Nicotine tablets

Abstract

A water-soluble nicotine tablet is disclosed, the nicotine tablet comprising at least a first compression module and a second compression module, the first compression module being an FDT module and comprising nicotine, an alkaline pH adjuster, and a disintegrant, and the second compression module being a lozenge module and comprising an acidic pH adjuster. Also disclosed is a method of producing the nicotine tablet.

Description

[Technical field]

[0001] The present invention relates to a nicotine tablet and a method for producing such a nicotine tablet. [Background technology]

[0002] Oral tobacco compositions are known to cause an undesirable sensation in the user's throat, often referred to as a burning sensation.

[0003] The present invention has addressed this challenge by providing a nicotine delivery vehicle that is specifically optimized for improved user expectations and experience. Summary of the Invention

[0004] The present invention provides a water-soluble nicotine tablet comprising at least a first compression module and a second compression module, The first compression module is an FDT module; nicotine, Alkaline pH adjuster, and Contains a disintegrant, the second compression module is a lozenge module; This invention relates to a water-soluble nicotine tablet that contains an acidic pH adjuster.

[0005] In the context of the present invention, a module is defined as a plurality of compressed particles. An implementation of such a tablet is a tablet consisting of two modules, a first and a second module, each module being a layer of the tablet. In other words, such an example would be a bilayer tablet. Another implementation of such a tablet is a tablet consisting of two modules, a first and a second module, the second module being the tablet core and the first module being the compressed coating surrounding the first module, i.e. the tablet core. Other configurations of modules may be applied within the scope of the present invention. Also, some other modules may be applied within the scope of the present invention.

[0006] It should be noted that the understanding of a module in this context is a module that allows and facilitates the effective delivery or administration of the intended effect, i.e. nicotine, while providing the intended masking of undesirable flavors and reducing the undesirable burning sensation. This imposes some structural constraints on the module in the sense that it must be large enough to be able to deliver not only nicotine, but also the desired compounds used to mask the flavor and reduce the burning sensation. Furthermore, the module should facilitate the release of the components at the appropriate time.

[0007] Thus, a module in the context of the present invention, in an advantageous embodiment, comprises a population of compressed particles with a weight of at least 10% by weight of the tablet, in other words, a module is not intended to refer to an individual particle as conventionally understood from the art of tableting.

[0008] The first compression module is designed and provided as a module that is characterized as being an FDT module, i.e. a module that has the properties of a so-called fast dissolving tablet. Fast dissolving tablets, sometimes called orally disintegrating tablets (ODT), generally exhibit rapid disintegration in the mouth without the need to chew or drink liquid to ingest these products.

[0009] The FDT modules of the present invention typically exhibit rapid degradation, such as less than 60 seconds after placement in the mouth, or even faster, such as 30 seconds after placement in the mouth.

[0010] Therefore, the FDT module may be referred to as a fast dissolving module or a fast dissolving tablet module.

[0011] Disintegrants contribute to the rapid disintegration of the FDT module when it comes into contact with saliva. Disintegrants may often be thought of as a means to facilitate the breakdown of the module into smaller fragments upon administration to facilitate the release and ultimate absorption of nicotine.

[0012] The presence of an alkaline pH adjuster may advantageously promote efficient uptake of nicotine due to the resulting high pH value. An alkaline pH adjuster is a substance that, when dissolved in water having a pH of 7.0, raises the pH to above 7.5, measured at 25 degrees Celsius and atmospheric pressure.

[0013] The alkaline pH modifier may promote a desirable high proportion of non-protonated nicotine species, i.e., nicotine free base, present and available for absorption on the mucous membranes in the oral cavity.The presence of the alkaline pH modifier may also promote a desirable high pH in the oral cavity, thereby reducing undesirable protonation of the released nicotine free base during the fast release and absorption period, i.e., within the first period of use, thereby ensuring effective absorption of nicotine.

[0014] Thus, the presence of a disintegrant and an alkaline pH adjuster in the FDT module ensures that nicotine is rapidly released and available for transport across the mucosa into the bloodstream.

[0015] Achieving a fast release rate and efficient uptake / absorption of nicotine may be desirable as this ensures a rapid effect for the user, i.e., reduced cravings. Furthermore, the combination of having efficient release and efficient absorption advantageously allows for a relatively high utilization of the nicotine dose within the FDT module.

[0016] The relatively high utilization of the nicotine dose in the tablet may further reduce the required nicotine dose of the tablet without compromising the resulting effect. Since nicotine may be relatively expensive, a low nicotine dose may reduce production costs, but may also assist users who wish to reduce their nicotine intake. Furthermore, due to the low dose of nicotine, side effects such as nicotine burning may be reduced.

[0017] Regarding the second compressed module, which is the lozenge module, lozenge is a well-known term for medicinal tablets that are intended to dissolve or disintegrate over a period of minutes when placed in the oral cavity, typically releasing an active ingredient. Lozenges with different active ingredients are known, for example nicotine lozenges.

[0018] The lozenge module contains an acidic pH adjusting agent.

[0019] An acidic pH adjuster according to the present invention is a material which when dissolved in water having a pH of 7.0 induces a pH of less than 7.5 measured at 25 degrees Celsius and atmospheric pressure.

[0020] By providing a nicotine tablet that promotes the initiation of release of the acidic pH adjuster at a relatively slow release rate, either sequentially, i.e., after the rapid disintegration of the first compressed module, or simultaneously with the rapid disintegration of the first compressed module, the acidic pH adjuster induces a decrease in pH from above 7.5 induced by the first compressed module.

[0021] A decrease in oral pH from above 7.5 to below 7.5, for example below 7.0, promotes a decrease in the proportion of unprotonated unabsorbed nicotine present after the first period of use as more unabsorbed nicotine becomes protonated due to the decrease in pH.

[0022] It is therefore understood that an acidic pH modifier is an acidifying agent that promotes a decrease in oral pH, i.e., the acidic pH modifier causes acidification of the oral cavity and protonation of unabsorbed nicotine, thereby reducing the burning sensation.

[0023] In some embodiments, the acidic pH adjusting agent induces a decrease in oral pH, i.e., oral saliva, from greater than 7.5 to less than 7.5, including the neutral range of about 6.5 to 7.5.

[0024] In some embodiments, the acidic pH adjusting agent induces a decrease in oral pH below 7.

[0025] In other embodiments, the acidic pH adjusting agent induces a decrease in oral pH from above 7.5 to below 7.0.

[0026] In an advantageous embodiment, the acidic pH adjuster, when added to water having a pH of 7.0 at a temperature of 25 degrees Celsius, induces a pH of less than 7.0 when measured at 25 degrees Celsius and atmospheric pressure.

[0027] In some embodiments, the acidic pH adjuster induces an oral pH of less than 7.0. A decrease in oral pH from above 7.5 to below 7.0 promotes a decrease in the proportion of unprotonated unabsorbed nicotine present after the first period of use as more unabsorbed nicotine becomes protonated due to the decrease in pH.

[0028] In some embodiments, the acidic pH adjusting agent induces an oral pH of less than 6.5.

[0029] It has been found that by providing a tablet containing an acidic pH modifier in a second module that releases the ingredient over a period of several minutes, the undesirable burning sensation is reduced. It is believed that it is unprotonated, unabsorbed nicotine that causes the burning sensation.

[0030] By providing a nicotine tablet that promotes the initiation of release of the acidic pH adjuster at a relatively slow release rate, either sequentially, i.e., after the rapid disintegration of the first compressed module, or simultaneously with the rapid disintegration of the first compressed module, the proportion of unprotonated, unabsorbed nicotine present after the first period of use is reduced, i.e., the unabsorbed nicotine is protonated.

[0031] In sequential release, such as from a tablet comprising a core surrounded by compressed FDT modules, most of the alkaline pH modifier released from the FDT modules may gradually disappear from the oral cavity via swallowing saliva. The acidic pH modifier begins to release from the core after the collapse of the first compressed module, causing acidification of the oral cavity and protonation of unabsorbed nicotine, thereby reducing the burning sensation. It should be noted that in tablet designs that promote sequential release from modules, some overlap may occur in the release periods of the first and second modules, such as when the first compressed module disintegrates unevenly during use, exposing a portion of the second compressed module to the surface before the first compressed module completely disintegrates.

[0032] In simultaneous release, such as from a bilayer tablet, the two layers begin to release at the same time. Most of the alkaline pH modifier released from the FDT layer is gradually lost from the oral cavity via swallowing saliva. The lozenge layer begins to release the acidic pH modifier at the same time as the FDT layer, i.e., upon oral administration, but at a much slower rate, causing acidification of the oral cavity and protonation of unabsorbed nicotine that begins to take effect after the first period of use, thereby reducing the burning sensation.

[0033] The idea of ​​combining two structurally differently designed modules, one of which contains nicotine, makes it possible to provide a fast-release nicotine tablet, while also providing a tablet that promotes increased pleasure, such as reduced burning sensation and improved taste, combined with an impressive effect on the user.

[0034] The first compression module is typically designed to disintegrate in less than 60 seconds when administered orally in a nicotine tablet.

[0035] Fast-dissolving tablets represent an ideal way to provide nicotine users with a quick dose / burst of nicotine, giving them a fast effect.However, if too high a nicotine load is delivered too quickly, undesirable side effects may occur.Also, this quick relief of cravings does not fully cover the pleasure that is often associated with the desired pleasure for nicotine users.

[0036] Thus, a long-lasting sensation of pleasure may be obtained by combining a fast sensation of craving relief with a second phase sensation in one tablet.

[0037] However, it is surprising that the desired effects as perceived by the user, i.e. reduced nicotine craving, taste and / or pleasure, e.g. reduced burning sensation, may be obtained in one tablet comprising at least two modules designed to provide these desired effects.

[0038] The user time of the tablet may be easily designed to be about 5 minutes, i.e. similar to smoking a cigarette. The bitter taste of nicotine and the unwanted burning sensation may be reduced.

[0039] In an advantageous embodiment of the present invention, the second module provides a desired sensation of pleasure by reducing the burning sensation, while at the same time the first module provides a very fast release of nicotine and an alkaline pH modifier at concentrations that ensure craving relief.

[0040] The combination of the FDT module and the lozenge module facilitates the production of a robust tablet, providing both a rapid release of nicotine and a sustained release of the masking compound, while prolonging the salivation induced during use of the tablet. It is believed that the prolonged salivation induced helps reduce the burning sensation, as increased saliva secretion aids in the distribution of the acidic pH modifier both in the mouth and throat upon swallowing.

[0041] In an advantageous embodiment of the invention, the water-soluble nicotine tablet comprises nicotine in an amount of at least 0.2 mg, such as at least 0.5 mg, such as at least 1.0 mg.

[0042] In an advantageous embodiment of the invention, the water soluble nicotine tablet comprises nicotine in an amount between 0.2 mg and 5.0 mg, such as between 0.5 mg and 4.0 mg, such as between 1.0 mg and 3.0 mg, such as between 1.0 mg and 2.0 mg.

[0043] In an advantageous embodiment of the invention, the nicotine is contained in the first compression module.

[0044] In an embodiment of the invention, the first compressed module comprises nicotine in an amount between 0.2 mg and 5.0 mg of nicotine, such as between 0.5 mg and 4.0 mg of nicotine, for example between 1.0 mg and 3.0 mg of nicotine, such as between 1.0 mg and 2.0 mg of nicotine.

[0045] In an embodiment of the invention, the first compressed module comprises nicotine in an amount of less than 5% by weight of the first compressed module, such as less than 3% by weight of the first compressed module, such as less than 2% by weight of the first compressed module.

[0046] The advantage of the present invention may be that it provides surprisingly effective craving relief. By providing a first compressed module that is an FDT module containing nicotine, the tablet of the present invention has been shown to provide sustained craving relief by promoting the rapid onset of nicotine, but at the same time, promoting a desirable sustained pleasure sensation that is highly effective. Having highly effective craving relief may further provide that the required nicotine dose of the tablet may be reduced without compromising the resulting effect. Since nicotine may be relatively expensive, a lower nicotine dose may reduce production costs, but may also assist users who wish to lower their nicotine intake.

[0047] In an embodiment of the invention, the first compression module comprises nicotine in an amount of 0.2-5% by weight of the first compression module, such as 0.3-3% by weight of the first compression module, for example 0.5-2% by weight of the first compression module.

[0048] In an embodiment of the invention, the second compression module does not contain nicotine.

[0049] The advantage of the present invention is that by providing a first compressed module that is an FDT module containing nicotine and an alkaline pH modifier, the tablet of the present invention promotes rapid nicotine action and craving relief. Furthermore, it has been found that the tablet provides sustained craving relief by promoting a desirable and sustained pleasure sensation that is highly effective. Thus, acceptable craving relief may be achieved from a tablet that contains nicotine only in the first compressed module. Also, by providing a tablet with a second compressed module that does not contain nicotine, the burning sensation is reduced.

[0050] Thus, in the above embodiments, the nicotine is contained in the first compression module, for example in embodiments where the tablet comprises a first and a second compression module, the first compression module contains the nicotine.

[0051] In an embodiment of the invention, the nicotine is contained in a first compression module.

[0052] In an advantageous embodiment of the invention, the nicotine is selected from the list consisting of nicotine free base and nicotine salts, or combinations thereof.

[0053] In an advantageous embodiment of the invention, the nicotine comprises nicotine free base.

[0054] Free base nicotine includes nicotine mixed with sugar alcohols, modified calcium carbonate, water soluble fiber, water insoluble fiber, and combinations thereof.

[0055] In an embodiment of the invention, the nicotine is nicotine free base.

[0056] In an advantageous embodiment of the invention, the nicotine comprises a nicotine salt.

[0057] An advantage of such embodiments may be that, for example, the rapid dissociation of the nicotine salt may facilitate rapid relief of nicotine cravings.

[0058] In an advantageous embodiment of the invention, the nicotine is a nicotine salt.

