active agents to be used in connection with the present invention may be any substance desired to be released from the tablet. The active agents, for which a controlled and/or accelerated rate of release is desired, are primarily substances with a limited water-solubility, typically below 10 g/100 ml inclusive of substances which are totally water-insoluble. Examples are medicines, dietary supplements, oral compositions, anti-smoking agents, highly potent sweeteners, pH adjusting agents, flavorings etc.

(80) Other active ingredients are, for instance, paracetamol, benzocaine, cinnarizine, menthol, carvone, caffeine, chlorhexidine-di-acetate, cyclizine hydrochloride, 1,8-cineol, nandrolone, miconazole, mystatine, sodium fluoride, nicotine, cetylpyridinium chloride, other quaternary ammonium compounds, vitamin E, vitamin A, vitamin D, glibenclamide or derivatives thereof, progesterone, acetylsalicylic acid, dimenhydrinate, cyclizine, metronidazole, sodium hydrogen carbonate, the active components from ginkgo, the active components from propolis, the active components from ginseng, methadone, oil of peppermint, salicylamide, hydrocortisone or astemizole.

(81) Examples of active agents in the form of dietary supplements are for instance salts and compounds having the nutritive effect of vitamin B2 (riboflavin), B12, folinic acid, folic acid, niacine, biotine, poorly soluble glycerophosphates, amino acids, the vitamins A, D, E and K, minerals in the form of salts, complexes and compounds containing calcium, phosphorus, magnesium, iron, zinc, copper, iodine, manganese, chromium, selenium, molybdenum, potassium, sodium or cobalt.

(82) Furthermore, reference is made to lists of nutritionists accepted by the authorities in different countries such as for instance US code of Federal Regulations, Title 21, Section 182.5013.182 5997 and 182.8013-182.8997.

(83) Examples of active agents in the form of compounds for the care or treatment of the oral cavity and the teeth are for instance bound hydrogen peroxide and compounds capable of releasing urea during chewing.

(84) Examples of active agents in the form of antiseptics are for instance salts and compounds of guanidine and biguanidine (for instance chlorhexidine diacetate) and the following types of substances with limited water-solubility: quaternary ammonium compounds (for instance ceramine, chloroxylenol, crystal violet, chloramine), aldehydes (for instance paraformaldehyde), compounds of dequaline, polynoxyline, phenols (for instance thymol, para chlorophenol, cresol) hexachlorophene, salicylic anilide compounds, triclosan, halogenes (iodine, iodophores, chloroamine, dichlorocyanuric acid salts), alcohols (3,4 dichlorobenzyl alcohol, benzyl alcohol, phenoxyethanol, phenylethanol), cf. furthermore Martindale, The Extra Pharmacopoeia, 28th edition, pages 547-578; metal salts, complexes and compounds with limited water-solubility, such as aluminum salts, (for instance aluminum potassium sulphate AlK(SO4)2,12H2O) and furthermore salts, complexes and compounds of boron, barium, strontium, iron, calcium, zinc, (zinc acetate, zinc chloride, zinc gluconate), copper (copper chloride, copper sulfate), lead, silver, magnesium, sodium, potassium, lithium, molybdenum, vanadium should be included; other compositions for the care of mouth and teeth: for instance; salts, complexes and compounds containing fluorine (such as sodium fluoride, sodiummonofluorophosphate, amino fluorides, stannous fluoride), phosphates, carbonates and selenium.

(85) Cf. furthermore J. Dent. Res. Vol. 28 No. 2, pages 160-171, 1949, wherein a wide range of tested compounds is mentioned.

(86) Examples of active agents in the form of agents adjusting the pH in the oral cavity include for instance: acceptable acids, such as adipic acid, succinic acid, fumaric acid, or salts thereof or salts of citric acid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoric acid and glutaric acid and acceptable bases, such as carbonates, hydrogen carbonates, phosphates, sulfates or oxides of sodium, potassium, ammonium, magnesium or calcium, especially magnesium and calcium.

(87) Examples of active agents in the form of anti-smoking agents include for instance: nicotine, tobacco powder or silver salts, for instance silver acetate, silver carbonate and silver nitrate.

