Adhesive oral discs for sustained cannabinoid release

Abstract

The present invention relates to an adhesive intraoral disc for sustained release of cannabinoids. The disc comprises one or more cannabinoids and consists of a mucosal contact layer having a mucosal contact surface usable to be fixed to the gingiva of a person requiring relief or treatment of a medical condition, comprising one or more mucosal adhesive polymers that enable the adhesive intraoral disc to adhere to the gingiva for an extended period. Furthermore, the disc comprises a non-mucosal adhesive module fused with the mucosal contact layer, comprising a solid tablet composition that enables the non-mucosal adhesive module to dissolve for an extended period when the adhesive intraoral disc adheres to the gingiva. The present invention is particularly useful for the relief or treatment of ulcers.

Description

Technical Field

[0001] The present invention relates to an adhesive oral disc suitable for the oral administration of cannabinoids. In particular, the present invention is useful for the sustained release of cannabinoids and for the alleviation or treatment of medical indications, such as medical indications in the oral cavity.

Background Art

[0002] Cannabinoids are a group of chemical substances found in Cannabis sativa, Cannabis indica, Cannabis ruderalis, marijuana plants and related plant species. They are known to activate cannabinoid receptors (CB1 and CB2). These chemical substances are also endogenously produced in humans and other animals. Cannabinoids are cyclic molecules that exhibit certain properties such as being lipophilic, having the ability to easily cross the blood-brain barrier, and having low toxicity.

[0003] Cannabis sativa contains more than 400 chemical substances and approximately 120 cannabinoids, which are the active ingredients of cannabis, including tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabivarin (THCV) and cannabigerol (CBG). Pharmacologically, the main psychoactive component of cannabis is tetrahydrocannabinol (THC), which is used for the treatment of a wide range of medical conditions including glaucoma, AIDS wasting, neuropathic pain, spasticity associated with multiple sclerosis, fibromyalgia and chemotherapy-induced nausea. THC is also effective in the treatment of allergies, inflammation, infection, depression, migraine, bipolar disorder, anxiety disorders, and drug dependence and drug withdrawal syndromes.

[0004] Various attempts have been made to formulate tablets for the oral delivery of cannabinoids, such as cannabidiol (CBD). However, providing long-term delivery that is active, safe, and convenient presents various challenges. This is especially important when the medical indication is a localized medical indication in the oral cavity, such as ulcers or gingivitis. In these cases, it would be advantageous to provide local delivery of cannabinoids, such as cannabidiol, with sustained release of the active substance targeting the medical indication. Various conventional tablets useful for the broad release of cannabinoids into the oral cavity have been provided in this art. However, these tablets generally cannot deliver cannabinoids to localized targets in the oral cavity with improved release times, such as long-term release times, to obtain optimal conditions for the medical indication, such as the alleviation or treatment of ulcers.

[0005] In some cases, various oral disorders may manifest as localized oral lesions, such as ulcers. By targeting these areas in the oral cavity for relief or treatment, the active substance can be applied at increased concentrations and / or with greater precision regarding the appropriate release time for the relief or treatment of the condition.

[0006] Furthermore, it is important to provide formulations that can help achieve increased convenience and efficacy. Generally, prior art has not paid much attention to the impact of formulation of oral delivery platforms on the sensory characteristics of oral cannabinoid delivery. These characteristics are important from the standpoint of convenience of oral administration, as well as to ensure proper delivery of cannabinoids and avoid adverse side effects of cannabinoids. [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] the Guidance for Industry Botanical Drug Products Draft Guidance, August 2000, US Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research [Non-Patent Document 2] A. Douglas Kinghorn et al., Phytocannabinoids, Vol. 103, Chapter 1, pp. 1-30. [Overview of the Initiative] [Problems that the invention aims to solve]

[0008] Therefore, there is a need for improved delivery vehicles in the prior art that solve the problems and issues mentioned above. In particular, there is a need in the prior art for novel delivery vehicles that support appropriate sustained delivery of cannabinoids while possessing beneficial sensory properties. Furthermore, there is a need in the prior art for novel delivery vehicles that support topical administration of cannabinoids while possessing optimized release timing for the active substance. [Means for solving the problem]

[0009] Accordingly, a first aspect of the present invention provides an adhesive intraoral disc for sustained release of cannabinoids, comprising one or more cannabinoids, and comprising a mucosal contact layer having a mucosal contact surface usable to be fixed to the gingiva of a person requiring relief or treatment of a medical condition, comprising one or more mucosal adhesive polymers that enable the adhesive intraoral disc to adhere to the gingiva for an extended period; and a non-mucosal adhesive module fused with the mucosal contact layer, comprising a non-mucosal adhesive module comprising a solid tablet composition that enables the non-mucosal adhesive module to dissolve for an extended period when the adhesive intraoral disc adheres to the gingiva.

[0010] In a second embodiment, an adhesive intraoral disc is provided for the sustained release of cannabinoids, comprising one or more cannabinoids, and comprising a mucosal contact layer having a mucosal contact surface usable to be fixed to the gingiva of a person requiring relief or treatment of a medical condition, comprising one or more mucosal adhesive polymers that enable the adhesive intraoral disc to adhere to the gingiva for an extended period; and a non-mucosal adhesive module fused with the mucosal contact layer, comprising a non-mucosal adhesive module that does not have mucosal adhesive polymers and comprises a solid tablet composition that enables the non-mucosal adhesive module to dissolve for an extended period when the adhesive intraoral disc adheres to the gingiva.

[0011] In a third embodiment, an adhesive oral disc is provided for the sustained release of cannabinoids, comprising: one or more cannabinoids; one or more sugar alcohol particles in an amount of at least 40% by mass of the adhesive oral disc; and one or more mucosal adhesive polymers in an amount of at least 5% by mass of the adhesive oral disc, which enables the adhesive oral disc to adhere for a long period of time to the gums of a person who requires relief or treatment of a medical condition.

[0012] Importantly, the present invention does not necessarily have to be provided in a so-called "multilayer" configuration, that is, it does not have to include one mucosal contact layer and one non-mucosal adhesive module. The present invention may also be provided in a configuration without these layers and / or modules, for example, a configuration having only one layer or module. In some embodiments of the present invention, this configuration has provided certain advantages that the inventors did not anticipate being possible.

[0013] In a fourth aspect, an adhesive intraoral disc for sustained release of cannabinoids is provided, comprising: a mucosal contact layer having a mucosal contact surface usable to be fixed to the gingiva of a person requiring relief or treatment of a medical condition, the mucosal contact layer comprising one or more mucosal adhesive polymers that enable the adhesive intraoral disc to adhere to the gingiva for an extended period; and a non-mucosal adhesive module fused with the mucosal contact layer, comprising a solid tablet composition comprising one or more binders that enable the non-mucosal adhesive module to dissolve for an extended period when the adhesive intraoral disc adheres to the gingiva.

[0014] As used herein, the term “dissolution” refers to the process by which a solid substance enters a solvent (saliva) to produce a solution. Unless otherwise indicated, dissolution refers to the complete dissolution of the compound.

[0015] In this context, the term “sustained release” refers to the release of cannabinoids over a prolonged period, particularly for at least 30 minutes, for example, at least 45 minutes, or for example, at least 1 hour.

[0016] One advantage of the present invention is that sustained release and / or delivery of cannabinoids, such as cannabidiol, can be achieved. Another advantage of the present invention is that local delivery of cannabinoids can be achieved. Due to the mucosal contact layer, the oral disc can target an intended location between the gums and lips, for example, attachment to the gingiva.

[0017] In certain embodiments, the non-mucosal module does not contain a mucosal polymer. This is particularly useful to avoid adhesion of the disc to the lips, which can result in discomfort and challenges to the disc's proper function. While not bound by theory, it is thought that if the non-mucosal module contains a mucosal polymer, especially in relatively high concentrations, this could significantly affect the release of cannabinoids from the disc and / or affect the precise positioning of the disc to the target area. If the non-mucosal module adheres to the lips away from the intraoral disc attached to the gingiva, this could significantly affect the usefulness of the intraoral disc. However, non-substantial amounts of mucosal polymer may not result in these drawbacks and may even be advantageous in some embodiments.

[0018] In certain embodiments, the non-mucosal-adherent module includes a binder, such as a cellulose derivative binder. This is particularly advantageous for minimizing the use of mucosal-adherent substances that might otherwise be applied to the non-mucosal-adherent module. To the inventors' surprise, it was found that the use of a binder, such as a cellulose derivative binder, is applicable instead of a mucosal-adherent substance. These binders can greatly enhance the texture of the non-mucosal-adherent module, including its proper dissolution.

[0019] Furthermore, a convenient user experience may be provided due to effective adhesion facilitated by the mucosal contact layer. Because the disc adheres to the gums, the concentration of cannabinoids, such as cannabidiol, will be locally higher compared to tablets in which the cannabinoid is released throughout the oral cavity. This may lead to increased efficiency compared to cannabinoid tablets with unfocused delivery of cannabinoids to the oral mucosa, and subsequently to the provision of smaller discs.

[0020] Typically, smaller tablets positioned between the gums and lips, for example on the gingiva, can easily detach from these intended positions and therefore may be unintentionally chewed, swallowed, or even fall out of the mouth. Such unintentional detachment can also lead to an excess of cannabinoids in the mouth and throat, resulting in a faster-than-intended release of cannabinoids, followed by swallowing. This, in turn, also results in the ineffective utilization of the cannabinoids intended for topical oral action.

[0021] When an orally delivered vehicle is provided in a relatively small size compared to conventional cannabinoid tablets and adheres to the gums, the user may be able to swallow or even eat it during that time without affecting the positioning of the oral disc or the substantial release of cannabinoids from the oral disc. These advantages can be obtained without requiring any subsequent user action, such as special use or removal of residual product.

[0022] In this context, when a non-mucosal adhesive module is referred to as "fusing with the mucosal contact layer," the intended meaning is that these two parts are fixed to each other during storage and use. This can be done by compressing or pressing the two parts together in a tablet press, or by first compressing one or both parts of the intraoral disc and then bonding the two parts together by appropriate means. According to an advantageous embodiment of the present invention, the intraoral disc is a compressed intraoral disc in which both parts are compressed.

[0023] In this context, the term "compressed" refers to being formed by compression from a plurality of particles and / or granules, for example by means of a tableting machine, such as a rotary press. The oral disk of the above embodiment is formed by compression of at least a first powder composition and a second powder composition, resulting in a compressed oral disk with a mucosal contact layer as the "first layer" and a non-mucosal adhesion module as the "second layer" respectively. Thus, in this context, the term "first layer" generally refers to the mucosal contact layer, while the term "second layer" generally refers to the non-mucosal adhesion module of the oral disk.

[0024] Typically, an oral disk can be manufactured by first compressing the "first layer" or "second module" and then sequentially compressing other layers or modules in a multi-step process to obtain a multi-layer oral disk. When the oral disk is a two-layer tablet, it can be manufactured by compressing the "first layer" or "second module" in a two-step process and then compressing the other layer or module to obtain a two-layer oral disk.

[0025] In this context, the term "layer" is generally applied to the mucosal contact layer due to this "layer" having a relatively thin thickness compared to the "module" of the thicker non-mucosal adhesion module. However, generally, the two parts of an oral disk can be considered as "layers" but can also be considered as "modules" depending on the context. Typically, the two parts of an oral disk have the appearance of a layered tablet. When applying the term "oral disk", it is to be noted that its intention is that the thickness of the oral vehicle, i.e., the "oral disk" is generally considered to be thinner compared to an "oral tablet".

[0026] To avoid ambiguity, in this context, "layer" or "module" should not be understood as an outer "coating". In some embodiments, a "coating" can be applied onto an adhesive oral disk. In some embodiments, an adhesive oral disk does not include an outer coating.

[0027] In one embodiment of the present invention, the mucosal contact layer is compressed. In one embodiment of the present invention, the non-mucosal adhesive module is compressed. According to an advantageous embodiment of the present invention, the oral disc is composed of a plurality of compressed particles. In one embodiment of the present invention, the mucosal contact layer is composed of a plurality of compressed particles. In one embodiment of the present invention, the non-mucosal adhesive module is composed of a plurality of compressed particles. According to an advantageous embodiment of the present invention, the mucosal contact layer and the non-mucosal adhesive module are fused by compression.

[0028] In some embodiments of the present invention, the solid tablet composition comprises one or more other binders, for example, one or more other cellulose derivative binders. This particular embodiment excludes, for example, binders, such as lactose binders or other binders not derived from cellulose. These other binders are less beneficial due to the properties of these binders.

