Autoemulsification system for cannabinoids

Abstract

The present invention relates to an orally soluble or chewable tablet powder formulation. The formulation comprises one or more carrier systems containing one or more liquid or solid self-emulsifying systems, each containing at least 10% by mass of cannabinoids of the tablet powder formulation, wherein the one or more self-emulsifying systems include, i) if the self-emulsifying system is a liquid self-emulsifying system, at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, and ii) if the self-emulsifying system is a solid self-emulsifying system, at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids. The formulation further comprises one or more water-soluble agents and one or more flavoring agents in an amount of 20 to 80% by mass of the tablet powder formulation. The one or more surfactants include one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety.

Description

Technical Field

[0001] The present invention relates to the field of cannabinoids. In particular, the present invention relates to self-emulsifying systems for cannabinoids, for example, self-emulsifying systems containing surfactants having polyethylene glycol moieties.

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). Also, these chemical substances are endogenously produced in humans and other animals. Cannabinoids are cyclic molecules exhibiting certain properties such as being lipophilic, having the ability to easily cross the blood-brain barrier, and having low toxicity.

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

[0004] Gastrointestinal delivery of cannabinoids may offer some advantages over oral mucosal uptake, particularly regarding cannabinoid uptake in the small or colon of the gastrointestinal tract, including both short-term and long-term uptake. However, certain difficulties arise when cannabinoids are intended to be delivered orally as part of a powder formulation, such as a chewable tablet, but also to the mucosal surface of the gastrointestinal tract to gain the benefits of improved uptake. Considering the ability to tolerate the low pH of the stomach, or various chemical or physical difficulties, it can be implied that powder formulations may be problematic as a delivery platform for cannabinoids intended for gastrointestinal uptake. In addition, considering these circumstances, obtaining suitable uptake in the gastrointestinal tract may be problematic.

[0005] Specifically, certain systems for cannabinoid gastrointestinal delivery may be highly degraded, and therefore expected to result in less uptake in the gastrointestinal tract, such as the colon. Other systems for cannabinoid gastrointestinal delivery may be sterically impaired, leading to less cellular uptake, and thus less uptake in the gastrointestinal tract, such as the small intestine.

[0006] Oral administration of cannabinoids is a common route of administration, but prior art has not paid much attention to carrier systems that could enable the delivery of high doses of cannabinoids to patients who require them. In particular, little attention has been paid to carrier systems for cannabinoids that would allow for high concentrations of cannabinoids while simultaneously providing convenience during oral administration. Typically, carrier systems can be expected to provide an unpleasant mouthfeel in oral formulations that are intended to dissolve or disintegrate in the mouth.

[0007] Special difficulties arise when a carrier system is intended to be released in the oral cavity, for example, when the oral application form is partially dissolved or partially disintegrated in the oral cavity, but the carrier system containing cannabinoids is intended to be delivered into the gastrointestinal tract for cannabinoid absorption. Under these circumstances, it may be important to provide a special carrier system that can allow cannabinoids to remain contained in the carrier for a relatively long period of time in order for the carrier system to be delivered into the gastrointestinal tract with a high concentration of cannabinoids.

[0008] In addition, little attention has been paid to the administration of high doses of cannabinoids and the associated mouthfeel during or after the partial dissolution or partial disintegration of the application form in the oral cavity. Typically, if a carrier system is present, the carrier system itself may be expected to have an undesirable mouthfeel, such as a gritty texture or even a grinding sound, when chewing an application form that contains the carrier system as its contents.

[0009] High concentrations of cannabinoids should be present, and therefore, when high concentrations of carrier systems are present in the formulation, difficulties with the carrier system can be particularly problematic. At the same time, homogeneity and / or release of cannabinoids in the application form is important, and homogeneity and / or release can be difficult in some cases when cannabinoids are applied in a carrier system.

[0010] Furthermore, it is desirable to provide formulations that can also help improve the sensory characteristics of oral cannabinoid delivery. Here, important sensory characteristics include texture, flavor perception, sweetness perception, and off-flavor (off-note) associated with cannabinoids. These characteristics are relevant in terms of convenience in solid dosage forms, and of course, in supporting proper delivery of cannabinoids from tablets and avoiding harmful side effects of cannabinoids.

[0011] Therefore, there is a need in the prior art for powders and formulations that solve the difficulties and problems of the prior art mentioned above. In particular, there is a need in the prior art for powders that can be applied in various forms of administration, such as tablets, pouches, chewing gum, and lozenges, which are associated with suitable homogeneity of cannabinoids as contents and provide suitable sensory properties.

