Multi-layered dextrose tablets

Abstract

The present invention relates to an oral chewable tablet comprising dextrose in an amount of 50-95% by weight of the tablet; and one or more active ingredients in an amount of 0.1-50% by weight of the tablet. The oral chewable tablet comprises at least two compressed layers containing said dextrose and one or more active ingredients, a first layer of the compressed layers being contiguous with and adjacent to a second layer.

Description

[Technical field]

[0001] The present invention relates to the field of chewable tablets for oral delivery of active ingredients. In particular, the present invention relates to multi-layer tablets suitable for high load delivery of active ingredients. [Background technology]

[0002] Various attempts have been proposed in the past to incorporate high loads of active ingredients into oral tablets, and while these solutions may offer some advantages in terms of containing a high content of active substance in the tablet, they often suffer from obvious drawbacks that prevent them from being commercialized.

[0003] Difficulties often arise during the manufacturing process, particularly with respect to tablets containing high loads of active ingredients, which often result in fragile tablets during the manufacturing process that can cause processing problems during storage and transportation of the tablets.

[0004] In particular, multi-layer tablets can be difficult to produce with good results. In many cases, these tablets are fragile and therefore undesirable for the storage and transportation drawbacks of tablets. Typically, when multi-layer tablets are prepared in a tablet press, the compression process somewhat limits the amount of active material that can be incorporated into the tablet layers.

[0005] For example, a prior compression step in the tabletting procedure for the first layer of a tablet can cause problems with friability when a second layer is applied on top of the first layer. High pressure is usually required for the second layer to provide a suitable tablet that is robust and will coalesce to form a sealed structure for the multi-layer tablet.

[0006] Also, high loading of active ingredients can cause problems with the overall sensory properties of the multi-layer tablet: both the nature of the active ingredients with regard to taste properties and the pronounced bitterness of some active ingredients, and the high amount of active material in multi-layer tablets compared to other ingredients, can pose challenges for formulation specialists.

[0007] One of the more important problems is that it is often difficult to formulate a multi-layer tablet for oral delivery with suitable sensory properties.Sensory properties in this context include the overall texture of the multi-layer tablet when chewed and the resulting delivery of active ingredients to the oral cavity.For example, a significant powdery feeling is often inconvenient for users, and can result in poor multi-layer tablets that are not used frequently.

[0008] Preferably, a multi-layer tablet should be provided that may also serve to obtain improved sensory properties, where important sensory properties include friability, texture, flavor perception, sweetness perception and off-notes related to the active substance, all of which are relevant in terms of convenience in chewable multi-layer tablets, but also certainly to support proper delivery of the active substance from the multi-layer tablet and to avoid adverse side effects of the active substance.

[0009] One of the challenges with chewable multi-layer tablets as active substance delivery vehicles is that active substances may tend to be associated with off-notes during administration due to the specific physicochemical properties of the compounds.When the release of more active substances is delivered by such multi-layer tablets, the problem of taste masking becomes even more serious.When off-notes are the main sensation during administration, it may affect convenience, and even more importantly, it may affect the delivery of active substances.Saliva production may also be suppressed, and delivery vehicles cannot be handled accurately.

[0010] Furthermore, even if sensory properties are to be respected to some extent, there will usually also be a desire for relatively rapid delivery of the active ingredient upon oral administration. In many cases, this desire for relatively rapid release runs counter to the desire for taste masking of the active ingredient.

[0011] In particular, little attention has been paid to the advantages of chewable multi-layer tablet formulations, which can also be useful to obtain active substance release characteristics that provide convenience and increased efficacy.One of these release characteristics is the increased saliva production during chewing.Increased saliva production, and especially the experience of increased saliva production during administration, can have some significant advantages for the delivery of active substances.

[0012] Thus, there is a need for a multi-layer tablet for oral delivery of an active ingredient that provides advantageous sensory properties while at the same time providing relatively rapid delivery of the active ingredient, which may be particularly desirable for active ingredients at high loads, but also for active ingredients at low loads, such as those that have a pronounced bitter taste profile. [Prior art documents] [Patent documents]

[0013] [Patent Document 1] WO 00 / 25598 [Non-patent literature]

[0014] [Non-Patent Document 1] European Pharmacopoeia 9.1, test method 2.9.7 [Non-Patent Document 2] European Pharmacopoeia 9.1, test method 2.9.8 [Non-Patent Document 3] European Pharmacopoeia 9.1 [Non-Patent Document 4] European Pharmacopeia 9.0, section 2.9.1, Disintegration of tablets and capsules [Non-Patent Document 5] Martindale, The Extra Pharmacopoeia, 28th edition, pp. 547-578. [Non-Patent Document 6] Pharm. Int., Nov. 85, pp. 267-271, Barney H. Hunter and Robert L. Talbert Summary of the Invention

[0015] Thus, an oral chewable tablet comprising: Dextrose in an amount of 50 to 95% by weight of the tablet; and Contains one or more active ingredients in an amount of 0.1 to 50% by weight of the tablet, An oral chewable tablet is provided that includes at least two compressed layers containing the dextrose and one or more active ingredients, a first layer of the compressed layers being contiguous with and adjacent to a second layer of the compressed layers.

[0016] The provision of a chewable multi-layer tablet according to the present invention is able to solve various problems of the prior art and aims to establish a chewable multi-layer tablet which combines advantageous delivery properties of active substances combined with advantageous sensory properties.

[0017] In general, the objective of the oral chewable multi-layer tablet according to the present invention is the combination of relatively high amounts of dextrose and one or more active ingredients in a configuration that simultaneously allows for greater flexibility than conventional oral chewable monolayer tablets.

[0018] One advantage of the present invention is the surprisingly strong saliva production compared to conventional chewable tablets and lozenges.The increased saliva production can have a significant effect on the delivery of one or more active ingredients.Specifically, when the increased saliva production is coordinated with the release of one or more active ingredients from the multi-layer tablet, a relatively rapid delivery is obtained.Therefore, the synergistic effect between the action of one or more active ingredients and the increased saliva production can be seen by the present invention.

[0019] One unexpected advantage over the prior art is the surprising continuation of saliva production after the user has swallowed the bulk of the dextrose, which can be advantageous for many applications of chewable multi-layer tablets ranging from texture, taste, flavor perception, and the like.

[0020] In terms of release characteristics, the present invention can provide an improved release profile of one or more active ingredients compared to conventional chewable monolayer tablets. In particular, the specific tablet formulation platform of the present invention can be useful for providing an improved release profile of one or more active ingredients compared to conventional chewable monolayer tablet formulation platforms administered in combination with one or more active ingredients.

[0021] A very important aspect of the present invention is the provision of advantageous sensory properties. Here, important sensory properties include mouthfeel, ease of chewing / dissolving in liquid, friability (mechanical durability), texture, flavor perception, sweetness perception and off-notes associated with one or more active ingredients. All of these properties are related to the convenience aspect of chewable multi-layer tablets, but also certainly to support the proper delivery of one or more active ingredients from chewable multi-layer tablet formulations, such as improving release profile, and to avoid adverse side effects of one or more active ingredients.

[0022] The inventors have shown very surprising results with the specific combination of features of the invention in terms of these sensory properties, and it was an unexpected result that the invention can also provide very advantageous sensory properties that can contribute to an improved release profile, such as a rapid release of one or more active ingredients, and at the same time, in that regard, can also support an adequate delivery of one or more active ingredients from the chewable multi-layer tablet.

[0023] One particularly advantageous sensory property is the texture. The texture of an oral multilayer tablet during use is important for the release and experience of one or more active ingredients, as well as for convenience during use. The texture has been improved, which was not predicted by the inventors of the present invention.

[0024] It was also not expected that a relatively large amount of dextrose according to the invention combined with one or more active ingredients according to the invention in a multi-layer arrangement would provide favorable friability and other properties. It is important that the friability is balanced. Without being bound by theory, it was expected that the layers of the multi-layer tablet would not adhere properly or at least would cause fracture during the compression process and even capping or de-lamination when the tablet is ejected from the tablet press. However, the multi-layer tablet according to the invention has provided surprising results in terms of friability and also sensory properties.

[0025] In the context of the present invention, "chewable tablet" is intended to mean an oral tablet that is chewed for oral administration and that has characteristics that allow for convenient chewing without the adverse side effects associated with oral tablet texture.

[0026] The provision of a layered tablet structure according to the present invention aims at establishing a platform which may solve various problems of the prior art and which combines advantageous delivery properties of active substances combined with advantageous sensory properties.

[0027] In this context, a "layer" should be understood as a matrix resulting from pressing a portion of the particles according to the invention. This portion may comprise one or more populations of particles. Thus, when a portion of the particles according to the invention is applied to a tablet press and this portion is pressed into a coherent tablet, this will correspond to one "layer" or "first layer". Optionally, such a layer can be pressed in two steps with varying pressure.

[0028] Typically, a pre-compression pressure is applied to the first part to be pressed. This pressure will typically be lower than for the "second layer". Pre-compression serves a variety of purposes, such as aligning the first part with a sharp visual line at the periphery of the multi-layer tablet. Another purpose of the important feature is that it provides a solid support for the "second layer", thereby helping to establish bonds between the particles of material.

[0029] If another portion of the particles according to the invention is applied and pressed on top of the already pressed layer in the tablet press, this will correspond to another "layer" or "second layer". This portion may comprise one or more populations of particles. In the context of the present invention, the second layer may be applied to the tablet press first and the first layer may be applied to the tablet press in a second step.

[0030] Due to the inherent nature of conventional tablet presses, when layers are pressed in two or more subsequent steps, the individual layers of the tableted composition will have sharp lines between the layers. This is seen from the side of the tablet as separate layers on top of each other. In an alternative embodiment, two or more parts are applied to the tableting apparatus in subsequent steps and pressed in one sequence. In this case, from the side, there will be no sharp lines between the layers, which will still be considered a layered tablet according to the present invention, although the lines between the layers will be irregular. Therefore, in some embodiments, it is not necessary to process the layers in separate tableting steps, preferably with a prior compression step.

[0031] In this context, "contiguous with" is intended to mean that two layers are pressed together, one above and one below, of two portions of particles that contain one or more populations of particles. Thus, one surface of a layer is attached to one surface of another layer, and the additional surfaces of the portions are not mutually exposed. Viewed from the side, the layers have the appearance of a tablet slice. In some embodiments of the present invention, the tablet consists of two layers.

[0032] In some embodiments of the present invention, the mass ratio of the first layer to the second layer is from 1:10 to 10:1.

[0033] By adjusting the "thickness" of the layers, i.e., the mass ratio, it is possible to facilitate the controlled release of one or more active ingredients and to improve the sensory properties of the tablet.

[0034] In some embodiments of the present invention, the mass ratio of the first layer to the second layer is 1:5 to 5:1. In some embodiments of the present invention, the mass ratio of the first layer to the second layer is 3:10 to 10:3. In some embodiments of the present invention, the mass ratio of the first layer to the second layer is 1:2 to 2:1.

[0035] In some embodiments of the invention, the tablet comprises three layers, a first layer is an intermediate layer, a second layer is conjoined to and adjacent to one side of the first layer, and a third layer is conjoined to and adjacent to the opposite side of the first layer.

[0036] In the present context, "contiguous with" is intended to mean that two outer layers are disposed and attached, one above and one below, to an intermediate layer. Viewed from the side, the layers have the appearance of a tablet slice.

[0037] In some embodiments of the present invention, the mass ratio of the first layer to the second layer to the third layer is 1:5:5 to 10:1:1. In some embodiments of the present invention, the mass ratio of the first layer to the second layer to the third layer is 1:3:3 to 3:1:1.

[0038] By adjusting the "thickness" of the layers, i.e., the mass ratio, it is possible to facilitate the controlled release of one or more cannabinoids and to improve the sensory properties of the tablet.

