Orally disintegrating nicotine tablet with low flavoring agent content

Abstract

An orally disintegrating nicotine tablet for alleviating nicotine craving is disclosed, the tablet comprising nicotine, a disintegrant, and at least one sugar alcohol, the tablet comprising less than 0.4% by weight of a flavoring agent. The invention also discloses another orally disintegrating nicotine tablet and an oral nicotine tablet.

Description

Invention Field

[0001] This invention relates to orally disintegrating nicotine tablets according to the claims. Furthermore, this invention relates to oral nicotine tablets according to the claims. Background Technology

[0002] Nicotine sustained-release tablets, which deliver nicotine to a user's mouth over a period of time, are well-known. Existing technologies have invested considerable effort in simulating the nicotine release and oral sensation experienced when a user smokes, meaning that the release characteristics of nicotine tablets have been extensively studied.

[0003] However, it is an undeniable fact that currently, apart from cigarettes, there is no other means to completely simulate smoking.

[0004] In addition, users may experience improved perception of nicotine tablets, for example, because the release of nicotine is accompanied by an unpleasant irritation to the throat, a side effect known as nicotine burning, or simply burning sensation.

[0005] Fertin Pharma A / S’ PCT application WO 2019 / 110072 A1 relates to an example of an orally disintegrating nicotine tablet that disintegrates within 60 seconds after oral administration. Invention Overview

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

[0007] One advantage of this invention is that it can achieve an ideal user experience.

[0008] Typically, nicotine tablets contain a large amount of flavoring agents to mask the taste of nicotine, as well as the taste of the pH adjusters (which may have an off-putting odor). Therefore, after the tablet disintegrates, the flavoring agent's taste often lingers in the mouth for a period of time. The inventors unexpectedly discovered that many users find this persistent taste unpleasant, and this can be addressed by reducing the amount of flavoring agent to below the usual dosage while maintaining an acceptable overall user experience.

[0009] Typically, oral release of nicotine can be accompanied by unpleasant taste and mouthfeel, including local irritation in the mouth and throat, also known as a nicotine burn. However, in some embodiments of the present invention, the inventors unexpectedly discovered that reducing the amount of flavoring agent in the tablets does not significantly increase the nicotine burn.

[0010] Another advantage of this invention is that the tablet induces less saliva production. Without being strictly bound by theory, it is believed that reduced saliva production facilitates buccal absorption due to prolonged nicotine retention and limits nicotine swallowing. Therefore, tablets with minimal or no flavoring help reduce the saliva production experienced when using the tablet. This reduced saliva production may be an advantage for users who, for example, wish to use the tablet discreetly.

[0011] Another advantage of this invention is that reducing the amount of flavoring may be ideal for users who place the tablets under their lips (i.e., between the gums and lips). This usage can be advantageous, for example, in terms of efficient nicotine absorption and reduced nicotine burning sensation. Furthermore, by adding only a small amount or no flavoring at all, local irritation associated with flavoring can be minimized or even avoided.

[0012] It is also noted that one advantage of the present invention is the combination of: rapid delivery of nicotine, promoting rapid relief of nicotine cravings, minimizing nicotine burning sensation, and / or minimizing aftertaste of the tablet.

[0013] It should be noted that in this context, "orally disintegrating nicotine tablet" refers to an orally disintegrating tablet containing nicotine, also known as nicotine ODT, which is a tablet that disintegrates relatively quickly. It should also be noted that orally disintegrating tablets or ODTs are sometimes referred to as fast disintegrating tablets or FDTs. In embodiments of the invention, the orally disintegrating nicotine tablet can therefore disintegrate within 90 seconds after oral administration, preferably applied to the tongue. In embodiments of the invention, the orally disintegrating nicotine tablet can therefore disintegrate within 90 seconds after oral administration, preferably applied sublingually. In embodiments of the invention, the orally disintegrating nicotine tablet can therefore disintegrate within 5 minutes, for example within 4 minutes, or for example within 3 minutes after oral administration, preferably applied between the gums and lip. In embodiments of the present invention, the orally disintegrating nicotine tablets disintegrate within 60 seconds in vitro, preferably as measured according to section 2.9.1 of the European Pharmacopeia 9.0, "Disintegration of tablets and capsules".

[0014] According to an embodiment of the invention, the in vivo disintegration time is measured by at least six trained evaluators who have fasted and abstained from water for at least 30 minutes prior to starting any test. The tablet is weighed and placed in the mouth on the tongue, and the time at which the tablet has substantially disintegrated is recorded as the in vivo disintegration time. During the test, the evaluators refrain from chewing or allowing the tablet to move significantly out of its initial position. It is noteworthy that although the in vivo disintegration time is tested as described above by placing the tablet on the tongue, in some embodiments the tablet may be intended as a sublingual tablet, i.e., placed under the tongue. Furthermore, in some embodiments, the tablet may be intended for use between the gums and lips. It is noteworthy that using the tablet between the gums and lips results in a longer disintegration time.

[0015] In embodiments of the invention, trained evaluators (e.g., for in vivo disintegration time measurement) are selected as follows. Trained evaluators are selected based on the following criteria. First, the subject chews a gum base without buffer for 1 minute, and then the initial pH of each subject's saliva sample is measured using a suitable pH electrode system (e.g., stainless steel electrode PHW77-SS). Only subjects whose initial saliva pH is in the range of 6.7 to 7.3 after chewing the gum base without buffer for 1 minute are selected. These subjects are therefore qualified evaluators. At least six evaluators apply one dose of the tablet to the tongue. Subsequently, the disintegration time is evaluated by these six evaluators. Each evaluator evaluates each sample twice. Therefore, the evaluation result for each parameter is the arithmetic mean of 12 evaluations performed on the samples by the six evaluators. During the test, the evaluators refrain from chewing or allowing the tablet to move significantly away from its initial position.

[0016] According to an advantageous embodiment of the invention, the tablet contains no more than 0.3% by weight of flavoring agent, for example no more than 0.2% by weight of flavoring agent, for example no more than 0.1% by weight of flavoring agent, for example no flavoring agent, or no flavoring agent.

[0017] In an embodiment of the invention, the tablet contains 0% to less than 0.4% by weight of flavoring agent, such as 0.01% to 0.3% by weight of flavoring agent, such as 0.05% to 0.2% by weight of flavoring agent, such as 0.05% to 0.1% by weight of flavoring agent, or contains no flavoring agent.

[0018] In embodiments of the present invention, one or more flavoring agents are selected from: peppermint, menthol, almond, almond amaretto, apple, Bavarian cream, black cherry, black sesame seed, blueberry, brown sugar, bubble gum, butterscotch, cappuccino, caramel, caramel cappuccino, cheesecake (graham crust), cinnamon redhots, 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. rum), Kentucky bourbon, kiwi, koolada, lemon, lemon lime, maple syrup, maraschino cherry, marshmallow, milk chocolate, mocha, Mountain Dew, peanut butter, pecan, mint, raspberry, banana, ripe banana, root beer, RY 4, spearmint, strawberry, sweet cream, sweet tarts, sweetener, roasted almonds, tobacco, tobacco blend, vanilla bean ice cream, vanilla cupcake, vanilla swirl Swirl), vanillin, waffles, Belgian waffles, watermelon, whipped cream, white chocolate, wintergreen, amaretto(Almond liqueur), Banana acream, Black walnut, Blackberry, Butter rum, Cherry, Chocolate hazelnut, Cinnamon roll, Cola, Creme de Menthe, Eggnog, English toffee, Guava, Lemonade, Licorice, Maple syrup, Mint chocolate chip, Orange cream, Peach, Pina colada (Puerto Rican sweet cocktail), Pineapple, Plum, Pomegranate, Pralines and cream, Red licorice, Salt water taffy, Strawberry banana, Strawberry kiwi, Tropical punch, Tutti frutti Mixed fruits, vanilla, or any combination thereof.