(88) In a further embodiment, the sucrose fatty acid esters may also be utilized for increased release of sweeteners including for instance the so-called highly potent sweeteners, such as for instance saccharin, cyclamate, aspartame, thaumatin, dihydrocalcones, stevioside, glycyrrhizin or salts or compounds thereof. For increased released of sweetener, the sucrose fatty acids preferable have a content of palmitate of at least 40% such as at least 50%.

(89) Further examples of active agents are medicines of any type.

(90) Examples of active agents in the form of medicines include caffeine, salicylic acid, salicyl amide and related substances (acetylsalicylic acid, choline salicylate, magnesium salicylate, sodium salicylate), paracetamol, salts of pentazocine (pentazocine hydrochloride and pentazocinelactate), buprenorphine hydrochloride, codeine hydrochloride and codeine phosphate, morphine and morphine salts (hydrochloride, sulfate, tartrate), methadone hydrochloride, ketobemidone and salts of ketobemidone (hydrochloride), beta-blockers, (propranolol), calcium antagonists, verapamil hydrochloride, nifedinpine as well as suitable substances and salts thereof mentioned in Pharm. Int., November 85, pages 267-271, Barney H. Hunter and Robert L. Talbert, nitroglycerine, erythrityl tetranitrate, strychnine and salts thereof, lidocaine, tetracaine hydrochloride, etorphine hydrochloride, atropine, insulin, enzymes (for instance papain, trypsin, amyloglucosidase, glucoseoxidase, streptokinase, streptodornase, dextranase, alpha amylase), polypeptides (oxytocin, gonadorelin, (LH.RH), desmopressin acetate (DDAVP), isoxsuprine hydrochloride, ergotamine compounds, chloroquine (phosphate, sulfate), isosorbide, demoxytocin, heparin.

(91) Other active ingredients include beta-lupeol, Letigen®, Sildenafil citrate and derivatives thereof.

(92) Dental products include Carbamide, CPP Caseine Phosphor Peptide; Chlorhexidine, Chlorhexidine di acetate, Chlorhexidine Chloride, Chlorhexidine di gluconate, Hexetedine, Strontium chloride, Potassium Chloride, Sodium bicarbonate, Sodium carbonate, Fluor containing ingredients, Fluorides, Sodium fluoride, Aluminum fluoride.

(93) Ammonium fluoride, Calcium fluoride, Stannous fluoride, Other fluor containing ingredients Ammonium fluorosilicate, Potassium fluorosilicate, Sodium fluorosilicate, Ammonium monofluorphosphate, Calcium monofluorphosphate, Potassium monofluorphosphate, Sodium monofluorphosphate, Octadecentyl Ammonium fluoride, Stearyl Trihydroxyethyl Propylenediamine Dihydrofluoride,

(94) Vitamins include A, B1, B2, B6, B12, Folinic acid, Folic acid, niacin, Pantothenic acid, biotine, C, D, E, K. Minerals include Calcium, phosphor, magnesium, iron, Zinc, Cupper, Iod, Mangan, Crom, Selene, Molybden. Other active ingredients include: Q100, enzymes. Natural drugs including Ginkgo Biloba, ginger, and fish oil.

(95) The invention also relates to use of migraine drugs such as Serotonin antagonists: Sumatriptan, Zolmitriptan, Naratriptan, Rizatriptan, Eletriptan; nausea drugs such as Cyclizin, Cinnarizin, Dimenhydramin, Difenhydrinat; hay fever drugs such as Cetrizin, Loratidin, pain relief drugs such as Buprenorfin, Tramadol, oral disease drugs such as Miconazol, Amphotericin B, Triamcinolonaceton; and the drugs Cisaprid, Domperidon, Metoclopramid. In a preferred embodiment the invention relates to the release of Nicotine and its salts.

(96) The following non-limiting examples illustrate different variations of the present invention. The examples are meant for indicating the inventive concept; hence the mentioned examples should not be understood as exhaustive for the present invention.

(97) FIGS. 1a and 1b illustrates an embodiment of an oral tablet 10 according to an embodiment of the invention. FIG. 1a shows the oral tablet from the side and FIG. 1b shows the tablet from above.

(98) The composition and the way the tablet is or can be made is described elsewhere in the application and details regarding the structure and functioning of this tablet 10 is also indicated and explained further with reference to FIG. 4 and FIG. 5.

