Orally disintegrating nicotine tablets with low levels of flavorings

Abstract

An orally disintegrating nicotine tablet for rapid relief of nicotine cravings is disclosed, the tablet comprising nicotine, a disintegrant, and at least one sugar alcohol, and the tablet comprising less than 0.4% by weight of a flavoring. Further orally disintegrating nicotine tablets and oral nicotine tablets are disclosed. 5

Description

[Technical Field]

[0001] The present invention relates to the orally disintegrating nicotine tablet described in the claims. The present invention also relates to the oral nicotine tablet described in the claims. [Background Art]

[0002] Nicotine-releasing tablets applied for the purpose of providing nicotine release in the user's mouth over a specific period of time are well known. In the prior art, great efforts have been made to mimic the nicotine release and oral perception of tobacco when a user smokes, which means that the release profile from nicotine tablets has been thoroughly investigated in the prior art.

[0003] However, it is an established fact that one-to-one mimicry of smoking by means other than tobacco has not yet been achieved.

[0004] Furthermore, the perception of users of nicotine tablets can be improved, for example, because nicotine release is associated with undesirable irritation in the throat, which is a side effect known as nicotine burning sensation or simply burning sensation.

[0005] An example of an orally disintegrating nicotine tablet is known from WO2019 / 110072(A1) of Fertin Pharma A / S, which relates to orally disintegrating tablets that disintegrate within 60 seconds after oral administration. [Summary of the Invention]

[0006] The present invention relates to an orally disintegrating nicotine tablet for rapid relief of nicotine craving, wherein the tablet comprises nicotine, a disintegrant, and at least one sugar alcohol, the present invention relates to the orally disintegrating nicotine tablet, wherein the tablet comprises less than 0.4% by weight of a flavoring agent.

[0007] An advantage of the present invention is that a desirable user experience can be obtained.

[0008] Typically, nicotine-containing tablets may contain a substantial amount of flavoring to mask the taste, both in terms of nicotine and, typically, in terms of the pH adjusters they contain (which may have off-flavors). Therefore, the flavor-induced taste experience often lingers in the mouth for some time after the tablet has disintegrated. The inventors unexpectedly found that many users find this lingering taste undesirable, and that this can be resolved by reducing the amount of flavoring compared to conventionally used amounts while maintaining an acceptable overall user experience.

[0009] Typically, oral release of nicotine can be associated with an undesirable taste and mouthfeel, including local irritation of the mouth and throat, also known as nicotine burning. However, in some embodiments of the present invention, the inventors unexpectedly found that reducing the amount of flavoring in the tablets did not result in a significant increase in nicotine burning sensation.

[0010] A further advantage of the present invention may be that the tablets induce less saliva production. While not theoretically bound, it is thought that less saliva production increases nicotine retention time, thereby promoting oral absorption and limiting nicotine swallowing. Having a low amount of flavoring, or even the absence of flavoring, may promote the reduction in saliva secretion perceived when using the tablets. Reduced saliva secretion may be advantageous, for example, for users who wish to use the tablets individually.

[0011] A further advantage of the present invention may be that a reduction in flavoring may be desirable for users who use the tablet by placing it under the lip, i.e., between the gums and the lip. Such use may be advantageous, for example, with respect to efficient nicotine uptake and a lower nicotine burning sensation. Furthermore, by containing only the requested low amount of flavoring, or by omitting flavoring altogether, it is possible to minimize or even avoid local irritation associated with flavoring.

[0012] It should be further noted that the advantages of the present invention may be a combination of rapid nicotine delivery, promotion of rapid nicotine craving relief, minimization of nicotine burning sensation, and / or minimization of after-effects after tablet use.

[0013] In this context, it should be noted that the term "orally disintegrating nicotine tablet" refers to a nicotine-containing orally disintegrating tablet, also known as nicotine ODT, i.e., a tablet that disintegrates relatively quickly. It should be noted that orally disintegrating tablets, or ODTs, are sometimes also called rapid disintegrating tablets, or FDTs. In embodiments of the present invention, the orally disintegrating nicotine tablet may therefore disintegrate within 90 seconds when administered orally, preferably on the tongue. In embodiments of the present invention, the orally disintegrating nicotine tablet may therefore disintegrate within 90 seconds when administered orally, preferably under the tongue (sublingually). In embodiments of the present invention, the orally disintegrating nicotine tablet may therefore disintegrate within 5 minutes of oral administration, for example, within 4 minutes of oral administration, or for example, within 3 minutes of oral administration, when preferably administered between the gums and lips. In embodiments of the present invention, the orally disintegrating nicotine tablet may disintegrate within 60 seconds in vitro, preferably when the in vitro disintegration time is measured according to European Pharmacopoeia 9.0, section 2.9.1, Disintegration of tablets and capsules.

[0014] According to embodiments of the present invention, the in vivo disintegration time is measured by at least six trained evaluators, who refrain from eating or drinking for at least 30 minutes prior to the start of any test, the tablet is weighed, placed on the tongue in the mouth, and the in vivo disintegration time is recorded as the point at which the tablet has substantially completed disintegration. During the test, the evaluators refrain from chewing and do not substantially move the tablet from its initial position. While the in vivo disintegration time is tested by placing the tablet on the tongue as described above, it should be noted that in some embodiments, the tablet may be intended as a sublingual tablet, i.e., for use below the tongue. Also, in some embodiments, the tablet may be intended for use between the gums and lips. It should be noted that using the tablet between the gums and lips results in a longer disintegration time.

[0015] In embodiments of the present invention, for example, trained evaluators for in vivo measurement of disintegration time may be selected as described below. The trained evaluators are selected based on the following criteria: First, individuals chew a buffer-free chewing gum base for 1 minute, and then the initial pH in each individual's saliva sample is measured using a suitable pH electrode system, e.g., a stainless steel electrode PHW77-SS. Only individuals whose initial saliva pH is within the range of 6.7 to 7.3 after chewing a buffer-free chewing gum base for 1 minute are selected. This qualifies these individuals as evaluators. A single dose of the tablet is administered on the tongue to at least six evaluators. The disintegration time is then evaluated by the six evaluators. Each evaluator evaluates each sample twice. Thus, each parameter evaluation is the arithmetic mean of 12 evaluations performed on the sample from the six evaluators. During the test, evaluators refrained from chewing and did not substantially move the tablet from its initial position.

[0016] According to an advantageous embodiment of the present invention, the tablet contains 0.3% by weight or less of a flavoring agent, for example, 0.2% by weight or less of a flavoring agent, for example, 0.1% by weight or less of a flavoring agent, or no flavoring agent at all.

[0017] In embodiments of the present invention, the tablets contain 0% to less than 0.4% by weight of flavoring, for example, 0.01% to 0.3% by weight of flavoring, for example, 0.05% to 0.2% by weight of flavoring, for example, 0.05% to 0.1% by weight of flavoring, or for example, no flavoring at all.

[0018] In embodiments of the present invention, one or more flavorings include peppermint, menthol, almond, almond amaretto, apple, bavarian cream, black cherry, black sesame, blueberry, brown sugar, bubble gum, butterscotch, cappuccino, caramel, caramel cappuccino, cheesecake (graham crust), cinnamon red hot, cotton candy, circus cotton candy, clove, coconut, coffee, clear coffee, double chocolate, energy cow, graham cracker, grape juice, green apple, Hawaiian punch, honey, Jamaican rum, Kentucky bourbon, kiwi, koolada, lemon, lemon lime, tobacco, maple syrup, maraschino cherry, marshmallow, menthol, milk chocolate, mocha, and Mountain Dew. Dew, peanut butter, pecan, peppermint, raspberry, banana, ripe banana, root beer, RY 4, spearmint, strawberry, sweet cream, sweet tart, sweetener, toasted almond, tobacco, tobacco blend, vanilla bean ice cream, vanilla cupcake, vanilla swirl Choose from swirl, vanillin, waffle, Belgian waffle, watermelon, whipped cream, white chocolate, wintergreen, amaretto, banana cream, black walnut, blackberry, butter, butter rum, cherry, chocolate hazelnut, cinnamon roll, cola, crème de mento, eggnog, English toffee, guava, lemonade, licorice, maple, mint chocolate chip, orange cream, peach, piña colada, pineapple, plum, pomegranate, praline and cream, red licorice, saltwater toffee, strawberry banana, strawberry kiwi, tropical punch, tutti frutti, vanilla, or any combination thereof.

[0019] According to embodiments of the present invention, the flavoring agent includes menthol.

[0020] According to an embodiment of the present invention, the flavor comprises a tobacco flavor.

[0021] According to an embodiment of the present invention, the flavor consists of menthol and / or tobacco flavor.

[0022] According to an embodiment of the present invention, the flavor consists of menthol.

[0023] According to an embodiment of the present invention, the flavor consists of tobacco flavor.

[0024] According to an advantageous embodiment of the present invention, the tablet comprises a liquid flavor.

[0025] According to an advantageous embodiment of the present invention, the tablet comprises less than 0.4% by weight of liquid flavor, for example, 0.3% by weight or less of liquid flavor, for example, 0.2% by weight or less of liquid flavor, for example, 0.1% by weight or less of liquid flavor, for example, contains no liquid flavor.

[0026] In an embodiment of the present invention, the tablet comprises from 0% by weight to less than 0.4% by weight of liquid flavor, for example, from 0.01% by weight to 0.3% by weight of liquid flavor, for example, from 0.05% by weight to 0.2% by weight of liquid flavor, for example, from 0.05% by weight to 0.1% by weight of liquid flavor.