[0019] According to an embodiment of the present invention, the flavoring agent contains menthol.

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

[0021] According to embodiments of the present invention, the flavoring agent consists of menthol and / or tobacco flavoring agent.

[0022] According to an embodiment of the present invention, the flavoring agent is composed of menthol.

[0023] According to an embodiment of the present invention, the flavoring agent is composed of tobacco flavoring agent.

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

[0025] According to an embodiment of the present invention, the tablet contains less than 0.4% by weight of liquid flavoring, for example, no more than 0.3% by weight of liquid flavoring, for example, no more than 0.2% by weight of liquid flavoring, for example, no more than 0.1% by weight of liquid flavoring, for example, without liquid flavoring.

[0026] In an embodiment of the invention, the tablet contains 0% to less than 0.4% by weight of liquid flavoring, such as 0.01% to 0.3% by weight of liquid flavoring, such as 0.05% to 0.2% by weight of liquid flavoring, such as 0.05% to 0.1% by weight of liquid flavoring.

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

[0028] According to an embodiment of the present invention, the tablet contains less than 0.4% by weight of powdered flavoring agent, for example, no more than 0.3% by weight of powdered flavoring agent, for example, no more than 0.2% by weight of powdered flavoring agent, for example, no more than 0.1% by weight of powdered flavoring agent, for example, without powdered flavoring agent.

[0029] In an embodiment of the invention, the tablet contains 0% to less than 0.4% by weight of a powdered flavoring agent, such as 0.01% to 0.3% by weight of a powdered flavoring agent, such as 0.05% to 0.2% by weight of a powdered flavoring agent, such as 0.05% to 0.1% by weight of a 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 invention, the tablets are free of flavoring agents.

[0032] According to an embodiment of the present invention, the tablet does not contain liquid flavoring.

[0033] According to an embodiment of the present invention, the tablet does not contain powdered flavoring agents.

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

[0035] In an embodiment of the invention, the tablet contains 0% to less than 0.4% by weight of a high-intensity sweetener, such as 0.01% to 0.2% by weight of a high-intensity sweetener, such as 0.05% to 0.1% by weight of a high-intensity sweetener.

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

[0037] According to an advantageous embodiment of the invention, the tablet does not contain a high-intensity sweetener.

[0038] According to an advantageous embodiment of the invention, the tablets are free of flavoring agents and high-intensity sweeteners.

[0039] In an embodiment of the present invention, the sugar alcohol is a solid sugar alcohol at 25 degrees Celsius.

[0040] Solid sugar alcohols have satisfactory compressibility; therefore, it is preferable to use solid sugar alcohols when forming tablets.

[0041] It is worth noting that sugar alcohols (sometimes also called polyols) are different from sugars.

[0042] According to an embodiment of the present invention, the sugar alcohol is selected from sugar alcohols containing at least 4 carbon atoms (e.g., 4 to 16 carbon atoms, e.g., 5 to 12 carbon atoms).

[0043] In embodiments of the present invention, the tablets do not contain sugar alcohols with no more than three carbon atoms. Examples of sugar alcohols with no more than three carbon atoms include glycerol, propylene glycol, and ethylene glycol.

[0044] In one embodiment, the nicotine tablets do not contain glycerin.

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

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

[0047] According to an advantageous embodiment of the invention, the at least one sugar alcohol includes sugar alcohols selected from xylitol, maltitol, mannitol, erythritol, isomaltitol, sorbitol, lactitol, and any combination thereof.

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

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

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

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

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

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

[0054] In embodiments of the present invention, the at least one sugar alcohol comprises or is composed of isomaltose.

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

[0056] In embodiments of the present invention, the tablet comprises at least one sugar alcohol selected from xylitol, maltitol, mannitol, erythritol, isomaltitol, sorbitol, lactitol, and any combination thereof, wherein the amount of the sugar alcohol is at least 40% of the tablet weight, for example at least 50%, at least 60%, at least 70%, or at least 80% of the tablet weight.

[0057] According to the above embodiments, the tablet may contain additional sugar alcohols, which are not selected from xylitol, maltitol, mannitol, erythritol, isomaltitol, sorbitol, lactitol, or any combination thereof.

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

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

[0060] According to an advantageous embodiment of the invention, the disintegrant is selected from starch, pregelatinated starch, modified cellulose, ion exchange resin, calcium silicate, cross-linked cellulose, cross-linked polyvinylpyrrolidone, cross-linked starch, cross-linked alginate, and combinations thereof.

[0061] In the context of this article, the terms "crosslinked alginate" and "salt of crosslinked alginate" can be used interchangeably.

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

[0063] In the context of this article, starch refers to starch from various sources, such as potato starch, corn starch, wheat starch, pea starch, etc.

[0064] Examples of pregelatinized starch disintegrants include structures and brand names such as pregelatinized potato starch, pregelatinized wheat starch, pregelatinized corn starch, Lycatab®, Starch 1500®, etc.

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

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

[0067] According to an embodiment of the present invention, the disintegrant is composed of pregelatinized starch.

[0068] It should be understood that some disintegrants are called superdisintegrants.

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

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

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

[0072] In some implementations, the disintegrant may comprise a combination of conventional disintegrants and superdisintegrants.

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

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

[0075] Examples of cross-linked cellulose superdisintegrants include structures and brand names such as croscarmellose®, Ac-Di-Sol®, Solut®, etc.

[0076] Examples of cross-linked polyvinylpyrrolidone (PVP) superdisintegrants include structures and brand names such as Kollidon®, Polyplasdone®, polyplasdone XL®, and Kollidon CL®. Cross-linked polyvinylpyrrolidone (PVP) disintegrants are sometimes also referred to as cross-linked polyvinylpyrrolidone.

[0077] Examples of cross-linked starch superdisintegrants include structures and brand names such as sodium carboxymethyl starch (sodium starch glycolate), Glycolys®, Explotab®, Primogel®, Vivastar®, Tablo®, etc.

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

[0079] According to an advantageous embodiment of the invention, the disintegrant is a superdisintegrant selected from croscarmellose, sodium carboxymethyl starch, and any combination thereof.

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

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

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

[0083] In embodiments of the present invention, ready-to-use systems may be used. Typically, such ready-to-use systems can use a single powder mixture instead of fillers, disintegrants, gliding agents, or similar components. Ready-to-use systems suitable 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 above embodiments, a ready-to-use system may be included as a convenient way to include, for example, both sugar alcohols and disintegrants.

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

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

[0087] According to an advantageous embodiment of the invention, the tablet consists of a plurality of compressed granules.

[0088] According to an advantageous embodiment of the invention, the tablets are compressed with a compression force of 1 to 35 kN (e.g., 2 to 30 kN, e.g., 2-20 kN).