(99) FIGS. 2a and 2b illustrates a two-module version of an oral tablet according to an embodiment of the invention. FIG. 2a shows the oral tablet from the side and FIG. 2b shows the tablet from above.

(100) The composition and the way the tablet is made is described elsewhere in the application.

(101) Details regarding the structure and functioning of this tablet 10 is also indicated and explained further with reference to FIGS. 4, 5 and 6.

(102) The intention with this illustration is to give an example of a physical form, which may be applicable within the scope of the invention. The intention is also to illustrate how the term “a module” is understood and applied throughout the description, i.e. that a module is referring to a population of a plurality particles and the particles have been tableted together to form a module. The term module is applied to indicate that one module comprises one population of tableted particles and another module comprises another population of tableted particles. A population of particles in the present context is thus understood to refer to a plurality of particles. A singular particle is thus of course not understood as a module.

(103) Modules are typically, but not necessarily, distinguishable by the human eye, in particular if the applied compounds in the different modules are formed by differently colored population of particles or mixtures of particles.

(104) The oral tablet 20 comprises an upper module 21 and a lower module 22. The modules, here in the shapes of layers, are thus physically distinct and each comprises a population of particles which has been tableted. The population of the different modules, 21 and 22, may typically be different for many purposes. Examples include use for visual conception, for mechanical purposes e.g. providing strength, for medical purposes, and of course also for maximizing the desired effect of non-DC sugar alcohol contained in the tablet.

(105) In a preferred embodiment, most of the applied non-DC sugar alcohol(s) is comprised in the upper module 21 and the lower module 22 is mostly comprised of DC-components, i.e. components such as sugar alcohols, fillers, flavors, colors etc. conventionally used for direct compression. In embodiments of the invention, a first module, here the lower module 22 may be regarded and applied as a support module supporting another module, here the upper module 21. The benefit of this division in the designing of properties is that the module containing the non-DC sugar alcohol particles may comprises substantial amounts of non-DC sugar alcohol particles even in spite of the fact that the modules own mechanical strength is substantially weakened, as the supporting modules structural strength may be designed to ensure that the overall structural strength of the tablet is sufficient to obtain the desired friability and tablet appearance. This multi-modular design approach is of even more interest as the tablets designed according to this principle benefits, in terms of disintegration and dissolving of the tablet matrix or part thereof during mastication of the tablet, from the increased salivation effect obtained from the applied high content of non-DC sugar alcohol particles in the relatively weak module.

(106) FIGS. 3a and 3b illustrates a three-module version of an oral tablet 30 according to an embodiment of the invention. FIG. 3a shows the oral tablet 30 from the side and FIG. 3b shows the tablet from above.

(107) The illustrated tablet 30 comprises an upper module 31, and intermediate module 33 and a lower module 32.

(108) The upper module 31 may, as explained in relation to the upper module of FIGS. 2a and 2b, be formed by a population of particles comprising an effective amount of non-DC sugar alcohol particles. The intermediate layer may comprise further non-DC sugar alcohol particles and or a desired active ingredient.

(109) The lower module 32 may comprise substantial amounts of DC-particles such as sugar alcohol(s), fillers, some binder and other relevant ingredients enabling the lower module 32 to form a structural support for at least the upper module 31.

(110) FIG. 4 illustrates a part 40 of a cross-section of one of the oral tablets in FIG. 1-3. The part of the oral tablet, illustrated in FIG. 4 may thus correspond to a view of a part of the upper layers 21 or 31 or a part of the tablet 1.

(111) Such part 40 of a tablet may within the scope of the invention comprise at least two different types of particles, namely non-DC sugar alcohol particles 41 and DC-particles 42. Preferred but non-limiting non-DC sugar alcohols are non-DC erythritol and non-DC xylitol as these non-DC sugar alcohols have shown effective to obtain the desired effect. The illustrated non-DC particles 41, although indicated on the figures with the same graphical expression may of course comprise non-DC sugar alcohol particles of the same type, but also comprise a mixture of two or more non-DC sugar alcohol particles.