[0027] According to an advantageous embodiment of the present invention, the tablet comprises a powdered flavor.

[0028] According to an advantageous embodiment of the present invention, the tablet comprises less than 0.4% by weight of powdered flavor, for example, 0.3% by weight or less of powdered flavor, for example, 0.2% by weight or less of powdered flavor, for example, 0.1% by weight or less of powdered flavor, for example, contains no powdered flavor.

[0029] In an embodiment of the present invention, the tablet comprises 0 wt% to less than 0.4 wt% of a powdered flavoring agent, for example, 0.01 wt% to 0.3 wt% of the powdered flavoring agent, for example, 0.05 wt% to 0.2 wt% of the powdered flavoring agent, for example, 0.05 wt% to 0.1 wt% of the powdered flavoring agent.

[0030] According to an embodiment of the present invention, the tablet comprises a powdered flavoring agent and a liquid flavoring agent.

[0031] According to an advantageous embodiment of the present invention, the tablet comprises no flavoring agent.

[0032] According to an embodiment of the present invention, the tablet comprises no liquid flavoring agent.

[0033] According to an embodiment of the present invention, the tablet comprises no powdered flavoring agent.

[0034] According to an advantageous embodiment of the present invention, the tablet comprises less than 0.4 wt% of a high-intensity sweetener, for example, 0.2 wt% or less of the high-intensity sweetener, for example, 0.1 wt% or less of the high-intensity sweetener, for example, comprises no high-intensity sweetener.

[0035] In an embodiment of the present invention, the tablet comprises 0 wt% to less than 0.4 wt% of a high-intensity sweetener, for example, 0.01 wt% to 0.2 wt% of the high-intensity sweetener, for example, 0.05 wt% to 0.1 wt% of the high-intensity sweetener.

[0036] According to an embodiment of the present invention, the high-intensity sweetener is selected from the group consisting of sucralose, aspartame, acesulfame salts such as acesulfame potassium, alitame, saccharin and salts thereof, cyclamic acid and salts thereof, glycyrrhizin, dihydrochalcone, thaumatin, monellin, stevioside, and any combination thereof.

[0037] According to an advantageous embodiment of the present invention, the tablet comprises no high-intensity sweetener.

[0038] According to an advantageous embodiment of the present invention, the tablets do not contain flavorings or high-intensity sweeteners.

[0039] In embodiments of the present invention, the sugar alcohol is a solid sugar alcohol at 25°C.

[0040] Solid sugar alcohols possess desirable compressibility, and therefore, the use of solid sugar alcohols is desirable when forming compressible tablets.

[0041] Sugar alcohols are sometimes called polyols, and it should be noted that they are different from sugars.

[0042] According to embodiments of the present invention, the sugar alcohol is selected from sugar alcohols containing at least four carbon atoms, for example, 4 to 16 carbon atoms, for example, 5 to 12 carbon atoms.

[0043] In embodiments of the present invention, the tablets do not contain sugar alcohols containing three or fewer carbon atoms. Examples of sugar alcohols containing three or fewer carbon atoms include glycerol, propylene glycol, and ethylene glycol.

[0044] In this embodiment, the nicotine tablet does not contain glycerol.

[0045] According to an advantageous embodiment of the present invention, the tablet contains at least one sugar alcohol in an amount of at least 40% by weight of the tablet, for example, at least 50% by weight of the tablet, for example, at least 60% by weight of the tablet, for example, at least 70% by weight of the tablet, for example, at least 80% by weight of the tablet.

[0046] In embodiments of the present invention, the tablet contains at least one sugar alcohol in an amount of 40-95% by weight of the tablet, for example, 50-95% by weight of the tablet, for example, 60-90% by weight of the tablet, for example, 70-90% by weight of the tablet, for example, 80-90% by weight of the tablet.

[0047] According to an advantageous embodiment of the present invention, at least one sugar alcohol is selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof.

[0048] Therefore, in the above embodiment, at least one sugar alcohol may include a mixture of different types of sugar alcohols.

[0049] In embodiments of the present invention, at least one sugar alcohol is selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof.

[0050] In embodiments of the present invention, at least one sugar alcohol is selected from the group consisting of xylitol, maltitol, mannitol, isomalt, sorbitol, and any combination thereof.

[0051] In embodiments of the present invention, at least one sugar alcohol is selected from the group consisting of xylitol, mannitol, isomalt, sorbitol, and any combination thereof.

[0052] In embodiments of the present invention, at least one sugar alcohol is selected from the group consisting of mannitol, isomalt, sorbitol, and any combination thereof.

[0053] In embodiments of the present invention, at least one sugar alcohol comprises or consists of mannitol.

[0054] In embodiments of the present invention, at least one sugar alcohol comprises or consists of isomalt.

[0055] In embodiments of the present invention, at least one sugar alcohol comprises or consists of sorbitol.

[0056] In embodiments of the present invention, the tablet contains at least one sugar alcohol selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof, in an amount of at least 40% by weight of the tablet, for example, at least 50% by weight of the tablet, for example, at least 60% by weight of the tablet, for example, at least 70% by weight of the tablet, for example, at least 80% by weight of the tablet.

[0057] According to the above embodiment, the tablet may further contain sugar alcohols not selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof.

[0058] According to an advantageous embodiment of the present invention, the tablet contains the disintegrant in an amount of at least 0.5% by weight of the tablet, for example, at least 1% by weight of the tablet, for example, at least 2% by weight of the tablet, for example, at least 3% by weight of the tablet, for example, at least 5% by weight of the tablet.

[0059] According to embodiments of the present invention, the tablet contains a disintegrant in an amount of 0.5 to 15% by weight of the tablet, for example, 1 to 15% by weight of the tablet, for example, 2 to 14% by weight of the tablet, for example, 3 to 12% by weight of the tablet, for example, 5 to 10% by weight of the tablet.

[0060] According to an advantageous embodiment of the present invention, the disintegrant is selected from a list consisting of starch, pregelatinized starch, modified cellulose, ion exchange resin, calcium silicate, crosslinked cellulose, crosslinked polyvinylpyrrolidone, crosslinked starch, crosslinked alginate, and combinations thereof.

[0061] In this context, the terms "cross-linked alginate" and "cross-linked alginic acid salt" are used interchangeably.

[0062] According to embodiments of the present invention, the disintegrant is selected from a list consisting of starch, pregelatinized starch, cellulose, modified cellulose, microcrystalline cellulose, ion exchange resin, calcium silicate, crosslinked cellulose, crosslinked polyvinylpyrrolidone, crosslinked starch, crosslinked alginate, and combinations thereof.

[0063] In the context of this invention, starch refers to starches of various origins, such as potato starch, corn starch, wheat starch, and pea starch.

[0064] Examples of pregelatinized starch disintegrants include pregelatinized potato starch, pregelatinized wheat starch, pregelatinized corn starch, Lycatab®, and Starch 1500®, as well as their structures and trademark names.

[0065] Examples of modified cellulose disintegrants include structural names such as methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose.

[0066] According to an advantageous embodiment of the present invention, the disintegrant comprises pregelatinized starch.

[0067] According to embodiments of the present invention, the disintegrant comprises pregelatinized starch.

[0068] Some disintegrants are understood to be called superdisintegrants.

[0069] According to an advantageous embodiment of the present invention, the disintegrant includes a superdisintegrant.

[0070] According to an advantageous embodiment of the present invention, the tablet contains a superdisintegrant in an amount of at least 0.5% by weight of the tablet, for example, at least 1% by weight of the tablet, for example, at least 2% by weight of the tablet, for example, at least 3% by weight of the tablet, for example, at least 5% by weight of the tablet.

[0071] According to embodiments of the present invention, the tablet contains a superdisintegrant in an amount of 0.5 to 15% by weight of the tablet, for example, 1 to 15% by weight of the tablet, for example, 2 to 14% by weight of the tablet, for example, 3 to 12% by weight of the tablet, for example, 5 to 10% by weight of the tablet.

[0072] In some embodiments, the disintegrant may include a combination of a conventional disintegrant and a super-disintegrant.

[0073] In embodiments of the present invention, the disintegrant comprises a superdisintegrant.

[0074] According to an advantageous embodiment of the present invention, the super-disintegrant is selected from the group consisting of cross-linked cellulose, cross-linked polyvinylpyrrolidone, cross-linked starch, cross-linked alginate, and any combination thereof.

[0075] Examples of cross-linked cellulose superdisintegrants include the structures and trade names of cross-linked carboxymethylcellulose sodium, Croscarmellose®, Ac-Di-Sol®, and Solutab®.

[0076] Examples of cross-linked polyvinyl pyrrolidone (PVP) disintegrants include structures and trademark names such as Kollidon®, Polyplasdone®, polyplasdone XL®, and Kollidon CL®. Cross-linked polyvinyl pyrrolidone (PVP) disintegrants are sometimes referred to as crospovidone.

[0077] Examples of cross-linked starch disintegrants include sodium starch glycolate, Glycolys®, Explotab®, Primogel®, Vivastar®, and Tablo®, among others, and their structures and trademark names.

[0078] According to an advantageous embodiment of the present invention, the disintegrant is a superdisintegrant selected from the group consisting of cross-linked cellulose, cross-linked polyvinylpyrrolidone (PVP), cross-linked starch, and any combination thereof.

[0079] According to an advantageous embodiment of the present invention, the disintegrant is a superdisintegrant selected from the group consisting of cross-linked polyvinylpyrrolidone, croscarmellose, sodium starch glycolate, and any combination thereof.