[0089] According to an advantageous embodiment of the invention, the nicotine is selected from nicotine salts, free base nicotine, nicotine-ion exchange resin combinations, nicotine inclusion complexes or any non-covalently bound 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, the nicotine is selected from free nicotine and nicotine salts, or combinations thereof. It should be noted that when free nicotine and / or nicotine salts are used, it means that the nicotine is provided without a carrier, unless otherwise expressly stated.

[0091] According to an advantageous embodiment of the invention, the nicotine comprises nicotine freebase.

[0092] Free nicotine bases include nicotine mixed with sugar alcohols, modified calcium carbonate, water-soluble fibers, water-insoluble fibers, and combinations thereof.

[0093] In an embodiment of the present invention, the nicotine is free alkali nicotine.

[0094] In embodiments of the invention, the nicotine comprises nicotine inclusion complexes. In embodiments of the invention, the nicotine comprises nicotine bound to an ion exchange resin. In embodiments of the invention, the nicotine comprises nicotine bound to a polacrilex resin. As used herein, “NPR” refers to nicotine bound to a polacrilex resin.

[0095] According to an advantageous embodiment of the invention, the nicotine comprises nicotine salt.

[0096] One advantage of the above-described embodiments is that they facilitate the rapid relief of nicotine cravings, for example, due to the rapid dissociation of nicotine salts.

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

[0098] According to an advantageous embodiment of the present invention, the nicotine salt is selected from ascorbic acid nicotine, aspartic acid nicotine, benzoic acid nicotine, tartrate nicotine, tartrate hydronicotine, nicotine chloride, citrate nicotine, fumarate nicotine, lactic acid nicotine, nicotine nucate, laurate nicotine, nicotine levulinate, malate nicotine, perchlorate nicotine, pyruvate nicotine, salicylate nicotine, sorbate nicotine, succinate nicotine, nicotine sulfate, and any combination thereof.

[0099] It should be understood that the nicotine salt may be a hydrated salt, or a combination of a hydrated salt and a non-hydrated salt.

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

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

[0102] According to an advantageous embodiment of the invention, the nicotine comprises nicotine tartrate.

[0103] The term NBT can be used as an abbreviation for nicotine tartrate.

[0104] One advantage of the above-described embodiments is that they facilitate the rapid relief of nicotine cravings, for example, due to the rapid dissociation of nicotine tartrate.

[0105] In an embodiment of the present invention, the nicotine is nicotine tartrate.

[0106] In an embodiment of the present invention, the nicotine forms an ionic complex with at least one water-soluble anionic polymer that adheres to the mucous membrane.

[0107] In an embodiment of the present invention, the nicotine comprises synthetic nicotine.

[0108] In an embodiment of the present invention, the nicotine is composed of synthetic nicotine.

[0109] According to an advantageous embodiment of the 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 invention, the tablet contains nicotine in an amount of 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 mg to 3.0 mg, for example 1.0 mg to 2.0 mg.

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

[0112] In an embodiment of the invention, the tablet contains nicotine at a concentration of 0.2% to 5% of the tablet weight, for example, 0.3% to 3% of the tablet weight, or for example, 0.5% to 2% of the tablet weight.

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

[0114] According to an advantageous embodiment of the invention, the pH adjuster is an alkaline pH adjuster, such as an alkaline buffer.

[0115] In embodiments of the present invention, the pH adjuster does not contain an acidic pH adjuster.

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

[0117] According to an advantageous embodiment of the invention, the pH adjuster comprises a pH adjuster selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, tromethamine, amino acids, dibasic phosphate, tribasic phosphate, or any combination thereof.

[0118] In embodiments of the present invention, the pH adjuster is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, tromethamine, 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 sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, tromethamine, amino acids, or any combination thereof.

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

[0121] Combinations of carbonates and bicarbonates may be particularly advantageous. For example, such a combination could be a sodium carbonate-sodium bicarbonate buffer system, with a weight ratio of sodium carbonate to sodium bicarbonate of 5:1 to 1:1, preferably 4.1:1 to 1.5:1.

[0122] According to an advantageous embodiment of the invention, the pH adjuster comprises or consists of sodium carbonate.

[0123] One advantage of the above-described implementation is the increased intake of nicotine in the oral cavity.

[0124] In embodiments of the present invention, the pH adjuster is selected from tromethamine, 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 adjuster is selected from tromethamine, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, or any combination thereof.

[0126] In embodiments of the present invention, the pH adjuster comprises diphosphate and / or triphosphate, such as disodium phosphate, dipotassium phosphate, trisodium phosphate and / or tripotassium phosphate.

[0127] Tromethamine and phosphate buffer have ideally neutral tastes, so using these pH adjusters may not impair the taste and mouthfeel of nicotine tablets.

[0128] In embodiments of the present invention, the pH adjuster comprises trometamol.

[0129] In an embodiment of the present invention, the pH adjuster is composed of tromethamine.

[0130] In the context of this article, the term tromethamine refers to (tris(hydroxymethyl)aminomethane), sometimes also called tris buffer.

[0131] In embodiments of the present invention, the pH adjuster comprises amino acids.

[0132] In embodiments of the present invention, the pH adjuster is composed of amino acids.

[0133] According to an advantageous embodiment of the invention, the tablet contains a pH adjuster comprising at least 0.2% of the tablet weight, for example at least 0.5% of the tablet weight, for example at least 1% of the tablet weight, for example at least 2% of the tablet weight.

[0134] In an embodiment of the invention, the tablet contains a pH adjuster of 0.2% to 10% of the tablet weight, for example 0.5% to 8% of the tablet weight, for example 1% to 6% of the tablet weight, for example 2% to 4% of the tablet weight.

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

[0136] According to an advantageous embodiment of the invention, the tablet does not contain effervescent agents.

[0137] One advantage of the above-described implementation is the improved user experience. Typically, the presence of effervescent tablets can cause a stinging sensation, which can be quite uncomfortable, especially when the tablet is applied between the gums and lips.

[0138] Another advantage is that using effervescent tablets may cause the oral pH level to drop below the optimal range for effective nicotine absorption via the mucous membranes. Therefore, avoiding the use of effervescent tablets may help improve nicotine absorption.

[0139] According to an advantageous embodiment of the invention, the weight of the tablet does not exceed 600 mg, for example, not more than 500 mg, for example, not more than 400 mg, for example, not more than 300 mg, for example, not more than 200 mg, for example, not more than 150 mg, for example, not more than 120 mg, for example, not more than 100 mg, for example, not more than 50 mg.

[0140] In embodiments of the invention, the tablet weighs 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 mg to 50 mg.

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

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

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

[0144] In the context of this article, the term "layer" refers to a tablet module that constitutes a significant portion of the tablet (e.g., at least 20% of the tablet weight, at least 30% of the tablet weight, at least 40% of the tablet weight).

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

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

[0147] According to an advantageous embodiment of the invention, the solubility regulator is selected from xanthan gum, guar gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, monovalent alginate, pullulan, tragacanth gum, gum karaya, fenugreek gum, cassia gum, carrageenan, agar, alginic acid, and their monovalent salts, as well as any combination thereof.

[0148] Note that in this context, the terms "monovalent alginate," "monovalent salt of alginate," and "monovalent salt of alginate" are used interchangeably. It should also be noted that in this document, the solubility regulators include non-crosslinked alginates, not crosslinked alginates.