(112) The particles are evenly distributed amongst a plurality of DC particles 42 within the specified module. The DC particles 42, although indicated in the figure as same type particles may include different types of DC sugar alcohol particles, flavor particles, binders, etc. The intention with the figure is to illustrate that the non-DC sugar alcohol particles 41 in practice have to be homogenously distributed amongst the DC particles 42 in the final oral tablet 40. It may not be enough that the non-DC particles and DC particles are mixed homogenously at some stage during the preparation of the tableting process. The homogenous mix should preferably be maintained in the final oral tablet 40 in order to promote the desired effect and to obtain a mechanically stable tablet. A further advantageous effect of the evenly distributed non-DC sugar alcohol particles may be obtained through an advantageous and increased salivation during mastication of a tablet.

(113) The understanding and conception of the evenly distribution of the non-DC sugar alcohol particles in the relevant tablet module may in practical terms be very difficult to define as such definitions are very difficult to monitor and control during the processing of the tablet but it has been possible to establish an industrial scale process, where the mixture containing the substantial amounts of non-DC sugar alcohol(s) may be established all the way through the process into the final tablet. Such process may e.g. be validated by test manufacturing of a sequence of tablets where the variation of the non-DC sugar alcohol content of the manufactured tablets are determined.

(114) It is noted that the non-DC particles 41 forms small sub-areas or sub spaces in the final oral tablet or the relevant module of the final tablet, e.g. the upper modules 21 and 31. These sub-areas are elsewhere in the present application referred to as discrete non-DC areas and may be formed by single non-DC particles or very small groups of these non-DC particles. These discrete non-DC areas are thus intended to be contained within a matrix formed by DC-sugar alcohol particles or other DC-particles.

(115) The non-DC areas, in the present embodiment, the non-DC sugar alcohol particles 41 are thus included in substantial amounts in the tablet and from a mechanical perspective supported and contained by the DC-particles 42 and together forming a matrix which, when chewed, may bring the non-DC sugar alcohol particles 41 into contact with the oral cavity and promote salivation. The promoted salivation, together with relatively weak mechanical structure of the module or tablet comprising the non-DC sugar alcohol particles induces a fast breakup of the tablet and thereby pushes the non-DC particles into contact with the oral cavity in a way which is completely different from compressed tablets made from DC-sugar alcohol particles, such as granulated erythritol or xylitol.

(116) The non-DC areas may thus result in induced saliva generation upon mastication of the tablet and also induce and promote a very fast and pleasant dissolving of the tablet matrix or part thereof when compared to conventional compressed tablets.

(117) Active ingredients may be present as both DC and non-DC particles as long as the active ingredient as such does not interfere significant with other compounds. If the active ingredients are non-DC particles, the amount should be kept low enough to ensure the mechanical stability of the tablet or modules or alternatively compensated by relevant DC-particles or binders. It should be noted that such a compensation should be carefully considered as this compensation may both compromise salivation effect and texture/mouthfeel during mastication.

(118) FIG. 5 illustrates a part of a cross-section of one of the oral tablets in FIG. 1-3. The part of the oral tablet, illustrated in FIG. 5 may thus correspond a view of a part of the upper modules 21 or 31 or the tablet 1.

(119) In terms of components applied, the tablet part illustrated in FIG. 5 may largely correspond to the above-described embodiment of FIG. 4, but now the tablet part comprises larger sized non-DC particles 51 containing in a compression of particles of DC particles 52.

(120) The intention with the present FIG. 5 is merely to indicate that in particular the non-DC sugar alcohol particles may be larger in size than the DC particles and it is also noted in this context that the use of larger sized non-DC sugar alcohol particles may indeed increase the obtained salivation or the desired effect.

(121) FIG. 6 illustrates a particular transition in a tablet 60 with two adjacent modules according to an embodiment of the invention. The presently illustrated part of such tablet may e.g. refer to the transition between the modules 21 and 22 of the tablet 20 as seen in FIG. 2a. The tablet 60 comprises non-DC sugar alcohol particles 61 and DC particles 62 in one module and another module comprising DC particles 63. The understanding of a module is here easily conceivable as the population of non-DC sugar alcohol particles 61 and DC particles 62 forms one module and the population of DC particles 63 forms another module. Often, the compositions of the DC sugar alcohol particles 62 and the DC sugar alcohol particles 63 may be different, depending on the specific circumstances.