[0012] In particular, it is desirable that these formulations are acceptable or improved in terms of taste masking, and that they provide the desired release of the carrier system in the oral cavity and the desired release of cannabinoids for gastrointestinal absorption.

[0013] Finally, there is a need in the prior art for a system that can promote increased cannabinoid uptake in the gastrointestinal tract, such as the small intestine or colon. At the same time, there is a need for a system that provides suitable stability for cannabinoids, for example, when cannabinoid uptake is expected to occur in the small intestine or colon. [Prior art documents] [Non-patent literature]

[0014] [Non-Patent Document 1] European Pharmacopoeia 9.1 [Non-Patent Document 2] 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 3] A. Douglas Kinghorn et al., Phytocannabinoids, Vol. 103, Chapter 1, pp. 1-30. [Non-Patent Document 4] European Pharmacopoeia 10.8 [Overview of the project] [Means for solving the problem]

[0015] Accordingly, an orally soluble or chewable tablet powder formulation is provided, comprising one or more carrier systems containing one or more liquid or solid self-emulsifying systems, each containing at least 10% by mass of cannabinoids of the tablet powder formulation, wherein the one or more self-emulsifying systems include, i) if the self-emulsifying system is a liquid self-emulsifying system, at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, and ii) if the self-emulsifying system is a solid self-emulsifying system, at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, and the powder formulation further comprises 20 to 80% by mass of one or more water-soluble agents and one or more flavoring agents of the tablet powder formulation.

[0016] Furthermore, the oral-soluble or chewable tablet powder formulation comprises one or more carrier systems containing one or more liquid or solid self-emulsifying systems, each containing at least 10% by mass of cannabinoids in the tablet powder formulation, wherein the one or more self-emulsifying systems include, i) if the self-emulsifying system is a liquid self-emulsifying system, at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, and ii) if the self-emulsifying system is a solid self-emulsifying system, at least one or more An orally soluble or chewable tablet powder formulation is provided, comprising several surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, wherein the powder formulation further comprises one or more water-soluble agents in an amount of 20-80% by mass of the tablet powder formulation, and one or more flavoring agents, wherein the one or more self-emulsifying systems are stable at a pH of about 1-4, and when one or more carrier systems are released in the oral cavity, they are activatable for the gastrointestinal delivery of one or more cannabinoids.

[0017] In some embodiments of the present invention, one or more self-emulsifying systems are stable at a pH of about 1 to 4.

[0018] In some embodiments of the present invention, one or more self-emulsifying systems are operable for gastrointestinal delivery of one or more cannabinoids when one or more carrier systems are released in the oral cavity.

[0019] In some embodiments of the present invention, one or more self-emulsifying systems are stable at a pH of about 1 to 4 and are operable for gastrointestinal delivery of one or more cannabinoids when one or more carrier systems are released in the oral cavity.

[0020] One advantage of the present invention is that a carrier system is provided that can allow a cannabinoid to be contained in the carrier for a relatively long time because the carrier system is delivered into the gastrointestinal tract at a relatively high concentration.

[0021] In addition, it has been found that the carrier system can withstand such conditions without being critically affected by gastric conditions such as low pH values and enables effective delivery of cannabinoids in the gastrointestinal tract such as the intestine.

[0022] In accordance with the present invention, it was not expected that a high-concentration cannabinoid could be obtained without the difficulties disclosed in the prior art and that at the same time a tablet powder formulation could function to deliver the cannabinoid to the gastrointestinal target. A high-concentration cannabinoid should be present, and thus, when a high-concentration carrier system is present in the formulation, the difficulties of the carrier system are particularly problematic.

[0023] A particular advantage of the present invention is that the system is suitable for subsequent delivery of the carrier system in the gastrointestinal tract for release of the carrier system in the oral cavity and absorption of the cannabinoid, especially when the oral application form is partially dissolved or partially disintegrated in the oral cavity. Under these circumstances, it has been found that the carrier system can allow the cannabinoid to be contained in the carrier for a relatively long time because the carrier system is delivered into the gastrointestinal tract with a high-concentration cannabinoid.

[0024] At the same time, the homogeneity of the cannabinoids in the application form is important, and homogeneity can be difficult in some cases when the cannabinoids are applied in the carrier system. These difficulties can also be overcome by the present invention. Thus, fluctuations can be avoided and a safe and convenient delivery can be obtained.

[0025] Furthermore, there is provided a formulation that can also help in improving the sensory properties of oral cannabinoid delivery. Here, the important sensory properties include texture, flavor perception, sweet taste perception, and off-flavors associated with cannabinoids. These properties are relevant from the perspective of convenience in solid dosage forms and, of course, to support proper delivery of cannabinoids from tablets and to avoid harmful side effects of cannabinoids.