[0149] One advantage of the above-described embodiments is that a small amount of dissolving agent can improve the taste.

[0150] According to embodiments of the present invention, the solubility regulator is selected from xanthan gum, guar gum, and any combination thereof.

[0151] One advantage of the above-described embodiments is that a small amount of dissolving agent can improve the taste.

[0152] In embodiments of the present invention, the solubility regulator comprises xanthan gum.

[0153] In embodiments of the present invention, the dissolution regulator comprises guar gum.

[0154] According to an advantageous embodiment of the invention, the tablet does not contain a solubility modifier.

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

[0156] In an embodiment of the present invention, the tablet does not contain xanthan gum.

[0157] According to an advantageous embodiment of the invention, the tablet is free of mucoadhesives.

[0158] Therefore, according to embodiments of the present invention, the tablet is not an adhesive tablet, for example, it does not contain any mucosal adhesive, or contains only a small amount of mucosal adhesive, for example, not more than 10% of the tablet weight, for example, not more than 5% of the tablet weight, for example, not more than 2% of the tablet weight, for example, not more than 1% of the tablet weight.

[0159] In embodiments of the invention, the tablet contains a lubricant, such as sodium stearate fumarate (SSF) or magnesium stearate.

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

[0161] Note that the tablets described in the above embodiments are non-chewable, meaning they are not intended for chewing.

[0162] The present invention also relates to an orally disintegrating nicotine tablet for rapid relief of nicotine cravings, the tablet comprising nicotine, a disintegrant and at least one sugar alcohol, wherein the total amount of flavoring agent and high-intensity sweetener in the tablet is less than 0.8% of the tablet weight.

[0163] According to an advantageous embodiment of the invention, the total amount of flavoring agent and high-intensity sweetener in the tablet does not exceed 0.6% of the tablet weight, for example, not more than 0.4% of the tablet weight, for example, not more than 0.3% of the tablet weight, for example, not more than 0.2% of the tablet weight.

[0164] In embodiments of the present invention, the total amount of flavoring agent and high-intensity sweetener in the tablet is 0 to 0.8% of the tablet weight, for example 0.01 to 0.6% of the tablet weight, for example 0.05 to 0.4% of the tablet weight, for example 0.1 to 0.3% of the tablet weight, for example 0.1 to 0.2% of the tablet weight.

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

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

[0167] According to an advantageous embodiment of the invention, the second module is a lozenge module.

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

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

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

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

[0172] According to an advantageous embodiment of the invention, at least one sugar alcohol in the second module includes sugar alcohols selected from xylitol, maltitol, mannitol, erythritol, isomaltitol, sorbitol, lactitol, and any combination thereof.

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

[0174] In an embodiment of the present invention, the second module includes a dissolving regulator in an amount of 1% to 15% of the weight of the second module, for example 2% to 10% of the weight of the second module, for example 3% to 8% of the weight of the second module.

[0175] According to embodiments of the present invention, the solubility regulator is selected from xanthan gum, guar gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, alginate, pullulan, tragacanth gum, kalaya 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 solubility regulator is selected from xanthan gum, guar gum, and any combination thereof.

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

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

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

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

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

[0182] Therefore, in the above embodiments, both the first module and the second module are compressed, that is, the tablet is composed of multiple compressed particles.

[0183] In an embodiment of the present invention, both the first module and the second module are layers. Therefore, in this embodiment, the first module is the first layer, and the second module is the second layer. Detailed description

[0184] In this article, the term "orally disintegrating tablet" refers to an orally administered tablet that disintegrates relatively quickly (e.g., within 60 seconds) in the oral cavity after administration.

[0185] Orally disintegrating tablets are also called "orally dissolving tablets," and these two terms are used interchangeably herein. These terms are also commonly abbreviated as ODT. Similarly, "fast dissolving tablet," "fast disintegrating tablet," and the abbreviation FDT all refer to orally disintegrating tablets herein. It should be noted that disintegrating tablets are considered to be completely disintegrating, meaning they completely disintegrate upon application to the oral cavity. In some embodiments, disintegrating tablets consist only of water-soluble substances and are therefore completely water-soluble. In other embodiments, disintegrating tablets contain a certain amount of water-insoluble components, provided these components do not impede the complete disintegration of the tablet. Therefore, it should be understood that disintegrating tablets do not include, for example, chewing gum, because chewing gum cannot completely disintegrate or dissolve; furthermore, disintegrating tablets do not include hard candies, i.e., tablets based on cooked sugars and / or sugar alcohols, which can only dissolve slowly rather than disintegrate.

[0186] In this document, the term "disintegrate" refers to the breakdown of the substance into components, fragments, or particles. Disintegration can refer to both in vivo disintegration (the methods of which are defined herein) and in vitro disintegration. In vitro disintegration tests were performed in accordance with Section 2.9.1, "Disintegration of Tablets and Capsules," of the European Pharmacopoeia 9.0.

[0187] In this article, the term "dissolution" refers to the process by which a solid substance enters a solvent (oral saliva) to form a solution. Unless otherwise stated, dissolution means the complete dissolution of the compound discussed.

[0188] In this document, "disintegrant" refers to a component that promotes the disintegration of a tablet upon contact with saliva. Disintegrants usable within the scope of this invention include starch, pregelatinized starch, modified starch (including potato starch, corn starch, starch 1500, sodium carboxymethyl starch, and starch derivatives), croscarmellose, ion exchange resins, and superdisintegrants such as croscarmellose (e.g., sodium carboxymethyl cellulose), croscarmellose (PVP), croscarmellose, croscarmellose, natural superdisintegrants, and calcium silicate. Disintegrants are generally considered a means to promote the disintegration of a dosage form into smaller fragments after administration, allowing the drug to begin dissolving and ultimately be absorbed.

[0189] In this document, the term "nicotine" refers to nicotine in any form, including free nicotine bases, nicotine salts, nicotine bound to ion exchange resins (e.g., nicotine polacrilex), nicotine bound to zeolites, nicotine bound to cellulose (e.g., microcrystalline cellulose, such as microcrystalline cellulose derived from microorganisms) or starch microspheres, nicotine bound to CaCO3, and mixtures thereof. Therefore, when referring to the amount of nicotine, it means the amount of pure nicotine. Thus, when measuring the concentration of nicotine added in the form of nicotine salts, it is the mass of an equivalent amount of pure nicotine, not the mass of the nicotine salts. Nicotine also includes nicotine from non-tobacco sources, commonly referred to as synthetic nicotine.

[0190] In this article, the term "nicotine salt" refers to nicotine in ionic form that is electrostatically bound to counterions.

[0191] In this article, the term "NBT" refers to nicotine tartrate and its hydrate.

[0192] Unless otherwise stated, the terms “%” and “percentage” in this document refer to weight percentage.

[0193] In this document, the term "pH adjuster" refers to a reagent that actively adjusts and regulates the pH of a solution to which such adjusters have been added or will be added. Therefore, pH adjusters can be acids and bases, including acidic buffers and basic buffers. On the other hand, pH adjusters do not include substances and compositions that affect pH only through dilution. Furthermore, pH adjusters do not include, for example, flavoring agents, fillers, etc. In an advantageous embodiment of the invention, the pH adjuster is alkaline.

[0194] In this article, the terms "buffer" and "buffer solution" are used interchangeably to refer to reagents used to obtain buffer solutions. Buffers include basic buffers (i.e., buffer solutions used to obtain an alkaline pH).