(122) In the present context, the tablet comprises particles comprising gum base. Thus, when the particles 42, 52 62, 63 above are described as DC sugar alcohol particles, it is merely for illustrative purposes, and could also comprise e.g. a mixture of DC sugar alcohol particles and particles comprising gum base.

(123) Again, in relation to FIG. 5 and FIG. 6, active ingredients may be present as both DC and non-DC particles as long as the active ingredient as such does not interfere significant with other compounds. If the active ingredients are non-DC particles, the amount should be kept low enough to ensure the mechanical stability of the tablet or modules or alternatively compensated by relevant DC-particles or binders. It should be noted that such a compensation should be carefully considered as this may compensation may both compromise salivation effect and texture/mouthfeel during mastication.

(124) Particles comprising gum base, may also be present both as non-DC and DC particles, although DC-particles comprising gum base are highly preferred over non-DC gum base-containing particles. When applying particles comprising gum base, these particles are preferably but not necessarily included in a supporting module as DC particles 63 e.g. with mixed with sugar alcohol particles 63 as illustrated in FIG. 6.

(125) The above illustrated modules are all designed as layers. It is stressed that other shapes of modules may be applicable within the scope of the invention. Non-limiting examples are modules having a sphere shape, diamond shape, oval shape, cone shape, etc. All the relevant shapes must of course be adapted to fit the tableting process according to known measures within the art.

EXAMPLES

Examples 1-7. Gum Bases

(126) Seven different samples, given samples numbers 101-107, of gum bases are provided in Examples 1-7. The compositions are given in table 1 and the samples were prepared by the following process:

(127) Elastomers and about ⅓ of the resin are mixed at 120° C. together with filler in a pre-heated mixer having horizontally placed Z-shaped arms for mixing. The fillers are talc or non-DC calcium carbonate. The mechanical action of the mixer causes shearing and grinding resulting in softening of the elastomers.

(128) When the elastomers are softened, more resin is slowly added to the elastomer, resin and filler until the mixture becomes homogeneous. The remaining resin is then added to the mixer and mixed for 10-20 minutes. The softeners, i.e. emulsifier, wax and vegetable fat, are then added and mixed for 20-40 minutes until the whole mixture becomes homogeneous.

(129) After a total mixing time of about 45-60 minutes, the mixture is subjected to pelletizing in a standard under water pelletizing (UWP) unit resulting in coherent granules with an average diameter of approximately 1 mm.

(130) The applied polyisobutylene may eg. be Oppanol B12, polyvinyl acetate (PVA) may eg. be Vinnapas B 1.5 sp, VA-VL copolymers (vinyl acetate-vinyl laurate copolymers) may eg. be Vinnapas B 500/20 VL, natural resin may eg. be Staybelite 5E or Piccolyte C85, softener may eg. be hydrogenated vegetable fat such as hydrogenated sunflower oil, Bulk sweetener may eg. be sorbitol, flavor may eg. be menthol crystals. It is stressed that the specifically mentioned components are of course a non-limiting disclosure intended to assist a skilled person in reproducing the present invention.

(131) In case of Example 7 (sample no. 107), the homogeneous mixture is not subjected to pelletizing but merely discharged into a pan and allowed to cool to room temperature.

(132) Then the mixture is added to another mixer having horizontally placed Z-shaped arms for mixing operating at a temperature of about 40° C. Bulk sweetener is added and mixed until a homogenous mass is obtained.

(133) The mass is discharged and cooled by liquid nitrogen before being introduced to a milling device, in which the mass is milled to obtain particulate material that is ready for tableting.

(134) TABLE-US-00001 TABLE 1 Numbers are given in percent by weight of the gum base Gum base Ex. 1 Ex. 2 Ex. 3 Ex. 4 Ex. 5 Ex. 6 Ex. 7 Sample no. 101 102 103 104 105 106 107 Elastomers (butyl 18 21 21 10 10 5 16 rubber and polyisobutylene) Resins (polyvinyl 38 44 44 50 50 55 31 acetate (PVA), VA-VL copolymers and natural resins (ester gums and terpene resins) Softeners (wax, fats, 23 21 21 22 23 20 19 emulsifiers) Filler (talc) 18 11 17 20 14 Filler (Calcium 12 15 carbonate) Bulk sweetener 20 Flavor 3 3 2 3 Total 100 100 100 100 100 100 100

Example 8-22

(135) Preparation of Tablets

(136) Tablets according to Examples 8-22 using the compounds as outlined below in Table 2, Table 3 and Table 4 were prepared as follows:

(137) The compounds of Examples 1-7 are present in the form of particles/granules.