[0080] In embodiments of the present invention, the disintegrant includes cross-linked polyvinylpyrrolidone.

[0081] In embodiments of the present invention, at least 50% by weight of crosslinked polyvinylpyrrolidone has a particle size of less than 50 micrometers, for example, 50 to 100% by weight of crosslinked polyvinylpyrrolidone has a particle size of less than 50 micrometers.

[0082] In embodiments of the present invention, at least 25% by weight of crosslinked polyvinylpyrrolidone has a particle size of less than 15 micrometers, for example, 25 to 100% by weight of crosslinked polyvinylpyrrolidone has a particle size of less than 15 micrometers.

[0083] In embodiments of the present invention, ready-to-use systems can be used. Typically, such ready-to-use systems may replace, for example, fillers, disintegrants, lubricants, or similar substances with a single powder mixture. Suitable ready-to-use systems for this purpose include, but are not limited to, Pearlitol Flash (Roquette), Pharmaburst 500 (SPI Pharma), Ludiflash (BASF), ProSolv (JRS Pharma), ProSolv EasyTab (JRS Pharma), F-Melt (Fuji Chemical), SmartEx50, or SmartEx100 (Shin Etsu / Harke Pharma).

[0084] Therefore, in the embodiments described above, a readily available system may be included, for example, as a convenient method comprising both a sugar alcohol and a disintegrant.

[0085] According to an advantageous embodiment of the present invention, the tablet is a compressed tablet.

[0086] Therefore, in the above embodiment, the tablet is a compressed orally disintegrating nicotine tablet, also known as compressed nicotine ODT.

[0087] According to an advantageous embodiment of the present invention, the tablet is composed of a plurality of compressed particles.

[0088] According to an advantageous embodiment of the present invention, the tablet is compressed using a compressive force of 1 to 35 kN, for example, 2 to 30 kN, for example, 2 to 20 kN.

[0089] According to an advantageous embodiment of the present invention, nicotine is selected from the group consisting of nicotine salts, free nicotine bases, nicotine-ion exchange resin combinations, nicotine inclusion complexes or any non-covalent nicotine, nicotine bound to zeolite, nicotine bound to cellulose, nicotine bound to starch microspheres, and any combination thereof.

[0090] In embodiments of the present invention, nicotine is selected from a list consisting of nicotine free bases and nicotine salts, or combinations thereof. Note that when nicotine free bases and / or nicotine salts are used, it is implied that nicotine is provided without a carrier unless otherwise explicitly specified.

[0091] According to an advantageous embodiment of the present invention, nicotine includes nicotine free base.

[0092] Free base nicotine is a sugar alcohol, modified calcium carbonate, Contains nicotine mixed with water-soluble fibers, non-water-soluble fibers, and combinations thereof.

[0093] In embodiments of the present invention, nicotine is a free nicotine base.

[0094] In embodiments of the present invention, nicotine comprises a nicotine inclusion complex. In embodiments of the present invention, nicotine comprises nicotine bound to an ion exchange resin. In embodiments of the present invention, nicotine comprises nicotine bound to a polarilex resin. As used herein, the term "NPR" refers to nicotine bound to a polarilex resin.

[0095] According to an advantageous embodiment of the present invention, nicotine includes a nicotine salt.

[0096] An advantage of the above embodiment may be that, for example, the rapid dissociation of the nicotine salt may facilitate a rapid reduction of nicotine craving.

[0097] In embodiments of the present invention, nicotine is a nicotine salt.

[0098] According to an advantageous embodiment of the present invention, the nicotine salt is selected from the group consisting of nicotine ascorbate, nicotine aspartate, nicotine benzoate, nicotine monotartrate, nicotine bicarbonate, nicotine chloride, nicotine citrate, nicotine fumarate, nicotine lactate, nicotine mucinate, nicotine laurate, nicotine levulinate, nicotine malate, nicotine perchlorate, nicotine pyruvate, nicotine salicylate, nicotine sorbate, nicotine succinate, nicotine sulfate, and any combination thereof.

[0099] It is understood that nicotine salts may also be provided as hydrated salts or as a combination of hydrated and unhydrated salts.

[0100] Nicotine chloride may be, for example, nicotine hydrochloride and / or nicotine dihydrochloride.

[0101] In embodiments of the present invention, the nicotine salt is selected from a list consisting of nicotine benzoate, nicotine monotartrate, nicotine hydrogen tartrate, nicotine hydrochloride, nicotine dihydrochloride, nicotine lactate, nicotine malate, nicotine pyruvate, nicotine succinate, and combinations thereof.

[0102] According to an advantageous embodiment of the present invention, nicotine includes nicotine bicarbonate.

[0103] The term NBT can be used as an abbreviation to refer to nicotine bitartrate.

[0104] An advantage of the above embodiment may be that, for example, the rapid dissociation of nicotine bitartrate may facilitate a rapid reduction of nicotine craving.

[0105] In embodiments of the present invention, nicotine is nicotine bicarbonate.

[0106] In embodiments of the present invention, the nicotine is provided as an ionic complex with at least one mucosal-adhering, water-soluble anionic polymer.

[0107] In embodiments of the present invention, nicotine includes synthetic nicotine.

[0108] In embodiments of the present invention, nicotine is synthetic nicotine.

[0109] According to an advantageous embodiment of the present invention, the tablet contains at least 0.2 mg, for example, at least 0.5 mg, for example, at least 1.0 mg of nicotine.

[0110] In embodiments of the present invention, the tablets contain an amount of nicotine ranging from 0.2 mg to 12.0 mg, for example, 0.2 mg to 10.0 mg, for example, 0.5 mg to 8.0 mg, for example, 0.5 mg to 6.0 mg, for example, 1.0 mg to 4.0 mg, for example, 1.0 to 3.0 mg, for example, 1.0 to 2.0 mg.

[0111] According to an advantageous embodiment of the present invention, the tablet contains nicotine in an amount of at least 0.2% by weight of the tablet, for example, at least 0.3% by weight of the tablet, for example, at least 0.5% by weight of the tablet.

[0112] In embodiments of the present invention, the tablet contains nicotine in an amount of 0.2 to 5% by weight of the tablet, for example, 0.3 to 3% by weight of the tablet, for example, 0.5 to 2% by weight of the tablet.

[0113] According to an advantageous embodiment of the present invention, the tablet contains a pH adjuster.

[0114] According to an advantageous embodiment of the present invention, the pH adjusting agent is an alkaline pH adjusting agent, for example, an alkaline buffering agent.

[0115] In embodiments of the present invention, the pH adjusting agent does not include an acidic pH adjusting agent.

[0116] In embodiments of the present invention, the pH adjuster is a buffering agent.

[0117] According to an advantageous embodiment of the present invention, the pH adjusting agent includes a pH adjusting agent selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol, amino acids, dialkali hydrogen phosphate, trialkali phosphate, or any combination thereof.

[0118] In embodiments of the present invention, the pH adjusting agent is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol, amino acids, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, or any combination thereof.

[0119] In embodiments of the present invention, the pH adjuster is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol, amino acids, or any combination thereof.

[0120] According to an advantageous embodiment of the present invention, the pH adjusting agent is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, or any combination thereof.

[0121] A combination of carbonate and bicarbonate may be particularly advantageous. Such a combination may be, for example, a sodium carbonate-sodium bicarbonate buffer system, for example, sodium carbonate and sodium bicarbonate in a weight ratio of 5:1 to 1:1, preferably 4.1:1 to 1.5:1.

[0122] According to an advantageous embodiment of the present invention, the pH adjusting agent contains or consists of sodium carbonate.

[0123] An advantage of the above embodiment may be the increased uptake of nicotine in the oral cavity.

[0124] In embodiments of the present invention, the pH adjusting agent is selected from the group consisting of trometamol, amino acids, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, or any combination thereof.

[0125] In embodiments of the present invention, the pH adjusting agent is selected from the group consisting of trometamol, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, or any combination thereof.

[0126] In embodiments of the present invention, the pH adjusting agent includes dialkali hydrogen phosphate and / or trialkali phosphate, for example, disodium phosphate, dipotassium phosphate, trisodium phosphate and / or tripotassium phosphate.

[0127] Since trometamol and phosphate buffer have a desirable relative neutral taste, it may be found that the use of these pH adjusters does not impair the taste and mouthfeel of nicotine tablets.

[0128] In embodiments of the present invention, the pH adjusting agent includes trometamol.

[0129] In embodiments of the present invention, the pH adjusting agent is trometamol.

[0130] In the context of this invention, the term trometamol refers to (tris(hydroxymethyl)aminomethane), and is sometimes also called Tris buffer.

[0131] In embodiments of the present invention, the pH adjusting agent includes an amino acid.

[0132] In embodiments of the present invention, the pH adjusting agent consists of an amino acid.

[0133] According to an advantageous embodiment of the present invention, the tablet contains a pH adjusting agent in an amount of at least 0.2% by weight of the tablet, for example, at least 0.5% by weight of the tablet, for example, at least 1% by weight of the tablet, for example, at least 2% by weight of the tablet.

[0134] In embodiments of the present invention, the tablet contains a pH adjusting agent in an amount of at least 0.2 to 10% by weight of the tablet, for example, at least 0.5 to 8% by weight of the tablet, for example, at least 1 to 6% by weight of the tablet, for example, at least 2 to 4% by weight of the tablet.

[0135] According to an advantageous embodiment of the present invention, the tablet contains a pH adjuster in an amount of up to 2% by weight of the tablet, for example, up to 1.5% by weight of the tablet, for example, up to 1% by weight of the tablet, for example, at least 0.5% by weight of the tablet, for example, up to 0.2% by weight of the tablet, for example, up to 0.1% by weight of the tablet.