[0029] It was a surprise to the inventors that the addition of one or more binders contributed to a favorable improvement of the intraoral disc, particularly in non-mucosal modules. The addition of one or more other binders appeared to compensate for the addition of mucosal polymers, especially in non-mucosal modules. Therefore, the presence of mucosal polymers could be reduced by adding one or more other binders, particularly in non-mucosal modules. One of the advantages appeared to be an improved texture and dissolution profile in non-mucosal modules. With respect to the mucosal contact layer, when one or more other binders were added, similar adhesion could be maintained even while reducing the amount of mucosal adhesion.

[0030] In this context, when one or more binders are referred to as "separate," the intention is to exclude binders that would otherwise be present in the particles along with other components, such as sugar alcohols.

[0031] For example, binders may be applied in granulated sugar alcohol particles together with sugar alcohols. These are not included in the meaning of “another binder” in this invention. The term “another binder” also excludes binders that would otherwise be applied in wet or dry granulation. As used herein, the term “binder” refers to a component that promotes cohesiveness to a powder composition during the manufacturing process, thereby facilitating the production of layers / modules and, by extension, discs having the desired mechanical strength. Binders may be advantageously included in non-mucosal-adherent modules, thereby achieving the desired cohesiveness during tableting.

[0032] The term "solid tablet composition" is intended to mean that the components of the non-mucosal adhesive module consist of particulate matter. In some embodiments, the non-mucosal adhesive module includes more than 80% by mass, for example more than 90% by mass, for example more than 95% by mass, for example more than 98% by mass, for example 100% by mass of the solid tablet composition.

[0033] In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of 1 to 15% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of 2 to 10% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of 2 to 10% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of 2 to 8% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of 4 to 8% by mass of the non-mucosal adhesive module.

[0034] In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount exceeding 1% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount exceeding 2 to 10% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount exceeding 4% by mass of the non-mucosal adhesive module.

[0035] In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of less than 15% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of less than 10% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of less than 8% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of less than 6% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of less than 4% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of less than 2% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more other binders in an amount of less than 1% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition does not contain one or more other binders in the non-mucosal adhesive module.

[0036] In some embodiments of the present invention, the solid tablet composition comprises one or more other binders selected from the group consisting of cellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, and any combination thereof.

[0037] In some embodiments of the present invention, the solid tablet composition comprises one or more other cellulose derivative binders selected from the group consisting of carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, and any combination thereof.

[0038] In some embodiments of the present invention, the solid tablet composition comprises one or more other binders selected from the group consisting of hydroxypropylcellulose, hydroxypropylmethylcellulose, and any combination thereof.

[0039] In some embodiments of the present invention, the solid tablet composition comprises hydroxypropyl cellulose (HPC).

[0040] In some embodiments of the present invention, the solid tablet composition comprises hydroxypropyl methylcellulose (HPMC).

[0041] In some embodiments of the present invention, the solid tablet composition comprises one or more sugar alcohol particles.

[0042] In some embodiments of the present invention, the solid tablet composition contains one or more sugar alcohol particles in an amount of at least 40% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more sugar alcohol particles in an amount of at least 50% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more sugar alcohol particles in an amount of at least 60% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more sugar alcohol particles in an amount of at least 70% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more sugar alcohol particles in an amount of at least 80% by mass of the non-mucosal adhesive module.

[0043] In some embodiments of the present invention, the solid tablet composition contains one or more sugar alcohol particles in an amount of 40 to 98% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more sugar alcohol particles in an amount of 45 to 95% by mass of the non-mucosal adhesive module. In some embodiments of the present invention, the solid tablet composition contains one or more sugar alcohol particles in an amount of 50 to 90% by mass of the non-mucosal adhesive module.

[0044] In some embodiments of the present invention, the solid tablet composition comprises one or more sugar alcohol particles selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof.

[0045] The presence of one or more sugar alcohols is particularly advantageous according to the present invention. In particular, the presence of one or more sugar alcohols allows for adjustment of the dissolution time of the module.

[0046] In some embodiments of the present invention, the solid tablet composition does not contain a flavoring agent.

[0047] In some embodiments of the present invention, the oral disc does not contain edible alcohol, for example, in the non-mucosal-adherent module. If present, edible alcohol can be detrimental to the overall composition.

[0048] In this context, the term "edible alcohol" is intended to mean liquid alcohol with an alcohol content of 25 degrees Celsius, such as ethanol, methanol, propylene glycol, glycerol, etc.

[0049] In some embodiments of the present invention, the solid tablet composition contains one or more cannabinoids. In some embodiments of the present invention, the solid tablet composition contains one or more cannabinoids in an amount of 1 to 100 mg. In some embodiments of the present invention, the solid tablet composition contains one or more cannabinoids in an amount of 2 to 50 mg. In some embodiments of the present invention, the solid tablet composition contains one or more cannabinoids in an amount of 5 to 30 mg. In some embodiments of the present invention, the solid tablet composition contains one or more cannabinoids in an amount of 10 to 20 mg, which is particularly advantageous for the relief or treatment of ulcers.

[0050] In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of at least 20% by mass of the mucosal contact layer. In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of at least 40% by mass of the mucosal contact layer. In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of at least 60% by mass of the mucosal contact layer. These amounts are intended to refer to the amount of mucosal adhesive polymer in the mucosal contact layer. In this context, a considerable amount of mucosal adhesive polymer is present in the layer in order to define the "mucosal contact layer" as adhesive.

[0051] In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of 20 to 95% by mass of the mucosal contact layer. In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of 25 to 90% by mass of the mucosal contact layer. In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of 30 to 85% by mass of the mucosal contact layer. In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of 35 to 80% by mass of the mucosal contact layer. In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of 40 to 80% by mass of the mucosal contact layer. In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of 45 to 80% by mass of the mucosal contact layer. In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of 50 to 80% by mass of the mucosal contact layer. In some embodiments of the present invention, one or more mucosal adhesive polymers are present in an amount of 60 to 80% by mass of the mucosal contact layer.

[0052] An advantage of the above embodiments is that the mucosal adhesive may provide a gel-like structure at the end of dissolution. For some users, the gel-like structure may be preferred over mucosal adhesives that do not contain cellulose derivatives, because mucosal adhesives without cellulose derivatives may provide a firmer structure during dissolution. While not bound by theory, the gel-like structure is thought to occur as a result of excessive expansion of the cellulose derivative during prolonged exposure to saliva.

[0053] In some embodiments of the present invention, one or more mucosal-adhering polymers are further present in the non-mucosal-adhering module in an amount of less than 20% by mass of the non-mucosal-adhering module.

[0054] In some embodiments of the present invention, one or more mucosal-adhering polymers are further present in the non-mucosal-adhering module in an amount of less than 15% by mass of the non-mucosal-adhering module.

[0055] In some embodiments of the present invention, one or more mucosal-adhering polymers are further present in the non-mucosal-adhering module in an amount of less than 10% by mass of the non-mucosal-adhering module.

[0056] In some embodiments of the present invention, one or more mucosal-adhering polymers are further present in the non-mucosal-adhering module in an amount of less than 5% by mass of the non-mucosal-adhering module.

[0057] In some embodiments of the present invention, one or more mucosal-adhering polymers are further present in the non-mucosal-adhering modules in an amount of 1 to 20% by mass of the non-mucosal-adhering modules. In some embodiments of the present invention, one or more mucosal-adhering polymers are further present in the non-mucosal-adhering modules in an amount of 1 to 10% by mass of the non-mucosal-adhering modules. In some embodiments of the present invention, one or more mucosal-adhering polymers are further present in the non-mucosal-adhering modules in an amount of 1 to 5% by mass of the non-mucosal-adhering modules.

[0058] In some embodiments of the present invention, one or more mucosal-adhering polymers are not present in the non-mucosal-adhering module. In some embodiments of the present invention, one or more mucosal-adhering polymers are substantially not present in the non-mucosal-adhering module.

[0059] In some embodiments of the present invention, one or more mucosal adhesive polymers are selected from the group consisting of xanthan gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, alginic acid, alginate, pullulan, tragacanth gum, karaya gum, fenugreek gum, cassia gum, carrageenan, agar, pectin, dextran, guar gum, polyvinylpyrrolidone (PVP), gelatin, casein, acrylic acid polymer (carbomer), acrylic acid ester, acrylic acid copolymer, polyethylene oxide, and any combination thereof.

[0060] In some embodiments of the present invention, one or more mucosal adhesive polymers are selected from the group consisting of xanthan gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, alginic acid, alginate, pullulan, tragacanth gum, karaya gum, fenugreek gum, cassia gum, carrageenan, agar, pectin, dextran, guar gum, polyvinylpyrrolidone (PVP), gelatin, casein, acrylic acid polymer (carbomer), acrylic acid ester, acrylic acid copolymer, and any combination thereof.

[0061] In one embodiment of the present invention, the mucosal adhesive substance includes natural gum.

[0062] In one embodiment of the present invention, the mucosal adhesive substance consists of natural gum.

[0063] In some embodiments of the present invention, one or more mucosal adhesive polymers include natural gums selected from the group consisting of xanthan gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, alginic acid, alginate, pullulan, tragacanth gum, karaya gum, fenugreek gum, cassia gum, carrageenan, agar, pectin, and combinations thereof. In some embodiments of the present invention, one or more mucosal adhesive polymers include gum arabic.

[0064] In some embodiments of the present invention, one or more mucosal adhesive polymers include synthetic mucosal adhesives (hydrophilic adhesives) selected from the group consisting of polyvinylpyrrolidone (PVP), acrylic acid polymers (carbomers), acrylic acid esters, acrylic acid copolymers, and any combination thereof.

[0065] In some embodiments of the present invention, one or more mucosal-adhering polymers include hydrophilic polymers selected from the group consisting of polyvinylpyrrolidone (PVP), acrylic acid polymers (carbomers), crosslinked polyacrylic acid copolymers with divinyl glycol and its salts (polycarbophils), monoalkyl ester copolymers of poly(methyl vinyl ether / maleic acid) (Gantrez polymers), acrylic acid esters, acrylic acid copolymers, and any combination thereof.

[0066] In some embodiments of the present invention, one or more mucosal adhesive polymers include polyvinylpyrrolidone (PVP). In some embodiments of the present invention, one or more mucosal adhesive polymers include acrylic acid polymers (carbomers). In some embodiments of the present invention, one or more mucosal adhesive polymers include a copolymer of polyacrylic acid crosslinked with divinyl glycol and its salts (polycarbophil). In some embodiments of the present invention, one or more mucosal adhesive polymers include a copolymer of poly(methyl vinyl ether / maleic acid) monoalkyl esters (Gantrez polymers). In some embodiments of the present invention, one or more mucosal adhesive polymers include acrylic acid esters. In some embodiments of the present invention, one or more mucosal adhesive polymers include acid copolymers.

[0067] In some embodiments of the present invention, one or more mucosal adhesive polymers include ionic mucosal adhesive substances. As used herein, the term “ionic mucosal adhesive substance” refers to an ionizable polysaccharide mucosal adhesive substance, which may also be referred to as a polymer electrolyte. Therefore, the ionic mucosal adhesive substance does not include, for example, polyvinylpyrrolidone. An advantage of the above embodiments may be that the release profile of the active ingredient can be altered / modified.

[0068] In some embodiments of the present invention, one or more mucosal adhesive polymers include mucosal adhesive substances selected from the group consisting of xanthan gum, gellan gum, gum arabic, alginic acid, alginate, carrageenan, agar, and any combination thereof. In some embodiments of the present invention, one or more mucosal adhesive polymers include xanthan gum and / or gum arabic. In some embodiments of the present invention, one or more mucosal adhesive polymers include gum arabic. In some embodiments of the present invention, one or more mucosal adhesive polymers include xanthan gum.

[0069] In some embodiments of the present invention, one or more mucosal adhesive polymers include sodium alginate.

[0070] In some embodiments of the present invention, one or more mucosal-adhering polymers are added to the adhesive intraoral disc as separate components.

[0071] In some embodiments of the present invention, one or more mucosal adhesive polymers are added to the adhesive oral disc as another component from one or more cannabinoids.

[0072] In some embodiments of the present invention, one or more cannabinoids are not bound to one or more mucosal-adhesive polymers in the adhesive intraoral disc.

[0073] In some embodiments of the present invention, the mucosal contact layer comprises one or more other binders. In some embodiments of the present invention, the mucosal contact layer comprises one or more other cellulose derivative binders.

[0074] An advantage of the above embodiments is that the mucosal adhesive may provide a gel-like structure at the end of dissolution. For some users, the gel-like structure may be preferred over mucosal adhesives that do not contain cellulose derivatives, because mucosal adhesives without cellulose derivatives may provide a firmer structure during dissolution. While not bound by theory, the gel-like structure is thought to occur as a result of excessive expansion of the cellulose derivative during prolonged exposure to saliva.