[0059] In an advantageous embodiment of the invention, the nicotine salt is selected from the list consisting of nicotine ascorbate, nicotine aspartate, nicotine benzoate, nicotine monotartrate, nicotine bitartrate, nicotine hydrochloride, nicotine dihydrochloride, nicotine citrate, nicotine fumarate, nicotine gensitate, nicotine lactate, nicotine mucate, nicotine laurate, nicotine levulinate, nicotine malate, nicotine perchlorate, nicotine pyruvate, nicotine salicylate, nicotine sorbate, nicotine succinate, nicotine zinc chloride, nicotine sulfate, nicotine tosylate, and combinations thereof.

[0060] It is understood that the nicotine salt may also be provided as a hydrated salt.

[0061] In an embodiment of the invention, the nicotine salt is selected from the list consisting of nicotine aspartate, nicotine benzoate, nicotine monotartrate, nicotine bitartrate, nicotine hydrochloride, nicotine dihydrochloride, nicotine citrate, nicotine fumarate, nicotine lactate, nicotine mucinate, nicotine laurate, nicotine levulinate, nicotine malate, nicotine pyruvate, nicotine sorbate, nicotine succinate, nicotine sulfate, and combinations thereof.

[0062] In an embodiment of the invention, the nicotine salt is selected from the 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.

[0063] In an advantageous embodiment of the invention, the nicotine comprises nicotine bitartrate.

[0064] An advantage of such embodiments may be that the rapid release of nicotine bitartrate, for example, may facilitate rapid relief of nicotine cravings.

[0065] In an advantageous embodiment of the invention, the nicotine is nicotine bitartrate.

[0066] In an advantageous embodiment of the invention, the first compression module comprises an alkaline pH adjuster in an amount of at least 0.2% by weight of the first compression module, such as at least 0.3% by weight of the first compression module, such as at least 0.4% by weight of the first compression module, for example at least 0.5% by weight of the first compression module.

[0067] The amount of alkaline pH adjuster should promote a desirable pH in the oral cavity of above 7.5, such as a pH of 7.5 to 10, such as a pH of 7.5 to 9.5, such as a pH of 7.5 to 9.0.

[0068] The desired high pH promotes absorption of nicotine on the oral mucosa and therefore the oral pH is ideally greater than 7.5 during at least the first 60 seconds of use, e.g., between 7.5 and 9.0 during at least the first 60 seconds of use, or greater than 7.5 during at least the disintegration time of the first compressed module, e.g., between 7.5 and 9.0 during the disintegration time of the first compressed module.

[0069] The alkaline pH adjusting agent released from the FDT module dissolves in saliva, raises the pH in the oral cavity, and is then carried away from the oral cavity via swallowing of the saliva. Thus, the amount of alkaline pH adjusting agent, even if an excess amount is included in the first module, does not prevent the desired effect from being achieved from the acidic pH adjusting agent released from the second compressed module, i.e., protonation of unabsorbed unprotonated nicotine.

[0070] The resulting high pH value may also advantageously provide a tingling sensation in the mouth that may be perceived as a desirable mouthfeel, for example due to its similarity to tobacco-based products.

[0071] In an embodiment of the invention, the first compressed module comprises an alkaline pH adjuster in an amount of 10% by weight of the first compressed module or less, such as 7% by weight of the first compressed module or less, such as 6% by weight of the first compressed module or less, such as 5% by weight of the first compressed module or less, such as 3% by weight of the first compressed module or less, such as 2% by weight of the first compressed module or less.

[0072] Some alkaline pH adjusters have a different taste and may therefore induce undesirable inferior qualities in the taste or flavor profile of the tablet. Therefore, it may be desirable not to include too much alkaline pH adjuster, such as no more than 10% by weight of the first compression module.

[0073] Also, too much alkaline pH adjuster may cause irritation in the oral cavity.

[0074] In an advantageous embodiment of the invention, the first compression module comprises an alkaline pH adjuster in an amount of 0.2-10% by weight of the first compression module, such as 0.2-7% by weight of the first compression module, for example 0.2-6% by weight of the first compression module, for example 0.2-5% by weight of the first compression module, for example 0.3-4% by weight of the first compression module, for example 0.4-3% by weight of the first compression module, for example 0.5-2% by weight of the first compression module.

[0075] In an embodiment of the invention, the first compressed module comprises an alkaline pH adjuster in an amount of 0.5 mg to 30 mg, such as 1 mg to 20 mg, for example 5 to 15 mg.

[0076] It is understood that the pH adjusting effect of the first compression module should be alkaline, and therefore any embodiment in which the first compression module includes some amount of acidic pH adjuster and an excess amount of alkaline pH adjuster to provide an overall alkaline effect is considered within the scope of the present invention.

[0077] However, for economy of composition, it may be advantageous to have a first compression module that does not contain an acidic pH modifier.

[0078] In an embodiment of the invention, the first compression module does not include an acidic pH adjuster.

[0079] In an advantageous embodiment of the invention, the acidic pH adjuster is included in the second compression module.

[0080] In an advantageous embodiment of the invention, the alkaline pH adjuster comprises an alkaline pH adjuster selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol, amino acids, di-alkali hydrogen phosphates, tri-alkali phosphates, or any combination thereof.

[0081] In an embodiment of the invention, the alkaline pH adjuster 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.

[0082] In an embodiment of the invention, the alkaline pH adjuster is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol, amino acids, or any combination thereof.

[0083] In an advantageous embodiment of the present invention, the alkaline pH adjuster is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, or any combination thereof.

[0084] Combinations of carbonate and bicarbonate may be particularly advantageous, such as a sodium carbonate-sodium bicarbonate buffer system, for example sodium carbonate and sodium bicarbonate in a weight ratio of 5:1 to 2.5:1, preferably 4.1:1 to 3.5:1.

[0085] In an advantageous embodiment of the invention, the pH adjuster comprises or is sodium carbonate.

[0086] In an embodiment of the invention, the alkaline pH adjuster is selected from the group consisting of trometamol, amino acids, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, or any combination thereof.

[0087] In an embodiment of the invention, the alkaline pH adjuster is selected from the group consisting of trometamol, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, or any combination thereof.

[0088] In an embodiment of the invention, the alkaline pH adjuster comprises a di-alkali hydrogen phosphate and / or a tri-alkali phosphate, for example disodium phosphate, dipotassium phosphate, trisodium phosphate and / or tripotassium phosphate.

[0089] Because trometamol and phosphate buffers have a desirable relatively neutral flavor, the use of these pH adjusters may be found not to detract from the flavor and mouthfeel of the nicotine tablet.

[0090] In an embodiment of the invention, the alkaline pH adjuster comprises trometamol.

[0091] In an embodiment of the invention, the alkaline pH adjuster comprises trometamol.

[0092] In the context of the present invention, the term trometamol refers to (tris(hydroxymethyl)aminomethane), also sometimes called Tris buffer.

[0093] In an embodiment of the invention, the alkaline pH adjuster comprises an amino acid.

[0094] In an embodiment of the invention, the alkaline pH adjuster comprises an amino acid.

[0095] In an advantageous embodiment of the invention, the first compression module induces a pH greater than 7.5 when dissolved in water having a pH of 7.0, measured at 25 degrees Celsius and atmospheric pressure.

[0096] In an advantageous embodiment of the invention, the first compression module comprises a disintegrant in an amount of at least 0.5% by weight of the first compression module, such as at least 1% by weight of the first compression module, for example at least 2% by weight of the first compression module, such as at least 3% by weight of the first compression module, for example at least 4% by weight of the first compression module, for example at least 5% by weight of the first compression module.

[0097] In an advantageous embodiment of the invention, the first compression module comprises disintegrant in an amount of 0.5% to 25% by weight of the first compression module, such as 0.5% to 15% by weight, for example 5% to 15% by weight, such as 5% to 10% by weight.

[0098] In an embodiment of the invention, the first compression module comprises a disintegrant in an amount of 0.5% to 25% by weight of the first compression module, such as 5% to 25% by weight, for example 10% to 25% by weight, such as 10% to 20% by weight.

[0099] In an embodiment of the invention, the first compression module comprises a superdisintegrant in an amount of 0.5% to 25% by weight of the first compression module, such as 0.5% to 15% by weight, for example 5% to 15% by weight, such as 5% to 10% by weight.

[0100] In an embodiment of the invention the disintegrant has a particle size of less than 125 micrometers, such as less than 75 micrometers, for example less than 50 micrometers.

[0101] It is understood that a particle size of less than 125 micrometers refers to particles capable of passing through a sieve of 120 mesh size (US standard mesh), a particle size of less than 75 micrometers refers to particles capable of passing through a sieve of 200 mesh size (US standard mesh), a particle size of less than 50 micrometers refers to particles capable of passing through a sieve of 325 mesh size (US standard mesh), and a particle size of less than 15 micrometers refers to particles capable of passing through a sieve of 800 mesh size (US standard mesh).

[0102] An advantage of the above embodiment using a disintegrant with a smaller particle size is, for example, that the relative surface area of ​​the disintegrant particles is greater, facilitating shorter disintegration times.

[0103] Furthermore, the use of a disintegrant with a particle size of less than 125 micrometers improves the mouthfeel of the tablet during use: the rapid disintegration of the first compressed module containing a disintegrant with a particle size of less than 125 micrometers does not cause a gritty or lumpy sensation in the user's mouth.

[0104] In an embodiment of the invention, at least 50% by weight of the disintegrant has a particle size of less than 50 micrometers.

[0105] In an embodiment of the invention, at least 25% by weight of the disintegrant has a particle size of less than 15 micrometers.

[0106] In an advantageous embodiment of the invention, the disintegrant is selected from the list consisting of starch, pregelatinized starch, cellulose, modified cellulose, microcrystalline cellulose, alginates, ion exchange resins, calcium silicate, crosslinked cellulose, crosslinked polyvinylpyrrolidone, crosslinked starch, crosslinked alginic acid, and combinations thereof.

[0107] In the context of the present invention, starch refers to starches of various origins such as potato starch, corn starch, wheat starch, pea starch, etc.

[0108] Examples of pregelatinized starch disintegrants include structures and trade names such as pregelatinized potato starch, pregelatinized wheat starch, pregelatinized corn starch, Lycatab®, Starch 1500®, and the like.

[0109] Examples of modified cellulose disintegrating agents include structural names such as methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose.

[0110] Microcrystalline cellulose is a refined form of natural cellulose. Examples of microcrystalline cellulose disintegrants include trade names such as Avicel®, Emcocel®, and Vivapor® MCC.

[0111] Examples of alginate disintegrants include various alkaline alginates and trade names such as Vivapur® alginate.

[0112] It is understood that some disintegrants are referred to as superdisintegrants.

[0113] In an advantageous embodiment of the invention, the disintegrant comprises a superdisintegrant.

[0114] In some embodiments, the disintegrant may include a combination of a regular disintegrant and a superdisintegrant.

[0115] In an advantageous embodiment of the invention, the disintegrant is a superdisintegrant.

[0116] In an advantageous embodiment of the invention, the disintegrant is a superdisintegrant selected from the group consisting of cross-linked cellulose, cross-linked polyvinylpyrrolidone, cross-linked starch, cross-linked alginic acid, and any combination thereof.

[0117] Examples of crosslinked cellulose superdisintegrants include structures and trade names such as Croscarmellose®, Ac-Di-Sol®, L-HPC, Solutab®, and the like.

[0118] Examples of cross-linked polyvinylpyrrolidone (PVP) superdisintegrants include structures and trade names such as Crosspovidone M®, Kollidon®, Polyplasdone®, polyplasdone XL®, Kollidon CL®, and the like.

[0119] Examples of crosslinked starch superdisintegrants include structures and trade names such as sodium starch glycolate, Glycolys®, Explotab®, Primogel®, Vivastar®, and Tablo®.

[0120] Examples of cross-linked alginates include structures and trade names such as Alginic acid NF® and Staialgine®.

[0121] In an embodiment of the invention, the disintegrant is a superdisintegrant selected from the group consisting of crosslinked cellulose, crosslinked polyvinylpyrrolidone (PVP), crosslinked starch, and any combination thereof.

[0122] In an embodiment of the invention, the first compression module comprises a superdisintegrant selected from the group consisting of crosslinked cellulose, crosslinked polyvinylpyrrolidone, crosslinked starch, crosslinked alginic acid, and any combination thereof, in an amount of 0.5% to 25% by weight of the first compression module, such as 0.5% to 15% by weight, for example 5% to 15% by weight, for example 5% to 10% by weight.

[0123] In an advantageous embodiment of the present invention, the superdisintegrant is cross-linked polyvinylpyrrolidone (PVP).

[0124] In an embodiment of the invention, at least 50% by weight of the cross-linked polyvinylpyrrolidone (PVP) has a particle size of less than 50 micrometers.

[0125] In an embodiment of the invention, at least 25% by weight of the cross-linked polyvinylpyrrolidone (PVP) has a particle size of less than 15 micrometers.

[0126] An advantage of using cross-linked polyvinylpyrrolidone as a superdisintegrant may be that it reduces the dependence of disintegration time on compression force, allowing for fairly low disintegration times even when high compression forces are used.

[0127] In an embodiment of the invention, the disintegrant is a non-ionic disintegrant.

[0128] In an embodiment of the invention, the disintegrant is a non-ionic superdisintegrant such as cross-linked polyvinylpyrrolidone (PVP).

[0129] In an embodiment of the invention, the first compression module has a moisture content of less than 10% by weight, such as less than 5% by weight, such as less than 2% by weight, such as less than 1% by weight.

[0130] In an embodiment of the invention, the first compression module has a water content of 0-10% by weight, such as 0.01-5% by weight, such as 0.05-2% by weight, such as 0.1-1% by weight.

[0131] That is, in the above embodiment, the first compression module may not contain water.

[0132] An advantage of the above embodiment may be that the stability of the first compression module is improved, particularly when the first compression module includes a disintegrant, such as a superdisintegrant.

[0133] In an advantageous embodiment of the invention, the second compression module comprises an acidic pH modifier in a molar ratio of up to 10 relative to the nicotine in the first compression module, such as up to 8 relative to the nicotine in the first compression module, such as up to 7 relative to the nicotine in the first compression module, such as up to 6 relative to the nicotine in the first compression module, such as up to 5 relative to the nicotine in the first compression module, such as up to 3 relative to the nicotine in the first compression module.