[0039] In some embodiments of the present invention, the mass ratio of the first layer to the second layer to the third layer is 1:4:4 to 8:1:1. In one embodiment of the present invention, the mass ratio of the first layer to the second layer to the third layer is 1:4:4 to 6:1:1. In one embodiment of the present invention, the mass ratio of the first layer to the second layer to the third layer is 1:4:4 to 4:1:1.

[0040] According to the present invention, tableting means that the particles are reduced in volume as a result of the pressure applied in the tableting machine. Thus, the particles may be flowable before tableting, but once the particles are pressed, the volume of the particles is reduced and the particles are coalesced together into a continuous matrix, which in this context is referred to as a "layer". In this context, it should be understood that the individual particles are not merged after tableting, but maintain individual and "distinct" regions after tableting to constitute individual particles. There may be some incorporation of the particles, but generally the particles maintain the distinct regions of the tablet.

[0041] In some embodiments of the present invention, the oral chewable tablet is made by direct compression on a tablet press. In some embodiments of the present invention, the first layer is a pre-compressed layer, and the second layer is compressed on top of the first layer. In some embodiments of the present invention, the first layer is pre-compressed by direct compression on a tablet press, and the second layer is compressed on top of the first layer in a tablet press. In some embodiments of the present invention, the first layer is pre-compressed by direct compression on a tablet press, and the second layer is compressed on top of the first layer in a tablet press at a higher pressure.

[0042] In some embodiments of the invention, the second layer is compressed on top of the first layer with a pressure that is operable to avoid tablet fracture during compression. In the present context, "tablet fracture during compression" is intended to mean that the tablet breaks, to a more or less pronounced extent, during compression.

[0043] In some embodiments of the present invention, the second layer is compressed on top of the first layer with a pressure that is operable to avoid tablet capping. Tablet capping is the most common defect. This is when the molded dome part of the tablet breaks away from the body part of the tablet. When compressing the tablet, air is expelled between the granules, which can cause them to stick together. If the particles are too dry, too lubricated, or highly elastic, they will not bond together well. The stress of ejection can open small microcracks in the compact, which will expand and cause the cap part to shear away from the body part.

[0044] In some embodiments of the present invention, the second layer is compressed on top of the first layer with a pressure that is operable to avoid tablet delamination. Tablet layering can occur when the product separates into horizontal layers. Layering is very similar to capping, but occurs in the main body of the tablet rather than on top, and can occur immediately after compression or during storage.

[0045] In some embodiments of the invention, dextrose is present in an amount of 55-95% by weight of the tablet. In some embodiments of the invention, dextrose is present in an amount of 60-95% by weight of the tablet. In some embodiments of the invention, dextrose is present in an amount of 65-95% by weight of the tablet. In some embodiments of the invention, dextrose is present in an amount of 70-95% by weight of the tablet. In some embodiments of the invention, dextrose is present in an amount of 70-90% by weight of the tablet.

[0046] In some embodiments of the invention, the oral chewable tablets consist essentially of dextrose, one or more active ingredients, one or more binders which are added separately to the formulation and are separate from any binders incorporated into other ingredients within the tablet, and auxiliary ingredients which are present in up to about 5% by weight of the tablet.

[0047] In some embodiments of the present invention, the oral chewable tablets consist essentially of dextrose, one or more active ingredients, and accessory ingredients present in up to about 5% by weight of the tablet.

[0048] Flavoring agents, intense sweeteners and flow enhancers are examples of adjunct ingredients that may be added in low amounts according to the present invention without compromising the platform according to the present invention.

[0049] However, in the present context, it is understood that the bulk of the chewable tablet is comprised of dextrose and one or more active ingredients according to the present invention, the entire system of the chewable tablet being controlled by these ingredients, including the specific improved sensory benefits of the present invention, such as improved mouthfeel, as well as saliva production, as well as friability properties.

[0050] In some embodiments of the present invention, the oral chewable tablets consist essentially of dextrose, one or more active ingredients, and one or more binders.

[0051] In some embodiments of the present invention, the oral chewable tablet does not contain sugar alcohol. Sugar alcohol is expected to be detrimental to the platform properties according to the present invention, including sensory properties such as texture, in some embodiments. However, in some embodiments, low amounts of sugar alcohol, such as mannitol, such as less than 5% by weight, may be added.

[0052] In some embodiments of the present invention, the oral chewable tablet does not include a rubber base, the presence of which may affect the sensory properties of the tablet as well as the release of the active ingredient.

[0053] In some embodiments of the present invention, the dextrose is based on the controlled enzymatic hydrolysis of starch.

[0054] In some embodiments of the invention, the dextrose comprises anhydrous dextrose. In some embodiments of the invention, the dextrose comprises hydrated dextrose. In some embodiments of the invention, the dextrose comprises dextrose monohydrate. In some embodiments of the invention, the dextrose comprises at least 90% dextrose equivalent calculated on a dry basis. In some embodiments of the invention, the dextrose comprises at least 93% dextrose equivalent calculated on a dry basis. In some embodiments of the invention, the dextrose comprises at least 95% dextrose equivalent calculated on a dry basis. In some embodiments of the invention, the dextrose comprises at least 98% dextrose equivalent calculated on a dry basis.

[0055] In some embodiments of the invention, the dextrose comprises a mixture of refined sugars. In some embodiments of the invention, the dextrose comprises oligosaccharides. In some embodiments of the invention, the dextrose comprises at least 93-97% dextrose equivalent calculated on a dry basis. In some embodiments of the invention, the dextrose comprises microcrystalline dextrose. In some embodiments of the invention, the dextrose comprises dextrates.

[0056] In some embodiments of the present invention, the dextrose does not include maltodextrin.

[0057] In some embodiments of the present invention, the dextrose contains 100% dextrose equivalent calculated on a dry basis. Dextrose in a pure version contains 100% dextrose equivalent calculated on a dry basis and is currently preferred as the dextrose administered in the present invention. In some embodiments, the dextrose is pure and based on 100% conversion of starch to dextrose.

[0058] In some embodiments of the invention, the dextrose is directly compressible (DC).

[0059] In some embodiments of the present invention, the dextrose is a powder.

[0060] In some embodiments of the present invention, the oral chewable tablet comprises at least one grade of dextrose. In some embodiments of the present invention, the oral chewable tablet comprises at least two grades of dextrose. In some embodiments of the present invention, the oral chewable tablet comprises at least three grades of dextrose.

[0061] In some embodiments of the present invention, the oral chewable tablet comprises different grades of dextrose in different layers of the tablet. In some embodiments of the present invention, the oral chewable tablet comprises at least one grade of dextrose containing a binder. In some embodiments of the present invention, the oral chewable tablet comprises at least one grade of dextrose containing maltodextrin. In some embodiments of the present invention, the oral chewable tablet comprises at least one grade of dextrose, which is a granule comprising dextrose and one or more binders. In some embodiments of the present invention, the oral chewable tablet comprises at least one grade of dextrose, in which one or more binders are not incorporated into the grade.

[0062] In some embodiments of the invention, the dextrose comprises at least 30% by weight of particles in the range of 180-500 microns. In some embodiments of the invention, the dextrose comprises at least 50% by weight of particles in the range of 180-500 microns. In some embodiments of the invention, the dextrose comprises at least 30% by weight of particles in the range of 250-500 microns. In some embodiments of the invention, the dextrose comprises at least 50% by weight of particles greater than 250 microns. In some embodiments of the invention, the dextrose comprises at least 10% by weight of particles greater than 500 microns.

[0063] In some embodiments of the invention, the dextrose comprises at most 35% by weight of particles less than 100 microns. In some embodiments of the invention, the dextrose comprises at most 10% by weight of particles greater than 500 microns. One currently preferred grade of dextrose includes C*Dex™ 02001 offered by Cargill. This grade is also referred to as fine grade dextrose due to its particle size distribution that includes a relatively high percentage of particles having small particle sizes. Another grade of dextrose includes Cerelose® Dextrose 020010 offered by Ingredion, which is C*Dex™ 020010. * It has a similar particle size distribution as Dex™ 02001.

[0064] In some embodiments of the invention, the dextrose comprises at most 5% by weight of particles less than 100 microns. In some embodiments of the invention, the dextrose comprises at most 20% by weight of particles less than 250 microns. One grade of dextrose includes C*Dex™ 02032 provided by Cargill. Another grade of dextrose includes C*Dex™ 02030 provided by Cargill. This grade is also referred to as coarse grade dextrose due to its particle size distribution that includes a relatively high proportion of particles with large sizes.

[0065] In some embodiments of the present invention, the dextrose comprises at most 25% by weight of particles less than 149 microns. In some embodiments of the present invention, the dextrose comprises at most 35% by weight of particles less than 177 microns. In some embodiments of the present invention, the dextrose comprises at least 5% by weight of particles greater than 1190 microns. One grade of dextrose includes Royal-T® provided by Ingredion. This grade contains maltodextrin within the particles, i.e., the particles are subjected to granulation with maltodextrin.

[0066] It has been found that in some embodiments, the grade of dextrose can affect the compression placement. For example, by providing a coarse grade dextrose, some difficulties of capping or delamination can be avoided during compression of multi-layer tablets according to the present invention. Thus, in some embodiments, a coarser grade of dextrose, or a grade incorporating a content of maltodextrin, is preferred.

[0067] In some embodiments of the present invention, the oral chewable tablets contain one or more binders that are added separately to the formulation and are separate from any binders incorporated into other components within the tablet.

[0068] In some embodiments of the invention, the one or more binders are present in an amount of 0.4-5% by weight of the tablet. In some embodiments of the invention, the one or more binders are present in an amount of 0.5-4% by weight of the tablet. In some embodiments of the invention, the one or more binders are present in an amount of 0.7-3% by weight of the tablet. In some embodiments of the invention, the one or more binders are present in an amount of 0.7-2% by weight of the tablet. In some embodiments of the invention, the one or more binders are present in an amount of 0.7-1.3% by weight of the tablet.

[0069] In some embodiments of the invention, the one or more binders are present in an amount of 2-15% by weight of the tablet.In some embodiments of the invention, the one or more binders are present in an amount of 3-10% by weight of the tablet.

[0070] In some embodiments of the invention, the one or more binders are present in an amount of 4-6% by weight of the tablet. In some embodiments of the invention, the one or more binders are present in an amount of 2-7% by weight of the tablet. In some embodiments of the invention, the one or more binders are present in an amount of 2-5% by weight of the tablet. In some embodiments of the invention, the one or more binders are present in an amount of 3-7% by weight of the tablet. In some embodiments of the invention, the one or more binders are present in an amount of 3-6% by weight of the tablet. In some embodiments of the invention, the one or more binders are present in an amount of 3-5% by weight of the tablet.

[0071] In some embodiments of the present invention, the one or more binders are selected from the group consisting of hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), maltodextrin, and combinations thereof.

[0072] In some embodiments of the present invention, the one or more binders are selected from the group consisting of hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and combinations thereof.

[0073] In some embodiments of the present invention, the one or more binders include hydroxypropyl cellulose (HPC). In some embodiments of the present invention, the one or more binders are hydroxypropyl cellulose (HPC). HPC can be applied as a unique and attractive binder. Thus, this binder, when used with dextrose, shows a favorable sensory experience when compared to other well-known binders.

[0074] In some embodiments of the present invention, the one or more binders include hydroxypropyl methylcellulose (HPMC). In some embodiments of the present invention, the one or more binders are hydroxypropyl methylcellulose (HPMC). HPMC can be applied as a unique and attractive binder. Thus, this binder, when used with dextrose, shows a favorable sensory experience when compared to other well-known binders.