[0195] In embodiments of the invention, the tablet comprises a filler. In embodiments of the invention, the filler is selected from microcrystalline cellulose, magnesium carbonate and calcium carbonate, sodium sulfate, ground limestone, silicate compounds (e.g., magnesium silicate and aluminum silicate), kaolin and clay, alumina, silica, talc, titanium dioxide, monocalcium phosphate, dicalcium phosphate and tricalcium phosphate, cellulose polymers (e.g., wood), starch polymers, fibers, and combinations thereof.

[0196] In embodiments of the invention, the tablet comprises a bulk sweetener. In embodiments of the invention, the bulk sweetener comprises or consists of sugar sweeteners and / or sugar-free sweeteners.

[0197] Bulk sweeteners can typically enhance the flavor profile of a formulation.

[0198] In embodiments of the present invention, the sugar sweetener is selected from carbohydrate-containing components, such as sucrose, dextrose, maltose, lactose, sorbitol, dextrin, trehalose, D-tagatose, dried invert sugar, fructose, levulose, galactose, etc., and can be used alone or in combination. These sugar sweeteners can also be used as humectants.

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

[0200] In embodiments of the present invention, the disintegrant is selected from croscarmellose sodium (croscarmellose sodium) and carboxymethyl starch sodium. In embodiments of the present invention, the disintegrant is selected from starch, pregelatinized starch, modified starch (including potato starch, corn starch, starch 1500, carboxymethyl starch sodium, and starch derivatives), ion exchange resins, and superdisintegrants (e.g., croscarmellose (e.g., carboxymethyl cellulose sodium), croscarmellose (PVP), croscarmellose starch, croscarmellose alginate, natural superdisintegrants), calcium silicate, and combinations thereof.

[0201] In embodiments of the present invention, the tablet comprises a high-intensity sweetener. In embodiments of the present invention, the high-intensity sweetener is selected from sucralose, aspartame, salts of acesulfame potassium such as acesulfame potassium, alitane, saccharin and its salts, cyclosporine and its salts, glycyrrhizin, dihydrochalcone, thomaline, monetarine, steviol glycosides, etc., used alone or in combination.

[0202] In embodiments of the present invention, the tablet comprises one or more flavoring agents. In embodiments of the present invention, one or more flavoring agents are selected from: peppermint, menthol, almond, almond amaretto, apple, Bavarian butter, black cherry, black sesame seeds, blueberry, brown sugar, bubble gum, butter Scotch candy, cappuccino, caramel, caramel cappuccino, cheesecake (whole wheat crust), cinnamon red hot candy, marshmallow, circus marshmallow, clove, coconut, coffee, black 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, marshmallow, menthol, milk chocolate, mocha, Mountain Dew, peanut butter, pecan, peppermint, raspberry, banana, ripe banana, root juice soda, RY 4, spearmint, strawberry, sweet cream, sweet tarts. Sweeteners, sweeteners, roasted almonds, tobacco, blended tobacco, vanilla bean ice cream, vanilla cupcakes, vanilla swirls, vanillin, waffles, Belgian waffles, watermelon, whipped cream, white chocolate, holly, amaretto, banana cream, black walnuts, blackberries, butter, butter rum, cherries, chocolate hazelnuts, cinnamon rolls, cola, mint liqueur, eggnog, English toffee, guava, lemonade, licorice, maple syrup, mint chocolate chips, orange cream, peach, pina colada, pineapple, plum, pomegranate, praline cream, red licorice, salted toffee, strawberry banana, strawberry kiwi, tropical punch, tutti frutti, vanilla, or any combination thereof.

[0203] According to an embodiment of the present invention, flavoring agents can 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 carbonates (including monocarbonates, bicarbonates, and sesquicarbonates), glycerates, phosphates, glycerophosphates, acetates, alkali metal glycolates or citrates, ammonium salts, Tris buffers, amino acids, and mixtures thereof. Encapsulated buffers, such as Effersoda, may also be used.

[0205] The buffer in the tablet can be used to bring the saliva of the tablet user to the desired pH level.

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

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

[0208] In embodiments of the present invention, silica is used as a glidant. Other glidants suitable for this formulation 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 suitable for this formulation may also be used within the scope of the present invention.

[0210] In embodiments of the present invention, ready-to-use systems may be used. Typically, such ready-to-use systems can use a single powder mixture to replace fillers, disintegrants, flow aids, or similar components. Ready-to-use systems suitable 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 (FujiChemical), SmartEx50, or SmartEx100 (Shin Etsu / Harke Pharma).

[0211] To obtain orally disintegrating tablets that disintegrate within a desired time, such as those that disintegrate within 60 seconds after oral administration or in vitro, a series of parameters can be adjusted.

[0212] First, the disintegration time can be altered by changing the composition. Using highly water-soluble components can help shorten the disintegration time.

[0213] Specifically, by changing the amount and type of disintegrant, the disintegration time can be significantly affected, and the disintegration time can be further adjusted. For example, if a tablet with a shorter disintegration time is required, the percentage content of the disintegrant can be increased, and / or the type of disintegrant can be at least partially replaced with a more effective disintegrant. In this regard, superdisintegrants are generally considered to be more effective disintegrants than non-superdisintegrants.

[0214] Furthermore, the addition of a disintegration modifier can significantly affect disintegration time by altering its amount and type. For example, if a shorter disintegration time is desired, the amount of disintegration modifier can be reduced (or even eliminated), and / or the type of disintegration modifier can be at least partially replaced with one that more effectively delays dissolution.

[0215] In addition, reducing the particle size of disintegrants often shortens the disintegration time, likely due to an increase in the surface area to volume ratio.

[0216] Furthermore, the compression force used for tableting is significantly correlated with the resulting hardness; higher compression forces generally increase the hardness of the resulting tablets. Adjusting the tablet hardness can also affect disintegration time, with lower hardness typically resulting in shorter disintegration times. It was observed that for various compositions, by applying appropriate compression forces, disintegration times can be less than 60 seconds in oral and / or in vitro settings; while excessively high compression forces may lead to longer disintegration times, exceeding 60 seconds in vivo or in vitro. In this regard, it should be noted that the threshold compression force can fluctuate significantly due to other parameters such as overall composition, amount and type of disintegrant, etc. For example, when a particular setup results in excessively slow disintegration, another adjustment could be to replace the conventional disintegrant with a superdisintegrant (i.e., a more effective disintegrant promoter).

[0217] Improving water solubility can also be achieved by replacing less water-soluble components with more water-soluble ones. For example, using sugar alcohols as fillers can be very advantageous because sugar alcohols are more water-soluble than other fillers.

[0218] Furthermore, using sugar alcohols with low compressibility can lead to a shorter disintegration time. Excessive compressibility can reduce the mechanical strength of tablets, resulting in excessive friability and a risk of cracking.

[0219] Other examples of parameters that can be adjusted to obtain orally disintegrating nicotine tablets include tablet size and shape. Larger tablets have longer disintegration times, and therefore longer release times for the tablet contents (such as nicotine).

[0220] For example, for disc-shaped tablets, increasing their flatness (e.g., quantified by the ratio of diameter to height) typically increases the surface area to volume ratio, thereby prolonging disintegration time. Flatness can be improved as long as the tablet has satisfactory mechanical strength.