(138) The particulate compounds of Examples 1-7 and further tablet compounds are weighed into the proper amounts according to the exampled compositions of Table 2 to Table 4. In the compositions, the abbreviation “HIS” means high intensity sweetener.

(139) The weighed amounts are then added to a Turbula mixer in a stainless steel container and blended at 50 rpm for 4 minutes and then adding magnesium stearate and blending one additional minute.

(140) The mixtures are then tableted by means of a Piccola RIVA DC-SC-041-2. A Fette 3090i may also be used.

(141) The resulting tablets according to Examples 8-22 are then obtained by tableting with a suitable pressure force.

(142) For each tablet of examples 8-22, the second layer as outlined in Table 2, Table 3 and Table 4 is pressed initially at a first relatively low pressure. The blended composition of the so-called first layer, i.e. compositions of Table 2 to 4 is then fed to the mold and a final two-layer tablet is then compressed at higher pressure than the pressure applied on the first layers, thereby producing final two-layer tablets according to Examples 8-17. It is noted that the final two-layer tablets of the present examples are 2.0 gram tablets and that the first layer of the tablets weighs 0.9 gram and the second layer of the tablets weighs 1.1 gram.

(143) TABLE-US-00002 TABLE 2 Numbers are given in percent by weight of each layer of the tablet Ex8 Ex 9 Ex 10 Ex 11 Ex 12 Raw material (wt %) First layer Non-DC 48 48 50 50 48 Erythritol DC Isomalt 47.75 45.75 43.75 41.75 Sorbitol — — — — 48.75 Flavor 2 2 4 4 2 HIS 0.25 0.25 0.25 0.25 0.25 Magnesium 1 1 1 1 1 Stearate Binder HPC 1 3 1 3 — Raw material (wt %) Second layer Gum base 30 20 10 40 30 sample no. 101 Gum base 10 20 30 0 10 sample no. 102 DC Xylitol 27.50 27.75 — — 54.50 Non-DC Xylitol 27 27 — — — DC Isomalt — — 27.50 27.75 — Non DC Isomalt — — 27 27 — Salivation flavor 0.25 — 0.25 — 0.25 Flavor 4 4 4 4 4 HIS 0.25 0.25 0.25 0.25 0.25 Magnesium 1 1 1 1 1 Stearate Friability % 2.9 1.7 2.76 1.58 0.77

(144) TABLE-US-00003 TABLE 3 Examples with different types of active ingredients. Numbers are given in percent by weight of each layer of the tablet Ex13 Ex 14 Ex 15 Ex 16 Ex 17 Raw material (wt %) First layer Non-DC 48 48 48 48 48 Erythritol DC Isomalt 47.75 47.75 27.75 47.75 47.75 Flavor 2 2 2 2 2 HIS 0.25 0.25 0.25 0.25 0.25 Magnesium 1 1 1 1 1 Stearate Binder HPC 1 1 1 1 1 DC CaCO3 20 Raw material (wt %) Second layer Gum base 20 20 20 20 20 sample no. 101 Gum base 20 20 20 20 20 sample no. 102 DC Xylitol 27.55 22.75 27.75 26.75 27.25 Non-DC Xylitol 27 27 27 27 27 Flavor 4 4 4 4 4 HIS 0.25 0.25 0.25 0.25 0.25 Magnesium 1 1 1 1 1 Stearate Nicotine 0.2 Caffeine 5 Bromhexine 1 Diphenhydramine 0.5