[0136] According to an advantageous embodiment of the present invention, the tablets do not contain an effervescent agent.

[0137] The advantage of the above embodiment may be an improved user experience. Often, the inclusion of a foaming agent can lead to a tingling sensation, which can be quite undesirable, especially when the tablet is administered between the gums and lips.

[0138] A further advantage may be that the use of foaming agents can lower the oral pH value below the optimal range for efficient nicotine absorption through the mucous membrane. Therefore, avoiding the use of foaming agents may improve nicotine absorption.

[0139] According to an advantageous embodiment of the present invention, the tablet has a weight of 600 mg or less, for example, 500 mg or less, for example, 400 mg or less, for example, 300 mg or less, for example, 200 mg or less, for example, 150 mg or less, for example, 120 mg or less, for example, 100 mg or less, for example, 50 mg or less.

[0140] In embodiments of the present invention, the tablets have a weight of 25 to 600 mg, for example, 25 to 500 mg, for example, 25 to 400 mg, for example, 25 to 300 mg, for example, 25 to 200 mg, for example, 50 to 150 mg, for example, 70 to 120 mg, for example, about 75 mg or about 100 mg, or for example, 25 to 50 mg.

[0141] According to an advantageous embodiment of the present invention, the tablet is a multilayer tablet comprising a first layer and a second layer.

[0142] According to embodiments of the present invention, the first layer and the second layer are fused by compression.

[0143] According to an advantageous embodiment of the present invention, the tablet is a single-layer tablet.

[0144] In this context, the term "layer" refers to a module of the tablet that constitutes a substantial portion of the tablet, for example, at least 20% by weight of the tablet, for example, at least 30% by weight of the tablet, for example, at least 40% by weight of the tablet.

[0145] In embodiments of the present invention, the tablet is a multilayer tablet. The multilayer tablet may contain three or more layers.

[0146] According to an advantageous embodiment of the present invention, the tablet further comprises a dissolution modifier in an amount of up to 2% by weight of the tablet, for example, up to 1% by weight of the tablet, for example, up to 0.5% by weight of the tablet, for example, up to 0.25% by weight of the tablet, for example, up to 0.1% by weight of the tablet.

[0147] According to an advantageous embodiment of the present invention, the solvent modifier is selected from xanthan gum, guar gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, monovalent alginates, pullulan, tragacanth gum, karaya gum, fenugreek gum, cassia gum, carrageenan, agar, alginic acid and its monovalent salts, and any combination thereof.

[0148] In this context, the terms "monovalent alginate," "monovalent alginate," and "monovalent salt of alginic acid" are used interchangeably. Furthermore, in this context, it should be noted that the solubilizer includes non-crosslinked alginates, while the solubilizer does not include crosslinked alginates.

[0149] An advantage of the above embodiment may be that a small amount of solvent modifier can improve the mouthfeel.

[0150] According to an advantageous embodiment of the present invention, the solvent modifier is selected from the group consisting of xanthan gum, guar gum, and any combination thereof.

[0151] An advantage of the above embodiment may be that a small amount of solvent modifier can improve the mouthfeel.

[0152] In embodiments of the present invention, the dissolution modifier includes xanthan gum.

[0153] In embodiments of the present invention, the dissolution modifier includes guar gum.

[0154] According to an advantageous embodiment of the present invention, the tablets do not contain a dissolution modifier.

[0155] In embodiments of the present invention, the tablets are substantially free of dissolution modifiers, for example, they are free of dissolution modifiers.

[0156] In embodiments of the present invention, the tablets do not contain xanthan gum.

[0157] According to an advantageous embodiment of the present invention, the tablets do not contain a mucosal adhesive.

[0158] Therefore, according to embodiments of the present invention, the tablets are not adhesive tablets, for example, by not containing any mucosal adhesive at all, or by containing only a small amount of mucosal adhesive, for example, 10% by weight or less of the tablet, for example, 5% by weight or less of the tablet, for example, 2% by weight or less of the tablet, for example, 1% by weight or less of the tablet.

[0159] According to an advantageous embodiment of the present invention, the tablet contains a lubricant such as sodium stearyl fumarate (SSF) or magnesium stearate.

[0160] According to an advantageous embodiment of the present invention, the tablet is a non-chewable tablet.

[0161] It should be noted that the tablets in the above embodiments are non-chewable in the sense that they are not intended for chewing.

[0162] The present invention is an orally disintegrating nicotine tablet for rapid relief of nicotine cravings, Regarding tablets comprising nicotine, a disintegrant, and at least one sugar alcohol, The present invention relates to orally disintegrating nicotine tablets having a total amount of flavorings and high-intensity sweeteners of less than 0.8% by weight of the tablet.

[0163] Therefore, according to embodiments of the present invention, the tablet contains a total amount of flavoring and high-intensity sweetener of 0.6% by weight or less of the tablet, for example, 0.4% by weight or less of the tablet, for example, 0.3% by weight or less of the tablet, for example, 0.2% by weight or less of the tablet.

[0164] According to embodiments of the present invention, the tablet contains a total amount of flavoring and high-intensity sweetener in the following proportions: 0 to 0.8% by weight of the tablet, for example, 0.01 to 0.6% by weight of the tablet, for example, 0.05 to 0.4% by weight of the tablet, for example, 0.1 to 0.3% by weight of the tablet, for example, 0.1 to 0.2% by weight of the tablet.

[0165] The present invention provides an orally disintegrating nicotine tablet comprising, as a first module, the orally disintegrating nicotine tablet described in any one of claims 1 to Y, and further comprising a second module, The second module further relates to oral nicotine tablets, which have a different composition compared to the first module.

[0166] Therefore, in this context, it is understood that the second module has a different composition from the first module.

[0167] According to an advantageous embodiment of the present invention, the second module does not include a lozenge module.

[0168] According to an advantageous embodiment of the present invention, the second module comprises at least one sugar alcohol.

[0169] According to an advantageous embodiment of the present invention, the second module includes a dissolution modifier.

[0170] According to an advantageous embodiment of the present invention, the second module contains at least one sugar alcohol in an amount of at least 40% by weight of the second module, for example, at least 50% by weight of the second module, for example, at least 60% by weight of the second module, for example, at least 70% by weight of the second module, for example, at least 80% by weight of the second module.

[0171] In embodiments of the present invention, the second module contains at least one sugar alcohol in an amount of 40-95% by weight of the second module, for example, 50-95% by weight of the second module, for example, 60-90% by weight of the second module, for example, 70-90% by weight of the second module, for example, 80-90% by weight of the second module.

[0172] According to an advantageous embodiment of the present invention, at least one sugar alcohol of the second module is a sugar alcohol selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof.

[0173] According to an advantageous embodiment of the present invention, the second module contains a dissolution modifier in an amount of at least 1% by weight of the second module, for example, at least 2% by weight of the second module, for example, at least 3% by weight of the second module.

[0174] In embodiments of the present invention, the second module contains a dissolution modifier in an amount of 1 to 15% by weight of the second module, for example, 2 to 10% by weight of the second module, for example, 3 to 8% by weight of the second module.

[0175] According to embodiments of the present invention, the dissolution modifier is selected from the group consisting of xanthan gum, guar gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, alginate, pullulan, tragacanth gum, karaya gum, fenugreek gum, cassia gum, carrageenan, agar, alginic acid and its monovalent salts, and any combination thereof.

[0176] According to embodiments of the present invention, the dissolution modifier is selected from the group consisting of xanthan gum, guar gum, and any combination thereof.

[0177] According to an advantageous embodiment of the present invention, the second module contains nicotine.

[0178] According to an advantageous embodiment of the present invention, the second module contains less than 0.4% by weight of flavoring.

[0179] In embodiments of the present invention, the second module contains 0 to 0.4% by weight of a flavoring, for example, 0.05 to 0.4% by weight of a flavoring.

[0180] According to an advantageous embodiment of the present invention, the second module does not contain flavorings.

[0181] According to an advantageous embodiment of the present invention, the tablet is compressed.

[0182] Therefore, in the above embodiment, both the first and second modules are compressed, i.e., the tablet is composed of a plurality of compressed particles.

[0183] In embodiments of the present invention, the first and second modules are layers. Therefore, in these embodiments, the first module is the first layer, and the second module is the second layer. [Modes for carrying out the invention]

[0184] In this specification, "orally disintegrating tablet" refers to a tablet for oral administration that disintegrates in the oral cavity relatively quickly after administration, such as after 60 seconds.

[0185] Orally disintegrating tablets are also called "orally dissolving tablets," and these two terms are used interchangeably herein. Generally, these terms are also referred to by their abbreviation, ODT. Similarly, the terms "rapidly dissolving tablet" and "rapidly disintegrating tablet," as well as the abbreviation FDT, refer herein to orally disintegrating tablets. It should be noted that disintegrating tablets are considered to be fully disintegrable, i.e., to disintegrate completely when administered orally. In some embodiments, disintegrating tablets consist solely of water-soluble substances and are therefore completely water-soluble. In other embodiments, disintegrating tablets contain some amount of water-insoluble composition, as long as it does not prevent the tablet from disintegrating completely. Therefore, it should be understood that disintegrating tablets do not include, for example, chewing gum that does not disintegrate or dissolve completely, nor do they include hard-boiled candy, i.e., tablets based on cooked sugars and / or sugar alcohols that disintegrate only slowly instead of disintegrating.