[0134] By providing a tablet that releases an acidic pH modifier from the second module, the pH in the oral cavity is acidified and unabsorbed, unprotonated nicotine is protonated, which has been found to correlate with the reduced burning sensation demonstrated in Examples 3C and 3D.

[0135] When a desired amount of an acidic pH modifier is included in the tablet, it may be found to improve or support the taste or flavor profile of the tablet, thereby also improving the overall sense of enjoyment of the tablet, which may typically be the case when fruit flavors are used.

[0136] However, including too much acidic pH modifier may detract from the taste and flavor of the tablet, thereby diminishing the overall sense of enjoyment.

[0137] Here, molar ratio refers to the molar content of the acidic pH adjuster divided by the molar content of nicotine.

[0138] In an advantageous embodiment of the invention, the second compression module comprises an acidic pH adjuster in a molar ratio of at least 0.5 relative to the nicotine in the first compression module, such as at least 0.75 relative to the nicotine in the first compression module, such as at least 1 relative to the nicotine in the first compression module, such as at least 2 relative to the nicotine in the first compression module.

[0139] Nicotine and alkaline pH modifier are released from the first compressed module, thereby absorbing a significant amount of nicotine, e.g., about 50% of the nicotine is absorbed, e.g., about 60% of the nicotine is absorbed, e.g., about 70% of the nicotine is absorbed, e.g., about 80% of the nicotine is absorbed, or more. Thus, the amount of acidic pH modifier in the second module should be matched to the effect of the first compressed module, i.e., the first compressed module is designed to provide high nicotine absorption, i.e., craving relief, and the second compressed module is designed to prolong the effect of the first compressed module, i.e., promote sustained craving relief and reduce the side effects of the effect of the first compressed module, i.e., reduce the burning sensation and increase the pleasure sensation.

[0140] An excess of acidic pH modifier may be advantageously added to accommodate the amount of acidic pH modifier that reacts with other components in the oral cavity besides unabsorbed nicotine, such as saliva components, alkaline pH modifiers, etc., i.e., to ensure an effective amount is available for protonating any unabsorbed nicotine.

[0141] Also, the second compressed module has a lower release rate than the first compressed module, and therefore the effect of the acidic pH modifier, i.e., acidification of the oral cavity and protonation of nicotine, may be achieved more quickly when a greater amount of acid, such as an excess amount relative to nicotine, is included in the tablet.

[0142] Additionally, the acidic pH modifier may, in some embodiments, enhance the flavor of the tablet.

[0143] In an advantageous embodiment of the invention, the second compression module comprises an acidic pH adjuster in a molar ratio of 0.5 to 10 relative to the nicotine in the first compression module, such as 0.75 to 8 relative to the nicotine in the first compression module, for example 0.75 to 7 relative to the nicotine in the first compression module, for example 1 to 6 relative to the nicotine in the first compression module.

[0144] In an embodiment of the invention, the first compression module comprises a pH adjuster in an amount of 0.2-10% by weight of the first compression module, such as 0.2-7% by weight of the first compression module, for example 0.2-6% by weight of the first compression module, for example 0.2-5% by weight of the first compression module, for example 0.3-4% by weight of the first compression module, for example 0.4-3% by weight of the first compression module, for example 0.5-2% by weight of the first compression module, and the second compression module comprises an acidic pH adjuster in a molar ratio of 0.5-10 relative to the nicotine in the first compression module, for example 0.75-8 relative to the nicotine in the first compression module, for example 0.75-7 relative to the nicotine in the first compression module, for example 1-6 relative to the nicotine in the first compression module.

[0145] In an embodiment of the invention, the second compressed module comprises an acidic pH adjuster in an amount of 15% by weight of the second compressed module or less, such as 10% by weight of the second compressed module or less, such as 5% by weight of the second compressed module or less.

[0146] In an embodiment of the invention, the second compressed module comprises an acidic pH adjuster in an amount of at least 0.5% by weight of the second compressed module, such as at least 1.0% by weight of the second compressed module.

[0147] In an embodiment of the invention, the second compressed module comprises an acidic pH adjuster in an amount of 0.5 to 15% by weight of the second compressed module, such as 0.5 to 10% by weight of the second compressed module, for example 0.5 to 5% by weight of the second compressed module, for example 0.5 to 3% by weight of the second compressed module.

[0148] In an embodiment of the invention, the first compressed module comprises a pH adjuster in an amount of 0.2-10% by weight of the first compressed module, such as 0.2-7% by weight of the first compressed module, for example 0.2-6% by weight of the first compressed module, for example 0.2-5% by weight of the first compressed module, for example 0.3-4% by weight of the first compressed module, for example 0.4-3% by weight of the first compressed module, for example 0.5-2% by weight of the first compressed module, and the second compressed module comprises an acidic pH adjuster in an amount of 0.5-15% by weight of the second compressed module, for example 0.5-10% by weight of the second compressed module, for example 0.5-5% by weight of the second compressed module, for example 0.5-3% by weight of the second compressed module.

[0149] In an embodiment of the invention, the second compressed module comprises an acidic pH adjuster in an amount of 30 mg or less, such as 25 mg or less, such as 20 mg or less, such as 15 mg or less, such as 10 mg or less.

[0150] In an advantageous embodiment of the invention, the second compression module comprises an acidic pH adjuster in an amount of 0.5 mg to 30 mg, such as 1 mg to 20 mg, for example 5 to 15 mg.

[0151] In an embodiment of the invention, the first compressed module contains nicotine in an amount of 0.2 mg to 5.0 mg, an alkaline pH adjuster in an amount of 0.5 mg to 30 mg, such as 1 mg to 20 mg, for example 5 to 15 mg, and the second compressed module contains an acidic pH adjuster in an amount of 0.5 mg to 30 mg.

[0152] In an embodiment of the invention, the acidic pH adjuster has at least one pKa value at 25 degrees Celsius that is less than 7, such as less than 6, for example less than 5. In an embodiment of the invention, the acidic pH adjuster has at least one pKa value at 25 degrees Celsius that is less than 7.0, such as less than 6.0, for example less than 5.0.

[0153] In an advantageous embodiment of the invention, the acidic pH adjuster comprises an acidic pH adjuster selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0154] In an embodiment of the invention, the second compression module comprises an acidic pH adjuster in a molar ratio of at least 0.5 relative to the nicotine in the first compression module, the acidic pH adjuster comprising an acidic pH adjuster selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0155] In an embodiment of the invention, the second compression module comprises an acidic pH adjuster in a molar ratio of 0.5 to 10 relative to the nicotine in the first compression module, the acidic pH adjuster comprising an acidic pH adjuster selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0156] Thus, the molar ratio refers to the molar amount of acidic pH adjuster relative to the molar amount of nicotine in the first compression module.

[0157] In an embodiment of the invention, the first compression module comprises nicotine in an amount between 0.2 mg and 5.0 mg of nicotine, the nicotine being selected from the list consisting of nicotine free base and nicotine salts, or combinations thereof, and the second compression module comprises an acidic pH adjuster in a molar ratio of 0.5 to 10 relative to the nicotine in the first compression module.

[0158] In an embodiment of the invention, the first compression module comprises nicotine in an amount between 0.2 mg and 5.0 mg of nicotine, the nicotine being a nicotine salt, and the second compression module comprises an acidic pH adjuster in a molar ratio of between 0.5 and 10 relative to the nicotine in the first compression module, the acidic pH adjuster comprising an acidic pH adjuster selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0159] In an embodiment of the invention, the acidic pH adjuster comprises an acidic pH adjuster selected from the list consisting of phosphoric acid, monosodium dihydrogen phosphate, monopotassium dihydrogen phosphate, citric acid, monosodium dihydrogen citrate, monopotassium dihydrogen citrate, disodium hydrogen citrate, dipotassium hydrogen citrate, malic acid, monosodium malate, monopotassium malate, succinic acid, monosodium succinate, monopotassium succinate, tartaric acid, monosodium tartrate, monopotassium tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0160] In an embodiment of the invention, the acidic pH adjuster is selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, monoalkaline dihydrogen phosphate-dialkaline hydrogen phosphate mixture, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0161] In an embodiment of the invention, the second compression module comprises an acidic pH adjuster in a molar ratio of at least 0.5 relative to the nicotine in the first compression module, the acidic pH adjuster comprising an acidic pH adjuster selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, monoalkaline dihydrogen phosphate-dialkaline hydrogen phosphate mixture, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0162] In embodiments where the acidic pH adjuster is a mixture of pH adjusters, the molar ratio refers to the total molar amount of acidic pH adjuster(s) relative to the molar amount of nicotine in the first compression module.

[0163] In an advantageous embodiment of the invention, the acidic pH adjuster is selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0164] In an embodiment of the invention, the acidic pH adjuster is selected from the list consisting of phosphoric acid, monosodium dihydrogen phosphate, monopotassium dihydrogen phosphate, citric acid, monosodium dihydrogen citrate, monopotassium dihydrogen citrate, disodium hydrogen citrate, dipotassium hydrogen citrate, malic acid, monosodium malate, monopotassium malate, succinic acid, monosodium succinate, monopotassium succinate, tartaric acid, monosodium tartrate, monopotassium tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0165] In an embodiment of the invention, the acidic pH adjuster is selected from the list consisting of citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0166] In an embodiment of the invention, the acidic pH adjuster is selected from the list consisting of citric acid, monosodium dihydrogen citrate, monopotassium dihydrogen citrate, disodium hydrogen citrate, dipotassium hydrogen citrate, malic acid, monosodium malate, monopotassium malate, succinic acid, monosodium succinate, monopotassium succinate, tartaric acid, monosodium tartrate, monopotassium tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0167] In an advantageous embodiment of the invention, the acidic pH adjuster is selected from the list consisting of citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, and combinations thereof.

[0168] In an embodiment of the invention, the acidic pH adjuster is selected from the list consisting of citric acid, monosodium dihydrogen citrate, monopotassium dihydrogen citrate, disodium hydrogen citrate, dipotassium hydrogen citrate, malic acid, monosodium malate, monopotassium malate, and combinations thereof.

[0169] In an embodiment of the invention, the acidic pH adjuster is phosphoric acid, mono-alkali dihydrogen phosphate, or a combination thereof.

[0170] In an embodiment of the invention, the second compression module induces a pH of less than 7.5 when dissolved in water having a pH of 7.0, when measured at 25 degrees Celsius and atmospheric pressure.

[0171] It is understood that the pH adjusting effect of the second compressed module should be acidic relative to the pH induced by the first compressed module. The acidic pH adjusting agent(s) of the second compressed module should provide a reduced oral pH upon dissolution, i.e., the second compressed module should provide a reduction in the oral pH from above 7.5 induced by the first compressed module to below 7.5. Thus, the second compressed module induces a pH of less than 7.5 when added to water with a pH of 7.0, measured at 25° C. and atmospheric pressure.

[0172] In an embodiment of the invention, the second compression module induces a pH of less than 7.0 when dissolved in water having a pH of 7.0 when measured at 25 degrees Celsius and atmospheric pressure.

[0173] It is understood that in a preferred embodiment of the present invention, the pH adjusting effect of the second compressed module should be acidic. In a preferred embodiment of the present invention, the pH adjuster of the second compressed module should provide a lower pH when added to water with a pH of 7.0 when measured at 25 degrees Celsius and atmospheric pressure. Thus, any embodiment in which some amount of alkaline pH adjuster and an excess amount of acidic pH adjuster are included in the second module to provide an overall acidic effect is considered to be within the scope of the present invention.

[0174] However, for economy of composition, it may be advantageous to have a second compression module that does not contain an alkaline pH adjuster.

[0175] In some embodiments, an acidic pH adjuster, when added to water having a pH of 7.0 at a temperature of 25 degrees Celsius, will induce a pH of less than 7.0, while an alkaline pH adjuster, when added to water having a pH of 7.0, will induce a pH of greater than 7.5.

[0176] In an embodiment of the invention, the second compression module does not include an alkaline pH adjuster.

[0177] In an advantageous embodiment of the invention, the alkaline pH adjuster is included in the first compression module.

[0178] In an advantageous embodiment of the invention, the nicotine tablet comprises a flavouring, which may be advantageously used as taste masking for the nicotine.

[0179] In an embodiment of the invention, the nicotine tablet comprises flavouring in an amount of at least 0.1% by weight of the nicotine tablet.

[0180] In an advantageous embodiment of the invention, the nicotine tablet comprises flavouring in an amount of 0.1 to 15.0% by weight of the nicotine tablet, such as 0.1 to 10.0% by weight of the nicotine tablet, for example 0.1 to 5.0% by weight of the nicotine tablet, for example 0.2 to 3.0% by weight of the nicotine tablet.

[0181] In an embodiment of the invention, flavouring is contained in the first and second compression modules, ie, both modules contain flavouring.

[0182] In an embodiment of the invention, the second compression module contains a flavoring.

[0183] In an advantageous embodiment of the invention, the flavouring is contained in a second compression module.

[0184] In an embodiment of the invention, the second compressed module comprises flavouring in an amount of 0.1 to 15.0% by weight of the second compressed module, such as 0.1 to 10.0% by weight of the second compressed module, for example 0.1 to 5.0% by weight of the second compressed module, for example 0.2 to 3.0% by weight of the second compressed module.

[0185] In an advantageous embodiment of the invention, the flavouring is contained in a second compression module.

[0186] Thus, in the above embodiment, all of the flavouring is contained in the second compression module, ie the first compression module does not contain any flavouring.

[0187] In embodiments of the invention where the tablet is comprised of a first and second compression module and all flavoring is contained in the second compression module, the first compression module does not contain any flavoring.

[0188] In an embodiment of the invention, the first compression module does not contain any flavouring.

[0189] An advantage of the above embodiment may be that nicotine stability is increased by facilitating separation of nicotine from flavoring, thereby minimizing flavoring-induced degradation of nicotine in the first compression module.A further advantage of the above embodiment may be that the nicotine tablet is relatively simple to manufacture due to the limited amounts of ingredients in each module, while providing surprisingly good results in terms of taste and flavor perception to the user.