[0075] In some embodiments of the present invention, the one or more binders comprise maltodextrin.

[0076] In some embodiments of the invention, the one or more binders do not include microcrystalline cellulose (MCC), which is considered deficient in relation to sensory properties according to the invention.

[0077] In some embodiments of the invention, the one or more binders do not include silica, cellulose, silicified microcrystalline cellulose, clay, talc, starch, pregelatinized starch, calcium carbonate, dicalcium phosphate, magnesium carbonate, magnesium-alumino-metasilicate, superporous silica, and mixtures thereof.

[0078] In some embodiments of the present invention, the oral chewable tablet does not include one or more binders that are added separately to the formulation and are separate from any binders that are incorporated into other ingredients in the tablet. In some embodiments of the present invention, the oral chewable tablet includes one or more binders that are incorporated into other ingredients in the tablet, such as one or more binders present in granules that include dextrose.

[0079] In some embodiments of the invention, the active ingredient or ingredients are present in an amount of 5-50% by weight of the tablet.

[0080] In some embodiments of the invention, the active ingredient or ingredients are present in an amount of 10-50% by weight of the tablet.

[0081] In some embodiments of the invention, the active ingredient or ingredients are present in an amount of 20-50% by weight of the tablet.

[0082] In some embodiments of the invention, the active ingredient or ingredients are present in an amount of 30-50% by weight of the tablet.

[0083] In some embodiments of the invention, the active ingredient or ingredients are present in an amount of 5-40% by weight of the tablet.

[0084] In some embodiments of the invention, the active ingredient or ingredients are present in an amount of 5-30% by weight of the tablet.

[0085] In some embodiments of the invention, the active ingredient or ingredients are present in an amount of 10-30% by weight of the tablet.

[0086] In some embodiments of the present invention, the one or more active ingredients comprises a non-directly compressible (non-DC) active ingredient.

[0087] In some embodiments of the present invention, one or more active ingredients are disposed in the first layer of the tablet. In some embodiments of the present invention, one or more active ingredients are disposed in the second layer of the tablet. In some embodiments of the present invention, one or more active ingredients are disposed in both the first layer and the second layer of the tablet. In some embodiments of the present invention, one active ingredient is disposed in the first layer of the tablet and another active ingredient is disposed in the second layer of the tablet. In some embodiments of the present invention, one of the layers of the tablet does not contain one or more active ingredients.

[0088] In some embodiments of the invention, the one or more active ingredients include a non-directly compressible (non-DC) active ingredient. In some embodiments of the invention, the one or more active ingredients include a non-directly compressible (non-DC) active ingredient in an amount of 5-50% by weight of the tablet. In some embodiments of the invention, the one or more active ingredients include a non-directly compressible (non-DC) active ingredient in an amount of 10-50% by weight of the tablet. In some embodiments of the invention, the one or more active ingredients include a non-directly compressible (non-DC) active ingredient in an amount of 20-50% by weight of the tablet. In some embodiments of the invention, the one or more active ingredients include a non-directly compressible (non-DC) active ingredient in an amount of 30-50% by weight of the tablet.

[0089] In some embodiments of the present invention, the one or more active ingredients comprises a directly compressible (DC) active ingredient.

[0090] In some embodiments of the invention, the one or more active ingredients comprises an immune-supporting active ingredient.

[0091] In some embodiments of the invention, the one or more active ingredients comprises a mixture of immune-supporting active ingredients.

[0092] In some embodiments of the present invention, the one or more active ingredients comprises an energy stimulating active ingredient.

[0093] In some embodiments of the present invention, the one or more active ingredients include a mixture of vitamins, minerals, and herbs.

[0094] In some embodiments of the present invention, the one or more active ingredients include vitamin C. In some embodiments of the present invention, the one or more active ingredients include melatonin. In some embodiments of the present invention, the one or more active ingredients include theanine. In some embodiments of the present invention, the one or more active ingredients include calcium carbonate. In some embodiments of the present invention, the one or more active ingredients include caffeine.

[0095] In some embodiments of the present invention, the one or more active ingredients include a multivitamin. In some embodiments of the present invention, the one or more active ingredients include Zn oxide. In some embodiments of the present invention, the one or more active ingredients include Zn citrate. In some embodiments of the present invention, the one or more active ingredients include Zn gluconate. In some embodiments of the present invention, the one or more active ingredients include Vitamin D.

[0096] In some embodiments of the present invention, the one or more active ingredients include acetaminophen. In some embodiments of the present invention, the one or more active ingredients include phenylephrine. In some embodiments of the present invention, the one or more active ingredients include dextromethorphan. In some embodiments of the present invention, the one or more active ingredients include guaifenesin. In some embodiments of the present invention, the one or more active ingredients include a combination of acetaminophen, phenylephrine, dextromethorphan, and guaifenesin.

[0097] In some embodiments of the present invention, the one or more active ingredients include diphenhydramine. In some embodiments of the present invention, the one or more active ingredients include loratadine. In some embodiments of the present invention, the one or more active ingredients include nicotine.

[0098] In one embodiment of the present invention, the active ingredient is selected from acetylcysteine, ambroxol, amylmetacresol, benzocaine, bisacodyl, bismuth subsalicylate, bromhexine, cetirizine, dextromethorphan hydrobromide, 2,4-dichlorobenzyl alcohol, doxylamine succinate, flurbiprofen, glycerin, hexylresorcinol, lidocaine, menthol, myrrh, paracetamol, pectin, peppermint oil, phenol, phenylephrine hydrochloride, povidone iodine, pseudoephedrine, ranitidine, simethicone, sodium docusate, spearmint, zinc, or any combination thereof.

[0099] Listed above are the active ingredients that can be delivered to the throat.

[0100] In some embodiments, the tablet may contain further active ingredients, for example a combination of two or more active ingredients from the list above, or a combination of an active ingredient from the list above and another active ingredient.

[0101] In one embodiment of the present invention, the active ingredient is an analgesic. Examples of analgesics include, for example, ibuprofen, paracetamol (acetaminophen), ketoprofen, aspirin (acetylsalicylic acid), and naproxen. In one embodiment of the present invention, the active ingredient is an anesthetic. In one embodiment of the present invention, the active ingredient is an anti-inflammatory drug. In one embodiment of the present invention, the active ingredient is an antiseptic.

[0102] In one embodiment of the invention, the active ingredient is an antitussive. Examples of antitussives include, for example, dextromethorphan.

[0103] In one embodiment of the invention, the active ingredient is an expectorant, such as guaifenesin.

[0104] In one embodiment of the invention, the active ingredient is a local anesthetic. Examples of local anesthetics include, for example, ambroxol, benzocaine, and hexylresorcinol.

[0105] In one embodiment of the invention, the active ingredient is a member of the morphinan class. Examples of members of the morphinan class include, for example, dextromethorphan.

[0106] In one embodiment of the invention, the active ingredient is a non-steroidal anti-inflammatory drug (NSAID). Examples of non-steroidal anti-inflammatory drugs (NSAIDs) include, for example, flurbiprofen.

[0107] In one embodiment of the invention, the active ingredient is an anti-inflammatory agent.In one embodiment of the invention, the active ingredient is an antiseptic agent.

[0108] In one embodiment of the invention, the active ingredient is a cough and cold medication.

[0109] In one embodiment of the invention, the tablet contains a cough and cold medication including acetaminophen, dextromethorphan hydrobromide, guaifenesin and phenylephrine hydrochloride.

[0110] In one embodiment of the invention, the tablet contains a cough and cold medication including acetaminophen, dextromethorphan hydrobromide and phenylephrine hydrochloride.

[0111] In one embodiment of the invention, the active ingredient is an antihistamine. In one embodiment of the invention, the active ingredient is an antibiotic. Examples of antibiotics include, for example, ampicillin, erythromycin, tetracycline, clarithromycin, penicillin, and metronidazole.

[0112] In one embodiment of the present invention, the active ingredient is an enzyme. One advantage of enzymes is that they can enhance digestion and / or restore or improve intestinal balance. In one embodiment of the present invention, the active ingredient is an opioid.

[0113] In one embodiment of the invention, the tablet is a medical device for alleviating or treating dysphagia by inducing saliva production. In one embodiment of the invention, the active ingredient is cetirizine. In one embodiment of the invention, the active ingredient is bromhexine. In one embodiment of the invention, the active ingredient is amylmetacresol. In one embodiment of the invention, the active ingredient is paracetamol. In one embodiment of the invention, the active ingredient is acetaminophen. In one embodiment of the invention, the active ingredient is dextromethorphan HBr. In one embodiment of the invention, the active ingredient is guaifenesin. In one embodiment of the invention, the active ingredient is phenylephrine HCl. In one embodiment of the invention, the active ingredient is penicillin.

[0114] In one embodiment of the invention, the tablet further comprises a water soluble fiber such as inulin.

[0115] In one embodiment of the invention, the active ingredient comprises zinc gluconate and ascorbic acid.In one embodiment of the invention, the active ingredient comprises zinc.

[0116] In one embodiment of the invention, the tablet further comprises a plant metabolite, such as red clover or willow extract. In one embodiment of the invention, the tablet further comprises a plant extract, such as echinacea, camille or lavender. In one embodiment of the invention, the plant extract is combined in the tablet with zinc gluconate and ascorbic acid.

[0117] In one advantageous embodiment of the present invention, the oral tablet consists essentially of naturally occurring ingredients.

[0118] In one advantageous embodiment of the present invention, the oral tablet contains a natural high-intensity sweetener, such as stevioside.

[0119] In some embodiments, the one or more active ingredients are alginates, atenolol, aspirin (acetylsalicylic acid), ampicillin, aminosalicylate, anhydrous citric acid, aspirin, bisacodyl, bismuth subsalicylate, bupropion, caffeine, calcium, calcium carbonate, cetirizine, cimetidine, cisapride, clarithromycin, desloratadine, dexlansoprazole, diphenhydramine HCl, diphenhydramine citrate, dimenhydrinate, docusate Erythromycin, Dopamine, Esomeprazole, Famotidine, Fexofenadine HCl, Guaiphenesin, Hydrotalcite, Ibuprofen, Ketoprofen, Lactase Enzyme, Lansoprazole, Loratadine, Lorcaserin, Loperamide, Loperamide HCl, Magnesium, Magnesium Carbonate, Magnesium Hydroxide, Melatonin, Methamphetamine HCl, Metoclopramide, Metronidazole, Montelukast, Mycostatin, Naltrexone, Naproxen, Naproxen Sodium, nizatidine, omeprazole, ondansetron, orlistat, pantoprazole, paracetamol (acetaminophen), pectin, phentermine HCl, polypodium leucotomos, prednisolone, prednisone, progesterone, propranolol, propantheline bromide, pseudoephedrene HCl, phentermine, rabeprazole, ranitidine, roflumilast, scopolamine butyl hydroxide, simethicone, sodium, sodium bicarbonate, sodium docusate, sumatriptan, testosterone, tetracycline, topiramate, vitamin A, vitamin B, vitamin B12, vitamin C (ascorbic acid), vitamin D, and vitamin E, vitamin K, prebiotics, probiotics, inulin fiber, citicoline, L-theanine, taurine, tryptophan, gamma-aminobutyric acid, or any combination thereof. In some embodiments of the present invention, the active ingredient comprises L-theanine. In some embodiments of the present invention, the active ingredient comprises GABA. In some embodiments of the present invention, the active ingredient comprises Bacopa. In some embodiments of the present invention, the active ingredient comprises Magnesium.

[0120] In some embodiments of the invention, the active ingredient comprises vitamin B. In some embodiments of the invention, the active ingredient comprises vitamin B3. In some embodiments of the invention, the active ingredient comprises vitamin B6. In some embodiments of the invention, the active ingredient comprises vitamin B12.