[0186] As used herein, the term “disintegrate” refers to the transformation of the object into components, fragments, or particles. Disintegration may refer to both in vivo disintegration or in vitro disintegration as defined herein. In vitro measurements are performed in accordance with European Pharmacopoeia 9.0, Section 2.9.1, Tablets and Capsules.

[0187] As used herein, the term “dissolve” refers to the process by which a solid substance enters a solvent (oral saliva) and produces a solution. Unless otherwise stated, “elution” means the complete dissolution of the compound in question.

[0188] As used herein, the term “disintegrant” refers to a component that facilitates the disintegration of a disintegrating tablet when it comes into contact with saliva. Disintegrants usable within the scope of the present invention may include starch, pregelatinized starch, modified starch (including potato starch, corn starch, starch 1500, sodium starch glycolate, and starch derivatives), crosslinked alginates, ion exchange resins, and superdisintegrants, such as crosslinked cellulose (e.g., sodium carboxymethylcellulose), crosslinked polyvinylpyrrolidone (PVP), crosslinked starch, crosslinked alginate, natural superdisintegrants, and calcium silicate. Disintegrants are often considered as means to facilitate the breakdown of a dosage form into smaller fragments upon administration, thereby facilitating the initiation of drug dissolution and final absorption.

[0189] As used herein, the term “nicotine” refers to any form of nicotine, including free base nicotine, nicotine salts, nicotine bound to ion exchange resins, e.g., nicotine polarilex, nicotine bound to zeolites, nicotine bound to cellulose, e.g., microcrystalline cellulose, e.g., of microbial origin, or starch microspheres, nicotine bound to CaCO3, and mixtures thereof. Therefore, when referring to the amount of nicotine, that amount refers to the amount of pure nicotine. Thus, when measuring the concentration of nicotine added as a nicotine salt, what is relevant is the mass of an equivalent amount of pure nicotine, not the mass of the salt. Nicotine also includes nicotine not obtained from tobacco, which is often called synthetic nicotine.

[0190] As used herein, the term “nicotine salt” refers to nicotine in an ionized form electrostatically bonded to a counterion.

[0191] As used herein, the term "NBT" refers to nicotine bicarbonate and its hydrate.

[0192] As used herein, the terms "%" and "percent" refer to weight percentages unless otherwise specified.

[0193] As used herein, the term "pH adjuster" refers to an agent that actively adjusts and regulates the pH value of a solution to which the agent has been added or to which it is to be added. Therefore, pH adjusters may be acids and bases, including acidic buffers and alkaline buffers. On the other hand, pH adjusters do not include substances and compositions that can only affect pH by dilution. Furthermore, pH adjusters do not include, for example, flavoring agents, fillers, etc. In advantageous embodiments of the present invention, the pH adjuster is alkaline.

[0194] As used herein, the term “buffer” is used interchangeably with “buffer solution” and refers to a chemical agent used to obtain a buffer solution. A buffer may include an alkaline buffer, i.e., one used to obtain a buffer solution having an alkaline pH.

[0195] In embodiments of the present invention, the tablet includes a filler. In embodiments of the present invention, the filler is selected from the group consisting of microcrystalline cellulose, magnesium carbonate and calcium carbonate, sodium sulfate, crushed limestone, silicate compounds such as magnesium silicate and aluminum silicate, kaolin and clay, aluminum oxide, silicon oxide, talc, titanium dioxide, monocalcium phosphate, dicalcium phosphate and tricalcium phosphate, cellulose polymers, such as wood, starch polymers, fibers, and combinations thereof.

[0196] In embodiments of the present invention, the tablets contain a bulk sweetener. In embodiments of the present invention, the bulk sweetener contains or consists of a sugar sweetener and / or a sugarless sweetener.

[0197] Bulk sweeteners may often support the flavor profile of the formulation.

[0198] In embodiments of the present invention, sugar sweeteners and sugar-containing components, such as sucrose, dextrose, maltose, saccharose, lactose, sorbose, dextrin, trehalose, D-tagatose, dried invert sugar, fructose, levulose, and galactose, are selected individually or in combination. These sugar sweeteners may also be included as humectants.

[0199] In embodiments of the present invention, the sugarless sweetener is selected from sugar alcohols (sometimes called polyols) such as sorbitol, erythritol, xylitol, maltitol, mannitol, lactitol, and isomalt.

[0200] In embodiments of the present invention, the disintegrant is selected from crospovidone, croscarmellose sodium, and starch glycolate sodium. In embodiments of the present invention, the disintegrant is selected from starch, pregelatinized starch, modified starch (including potato starch, corn starch, starch 1500, starch glycolate sodium, and starch derivatives), ion exchange resins, and superdisintegrants, such as cross-linked cellulose (e.g., carboxymethylcellulose sodium), cross-linked polyvinylpyrrolidone (PVP), cross-linked starch, cross-linked alginic acid, natural superdisintegrants, and calcium silicate, and combinations thereof.

[0201] In embodiments of the present invention, the tablets contain a high-intensity sweetener. In embodiments of the present invention, the high-intensity sweetener is selected from sucralose, aspartam, acesulfame salts such as acesulfame potassium, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, monellin, stevioside, etc., either alone or in combination. In embodiments of the present invention, the tablets do not contain a high-intensity sweetener.

[0202] In embodiments of the present invention, the tablet contains one or more flavorings. In embodiments of the present invention, one or more flavorings include peppermint, menthol, almond, almond amaretto, apple, bavarian cream, black cherry, black sesame, blueberry, brown sugar, bubble gum, butterscotch, cappuccino, caramel, caramel cappuccino, cheesecake (graham crust), cinnamon red hot, cotton candy, circus cotton candy, clove, coconut, coffee, clear coffee, double chocolate, energy cow, graham cracker, grape juice, green apple, Hawaiian punch, honey, Jamaican rum, Kentucky bourbon, kiwi, koolada, lemon, lemon lime, tobacco, maple syrup, maraschino cherry, marshmallow, menthol, milk chocolate, mocha, Mountain Dew, peanut butter, pecan, peppermint, raspberry, banana, ripe banana, root beer, and RY. 4. Spearmint, Strawberry, Sweet Cream, Sweet Tart, Sweetener, Toasted Almond, Tobacco, Tobacco Blend, Vanilla Bean Ice Cream, Vanilla Cupcake, Vanilla Swirl, Vanillin, Waffle, Belgian Waffle, Watermelon, Whipped Cream, White Chocolate, Wintergreen, Amaretto, Banana Cream, Black Walnut, Blackberry, Butter, Butter Rum, Cherry, Chocolate Hazelnut, Cinnamon Roll, Cola, Crème de Menthol, Eggnog, English Toffee, Guava, Lemonade, Licorice, Maple, Mint Chocolate Chip, Orange Cream, Peach, Piña Colada, Pineapple, Plum, Pomegranate, Pralines and Cream, Red Licorice Choose from licorice, saltwater toffee, strawberry banana, strawberry, kiwi, tropical punch, tutti frutti, vanilla, or any combination thereof.

[0203] According to embodiments of the present invention, the flavoring agent may be used to mask the taste of nicotine.

[0204] In embodiments of the present invention, the pH adjuster is a buffer. In embodiments of the present invention, the buffer is sodium carbonate. In embodiments of the present invention, the buffer is selected from alkali metals, ammonium carbonates, such as monocarbonates, bicarbonates and sesquicarbonates, glycerolates, phosphates, glycerophosphates, acetates, glyconates or citrates, Tris buffer, amino acids, and mixtures thereof. Encapsulated buffers such as Effersoda can also be used.

[0205] The buffering agent in the tablet may be used to obtain a desired pH value in the user's saliva.

[0206] In some embodiments, the buffer contains sodium carbonate and sodium bicarbonate in a weight ratio of, for example, 5:1 to 2.5:1, preferably 4.1:1 to 3.5:1.

[0207] A highly preferred buffer according to an advantageous embodiment of the present invention is a sodium carbonate-sodium bicarbonate buffer system.

[0208] In embodiments of the present invention, silicon dioxide is used as a lubricant. Other lubricants available for use in formulations may also be used within the scope of the present invention.

[0209] In embodiments of the present invention, magnesium stearate is used as a lubricant. Other lubricants available for use in formulations may also be used within the scope of the present invention.

[0210] In embodiments of the present invention, ready-to-use systems can be used. Typically, such ready-to-use systems may replace, for example, fillers, disintegrants, lubricants, or similar substances with a single powder mixture. Suitable ready-to-use systems for this purpose include, but are not limited to, Pearlitol Flash (Roquette), Pharmaburst 500 (SPI Pharma), Ludiflash (BASF), ProSolv (JRS Pharma), ProSolv EasyTab (JRS Pharma), F-Melt (Fuji Chemical), SmartEx50, or SmartEx100 (Shin Etsu / Harke Pharma).

[0211] The parameter range can be adjusted to obtain orally disintegrating tablets, such as orally disintegrating tablets that disintegrate within 60 seconds of oral administration on the tongue, or disintegrating tablets that disintegrate within 60 seconds in vitro.

[0212] Firstly, the decay time can be altered by changing the composition. Using components with high water solubility may help to shorten the decay time.

[0213] In particular, by changing the amount and type of disintegrant, the disintegrant may significantly affect the disintegration time, and the disintegration time may be further adjusted. For example, if a tablet with a shorter disintegration time is desired, the content of the disintegrant may be increased, and / or the type of disintegrant may be replaced, at least partially, with a more effective disintegrant. In this respect, super-disintegrants are generally considered to be more effective disintegrants than non-super-disintegrants.