[0075] In some embodiments of the present invention, the mucosal contact layer comprises one or more other binders, each containing one or more other cellulose derivative binders selected from the group consisting of hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose, ethyl cellulose (EC), carboxymethyl cellulose (CMC) and their salts, and any combination thereof.

[0076] In some embodiments of the present invention, the mucosal contact layer comprises one or more other binders selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, and any combination thereof.

[0077] In some embodiments of the present invention, the mucosal contact layer comprises one or more other binders, including hydroxypropyl cellulose (HPC). In some embodiments of the present invention, the mucosal contact layer comprises one or more other binders, including hydroxypropyl methylcellulose (HPMC).

[0078] In some embodiments of the present invention, the mucosal contact layer contains one or more other binders in an amount of 1 to 15% by mass of the mucosal contact layer. In some embodiments of the present invention, the mucosal contact layer contains one or more other binders in an amount of 2 to 10% by mass of the mucosal contact layer. In some embodiments of the present invention, the mucosal contact layer contains one or more other binders in an amount of 4 to 8% by mass of the mucosal contact layer.

[0079] In some embodiments of the present invention, the mucosal contact layer comprises one or more other binders selected from the group consisting of cellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, and any combination thereof.

[0080] In some embodiments of the present invention, the mucosal contact layer comprises one or more other cellulose derivative binders selected from the group consisting of carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, and any combination thereof. In some embodiments of the present invention, the mucosal contact layer comprises hydroxypropylcellulose (HPC). In some embodiments of the present invention, the mucosal contact layer comprises hydroxypropylmethylcellulose (HPMC).

[0081] An advantage of the above embodiments is that the mucosal adhesive may provide a gel-like structure at the end of dissolution. For some users, the gel-like structure may be preferred over mucosal adhesives that do not contain cellulose derivatives, because mucosal adhesives without cellulose derivatives may provide a firmer structure during dissolution. While not bound by theory, the gel-like structure is thought to occur as a result of excessive expansion of the cellulose derivative during prolonged exposure to saliva.

[0082] In one embodiment of the present invention, the dissolution time in the above embodiment is the in vivo dissolution time.

[0083] According to one embodiment of the present invention, the in vivo dissolution time was evaluated by at least six trained evaluators, each of whom refrained from eating or drinking for at least 30 minutes before the start of any test, weighed the disc, placed it between the upper lip and gums in the mouth, initially facing the gums, and registered the in vivo dissolution time as the point at which the dissolution of the oral disc was substantially complete.

[0084] In some embodiments of the present invention, the mucosal contact layer contains one or more sugar alcohol particles. In some embodiments of the present invention, the mucosal contact layer contains one or more sugar alcohol particles in an amount of 5 to 80% by mass of the mucosal contact layer. In some embodiments of the present invention, the mucosal contact layer contains one or more sugar alcohol particles in an amount of 10 to 80% by mass of the mucosal contact layer. In some embodiments of the present invention, the mucosal contact layer contains one or more sugar alcohol particles in an amount of 20 to 80% by mass of the mucosal contact layer. In some embodiments of the present invention, the mucosal contact layer contains one or more sugar alcohol particles in an amount of 30 to 80% by mass of the mucosal contact layer. In some embodiments of the present invention, the mucosal contact layer contains one or more sugar alcohol particles in an amount of 40 to 80% by mass of the mucosal contact layer. In some embodiments of the present invention, the mucosal contact layer contains one or more sugar alcohol particles in an amount of 50 to 80% by mass of the mucosal contact layer.

[0085] In some embodiments of the present invention, the mucosal contact layer contains one or more sugar alcohol particles in an amount of 10 to 60% by mass of the mucosal contact layer. In some embodiments of the present invention, the mucosal contact layer contains one or more sugar alcohol particles in an amount of 10 to 40% by mass of the mucosal contact layer.

[0086] In some embodiments of the present invention, the mucosal contact layer comprises one or more sugar alcohol particles selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof.

[0087] In some embodiments of the present invention, the mucosal contact layer includes a filler.

[0088] In some embodiments of the present invention, the mucosal contact layer comprises a filler selected from the group consisting of calcium carbonate, magnesium carbonate, magnesium hydroxide, and combinations thereof.

[0089] In some embodiments of the present invention, the mucosal contact layer does not contain flavoring agents.

[0090] In some embodiments of the present invention, the mucosal contact layer contains one or more cannabinoids. In some embodiments of the present invention, the mucosal contact layer contains one or more cannabinoids in an amount of 1 to 100 mg. In some embodiments of the present invention, the mucosal contact layer contains one or more cannabinoids in an amount of 2 to 50 mg. In some embodiments of the present invention, the mucosal contact layer contains one or more cannabinoids in an amount of 5 to 30 mg.

[0091] In some embodiments of the present invention, the mucosal contact layer does not contain one or more cannabinoids.

[0092] In some embodiments of the present invention, the mucosal contact layer comprises at least 10% by mass of the adhesive intraoral disc, for example, at least 20% by mass of the adhesive intraoral disc, for example, at least 30% by mass of the adhesive intraoral disc.

[0093] In some embodiments of the present invention, the non-mucosal module accounts for at least 40% by mass of the adhesive intraoral disc, for example, at least 50% by mass of the adhesive intraoral disc, for example, at least 60% by mass of the adhesive intraoral disc.

[0094] In some embodiments of the present invention, the mucosal contact layer accounts for 10 to 50% by mass of the adhesive intraoral disc, for example, 20 to 50% by mass of the adhesive intraoral disc, for example, 20 to 40% by mass of the adhesive intraoral disc.

[0095] In some embodiments of the present invention, the adhesive intraoral disc has a mass of at least 100 mg, for example, at least 150 mg, for example, at least 200 mg.

[0096] In some embodiments of the present invention, the adhesive intraoral disc has a mass of 600 mg or less, for example, 500 mg or less, for example, 400 mg or less.

[0097] In some embodiments of the present invention, the mucosal contact layer is substantially flat.

[0098] In some embodiments of the present invention, the mucosal contact layer is concave, dimpled, or donut-shaped, or the mucosal contact surface of the mucosal contact layer includes one or more of these shapes.

[0099] In some embodiments of the present invention, the mucosal contact surface of the mucosal contact layer includes inwardly curved depressions that allow the layer to be fixed to the gingiva as a first mechanism by pressure difference.

[0100] In some embodiments of the present invention, the mucosal contact layer includes an inward-facing recess that allows the layer to be fixed to the gingiva as a first mechanism by pressure difference.

[0101] In some embodiments of the present invention, the adhesive intraoral disc does not include a gel layer or a cast film strip layer.

[0102] In some embodiments of the present invention, the adhesive intraoral disc contains less than 15% by mass of water. In some embodiments of the present invention, the adhesive intraoral disc contains less than 10% by mass of water. In some embodiments of the present invention, the adhesive intraoral disc contains less than 5% by mass of water.

[0103] In some embodiments of the present invention, the mucosal contact layer contains less than 15% by mass of water. In some embodiments of the present invention, the mucosal contact layer contains less than 10% by mass of water. In some embodiments of the present invention, the mucosal contact layer contains less than 5% by mass of water.

[0104] In some embodiments of the present invention, the mucosal contact layer is a compressed layer.

[0105] In some embodiments of the present invention, the non-mucosal-adherent module is a compression module.

[0106] In some embodiments of the present invention, the mucosal contact layer and the non-mucosal adhesive module are fused by compression.

[0107] In some embodiments of the present invention, the non-mucosal-adherent module does not extend onto any side surface of the mucosal contact layer.

[0108] In some embodiments of the present invention, the non-mucosal-adherent module does not extend onto any side surfaces of the mucosal contact layer, thereby exposing a larger contact area to the oral mucosa compared to a configuration in which the non-mucosal-adherent module extends onto the side surfaces of the mucosal contact layer and only the bottom surface of the mucosal-adherent module is exposed to the oral mucosa at the time of administration.

[0109] In some embodiments of the present invention, the non-mucosal-adherent module is positioned on the mucosal contact layer.

[0110] In some embodiments of the present invention, the adhesive intraoral disc has a dissolution time of at least 15 minutes, for example, at least 20 minutes, for example, at least 30 minutes, for example, at least 45 minutes.

[0111] In some embodiments of the present invention, the adhesive intraoral disc has a dissolution time of 10 hours or less, for example, 8 hours, for example, 5 hours, for example, 2.5 hours, for example, 2 hours or less, for example, 1.5 hours or less, for example, 1 hour or less.

[0112] In some embodiments of the present invention, the adhesive intraoral disc has a dissolution time between 15 minutes and 2.5 hours, for example between 20 minutes and 1.5 hours, or for example between 30 minutes and 1 hour.

[0113] In some embodiments of the present invention, the adhesive intraoral disc has a dissolution time between 45 minutes and 2.5 hours. In some embodiments of the present invention, the adhesive intraoral disc has a dissolution time between 1 hour and 2 hours.

[0114] In some embodiments of the present invention, the adhesive intraoral disc has a dissolution time between 6 and 12 hours. In some embodiments of the present invention, the adhesive intraoral disc has a dissolution time between 7 and 11 hours. In some embodiments of the present invention, the adhesive intraoral disc has a dissolution time between 8 and 10 hours.

[0115] In some embodiments of the present invention, the dissolution time of the mucosal contact layer is substantially synchronized with the dissolution time of the non-mucosal adhesive module.

[0116] In some embodiments of the present invention, the long-term adhesion of the mucosal contact layer of the adhesive intraoral disc to the gingiva corresponds to the long-term dissolution of the non-mucosal adhesive module of the adhesive intraoral disc.

[0117] In some embodiments of the present invention, one or more cannabinoids are selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), cannabiersoin (CBE), isotetrahydrocannabinol (iso-THC), cannabicyclol (CBL), cannabicitran (CBT), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabiclomevalin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), and combinations thereof.

[0118] In some embodiments of the present invention, one or more cannabinoids are selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), and combinations thereof.

[0119] In some embodiments of the present invention, one or more cannabinoids are selected from the group consisting of tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and combinations thereof.

[0120] In some embodiments of the present invention, one or more cannabinoids include cannabidiol (CBD).

[0121] In some embodiments of the present invention, one or more cannabinoids include isolated cannabinoids.

[0122] In some embodiments of the present invention, one or more cannabinoids are isolated cannabinoids.

[0123] In some embodiments of the present invention, one or more cannabinoids are synthetic cannabinoids.

[0124] In some embodiments of the present invention, one or more cannabinoids are not cannabinoid extracts with a cannabinoid purity of less than 80%.

[0125] In some embodiments of the present invention, one or more cannabinoids exist as particles with a size of 400 to 1200 nanometers. In some embodiments of the present invention, one or more cannabinoids exist as particles with a size of 500 to 1000 nanometers.

[0126] In some embodiments of the present invention, one or more cannabinoids are present in the mucosal contact layer.

[0127] In some embodiments of the present invention, one or more cannabinoids are present in a non-mucosal module.

[0128] In some embodiments of the present invention, one or more cannabinoids are present in both the mucosal contact layer and the non-mucosal adhesive module.

[0129] In some embodiments of the present invention, one or more cannabinoids are not present in the mucosal contact layer.

[0130] In some embodiments of the present invention, one or more cannabinoids are not present in the non-mucosal module.

[0131] In some embodiments of the present invention, the adhesive intraoral disc includes one or more self-emulsifying systems.

[0132] In some embodiments of the present invention, the adhesive intraoral disc comprises one or more liquid self-emulsifying systems.

[0133] In some embodiments of the present invention, the adhesive intraoral disc comprises one or more liquid self-emulsifying systems containing one or more surfactants having an HLB value greater than 6.

[0134] In some embodiments of the present invention, the adhesive oral disc comprises one or more liquid self-emulsifying systems comprising one or more surfactants selected from the group consisting of PEG-35 castor oil, PEG-6 oleoyl glyceride, PEG-6 linoleoyl glyceride, PEG-8 caprylic / capric acid glyceride, sorbitan monolaurate, sorbitan monooleate, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (60) sorbitan monostearate, polyoxyethylene (80) sorbitan monooleate, lauroyl polyoxyl-32 glyceride, stearoyl polyoxyl-32 glyceride, polyoxyl-32 stearate, propylene glycol monolaurate, propylene glycol dilaurate, and mixtures and combinations thereof.

[0135] In some embodiments of the present invention, the adhesive intraoral disc comprises one or more liquid self-emulsifying systems containing one or more cosolvents.