[0190] The flavoring may induce saliva secretion during use of the tablet. By only including the flavoring in the second module, flavoring-induced saliva production during the collapse of the first compressed module may be limited or even avoided. Thus, the user's desire to swallow during the collapse of the first compressed module is reduced, thereby reducing the nicotine's ability to reach the throat and cause a burning sensation.

[0191] Also, in embodiments where the first and second compressed modules are tablet layers, such tablets may allow for the simultaneous release of flavor from the second compressed module while nicotine is released from the first compressed module, thereby reducing the bitter taste of nicotine.

[0192] In an advantageous embodiment of the invention, the flavoring is selected from the group of menthol, peppermint, wintergreen, sweet mint, spearmint, vanillin, chocolate, coffee, cinnamon, clove, tobacco, citrus and fruit flavors and mixtures thereof.

[0193] In an embodiment of the invention, the nicotine and flavorings are contained in opposing modules.

[0194] In an embodiment of the invention, the first compression module does not contain flavouring and the second compression module does not contain nicotine.

[0195] An advantage of the above embodiment may be that nicotine stability is increased by facilitating separation of nicotine from flavorants, thereby minimizing flavor-induced degradation of nicotine.

[0196] In an advantageous embodiment of the invention, the flavouring is contained in the second compression module and the nicotine is contained in the first compression module.

[0197] In an embodiment of the invention, the second compression module comprises a fruit flavoring and the acidic pH adjuster is selected from the group consisting of citric acid, mono-alkaline dihydrogen citrate, di-alkaline hydrogen citrate, malic acid, mono-alkaline malate, and combinations thereof.

[0198] In an advantageous embodiment of the invention, the nicotine tablet comprises a sugar alcohol.

[0199] Sugar alcohols may be advantageously used to achieve desirable flavors and are attractive alternatives to sugar sweeteners.

[0200] In an advantageous embodiment of the invention, the nicotine tablet comprises sugar alcohol in an amount of at least 50% by weight of the nicotine tablet, such as at least 60% by weight of the nicotine tablet, such as at least 70% by weight of the nicotine tablet, such as at least 75% by weight of the nicotine tablet, such as at least 80% by weight of the nicotine tablet, such as at least 85% by weight of the nicotine tablet.

[0201] Sugar alcohols have desirable solubility properties, and therefore, it has been found that nicotine tablets containing a significant amount of sugar alcohol promote desirable dissolution of the nicotine tablet.

[0202] In an advantageous embodiment of the invention, the nicotine tablet comprises sugar alcohol in an amount of 50-97% by weight of the nicotine tablet, such as 60-97% by weight of the nicotine tablet, for example 70-97% by weight of the nicotine tablet, such as 70-90% by weight of the nicotine tablet.

[0203] In an embodiment of the invention, the nicotine tablet comprises sugar alcohol in an amount of 50-97% by weight of the nicotine tablet, such as 60-95% by weight of the nicotine tablet, for example 70-95% by weight of the nicotine tablet, such as 75-95% by weight of the nicotine tablet, for example 80-95% by weight of the nicotine tablet, such as 85-95% by weight of the nicotine tablet.

[0204] In an embodiment of the invention, the first compression module comprises a sugar alcohol.

[0205] The sugar alcohol has desirable saliva solubility, so that when the nicotine tablet is in use, the sugar alcohol dissolves and aids in release from the modules, such as the rapid release of nicotine and the alkaline pH adjuster from the first compressed module, and the release of the acidic pH adjuster from the second compressed module.

[0206] In an embodiment of the invention, the first compression module comprises sugar alcohol in an amount of at least 50% by weight of the first compression module, such as at least 60% by weight of the first compression module, such as at least 70% by weight of the first compression module, such as at least 80% by weight of the first compression module, for example at least 85% by weight of the first compression module.

[0207] In an advantageous embodiment of the invention, the first compression module comprises sugar alcohol in an amount between 50% and 97% by weight of the first compression module, such as between 60% and 95% by weight of the first compression module, for example between 70% and 90% by weight of the first compression module.

[0208] In an embodiment of the invention, the first compression module comprises sugar alcohol in an amount of 50-97% by weight of the first compression module, such as 60-97% by weight of the first compression module, for example 70-97% by weight of the first compression module.

[0209] In an embodiment of the invention, the first compression module comprises sugar alcohol in an amount of 75-97% by weight of the first compression module, such as 80-97% by weight of the first compression module, for example 85-97% by weight of the first compression module.

[0210] In an embodiment of the invention, the second compression module comprises sugar alcohol in an amount of at least 50% by weight of the second compression module, such as at least 60% by weight of the second compression module, such as at least 70% by weight of the second compression module, such as at least 80% by weight of the second compression module, such as at least 85% by weight of the second compression module, for example at least 90% by weight of the second compression module.

[0211] In an advantageous embodiment of the invention, the second compression module comprises sugar alcohol in an amount between 50% and 97% by weight of the second compression module, such as between 60% and 95% by weight of the second compression module, for example between 70% and 90% by weight of the second compression module.

[0212] In an embodiment of the invention, the second compression module comprises sugar alcohol in an amount of 50-97% by weight of the second compression module, such as 60-97% by weight of the second compression module, for example 70-97% by weight of the second compression module.

[0213] In an embodiment of the invention, the second compression module comprises sugar alcohol in an amount of 75-97% by weight of the second compression module, such as 80-97% by weight of the second compression module, for example 85-97% by weight of the second compression module, for example 90-97% by weight of the second compression module.

[0214] In an embodiment of the invention, the sugar alcohol is a sugar alcohol that is solid at 25 degrees Celsius.

[0215] Solid sugar alcohols have desirable compressibility properties and therefore their use is desirable when forming compressed tablets.

[0216] In an embodiment of the invention the sugar alcohol is selected from sugar alcohols containing at least 4 carbon atoms.

[0217] In an embodiment of the invention, the tablet does not contain sugar alcohols containing 3 or fewer carbons. Examples of sugar alcohols containing 3 or fewer carbons include glycerol, propylene glycol, and ethylene glycol.

[0218] In an embodiment, the nicotine tablet does not contain glycerol.

[0219] The compression and fusion of two such different modular compositions into a single multi-module nicotine tablet may not necessarily be obvious, as the present invention requires specific design to achieve the desired effect.

[0220] In an advantageous embodiment of the invention, the first and second compression modules comprise a sugar alcohol.

[0221] In an embodiment of the invention, the sugar alcohol is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0222] In an advantageous embodiment of the invention, the sugar alcohol of the first compression module is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0223] In an embodiment of the invention, the first compression module comprises sugar alcohol in an amount of at least 50% by weight of the first compression module, such as at least 60% by weight of the first compression module, such as at least 70% by weight of the first compression module, such as at least 80% by weight of the first compression module, such as at least 85% by weight of the first compression module, wherein the sugar alcohol is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0224] In an embodiment of the invention, the first compression module comprises nicotine selected from the list consisting of nicotine free base and nicotine salts, or combinations thereof, an alkaline pH adjuster 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, a sugar alcohol in an amount of at least 50% by weight of the first compression module, such as at least 60% by weight of the first compression module, such as at least 70% by weight of the first compression module, such as at least 80% by weight of the first compression module, for example at least 85% by weight of the first compression module, wherein the sugar alcohol is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0225] An advantage of the above embodiment may be that the nicotine, alkaline pH adjuster and sugar alcohol dissolve relatively quickly after the collapse of the first module, thereby achieving efficient nicotine absorption, resulting in a rapid effect for the user, i.e., reduced cravings.

[0226] In an embodiment of the invention, the sugar alcohol of the first compression module is selected from the list consisting of xylitol, mannitol, erythritol, isomalt, or any combination thereof.

[0227] In an advantageous embodiment of the invention, the sugar alcohol of the second compression module is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0228] In an embodiment of the invention, the second compression module comprises sugar alcohol in an amount of at least 50% by weight of the second compression module, such as at least 60% by weight of the second compression module, such as at least 70% by weight of the second compression module, such as at least 80% by weight of the second compression module, such as at least 85% by weight of the second compression module, wherein the sugar alcohol is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0229] In an embodiment of the invention, the second compression module comprises an acidic pH adjuster selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, monoalkaline dihydrogen phosphate-dialkaline hydrogen phosphate mixture, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof, and a sugar alcohol in an amount of at least 50% by weight of the second compression module, such as at least 60% by weight of the second compression module, such as at least 70% by weight of the second compression module, such as at least 80% by weight of the second compression module, for example at least 85% by weight of the second compression module, wherein the sugar alcohol is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0230] In an embodiment of the invention, the sugar alcohol of the second compression module is selected from the list consisting of mannitol, erythritol, isomalt, sorbitol, xylitol, or any combination thereof.

[0231] In an embodiment of the invention, the sugar alcohol comprises a DC (directly compressible) grade sugar alcohol.

[0232] In an embodiment of the invention, at least 50% by weight of the sugar alcohol is a DC (directly compressible) grade sugar alcohol.

[0233] In an embodiment of the invention, the nicotine tablet is substantially free of mono- and disaccharides.

[0234] In an embodiment of the present invention, the nicotine tablet does not contain sugar. Thus, in this embodiment, the nicotine tablet does not contain any sugar.

[0235] In an embodiment of the invention, the nicotine tablet comprises a high intensity sweetener.

[0236] In an embodiment of the present invention, the intense sweetener is selected from sucralose, aspartame, salts of acesulfame such as acesulfame potassium, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, monellin, stevioside, and any combination thereof.

[0237] In an embodiment of the invention, the nicotine tablet comprises no more than 0.2% by weight of high intensity sweetener, such as no more than 0.1% by weight of high intensity sweetener.

[0238] In an embodiment of the invention, the second compression module contains a high intensity sweetener.

[0239] In an embodiment of the invention, the first compression module contains a high intensity sweetener.

[0240] In an embodiment of the present invention, the intense sweetener is contained in the second compression module.

[0241] Thus, in the above embodiment, all of the high intensity sweeteners are contained in the second compression module, i.e., the first compression module does not contain any high intensity sweeteners.

[0242] An advantage of this embodiment may be that the nicotine tablet is relatively simple to manufacture due to the limited amounts of ingredients in each module, whilst providing surprisingly good results in terms of taste and flavour perception to the user.

[0243] In an embodiment of the present invention, the intense sweeteners and flavors are contained in a second compression module.

[0244] In an embodiment of the invention, the second compressed module comprises a binder in an amount of 10% by weight of the second compressed module or less, such as 8% by weight of the second compressed module or less, such as 6% by weight of the second compressed module or less.

[0245] A binder may be advantageously added in the second compression module to obtain the desired adhesion and mechanical strength.

[0246] Additionally, binders may be used to facilitate disintegration times of greater than 2 minutes, so that the second compression module provides adequate long-term masking of the nicotine.

[0247] The use of a second compression module, a lozenge module, also facilitates the production of robust tablets and provides extended release of the masking compound.

[0248] In an advantageous embodiment of the invention, the second compressed module comprises a binder in an amount of 1-10% by weight of the second compressed module, such as 1-8% by weight of the second compressed module, for example 2-5% by weight of the second compressed module.

[0249] In an advantageous embodiment of the invention, the first compressed module comprises a binder in an amount of 5% by weight or less of the first compressed module, such as 4% by weight or less of the first compressed module, for example 3% by weight or less of the first compressed module.

[0250] In an advantageous embodiment of the invention, the first compressed module comprises a binder in an amount of 0.5-5% by weight of the first compressed module, such as 0.5-4% by weight of the first compressed module, for example 1-3% by weight of the first compressed module.

[0251] In an advantageous embodiment of the invention, the first compression module comprises a binder in an amount of 5% or less by weight of the first compression module and a superdisintegrant in an amount of at least 5% by weight of the first compression module.

[0252] The above embodiments may ensure desirable cohesion of the module composition during tableting and desirable short disintegration times during use of the tablet.

[0253] In an embodiment of the invention, the first compression module constitutes at least 10% by weight of the nicotine tablet, such as at least 20% by weight of the nicotine tablet.

[0254] In an advantageous embodiment of the invention, the first compression module constitutes between 10% and 50% by weight of the nicotine tablet, such as between 20% and 40% by weight of the nicotine tablet, such as between 10% and 30% by weight of the nicotine tablet, such as between 20% and 30% by weight of the nicotine tablet.

[0255] In an embodiment of the invention, the second compression module constitutes at least 50% by weight of the nicotine tablet, such as at least 60% by weight of the nicotine tablet.

[0256] In an embodiment of the invention, the second compression module constitutes 50% to 90% by weight of the nicotine tablet, such as 50% to 90% by weight of the nicotine tablet, for example 60% to 90% by weight of the nicotine tablet, for example 70% to 90% by weight of the nicotine tablet, for example 70% to 80% by weight of the nicotine tablet, for example 80% to 90% by weight of the nicotine tablet, for example 65% to 75% by weight of the nicotine tablet.

[0257] In an embodiment of the present invention, a first compression module encapsulates a second compression module.

[0258] Obtaining a nicotine tablet having a second compression module encapsulated by a first compression module may be obtained by applying a press coat around the second compression module as the first compression module.

[0259] In an advantageous embodiment of the invention, a first compression module surrounds a second compression module, which is a compressed tablet core.

[0260] In an embodiment of the invention, the first compressed module is a compressed coating that surrounds the second compressed module, which is a compressed tablet core.

[0261] In an embodiment of the invention, the first compression module partially surrounds the second compression module, where it is understood that the second compression module is partially surrounded by the first compression module, i.e. the second compression module has a partially exposed surface.

[0262] In an advantageous embodiment of the invention, the first compression module and the second compression module are two layers fused together by compression.

[0263] In an advantageous embodiment of the invention, the first compression module and the second compression module are tablet layers.

[0264] Here, tablet module is understood to refer to a layer having an exposed surface area, such as the first compressed module, which is a layer having an exposed surface area of ​​up to 50% of the total exposed surface area of ​​the nicotine tablet, such as 40% of the total exposed surface area of ​​the nicotine tablet, 30% of the total exposed surface area of ​​the nicotine tablet, etc.