[0221] Furthermore, changing the cross-sectional shape of the tablet from convex to concave can shorten the disintegration time. It should be noted that this may reduce the mechanical strength of the tablet to some extent; however, as long as the effect is satisfactory, using a concave cross-section helps to improve the disintegration rate, thereby shortening the disintegration time.

[0222] In addition, when using binders (e.g., to achieve higher cohesiveness and mechanical strength in tablets), the amount of such binders can be minimized to obtain a higher disintegration rate, thereby shortening the disintegration time.

[0223] Furthermore, adding salivation stimulants to tablets can promote saliva production around the tablet, which will also support tablet dissolution and disintegration, shortening disintegration time. Therefore, sweeteners, especially sugar alcohols, may have an advantage in this regard.

[0224] In addition, the type and amount of lubricant (if applicable) can be adjusted to optimize disintegration time. For example, using sodium stearate fumarate (SSF) generally results in a shorter disintegration time than using magnesium stearate (MgSt).

[0225] Therefore, a wide range of parameters can be adjusted when designing a nicotine disintegrating tablet that is to disintegrate within a desired time (e.g., within 60 seconds in vitro, or within 60 seconds after administration to the tongue).

[0226] Typically, the formulation comprises components selected from the following: bulk sweeteners, fillers, ready-to-use systems, flavoring agents, dry binders, disintegrants, superdisintegrants according to this document, tableting aids, anti-caking agents, emulsifiers, antioxidants, synergists, absorption enhancers, buffers, high-intensity sweeteners, colorants, flow aids, lubricants, or any combination thereof. Absorption enhancers may include, for example, pH adjusters (such as buffers) and mucosal adhesives.

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

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

[0229] According to an embodiment of the present invention, at least a portion of the nicotine adheres to the dry-adhesive particles.

[0230] According to an embodiment of the present invention, a certain amount of dry adhesive is used to adhere nicotine to a bulk sweetener.

[0231] According to an embodiment of the present invention, the orifice-disintegrating sheet includes one or more packaging and delivery systems.

[0232] According to embodiments of the present invention, a nicotine tablet may serve as a first module, the tablet further comprising a module with a different composition. This additional module may be a slow-dissolving lozenge module. Of course, the tablet does not include, for example, a water-insoluble chewing gum module. Furthermore, the lozenge is water-soluble, meaning it disintegrates and dissolves its main components in water. In one embodiment, the nicotine tablet according to the above embodiments may be a compressed tablet, obtained by compressing at least a first powder composition and a second powder composition to obtain the first and second modules, respectively. The tablet may contain a certain amount of a water-insoluble substance, such as MCC (microcrystalline cellulose). For example, the tablet may dissolve within at least 2 minutes (e.g., at least 3 minutes, at least 4 minutes, at least 5 minutes) after oral administration.

[0233] In this document, the term "lozenge module" refers to a module that imparts the properties of a lozenge, namely, a module that slowly dissolves or disintegrates in the oral cavity, and whose components (such as pH adjusters, flavoring agents, nicotine, etc., depending on the specific implementation) are slowly released. For example, a lozenge module may dissolve within at least 2 minutes (e.g., at least 3 minutes, at least 4 minutes, or at least 5 minutes) after oral administration.

[0234] Therefore, in this context, in an advantageous embodiment, the module comprises at least 10% of the tablet weight. For compressed oral nicotine tablets, a module may comprise a group of compressed particles that comprise at least 10% of the tablet weight. In other words, a module does not refer to a single particle as commonly understood in the field of compressed tablet technology. Example

[0235] Example 1

[0236] Preparation of single-layer tablets

[0237] Remove the raw materials from the bag or bucket and weigh them in a separate weighing container.

[0238] All excipients are sieved through an 800 μm sieve into a stainless steel or plastic bin in the following order:

[0239] Half of the filler / large amount of sweetener

[0240] • API (active pharmaceutical ingredient) and all other excipients, except lubricants (if any).

[0241] • Remaining half of the filler / bulk sweetener

[0242] Place these raw materials into a Turbula mixer and mix at 25 RPM for 4–10 minutes. Then, sieve a lubricant (e.g., magnesium stearate) through an 800 μm sieve into the mixing bin and mix for an additional 1–2 minutes at 25 RPM for lubrication. Maintain the mixing bin at 40%–70% fill level according to standard operating procedures. The lubricated powder mixture is then fed into the tableting machine hopper.

[0243] Orally disintegrating tablets are produced on laboratory-scale machines such as the RIVA Piccola double-layer tableting machine. The tableting machine is tuned by adjusting the filling depth and compression force to ensure that the weight and hardness of the tablets meet acceptance criteria. Pre-pressure may be included to prevent tablet capping.

[0244]

[0245] Table 1: Suggested startup parameters. *The punch design is not fixed. Since curvature affects thickness, thickness is not a fixed target at this stage of development.

[0246] In order for the resulting orally disintegrating tablets to be packaged, they should meet the acceptance criteria for friability. However, in this embodiment, the bulk sweeteners and / or fillers should have relatively good compressibility while still exhibiting rapid disintegration. The orally disintegrating tablets according to the invention may contain colorants. According to embodiments of the invention, the orally disintegrating tablets may contain colorants and whitening agents such as FD&C type dyes and lakes, fruit and vegetable extracts, titanium dioxide, and combinations thereof.

[0247] Example 2

[0248] Preparation of tablets comprising a first module and a second module

[0249] The composition of the second module (which has a different composition compared to the orally disintegrating tablet module) is prepared as follows: approximately half of the sugar alcohol is poured into a mixing bowl, then all ingredients except the lubricant are added, and finally the remaining sugar alcohol is added. These ingredients are then tumbled / mixed at 49 rpm for 4-10 minutes using a mixer (e.g., Turbula or Duma).

[0250] Add the lubricant and stir the ingredients further at 49 rpm for 1-2 minutes.

[0251] The composition of the first module (i.e., the orally disintegrating tablet module) is prepared as follows: All components except the lubricant are poured into a mixing bowl. These components are then tumbled / mixed with a mixer (e.g., Turbula or Duma) at 49 rpm for 4-10 minutes.

[0252] Add the lubricant and stir the ingredients further at 49 rpm for 1-2 minutes.

[0253] The lubricating powder mixture is fed sequentially into the hopper of the tablet press.

[0254] The second module is then compressed with a force of approximately 3-8 kN. Subsequently, the first module is fused to the second module by compression with a force of approximately 20-30 kN. Unless otherwise specified, the punch used is: 12.00 mm, round, shallowly concave, type B die.

[0255] The tablets are produced on a laboratory-scale tablet press (e.g., the RIVA Piccola tablet press). The tablet press is calibrated by adjusting the filling depth and compression force to ensure the tablet weight and hardness meet acceptance criteria. Pre-compression force may be applied to prevent tablet chipping.

[0256] Example 3: Tablet composition, single-layer tablet

[0257] Example 3A

[0258] All tablets were prepared according to Example 1, unless otherwise stated.

[0259] In this example, the following conditions were used: Punch used: 7.00 mm, round, shallow concave, type B die. Tablet weight: 100.0 mg.

[0260]

[0261] Table 2: Composition of each tablet. NBT = Nicotine Tartrate (nicotine content 32.38% by weight). MCC = Microcrystalline Cellulose. HIS = High-Intensity Sweetener.