(145) TABLE-US-00004 TABLE 4 Examples with different oral care or nutraceutical embodiments. Numbers are given in percent by weight of each layer of the tablet Ex18 Ex 19 Ex 20 Ex 21 Ex 22 Raw material (wt %) First layer Non-DC 48 48 48 48 48 Erythritol DC Isomalt 47.75 47.75 47.75 47.75 47.75 Flavor 2 2 2 2 2 HIS 0.25 0.25 0.25 0.25 0.25 Magnesium 1 1 1 1 1 Stearate Binder HPC 1 1 1 1 1 Raw material (wt %) Second layer Gum base 20 20 20 20 20 sample no. 101 Gum base 20 20 20 20 20 sample no. 102 DC Xylitol 27.295 27.025 22.188 25.03 24.55 Non-DC Xylitol 27 27 27 27 27 Flavor 4 4 4 4 4 Magnesium 1 1 1 1 1 Stearate HIS 0.25 0.25 0.25 0.25 0.25 Sodium fluoride 0.022 0.022 0.022 0.02 0.023 Zinc acetate 0.433 0.433 0.430 — — Sodium — 0.270 0.270 — — bicarbonate Calcium — — 4.84 2.7 2.702 pyrophosphate Vitamin D3 - — — — — 0.475 CaCO3premix

(146) A specification of relevant compounds applied in the examples explained above are listed below.

(147) HPC: Hydroxy propyl cellulose. Klucel Nutra D from Ashland

(148) Non DC Xylitol: Xivia C from Dupont

(149) Non granulated Sorbitol: Pharm Sorbidex P 16656 from Cargill

(150) Non DC Isomalt: Isomalt GS from Beneo Paltinit

(151) Non DC Mannitol: Pearlitol from Roquette

(152) Non DC Maltitol: Maltisorb. P200 from Roquette

(153) Non DC Erythritol: Zerose 16952 from Cargill

(154) DC Erythritol—Zerose 16966 from Cargill

(155) DC Xylitol—Xylitab 200 from Dupont

(156) DC Isomalt—Isomalt DC 101 from Beneo Paltinit

(157) DC Mannitol—Pearlitol SD200 from Roquette

(158) DC Maltitol—Sweetpearl 300 DC from Roquette

(159) TABLE-US-00005 TABLE 5 Sensory evaluation of examples 8-12. Initial Total sensory Watering effect experience Good/ Suitable mouthfeel 1-5 Acceptable(Acc)/ during 10 minutes 1 low Ex Poor of chewing 5 high 8 Acc. Nice crunchy initial chew. Fast 5 dissolving mint layer. Nice cooling mouthfeel and flavor burst. Ok softness texture. Ok lasting watering effect 9 Good Nice crunchy initial chew. Fast 4 dissolving mint layer. Nice cooling mouthfeel and flavor burst. Soft texture. Long lasting watering effect 10 Acc Nice crunchy fast dissolving 5 mint layer. High flavor burst. Sandy particles over a long chewing period. Soft texture Long lasting watering effect 11 Poor Nice crunchy fast dissolving 3 mint layer. Lower flavor burst. Sandy particles over a long chewing period. A bit hard texture over time Some lasting watering effect 12 Good Soft crunchy initial chew. Fast 4 dissolving mint layer Fast flavor burst and high juiciness. Long lasting watering effect
Evaluation

(160) The tablets of Example 8-12 were evaluated with respect to mouthfeel.

(161) The friability of Examples 8-12 was also measured according to European Pharmacopoeia 9.1, test method 2.9.7. by using a pharmaceutical friability-tester PTF 10E from Pharma Test.

(162) In particular Examples 8 and 12 were mentioned as having a very attractive and nice initial crunch and the tablet polyols was dissolving very fast when masticated. It is noted in this context that the perceived salivation also promoted an initial fast transition of the particles comprising gum base into a coherent residual.

(163) It was also noted that the flavor perception was more fresh even in spite of the fact the applied flavor and amount of flavor was the same in both the inventive Examples and the “conventional” comparative examples (not shown) based on DC-erythritol in the first layer instead of the non-DC erythritol applied in Examples 8-12.

(164) In terms of active ingredients, Examples 13-17 did exhibit an attractive mouthfeel, an attractive taste and the tablet was unexpectedly considered attractive in terms of e.g. buccal delivery of active ingredients, such as nicotine of example 13. Also active ingredients such as the caffeine Example 14 were considered surprisingly pleasant when considering that caffeine is known for its bitter taste.

(165) Overall, the salivation was considered impressive.