[0265] In an embodiment of the present invention, the first compression module at least partially encapsulates the second compression module.

[0266] In an embodiment of the invention, the first compression module is a tablet layer having an exposed surface area of ​​up to 50% of the total exposed surface area of ​​the nicotine tablet, such as 40% of the total exposed surface area of ​​the nicotine tablet, such as 30% of the total exposed surface area of ​​the nicotine tablet.

[0267] The advantage of providing a tablet with layers may be that upon oral administration, the ingredients are released from the layers. Thus, the first compressed module, which is the fast dissolving layer, will begin to release nicotine upon oral administration, and the second compressed module, which is the lozenge layer, will begin to release its ingredients, albeit at a slower release rate. This may be advantageously used to reduce the burning sensation caused by the nicotine provided in the fast dissolving layer by accelerating the release of the acidic pH modifier from the lozenge layer.

[0268] This may also be advantageously used to mask the bitter taste of nicotine, for example by providing nicotine in the fast dissolving layer and a masking ingredient, such as a flavoring, in the lozenge layer, which may further be used to mask an unpleasant alkaline sensation that may occur due to the rapid release of an alkaline pH adjusting agent from the fast dissolving layer, by releasing the flavoring from a second layer.

[0269] In an embodiment of the invention, the nicotine tablet comprises a first compressed module and a second compressed module, the first and second compressed modules being two layers fused together by compression.

[0270] The layers or modules of the nicotine tablets may be formed in many different ways within the scope of the present invention. As can be seen from above, the nicotine tablets may be round, oval or edged, for example square.

[0271] In an embodiment of the invention, the compressed first module and the compressed second module are solid modules.

[0272] In an advantageous embodiment of the invention, the nicotine tablet consists of a solid module.

[0273] It is therefore understood that tablets according to the above embodiments do not include a liquid or fluid module, such as a liquid or fluid center.

[0274] In an advantageous embodiment of the invention, the first compression module and the second compression module are solid tablet layers.

[0275] In an advantageous embodiment of the invention, the first compression module has a water content of less than 10% by weight, such as less than 5% by weight, such as less than 2% by weight, such as less than 1% by weight.

[0276] An advantage of the above embodiment may be increased stability of the first compression module, particularly with the first compression module including a disintegrant, such as a superdisintegrant.

[0277] In an embodiment of the invention, the first compression module has a water content of 0-10% by weight, such as 0.01-5% by weight, such as 0.05-2% by weight, such as 0.1-1% by weight.

[0278] That is, in the above embodiment, the first compression module may not contain water.

[0279] In an embodiment of the invention, the second compression module has a moisture content of less than 10% by weight, such as less than 5% by weight, such as less than 2% by weight, such as less than 1% by weight.

[0280] In an embodiment of the invention, the second compression module has a water content of 0-10% by weight, such as 0.01-5% by weight, such as 0.05-2% by weight, such as 0.1-1% by weight.

[0281] That is, in the above embodiment, the second compression module may not contain water.

[0282] In an advantageous embodiment of the invention, the water soluble nicotine tablet has a water content of less than 10% by weight, such as less than 5% by weight, such as less than 2% by weight, such as less than 1% by weight.

[0283] In an embodiment of the invention, the water-soluble nicotine tablet has a water content of 0 to 10% by weight, such as 0.01 to 5% by weight, such as 0.05 to 2% by weight, such as 0.1 to 1% by weight.

[0284] That is, in the above embodiments, the water-soluble nicotine tablet may not contain water.

[0285] In an advantageous embodiment of the invention the nicotine tablet has a maximum total weight of 1 gram, such as 0.9 gram, such as 0.75 gram, such as 0.5 gram, such as 0.4 gram, such as 0.3 gram.

[0286] The advantage of a nicotine tablet having a volume less than the maximum prescribed volume is the possibility of using the nicotine tablet individually. Moreover, it offers the option of self-titration.

[0287] In an advantageous embodiment of the invention, the nicotine tablet has a total weight of 0.2 to 1 gram, such as 0.2 to 0.9 gram, for example 0.2 to 0.75 gram, for example 0.2 to 0.5 gram.

[0288] In an embodiment of the invention the nicotine tablet has a maximum total volume of 0.7 cm3, such as 0.6 cm3, for example 0.5 cm3, such as 0.4 cm3, for example 0.3 cm3.

[0289] A nicotine tablet having a volume less than the maximum specified volume may provide the user with a desired disintegration and dissolution time.

[0290] In an embodiment of the invention, the nicotine tablet comprises a third module.

[0291] In an embodiment of the invention, the third module is a surrounding coating layer.

[0292] The nicotine tablet may advantageously include an outer coating. The outer coating may protect the modular tablet from physical degradation, such as separation of the modules, or prevent moisture attraction. Additionally, the outer coating may protect the ingredients from chemical degradation.

[0293] In an embodiment of the invention, the third module, which is the peripheral coating layer, is selected from the group consisting of a hard coating, a soft coating, and an edible film coating, or any combination thereof.

[0294] In an embodiment of the invention, the third module does not contain nicotine.

[0295] In an advantageous embodiment of the invention, the nicotine tablet comprises a first compression module and a second compression module.

[0296] In an embodiment of the invention, the nicotine tablet does not include a coating.

[0297] In an advantageous embodiment of the invention, the nicotine tablet does not include a coating.

[0298] In an advantageous embodiment of the invention, the first compressed module completely disintegrates upon oral administration within 60 seconds, such as within 45 seconds, for example within 30 seconds.

[0299] The collapse time of the first compression module may be measured as described in Example 3A.

[0300] In an advantageous embodiment of the invention, the nicotine tablet disintegrates completely within 15 minutes, such as within 10 minutes, after oral administration.

[0301] The disintegration time of the nicotine tablets may be measured as described in Example 3B.

[0302] In an advantageous embodiment of the invention, the nicotine tablet is a non-tobacco tablet.

[0303] In an embodiment of the invention, the nicotine tablet is tobacco-free.

[0304] In an embodiment of the invention, the first module comprises a sugar alcohol selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof, and the second module comprises a sugar alcohol selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0305] In an embodiment of the invention, the first module comprises sugar alcohol in an amount of at least 50% by weight of the first compression module, such as at least 60% by weight of the first compression module, such as at least 70% by weight of the first compression module, such as at least 80% by weight of the first compression module, such as at least 85% by weight of the first compression module, the sugar alcohol of the first module being selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof, and the sugar alcohol of the second compression module is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof. The module comprises sugar alcohol in an amount of at least 50% by weight of the second compression module, such as at least 60% by weight of the second compression module, for example at least 70% by weight of the second compression module, such as at least 80% by weight of the second compression module, for example at least 85% by weight of the second compression module, for example at least 90% by weight of the second compression module, wherein the sugar alcohol of the second module is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0306] In an embodiment of the invention, the alkaline pH adjuster 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, and the acidic pH adjuster is selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, monoalkaline dihydrogen phosphate-dialkaline hydrogen phosphate mixture, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0307] In an embodiment of the invention, the sugar alcohol of the first module is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof, the sugar alcohol of the second module is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof, the alkaline pH adjuster 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, and the acidic pH adjuster is selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, monoalkaline dihydrogen phosphate-dialkaline hydrogen phosphate mixture, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0308] In an embodiment of the invention, the first module comprises sugar alcohol in an amount of at least 50% by weight of the first compression module, such as at least 60% by weight of the first compression module, such as at least 70% by weight of the first compression module, such as at least 80% by weight of the first compression module, such as at least 85% by weight of the first compression module, wherein the sugar alcohol of the first module is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof, and the second compression module comprises sugar alcohol in an amount of at least 50% by weight of the second compression module, such as at least 60% by weight of the second compression module, such as at least 70% by weight of the second compression module, such as at least 80% by weight of the second compression module, such as at least 85% by weight of the second compression module, such as at least 100% by weight of the second compression module. The sugar alcohol of the second module is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof; the alkaline pH adjuster 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; and the acidic pH adjuster is selected from the list consisting of phosphoric acid, monoalkaline dihydrogen phosphate, monoalkaline dihydrogen phosphate-dialkaline hydrogen phosphate mixture, citric acid, monoalkaline dihydrogen citrate, dialkaline hydrogen citrate, malic acid, monoalkaline malate, succinic acid, monoalkaline succinate, tartaric acid, monoalkaline tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0309] In an embodiment of the invention, the first compression module comprises a disintegrant in an amount of at least 0.5% by weight of the first compression module, such as at least 1% by weight of the first compression module, such as at least 2% by weight of the first compression module, such as at least 3% by weight of the first compression module, such as at least 4% by weight of the first compression module, such as at least 5% by weight of the first compression module, wherein the disintegrant is selected from the list consisting of starch, pregelatinized starch, cellulose, modified cellulose, microcrystalline cellulose, alginate, ion exchange resins, calcium silicate, crosslinked cellulose, crosslinked polyvinylpyrrolidone, crosslinked starch, crosslinked alginic acid, and combinations thereof.

[0310] In an embodiment of the invention, the first compression module comprises a disintegrant in an amount of at least 0.5% by weight of the first compression module, such as at least 1% by weight of the first compression module, such as at least 2% by weight of the first compression module, such as at least 3% by weight of the first compression module, such as at least 4% by weight of the first compression module, such as at least 5% by weight of the first compression module, wherein the disintegrant is selected from the list consisting of starch, pregelatinized starch, cellulose, modified cellulose, microcrystalline cellulose, alginate, ion exchange resins, calcium silicate, crosslinked cellulose, crosslinked polyvinylpyrrolidone, crosslinked starch, crosslinked alginic acid, and combinations thereof, and the sugar alcohol of the tablet is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0311] In an embodiment of the invention the first compression module comprises a disintegrant in an amount of at least 0.5% by weight of the first compression module, such as at least 1% by weight of the first compression module, such as at least 2% by weight of the first compression module, such as at least 3% by weight of the first compression module, such as at least 4% by weight of the first compression module, such as at least 5% by weight of the first compression module, the disintegrant being selected from the group consisting of starch, pregelatinized starch, cellulose, modified cellulose, microcrystalline cellulose, alginates, ion exchange resins, calcium silicate, crosslinked cellulose, cross-linked polyvinylpyrrolidone, cross-linked starch, cross-linked alginic acid, and combinations thereof; and the tablet comprises a sugar alcohol in an amount of at least 50% by weight of the tablet, such as at least 60% by weight of the tablet, for example at least 70% by weight of the tablet, such as at least 80% by weight of the tablet, for example at least 85% by weight of the tablet, such as at least 90% by weight of the tablet; the sugar alcohol is selected from the list consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof.

[0312] The present invention further provides a method for producing a nicotine tablet according to the present invention or any of its embodiments, the method comprising: providing a first powdered composition and a second powdered composition, the first powdered composition comprising nicotine, a disintegrant, and an alkaline pH adjuster, and the second powdered composition comprising an acidic pH adjuster; compressing the second powdered composition and the first powdered composition to obtain a nicotine tablet comprising modules fused together by compression.

[0313] In an advantageous embodiment of the invention, the method comprises the steps of: compressing the second powder composition to obtain a second module; and compressing the second module and the first powdered composition to obtain the first module fused to the second module by compression.

[0314] In an advantageous embodiment of the invention, the method comprises the steps of: compressing the first powder composition to obtain a first module; and compressing the first module and the second powdered composition to obtain a second module fused to the first module by compression.

[0315] In an advantageous embodiment of the invention, the method comprises the steps of: compressing the second powder composition to obtain a second module; compressing the first powdered composition to obtain a first module fused to the second module by compression; The first module surrounds the second module.

[0316] In an advantageous embodiment of the invention, the compression is performed with a compression force of at least 5 kN, such as at least 10 kN, such as at least 15 kN, such as at least 20 kN.

[0317] In an embodiment of the invention, the water soluble nicotine tablet of the invention or any of its embodiments is obtained by the process of the invention or any of its embodiments.

[0318] The present invention further provides a water-soluble nicotine tablet comprising at least a first compression module and a second compression module, The present invention relates to a water-soluble nicotine tablet in which a first compressed module is a fast-dissolving module containing nicotine and a second compressed module is a lozenge module containing an acidic pH modifier.

[0319] In an embodiment of the invention, the water-soluble compressed nicotine tablet according to the above embodiment is made according to the first described water-soluble compressed nicotine tablet or any of its embodiments or obtained by the method of the invention or any of its embodiments.

[0320] The present invention further provides a water-soluble nicotine tablet comprising at least a first compression module and a second compression module, The first compression module is nicotine, Alkaline pH adjuster, and a disintegrant in an amount of at least 5% by weight of the first compression module; The second compression module is This invention relates to a water-soluble nicotine tablet that contains an acidic pH adjuster.

[0321] In an embodiment of the invention, the water-soluble compressed nicotine tablet according to the above embodiment is made according to the first described water-soluble compressed nicotine tablet or any of its embodiments or obtained by the method of the invention or any of its embodiments.

[0322] The present invention further provides a water-soluble nicotine tablet comprising at least a first compression module and a second compression module, The first compression module is the FDT layer, nicotine, Alkaline pH adjuster, and Contains a disintegrant, The second compression module is This invention relates to a water-soluble nicotine tablet that contains an acidic pH adjuster.

[0323] In an embodiment of the invention, the water-soluble compressed nicotine tablet according to the above embodiment is made according to the first described water-soluble compressed nicotine tablet or any of its embodiments or obtained by the method of the invention or any of its embodiments.

[0324] The present invention further provides a water-soluble nicotine tablet comprising at least a first compression module and a second compression module, The first compression module is nicotine, Alkaline pH adjuster, and Contains a disintegrant, The second compression module is This invention relates to a water-soluble nicotine tablet that contains an acidic pH adjuster. The first compression module has a dissolution time that is shorter than the dissolution time of the second compression module.