[0214] In addition, the presence of a solubilizer can significantly affect the disintegration time by changing the amount and type of the solubilizer. For example, if a shorter disintegration time is desired, the content of the solubilizer may be reduced (or even eliminated), and / or the type of solubilizer may be replaced, at least partially, with a solubilizer that is ineffective by delaying dissolution.

[0215] Furthermore, reducing the particle size of the disintegrant tends to shorten the disintegration time, likely because it increases the surface area-to-volume ratio.

[0216] Furthermore, the compressive force used in compressing tablets significantly correlates with the resulting hardness, with higher compressive forces typically increasing the hardness of the resulting tablets. Disintegration time may also be affected by adjusting the tablet's hardness, with lower hardness typically resulting in shorter disintegration times. It has been observed that for some compositions, applying the correct compressive force can achieve disintegration times of less than 60 seconds or / or 60 seconds in vivo, while excessively high compressive forces can result in disintegration times exceeding 60 seconds in vivo or in vitro. In this regard, it should be noted that the threshold compressive force may vary considerably depending on other parameters such as the overall composition, the content and type of disintegrant. For example, if disintegration is too slow at a particular setting, a further adjustment may involve replacing the conventional disintegrant with a super-disintegrant, i.e., a super-disintegrant that promotes disintegration in a more efficient manner.

[0217] Increased water solubility may also be facilitated by replacing components with low water solubility with components with higher water solubility. For example, using sugar alcohols as fillers may be very advantageous, insofar as sugar alcohols have higher water solubility than alternative fillers.

[0218] Furthermore, using sugar alcohols with lower compressibility results in a shorter disintegration time. However, if the compressibility is too low, it can impair the mechanical strength of the tablet, potentially leading to undesirable high shatterability and cracking risks.

[0219] Further examples of parameters that can be adjusted to obtain orally disintegrating nicotine tablets include tablet size and shape. Larger tablets result in a longer disintegration time, and therefore a longer release of the tablet's contents, such as nicotine.

[0220] Furthermore, for disc-shaped tablets, increasing the flatness (quantified, for example, by the diameter-to-height ratio) typically increases the disintegration time by increasing the surface area-to-volume ratio. The flatness may be increased as long as the tablet has sufficient mechanical strength.

[0221] Furthermore, changing the cross-sectional profile from a convex to a concave tablet shortens the disintegration time. While this may reduce the mechanical strength of the tablet to some extent, it should be noted that pursuing a concave cross-section, as long as satisfactory results are achieved, can increase disintegration and thus shorten the disintegration time.

[0222] Furthermore, for example, when a binder is used to obtain higher tackiness and mechanical strength of the tablet, the amount of such binder may be reduced to maximize a higher disintegration rate and therefore a shorter disintegration time.

[0223] Furthermore, adding salivary secretion agents to the tablets can promote an increase in saliva volume near the tablets, which in turn supports the dissolution and disintegration of the tablets and reduces the disintegration time. Therefore, sweeteners, especially sugar alcohols, may be advantageous in this respect.

[0224] Furthermore, the type and amount of lubricant, if any, may be adjusted to optimize the decay time. For example, using sodium stearyl fumarate (SSF) typically results in a shorter decay time compared to using magnesium stearate (MgSt).

[0225] Therefore, a wide range of parameters can be adjusted when designing orally disintegrating nicotine tablets that are designed to disintegrate within a desired timeframe, for example, within 60 seconds in vitro, or within 60 seconds of administration on the tongue.

[0226] Typically, a formulation contains components selected from the group consisting of bulk sweeteners, fillers, ready-to-use systems, flavorings, drying binders, disintegrants (hereinafter referred to as super-disintegrants), tableting aids, anti-caking agents, emulsifiers, antioxidants, accelerators, absorption enhancers, buffers, high-intensity sweeteners, colorants, lubricants, lubricants, or any combination thereof. Absorption enhancers may include, for example, pH adjusters such as buffers, and mucosal adhesion agents.

[0227] In embodiments of the present invention, the tablet core is provided with an outer coating.

[0228] In embodiments of the present invention, the outer coating is selected from the group consisting of hard coatings, soft coatings, and edible film coatings, or any combination thereof.

[0229] According to embodiments of the present invention, at least a portion of the nicotine is attached to the drying binder particles.

[0230] According to an embodiment of the present invention, a certain amount of drying binder is used to attach nicotine to a bulk sweetener.

[0231] According to embodiments of the present invention, the disintegrating tablet comprises one or more encapsulation delivery systems.

[0232] According to embodiments of the present invention, the nicotine tablet may function as a first module, and the tablet further comprises modules having different compositions. The further modules may be slow-dissolving lozenge modules. The tablet, of course, does not contain, for example, a chewing gum module that does not dissolve in water. Furthermore, the lozenge is water-soluble in the sense that it disintegrates and its main component dissolves in water. The nicotine tablet according to the above embodiments may, in embodiments, be a compressed tablet formed by compressing at least a first powdered composition and a second powdered composition to obtain the first and second modules, respectively. The tablet may contain some amount of a water-insoluble material, for example, MCC. For example, the tablet may dissolve within a period of at least 2 minutes, for example, at least 3 minutes, for example, at least 4 minutes, for example, at least 5 minutes when administered orally.

[0233] As used herein, the term “lozenge module” refers to a module that imparts lozenge properties, i.e., a module that slowly dissolves or disintegrates in the mouth, thereby slowly releasing its components, such as pH adjusters, flavorings, nicotine, etc., depending on the particular embodiment. For example, a lozenge module may dissolve within a period of at least 2 minutes, e.g., at least 3 minutes, e.g., at least 4 minutes, e.g., at least 5 minutes, when administered orally.

[0234] Therefore, in the context of the present invention, a module in an advantageous embodiment comprises at least 10% by weight of the tablet. In the case of a compressed oral nicotine tablet, the module may therefore comprise a group of compressed particles weighing at least 10% by weight of the tablet. In other words, the module is not intended to refer to individual particles as conventionally understood from the art of tableting. [Examples]

[0235] Example 1: Preparation of single-layer tablets The raw materials are weighed out from the bags or buckets into a separate measuring container.

[0236] All excipients are transferred to a stainless steel or plastic container in the following order, passing through an 800-micrometer sieve. • Half the amount of filler / bulk sweetener • All other excipients except APIs and lubricants (if any) • The remaining half of the filler / bulk sweetener

[0237] These are mixed in a Turbula mixer at 25 RPM for 4-10 minutes. Then, a lubricant, such as magnesium stearate, is added to the mixing container through an 800-micrometer sieve and further mixed at 25 RPM for 1-2 minutes to lubricate the mixture. The filling level of the mixing container is maintained at 40-70% according to a standardized procedure. The lubricated powder blend is then transferred to the hopper of a tablet forming machine.

[0238] Orally disintegrating tablets are manufactured using laboratory-scale machinery, such as a RIVA Piccola two-layer tablet press. The tablet forming machine is operated by adjusting the filling depth and compression force so that the tablet weight and hardness meet acceptable standards. Pre-pressure may be included to avoid capping.

[0239] [Table 1]

[0240] The acceptable criteria for crushability should be met so that the resulting orally disintegrating tablets can be packaged, but in this embodiment, the bulk sweetener and / or filler should have relatively good compressibility and still be rapidly disintegrating.

[0241] The orally disintegrating tablets according to the present invention may contain a coloring agent. According to embodiments of the present invention, the orally disintegrating tablets may contain coloring agents and bleaching agents, such as FD&C type dyes and lakes, fruit and vegetable extracts, titanium dioxide, and combinations thereof.

[0242] Example 2: Preparation of tablets containing the first and second modules. The second module, which has a different composition from the orally disintegrating tablet module, is prepared by pouring about half of the sugar alcohol into a mixing bowl, followed by the other ingredients except the lubricant, and finally the remaining sugar alcohol. The ingredients are turned / mixed using a mixer (Turbula or Duma) at 49 rpm for 4 to 10 minutes.

[0243] Add the lubricant and mix the ingredients further at 49 rpm for 1-2 minutes.

[0244] The composition of the first module, i.e., the orally disintegrating tablet module, is prepared by pouring all components except the lubricant into a mixing bowl. The components are turned / mixed using a mixer (Turbula or Duma) at 49 rpm for 4 to 10 minutes.

[0245] Add the lubricant and mix the ingredients further at 49 rpm for 1-2 minutes.

[0246] The smoothed powder blend is sequentially transferred to the hopper of the tablet forming machine.

[0247] Next, the second module is compressed with a compressive force of approximately 3-8 kN, and then the first module is fused to the second module by compression with a compressive force of approximately 20-30 kN. Unless otherwise specified, the punch used was a 12.00 mm, circular, shallow concave, B-tool.

[0248] The tablets are manufactured using laboratory-scale machinery, such as a RIVA Piccola tablet press. The tablet forming machine is operated by adjusting the filling depth and compression force so that the tablet weight and hardness meet acceptable standards. Pre-pressure may be included to avoid capping.

[0249] Example 3: Tablet composition, single-layer tablet Example 3A: Unless otherwise specified, the tablets were prepared according to Example 1.

[0250] In this embodiment, the following conditions were applied: Punch used: 7.00 mm, circular, shallow concave, B tool. Tablet weight: 100.0 mg.

[0251] [Table 2]

[0252] Preferred high-intensity sweeteners (HIS) may include, for example, sucralose, acesulfame potassium, and mixtures thereof. Other high-intensity sweeteners, such as aspartame, acesulfame salts including acesulfame potassium, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, monellin, and stevioside, either alone or in combination, can also be used within the scope of the present invention.