[0121] The above list of active ingredients are those that can be delivered to the gastrointestinal tract.

[0122] In some embodiments, the tablet may contain further active ingredients, for example a combination of two or more active ingredients from the list above, or a combination of an active ingredient from the list above and another active ingredient.

[0123] Further ingredients include herbs such as ashwagandha, ginseng, elderberry, boswellia, green tea, unroasted coffee bean extract, coffee fruit extract, willow bark, ivy leaves, rose hips, chamomile, forsythia fruit extract, lemon balm, passion flower extract, zembrin, and marshmallow root. In some embodiments, the active ingredient comprises ginseng.

[0124] In one advantageous embodiment of the invention, the active ingredient is an analgesic. Examples of analgesics include, for example, ibuprofen, paracetamol (acetaminophen), ketoprofen, aspirin (acetylsalicylic acid), and naproxen. In one advantageous embodiment of the invention, the active ingredient is an anesthetic. In one advantageous embodiment of the invention, the active ingredient is an anti-inflammatory drug. In one advantageous embodiment of the invention, the active ingredient is an antiseptic. In one advantageous embodiment of the invention, the active ingredient is an antibiotic. Examples of antibiotics include, for example, ampicillin, erythromycin, tetracycline, clarithromycin, penicillin, and metronidazole.

[0125] In one advantageous embodiment of the invention, the active ingredient is selected from vitamins, minerals and supplements (VMS).

[0126] Examples of vitamins, minerals, and supplements include, for example, Vitamin A, Vitamin B, Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Vitamin K.

[0127] In some embodiments of the invention, the tablet comprises a combination of caffeine, L-theanine, vitamin B3, vitamin B6, and vitamin B12. In some embodiments of the invention, the tablet comprises a combination of caffeine and vitamin B6. In some embodiments of the invention, the tablet comprises a combination of ginseng and vitamin B12. In some embodiments of the invention, the tablet comprises a combination of melatonin, vitamin C, and zinc. In some embodiments of the invention, the tablet comprises a combination of L-theanine and GABA. In some embodiments of the invention, the tablet comprises a combination of L-theanine and bacopa.

[0128] In an advantageous embodiment of the present invention, the active ingredient is a hormone. In an advantageous embodiment of the present invention, the active ingredient is melatonin. Examples of hormones include, for example, progesterone, testosterone, and melatonin. In an advantageous embodiment of the present invention, the active ingredient is a steroid. Examples of steroids include, for example, prednisolone and prednisone. In an advantageous embodiment of the present invention, the active ingredient is a proton pump inhibitor. Examples of proton pump inhibitors include, for example, rabeprazole, pantoprazole, esomeprazole, dexlansoprazole, lansoprazole, and omeprazole.

[0129] In an advantageous embodiment of the present invention, the active ingredient is an antihistamine.Examples of antihistamines include, for example, cimetidine, ranitidine, famotidine, nizatidine, and desloratadine.Antihistamines are drugs for treating allergic rhinitis and other allergies.Antihistamines can provide relief to people who suffer from nasal congestion, sneezing, or hives, caused by, for example, pollen, dust mite, or animal allergies.

[0130] In one advantageous embodiment of the invention, the active ingredient is a triptan. Examples of triptans include, for example, sumatriptan.

[0131] In one advantageous embodiment of the invention, the active ingredient is a dry mouth reliever, such as a dry mouth reliever for cancer patients. In one advantageous embodiment of the invention, the active ingredient is a migraine treatment. In one advantageous embodiment of the invention, the active ingredient is an enzyme.

[0132] In one advantageous embodiment of the invention, the active ingredient is a probiotic ingredient.In one advantageous embodiment of the invention, the active ingredient is a prebiotic ingredient.

[0133] In one advantageous embodiment of the invention, the active ingredient is a gastrointestinal drug. In this context, a gastrointestinal drug is understood to be an active ingredient which acts in the digestive tract.

[0134] In one preferred embodiment of the invention, the active ingredient is an opioid. In one preferred embodiment of the invention, the active ingredient is an allergy medication. In one preferred embodiment of the invention, the active ingredient is loratadine. In one preferred embodiment of the invention, the active ingredient is diphenhydramine.

[0135] In one advantageous embodiment of the invention, the tablet is a medical device for alleviating or treating dysphagia by inducing saliva production.

[0136] In one preferred embodiment of the invention, the active ingredient is ampicillin. In one preferred embodiment of the invention, the active ingredient is ibuprofen. In one preferred embodiment of the invention, the active ingredient is ondansetron. In one preferred embodiment of the invention, the active ingredient is paracetamol (acetaminophen). In one preferred embodiment of the invention, the active ingredient is acetylsalicylic acid. In one preferred embodiment of the invention, the active ingredient is simethicone. In one preferred embodiment of the invention, the active ingredient is sodium docusate.

[0137] In some embodiments of the present invention, the one or more active ingredients comprise an active pharmaceutical ingredient.

[0138] In some embodiments of the invention, the friability of the tablets is less than 3%, such as less than 2%, such as less than 1.5%, where friability is measured according to European Pharmacopoeia 9.1, test method 2.9.7 by using a pharmaceutical friability tester PTF 10E from Pharma Test.

[0139] In some embodiments of the invention, the tablet generates more than 1.5 mL of saliva within 30 seconds from the start of chewing. In some embodiments of the invention, the tablet generates more than 1.5 mL of saliva within a period of 30 to 90 seconds from the start of chewing. In some embodiments of the invention, the tablet generates more than 1.5 mL of saliva within a period of 90 to 180 seconds from the start of chewing. In some embodiments of the invention, the tablet generates more than 1.5 mL of saliva within a period of 180 to 300 seconds from the start of chewing. In some embodiments of the invention, the oral chewable tablet further comprises a saliva production inhibitor for controlling saliva production.

[0140] In some embodiments of the present invention, the oral chewable tablet is designed to release the active ingredient in the oral cavity and deliver a portion of the active ingredient to the throat as part of the saliva produced when the tablet is chewed. In some embodiments of the present invention, the oral chewable tablet is designed to release the active ingredient in the oral cavity and deliver a portion of the active ingredient to the digestive tract as part of the saliva produced when the tablet is chewed. In some embodiments of the present invention, the oral chewable tablet comprises a means for facilitating the release of one or more active ingredients.

[0141] In some embodiments of the present invention, the oral chewable tablet comprises one or more disintegrants operable to disintegrate the tablet upon contact with oral saliva within a period of 2 minutes or less.

[0142] In this context, "disintegrated" or "disintegrate" is intended to mean that the tablet is no longer considered a tablet, but that the tablet has reduced in size and / or dispersed in saliva.

[0143] Specifically, the inclusion of a disintegrant significantly accelerates the disintegration of tablets according to the present invention. However, although disintegrants have been used previously in tablet formulation science, the specific combination of disintegrant and dextrose according to the present application would have been considered problematic in view of the specific properties of dextrose. Various problems, such as sensory drawbacks and concentration problems associated with high loading of active ingredients, were suspected by the inventors of the present application.

[0144] In some embodiments of the present invention, the oral chewable tablet comprises one or more disintegrants selected from the group consisting of sodium croscarmellose, crospovidone, sodium starch glycolate, and combinations thereof.

[0145] In one embodiment of the invention, the one or more disintegrants comprises cross-linked polyvinylpyrrolidone.

[0146] In one embodiment of the invention, the one or more disintegrants comprise cross-linked polyvinylpyrrolidone, wherein at least 50% by weight of the cross-linked polyvinylpyrrolidone has a particle size of less than 50 micrometers.

[0147] In one embodiment of the invention, the one or more disintegrants comprise cross-linked polyvinylpyrrolidone, wherein at least 25% by weight of the cross-linked polyvinylpyrrolidone has a particle size of less than 15 micrometers.

[0148] In some embodiments of the invention, the first layer is compressed under a compression pressure of 1-5 kN. In some embodiments of the invention, the second layer is compressed under a compression pressure of 6-40 kN. In some embodiments of the invention, the second layer is compressed under a compression pressure of 10-30 kN.

[0149] In some embodiments of the present invention, the oral chewable tablet in contact with saliva has a disintegration profile that changes by less than 10% under a compression pressure of 10-30 kN.

[0150] In some embodiments of the present invention, the unit mass of the tablet is about 100 mg to about 2000 mg. In some embodiments of the present invention, the unit mass of the tablet is about 100 mg to about 1800 mg. In some embodiments of the present invention, the unit mass of the tablet is about 500 mg to about 1600 mg. In some embodiments of the present invention, the unit mass of the tablet is about 600 mg to about 1500 mg.

[0151] In some embodiments of the invention, the active ingredient(s) are present in an amount of 1-1000 mg. In some embodiments of the invention, the active ingredient(s) are present in an amount of 1-800 mg. In some embodiments of the invention, the active ingredient(s) are present in an amount of 1-600 mg.

[0152] In some embodiments of the invention, the active ingredient(s) is present in an amount of 50-250 mg. In some embodiments of the invention, the active ingredient(s) is present in an amount of 100-250 mg.

[0153] In some embodiments of the invention, the active ingredient(s) are present in an amount of 1-50 mg. In some embodiments of the invention, the active ingredient(s) are present in an amount of 1-40 mg. In some embodiments of the invention, the active ingredient(s) are present in an amount of 1-30 mg. In some embodiments of the invention, the active ingredient(s) are present in an amount of 1-20 mg. In some embodiments of the invention, the active ingredient(s) are present in an amount of 1-10 mg. In some embodiments of the invention, the active ingredient(s) are present in an amount of 1-5 mg. In some embodiments of the invention, the active ingredient(s) are present in an amount of 1-4 mg.

[0154] In some embodiments of the present invention, the oral chewable tablets provide an improved mouthfeel compared to oral chewable tablets containing less than 50% dextrose by weight.

[0155] In some embodiments of the present invention, the oral chewable tablets provide an improved melt sensation compared to oral chewable tablets containing less than 50% dextrose by weight.

[0156] In some embodiments of the present invention, the oral chewable tablets provide an improved liquid feel compared to oral chewable tablets containing less than 50% dextrose by weight.

[0157] In some embodiments of the present invention, the oral chewable tablets provide a less sticky sensation compared to oral chewable tablets containing less than 50% dextrose by weight.

[0158] In some embodiments of the present invention, the oral chewable tablets provide less bitter taste sensation from one or more active ingredients compared to oral chewable tablets containing less than 50% dextrose by weight.

[0159] In some embodiments of the present invention, the oral chewable tablets provide improved taste masking compared to oral chewable tablets containing less than 50% dextrose by weight.

[0160] In some embodiments of the present invention, the oral chewable tablets provide an improved melt sensation as compared to oral chewable tablets that include one or more separate binders.

[0161] In some embodiments of the present invention, the oral chewable tablet is designed to become a liquid within 60 seconds of chewing.

[0162] In some embodiments of the present invention, the oral chewable tablet is designed to become a liquid within 30 seconds of chewing.

[0163] In some embodiments of the present invention, the oral chewable tablet is designed to become a liquid within 15 seconds of chewing.

[0164] In one embodiment of the invention, the dextrose is uniformly distributed in the tablet or at least one module of the tablet.

[0165] One advantage of the above embodiment may be that the uniform distribution of dextrose, for example, promotes effective disintegration of the modules during chewing due to the contribution of low mechanical strength by dextrose, thereby promoting effective contact of the resulting chew fragments formed by chewing with saliva, again increasing the dissolution of the tablet.The uniform distribution of dextrose also promotes a large number of chew fragments with dextrose, which again effectively promotes saliva secretion.Thus, the synergy between the use of dextrose as a disintegration promoter due to its lower mechanical strength and as a saliva secretion promoter in combination with the uniform distribution promotes the dispersion of the chew fragments into the oral cavity during chewing.