[0325] In an embodiment of the invention, the water-soluble compressed nicotine tablet according to the above embodiment is made according to the first described water-soluble compressed nicotine tablet or any of its embodiments or obtained by the method of the invention or any of its embodiments.

[0326] The present invention further provides a water-soluble nicotine tablet comprising at least a first compression module and a second compression module, The first compression module is nicotine, Alkaline pH adjuster, and Contains a disintegrant, The second compression module is This invention relates to a water-soluble nicotine tablet that contains an acidic pH adjuster. The difference in disintegration time between the first and second compression modules is at least 2 minutes.

[0327] In an embodiment of the invention, the water-soluble compressed nicotine tablet according to the above embodiment is made according to the first described water-soluble compressed nicotine tablet or any of its embodiments or obtained by the method of the invention or any of its embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0328] As used herein, the term "water-soluble nicotine tablet" refers to a compressed tablet that is entirely water-soluble. The nicotine lozenge of the present invention comprises a dissolvable FDT module, while also comprising a dissolvable lozenge module. Thus, the nicotine tablet does not of course comprise, for example, a chewing gum module or a gum base-containing module that is not soluble in water. Furthermore, the nicotine tablet is water-soluble in the sense that it disintegrates and the main components dissolve in water. The nicotine tablet of the present invention is a compressed tablet formed by compressing at least a first powdered composition and a second powdered composition to obtain a first and a second compressed module, respectively. The water-soluble nicotine tablet may contain an amount of water-insoluble material, for example MCC, such as, for example, 10% or less by weight of the tablet. Thus, the majority of the water-soluble nicotine tablet, for example, more than 90% by weight of the tablet, is composed of water-soluble material.

[0329] The nicotine tablet may disintegrate and dissolve within a period of at least 2 minutes, such as at least 3 minutes, such as at least 4 minutes, such as at least 5 minutes, upon oral administration.

[0330] As used herein, the term "FDT module" (fast dissolving tablet module) refers to a module that has the properties of so-called fast dissolving tablets. Fast dissolving tablets, sometimes called orally disintegrating tablets (ODT), generally exhibit rapid disintegration in the mouth without the need to chew or drink liquid to ingest these products.

[0331] The FDT modules of the present invention typically exhibit fast degradation, such as within 60 seconds of being placed in the mouth, or even faster, such as within 30 seconds of being placed in the mouth, in some embodiments of the present invention, the FDT module disintegrates within 30 seconds, such as within 20 seconds, such as within 15 seconds.

[0332] As used herein, the term "lozenge module" refers to a module that imparts lozenge properties, i.e., a module that dissolves or disintegrates in the mouth over a period of several minutes, thereby releasing the components of the module, e.g., an acidic pH modifier, flavorings, etc., depending on the particular embodiment. For example, the lozenge module may disintegrate and dissolve within a period of at least 2 minutes, such as at least 3 minutes, such as at least 4 minutes, for example at least 5 minutes, upon oral administration.

[0333] As used herein, the term "disintegrate" refers to the transformation of a body into components, fragments, or particles. Disintegration time may be measured in vitro or in vivo. Unless otherwise stated, in vitro measurements are performed according to European Pharmacopeia 9.0, section 2.9.1, Disintegration of tablets and capsules. In vivo measurements are performed as described in Example 3B.

[0334] As used herein, the term "dissolving" is the process by which a solid substance enters a solvent (oral saliva) to produce a solution. Unless otherwise stated, dissolution refers to complete dissolution of the compound in question.

[0335] As used herein, the term "disintegrant" refers to an ingredient that promotes the disintegration of the FDT module when it comes into contact with saliva. Disintegrants may often be thought of as a means to promote the breakdown of the module into smaller pieces upon administration to facilitate the release and ultimate absorption of nicotine.

[0336] As used herein, the term "binder" refers to an ingredient that promotes adhesion to the powder composition during tablet manufacture, thereby facilitating the production of modules, and thereby facilitating the production of nicotine tablets having desirable mechanical strength.

[0337] In a preferred embodiment of the invention, the second compression module comprises a binder.

[0338] As used herein, the term "nicotine" refers to any form of nicotine, including free base nicotine, nicotine salts, nicotine bound to a carrier, such as nicotine bound to an ion exchange resin, nicotine bound to a zeolite, nicotine bound to fibers or microparticles, nicotine bound to CaCO3, nicotine bound to a sugar alcohol, and mixtures thereof. In this specification, bound should be understood to mean that the nicotine is ionically bound, adsorbed, or absorbed onto the carrier, depending on the type of carrier.

[0339] When referring to an amount of nicotine in milligrams, this amount should be understood as a nicotine dose, i.e. this amount refers to the amount of pure nicotine.

[0340] When referring to a nicotine amount in weight percent, this amount should be understood as the actual amount of nicotine source associated with the designated term such as a first compressed module or a nicotine tablet, etc. That is, a 75 mg first compressed module containing nicotine bitartrate in an amount of 4% by weight of the first compressed module refers to a first compressed module containing 3 mg of nicotine bitartrate (i.e., 1 mg of pure nicotine).

[0341] Nicotine also encompasses nicotine not derived from tobacco, often referred to as synthetic nicotine. Nicotine is included in the first compression module. In an embodiment, nicotine is included in the first compression module but not in the second compression module.

[0342] As used herein, the term "free base nicotine" refers to the unprotonated form of nicotine. Free base nicotine may be provided as a liquid or mixed with an amount of an ion exchange resin; a water-soluble composition, such as or a sugar alcohol or a water-soluble fiber; or a water-insoluble fiber; or a modified calcium carbonate. Free base nicotine includes both free base nicotine extracted from tobacco and synthetically produced free base nicotine, but free base nicotine is not provided in the form of tobacco or powdered tobacco.

[0343] As used herein, the term "nicotine salt" refers to the ionized form of nicotine bound to a counterion.

[0344] As used herein, the term "NBT" refers to nicotine bitartrate and its hydrates.

[0345] As used herein, the terms "%" and "percent" refer to percent by weight, unless otherwise specified.

[0346] As used herein, the term "nicotine release" refers to nicotine becoming bioavailable, i.e., available for absorption through the mucous membranes in the oral cavity. Some forms of nicotine require dissolution to become bioavailable, while other forms may be readily absorbed by the body without dissolution. For example, the tablet matrix should disintegrate in order for nicotine to be bioavailable. Some forms of nicotine require that nicotine be further released, for example from the carrier, for example, that nicotine be released from a nicotine ion exchange resin, such as nicotine polacrilex. Other nicotine forms, such as nicotine salts (hereinafter nicotine bitartrate), may readily dissolve upon disintegration of the tablet matrix. Furthermore, some nicotine forms may not require dissolution. This applies, for example, to nicotine free base, which is released upon disintegration of the solid formulation matrix.

[0347] As used herein, the term "pH adjusting agent" refers to an agent that actively adjusts and regulates the pH value of the solution to which it is or will be added. Thus, pH adjusting agents may be acidic or alkaline.

[0348] An acidic pH adjuster induces a pH of less than 7.5 when added to water having a pH of 7.0 at a temperature of 25° C., and an alkaline pH adjuster induces a pH of greater than 7.5 when added to water having a pH of 7.0. When two or more pH adjusters are included in the same module, they form a combined pH adjuster. A combined pH adjuster is an acidic pH adjuster that induces a pH of less than 7.5 when added to water having a pH of 7.0 measured at a temperature of 25° C. and atmospheric pressure, or an alkaline pH adjuster that induces a pH of greater than 7.5 when added to water having a pH of 7.0 measured at a temperature of 25° C. and atmospheric pressure.

[0349] In other words, the acidic pH adjuster, in some embodiments, can be an acidic buffer system including, for example, a combination of pH adjusters, so long as the buffer system induces a pH of less than 7.5 when added to water having a pH of 7.0 measured at a temperature of 25 degrees Celsius and atmospheric pressure.

[0350] On the other hand, pH adjusters do not include substances and compositions that can affect pH only through dilution. Additionally, pH adjusters do not include, for example, flavorings, fillers, and the like.

[0351] In some preferred embodiments, the acidic pH adjuster, when added to water having a pH of 7.0, induces a pH of less than 7.0 when measured at 25 degrees Celsius and atmospheric pressure.

[0352] As used herein, "molar ratio" refers to the ratio of the molar content of a first component divided by the molar content of a second component.

[0353] The relative content between the first and second components may also be presented as equivalents of the first component to the second component. Thus, a second compression module containing an acidic pH adjuster in a molar ratio of 1.0 relative to the amount of nicotine in the first compression module may be presented as a nicotine tablet containing 1.0 equivalent of acidic pH adjuster relative to the amount of nicotine in the first compression module, i.e., a nicotine tablet containing 1.0 equivalent of acidic pH adjuster and 1.0 equivalent of nicotine in the first compression module.

[0354] When the amount of an ingredient is referred to by terms such as "less than," "or less than," this generally means that the particular ingredient is absent or present in a range from a trace amount to a specified maximum amount.

[0355] As used herein, the term "flavoring agent" is understood to have the ordinary meaning of the term in the art. Flavoring agents include liquid and powdered flavoring agents. Thus, flavoring agents do not include sweeteners (such as sugars, sugar alcohols, and high-intensity sweeteners), or acids that provide pure acidity / sourness, nor compounds that provide pure saltiness (e.g., NaCl) or pure bitterness. Flavoring agents can be natural or synthetic flavoring agents.

[0356] Typically, the nicotine tablet may comprise ingredients selected from the group consisting of fillers, flavorings, binders, disintegrants (hereinafter superdisintegrants), emulsifiers, antioxidants, pH adjusters (hereinafter alkaline and acidic pH adjusters), intense sweeteners, colorants, glidants, lubricants, or any combination thereof.

[0357] In an advantageous embodiment of the invention, the tablet comprises a bulk sweetener as a filler component.

[0358] In an advantageous embodiment of the invention, the first compression module includes a bulk sweetener as the filler component.

[0359] In an advantageous embodiment of the present invention, the second compression module includes a bulk sweetener as the filler component.

[0360] In an advantageous embodiment of the present invention, the first and second compression modules include bulk sweetener as a filler component.

[0361] In embodiments in which the nicotine tablet includes a bulk sweetener, different bulk sweeteners may be used, including sugar sweeteners and / or non-sugar sweeteners.

[0362] Sugar sweeteners generally include, but are not limited to, sugar-containing components such as sucrose, dextrose, maltose, saccharose, lactose, sorbose, dextrin, trehalose, D-tagatose, dry invert sugar, fructose, levulose, galactose, and the like, either alone or in combination.

[0363] Non-sugar sweeteners generally include, but are not limited to, sugar alcohols (sometimes called polyols), such as xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, and lactitol.

[0364] A combination of sugar and / or non-sugar sweeteners may be used in the nicotine tablet.

[0365] Bulk sweeteners may often support the flavor profile of the nicotine tablet.

[0366] In embodiments of the present invention, the bulk sweetener may be supplemented with other usable fillers including, by way of example, magnesium and calcium carbonate, sodium sulfate, ground limestone, silicate compounds such as magnesium and aluminum silicate, kaolin and clay, aluminum oxide, silicon oxide, talc, titanium oxide, monocalcium, dicalcium and tricalcium phosphates, fiber, vegetable fibers such as wheat fiber, oat fiber, pea fiber, and combinations thereof.

[0367] High-intensity artificial sweeteners can also be used in combination with the bulk sweeteners described above. For example, high-intensity sweeteners include, but are not limited to, sucralose, aspartame, acesulfame salts, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, monellin, stevioside (natural intensity sweetener), etc., alone or in combination.

[0368] The use level of artificial sweeteners can vary considerably and depends on factors such as sweetener potency, release rate, desired sweetness of the product, the level and type of flavoring used, and cost considerations, etc. Thus, the effective concentration of artificial sweeteners may vary from about 0.001 to about 8% by weight (e.g., from about 0.02 to about 8% by weight).

[0369] In embodiments in which the nicotine tablet includes a flavoring, different flavorings may be used.

[0370] Available flavorings include, for example, almond, almond amaretto, apple, bavarois, 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, 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, creme de menthe, eggnog, English toffee, guava, lemonade, licorice, maple, mint chocolate chip, orange cream, peach, pina colada, pineapple, plum, pomegranate, pralines and cream, red licorice licorice), salt water taffy, strawberry banana, strawberry, kiwi, tropical punch, tutti frutti, vanilla, or any combination thereof.

[0371] According to embodiments of the present invention, flavorings may be used for taste masking of nicotine and / or taste masking of alkaline pH adjusting agents.

[0372] In an embodiment of the invention, the nicotine tablet comprises a lubricant. Silicon dioxide may be used as the lubricant. Other lubricants that can be used in tablets may also be used within the scope of the invention.

[0373] In an embodiment of the invention, the nicotine tablet comprises a lubricant. Magnesium stearate and / or sodium stearyl fumarate may be used as lubricants. Other lubricants that can be used in tablets may also be used within the scope of the invention.

[0374] Ready-to-use systems may be used within the scope of the present invention. Typically, such ready-to-use systems may replace, for example, fillers, disintegrants, lubricants or the like with a single powder mixture. 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). It may be particularly advantageous to use ready-to-use systems that include disintegrants.

[0375] The range of parameters can be adjusted to obtain an FDT module designed to disintegrate within 60 seconds upon oral administration.

[0376] First, the disintegration time can be altered by varying the composition: the use of ingredients with high water solubility may help shorten the disintegration time.

[0377] In particular, the inclusion of a disintegrant may have a significant effect on the disintegration time, depending on the overall composition of the first compression module. The disintegration time may also be further adjusted by varying the amount and type of disintegrant. For example, if a first compression module with a shorter disintegration time is desired, the content of disintegrant may be increased and / or the type of disintegrant may be at least partially replaced with a more effective disintegrant, such as a superdisintegrant.

[0378] It should be noted that some ingredients have dual functions, e.g., some ingredients may be used as disintegrants in some situations and binders in other situations. For example, some disintegrants may have binding properties and vice versa. Thus, the list of binders may overlap with the list of disintegrants.