[0253] In the above examples, a powdered peppermint flavoring was used. A mixture of peppermint and menthol can also be used. Of course, other flavorings described herein may also be used in combination with or in place of menthol and / or peppermint. The flavoring may be liquid, powder, or a combination thereof, i.e., liquid and powder flavorings may be added.

[0254] In the above example, sodium stearyl fumarate is used as a lubricant. Other lubricants such as MgSt (magnesium stearate) may also be used within the scope of this invention.

[0255] Sodium carbonate is used as an alkaline pH adjuster. Further usable alkaline pH adjusters include sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol, amino acids, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, or any combination thereof.

[0256] Example 3B: Unless otherwise specified, the tablets were prepared according to Example 1.

[0257] In this embodiment, the following conditions were applied: Punch used: 7.00 mm, circular, shallow concave, B tool. Tablet weight: 100.0 mg.

[0258] [Table 3]

[0259] The alternative components described for LFT(1) to LFT(4) in Table 2 may also be applicable to LFT(11) to LFT(17).

[0260] Example 3D: Unless otherwise specified, the tablets were prepared according to Example 1.

[0261] In this embodiment, the following conditions were applied: Punch used: 7.00 mm, circular, shallow concave, B tool. Tablet weight: 100.0 mg.

[0262] [Table 4]

[0263] The alternative components described for LFT(1) to LFT(17) in Tables 2-3 may also be applicable to LFT(21) to LFT(24).

[0264] Example 3E: Unless otherwise specified, the tablets were prepared according to Example 1.

[0265] In this embodiment, the following conditions were applied: Punch used: 7.00 mm, circular, shallow concave, B tool. Tablet weight: 100.0 mg.

[0266] [Table 5]

[0267] The alternative components described for LFT(1) to LFT(25) in Tables 2-4 may also be applicable to LFT(31) to LFT(36).

[0268] Example 3F: Unless otherwise specified, the tablets were prepared according to Example 1.

[0269] In this embodiment, the following conditions were applied: Punch used: 7.00 mm, circular, shallow concave, B tool. Tablet weight: 100.0 mg.

[0270] [Table 6]

[0271] The alternative components described for LFT(1) to LFT(36) in Tables 2-5 may also be applicable to LFT(41) to LFT(45).

[0272] Example 3G: Unless otherwise specified, the tablets were prepared according to Example 1.

[0273] In this embodiment, the following conditions were applied: Punch used: 7.00 mm, circular, shallow concave, B tool. Tablet weight: 100.0 mg.

[0274] [Table 7]

[0275] The alternative components described for LFT(1) to LFT(45) in Tables 2-5 may also be applicable to LFT(51) to LFT(55).

[0276] Example 3H: Unless otherwise specified, the tablets were prepared according to Example 1.

[0277] In this example, the following conditions were applied. Punches used: 7.00 mm, round, shallow concave, B tool. Tablet weight: 100.0 mg.

[0278]

Table 8

[0279] Alternative ingredients described for LFT(1) to LFT(55) in Tables 2 to 7 can also be applied to LFT(61) to LFT(67).

[0280] Example 4: Tablet Composition, Bilayer Tablet Example 4A: Tablets were prepared according to Example 2, unless otherwise specified.

[0281] In this example, the following conditions were applied. Punches used: 7.00 mm, round, shallow concave, B tool. Weight of the first layer: 100.0 mg. Weight of the second layer: 300.0 mg. Tablet weight: 400.0 mg

[0282]

Table 9

[0283] Alternative ingredients described for LFT(1) to LFT(67) in Tables 2 to 8 can also be applied to LFT(71) to LFT(75).

[0284] Example 4B: Additional tablets were produced by using any of the tablets of LFT(1) to LFT(67) in Tables 2 to 8 as the first layer and the second layer among LFT(71) to LFT(75).

[0285] Example 5: Evaluation The manufactured tablets of the present invention were evaluated and found to be highly suitable as a nicotine delivery medium in that they provide a favorable release of nicotine while simultaneously providing a pleasant user experience with respect to an acceptable nicotine burning sensation, for example, by resulting in a less pronounced flavor and aftertaste.

[0286] Example 6: Evaluation The comparative orally disintegrating nicotine tablets C(1) and C(2) were evaluated by multiple evaluators. There were 84 evaluators for C(1) and 94 evaluators for C(2).

[0287] For C(1) and C(2), evaluators were asked to indicate whether the flavor intensity during use was too strong or too weak. Table 10 below shows the ratio of the number of evaluators who indicated a flavor intensity that was too strong to the number of evaluators who indicated a flavor intensity that was too weak. In addition, the duration of the flavor and the ratio of the number of evaluators who indicated a flavor duration that was too long to the number of evaluators who indicated a flavor duration that was too short were evaluated.

[0288] [Table 10]

[0289] As can be seen from Table 10, an unexpectedly high percentage of evaluators indicated that the flavor intensity was too high. Similarly, an unexpectedly high percentage of evaluators indicated that the flavor lingered too long.

[0290] Since flavorings are typically included to mask the taste of nicotine, it was completely unexpected that a relatively high percentage of evaluators found the flavor intensity to be too high.

[0291] Similarly, both comparison tablets were evaluated for aftertaste, observing the ratio of the number of evaluators reporting an aftertaste that was too strong to the number of evaluators reporting an aftertaste that was too weak. The duration of the aftertaste was evaluated by the ratio of the number of evaluators reporting an aftertaste that was too long to the number of evaluators reporting an aftertaste that was too short.

[0292] [Table 11]

[0293] As can be seen from Table 11, the evaluation of aftertaste showed an unexpected preference for shorter, less intense aftertastes.

[0294] The unexpected findings in Tables 10-11 indicate that a significant segment of evaluators prefers low amounts of flavorings, or even no flavorings at all, as provided by the orally disintegrating nicotine tablets of the present invention disclosed herein.

Claims

1. Orally disintegrating nicotine tablets for rapid relief of nicotine cravings, The tablet comprises nicotine, a disintegrant, and at least one sugar alcohol. The aforementioned tablet is an orally disintegrating nicotine tablet containing less than 0.4% by weight of a flavoring agent.

2. The orally disintegrating nicotine tablet according to claim 1, wherein the tablet contains 0.3% by weight or less of a flavoring, for example, 0.2% by weight or less of a flavoring, for example, 0.1% by weight or less of a flavoring, or for example, no flavoring.

3. The orally disintegrating nicotine tablet according to claim 1 or 2, wherein the tablet contains a liquid flavoring agent.

4. The orally disintegrating nicotine tablet according to any one of claims 1 to 3, wherein the tablet contains less than 0.4% by weight of a liquid flavoring, for example, 0.3% by weight or less of a liquid flavoring, for example, 0.2% by weight or less of a liquid flavoring, for example, 0.1% by weight or less of a liquid flavoring, or does not contain any liquid flavoring.

5. The orally disintegrating nicotine tablet according to any one of claims 1 to 4, wherein the tablet contains a powdered flavoring.

6. The orally disintegrating nicotine tablet according to any one of claims 1 to 5, wherein the tablet contains less than 0.4% by weight of powdered flavoring, for example, 0.3% by weight or less of powdered flavoring, for example, 0.2% by weight or less of powdered flavoring, for example, 0.1% by weight or less of powdered flavoring, or does not contain any powdered flavoring.

7. The orally disintegrating nicotine tablet according to any one of claims 1 to 6, wherein the tablet does not contain a flavoring agent.

8. The orally disintegrating nicotine tablet according to any one of claims 1 to 7, wherein the tablet contains less than 0.4% by weight of a high-intensity sweetener, for example, contains 0.2% by weight or less of a high-intensity sweetener, for example, contains 0.1% by weight or less of a high-intensity sweetener, or does not contain a high-intensity sweetener.

9. The orally disintegrating nicotine tablet according to any one of claims 1 to 8, wherein the tablet does not contain a high-intensity sweetener.

10. The orally disintegrating nicotine tablet according to any one of claims 1 to 9, wherein the tablet does not contain flavorings and does not contain high-intensity sweeteners.

11. The orally disintegrating nicotine tablet according to any one of claims 1 to 10, wherein the tablet contains the at least one sugar alcohol in an amount of at least 40% by weight of the tablet, for example, at least 50% by weight of the tablet, for example, at least 60% by weight of the tablet, for example, at least 70% by weight of the tablet, for example, at least 80% by weight of the tablet.

12. The orally disintegrating nicotine tablet according to any one of claims 1 to 11, wherein the at least one sugar alcohol comprises a sugar alcohol selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof.

13. An orally disintegrating nicotine tablet according to any one of claims 1 to 12, wherein the tablet contains the disintegrant in an amount of at least 0.5% by weight of the tablet, for example, at least 1% by weight of the tablet, for example, at least 2% by weight of the tablet, for example, at least 3% by weight of the tablet, for example, at least 5% by weight of the tablet.

14. An orally disintegrating nicotine tablet according to any one of claims 1 to 13, wherein the disintegrant is selected from a list consisting of starch, pregelatinized starch, modified cellulose, ion exchange resin, calcium silicate, crosslinked cellulose, crosslinked polyvinylpyrrolidone, crosslinked starch, crosslinked alginate, and combinations thereof.

15. An orally disintegrating nicotine tablet according to any one of claims 1 to 14, wherein the disintegrant comprises pregelatinized starch.

16. The orally disintegrating nicotine tablet according to any one of claims 1 to 15, wherein the disintegrant comprises pregelatinized starch.