[0136] In some embodiments of the present invention, the adhesive oral disc comprises one or more liquid self-emulsifying systems containing one or more cosolvents selected from the group consisting of polyglyceryl-3 dioleate, 1,2-propanediol, polyethylene glycol 300, polyethylene glycol 400, diethylene glycol monoethyl ether, and mixtures and combinations thereof.

[0137] In some embodiments of the present invention, the adhesive intraoral disc comprises one or more liquid self-emulsifying systems containing one or more solubilizing agents.

[0138] In some embodiments of the present invention, the adhesive intraoral disc comprises one or more liquid self-emulsifying systems comprising one or more solubilizers selected from the group consisting of lauroyl polyoxyl-32 glyceride; stearoyl polyoxyl-32 glyceride; polyoxyl-32 stearate; a synthetic copolymer of ethylene oxide (80) and propylene oxide (27); polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; alpha, beta, or gamma cyclodextrin and its derivatives; pea proteins (globulin, albumin, glutelin proteins) and mixtures and combinations thereof.

[0139] Due to the poor solubility of certain active ingredients in physiological fluids, solubilizing cannabinoids in mixtures containing the body's physiological fluids to facilitate bio-absorption is an unmet need. To overcome low bioavailability, various lipid-based drug delivery systems and self-emulsifying systems have been developed. Lipid-based delivery systems, and in particular self-emulsifying drug delivery systems (SEDDS), have been demonstrated to increase the solubility, dissolution, and bioavailability of many insoluble active ingredients.

[0140] With regard to SEDDS in particular, the formulation of the present invention may offer several obvious advantages, including enabling a higher load of the active ingredient during use and simultaneously resulting in improved sensory properties of the formulation. Other advantages also exist.

[0141] Importantly, the presence of SEDDS or at least an autoemulsifier was found to act synergistically with the formulation of the present invention. The presence of SEDDS or at least an autoemulsifier was found to further increase the uptake of the active ingredient through the mucosal surface.

[0142] Therefore, the synergistic effect between the presence of SEDDS or at least a self-emulsifier and cannabinoids was a surprise to the inventors. In particular, the potential of SEDDS, which have a high load of active ingredients, further contributes to the synergistic effect according to the present invention.

[0143] In this context, SEDDS are solid or liquid dosage forms containing at least a surfactant and optionally a cosurfactant, primarily characterized by their ability to spontaneously form an oil-in-water emulsion in the oral cavity or at ambient temperature (generally referring to body temperature, i.e., 37°C). When SEDDS enters a mucous membrane, it first self-emulsifies as emulsion droplets and rapidly disperses. The resulting micrometer or nanometer-level particles can penetrate the mucous membrane, and the absorbed oil droplets enter the bloodstream, thereby significantly improving the bioavailability of the active ingredient.

[0144] In some embodiments of the present invention, one or more cannabinoids are bound to cyclodextrins, such as thiolated cyclodextrins.

[0145] In some embodiments of the present invention, one or more cannabinoids are included in a premix containing one or more lipids.

[0146] In some embodiments of the present invention, one or more cannabinoids are included in a premix containing one or more triglycerides.

[0147] In some embodiments of the present invention, one or more cannabinoids are included in a premix comprising one or more vegetable oils.

[0148] In some embodiments of the present invention, the adhesive intraoral disc comprises one or more absorption enhancers.

[0149] According to an advantageous embodiment of the present invention, the disk contains a pH adjusting agent, for example, an alkaline pH adjusting agent, for example, an alkaline buffer. In one embodiment of the present invention, the mucosal adhesive contact layer contains a pH adjusting agent. In one embodiment of the present invention, the pH adjusting agent of the mucosal adhesive contact layer is an alkaline pH adjusting agent, for example, an alkaline buffer. In one embodiment of the present invention, the non-mucosal adhesive module contains a pH adjusting agent. In one embodiment of the present invention, the pH adjusting agent of the non-mucosal adhesive module is an alkaline pH adjusting agent, for example, an alkaline buffer.

[0150] In some embodiments of the present invention, the oral disc further comprises one or more alkaline pH adjusting agents, such as sodium carbonate or sodium bicarbonate.

[0151] In some embodiments of the present invention, the oral disc further comprises one or more acid neutralizing agents, such as calcium carbonate, sodium carbonate, or sodium bicarbonate.

[0152] In some embodiments of the present invention, the oral disc further comprises one or more active substances selected from the group consisting of chitosan, curcumin, propolis, hyaluronic acid, aloe vera, quercetin, and combinations thereof.

[0153] In some embodiments of the present invention, the adhesive intraoral disc includes further modules / layers.

[0154] In some embodiments of the present invention, the adhesive intraoral disc includes a second mucosal contact layer.

[0155] In some embodiments of the present invention, the adhesive intraoral disc further includes an orally disintegrating tablet (ODT) module.

[0156] In some embodiments of the present invention, the adhesive intraoral disc further includes a rapidly disintegrating tablet (FDT) module.

[0157] In some embodiments of the present invention, the adhesive intraoral disc comprises a further module / layer containing a disintegrant.

[0158] In a further aspect of the present invention, the oral disc according to the present invention is for use in a method for treating or alleviating a medical condition.

[0159] In a further aspect of the present invention, the oral disc according to the present invention is for use in a method for treating or alleviating ulcers.

[0160] In a further aspect of the present invention, the oral disc according to the present invention is for use in a method for treating or alleviating stomatitis.

[0161] In a further aspect of the present invention, the oral disc according to the present invention is for use in a method for treating or alleviating aphthous ulcers.

[0162] In a further aspect of the present invention, the intraoral disc according to the present invention is for use in a method for treating or alleviating oral disorders. [Modes for carrying out the invention]

[0163] The present invention will be described in more detail here with reference to certain aspects and embodiments of the invention. These aspects and embodiments are intended to be understood in connection with the remainder of this description, including the summary and examples of the invention.

[0164] As used herein, the numerical terms “approximately” or “about” generally mean, unless otherwise indicated or made clear from the context, numbers that fall within the range of 5%, 10%, 15%, or 20% of a number in either direction (greater than or less than that number) (except when such numbers are less than 0% or greater than 100% of the possible value).

[0165] As used herein, the terms "%" and "percent" refer to mass percentages unless otherwise indicated.

[0166] As used herein, the term “disintegrate” refers to the transformation of an object into its components, fragments, or particles. Disintegration time may be measured in vitro or in vivo. Unless otherwise indicated, in vitro measurements shall be performed in accordance with European Pharmacopoeia 9.0, Chapter 2.9.1, Disintegration of tablets and capsules.

[0167] As used herein, the term “dissolution” refers to the process by which a solid substance enters a solvent (saliva) to produce a solution. Unless otherwise indicated, dissolution refers to the complete dissolution of the compound.

[0168] The terms “tableting” or “compression” are intended to mean that an intraoral disc composition is pressed in a tableting apparatus and is composed primarily of particulate matter. While the terms suggest a process, in this context, the terms are intended to mean the resulting tablets obtained by the tableting of some of the particles. It should be noted that an intraoral disc or tableting composition referred to as ultimately containing particles is understood to be the particles pressed together in the tableting process.

[0169] A "self-emulsifier" is a substance that forms an emulsion when present with another phase with minimal energy requirements. In contrast, an emulsifier, as opposed to a self-emulsifier, requires additional energy to form an emulsion.

[0170] As used herein, the term "cannabinoid release" refers to making cannabinoids bioavailable, that is, making them available for absorption on the mucous membranes of the oral cavity. Some forms of cannabinoids require solubility to be bioavailable, while others can be readily absorbed by the body without solubility.

[0171] As used herein, the term "pH adjuster" refers to an agent that adjusts and modulates the pH value of a solution to which an active substance has been added or to which an active substance has been added. In this context, a pH adjuster does not contain an active ingredient.

[0172] When referring to the amount of an ingredient using terms such as "less than" or "less than," this generally refers to a specific ingredient that is either absent or present in trace amounts, or within a defined maximum amount.

[0173] As used herein, the term “flavoring” is understood to have its conventional meaning within the art. Flavorings include liquid and powdered flavorings. Therefore, flavorings do not include sweeteners (e.g., sugars, sugar alcohols, and high-strength sweeteners), acids that provide pure acidity / sourness, or compounds that provide pure saltiness (e.g., NaCl) or pure bitterness. Flavorings may be natural or synthetic.

[0174] Typically, an intraoral disc may contain components selected from the group consisting of fillers, flavorings, binders, disintegrants (in this case, superdisintegrants), emulsifiers, antioxidants, pH adjusters (in this case, alkaline and acidic pH adjusters), high-strength sweeteners, colorants, lubricants, slicks, or any combination thereof.

[0175] In an advantageous embodiment of the present invention, the oral disc contains a bulk sweetener as a filler component.

[0176] In an advantageous embodiment of the present invention, the first layer contains a bulk sweetener as a filler component.

[0177] In an advantageous embodiment of the present invention, the second layer contains a bulk sweetener as a filler component.

[0178] In an advantageous embodiment of the present invention, the first and second layers contain a bulk sweetener as a filler component.

[0179] The oral disc may contain different bulk sweeteners in addition to at least one sugar alcohol in the first layer and at least one sugar alcohol in the second layer. The bulk sweeteners include sugar sweeteners and / or sugar-free sweeteners.

[0180] Sweeteners generally include, but are not limited to, saccharin-containing components such as sucrose, dextrose, maltose, saccharose, lactose, sorbose, dextrin, trehalose, D-tagatose, dried invert sugar, fructose, levose, galactose, etc., either alone or in combination.

[0181] Sugar-free sweeteners generally include, but are not limited to, sugar alcohols (sometimes called polyols), such as xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and combinations thereof.

[0182] A combination of sugars and / or sugar-free sweeteners may be used in oral discs.

[0183] Bulk sweeteners can often support the flavor profile of the oral disc.

[0184] In embodiments of the present invention, the bulk sweetener may be supplemented with other usable fillers, including, for example, magnesium and calcium carbonate, sodium sulfate, crushed limestone, silicate compounds, such as magnesium silicate and aluminum silicate, kaolin and clay, aluminum oxide, silicon oxide, talc, titanium dioxide, calcium monophosphate, calcium diphosphate, calcium triphosphate, fiber, plant fiber, such as wheat fiber, oat fiber, pea fiber, and combinations thereof.

[0185] High-strength artificial sweeteners can also be used in combination with the bulk sweeteners mentioned above. For example, high-strength sweeteners include, but are not limited to, sucralose, aspartame, acesulfame salts, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, monellin, stevioside (natural high-strength sweetener), etc., either alone or in combination.

[0186] The level of artificial sweetener use varies considerably and depends on the potency of the sweetener, the rate of release, the desired sweetness of the product, the level and type of flavoring used, and cost considerations. Therefore, the activity level of artificial sweeteners can vary from about 0.001% to about 8% by mass (e.g., about 0.02% to about 8% by mass).

[0187] In embodiments where the oral disc contains a fragrance, different fragrances may be used.

[0188] Available flavors include, for example, almond, almond amaretto, apple, bavarian cream, black cherry, black sesame, blueberry, brown sugar, bubblegum, butterscotch, cappuccino, caramel, caramel cappuccino, cheesecake (graham crust), cinnamon red hots, cotton candy, circus cotton candy, clove, coconut, coffee, clear coffee, double chocolate, energy cow, graham cracker, grape juice, green apple, Hawaiian punch, honey, Jamaican rum, Kentucky bourbon, kiwi, coolada, lemon, lemon lime, tobacco, maple syrup, maraschino cherry, marshmallow, menthol, milk chocolate, mocha, Mountain Dew, peanut butter, pecan, peppermint, raspberry, banana, ripe banana, root beer, RY 4. Includes spearmint, strawberry, sweet cream, sweet tart, sweetener, toasted almond, tobacco, tobacco blend, vanilla bean ice cream, vanilla cupcake, vanilla swirl, vanillin, waffle, Belgian waffle, watermelon, whipped cream, white chocolate, wintergreen, amaretto, banana cream, black walnut, blackberry, butter, butter rum, cherry, chocolate hazelnut, cinnamon roll, cola, crème de mint, eggnog, English toffee, guava, lemonade, licorice, maple, mint chocolate chip, orange cream, peach, piña colada, pineapple, plum, pomegranate, praline and cream, red licorice, saltwater toffee, strawberry banana, strawberry, kiwi, tropical punch, tutti frutti, vanilla, or any combination thereof.