[0379] In some embodiments, the disintegrant may comprise a combination of a regular disintegrant and a superdisintegrant, where the regular disintegrant may contribute some disintegration properties upon oral administration and desirable binding properties during manufacturing, and the superdisintegrant ensures rapid disintegration upon oral administration.

[0380] Reducing the particle size of the disintegrant also tends to decrease the disintegration time, presumably due to an increase in the surface area to volume ratio.

[0381] Moreover, the compression force used to compress the first compression module is significantly correlated with the obtained hardness of the first compression module, so that a high compression force typically increases the hardness of the obtained first compression module. By adjusting the hardness of the first compression module, the disintegration time may be affected as well, so that a lower hardness typically leads to a shorter disintegration time. Here, it has been observed that for some compositions, by applying the correct compression force, a disintegration time of less than 60 seconds can be achieved when administered orally, while a compression force that is too high may result in a long disintegration time of more than 60 seconds. In this regard, it should be noted that the threshold compression force may vary significantly depending on other parameters such as the overall composition, the content and type of disintegrant. For example, if disintegration is too slow in a particular setting, a further adjustment method may be to replace the usual disintegrant with a superdisintegrant, i.e., a superdisintegrant that promotes disintegration in a more efficient manner.

[0382] Increasing water solubility may also be facilitated by replacing less water soluble components with more water soluble components. For example, using sugar alcohols as bulking agents may be highly advantageous as long as the sugar alcohols have a higher water solubility than the alternative bulking agents.

[0383] Furthermore, using a sugar alcohol with a lower compression capacity results in a shorter disintegration time. Too low a compression capacity may impair the mechanical strength of the first and second compression modules, leading to undesirably high friability, cracking, and other risks.

[0384] Another example of parameters that may be adjusted to obtain a first compression module designed to disintegrate within 60 seconds upon oral administration includes the overall design of the tablet. In some embodiments, such as a tablet with a second compression module that is a core and a first compression module that is a surrounding compression coating, the first compression module has a higher exposed surface area compared to a layered tablet design. Increasing the exposed surface area may decrease the disintegration time.

[0385] Further examples of parameters that may be adjusted to obtain a first compression module designed to disintegrate within 60 seconds upon oral administration include the size and shape of the first compression module and the overall tablet. A larger volume of the first compression module will result in a longer disintegration time and therefore a longer release time of nicotine and alkaline pH modifier.

[0386] For example, for a disc-shaped tablet, increasing the flatness (e.g., as quantified by the diameter to height ratio) of a layered tablet typically decreases disintegration time by increasing the surface area to volume. Flatness may be increased as long as the tablet has sufficient mechanical strength.

[0387] Also, changing the cross-sectional profile from a convex nicotine tablet to a concave tablet reduces the disintegration time. It is noted that although this may reduce the mechanical strength of the tablet to some extent, pursuing a concave cross-section, as long as it is satisfactory, may help increase disintegration and therefore reduce the disintegration time.

[0388] Additionally, the type and amount of lubricant, if any, may be adjusted to optimize disintegration time, for example, the use of sodium stearyl fumarate (SSF) typically results in shorter disintegration times compared to the use of magnesium stearate, MgSt.

[0389] Thus, when designing a first compressed module that has a disintegration time of 60 seconds upon oral administration, a wide range of parameters may be adjusted.

[0390] The same parameters may be adjusted if the second compression module is designed to have a disintegration time upon oral administration of at least 2 minutes, such as at least 3 minutes, such as at least 4 minutes, such as at least 5 minutes.

[0391] The first compressed module is designed to disintegrate within 60 seconds of oral administration, such that the disintegration time of the second compressed module is equal to the disintegration time of a nicotine tablet.

[0392] In an embodiment of the invention, the second compressed module of the nicotine tablet comprises a binder.

[0393] It should be noted that some ingredients may be used, for example, as disintegrants in some situations and as binders in others, and some ingredients have dual functions: for example, some disintegrants may have binding properties and vice versa. Thus, the list of binders may overlap with the list of disintegrants.

[0394] In an advantageous embodiment of the invention, the second compression module comprises a binder.

[0395] Binders that can be used include, but are not limited to, polysaccharides and modified polysaccharides such as gum acacia, agar, carrageenan, chitosan, inulin, xanthan gum, tragacanth, pullulan, guar gum, pectin, chitin, etc.; alginic acid or its salts; carbomer; cellulose; copovidone; gelatin; polycarbophil or its salts; microcrystalline cellulose; polyvinyl alcohol; starch; pregelatinized starch; modified celluloses such as carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose; polyethylene glycol; polyethylene oxide; and mixtures thereof.

[0396] In one embodiment, the binder included in the second compression module of the tablet of the present invention may be selected from the group consisting of alginic acid or a salt thereof, polycarbophil or a salt thereof, xanthan gum, microcrystalline cellulose, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), and mixtures thereof.

[0397] In one embodiment, the binder included in the second compression module of the tablet of the present invention may be selected from the group consisting of alginic acid or a salt thereof, polycarbophil or a salt thereof, xanthan gum, and mixtures thereof.

[0398] In one embodiment, the binder included in the second compression module of the tablet of the present invention may be selected from the group consisting of microcrystalline cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, or mixtures thereof.

[0399] In some embodiments, the first compression module includes a binder.

[0400] Also, for example, when a binder is used to obtain higher adhesion and mechanical strength of the compression module, the amount of such binder may be adjusted to obtain a higher or lower disintegration rate and thus a longer or shorter disintegration time.

[0401] In some embodiments, the first compression module comprises a binder and a superdisintegrant.

[0402] A binder may advantageously be included in the first compression module to achieve the desired cohesion during tableting. A superdisintegrant may also be included in the module to obtain the desired short disintegration time of the module. EXAMPLES

[0403] Example 1A: Preparation of a tablet comprising a second module, which is a tablet core completely surrounded by a first module. The composition of the second module is prepared by pouring approximately half of the filler into a mixing bowl, followed by the remaining ingredients except the lubricant, and finally the remaining filler. The ingredients are tumbled / mixed with a mixer (Turbula or Duma) at 49 rpm for 4-10 minutes.

[0404] The lubricant is added and the ingredients are further mixed for 1-2 minutes at 49 rpm.

[0405] The composition of the first module is prepared by pouring all ingredients except the lubricant into a mixing bowl. The ingredients are tumbled / mixed using a mixer (Turbula or Duma) at 49 rpm for 4-10 minutes.

[0406] The lubricant is added and the ingredients are further mixed for 1-2 minutes at 49 rpm.

[0407] The lubricated powder blend is then transferred into the hopper of a tablet press.

[0408] The composition of the second module is compressed at a compression force of about 3 kN to form tablet cores.

[0409] The tablet cores, i.e., the compressed second module, are transferred to a second compression apparatus and then the composition of the first module is press coated around the cores.

[0410] The composition is compressed with a compressive force of about 15-20 kN to form a first compressed module surrounding the second module.

[0411] The fast dissolving tablets are manufactured on a rotary press, such as a Manestry DryCota tablet press. The tablet press is operated by adjusting the fill depth and compression force so that the weight and hardness of the nicotine tablets meets the acceptance criteria.

[0412] Example 1B: Preparation of a tablet comprising a second module, which is a tablet core partially surrounded by a first module. The composition of the second module is prepared by pouring approximately half of the filler into a mixing bowl, followed by the remaining ingredients except the lubricant, and finally the remaining filler. The ingredients are tumbled / mixed with a mixer (Turbula or Duma) at 49 rpm for 4-10 minutes.

[0413] The lubricant is added and the ingredients are further mixed for 1-2 minutes at 49 rpm.

[0414] The composition of the first module is prepared by pouring all ingredients except the lubricant into a mixing bowl. The ingredients are tumbled / mixed using a mixer (Turbula or Duma) at 49 rpm for 4-10 minutes.

[0415] The lubricant is added and the ingredients are further mixed for 1-2 minutes at 49 rpm.

[0416] The lubricated powder blend is then transferred into the hopper of a tablet press.

[0417] The second module composition is compressed with a compressive force of about 3 kN to form the second module.

[0418] The composition of the first module is transferred to a tablet press, the second module is placed into the punch cylinder, and the first composition is compressed and fused by compressing it into the second module with a compression force of about 15-20 kN to form a first compressed module partially surrounding the second module.

[0419] The tablet press is operated by adjusting the fill depth and compression force so that the weight and hardness of the nicotine tablets meets the acceptance criteria.

[0420] Example 1C: Preparation of a tablet comprising a first and a second module which are tablet layers. The composition of the second module is prepared by pouring approximately half of the filler into a mixing bowl, followed by the remaining ingredients except the lubricant, and finally the remaining filler. The ingredients are tumbled / mixed with a mixer (Turbula or Duma) at 49 rpm for 4-10 minutes.

[0421] The lubricant is added and the ingredients are further mixed for 1-2 minutes at 49 rpm.

[0422] The composition of the first module is prepared by pouring all ingredients except the lubricant into a mixing bowl. The ingredients are tumbled / mixed using a mixer (Turbula or Duma) at 49 rpm for 4-10 minutes.

[0423] The lubricant is added and the ingredients are further mixed for 1-2 minutes at 49 rpm.

[0424] The lubricated powder blend is then transferred into the hopper of a tablet press.

[0425] The second module is then compressed with a compressive force of about 3-6 kN, after which the first module is compression fused to the second module with a compressive force of about 15-20 kN. Unless otherwise specified, punch used: 10.00 mm, circular, shallow concave, D tool.

[0426] Fast dissolving tablets are manufactured in a laboratory scale machine, e.g., a RIVA Piccola tablet press. The tablet press is operated by adjusting the fill depth and compression force so that the tablet weight and hardness meet the acceptance criteria. A preload force could be included to avoid capping.

[0427] Example 2: Tablet Composition Example 2A: Nicotine tablets of 450 mg each were made with a second module of 350 mg and a first module of 100 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0428] Punch used: 10.00mm, round, shallow concave, D tool.

[0429] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0430] [Table 1] * The amount of acidic pH adjuster in the second module is expressed as an equivalent amount relative to the nicotine in the first module.

[0431] Mannitol may be used as the sugar alcohol in the first and second modules. Other usable sugar alcohols for use in the second module may include xylitol, maltitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof. Of these, erythritol, isomalt, sorbitol, xylitol, or any combination thereof is particularly preferred. Other usable sugar alcohols for use in the first module may include xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, or any combination thereof. Of these, xylitol, erythritol, isomalt, or any combination thereof is particularly preferred.

[0432] The amount of disintegrant in the first module can be, for example, starch disintegrant.Other examples of disintegrants that can be used include pregelatinized starch, cellulose, modified cellulose, microcrystalline cellulose, alginate, ion exchange resin, calcium silicate, and combinations thereof.Alternatively, super disintegrants such as cross-linked cellulose, cross-linked polyvinylpyrrolidone, cross-linked starch, cross-linked alginic acid, and combinations thereof can be used, but the amount of super disintegrants used can be advantageously reduced.

[0433] Preferred high-intensity sweeteners (HIS) may be, for example, sucralose, acesulfame potassium, and mixtures thereof. Other high-intensity sweeteners, such as aspartame, acesulfame salts, such as acesulfame potassium, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, stevioside, alone or in combination, may also be used within the scope of the present invention.

[0434] Fruit flavors and mixtures thereof Menthol, peppermint, and mixtures thereof may be used as flavorings in the above formulations. Other flavorings may also be used within the scope of the present invention.

[0435] Sodium carbonate is used as the alkaline pH adjuster in the first module. Additional alkaline pH adjusters that may be used include sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol, amino acids, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, or any combination thereof.

[0436] Citric acid is used as the acidic pH adjuster in the second module. Additional acidic pH adjusters that may be used include phosphoric acid, monosodium dihydrogen phosphate, monopotassium dihydrogen phosphate, monosodium dihydrogen citrate, monopotassium dihydrogen citrate, disodium hydrogen citrate, dipotassium hydrogen citrate, malic acid, monosodium malate, monopotassium malate, succinic acid, monosodium succinate, monopotassium succinate, tartaric acid, monosodium tartrate, monopotassium tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0437] In the above, MgSt (magnesium stearate) is used as the lubricant. Other lubricants such as sodium stearyl fumarate may also be used within the scope of the present invention.

[0438] C1 is a comparative example that does not contain an acidic pH adjuster in the second compression module.

[0439] Example 2B Nicotine tablets of 450 mg each were made with a second module of 350 mg and a first module of 100 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0440] Punch used: 10.00mm, round, shallow concave, D tool.

[0441] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0442] [Table 2] * The amount of acidic pH adjuster in the second module is expressed as an equivalent amount relative to the nicotine in the first module.

[0443] In NT11 to NT18, cross-linked polyvinylpyrrolidone, here Crospovidone®, Kollidon CL-F, is used as the superdisintegrant. Alternative superdisintegrants may include, for example, cross-linked cellulose (such as Croscarmellose®), cross-linked starch (such as sodium starch glycolate) and cross-linked alginic acid (such as Alginic Acid NF®).

[0444] C2 is a comparative example that does not contain a disintegrant in the first compression module.

[0445] The alternative ingredients described in relation to NT1 to NT8 may be similarly applied to NT11 to NT18.

[0446] Example 2C Nicotine tablets of 450 mg each were made with a second module of 350 mg and a first module of 100 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0447] Punch used: 10.00mm, round, shallow concave, D tool.

[0448] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0449] [Table 3] * The amount of acidic pH adjuster(s) in the second module is expressed as an equivalent amount relative to the nicotine in the first module. If the acidic pH adjuster is a mixture of pH adjusters, the molar ratio refers to the total molar amount of acidic pH adjuster(s) relative to the molar amount of nicotine in the first compression module.

[0450] The first compression module uses a superdisintegrant. The superdisintegrant used may be, for example, cross-linked polyvinylpyrrolidone, such as Crosspovidone®. Other usable superdisintegrants could be applied, such as cross-linked cellulose, cross-linked starch, cross-linked alginic acid, and combinations thereof.

[0451] Sodium carbonate is used as the alkaline pH adjuster in the first module. Additional alkaline pH adjusters that may be used include sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol, amino acids, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, or any combination thereof.