[0166] In some embodiments of the present invention, the oral chewable tablet comprises further tablet modules having different disintegration times.

[0167] In one embodiment of the invention the resistance to chewing of the tablet is higher than 60N, such as higher than 70N, for example higher than 80N, such as higher than 90N, for example higher than 100N, such as higher than 110, for example higher than 130N, such as higher than 150N, wherein the resistance to chewing of the tablet is lower than 300N, for example lower than 250N, for example lower than 200N, wherein the resistance to chewing is determined according to European Pharmacopoeia 9.1, test method 2.9.8 by using a tester model of pharmaceutical resistance to chewing Pharma Test type PTB 311.

[0168] High-intensity artificial sweeteners can also be used alone or in combination with the above dextrose.Preferred high-intensity sweeteners include, but are not limited to, sucralose, aspartame, salts of acesulfame, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, monellin, stevioside (natural high-intensity sweetener), and the like, alone or in combination.To obtain a longer-lasting sweetness and flavor perception, it may be desirable to encapsulate or otherwise control the release of at least a portion of the artificial sweetener.Techniques such as wet granulation, wax granulation, spray drying, spray chilling, fluidized bed coating, preservation, encapsulation in yeast cells, and fiber extrusion can be used to achieve the desired release characteristics.Encapsulation of the sweetener can also be obtained using another tablet ingredient, such as a resin compound.

[0169] The use level of artificial sweeteners will vary considerably and will depend on factors such as sweetener potency, release rate, desired sweetness of the product, the level and type of flavoring used, and cost considerations.Accordingly, the active level of artificial sweeteners may vary from about 0.001 to about 3% by weight (preferably from about 0.02 to about 3% by weight).When a carrier used for encapsulation is included, the use level of encapsulated sweetener will be proportionately higher.Combinations of sugar and / or non-sugar sweeteners may be used in the formulation.

[0170] In one embodiment of the invention, the tablet comprises a flavoring agent.

[0171] The amount of flavouring agent may be, for example, from 0.1 to about 5% by weight of the tablet, for example, from 0.1 to about 3% by weight of the tablet.

[0172] Available flavorings include almond, almond amaretto, apple, bavarois cream, black cherry, black sesame, blueberry, brown sugar, bubble gum, butterscotch, cappuccino, caramel, caramel cappuccino, cheesecake (graham crust), chili, cinnamon red hot, cotton candy, circus cotton candy, clove, coconut, coffee, clear coffee, double chocolate, energy drink. cow), ginger, glutamate, graham crackers, grape juice, green apple, Hawaiian punch, honey, Jamaican rum, Kentucky bourbon, kiwi, kourada, 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, RY4, spearmint, strawberry, sweet cream, sweet tart, artificial sweeteners, toasted almonds, tobacco, tobacco blend, vanilla bean ice cream, vanilla cupcake, vanilla earl, 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, praline cream, red licorice, saltwater toffee, strawberry banana, strawberry kiwi, tropical punch, tutti frutti, vanilla, or any combination thereof. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0173] The invention will now be described in more detail with respect to certain specific aspects and embodiments of the invention. These aspects and embodiments are intended to be understood in conjunction with the remainder of the specification, including the Summary of the Invention and Examples of the Invention.

[0174] The verb "comprise" as used herein and in the claims and its applications is used in its open-ended sense to mean that the items following the term are included, but not that items not specifically mentioned are excluded. In addition, the reference of an element by the indefinite article "a" or "an" does not exclude the possibility that more than one of the element is present, unless the context clearly requires that only one of the elements is present. Thus, the indefinite article "a" or "an" usually means "at least one". In addition, the words "a" and "an" indicate "one or more" when used in connection with the word comprising or containing in this document. The expression "one or more" is intended to mean one, two, three or more.

[0175] As used herein, the terms "approximately" or "about" in reference to a number are generally interpreted as including numbers that fall within 5%, 10%, 15%, or 20% in either direction (greater or lesser) of that number, unless otherwise stated or otherwise clear from the context (except where such number would be less than 0% or greater than 100% of a possible value).

[0176] As used herein, the term "oral chewable tablet" refers to a tablet for oral use. In particular, oral tablets are considered to be formed by tableting, i.e., compression of a particle composition comprising a group of particles. Thus, tablets are considered to be compressed tablets formed by a plurality of particles. Typically, oral chewable tablets are also referred to as tablets or oral tablets.

[0177] The term "particle size" refers to the ability of a particle to pass through or be retained by a sieve hole of a fundamental size. As used herein, unless specifically stated otherwise, the term "particle size" refers to the average particle size as determined using test method 2.9.38 Estimation of Particle Size Distribution by Analytical Sieves in accordance with European Pharmacopoeia 9.1.

[0178] The term "particle" or similar phraseology is intended to indicate a single, discrete composition of solid matter, such as a granule or individual element in a powder, having a certain size that may deviate considerably.

[0179] The term "mass of an oral tablet" or similar phrases meaning the same are defined in the present context as the mass of an oral tablet not including the mass of any outer coatings such as hard coatings, soft coatings, and the like.

[0180] The phrase "texture" refers to a qualitative measure of the characteristics of an oral tablet and the overall texture experienced by the user during use. The term "texture" thus encompasses measurable quantities such as hardness as well as more subjective parameters relating to the sensation experienced by the user.

[0181] The term "release" in this context is intended to mean under "in vitro" conditions, unless otherwise stated. In particular, the "release rate" during a certain period of time is intended to mean the amount of active ingredient released in percentage during that period of time. In this context, the term "release" refers to the release of the substance from the water-soluble matrix. In some embodiments, the process of releasing the substance corresponds to the substance dissolving in saliva.

[0182] The term "sustained release" or "extended release" is intended herein to mean an extended release over time. The term "rapid release" or "quick release" or "fast release" is intended herein to mean a higher content is released in a given period of time. The term "controlled release" is intended to mean the release of a substance from an oral tablet by active use of the oral tablet in the oral cavity of a subject, whereby the active use controls the amount of substance released.

[0183] In the present context, the term "becomes liquid" is intended to mean that the tablet disintegrates and tablet fragments or particles become suspended or dissolved in the saliva and are perceived as a liquid by the test subject.

[0184] As used herein, the term "disintegrate" refers to the reduction 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.

[0185] As used herein, the term "dissolve" is the process by which a solid substance enters a solvent (oral saliva) to produce a solution. Unless otherwise stated, dissolving refers to complete dissolution of the compound in question.

[0186] 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 that can be used within the scope of the present invention can include starch, pregelatinized starch, modified starch (including potato starch, corn starch, starch 1500, sodium starch glycolate and starch derivatives), cellulose, microcrystalline cellulose, alginates, and superdisintegrants, such as cross-linked cellulose (such as sodium carboxymethylcellulose), cross-linked polyvinylpyrrolidone (PVP), cross-linked starch, cross-linked alginic acid, natural superdisintegrants, and calcium silicate. Disintegrants can often be considered as a means to promote the break-up of the module into smaller pieces upon administration, facilitating nicotine release and eventual absorption. Crospovidone can include various grades, such as Kollidon CL-F or Kollidon CL-SF, available from BASF.

[0187] In the case of induced saliva production, it is noted that this induces saliva production that is greater than any saliva production that would occur without the use of the tablet of the present invention or with a dextrose content of less than 50%. In particular, in one embodiment, the induced saliva production is greater than any saliva production that would occur with a conventional tablet that does not contain dextrose or contains less than 50% dextrose. The induced saliva production is then increased over any saliva production associated with the conventional product, for example, by comparing with a tablet that does not contain dextrose or contains less than 50% dextrose.

[0188] In the case of induced saliva production, saliva production can be tested using the following method: The subject refrains from eating or drinking for at least 30 minutes before the start of any test. Immediately before introducing the tablet into the oral cavity, the subject swallows. The subject refrains from swallowing during the test. Immediately after introducing the tablet into the oral cavity, the subject begins to chew the tablet for 20 seconds at a chewing frequency of 1 chew per second. The saliva and any tablet remains are then held in the oral cavity for 10 seconds while chewing. 30 seconds after the start of the test, the subject discards the saliva, including any tablet fragments, into a plastic cup which is weighed. Saliva is also discarded 90 seconds after the start of chewing, 180 seconds after the start of chewing, 300 seconds after the start of chewing, 420 seconds after the start of chewing, and 600 seconds after the start of chewing. At all times, the subject remains as still as possible and refrains from swallowing.

[0189] As used herein, the term "active ingredient" refers to a substance that is biologically active and has a physiological effect on the human body for the benefit of the human body or a portion thereof. Active ingredients include active pharmaceutical ingredients, but also other active substances such as nutritional supplements or immune-supporting active ingredients.

[0190] Hereinafter, raw material will refer to the mixed particles that are compressed into tablets according to embodiments of the present invention, unless otherwise stated.

[0191] The following description outlines a description of how the tablets of the invention can be produced and further details of what can be added to the compositions of the invention.

[0192] Typically, the process for producing tablets of the present invention can be carried out in a single tablet press, such as a rotary tablet press, although under some circumstances it may be beneficial to apply separate tablet presses.

[0193] Preferably, the upper punch is convex to impart a concave shape to the top surface of the tablet being pressed.

[0194] Of course, it should be noted that the shape of the punch may vary depending on the desired tablet shape.

[0195] In some embodiments of the invention, the tablet pressing is carried out with a force of 10-50 kN. In some embodiments of the invention, the tablet pressing is carried out with a force of 10-40 kN. In some embodiments of the invention, the tablet pressing is carried out with a force of 10-30 kN.

[0196] The oral tablet according to the invention is produced by applying pressure to the contents of the particles by suitable compression means. The particles or powder are then pressed into a compact, coherent tablet. The particles may for example comprise so-called primary particles or agglomerated primary particles. When they are pressed, bonds are established between the particles or granules, thereby imparting a certain mechanical strength to the compressed tablet.

[0197] It should be noted that the terms introduced above: powder, primary particles and agglomerated primary particles, can be somewhat misleading in the sense that the difference between primary particles and agglomerated primary particles can very often be considered differently depending on the user's background. Some may consider, for example, sweeteners as primary particles, despite the fact that the particles should rather be considered as some agglomerated primary particles due to the prior processing that typically takes place when they are sent to the customer. The definition adopted in the present description is that agglomerated primary particles refer to macroparticles that contain more or less previously processed primary particles.

[0198] When pressure is applied to the particles, the bulk volume decreases and the amount of air is reduced. During this process, energy is consumed. During the process of volume reduction, as the particles are in close proximity to each other, bonds can be established between the particles or granules. Since energy is released, the formation of bonds is associated with a reduction in the energy of the system. Volume reduction occurs by various mechanisms, and depending on the pressure applied and the properties of the particles or granules, different types of bonds can be established between the particles or granules. When powders are pressed, the first thing that happens is that the particles reorganize under low compaction pressure to form a close-packed structure. Particles with regular shapes seem to undergo reorganization more easily than those with irregular shapes. As the pressure increases, further reorganization is prevented and the subsequent volume reduction is obtained by plastic and elastic deformation and / or fragmentation of the tablet particles. Fragile particles are probably more susceptible to fragmentation, i.e., the breakdown of the original particles into smaller units. Plastic deformation is an irreversible process that results in a permanent change in particle shape, while after elastic deformation, the particles regain their original shape. Apparently, when compressing oral tablets, both plastic and elastic deformations can occur.

[0199] Several studies on the type of binding in pressed tablets have been done over the years, typically in the pharmaceutical context, providing several techniques to obtain powder-based pressed tablets that can be used. Such studies are entirely focused on what happens when volume reduction is performed and how the final product can be optimized for a given purpose. For example, several refinements on pressed tablets have been done, for example by adding binders to the tablet raw material, with the aim of giving the final pressed tablet sufficient strength while maintaining acceptable properties, for example with regard to release.