[0189] According to one embodiment of the present invention, a flavoring may be used to mask the taste of cannabinoids and / or alkaline pH adjusters. However, as outlined in other embodiments, flavorings may be preferably avoided in non-mucosal modules. Having a flavoring in a non-mucosal module can be a disadvantage. In particular, flavorings may interfere with the intended sustained release of cannabinoids. More specifically, flavorings may, in some cases, promote saliva production that can counteract the sustained release of cannabinoids, for example, when rapid dissolution of the non-mucosal module occurs. In addition, flavorings may also increase pain experienced at the location of the gingival sensitivity area. This may be more pronounced in medical indications, such as the alleviation or treatment of ulcers or gingivitis.

[0190] In one embodiment of the present invention, the intraoral disc contains a lubricant. Silicon dioxide may be used as the lubricant. Other lubricants usable for intraoral discs may also be used within the scope of the present invention.

[0191] In one embodiment of the present invention, the intraoral disc contains a lubricant. Magnesium stearate and / or sodium stearyl fumarate may be used as the lubricant. Other lubricants suitable for use in intraoral discs may also be used within the scope of the present invention.

[0192] According to the present invention, one or more cannabinoids can be selected from a variety of cannabinoids.

[0193] "Cannabinoids" is a group of compounds that include endocannabinoids, phytocannabinoids, and compounds that are neither endocannabinoids nor phytocannabinoids, hereinafter referred to as "synthocannabinoids."

[0194] Endocannabinoids are endogenous cannabinoids that may possess high-affinity ligands for CB1 and CB2 receptors.

[0195] Phytocannabinoids are cannabinoids of natural origin that can be found in the cannabis plant. Phytocannabinoids may be present in extracts containing plant-derived active pharmaceutical ingredients, isolated, or synthetically reproduced.

[0196] Syntocannabinoids are compounds capable of interacting with cannabinoid receptors (CB1 and / or CB2), but are not found endogenously or in the cannabis plant. Examples include WIN 55212 and limonabane.

[0197] "Isolated phytocannabinoids" are extracted from the cannabis plant and purified to such an extent that additional components, such as secondary and trace cannabinoids and non-cannabinoid fractions, are substantially removed.

[0198] "Synthetic cannabinoids" are cannabinoids produced by chemical synthesis. This term includes modifying isolated phytocannabinoids, for example, by forming pharmaceutically acceptable salts thereof.

[0199] "Substantially pure" cannabinoids are defined as cannabinoids that are purely present in greater than 95% (w / w) percentage. More preferably, greater than 96% (w / w), 97% (w / w), 98% (w / w) to 99% (w / w) and beyond.

[0200] "Highly purified" cannabinoids are defined as cannabinoids extracted from the cannabis plant and purified to such an extent that other cannabinoids and non-cannabinoid components co-extracted with cannabinoids are substantially removed, so that the highly purified cannabinoids are more than 95% (w / w) or as pure as that amount.

[0201] "Plant material" is defined as a plant or part of a plant (e.g., bark, wood, leaves, stems, roots, flowers, fruits, seeds, berries or parts thereof) and extracts, and includes materials that meet the definition of "botanical raw material" in the Guidance for Industry Botanical Drug Products Draft Guidance, August 2000, U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research.

[0202] In the context of this application, the terms “cannabinoid extract” or “cannabinoid extract” are used interchangeably and encompass “botanical drug substances” derived from cannabis plant material. “Botanical drug substances” are defined in the Guidance for Industry Botanical Drug Products Draft Guidance, August 2000, U.S. Department of Health and Human Services, Food and Drug Administration Centre for Drug Evaluation and Research, as “a drug substance derived from one or more plants, algae, or macrofungi.” These are prepared from botanical raw materials by one or more of the following processes: grinding, leaching, expression, aqueous extraction, ethanol extraction, or other similar processes. Botanical drug substances do not contain highly purified or chemically modified substances derived from natural resources. Therefore, in the case of cannabis, “botanical drug substances” derived from the cannabis plant do not contain highly purified pharmacopoeia-grade cannabinoids.

[0203] The term "cannabis plant" includes Cannabis sativa subspecies indica, Cannabis indica, Cannabis ruderalis, and also plants resulting from genetic crosses, self-crosses, or hybrids thereof, including cannabis chemical varieties, variants, and variants such as Cannabis indica and Cannabis kafiristanica that naturally contain varying amounts of individual cannabinoids, as well as wild-type Cannabis sativa and its variants. Therefore, the term "cannabis plant material" should be interpreted as including plant material derived from one or more cannabis plants. To avoid ambiguity, this specification explicitly states that "cannabis plant material" includes dried cannabis biomass.

[0204] Preferably, one or more cannabinoids are selected from cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and tetrahydrocannabivaric acid (THCV A). More preferably, one or more cannabinoids are CBD or THC. This enumeration is not exhaustive and is merely a detail of the cannabinoids specified in this application for reference.

[0205] To date, more than 120 different phytocannabinoids have been identified that fall within the scope of this invention.

[0206] Cannabinoids can be divided into different groups, such as phytocannabinoids, endocannabinoids, and synthetic cannabinoids.

[0207] For the purposes of the present invention, and whether expressly named herein, cannabinoid receptors are naturally lipophilic and can be activated by agonist ligands of three main groups, which are classified as: endocannabinoids (endogenously produced by mammalian cells); phytocannabinoids (e.g., cannabidiol produced from the cannabis plant); and synthetic cannabinoids (e.g., HU-210).

[0208] Phytocannabinoids can be found in either a neutral carboxylic acid form or a decarboxylated form, depending on the method used to extract the cannabinoids. For example, it is well known that heating of the carboxylic acid form results in the decarboxylation of most of the carboxylic acid form.

[0209] Phytocannabinoids can also arise as either pentyl (5 carbon atoms) or propyl (3 carbon atoms) variants. For example, the phytocannabinoid THC is known to be a CB1 receptor agonist, while the propyl variant THCV has been found to be a CB1 receptor antagonist, meaning it has almost the opposite effect.

[0210] According to the present invention, examples of phytocannabinoids may be cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and tetrahydrocannabivaric acid (THCV A). More preferably, one or more cannabinoids are CBD or THC.

[0211] The formulation according to the present invention may also include at least one cannabinoid selected from those disclosed in A. Douglas Kinghorn et al., Phytocannabinoids, Vol. 103, Chapter 1, pp. 1-30.

[0212] Endocannabinoids are molecules that activate cannabinoid receptors in the body. Examples include 2-arachidonylglycerol (2AG), 2-arachidonylglyceryl ether (2AGE), arachidonyldopamine, and arachidonylethanolamide (anandamide). Structurally related endogenous molecules, which share similar structural features but have been identified as exhibiting weak or no activity towards cannabinoid receptors, are also called endocannabinoids. Examples of these endocannabinoid lipids include 2-acylglycerol, alkyl or alkenylglyceryl ethers, acyldopamine, and N-acylethanolamides containing alternative fatty acid or alcohol moieties, as well as other fatty acid amides containing different head groups. These include N-acylserine and many other N-acylated amino acids. Examples of cannabinoid receptor agonists are neuromodulators that affect short-term memory, appetite, stress response, anxiety, immune function, and analgesia.

[0213] In one embodiment, the cannabinoid is palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the class of nuclear factor agonists.

[0214] Synthetic cannabinoids encompass a variety of other chemical classes: structurally related cannabinoids to THC, non-THC related cannabinoids such as aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulfonamides (cannabimimetics), and eicosanoids related to endocannabinoids. All or any of these cannabinoids can be used in the present invention.

[0215] The formulation preferably contains one or two major cannabinoids selected from the group consisting of cannabidiol (CBD) or cannabidivarin (CBDV), tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), tetrahydrocannabinolic acid (THCA), cannabigerol (CBG), and cannabidiolic acid (CBDA), or combinations thereof. The formulation preferably contains cannabidiol and / or tetrahydrocannabinol.

[0216] Preferably, the oral disc of the present invention may be used to treat or alleviate pain, epilepsy, cancer, nausea, inflammation, congenital disorders, neurological disorders, oral infections, toothaches, sleep apnea syndrome, mental disorders, gastrointestinal disorders, inflammatory bowel disease, loss of appetite, diabetes, and fibromyalgia.

[0217] In a further aspect of the present invention, oral cannabinoid preparations are suitable for use in the treatment of conditions requiring the administration of neuroprotective or anticonvulsant drugs.

[0218] Oral cannabinoid preparations may be used for the treatment of seizures.

[0219] Oral cannabinoid preparations may be used for the treatment of Dravet syndrome, Lennox-Gastaut syndrome, myoclonic seizures, juvenile myoclonic epilepsy, refractory epilepsy, schizophrenia, juvenile seizures, West syndrome, infantile seizures, refractory infantile seizures, tuberous sclerosis, brain tumors, neuropathic pain, cannabis use disorder, post-traumatic stress disorder, anxiety, early psychosis, Alzheimer's disease, and autism.

[0220] The following non-limiting examples illustrate various variations of the present invention. The examples are intended to illustrate the concept of the present invention, and therefore, the examples mentioned should not be understood as exhaustive of the present invention. In particular, while CBD is used as an exemplary compound, other cannabinoids may be used. [Examples]

[0221] (Example 1) Preparation of an intraoral disc including the first and second layers The composition of the second layer, i.e., the non-mucosal adhesive layer, is prepared with sugar alcohols unless otherwise specified. The composition is prepared by pouring about half of the sugar alcohol, followed by the other components excluding the lubricant, and finally the remaining sugar alcohol into a mixing bowl. The components are rotated / mixed in a mixer (Turbula or Duma) at 49 rpm for 4 to 10 minutes.

[0222] Add the lubricant and mix the ingredients further at 49 rpm for 1-2 minutes.

[0223] The composition of the first layer, i.e., the mucosal adhesion contact layer, is prepared by pouring all components except the lubricant into a mixing bowl. The components are mixed in a mixer (Turbula or Duma) at 49 rpm for 4 to 10 minutes.

[0224] Add the lubricant and mix the ingredients further at 49 rpm for 1-2 minutes.

[0225] The lubricating powder blend is sequentially transferred to the hopper of the tablet press.

[0226] Next, the second layer is compressed with a compressive force of approximately 1-5 kN, and then the first layer is fused with the second layer by compression with a compressive force of approximately 8-15 kN. Unless otherwise specified, the punch used is 8.00 mm, circular, convex dimple, D tooling.

[0227] In an alternative process configuration, the second layer is compressed with a compressive force of approximately 3-8 kN, and then the first layer is fused with the second layer by compression with a compressive force of approximately 20-30 kN. Unless otherwise specified, the punch used is 12.00 mm, circular, shallow concave, B tooling.

[0228] Intraoral discs are manufactured using a laboratory-scale machine, such as a RIVA Piccola tablet press. The tablet press is instructed to adjust the filling depth and compression force so that the mass and hardness of the intraoral discs meet the approved standards. A pre-compression force may be included to avoid capping.

[0229] (Example 1A) Preparation of an intraoral disc composed of no layers The intraoral discs are prepared with sugar alcohols unless otherwise specified. The composition of the intraoral discs is prepared by pouring approximately half of the sugar alcohol into a mixing bowl, followed by the other ingredients except the lubricant, and finally the remaining sugar alcohol into the mixing bowl. The ingredients are mixed in a mixer (Turbula or Duma) at 49 rpm for 4 to 10 minutes.

[0230] Add the lubricant and mix the ingredients further at 49 rpm for 1-2 minutes.

[0231] The lubricating powder blend is sequentially transferred to the hopper of the tablet press.

[0232] Next, compress the intraoral disc with a compressive force of approximately 20-30 kN. Unless otherwise specified, the punch used is 12.00 mm, circular, shallow concave, B tooling.

[0233] Intraoral discs are manufactured using a laboratory-scale machine, such as a RIVA Piccola tablet press. The tablet press is instructed to adjust the filling depth and compression force so that the disc mass and hardness meet the approved standards. Pre-compression force may be included to avoid capping.

[0234] (Example 1B) Preparation of a 3-layer intraoral disc The composition of the third layer is prepared by pouring all ingredients except the lubricant into a mixing bowl. The ingredients are mixed in a mixer (Turbula or Duma) at 49 rpm for 4 to 10 minutes.

[0235] Add the lubricant and mix the ingredients further at 49 rpm for 1-2 minutes.

[0236] The composition of the second layer, i.e., the non-mucosal adhesive layer, is prepared with sugar alcohols unless otherwise specified. The composition of the second layer is prepared by pouring about half of the sugar alcohol, followed by the other components excluding the lubricant, and finally the remaining sugar alcohol into a mixing bowl. The components are mixed in a mixer (Turbula or Duma) at 49 rpm for 4 to 10 minutes.

[0237] Add the lubricant and mix the ingredients further at 49 rpm for 1-2 minutes.

[0238] The composition of the first layer, i.e., the mucosal adhesion contact layer, is prepared by pouring all components except the lubricant into a mixing bowl. The components are mixed in a mixer (Turbula or Duma) at 49 rpm for 4 to 10 minutes.