17. An orally disintegrating nicotine tablet according to any one of claims 1 to 16, wherein the disintegrant comprises a superdisintegrant.

18. An orally disintegrating nicotine tablet according to any one of claims 1 to 17, wherein the tablet contains a superdisintegrant in an amount of at least 0.5% by weight of the tablet, for example, at least 1% by weight of the tablet, for example, at least 2% by weight of the tablet, for example, at least 3% by weight of the tablet, for example, at least 5% by weight of the tablet.

19. The orally disintegrating nicotine tablet according to any one of claims 1 to 18, wherein the super-disintegrating agent is selected from the group consisting of cross-linked cellulose, cross-linked polyvinylpyrrolidone, cross-linked starch, cross-linked alginate, and any combination thereof.

20. The orally disintegrating nicotine tablet according to any one of claims 1 to 19, wherein the disintegrant is a superdisintegrant selected from the group consisting of cross-linked cellulose, cross-linked polyvinylpyrrolidone (PVP), cross-linked starch, and any combination thereof.

21. The orally disintegrating nicotine tablet according to any one of claims 1 to 18, wherein the disintegrant is a superdisintegrant selected from the group consisting of cross-linked polyvinylpyrrolidone, croscarmellose, sodium starch glycolate, and any combination thereof.

22. The orally disintegrating nicotine tablet according to any one of claims 1 to 21, wherein the tablet is a compressed tablet.

23. The orally disintegrating nicotine tablet according to any one of claims 1 to 22, wherein the tablet is composed of a plurality of compressed particles.

24. The orally disintegrating nicotine tablet according to any one of claims 1 to 23, wherein the tablet is compressed using a compressive force of 1 to 35 kN, for example, 2 to 30 kN, for example, 2 to 20 kN.

25. An orally disintegrating nicotine tablet according to any one of claims 1 to 24, wherein the nicotine is selected from the group consisting of nicotine salts, free nicotine bases, nicotine-ion exchange resin combinations, nicotine inclusion complexes or any non-covalent nicotine, nicotine bound to zeolite, nicotine bound to cellulose, nicotine bound to starch microspheres, and any combination thereof.

26. The orally disintegrating nicotine tablet according to any one of claims 1 to 25, wherein the nicotine comprises a free nicotine base.

27. An orally disintegrating nicotine tablet according to any one of claims 1 to 26, wherein the nicotine comprises a nicotine salt.

28. The orally disintegrating nicotine tablet according to any one of claims 1 to 27, wherein the nicotine salt is selected from the group consisting of nicotine ascorbate, nicotine aspartate, nicotine benzoate, nicotine monotartrate, nicotine bicarbonate, nicotine chloride, nicotine citrate, nicotine fumarate, nicotine lactate, nicotine mucinate, nicotine laurate, nicotine levulinate, nicotine malate, nicotine perchlorate, nicotine pyruvate, nicotine salicylate, nicotine sorbate, nicotine succinate, nicotine sulfate, and any combination thereof.

29. An orally disintegrating nicotine tablet according to any one of claims 1 to 28, wherein the nicotine comprises nicotine bicarbonate.

30. The orally disintegrating nicotine tablet according to any one of claims 1 to 29, wherein the tablet contains nicotine in an amount of at least 0.2 mg, for example, at least 0.5 mg, for example, at least 1.0 mg.

31. The orally disintegrating nicotine tablet according to any one of claims 1 to 30, wherein the tablet contains nicotine in an amount of at least 0.2% by weight of the tablet, for example, at least 0.3% by weight of the tablet, for example, at least 0.5% by weight of the tablet.

32. The orally disintegrating nicotine tablet according to any one of claims 1 to 31, wherein the tablet comprises a pH adjuster.

33. The orally disintegrating nicotine tablet according to any one of claims 1 to 32, wherein the pH adjusting agent is an alkaline pH adjusting agent, for example, an alkaline buffering agent.

34. The orally disintegrating nicotine tablet according to any one of claims 1 to 33, wherein the pH adjusting agent comprises a pH adjusting agent selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol, amino acids, dialkali hydrogen phosphate, trialkali phosphate, or any combination thereof.

35. The orally disintegrating nicotine tablet according to any one of claims 1 to 34, wherein the pH adjusting agent is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, or any combination thereof.

36. The orally disintegrating nicotine tablet according to any one of claims 1 to 35, wherein the pH adjusting agent contains or consists of sodium carbonate.

37. The orally disintegrating nicotine tablet according to any one of claims 1 to 36, wherein the tablet contains the pH adjusting agent in an amount of at least 0.2% by weight of the tablet, for example, at least 0.5% by weight of the tablet, for example, at least 1% by weight of the tablet, for example, at least 2% by weight of the tablet.

38. An orally disintegrating nicotine tablet according to any one of claims 1 to 37, wherein the tablet contains the pH adjusting agent in an amount of up to 2% by weight of the tablet, for example, up to 1.5% by weight of the tablet, for example, up to 1% by weight of the tablet, for example, up to 0.5% by weight of the tablet, for example, up to 0.2% by weight of the tablet, for example, up to 0.1% by weight of the tablet.

39. The orally disintegrating nicotine tablet according to any one of claims 1 to 38, wherein the tablet does not contain a foaming agent.

40. The orally disintegrating nicotine tablet according to any one of claims 1 to 39, wherein the tablet has a weight of 600 mg or less, for example, 500 mg or less, for example, 400 mg or less, for example, 300 mg or less, for example, 200 mg or less, for example, 150 mg or less, for example, 120 mg or less, for example, 100 mg or less, for example, 50 mg or less.

41. The orally disintegrating nicotine tablet according to any one of claims 1 to 40, wherein the tablet is a multilayer tablet comprising a first layer and a second layer.

42. The orally disintegrating nicotine tablet according to any one of claims 1 to 41, wherein the tablet is a single-layer tablet.

43. An orally disintegrating nicotine tablet according to any one of claims 1 to 42, wherein the tablet further contains a dissolution modifier in an amount of up to 2% by weight of the tablet, for example, up to 1% by weight of the tablet, for example, up to 0.5% by weight of the tablet, for example, up to 0.25% by weight of the tablet, for example, up to 0.1% by weight of the tablet.

44. An orally disintegrating nicotine tablet according to any one of claims 1 to 43, wherein the solubilizing agent is selected from xanthan gum, guar gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, alginate, pullulan, tragacanth gum, karaya gum, fenugreek gum, cassia gum, carrageenan, agar, alginic acid and its monovalent salts, and any combination thereof.

45. The orally disintegrating nicotine tablet according to any one of claims 1 to 44, wherein the dissolution modifier is selected from the group consisting of xanthan gum, guar gum, and any combination thereof.

46. The orally disintegrating nicotine tablet according to any one of claims 1 to 45, wherein the tablet does not contain a dissolution modifier.

47. The orally disintegrating nicotine tablet according to any one of claims 1 to 46, wherein the tablet does not contain a mucosal adhesive.

48. The orally disintegrating nicotine tablet according to any one of claims 1 to 47, wherein the tablet contains a lubricant such as sodium stearyl fumarate (SSF) or magnesium stearate.

49. The orally disintegrating nicotine tablet according to any one of claims 1 to 48, wherein the tablet is a non-chewable tablet.

50. Orally disintegrating nicotine tablets for rapid relief of nicotine cravings, The tablet comprises nicotine, a disintegrant, and at least one sugar alcohol. An orally disintegrating nicotine tablet having a total amount of flavoring and a high-intensity sweetener of less than 0.8% by weight of the tablet.

51. The orally disintegrating nicotine tablet according to claim 50, wherein the tablet contains a total amount of flavoring and high-intensity sweetener of 0.6% by weight or less of the tablet, for example, 0.4% by weight or less of the tablet, for example, 0.3% by weight or less of the tablet, for example, 0.2% by weight or less of the tablet.

52. A tablet according to claim 50 or 51 and any one of claims 1 to 49.

53. The first module is an intraoral disintegration according to any one of claims 1 to 52. An oral nicotine tablet comprising a nicotine tablet and further comprising a second module, An oral nicotine tablet wherein the second module has a different composition from the first module.

54. The oral nicotine tablet according to claim 53, wherein the second module is a lozenge module.

55. The oral nicotine tablet according to claim 53 or 54, wherein the second module comprises at least one sugar alcohol.

56. The oral nicotine tablet according to any one of claims 53 to 55, wherein the second module comprises a dissolution modifier.

57. An oral nicotine tablet according to any one of claims 53 to 56, wherein the second module contains the at least one sugar alcohol in an amount of at least 40% by weight of the second module, for example, at least 50% by weight of the second module, for example, at least 60% by weight of the second module, for example, at least 70% by weight of the second module, for example, at least 80% by weight of the second module.

58. The oral nicotine tablet according to any one of claims 53 to 57, wherein the at least one sugar alcohol of the second module comprises a sugar alcohol selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof.

59. The oral nicotine tablet according to any one of claims 53 to 58, wherein the second module contains a dissolving agent in an amount of at least 1% by weight of the second module, for example, at least 2% by weight of the second module, for example, at least 3% by weight of the second module.

60. The oral nicotine tablet according to any one of claims 53 to 59, wherein the second module comprises nicotine.

61. The oral nicotine tablet according to any one of claims 53 to 60, wherein the second module contains less than 0.4% by weight of a flavoring agent.

62. The oral nicotine tablet according to any one of claims 53 to 61, wherein the second module does not contain flavorings.

63. The oral nicotine tablet according to any one of claims 53 to 62, wherein the tablet is compressed.

Images