[0262] Preferred high-intensity sweeteners (HIS) may be, for example, sucralose, acesulfame potassium, and mixtures thereof. Other high-intensity sweeteners, such as aspartame, salts of acesulfame potassium and other acesulfame acids, alitane, saccharin and its salts, cyclolataic acid and its salts, glycyrrhizin, dihydrochalcone, thomatose, monetarine, and steviol glycosides, may also be used, alone or in combination, within the scope of this invention.

[0263] The examples above use powdered peppermint flavoring. A mixture of peppermint and menthol can also be used. Of course, other flavorings described herein can also be used, in combination with menthol and / or peppermint, or in place of them. Flavorings can be liquid, powder, or a combination (i.e., adding both liquid and powdered flavorings).

[0264] Sodium stearate is used as a lubricant in the above-mentioned formulation. Other lubricants, such as MgSt (magnesium stearate), may also be used within the scope of this invention.

[0265] Sodium carbonate can be used as an alkaline pH adjuster. Other available alkaline pH adjusters include sodium bicarbonate, potassium carbonate, potassium bicarbonate, tromethamine, amino acids, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, or any combination thereof.

[0266] Example 3B

[0267] All tablets were prepared according to Example 1, unless otherwise stated.

[0268] In this example, the following conditions were used: Punch used: 7.00 mm, round, shallow concave, type B die. Tablet weight: 100.0 mg.

[0269]

[0270] Table 3: Composition of each tablet. NBT = Nicotine tartrate (nicotine content 32.38% by weight). MCC = Microcrystalline cellulose. HIS = High-intensity sweetener.

[0271] The alternative components described in LFT(1)-LFT(4) in Table 2 also apply to LFT(11)-LFT(17).

[0272] Example 3D

[0273] All tablets were prepared according to Example 1, unless otherwise stated.

[0274] In this example, the following conditions were used: Punch used: 7.00 mm, round, shallow concave, type B die. Tablet weight: 100.0 mg.

[0275]

[0276] Table 4. Composition of each tablet. NBT = Nicotine tartrate (nicotine content 32.38% by weight). MCC = Microcrystalline cellulose.

[0277] The alternative components described in LFT(1)-LFT(17) in relation to Table 2-3 also apply to LFT(21)-LFT(24).

[0278] Example 3E

[0279] All tablets were prepared according to Example 1, unless otherwise stated.

[0280] In this example, the following conditions were used: Punch used: 7.00 mm, round, shallow concave, type B die. Tablet weight: 100.0 mg.

[0281]

[0282] Table 5: Composition of each tablet. NBT = Nicotine tartrate (nicotine content 32.38% by weight). MCC = Microcrystalline cellulose. HIS = High-intensity sweetener.

[0283] The alternative components described in LFT(1)-LFT(25) in Table 2-4 also apply to LFT(31)-LFT(36).

[0284] Example 3F

[0285] All tablets were prepared according to Example 1, unless otherwise stated.

[0286] In this example, the following conditions were used: Punch used: 7.00 mm, round, shallow concave, type B die. Tablet weight: 100.0 mg.

[0287]

[0288] Table 6. Composition of each tablet. NBT = Nicotine tartrate (nicotine content 32.38% by weight). MCC = Microcrystalline cellulose. NPR = Nicotine polacrilex resin (nicotine content 16% by weight). HIS = High-intensity sweetener.

[0289] The alternative components described in LFT(1)-LFT(36) in Table 2-5 also apply to LFT(41)-LFT(45).

[0290] Example 3G

[0291] All tablets were prepared according to Example 1, unless otherwise stated.

[0292] In this example, the following conditions were used: Punch used: 7.00 mm, round, shallow concave, type B die. Tablet weight: 100.0 mg.

[0293]

[0294] Table 7: Composition of each tablet. NBT = Nicotine tartrate (nicotine content 32.38% by weight). MCC = Microcrystalline cellulose. HIS = High-intensity sweetener.

[0295] The alternative components described in LFT(1)-LFT(45) in Table 2-5 also apply to LFT(51)-LFT(55).

[0296] Example 3H

[0297] All tablets were prepared according to Example 1, unless otherwise stated.

[0298] In this example, the following conditions were used: Punch used: 7.00 mm, round, shallow concave, type B die. Tablet weight: 100.0 mg.

[0299]

[0300] Table 8: Composition of each tablet. NBT = Nicotine tartrate (nicotine content 32.38% by weight). MCC = Microcrystalline cellulose. HIS = High-intensity sweetener.

[0301] The alternative components described in LFT(1)-LFT(55) in Table 2-7 also apply to LFT(61)-LFT(67).

[0302] Example 4: Tablet composition, bilayer tablet

[0303] Example 4A

[0304] All tablets were prepared according to Example 2, unless otherwise stated.

[0305] In this example, the following conditions were used: Punch used: 7.00 mm, round, shallow concave, type B die. First layer weight: 100.0 mg. Second layer weight: 300.0 mg. Tablet weight: 400.0 mg.

[0306]

[0307] Table 9: Composition of each tablet. NBT = Nicotine Tartrate (nicotine content 32.38% by weight). MCC = Microcrystalline Cellulose. NPR = Nicotine Polacrilex Resin (nicotine content 16% by weight). HIS = High-Intensity Sweetener.

[0308] The alternative components described in LFT(1)-LFT(67) in Table 2-8 also apply to LFT(71)-LFT(75).

[0309] Example 4B

[0310] Use any one of the tablets from LFT(1) to LFT(67) in Table 2-8 as the first layer and any one of LFT(71) to LFT(75) as the second layer to make another tablet.

[0311] Example 5: Evaluation

[0312] The tablets produced by this invention were evaluated and found to be very suitable as nicotine delivery carriers because they provide good nicotine release while being comfortable for the user, for example, having an acceptable nicotine burn without producing excessive taste perception and aftertaste.

[0313] Example 6: Evaluation

[0314] The orally disintegrating nicotine tablets C(1) and C(2), used as references, were evaluated by several evaluators. There were 84 evaluators for C(1) and 94 evaluators for C(2).

[0315] For C(1) and C(2), evaluators were asked to indicate whether the flavor intensity was too strong or too weak during use. Table 10 below shows the ratio of evaluators who thought the flavor intensity was too strong to those who thought it was too weak. In addition, the flavor duration was also evaluated, as well as the ratio of evaluators who thought the flavor duration was too long to those who thought it was too short.

[0316]

[0317] Table 10. Taste Evaluation. N / A = No evaluation.

[0318] As shown in Table 10, a surprisingly high percentage of evaluators considered the flavor intensity to be too high. Similarly, a surprisingly high percentage of evaluators considered the flavor duration to be too long.

[0319] Since flavorings are usually added to mask the taste of nicotine, it was quite unexpected that a relatively high percentage of evaluators considered the flavor intensity too high, compared to the opposite.

[0320] Similarly, the aftertaste of the two reference tablets was also evaluated, and the ratio of evaluators who considered the aftertaste too strong to those who considered it too weak was observed. In addition, the duration of the aftertaste was also evaluated, with the ratio of evaluators who considered the aftertaste too long to those who considered it too short.

[0321]

[0322] Table 11. Evaluation of aftertaste.

[0323] As can be seen from Table 11, the assessment of the aftertaste shows an unexpected preference for shorter and less intense aftertastes.