[0239] Add the lubricant and mix the ingredients further at 49 rpm for 1-2 minutes.

[0240] The lubricating powder blend is sequentially transferred to the hopper of the tablet press.

[0241] The first layer is compressed with a compressive force of approximately 1-6 kN, and then the second layer is fused with the first layer by compression with a compressive force of approximately 2-8 kN. Next, the third layer is fused with the second layer by compression with a compressive force of approximately 20-40 kN. Unless otherwise specified, the punch used is 12.00 mm, circular, shallow concave, B tooling.

[0242] The intraoral discs were manufactured using the PZ-TRE rotary tablet press available from B&D Italia, but other standard instruments for manufacturing three-ply tablets, such as the PTK PR3500 or Hata three-ply tablet press, can also be used. The tablet press should be adjusted to ensure that the tablet mass and hardness meet the approved standards, adjusting the filling depth and compression force accordingly. Pre-compression force may be included to avoid capping.

[0243] (Example 2A) Cannabinoid sources An intraoral disc containing 150 mg was prepared using a second layer of 85 mg and a first layer of 65 mg, respectively. The intraoral disc was prepared according to Example 1.

[0244] Punch used: 8.00mm, circular, convex dimple, D-tooling.

[0245] The second layer is compressed with a compressive force of approximately 1 to 5 kN, and then the first layer is fused with the second layer by further compression with a compressive force of approximately 8 to 15 kN.

[0246] [Table 1]

[0247] For all samples, cannabinoids were applied using a premix of cannabinoids and mannitol.

[0248] Preferred high-strength sweeteners (HIS) may include, for example, sucralose, acesulfame potassium, and mixtures thereof.

[0249] The above-mentioned MgSt (magnesium stearate) was used as a lubricant. Other lubricants, such as sodium stearyl fumarate, may also be used within the scope of this invention.

[0250] (Example 2B) Modified forms of binders An intraoral disc containing 150 mg was prepared using a second layer of 85 mg and a first layer of 65 mg, respectively. The intraoral disc was prepared according to Example 1.

[0251] Punch used: 8.00mm, circular, convex dimple, D-tooling.

[0252] The second layer is compressed with a compressive force of approximately 1 to 5 kN, and then the first layer is fused with the second layer by further compression with a compressive force of approximately 8 to 15 kN.

[0253] [Table 2]

[0254] (Example 2C) Modified forms of binders An intraoral disc containing 150 mg was prepared using a second layer of 85 mg and a first layer of 65 mg, respectively. The intraoral disc was prepared according to Example 1.

[0255] Punch used: 8.00mm, circular, convex dimple, D-tooling.

[0256] The second layer is compressed with a compressive force of approximately 1 to 5 kN, and then the first layer is fused with the second layer by further compression with a compressive force of approximately 8 to 15 kN.

[0257] [Table 3]

[0258] (Example 2D) Variant forms of sugar alcohols A 300 mg intraoral disc was prepared using a 200 mg second layer and a 100 mg first layer. The intraoral disc was prepared according to Example 1.

[0259] Punch used: 12.00mm, circular, shallow concave, B tooling.

[0260] The second layer is compressed with a compressive force of approximately 3-8 kN, and then the first layer is fused with the second layer by compression with a compressive force of approximately 20-30 kN.

[0261] [Table 4]

[0262] (Example 2E) Modified forms of mucosal adhesive substances A 150 mg intraoral disc was prepared using a second layer of 75 mg and a first layer of 75 mg, respectively. The intraoral disc was prepared according to Example 1.

[0263] Punch used: 8.00mm, circular, convex dimple, D-tooling.

[0264] The second layer is compressed with a compressive force of approximately 1 to 5 kN, and then the first layer is fused with the second layer by further compression with a compressive force of approximately 8 to 15 kN.

[0265] [Table 5]

[0266] (Example 2F) Modified forms of binders An intraoral disc containing 150 mg was prepared using a second layer of 85 mg and a first layer of 65 mg, respectively. The intraoral disc was prepared according to Example 1.

[0267] Punch used: 8.00mm, circular, convex dimple, D-tooling.

[0268] The second layer is compressed with a compressive force of approximately 1 to 5 kN, and then the first layer is fused with the second layer by further compression with a compressive force of approximately 8 to 15 kN.

[0269] [Table 6]

[0270] (Example 2H) Addition of filler A 400 mg intraoral disc was prepared using a 300 mg second layer and a 100 mg first layer. The intraoral disc was prepared according to Example 1.

[0271] Punch used: 12.00mm, circular, shallow concave, B tooling.

[0272] Compress the second layer with a compressive force of about 3 - 8 kN, and then fuse the first layer with the second layer by compression with a compressive force of about 20 - 30 kN.

[0273]

Table 7

[0274] In Table 5A (Table 7), sucralose was used as a high-intensity sweetener. The flavoring agent can be, for example, a combination of peppermint and menthol.

[0275] (Example 2I) A 300 mg one-layer oral disk. The oral disk was prepared according to Example 1A.

[0276] Punch used: 12.00 mm, circular, shallow concave, B tooling.

[0277] Compress the oral disk with a compressive force of about 20 - 40 kN.

[0278]

Table 8

[0279] In Table 5B (Table 8), sucralose was used as a high-intensity sweetener. The flavoring agent can be, for example, a combination of peppermint and menthol.

[0280] (Example 2J) A 270 mg oral disk was made with a 70 mg first layer and a 200 mg second layer respectively. The oral disk was prepared according to Example 1.

[0281] Punch used: 8.00 mm, circular, convex dimple, D tooling.

[0282] Compress the second layer with a compressive force of about 3 - 8 kN, and then fuse the first layer with the second layer by compression with a compressive force of about 20 - 30 kN.

[0283] [Table 9]

[0284] In Table 5C (Table 9), sucralose was used as a high-strength sweetener. The flavoring could be, for example, a combination of peppermint and menthol.

[0285] (Example 2K) Intraoral discs of various sizes were prepared according to Example 1B.

[0286] Punch used for samples CD37-CD42: 12.00 mm, circular, shallow concave, B tooling.

[0287] Punch used for sample CD43: 10.00 mm, circular, convex dimple.

[0288] The first layer is compressed with a compressive force of approximately 1 to 6 kN, and then the second layer is fused with the first layer by compressing it with a compressive force of approximately 2 to 8 kN. Next, the third layer is fused with the second layer by compressing it with a compressive force of approximately 20 to 40 kN.

[0289] [Table 10]

[0290] In Table 5D (Table 10), sucralose was used as a high-strength sweetener. The flavoring could be, for example, a combination of peppermint and menthol.

[0291] Please note that Pearlitol Flash is a commercially available, ready-to-use system containing mannitol and starch in a mass ratio of approximately 4:1 of mannitol to starch.

[0292] (Example 2L) A 500 mg oral disk was prepared with a 100 mg first layer, a 300 mg second layer, and a 100 mg third layer. The oral disk was prepared according to Example 1B.

[0293] Punch used: 12.00 mm, circular, shallow concave, B tooling.

[0294] The first layer is compressed with a compression force of about 1 - 6 kN, and then the second layer is fused to the first layer by compression with a compression force of about 2 - 8 kN. Next, the third layer is fused to the second layer by compression with a compression force of about 20 - 40 kN.

[0295]

Table 11

[0296] In Table 5E (Table 11), sucralose was used as the high-intensity sweetener. The flavoring agent can be, for example, a combination of peppermint and menthol.

[0297] (Example 2M) A 500 mg oral disk was prepared with a 100 mg first layer, a 300 mg second layer, and a 100 mg third layer. The oral disk was prepared according to Example 1B.

[0298] Punch used: 12.00 mm, circular, shallow concave, B tooling.

[0299] The first layer is compressed with a compression force of about 1 - 6 kN, and then the second layer is fused to the first layer by compression with a compression force of about 2 - 8 kN. Next, the third layer is fused to the second layer by compression with a compression force of about 20 - 40 kN.

[0300]

Table 12

[0301] In Table 5F (Table 12), sucralose was used as a high-strength sweetener. The flavoring could be, for example, a combination of peppermint and menthol.

[0302] (Example 2N) An intraoral disc was prepared with a first layer of 70 mg and a second layer of 200 mg, totaling 270 mg. The intraoral disc was prepared according to Example 1.

[0303] Punch used: 12.00mm, circular, shallow concave, B tooling.

[0304] The second layer is compressed with a compressive force of approximately 3-8 kN, and then the first layer is fused with the second layer by compression with a compressive force of approximately 20-30 kN.

[0305] [Table 13]

[0306] In Table 5G (Table 13), sucralose was used as a high-strength sweetener. The flavoring could be, for example, a combination of peppermint and menthol. Other organic acids, such as malic acid, may be used instead of citric acid.

[0307] (Example 20) A 300 mg single-layer oral disc. Tablets were prepared according to Example 1A.

[0308] Punch used: 12.00mm, circular, shallow concave, B tooling.

[0309] The intraoral disc is compressed with a compressive force of approximately 20-40 kN.

[0310] [Table 14]

[0311] In Table 5H (Table 14), sucralose was used as a high-strength sweetener. The flavoring could be, for example, peppermint.

[0312] (Example 2P) A 400 mg intraoral disc was prepared using a 300 mg second layer and a 100 mg first layer. The intraoral disc was prepared according to Example 1.

[0313] Punch used: 12.00mm, circular, shallow concave, B tooling.

[0314] The second layer is compressed with a compressive force of approximately 3-8 kN, and then the first layer is fused with the second layer by compression with a compressive force of approximately 20-30 kN.

[0315] [Table 15]

[0316] In Table 5I (Table 15), sucralose was used as a high-strength sweetener. The flavoring could be, for example, peppermint.

[0317] (Example 3) Evaluation of intraoral discs A team of seven trained evaluators was used for the evaluation. Each evaluator repeated the evaluation twice.

[0318] Trained evaluators refrained from eating or drinking at least 30 minutes before the start of any test. Each trained evaluator was a healthy individual selected based on objective evidence according to specific requirements.

[0319] For the test, an intraoral disc was weighed and placed between the upper lip and gums of the mouth, with the first layer, i.e., the mucosal adhesive layer, facing the gums. At specific time points, e.g., 15, 30, and 60 minutes, the cannabinoid content in the intraoral disc residue was measured if still present. Once the desired test time was achieved, the intraoral disc was removed and weighed directly into a measuring cup used for cannabinoid content analysis. After extraction into the relevant buffer, the cannabinoid content was analyzed by standard HPLC techniques.

[0320] In some cases, the oral discs were evaluated during the test in terms of texture, flavor, and other sensory parameters.

[0321] If the dissolution of the oral disc was substantially completed before reaching a specific point in time, the dissolution time was registered as the in vivo dissolution time of the oral disc.

[0322] The evaluated intraoral disc was found to be a highly suitable delivery vehicle for cannabinoids, providing a remarkably sustained release of cannabinoids while delivering the desired texture and flavor profile.

[0323] (Example 4) Modification forms in sugar alcohols An intraoral disc was prepared according to Example 1.

[0324] Punch used: 12.00mm, circular, shallow concave, B tooling.

[0325] The second layer is compressed with a compressive force of approximately 3-8 kN, and then the first layer is fused with the second layer by compression with a compressive force of approximately 20-30 kN.

[0326] [Table 16]

[0327] (Example 5) In vivo dissolution time The in vivo dissolution time of the intraoral disc (measured according to Example 3) was tested and is shown in Table 7 (Table 17) below.

[0328] [Table 17]

[0329] As can be seen from Table 7 (Table 17), the dissolution time of the intraoral discs could be significantly varied, and the presence of a binder resulted in a longer dissolution time compared to intraoral discs without a binder.

[0330] (Example 6) Intraoral disc composition An intraoral disc containing 150 mg was prepared using a second layer of 85 mg and a first layer of 65 mg, respectively. The intraoral disc was prepared according to Example 1.

[0331] Punch used: 8.00mm, circular, convex dimple, D-tooling.

[0332] The second layer is compressed with a compressive force of approximately 1 to 5 kN, and then the first layer is fused with the second layer by further compression with a compressive force of approximately 8 to 15 kN.

[0333] [Table 18]

[0334] For all samples, cannabinoids were applied using a premix of cannabinoids and mannitol.

[0335] Preferred high-strength sweeteners (HIS) may include, for example, sucralose, acesulfame potassium, and mixtures thereof.

[0336] The above-mentioned MgSt (magnesium stearate) was used as a lubricant. Other lubricants, such as sodium stearyl fumarate, may also be used within the scope of this invention.