[0200] The process of the present invention allows for the formation of single or multi-layer tablets, such as bilayer or trilayer tablets.

[0201] In accordance with the present invention, the tableted oral tablet according to the present invention may include about 0.1 to about 75% by weight of an outer coating applied onto the oral tablet core. Thus, suitable coating types include hard coatings, film coatings and soft coatings of any composition, including those currently used in coating tableted oral tablets.

[0202] One of the preferred types of outer coatings herein is a hard coating, which is used in its conventional sense, including sugar coatings and sugarless (or sugar-free) coatings and combinations thereof. The purpose of the hard coating is to obtain a sweet, crunchy layer that is welcomed by the consumer, which may further protect the oral tablet core for various reasons. In a typical process for providing a protective sugar coating to an oral tablet core, the oral tablet core is treated successively in a suitable coating device with an aqueous solution of a crystallizable sugar, such as sucrose or dextrose, which may contain other functional ingredients, such as fillers, binders, dyes, etc., depending on the stage of coating that has been achieved. In this context, the sugar coating may contain further functional or active compounds, including flavoring compounds and / or active compounds.

[0203] In a typical hard coating process, as described in detail below, a suspension containing a crystallizable sugar and / or polyol is applied to the oral tablet center and the water it contains is evaporated by blowing air through it. This cycle must be repeated multiple times, typically 3 to 80 times, to achieve the required swelling. The term "swelling" refers to the increase in mass or thickness of the product as determined at the end of the coating operation compared to the beginning and relative to the final mass or thickness of the coated product. In accordance with the present invention, the coating layer comprises about 0.1 to about 75% by weight, such as about 10 to about 60% by weight, including about 15 to about 50% by weight, of the finished oral tablet element.

[0204] In a further useful embodiment, the outer coating of the oral tablet element of the present invention is an element that has undergone a film-coating process and therefore comprises one or more film-forming polymeric agents and optionally one or more auxiliary compounds, such as plasticizers, pigments and opacifiers. A film coating is a thin polymer-based coating applied to an oral tablet core of any of the above forms. The thickness of such a coating is usually between 20 and 100 μm.

[0205] Generally, a film coating is obtained by passing the oral tablet centers through a spray zone containing spray droplets of the coating material in a suitable aqueous or organic solvent vehicle, followed by drying of the material adhered to the oral tablet centers before the next portion of coating is applied, and the cycle is repeated until the coating is complete.

[0206] In one embodiment, the tablet according to the invention comprises a pharmaceutical, cosmetic or biological active agent, a comprehensive list of which can be found, for example, in WO 00 / 25598, which is incorporated herein by reference, examples of such active agents include drugs, dietary supplements, preservatives, pH regulators, smoking cessation agents. Examples of useful active substances in the form of preservatives include salts and derivatives of guanidine and biguanidine, and the following classes of substances with limited water solubility: quaternary ammonium compounds (e.g., ceramine, chloroxylenol, crystal violet, chloramine), aldehydes (e.g., paraformaldehyde), dequaline derivatives, polynoxylin, phenols (e.g., thymol, p-chlorophenol, cresol), hexachlorophene, salicylic acid anilide compounds, triclosan, halogens (iodine, iodophores, chloramine, dichlorocyanurate), alcohols (3,4 dichlorobenzyl alcohol, benzyl alcohol, phenoxyethanol, phenylethanol), Martindale, The Extra Pharmacopoeia, 28th see also pp. 547-578 of the 1990 edition; these should include metal salts, complexes and compounds with limited water solubility, such as aluminum salts (e.g. potassium aluminum sulfate AIK(SO4)2, 12H2O), and further salts, complexes and compounds of boron, barium, strontium, iron, calcium, zinc (zinc acetate, zinc chloride, zinc gluconate), copper (copper chloride, copper sulfate), lead, silver, magnesium, sodium, potassium, lithium, molybdenum, vanadium.

[0207] Examples of active substances in the form of agents that regulate the pH in the oral cavity include acids such as adipic acid, succinic acid, fumaric acid or their salts, or salts of citric acid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoric acid and glutaric acid, and acceptable bases such as carbonates, bicarbonates, phosphates, sulfates or oxides of sodium, potassium, ammonium, magnesium or calcium, especially magnesium and calcium.

[0208] The active ingredient may include, but is not limited to, the compounds described below or derivatives thereof: acetaminophen, acetylsalicylic acid, buprenorphine, bromhexine, cercoxib, codeine, diphenhydramine, diclofenac, etoricoxib, ibuprofen, indomethacin, ketoprofen, lumiracoxib, morphine, naproxen, oxycodone, parecoxib, piroxicam, pseudoephedrine, rofecoxib, tenoxicam, tramadol, valdecoxib, calcium carbonate, magaldrate, disodium. Rufilam, Bupropion, Nicotine, Azithromycin, Clarithromycin, Clotrimazole, Erythromycin, Tetracycline, Granisetron, Ondansetron, Promethazine, Tropisetron, Brompheniramine, Ceterizine, Leco-ceterizine, Chlorcyclizine, Chlorpheniramine, Chlorpheniramine, Diphenhydramine, Doxylamine, Fenphenazine, Guaiphenesin, Loratidine, Des-loratidine, Phenyltoloxamine, Promethazine, Pyridamine, Terfenadine, Troxerutine, Methyl Dopa, Methylphenidate, Benzalkonium chloride, Benzethonium chloride, Chloride, Ecabet sodium, Haloperidol, Allopurinol, Cortinine, Theophylline, Propanolol, Prednisolone, Prednisone, Urea, Actot, Glibenclamide, Glipizide, Metformin, Miglitol, Repaglinide, Rosiglitazone, Apomorphine, Cialis, Sildenafil, Vardenafil, Diphenoxylate, Simethicone, Cimetidine, Famotidine, Ranitidine, Latinidine, Cetrizine, Loratadine, Aspirin, benzocaine, dextromethorphan, phenylpropanolamine, pseudoephedrine, cisapride, domperidone, metoclopramide, acyclovir, dioctyl sulfosuccinate, phenolphthalein, almotriptan, eletriptan, ergotamine, migaea, naratriptan, rizatriptan, sumatriptan, zolmitriptan, aluminum salts, calcium salts, iron salts, silver salts, zinc salts, amphotericin B, miconazole, triamcinolone acetonide, melatonin, phenobarbitol, caffeine,Benzodiazepines, hydroxyzine, meprobamate, phenothiazines, buclizine, bromethazine, cinnarizine, cyclizine, diphenhydramine, dimenhydrinate, buflomedil, amphetamines, caffeine, ephedrine, orlistat, phenylephedrine, phenylpropanolamine, pseudoephedrine, sibutramine, ketoconazole, nitroglycerin, nystatin, progesterone, testosterone, vitamin B12, vitamin C, vitamin A, vitamin D, vitamin E, pilocarpine, aluminum aminoacetat, cimetidine, esomeprazole, famotidine, lansoprazole, magnesium oxide, nizatide and / or ranitidine.

[0209] The present invention is suitable for enhancing or accelerating the release of active agents selected from the group of dietary supplements, preservatives, pH adjusting agents, antismoking agents, sweeteners, flavoring agents, fragrances or drugs, some of which will be described below.

[0210] The active agent to be used in connection with the present invention can be any substance that is desired to be released from the tablet. The active agents for which it is desired to control and / or accelerate the release rate are mainly those with limited water solubility, typically less than 10g / 100ml, including those that are completely water insoluble. Examples are pharmaceuticals, dietary supplements, oral compositions, anti-smoking agents, high-intensity sweeteners, pH adjusters, flavoring agents, etc.

[0211] Other active ingredients are, for example, paracetamol, benzocaine, cinnarizine, menthol, carvone, caffeine, cyclizine hydrochloride, 1,8-cineole, nandrolone, miconazole, mystatin, nicotine, other quaternary ammonium compounds, vitamin E, vitamin A, vitamin D, glibenclamide or derivatives thereof, progesterone, acetylsalicylic acid, dimenhydrinate, cyclizine, metronidazole, sodium bicarbonate, active ingredients from ginkgo biloba, active ingredients from propolis, active ingredients from ginseng, methadone, oil of peppermint, salicylamide, hydrocortisone or astemizole.

[0212] Examples of active agents in the form of dietary supplements are, for example, vitamin B2 (riboflavin), B12, folinic acid, folic acid, niacin, biotin, poorly soluble glycerophosphate, amino acids, nutritional salts and compounds of vitamins A, D, E and K, minerals in the form of salts, complexes and compounds containing calcium, phosphorus, magnesium, iron, zinc, copper, iodine, manganese, chromium, selenium, molybdenum, potassium, sodium or cobalt.

[0213] Further reference is made to lists of nutrients approved by authorities of various countries, e.g., US Code of Federal Regulations, Title 21, Sections 182.5013.182 5997 and 182.8013-182.8997.

[0214] Examples of active agents in the form of preservatives are, for example, salts and compounds of guanidine and biguanidine, the following classes of substances having limited water solubility: quaternary ammonium compounds (for example, ceramine, chloroxylenol, crystal violet, chloramine), aldehydes (for example, paraformaldehyde), dequalin compounds, polynoxylin, phenols (for example, thymol, parachlorophenol, cresol), hexachlorophene, salicylic acid anilide compounds, triclosan, halogens (iodine, iodophores, chloramine, dichlorocyanurate), alcohols (3,4-dichlorobenzyl alcohol, benzyl alcohol, phenoxyethanol, phenylethanol), and also those of the following classes of substances having limited water solubility: edition, pages 547-578; these should include metal salts, complexes and compounds having limited water solubility, such as aluminium salts (e.g. potassium aluminium sulphate AIK(S04)2, 12H20), as well as salts, complexes and compounds of boron, barium, strontium, iron, calcium, zinc (zinc acetate, zinc chloride, zinc gluconate), copper (copper chloride, copper sulphate), lead, silver, magnesium, sodium, potassium, lithium, molybdenum, vanadium.

[0215] Examples of active agents in the form of agents that regulate the pH in the oral cavity include acceptable acids such as, for example, adipic acid, succinic acid, fumaric acid, or their salts, or the salts of citric acid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoric acid, and glutaric acid, and acceptable bases such as carbonates, bicarbonates, phosphates, sulfates, or oxides of sodium, potassium, ammonium, magnesium, or calcium, especially magnesium and calcium.

[0216] Examples of active agents in the form of smoking cessation agents include, for example, nicotine, tobacco powder or silver salts, such as silver acetate, silver carbonate and silver nitrate.

[0217] Further examples of active agents are pharmaceutical agents of any kind.

[0218] Examples of active agents in the form of pharmaceuticals include caffeine, salicylic acid, salicylamide and related substances (acetylsalicylic acid, choline salicylate, magnesium salicylate, sodium salicylate), paracetamol, salts of pentazocine (pentazocine hydrochloride and pentazocine lactate), buprenorphine hydrochloride, codeine hydrochloride and codeine phosphate, morphine and morphine salts (hydrochloride, sulfate, tartrate), methadone hydrochloride, ketobemidone and ketobemidone salts (hydrochloride), beta blockers (propranolol), calcium antagonists, verapamil hydrochloride, nifedinpine, as well as those described in Pharm. Int., Nov. 85, pp. 267-271, Barney H. Hunter and Robert L. Suitable substances include those described in Talbert and their salts, nitroglycerin, erythrityl tetranitrate, strychnine and its salts, lidocaine, tetracaine hydrochloride, etorphine hydrochloride, atropine, insulin, enzymes (e.g., papain, trypsin, amyloglucosidase, glucose oxidase, streptokinase, streptodornase, dextranase, alpha amylase), polypeptides (oxytocin, gonadorelin (LH.RH), desmopressin acetate (DDAVP), isoxsuprine hydrochloride, ergotamine compounds, chloroquine (phosphate, sulfate), isosorbide, demoxtocin, and heparin.