[0324] The above-mentioned unexpected findings in Tables 10-11 indicate that a significant number of evaluators prefer milder or even tasteless flavors, which are precisely the characteristics provided by the orally disintegrating nicotine tablets of this invention.

Claims

1. An orally disintegrating nicotine tablet for rapid relief of nicotine cravings, said tablet comprising nicotine, a disintegrant, and at least one sugar alcohol, wherein, The tablets contain less than 0.4% by weight of flavoring agent.

2. The orally disintegrating nicotine tablet of claim 1, wherein the tablet contains no more than 0.3% by weight of a flavoring agent, such as no more than 0.2% by weight of a flavoring agent, such as no more than 0.1% by weight of a flavoring agent, or contains no flavoring agent.

3. The orally disintegrating nicotine tablet of claim 1 or 2, wherein the tablet comprises a liquid flavoring agent.

4. The orally disintegrating nicotine tablet according to any one of claims 1-3, wherein the tablet contains less than 0.4% by weight of liquid flavoring, for example, no more than 0.3% by weight of liquid flavoring, for example, no more than 0.2% by weight of liquid flavoring, for example, no more than 0.1% by weight of liquid flavoring, for example, without liquid flavoring.

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

6. The orally disintegrating nicotine tablet according to any one of claims 1-5, wherein the tablet contains less than 0.4% by weight of a powdered flavoring agent, for example, no more than 0.3% by weight of a powdered flavoring agent, for example, no more than 0.2% by weight of a powdered flavoring agent, for example, no more than 0.1% by weight of a powdered flavoring agent, or for example, contains no powdered flavoring agent.

7. The orally disintegrating nicotine tablet according to any one of claims 1-6, wherein the tablet is free of flavoring agents.

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

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

10. The orally disintegrating nicotine tablet according to any one of claims 1-9, wherein the tablet is free of flavoring agents and high-intensity sweeteners.

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

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

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

14. The orally disintegrating nicotine tablet according to any one of claims 1-13, wherein the disintegrant is selected from starch, pregelatinized starch, modified cellulose, ion exchange resin, calcium silicate, cross-linked cellulose, cross-linked polyvinylpyrrolidone, cross-linked starch, cross-linked alginate, and combinations thereof.

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

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

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

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

19. The orally disintegrating nicotine tablet according to any one of claims 1-18, wherein the superdisintegrant is selected from 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 1-19, wherein the disintegrant is a superdisintegrant selected from 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 1-18, wherein the disintegrant is a superdisintegrant selected from croscarmellose, sodium carboxymethyl starch, and any combination thereof.

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

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

24. The orally disintegrating nicotine tablet according to any one of claims 1-23, wherein the tablet is formed by compression with a compression force of 1 to 35 kN, for example 2 to 30 kN, for example 2 to 20 kN.

25. The orally disintegrating nicotine tablet according to any one of claims 1-24, wherein the nicotine is selected from nicotine salts, free base nicotine, nicotine-ion exchange resin combinations, nicotine inclusion compounds or nicotine in any non-covalent bond, 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 1-25, wherein the nicotine comprises free nicotine base.

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

28. The orally disintegrating nicotine tablet according to any one of claims 1-27, wherein the nicotine salt is selected from nicotine ascorbic acid, nicotine aspartate, nicotine benzoate, nicotine monotartrate, nicotine hydrogen tartrate, nicotine chloride, nicotine citrate, nicotine fumarate, nicotine lactate, nicotine mucilage, nicotine laurate, nicotine acetylpropionic acid, nicotine malate, nicotine perchlorate, nicotine pyruvate, nicotine salicylate, nicotine sorbate, nicotine succinate, nicotine sulfate, and any combination thereof.

29. The orally disintegrating nicotine tablet according to any one of claims 1-28, wherein the nicotine comprises nicotine tartrate.

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

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

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

33. The orally disintegrating nicotine tablet according to any one of claims 1-32, wherein the pH adjuster is an alkaline pH adjuster, such as an alkaline buffer.

34. The orally disintegrating nicotine tablet according to any one of claims 1-33, wherein the pH adjuster comprises a pH adjuster selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, tromethamine, amino acids, dibasic phosphate, tribasic phosphate, or any combination thereof.

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

36. The orally disintegrating nicotine tablet according to any one of claims 1-35, wherein the pH adjuster comprises or is composed of sodium carbonate.

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

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

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

40. The orally disintegrating nicotine tablet according to any one of claims 1-39, wherein the weight of the tablet does not exceed 600 mg, for example not more than 500 mg, for example not more than 400 mg, for example not more than 300 mg, for example not more than 200 mg, for example not more than 150 mg, for example not more than 120 mg, for example not more than 100 mg, for example not more than 50 mg.

41. The orally disintegrating nicotine tablet according to any one of claims 1-40, 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 1-41, wherein the tablet is a single-layer tablet.

43. The orally disintegrating nicotine tablet according to any one of claims 1-42, the tablet further comprising a solubility modifier, the amount of said solubility modifier being up to 2% of the tablet weight, for example up to 1% of the tablet weight, for example up to 0.5% of the tablet weight, for example up to 0.25% of the tablet weight, for example up to 0.1% of the tablet weight.

44. The orally disintegrating nicotine tablet according to any one of claims 1-43, wherein the solubility modifier is selected xanthan gum, guar gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, alginate, pullulan, tragacanth gum, carrageenan gum, fenugreek gum, cassia gum, carrageenan, agar, alginic acid and their monovalent salts, and any combination thereof.

45. The orally disintegrating nicotine tablet according to any one of claims 1-44, wherein, The solubility regulator is selected from xanthan gum, guar gum, and any combination thereof.

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

47. The orally disintegrating nicotine tablet according to any one of claims 1-46, wherein the tablet is free of mucosal adhesives.

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

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

50. An orally disintegrating nicotine tablet for rapid relief of nicotine cravings, the tablet comprising nicotine, a disintegrant, and at least one sugar alcohol, wherein the total amount of flavoring agent and high-intensity sweetener in the tablet is less than 0.8% of the tablet weight.

51. The orally disintegrating nicotine tablet of claim 50, wherein the total amount of flavoring agent and high-intensity sweetener in the tablet does not exceed 0.6% of the tablet weight, for example, not more than 0.4% of the tablet weight, for example, not more than 0.3% of the tablet weight, for example, not more than 0.2% of the tablet weight.

52. A tablet, as claimed in claim 50 or 51 and any one of claims 1-49.

53. An oral nicotine tablet comprising, as a first module, the orally disintegrating nicotine tablet of any one of claims 1-52, and further comprising a second module, the composition of which differs from that of the first module.

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

55. The oral nicotine tablet of 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 53-55, wherein the second module comprises a solubility modifier.

57. The oral nicotine tablet of any one of claims 53-56, wherein the second module comprises at least 40% of the weight of the second module, for example at least 50%, for example at least 60%, for example at least 70%, for example at least 80% of the weight of the second module.

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

59. The oral nicotine tablet of any one of claims 53-58, wherein the amount of the solubility modifier contained in the second module is at least 1% of the weight of the second module, for example at least 2% of the weight of the second module, for example at least 3% of the weight of the second module.

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

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

62. The oral nicotine tablet according to any one of claims 53-61, wherein the second module is free of flavoring agent.

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

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