[0337] (Example 7) In vivo dissolution time The dissolution time of the oral disc was tested according to Example 3.

[0338] The dissolution times of the selected intraoral discs were tested and are shown in Table 9 (Table 19) below.

[0339] [Table 19]

[0340] (Example 8) In vivo dissolution time The in vivo dissolution times of the selected tablets (measured according to Example 3) were tested and are shown in Table 10 (Table 20) below.

[0341] [Table 20]

[0342] As can be seen from Table 10 (Table 20), the dissolution time of the tablets can be gradually varied by adjusting the amount of binder, for example, between 0 and 10% for CA37-CA39 and between 5 and 10% for CB38-CB39.

[0343] (Example 9) Evaluation of adhesiveness Tablets CA40 to CA42 were evaluated by a team of evaluators on a scale of 0 to 12 regarding perceived stickiness, according to Example 3. The results are shown in Table 11 (Table 21) below.

[0344] [Table 21]

[0345] As shown in Table 11 (Table 21), the tackiness is gradually improved by increasing the amount of natural gum mucosal adhesive material in the first layer.

Claims

1. An adhesive oral disc for sustained release of cannabinoids, comprising one or more cannabinoids, and at least, A mucosal contact layer having a mucosal contact surface that can be used to fix to the gingiva of a person requiring relief or treatment of a medical condition, comprising one or more mucosal adhesive polymers that enable the adhesive intraoral disc to adhere to the gingiva for an extended period of time; and A non-mucosal adhesive module fused with the mucosal contact layer, comprising a solid tablet composition that enables the non-mucosal adhesive module to dissolve for a long period of time when the adhesive intraoral disc adheres to the gingiva. An adhesive intraoral disc composed of the following materials.

2. The adhesive intraoral disc according to claim 1, wherein the solid tablet composition comprises one or more other binders, for example, one or more other cellulose derivative binders.

3. The adhesive intraoral disc according to claim 1 or 2, wherein the solid tablet composition comprises one or more other binders in an amount of 1 to 15% by mass of the non-mucosal adhesive module.

4. The adhesive intraoral disc according to any one of claims 1 to 3, wherein the solid tablet composition comprises one or more other binders in an amount of 2 to 10% by mass of the non-mucosal adhesive module.

5. The adhesive intraoral disc according to any one of claims 1 to 4, wherein the solid tablet composition comprises one or more other binders in an amount of 4 to 8% by mass of the non-mucosal adhesive module.

6. The adhesive intraoral disc according to any one of claims 1 to 5, wherein the solid tablet composition comprises one or more other binders selected from the group consisting of cellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, and any combination thereof.

7. The adhesive intraoral disc according to any one of claims 1 to 6, wherein the solid tablet composition comprises one or more other cellulose derivative binders selected from the group consisting of carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, and any combination thereof.

8. The adhesive intraoral disc according to any one of claims 1 to 7, wherein the solid tablet composition comprises one or more other binders selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, and any combination thereof.

9. The adhesive oral disc according to any one of claims 1 to 8, wherein the solid tablet composition comprises hydroxypropyl cellulose.

10. The adhesive oral disc according to any one of claims 1 to 8, wherein the solid tablet composition comprises hydroxypropyl methylcellulose.

11. The adhesive oral disc according to any one of claims 1 to 10, wherein the solid tablet composition comprises one or more sugar alcohol particles.

12. The adhesive intraoral disc according to any one of claims 1 to 11, wherein the solid tablet composition comprises one or more sugar alcohol particles in an amount of at least 40% by mass of the non-mucosal adhesive module.

13. The adhesive intraoral disc according to any one of claims 1 to 12, wherein the solid tablet composition comprises one or more sugar alcohol particles in an amount of at least 60% by mass of the non-mucosal adhesive module.

14. The adhesive intraoral disc according to any one of claims 1 to 13, wherein the solid tablet composition comprises one or more sugar alcohol particles in an amount of at least 80% by mass of the non-mucosal adhesive module.

15. The adhesive oral disc according to any one of claims 1 to 14, wherein the solid tablet composition comprises one or more sugar alcohol particles selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof.

16. The adhesive oral disc according to any one of claims 1 to 15, wherein the solid tablet composition does not contain a flavoring agent.

17. The adhesive oral disc according to any one of claims 1 to 16, wherein the solid tablet does not contain edible alcohol, for example, the non-mucosal adhesive module does not contain edible alcohol.

18. The adhesive oral disc according to any one of claims 1 to 17, wherein the solid tablet composition comprises one or more cannabinoids.

19. The adhesive oral disc according to any one of claims 1 to 18, wherein the solid tablet composition comprises one or more cannabinoids in an amount of 1 to 100 mg.

20. The adhesive oral disc according to any one of claims 1 to 19, wherein the solid tablet composition contains one or more cannabinoids in an amount of 2 to 50 mg.

21. The adhesive oral disc according to any one of claims 1 to 20, wherein the solid tablet composition contains one or more cannabinoids in an amount of 10 to 20 mg.

22. The adhesive intraoral disc according to any one of claims 1 to 21, wherein one or more of the mucosal adhesive polymers are present in an amount of at least 20% by mass of the mucosal contact layer.

23. The adhesive intraoral disc according to any one of claims 1 to 22, wherein one or more of the mucosal adhesive polymers are present in an amount of at least 40% by mass of the mucosal contact layer.

24. The adhesive intraoral disc according to any one of claims 1 to 23, wherein one or more of the mucosal adhesive polymers are present in an amount of at least 60% by mass of the mucosal contact layer.

25. The adhesive intraoral disc according to any one of claims 1 to 24, wherein the one or more mucosal adhesive polymers are further present in the non-mucosal adhesive module in an amount of less than 20% by mass of the non-mucosal adhesive module.

26. The adhesive intraoral disc according to any one of claims 1 to 25, wherein the one or more mucosal adhesive polymers are further present in the non-mucosal adhesive module in an amount of less than 15% by mass of the non-mucosal adhesive module.

27. The adhesive intraoral disc according to any one of claims 1 to 26, wherein the one or more mucosal adhesive polymers are further present in the non-mucosal adhesive module in an amount of less than 5% by mass of the non-mucosal adhesive module.

28. The adhesive intraoral disc according to any one of claims 1 to 27, wherein the one or more mucosal adhesive polymers are not present in the non-mucosal adhesive module.

29. The adhesive intraoral disc according to any one of claims 1 to 28, wherein the one or more mucosal adhesive polymers are selected from the group consisting of xanthan gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, alginic acid, alginate, pullulan, tragacanth gum, karaya gum, fenugreek gum, cassia gum, carrageenan, agar, pectin, dextran, guar gum, polyvinylpyrrolidone (PVP), gelatin, casein, acrylic acid polymer (carbomer), acrylic acid ester, acrylic acid copolymer, and any combination thereof.

30. The adhesive intraoral disc according to any one of claims 1 to 29, wherein the one or more mucosal adhesive polymers include hydrophilic polymers selected from the group consisting of polyvinylpyrrolidone (PVP), acrylic acid polymers (carbomers), crosslinked polyacrylic acid copolymers with divinyl glycol and its salts (polycarbophils), poly(methyl vinyl ether / maleic acid) monoalkyl ester copolymers (Gantrez polymers), acrylic acid esters, acrylic acid copolymers, and any combination thereof.

31. The adhesive intraoral disc according to any one of claims 1 to 30, wherein the one or more mucosal adhesive polymers comprises polyvinylpyrrolidone (PVP).

32. The adhesive intraoral disc according to any one of claims 1 to 31, wherein the one or more mucosal adhesive polymers comprises polyvinylpyrrolidone (PVP) in combination with one of the following: an acrylic acid polymer (carbomer), a polyacrylic acid copolymer (polycarbophil) crosslinked with divinyl glycol and its salts, a poly(methyl vinyl ether / maleic acid) monoalkyl ester copolymer (Gantrez polymer), an acrylic acid ester, or an acrylic acid copolymer.

33. The adhesive intraoral disc according to any one of claims 1 to 32, wherein the one or more mucosal adhesive polymers include an ionic mucosal adhesive substance.

34. The adhesive intraoral disc according to any one of claims 1 to 33, wherein the one or more mucosal adhesive polymers comprises a mucosal adhesive substance selected from the group consisting of xanthan gum, gellan gum, gum arabic, alginic acid, alginate, carrageenan, agar, and any combination thereof.

35. The adhesive oral disc according to any one of claims 1 to 34, wherein the one or more mucosal adhesive polymers comprises xanthan gum and / or gum arabic.

36. The adhesive oral disc according to any one of claims 1 to 35, wherein the one or more mucosal adhesive polymers include gum arabic.

37. The adhesive intraoral disc according to any one of claims 1 to 36, wherein the one or more mucosal adhesive polymers comprises xanthan gum.

38. The adhesive intraoral disc according to any one of claims 1 to 37, wherein the one or more mucosal adhesive polymers comprises sodium alginate.

39. The adhesive intraoral disc according to any one of claims 1 to 38, wherein one or more of the mucosal adhesive polymers are added to the adhesive intraoral disc as another component.

40. The adhesive oral disc according to any one of claims 1 to 39, wherein the one or more mucosal adhesive polymers are added to the adhesive oral disc as another component from one or more cannabinoids.

41. The adhesive oral disc according to any one of claims 1 to 40, wherein the one or more cannabinoids are not bound to the one or more mucosal adhesive polymers in the adhesive oral disc.

42. The adhesive intraoral disc according to any one of claims 1 to 41, wherein the mucosal contact layer comprises one or more other binders.

43. The adhesive intraoral disc according to any one of claims 1 to 42, wherein the mucosal contact layer comprises one or more other cellulose derivative binders.

44. The adhesive intraoral disc according to any one of claims 1 to 43, wherein the mucosal contact layer comprises one or more other binders, each comprising one or more other cellulose derivative binders selected from the group consisting of hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose, ethyl cellulose (EC), carboxymethyl cellulose (CMC) and salts thereof, and any combination thereof.

45. The adhesive intraoral disc according to any one of claims 1 to 44, wherein the mucosal contact layer comprises one or more other binders selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, and any combination thereof.

46. The adhesive intraoral disc according to any one of claims 1 to 45, wherein the mucosal contact layer comprises one or more other binders including hydroxypropyl cellulose.

47. The adhesive intraoral disc according to any one of claims 1 to 46, wherein the mucosal contact layer comprises one or more other binders including hydroxypropyl methylcellulose.

48. The adhesive intraoral disc according to any one of claims 1 to 47, wherein the mucosal contact layer contains one or more other binders in an amount of 1 to 15% by mass of the mucosal contact layer.

49. The adhesive intraoral disc according to any one of claims 1 to 48, wherein the mucosal contact layer contains one or more other binders in an amount of 2 to 10% by mass of the mucosal contact layer.

50. The adhesive intraoral disc according to any one of claims 1 to 49, wherein the mucosal contact layer contains one or more other binders in an amount of 4 to 8% by mass of the mucosal contact layer.

51. The adhesive intraoral disc according to any one of claims 1 to 50, wherein the mucosal contact layer comprises one or more other binders selected from the group consisting of cellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, and any combination thereof.

52. The adhesive intraoral disc according to any one of claims 1 to 51, wherein the mucosal contact layer comprises one or more other cellulose derivative binders selected from the group consisting of carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, and any combination thereof.

53. The adhesive oral disc according to any one of claims 1 to 52, wherein the mucosal contact layer comprises one or more sugar alcohol particles.

54. The adhesive intraoral disc according to any one of claims 1 to 53, wherein the mucosal contact layer contains one or more sugar alcohol particles in an amount of 5 to 80% by mass of the mucosal contact layer.

55. The adhesive intraoral disc according to any one of claims 1 to 54, wherein the mucosal contact layer contains one or more sugar alcohol particles in an amount of 10 to 60% by mass of the mucosal contact layer.

56. The adhesive intraoral disc according to any one of claims 1 to 55, wherein the mucosal contact layer contains one or more sugar alcohol particles in an amount of 10 to 40% by mass of the mucosal contact layer.

57. The adhesive oral disc according to any one of claims 1 to 56, wherein the mucosal contact layer comprises one or more sugar alcohol particles selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any combination thereof.

58. The adhesive intraoral disc according to any one of claims 1 to 57, wherein the mucosal contact layer comprises a filler.

59. The adhesive intraoral disc according to any one of claims 1 to 58, wherein the mucosal contact layer comprises a filler selected from the group consisting of calcium carbonate, magnesium carbonate, magnesium hydroxide, and combinations thereof.

60. The adhesive intraoral disc according to any one of claims 1 to 59, wherein the mucosal contact layer does not contain a flavoring agent.