[0219] Other active ingredients include beta-lupeol, Letigen®, sildenafil citrate and their derivatives.

[0220] Further examples of active ingredients include vitamins, including A, B1, B2, B6, B12, folinic acid, folic acid, niacin, pantothenic acid, biotin, C, D, E, and K. Minerals include calcium, phosphorus, magnesium, iron, zinc, copper, iodine, manganese, chromium, selenium, and molybdenum. Other active ingredients include Q10, enzymes. Natural drugs include ginkgo biloba, ginger, and fish oil.

[0221] Further examples of active ingredients include migraine medications such as serotonin antagonists: sumatriptan, zolmitriptan, naratriptan, rizatriptan, eletriptan; nausea medications such as cyclizine, cinaridine, dimenhydramine, difenhydrinat; hay fever medications such as cetrizine, loratidine, analgesics such as buprenorphine, tramadol, oral disease medications such as miconazole, amphotericin B, triamcinoloneacetone; and the drugs cisapride, domperidone, metoclopramide. In a preferred embodiment, the present invention relates to the delivery of nicotine and its salts.

[0222] In one advantageous embodiment of the invention, the active ingredient is acetylcysteine, ambroxol, amylmetacresol, benzocaine, bisacodyl, bismuth subsalicylate, bromhexine, cetirizine, dextromethorphan hydrobromide, 2,4-dichlorobenzyl alcohol, doxylamine succinate, eucalyptus oil, flurbiprofen, glycerin, hexylresorcinol, lidocaine, menthol, myrrh, paracetamol, pectin, peppermint oil, phenol, phenylephrine, povidone iodine, pseudoephedrine, ranitidine, an active ingredient for the throat selected from simethicone, sodium docusate, spearmint, zinc, or any combination thereof; alginate, atenolol, aspirin (acetylsalicylic acid), ampicillin, aminosalicylate, anhydrous citric acid, aspirin, bisacodyl, bismuth subsalicylate, bupropion, caffeine, calcium, calcium carbonate, cetirizine, cimetidine, cisapride, clarithromycin, desloratadine, dexlansoprazole, diphenhydramine HCl, diphenhydramine citrate, dimenhydrinate, docusate Sodium stearate, dopamine, esomeprazole, famotidine, fexofenadine HCl, guaifenesin, hydrotalcite, ibuprofen, ketoprofen, lactase enzyme, lansoprazole, loratadine, lorcaserin, loperamide, loperamide HCl, magnesium, magnesium carbonate, magnesium hydroxide, melatonin, methamphetamine HCl, metoclopramide, metronidazole, montelukast, mycostatin, naltrexone, naproxen, naproxen sodium, nizatidine, omeprazole, ondanse Thoron, Orlistat, Pantoprazole, Paracetamol (Acetaminophen), Pectin, Phentermine HCl, Polypodium Leucotomos, Prednisolone, Prednisone, Progesterone, Propranolol, Propantheline Bromide, Pseudoephedrene HCl, Phentermine, Rabeprazole, Ranitidine, Roflumilast, Scopolamine Butyl Hydroxide, Simethicone, Sodium, Sodium Bicarbonate, Sodium Docusate, Sumatriptan, Testosterone, Tetracycline, Topiramate, Vitamin A, Vitamin B,Active ingredients for the digestive tract selected from vitamin B12, vitamin C (ascorbic acid), vitamin D, and vitamin E, vitamin K, or any combination thereof, and active ingredients for buccal absorption selected from atenolol, baclofen, caffeine, carvedilol, chlorpheniramine, chlorpheniramine maleate, fluticasone propionate, maleate salt, desmopressin, diltiazem hydrochloride, doxylamine succinate, mycostatin, nicotine, nifedipine, nitroglycerin, omeprazole, ondansetron, oxymetazoline HCl, oxytocin, phenylephrine, piroxicam, prednisone, propranolol, salbutamol sulfate, scopolamine butyl hydroxide, sumatriptan, triamcinolone acetonide, and any combination thereof.

[0223] In one aspect of the invention, "tablet" is intended to mean a "rapidly disintegrating tablet" ("FDT"), such as an "orally disintegrating tablet" ("ODT"), or similar phraseology. Unless otherwise stated, if a tablet according to the invention is made as one module, rather than two or more modules, it is intended that the tablet is an FDT tablet. Conversely, if the tablet is made from more than one module, such as two modules, such additional module is intended to be a "lozenge" module or a "chewing gum module" that provides a longer disintegration time compared to the FDT module according to the invention. The combination of an "FDT" module and a "lozenge" module (or a "chewing gum module") contributes to another aspect of the invention. A "lozenge" module or a "chewing gum module" according to the invention may include elements from an "FDT" module, but generally has a different composition and provides a sustained disintegration time.

[0224] The term "module" is generally intended to mean that the entire module is composed of a material composition with substantially the same characteristics. Thus, if there are two modules, the two modules are different in composition and generally have two different characteristics in each module. In this context, if there is only one module, this module is considered to be an FDT tablet. On the other hand, if there are two modules, the tablet is composed of an FDT tablet or a lozenge tablet or an FDT tablet module fused with a lozenge module. The term "fused" is intended to mean that the tablet is assembled together by compression forces. Usually, if there are two modules, the lozenge module is made as the first module and the FDT module is made as the second module. The tablet may be composed of more than two modules. The lozenge module may be replaced by a rubber base module in certain embodiments. In this context, even if the delivery of nicotine is "monophasic", the present invention provides an attractive biphasic delivery of masking. EXAMPLES

[0225] Example 1 Preparation of dextrose tablets In the first step, dextrose was added to a mixing container. The active ingredient, flavoring, intense sweetener, and optional other ingredients were added to the container. The mixture was sieved and tumbled in a FUCHS Mixomat-A at approximately 25 rpm for 4 minutes. Processing aids were added and the mixture was tumbled for an additional minute at approximately 25 rpm. The mixture was then ready for tableting.

[0226] The mixture was then passed through a standard tablet press (3090i, available from Fette GmbH) equipped with a dosing device (P 3200 C, available from Fette GmbH, Germany) and pressed into bilayer tablets. Alternatively, a Riva Picoola Bi-layer DC-PL -015 was used. The tablets were pressed using a pre-compression force of about 2.2 kN to form the first layer. After the pre-compression of the first layer, another portion of powder was added to the device and a compression force of 10-30 kN was applied, unless otherwise indicated. There were 11 punches on the rotor and the rotor speed was 5 rpm. The individual tablets had a mass of approximately 1500 mg, unless otherwise stated in the examples below, and the layers constituted a mass ratio of approximately 1:1. Punch used: 15.00 mm, round, shallow concave, B tooling.

[0227] The dextrose administered in the examples was C dextrose commercially available from Cargill. * dex™ 02001, or C provided by Cargill * dex™ 02030, or C provided by Cargill * The binders were: dex™ 02032, Cerelose® dextrose 020010 provided by Ingredion, or Royal-T® provided by Ingredion. In some examples, separate binders were applied, such as HPC and HPMC. HPC was available as Klucel Nutra D from Ashland. HPMC was available as Methocel 4KM from Dow. When microcrystalline cellulose was applied as the comparable binder, it was Avicel PH-102, available from Dupont. When maltodextrin was applied as the binder, it was C*dry™ MD from Cargill.

[0228] Example 2 Composition of bilayer dextrose tablets in the presence of different amounts of active ingredient. Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below. In all of the tablet examples, the amounts of the various ingredients are listed as weight % of each layer of the tablet.

[0229] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0230] [Table 1]

[0231] Tablets 100-104 were prepared using C * This was repeated using Dex™ 02030 as tablets 100A-104A and using Royal-T® available from Ingredion as tablets 100B-104B.

[0232] Example 3 Composition of bilayer dextrose tablets using different grades of dextrose in each layer. Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below. In all of the tablet examples, the amounts of the various ingredients are listed as weight % of each layer of the tablet.

[0233] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0234] [Table 2]

[0235] Example 4 Composition of bilayer dextrose tablets using different grades of dextrose in each layer. Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below. In all of the tablet examples, the amounts of the various ingredients are listed as weight % of each layer of the tablet.

[0236] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0237] [Table 3]

[0238] Example 5 Composition of bilayer dextrose tablets using different grades of dextrose in each layer. Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below. In all of the tablet examples, the amounts of the various ingredients are listed as weight % of each layer of the tablet.

[0239] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0240] [Table 4]

[0241] Example 6 Composition of bilayer dextrose tablets. Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below. In all of the tablet examples, the amounts of the various ingredients are listed as weight % of each layer of the tablet.

[0242] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0243] [Table 5]

[0244] Tablets 140-144 were repeated as tablets 140A-144A using Cerelose® Dextrose 020010 available from Ingredion.

[0245] Example 7 Composition of bilayer dextrose tablets with different active substances in each layer. Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below. In all of the tablet examples, the amounts of the various ingredients are listed as weight % of each layer of the tablet.

[0246] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0247] [Table 6]

[0248] Example 8 Composition of bilayer dextrose tablets with different active substances in each layer. Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below. In all of the tablet examples, the amounts of the various ingredients are listed as weight % of each layer of the tablet.

[0249] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0250] [Table 7]

[0251] Example 9 Composition of bilayer dextrose tablets in the presence of different amounts of active ingredient. Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below. In all of the tablet examples, the amounts of the various ingredients are listed as weight % of each layer of the tablet.

[0252] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0253] [Table 8]

[0254] Tablets 170-174 were prepared using C * This was repeated using Dex™ 02030 as tablets 170A-174A and using Royal-T® available from Ingredion as tablets 170B-174B.

[0255] Example 10 Tablet evaluation Break point tests, friability tests and dissolution time measurements were performed for each version of the tablet. To measure the break point, a PTB 311 from Pharma Test was used.

[0256] The friability test was performed according to European Pharmacopoeia 9.1, test method 2.9.7 by using a pharmaceutical friability tester PTF 10E manufactured by Pharma Test.

[0257] To test the dissolution time, the following method was used: In a measuring tube with a screw cap, 15 mL of 0.02 M potassium dihydrogen phosphate buffer (pH adjusted to 7.4) is added to 50 mL of water. The tablet is inserted into the measuring tube and the screw cap is closed. The measuring tube is fixed horizontally. The measuring tube is vibrated at approximately 110 RPM so that the tablet can move back and forth within the measuring tube. The measuring tube is vibrated until the tablet or its corresponding module is completely dissolved and the vibration time is noted as the dissolution time.

[0258] Example 11 Sensory testing of tablets Sensory testing was performed to determine the most important features and characteristics of the tablets. These sensory parameters are important as indicators of the structure of the tablet composition. The test configuration consisted of 8 testers in one test panel. All testers were healthy individuals, objectively designated according to the specified requirements. The sensory analysis was performed according to ISO 4121-2003 under test conditions according to ISO 8589. The results are the average of the results of the 8 individuals.

[0259] Testers rated from "+" to "+++++", where "+" was poor and "+++++" was excellent. A "0" indicated it had not been tested.

[0260] Six different parameters were tested in the test panel:

[0261] "Ease of Chewing to Liquid" - The impression of a tablet when placed in the mouth and chewed regarding the ease with which the product can be chewed to liquid. The criteria are that upon completion there is no sensation of particles in the mouth and that the tablet powder has dissolved into a liquid.

[0262] "Liquid feel" - impression of the tablet when placed in the mouth and chewed, relating to the sensation of liquid in the mouth. For example, the more liquid felt during and / or after chewing, the higher the score.