[0452] Citric acid is used as the acidic pH adjuster in the second module of NT21-25 and NT30. Additional acidic pH adjusters that may be used include phosphoric acid, monosodium dihydrogen phosphate, monopotassium dihydrogen phosphate, monosodium dihydrogen citrate, monopotassium dihydrogen citrate, disodium hydrogen citrate, dipotassium hydrogen citrate, malic acid, monosodium malate, monopotassium malate, succinic acid, monosodium succinate, monopotassium succinate, tartaric acid, monosodium tartrate, monopotassium tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0453] A monosodium dihydrogen phosphate-disodium hydrogen phosphate mixture is used as the acidic pH adjusting system in the second module of NT 26 to 29. Further usable acidic pH adjusting agents include phosphoric acid, monosodium dihydrogen phosphate, monopotassium dihydrogen phosphate, citric acid, monosodium dihydrogen citrate, monopotassium dihydrogen citrate, disodium hydrogen citrate, dipotassium hydrogen citrate, malic acid, monosodium malate, monopotassium malate, succinic acid, monosodium succinate, monopotassium succinate, tartaric acid, monosodium tartrate, monopotassium tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

[0454] The alternative ingredients described in relation to NT1 to NT8 may be similarly applied to NT21 to NT30.

[0455] Example 2D - Various acidic pH adjusters and equivalents used Nicotine tablets of 300 mg each were made with a second module of 225 mg and a first module of 75 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0456] Punch used: 10.00mm, round, shallow concave, D tool.

[0457] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0458] [Table 4] * The amount of acidic pH adjuster in the second module is expressed as an equivalent amount relative to the nicotine in the first module.

[0459] The alternative ingredients described in relation to NT1 to NT30 may be similarly applied to NT31 to NT39.

[0460] Example 2E: Nicotine tablets of 300 mg each were made with a second module of 225 mg and a first module of 75 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0461] Punch used: 10.00mm, round, shallow concave, D tool.

[0462] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0463] [Table 5] * The amount of acidic pH adjuster in the second module is expressed as an equivalent amount relative to the nicotine in the first module.

[0464] Fruit flavors are used in NT41-49 and C3.

[0465] C3 is a comparative example that does not contain an alkaline pH adjuster in the first compression module.

[0466] The alternative ingredients described in relation to NT1 to NT39 may be applied to NT41 to NT49 as well.

[0467] Example 2F: Nicotine tablets of 300 mg each were made with a second module of 225 mg and a first module of 75 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0468] Punch used: 10.00mm, round, shallow concave, D tool.

[0469] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0470] [Table 6] * The amount of acidic pH adjuster in the second module is expressed as an equivalent amount relative to the nicotine in the first module.

[0471] The alternative ingredients described in relation to NT1 to NT49 may be similarly applied to NT51 to NT59.

[0472] Example 2G: Nicotine tablets of 300 mg each were made with a second module of 225 mg and a first module of 75 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0473] Punch used: 10.00mm, round, shallow concave, D tool.

[0474] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0475] [Table 7] * The amount of acidic pH adjuster in the second module is expressed as an equivalent amount relative to the nicotine in the first module.

[0476] The alternative ingredients described in relation to NT1 to NT59 may be similarly applied to NT61 to NT69.

[0477] Example 2H: Nicotine tablets of 300 mg each were made with a second module of 225 mg and a first module of 75 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0478] Punch used: 10.00mm, round, shallow concave, D tool.

[0479] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0480] [Table 8] * The amount of acidic pH adjuster in the second module is expressed as an equivalent amount relative to the nicotine in the first module.

[0481] The alternative ingredients described in relation to NT1 to NT69 may be similarly applied to NT71 to NT79.

[0482] Example 2I - Nicotine Source and Lubricant Nicotine tablets of 500 mg each were made with a second module of 350 mg and a first module of 150 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0483] Punch used: 10.00mm, round, shallow concave, D tool.

[0484] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0485] [Table 9] * The amount of acidic pH adjuster in the second module is expressed as an equivalent amount relative to the nicotine in the first module. ** Free nicotine base adsorbed on the support in a 1:2 weight ratio

[0486] The alternative ingredients described in relation to NT1 to NT79 may be similarly applied to NT81 to NT89.

[0487] Example 2J: Nicotine tablets of 500 mg each were made with a second module of 350 mg and a first module of 150 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0488] Punch used: 10.00mm, round, shallow concave, D tool.

[0489] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0490] [Table 10] * The amount of acidic pH adjuster in the second module is expressed as an equivalent amount relative to the nicotine in the first module.

[0491] The alternative ingredients described in relation to NT1 to NT89 may be similarly applied to NT91 to NT98.

[0492] Example 2K: Nicotine tablets of 300 mg each were made with a second module of 200 mg and a first module of 100 mg. The tablets were prepared according to Example 1C, i.e., layered design. However, the tablets could alternatively be prepared according to Examples 1A or 1B.

[0493] Punch used: 10.00mm, round, shallow concave, D tool.

[0494] The second compression module is compressed with a compression force of about 3 kN, and then the first module is compression fused to the second module with a compression force of about 15-20 kN.

[0495] [Table 11] * The amount of acidic pH adjuster in the second module is expressed as an equivalent amount relative to the nicotine in the first module. If the acidic pH adjuster is a mixture of pH adjusters, the molar ratio refers to the total molar amount of acidic pH adjuster(s) relative to the molar amount of nicotine in the first compression module.

[0496] The alternative ingredients described in relation to NT1 to NT98 may be similarly applied to NT101 to NT108.

[0497] For samples 106, 107 and 108, the compression force was adjusted to provide nicotine tablets with different hardness (breaking force).

[0498] [Table 12]

[0499] Example 3A: In vivo collapse time of the first compression module. The in vivo disintegration time of the first compression module may be determined using a colorant. Nicotine tablets were prepared by adding a colorant to the second compression module, resulting in a bicolor tablet.

[0500] The sample tablets containing the colored second compressed module were tested in a test panel of eight subjects. The test subjects refrained from eating or drinking at least 30 minutes before the start of the test. The subjects were healthy subjects who were objectively designated according to the specified requirements.

[0501] For the test, the tablet was placed in the mouth between the tongue and the roof of the mouth.

[0502] The tablets were visually inspected every 5 seconds to determine the time when the uncolored, white first compression module had completely disintegrated, ie, the time when no white color was observed in the remaining tablet.

[0503] [Table 13]

[0504] Conclusion: The first disintegration module was found to have a desirable short disintegration time of less than 15 seconds.

[0505] Example 3B: In vivo disintegration times of nicotine tablets. The sample tablets were tested in a test panel of eight subjects. The test subjects refrained from eating and drinking at least 30 minutes before the start of the test. The subjects were healthy subjects who were objectively designated according to the specified requirements.

[0506] Subjects were instructed to swallow their saliva after 1 minute and not to swallow before that time.

[0507] Subjects report the time it takes for the tablet to disintegrate completely. The mean disintegration time reported by subjects is calculated for each tablet.

[0508] [Table 14]

[0509] Conclusion: All the tablets tested were found to have a disintegration time of less than 5 minutes.

[0510] Nicotine tablets of samples 106, 107 and 108 having different hardness (breaking force) were also tested for in vivo disintegration time.

[0511] [Table 15]

[0512] Example 3C: In vivo testing of pH adjusting agent release The sample tablets were tested in a test panel of eight subjects. The test subjects refrained from eating and drinking at least 30 minutes before the start of the test. The subjects were healthy subjects who were objectively designated according to the specified requirements.

[0513] For the test, the tablet was placed in the mouth between the tongue and the roof of the mouth. Subjects were instructed to swallow saliva after the pH measurement was taken at 1 minute, but not before that time.

[0514] After 0, 0.5, 1, 2, 3 and 5 minutes, salivary pH was measured at the desired time points (15, 30, 45 seconds, 1, 1.5, 2, 3, 4 and 5 minutes). Salivary pH was measured directly in oral saliva using standard pH strips.

[0515] The average salivary pH of the subjects at different times is calculated.

[0516] The methods outlined above were applied to obtain in vivo pH profiles of selected samples.

[0517] [Table 16]

[0518] Conclusion: The tests demonstrate that tablets containing an alkaline pH adjuster in the first compression module and an acidic pH adjuster in the second compression module provide a desirable pH profile, i.e., a desired pH above 7.5 during the initial hours of use, followed by a drop in pH to below 7.5.

[0519] Example 3D: Evaluation of Burning Sensation in the Mouth and Throat Nicotine burning sensation was evaluated by a test panel of 10 trained evaluators. First, the nicotine burning sensation was calibrated by placing a representative standard nicotine tablet between the tongue and the palate in the mouth and inhaling until it completely disintegrated. For this purpose, a tablet corresponding to the first module of sample C5 was used. Then, each evaluator evaluates the burning sensation in the mouth and throat on a scale of 1 to 15, with 15 being the most intense burning sensation. Each evaluator evaluates all samples twice. The ratings are recorded for the indicated time periods. The average value is calculated.

[0520] [Table 17]

[0521] Conclusion: The study demonstrates that tablets containing an acidic pH modifier in the second compression module provide significantly lower burn scores at all time points compared to control tablets without an acidic pH modifier. Tablets containing an acidic pH modifier in the second compression module provided lower burning scores for both burning sensation in the mouth and throat.

Claims

1. 1. A water-soluble nicotine tablet comprising at least a first compression module and a second compression module, the first compression module is an FDT module; nicotine, an alkaline pH adjuster, and Contains a disintegrant, the second compression module is a lozenge module; A water-soluble nicotine tablet containing an acidic pH adjuster.

2. 10. The water-soluble nicotine tablet of claim 1, wherein the water-soluble nicotine tablet comprises nicotine in an amount of at least 0.2 mg.

3. 10. The water-soluble nicotine tablet of claim 1, wherein the nicotine is contained in the first compression module.

4. 2. The water-soluble nicotine tablet of claim 1, wherein the nicotine comprises a nicotine salt selected from the list consisting of nicotine ascorbate, nicotine aspartate, nicotine benzoate, nicotine monotartrate, nicotine bitartrate, nicotine hydrochloride, nicotine dihydrochloride, nicotine citrate, nicotine fumarate, nicotine gensiteate, nicotine lactate, nicotine mucinate, nicotine laurate, nicotine levulinate, nicotine malate, nicotine perchlorate, nicotine pyruvate, nicotine salicylate, nicotine sorbate, nicotine succinate, nicotine zinc chloride, nicotine sulfate, nicotine tosylate, and combinations thereof.

5. 10. The water-soluble nicotine tablet of claim 1, wherein the first compression module comprises an alkaline pH adjuster in an amount of at least 0.2% by weight of the first compression module.

6. 2. The water-soluble nicotine tablet of claim 1, wherein the alkaline pH adjuster comprises an alkaline pH adjuster selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trometamol, an amino acid, a di-alkali hydrogen phosphate, a tri-alkali phosphate, or any combination thereof.

7. 10. The water-soluble nicotine tablet of claim 1, wherein the first compression module, when dissolved in water having a pH of 7.0 when measured at 25 degrees Celsius and atmospheric pressure, induces a pH greater than 7.

5.

8. 10. The water-soluble nicotine tablet of claim 1, wherein the first compression module comprises a disintegrant in an amount of at least 0.5% by weight of the first compression module.

9. 10. The water-soluble nicotine tablet of claim 1, wherein the disintegrant comprises a superdisintegrant.

10. 10. The water-soluble nicotine tablet of claim 1, wherein the disintegrant is a superdisintegrant selected from the group consisting of cross-linked cellulose, cross-linked polyvinylpyrrolidone, cross-linked starch, cross-linked alginic acid, and any combination thereof.

11. 10. The water-soluble nicotine tablet of claim 1, wherein the acidic pH adjuster is contained in the second compression module.

12. 2. The water-soluble nicotine tablet of claim 1, wherein the acidic pH adjuster comprises an acidic pH adjuster selected from the list consisting of phosphoric acid, mono-alkali dihydrogen phosphate, citric acid, mono-alkali dihydrogen citrate, di-alkali hydrogen citrate, malic acid, mono-alkali malate, succinic acid, mono-alkali succinate, tartaric acid, mono-alkali tartrate, acetic acid, sorbic acid, benzoic acid, formic acid, and combinations thereof.

13. 10. The water-soluble nicotine tablet of claim 1, wherein the alkaline pH adjuster is contained in the first compression module.

14. 10. The water-soluble nicotine tablet of claim 1, wherein the water-soluble nicotine tablet comprises a flavoring, the flavoring being contained in the second compression module.

15. 10. The water-soluble nicotine tablet of claim 1, wherein the water-soluble nicotine tablet comprises a sugar alcohol.

16. 10. The water-soluble nicotine tablet of claim 1, wherein the water-soluble nicotine tablet comprises a sugar alcohol in an amount of at least 50% by weight of the water-soluble nicotine tablet.

17. 10. The water-soluble nicotine tablet of claim 1, wherein the first compression module comprises 10% to 50% by weight of the water-soluble nicotine tablet.

18. 10. The water-soluble nicotine tablet of claim 1, wherein the first compression module completely disintegrates within 60 seconds upon oral administration.

19. 10. The water-soluble nicotine tablet of claim 1, wherein the water-soluble nicotine tablet completely disintegrates within 15 minutes upon oral administration.

20. A water-soluble nicotine tablet as described in claim 1, wherein the first compression module does not contain an acidic pH adjuster.

21. A water-soluble nicotine tablet as described in claim 1, wherein the second compression module does not contain an alkaline pH adjuster.

22. A water-soluble nicotine tablet as described in claim 1, wherein the second compression module does not contain nicotine.

23. 23. A method for producing a water-soluble nicotine tablet according to any one of claims 1 to 22, said method comprising: providing a first powdered composition and a second powdered composition, wherein the first powdered composition comprises nicotine, a disintegrant, and an alkaline pH adjuster, and the second powdered composition comprises an acidic pH adjuster; compressing the second powdered composition and the first powdered composition to obtain the water-soluble nicotine tablet comprising modules fused together by compression.