61. The adhesive intraoral disc according to any one of claims 1 to 60, wherein the mucosal contact layer comprises one or more cannabinoids.

62. The adhesive oral disc according to any one of claims 1 to 61, wherein the mucosal contact layer contains one or more cannabinoids in an amount of 1 to 100 mg.

63. The adhesive oral disc according to any one of claims 1 to 62, wherein the mucosal contact layer contains one or more cannabinoids in an amount of 2 to 50 mg.

64. The adhesive oral disc according to any one of claims 1 to 63, wherein the mucosal contact layer contains one or more cannabinoids in an amount of 5 to 30 mg.

65. The adhesive intraoral disc according to any one of claims 1 to 64, wherein the mucosal contact layer does not contain one or more cannabinoids.

66. The adhesive oral disc according to any one of claims 1 to 65, wherein the mucosal contact layer constitutes at least 10% by mass of the adhesive oral disc, for example, at least 20% by mass of the adhesive oral disc, for example, at least 30% by mass of the adhesive oral disc.

67. The adhesive intraoral disc according to any one of claims 1 to 66, wherein the non-mucosal adhesive module accounts for at least 40% by mass of the adhesive intraoral disc, for example, at least 50% by mass of the adhesive intraoral disc, for example, at least 60% by mass of the adhesive intraoral disc.

68. An adhesive intraoral disc according to any one of claims 1 to 67, having a mass of at least 100 mg, for example, at least 150 mg, for example, at least 200 mg.

69. An adhesive intraoral disc according to any one of claims 1 to 68, having a mass of 600 mg or less, for example, 500 mg or less, for example, 400 mg or less.

70. The adhesive intraoral disc according to any one of claims 1 to 69, wherein the mucosal contact layer is substantially flat.

71. The adhesive intraoral disc according to any one of claims 1 to 69, wherein the mucosal contact layer is concave, dimpled, or donut-shaped, or the mucosal contact surface of the mucosal contact layer includes one or more of these shapes.

72. The adhesive intraoral disc according to any one of claims 1 to 71, wherein the mucosal contact surface of the mucosal contact layer includes an inward-facing recess that enables the layer to be fixed to the gingiva as a first mechanism by a pressure difference.

73. The adhesive intraoral disc according to any one of claims 1 to 72, wherein the mucosal contact layer includes an inward-facing recess that enables the layer to be fixed to the gingiva as a first mechanism by a pressure difference.

74. The adhesive intraoral disc according to any one of claims 1 to 73, wherein the adhesive intraoral disc does not include a gel layer or a cast film strip layer.

75. The adhesive intraoral disc according to any one of claims 1 to 74, wherein the mucosal contact layer contains less than 10% by mass of water.

76. The adhesive intraoral disc according to any one of claims 1 to 75, wherein the mucosal contact layer is a compressed layer.

77. The adhesive intraoral disc according to any one of claims 1 to 76, wherein the non-mucosal adhesive module is a compressed module.

78. The adhesive intraoral disc according to any one of claims 1 to 77, wherein the mucosal contact layer and the non-mucosal adhesive module are fused by compression.

79. The adhesive intraoral disc according to any one of claims 1 to 78, wherein the non-mucosal adhesive module does not extend onto any side surface of the mucosal contact layer.

80. The adhesive intraoral disc according to any one of claims 1 to 79, wherein the non-mucosal adhesive module does not extend onto the side surface of the mucosal contact layer, thereby exposing a larger contact area to the oral mucosa compared to a configuration in which the non-mucosal adhesive module extends onto the side surface of the mucosal contact layer and only the bottom surface of the mucosal adhesive module is exposed to the oral mucosa at the time of administration.

81. An adhesive intraoral disc according to any one of claims 1 to 80, having a dissolution time of at least 15 minutes, for example, at least 20 minutes, for example, at least 30 minutes, for example, at least 45 minutes.

82. An adhesive intraoral disc according to any one of claims 1 to 81, having a dissolution time of 10 hours or less, for example 8 hours, for example 5 hours, for example 2.5 hours, for example 2 hours or less, for example 1.5 hours or less, for example 1 hour or less.

83. An adhesive intraoral disc according to any one of claims 1 to 82, having a dissolution time between 15 minutes and 2.5 hours, for example between 20 minutes and 1.5 hours, or for example between 30 minutes and 1 hour.

84. The adhesive intraoral disc according to any one of claims 1 to 83, wherein the dissolution time of the mucosal contact layer is substantially synchronized with the dissolution time of the non-mucosal adhesive module.

85. The adhesive intraoral disc according to any one of claims 1 to 84, wherein the long-term adhesion of the mucosal contact layer of the adhesive intraoral disc to the gingiva corresponds to the long-term dissolution of the non-mucosal adhesive module of the adhesive intraoral disc.

86. The adhesive oral disc according to any one of claims 1 to 85, wherein the one or more cannabinoids is selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), cannabiersoin (CBE), isotetrahydrocannabinol (iso-THC), cannabicyclol (CBL), cannabicitran (CBT), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabiclomevalin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), and combinations thereof.

87. The adhesive oral disc according to any one of claims 1 to 86, wherein the one or more cannabinoids are selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), and combinations thereof.

88. The adhesive oral disc according to any one of claims 1 to 87, wherein the one or more cannabinoids are selected from the group consisting of tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and combinations thereof.

89. The adhesive oral disc according to any one of claims 1 to 88, wherein the one or more cannabinoids comprises cannabidiol (CBD).

90. The adhesive oral disc according to any one of claims 1 to 89, wherein the one or more cannabinoids comprises isolated cannabinoids.

91. The adhesive oral disc according to any one of claims 1 to 90, wherein the one or more cannabinoids are isolated cannabinoids.

92. The adhesive oral disc according to any one of claims 1 to 91, wherein the one or more cannabinoids are synthetic cannabinoids.

93. The adhesive oral disc according to any one of claims 1 to 92, wherein the one or more cannabinoids are not a cannabinoid extract having a cannabinoid purity of less than 80%.

94. The adhesive oral disc according to any one of claims 1 to 93, wherein the one or more cannabinoids are present as particles with a size of 400 to 1200 nanometers.

95. The adhesive oral disc according to any one of claims 1 to 94, wherein the one or more cannabinoids are present as particles with a size of 500 to 1000 nanometers.

96. The adhesive oral disc according to any one of claims 1 to 95, wherein one or more of the cannabinoids are present in the mucosal contact layer.

97. The adhesive intraoral disc according to any one of claims 1 to 96, wherein one or more of the cannabinoids are present in the non-mucosal adhesive module.

98. The adhesive intraoral disc according to any one of claims 1 to 97, wherein one or more of the cannabinoids are present in both the mucosal contact layer and the non-mucosal adhesive module.

99. The adhesive intraoral disc according to any one of claims 1 to 98, wherein one or more of the aforementioned cannabinoids are not present in the mucosal contact layer.

100. The adhesive intraoral disc according to any one of claims 1 to 99, wherein the one or more of the cannabinoids are not present in the non-mucosal adhesive module.

101. An adhesive intraoral disc according to any one of claims 1 to 100, comprising one or more self-emulsifying systems.

102. An adhesive intraoral disc according to any one of claims 1 to 101, comprising one or more liquid self-emulsifying systems.

103. An adhesive intraoral disc according to any one of claims 1 to 102, comprising one or more liquid self-emulsifying systems containing one or more surfactants.

104. An adhesive intraoral disc according to any one of claims 1 to 103, comprising one or more liquid self-emulsifying systems containing one or more surfactants having an HLB value greater than 6.

105. An adhesive oral disc according to any one of claims 1 to 104, comprising one or more liquid self-emulsifying systems comprising one or more surfactants selected from the group consisting of PEG-35 castor oil, PEG-6 oleoyl glyceride, PEG-6 linoleoyl glyceride, PEG-8 caprylic / capric acid glyceride, sorbitan monolaurate, sorbitan monooleate, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (60) sorbitan monostearate, polyoxyethylene (80) sorbitan monooleate, lauroyl polyoxyl-32 glyceride, stearoyl polyoxyl-32 glyceride, polyoxyl-32 stearate, propylene glycol monolaurate, propylene glycol dilaurate, and mixtures and combinations thereof.

106. An adhesive intraoral disc according to any one of claims 1 to 105, comprising one or more liquid self-emulsifying systems containing one or more cosolvents.

107. An adhesive oral disc according to any one of claims 1 to 106, comprising one or more liquid self-emulsifying systems comprising one or more cosolvents selected from the group consisting of polyglyceryl-3 dioleate, 1,2-propanediol, polyethylene glycol 300, polyethylene glycol 400, diethylene glycol monoethyl ether, and mixtures and combinations thereof.

108. An adhesive intraoral disc according to any one of claims 1 to 107, comprising one or more liquid self-emulsifying systems containing one or more solubilizing agents.

109. An adhesive intraoral disc according to any one of claims 1 to 108, comprising one or more liquid self-emulsifying systems comprising one or more solubilizers selected from the group consisting of lauroyl polyoxyl-32 glyceride; stearoyl polyoxyl-32 glyceride; polyoxyl-32 stearate; a synthetic copolymer of ethylene oxide (80) and propylene oxide (27); polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; alpha, beta, or gamma cyclodextrin and its derivatives; and pea proteins (globulin, albumin, glutelin proteins) and mixtures and combinations thereof.

110. The adhesive oral disc according to any one of claims 1 to 109, wherein one or more of the cannabinoids are bound to a cyclodextrin, such as a thiolated cyclodextrin.

111. An adhesive intraoral disc according to any one of claims 1 to 110, comprising one or more absorption enhancers.

112. The adhesive intraoral disc according to any one of claims 1 to 111, further comprising one or more alkaline pH adjusting agents, such as sodium carbonate or sodium bicarbonate.

113. An adhesive oral disc according to any one of claims 1 to 112, further comprising one or more active substances selected from the group consisting of chitosan, curcumin, propolis, hyaluronic acid, aloe vera, quercetin, and combinations thereof.

114. An adhesive intraoral disc according to any one of claims 1 to 113, comprising further modules / layers.

115. An adhesive intraoral disc according to any one of claims 1 to 114, comprising a second mucosal contact layer according to claims 1 to 113.

116. An adhesive oral disc according to any one of claims 1 to 113, further comprising an orally disintegrating tablet (ODT) module.

117. An adhesive intraoral disc according to any one of claims 1 to 113, comprising a further module / layer containing a disintegrant.

118. An adhesive intraoral disc according to any one of claims 1 to 117, for use in a method for treating or alleviating a medical condition.

119. An adhesive intraoral disc according to any one of claims 1 to 118, for use in a method for treating or alleviating ulcers.

120. An adhesive intraoral disc according to any one of claims 1 to 119, for use in a method for treating or alleviating an oral disorder.

121. An adhesive oral disc for sustained release of cannabinoids, comprising one or more cannabinoids, and at least, A mucosal contact layer having a mucosal contact surface that can be used to fix to the gingiva of a person requiring relief or treatment of a medical condition, comprising one or more mucosal adhesive polymers that enable the adhesive intraoral disc to adhere to the gingiva for an extended period of time; and A non-mucosal-adherent module fused with the mucosal contact layer, comprising a solid tablet composition containing one or more binders that enable the non-mucosal-adherent module to dissolve for a long period of time when the adhesive intraoral disc adheres to the gingiva. An adhesive intraoral disc composed of the following materials.

122. The adhesive intraoral disc according to claim 121, as further defined by any one of claims 1 to 120.

123. One or more cannabinoids; At least 40% by mass of the adhesive oral disc, one or more sugar alcohol particles: One or more mucosal adhesive polymers in an amount of at least 5% by mass of the adhesive intraoral disc, which enable the adhesive intraoral disc to adhere to the gums of a person requiring relief or treatment of a medical condition for an extended period of time. Adhesive oral discs for sustained release of cannabinoids, including those containing cannabinoids.

124. The adhesive intraoral disc according to claim 123, further defined by any one of claims 1 to 120.

125. An adhesive oral disc for sustained release of cannabinoids, comprising one or more cannabinoids, and at least, A mucosal contact layer having a mucosal contact surface that can be used to fix to the gingiva of a person requiring relief or treatment of a medical condition, comprising one or more mucosal adhesive polymers that enable the adhesive intraoral disc to adhere to the gingiva for an extended period of time; and A non-mucosal-adherent module fused with the mucosal contact layer, which does not contain a mucosal-adherent polymer and includes a solid tablet composition that allows the non-mucosal-adherent module to dissolve for a long period of time when the adhesive intraoral disc adheres to the gingiva. An adhesive intraoral disc composed of the following materials.

126. The adhesive intraoral disc according to claim 125, as further defined by any one of claims 1 to 120.

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