[0263] "Texture" - overall impression of the tablet during chewing in terms of texture including sensations of melting and sticking. A high texture score is associated with a clean liquid (no particulate sensation), no tablet residue sticking to the teeth, and a creamy sensation (more viscous than water). Conversely, a low texture score is associated with a sensation of particulates in the liquid (incomplete dissolution), tablet residue sticking to the teeth, and a watery sensation of the liquid.

[0264] "Overall taste" - overall impression of the taste of the tablet during chewing. For example, if the taste decreased rapidly, a very low rating was given.

[0265] "Overall sweetness" - overall impression of the sweetness of the tablet during chewing. For example, if the sweetness decreased rapidly, a very low rating was given.

[0266] "Overall sourness" - overall impression of the sourness of the tablet during chewing. For example, if the sourness decreased rapidly, a very low rating was given.

[0267] Example 12 Results of bilayer dextrose tablets in the presence of different amounts of active ingredient

[0268] [Table 9]

[0269] Overall, the results reveal that when compressed into bilayer tablets according to the invention, active substance contents in the range of 0.1-40% by weight of active ingredient were suitable. It was unexpected that higher contents of active ingredient were suitable in the bilayer arrangement.

[0270] (Example 13) Results for bilayer dextrose tablets containing different grades of dextrose in each layer

[0271] [Table 10]

[0272] Overall, the results reveal that when compressed into bilayer tablets according to the invention, active substance contents in the range of 0.1-40% by weight of active ingredient were suitable. It was unexpected that higher contents of active ingredient were suitable in the bilayer arrangement.

[0273] Example 14 Results for bilayer dextrose tablets containing different grades of dextrose in each layer

[0274] [Table 11]

[0275] Overall, the results reveal that the content of active substance was suitable in the range of 0.1-40% by weight of active ingredient when compressed into a bilayer tablet according to the present invention. In addition, the results reveal that two different grades in different layers of the tablet were suitable according to the present invention.

[0276] Example 15 Results for bilayer dextrose tablets containing different grades of dextrose in each layer

[0277] [Table 12]

[0278] Overall, the results reveal that when compressed into bilayer tablets according to the invention, the addition of a separate binder in layer 1 was suitable to obtain good results.

[0279] Example 16 Results for bilayer dextrose tablets containing different grades of dextrose in each layer

[0280] [Table 13]

[0281] Overall, the results reveal that when compressed into bilayer tablets according to the present invention, the addition of separate binders in both layers 1 and 2 was suitable to obtain good results.

[0282] (Example 17) Results for bilayer dextrose tablets with different active substances in each layer

[0283] [Table 14]

[0284] Overall, the results reveal that when compressed into bilayer tablets according to the invention, the active substance content was suitable in the range of 0.1-40% by weight of active ingredient.

[0285] (Example 18) Results for bilayer dextrose tablets with different active substances in each layer

[0286] [Table 15]

[0287] Overall, the results reveal that when compressed into bilayer tablets according to the invention, the active substance content was suitable in the range of 0.1-40% by weight of active ingredient.

[0288] (Example 19) Results of bilayer dextrose tablets containing different amounts of active ingredient

[0289] [Table 16]

[0290] Overall, the results reveal that when compressed into bilayer tablets according to the invention, the active substance content was suitable in the range of 0.1-40% by weight of active ingredient.

[0291] (Example 20) Composition of dextrose tablets containing different active ingredients with a focus on energy Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below, containing caffeine in an amount of 100 mg and optionally a vitamin B premix in an amount of 15 mg as active ingredients. In all of the tablet examples, the amounts of the various ingredients are given as weight % of each layer of the tablet.

[0292] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0293] [Table 17]

[0294] Example 21 Composition of dextrose tablets containing different active ingredients with a focus on energy Dextrose tablets based on the procedure in Example 1 were made with the formulation outlined in the examples below, which contained ginseng in an amount of 10 mg and optionally vitamin B premix in an amount of 10 mg as active ingredients. In all tablet examples, the amounts of the various ingredients are given as weight % of each layer of the tablet. For all samples in this example, the total tablet weight is 1000 mg.

[0295] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0296] [Table 18]

[0297] Example 22 Composition of dextrose tablets containing different active ingredients with a focus on energy Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below, containing L-theanine in an amount of 100 mg and optionally caffeine in an amount of 50 mg as active ingredients. In all of the tablet examples, the amounts of the various ingredients are given as weight % of each layer of the tablet.

[0298] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0299] [Table 19]

[0300] Example 23 Composition of dextrose tablets containing different active ingredients, with a focus on immunostimulants Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below, containing as active ingredients either Vitamin C in an amount of 500 mg or a herbal blend containing Vitamin C and other vitamins / minerals in an amount of 450 mg. In all of the tablet examples, the amounts of the various ingredients are listed as weight % of each layer of the tablet.

[0301] Unless specifically indicated, the same ingredients were applied to the different layers of the tablet, except for the type of flavoring, which may vary in the different layers. Small amounts of dyes were optionally added to one or more layers. The layers had the same weight percentage of the tablet weight.

[0302] [Table 20]

[0303] (Example 24) Composition of dextrose tablets containing different active ingredients, with a focus on cough and cold preparations Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below, containing active ingredients suitable for treating cough and cold symptoms. In all of the tablet examples, the amounts of the various ingredients are given as weight % of each layer of the tablet.

[0304] Unless otherwise specified, the same ingredients are applied to different layers of the tablet, except for the type of flavoring, which may vary in different layers. Small amounts of dyes are optionally added to one or more layers. The layers have the same weight percentage of the tablet weight. For all samples in this example, the total tablet weight is 1750mg.

[0305] [Table 21]

[0306] (Example 25) Results of a comparison of dextrose tablets 211 with a commercially available product containing an immunostimulant.

[0307] [Table 22]

[0308] Overall, the results demonstrate that the dextrose tablets provide superior texture and liquefaction sensations compared to Dextrose Tablet 211 and Airborne, a commercial product containing the same type of active ingredient.

[0309] (Example 26) Comparison of bilayer and single layer tablets In the following example, bilayer tablets according to the invention were compared to monolayer compressed tablets made with the same tooling and conditions as outlined in Example 1. All tablets were prepared and made according to Example 1, but the monolayer tablets were made by only adding one portion of tablet material and subjecting the tablets to one varying main compression force (no pre-compression force), and the bilayer tablets were made by applying a pre-compression force of about 2.2 kN to the first portion of material to form the first layer for all tablets, and then applying the varying main compression force after adding the second portion of material to form the final bilayer tablet.

[0310] [Table 23]

[0311] Example 27 Friability of the monolayer tablet of Example 26

[0312] [Table 24]

[0313] In general, the friability of single-layer tablets was grade C. * Dextrose Grade C compared to dex 02001 * Low levels were found for dex 02032 and Royal-T. Also, low friability levels were obtained for all tablets already with a compression force of about 20 kN.

[0314] (Example 28) Tablet hardness of the single-layer tablet of Example 26

[0315] [Table 25]

[0316] In general, the hardness of single-layer tablets is grade C. * Dextrose Grade C compared to dex 02001 * Similar or higher levels were found for dex 02032 and Royal-T.

[0317] (Example 29) Friability of the bilayer tablet of Example 26

[0318] [Table 26]

[0319] Surprisingly, it was found that the friability of the different grades was very low at a compression force of about 20 kN, with sample 235 having a significantly lower friability than sample 234 and even lower friability than sample 233. * In the 1000-milligram (1000-milligram) tablet, the tablets were capped with a compression force of about 30 kN, thus resulting in very high friability. This was very surprising, since the same capping problem was not observed with the monolayer tablets. It is noted that no separate binder was present in the samples.

[0320] (Example 30) Tablet hardness of the bilayer tablet of Example 26

[0321] [Table 27]

[0322] Surprisingly, despite the large differences observed in friability of the same tablets, the different grades were found to be close to each other at a compression force of about 20 kN. Considering the difference in friability at 20 kN, it was expected that a similar difference in hardness would be observed. * In the 1990-2001 (Dex 02001), the tablets were capped at a compression force of about 30 kN and therefore had a very low hardness, which was very surprising. No capping problems were observed with the monolayer tablets. It is noted that no separate binder was present in the samples.

Claims

1. An oral chewable tablet, Dextrose in an amount of 50 to 95% by weight of the tablet; and one or more non-directly compressible (non-DC) active ingredients in an amount of 5 to 50% by weight of the tablet; The oral chewable tablet comprises at least two compressed layers containing the dextrose and one or more active ingredients, wherein a first layer of the compressed layers is contiguous with and adjacent to a second layer, and the one or more active ingredients are disposed in both the first and second layers of the tablet.

2. 10. The oral chewable tablet of claim 1, which consists of two layers.

3. 2. The oral chewable tablet according to claim 1, wherein the mass ratio of the first layer to the second layer is 1:10 to 10:

1.

4. 2. The oral chewable tablet of claim 1, comprising three layers, a first layer being an intermediate layer, a second layer being conjoined and adjacent to one side of the first layer, and a third layer being conjoined and adjacent to the opposite side of the first layer.

5. 5. The oral chewable tablet according to claim 4, wherein the mass ratio of the first layer to the second layer to the third layer is 1:5:5 to 10:1:

1.

6. 10. The oral chewable tablet of claim 1, comprising one or more binders that are added separately to the formulation and that are separate from any binders incorporated into other ingredients within the tablet.

7. 10. The oral chewable tablet of claim 1, comprising one or more binders added separately to the formulation and separate from any binders incorporated in other components within the tablet, in an amount of 2 to 15% by weight of the tablet.

8. An oral chewable tablet as described in claim 1, comprising one or more binders selected from the group consisting of hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), maltodextrin, and combinations thereof, which are added separately to the formulation and are separate from any binders incorporated into other components within the tablet.

9. 10. The oral chewable tablet of claim 1, comprising one or more binders that are incorporated into other ingredients in the tablet, such as one or more binders present in granules that include dextrose.

10. 10. The oral chewable tablet of claim 1, consisting essentially of dextrose, one or more active ingredients, one or more binders that are added separately to the formulation and are separate from any binders incorporated into other ingredients within the tablet, and auxiliary ingredients present in up to about 5% by weight of the tablet.

11. 10. The oral chewable tablet of claim 1, consisting essentially of dextrose, one or more active ingredients, and accessory ingredients present in up to about 5% by weight of the tablet.

12. 2. The oral chewable tablet of claim 1, wherein the dextrose comprises anhydrous dextrose.

13. 2. The oral chewable tablet of claim 1, wherein the dextrose comprises hydrated dextrose.

14. 2. The oral chewable tablet of claim 1, wherein the dextrose comprises dextrose monohydrate.

15. 2. The oral chewable tablet of claim 1, wherein the dextrose comprises at least 90% dextrose equivalent calculated on a dry basis.

16. 10. The oral chewable tablet of claim 1, comprising at least one grade of dextrose containing maltodextrin.

17. 10. The oral chewable tablet of claim 1, wherein the one or more active ingredients are present in an amount of 20 to 50% by weight of the tablet.

18. 10. The oral chewable tablet of claim 1, wherein one active ingredient is disposed in a first layer of the tablet and another active ingredient is disposed in a second layer of the tablet.

19. 10. The oral chewable tablet of claim 1, wherein the one or more active ingredients comprises a non-directly compressible (non-DC) active ingredient.

20. 10. The oral chewable tablet of claim 1, wherein the one or more active ingredients comprise an active ingredient selected from the group consisting of immune-supporting active ingredients; energy-stimulating active ingredients; mixtures of vitamins, minerals, and herbs; and combinations thereof.

21. 10. The oral chewable tablet of claim 1, comprising one or more disintegrants selected from the group consisting of sodium croscarmellose, crospovidone, sodium starch glycolate, and combinations thereof.