[0026] Another difficulty is that cannabinoids tend to be accompanied by off-flavors when delivered in the oral cavity due to certain physicochemical properties of the compounds. Since the cannabinoids can be contained in the carrier according to the present invention, this off-flavor difficulty is not so predominant during administration according to the present invention.

[0027] In some embodiments of the present invention, the one or more surfactants include one or more surfactants having a chemical structure containing a polyethylene glycol (PEG) moiety. In this context, a "moiety" is what is normally understood in organic chemistry, that is, the polyethylene glycol moiety is a part of the molecule and can be identified as the polyethylene glycol moiety within the molecule. This may be present as the tail of the surfactant, or as a side chain group of the surfactant, or as a part of the chain within the surfactant, etc. In this context, the "polyethylene glycol moiety" specifically does not refer to free polyethylene glycol.

[0028] One of the advantages of including one or more surfactants having a chemical structure containing a polyethylene glycol (PEG) moiety as a self-emulsifying system according to the present invention is that the in vivo uptake of cannabinoids was found to be remarkably increased. This was highly unexpected, as it was theoretically predicted that a high content of PEG in the surfactant would result in less cellular uptake due to the expected high steric hindrance of surfactants containing the PEG moiety. However, the exact opposite was observed, which was a great surprise to the inventors.

[0029] Specifically, when applied in an in vivo test setting in rats, the cannabinoid plasma concentration was significantly higher initially as a function of time compared to a self-emulsifying system containing other surfactants, such as surfactants without a PEG portion. Therefore, the in vivo uptake of cannabinoids in rats by including a surfactant having a polyethylene glycol (PEG) portion as part of the self-emulsifying system according to the present invention was particularly remarkable on a short-term scale. Furthermore, the plasma concentration was significantly higher initially compared to Epidiolex®, a system containing a high content of sesame oil. Incidentally, high content of sesame oil is problematic due to its harmful laxative properties.

[0030] As used herein, the term "long-term scale" refers to more than 240 minutes after in vivo administration of cannabinoids in rats, and the term "short-term scale" refers to less than 240 minutes after in vivo administration of cannabinoids in rats. While not theoretically bound, the "short-term scale" may refer to uptake in the small intestine of rats, while the "long-term scale" may refer to uptake in the colon of rats.

[0031] However, by including one or more surfactants having a chemical structure containing a polyethylene glycol (PEG) moiety as part of the self-emulsifying system according to the present invention, not only was a remarkable initial uptake observed. Furthermore, total cannabinoid uptake was found to be high as a function of time, including relatively high uptake on long-term scales, indicated by high plasma concentrations of cannabinoids as a function of time. Compared to the baseline Epidiolex®, total cannabinoid uptake, including uptake on both short-term and long-term scales, was, on average, at the same level, and even higher.

[0032] Furthermore, the stability of the self-emulsifying system containing the PEG-containing surfactant stabilized the cannabinoid to a remarkably high degree, thereby limiting its degradation in the harsh environment of the gastrointestinal tract.

[0033] In some embodiments of the present invention, one or more surfactants having a chemical structure including a PEG portion are present in an amount of at least 20% by mass of one or more liquid or solid self-emulsifying systems.

[0034] In some embodiments of the present invention, one or more surfactants having a chemical structure including a PEG portion are present in an amount of at least 25% by mass of one or more liquid or solid self-emulsifying systems.

[0035] In some embodiments of the present invention, one or more surfactants having a chemical structure including a PEG portion are present in an amount of at least 30% by mass of one or more liquid or solid self-emulsifying systems.

[0036] In some embodiments of the present invention, one or more surfactants having a chemical structure including a PEG portion are present in an amount of at least 35% by mass of one or more liquid or solid self-emulsifying systems.

[0037] In some embodiments of the present invention, one or more surfactants having a chemical structure including a PEG portion are present in an amount of at least 40% by mass of one or more liquid or solid self-emulsifying systems.

[0038] In some embodiments of the present invention, one or more surfactants having a chemical structure including a PEG portion are present in an amount of at least 50% by mass of one or more liquid or solid self-emulsifying systems.

[0039] In some embodiments of the present invention, one or more surfactants having a chemical structure including a PEG portion are present in an amount of at least 60% by mass of one or more liquid or solid self-emulsifying systems.

[0040] In some embodiments of the present invention, one or more surfactants having a chemical structure including a PEG portion are present in an amount of 20 to 80% by mass of one or more liquid or solid self-emulsifying systems.

[0041] In some embodiments of the present invention, one or more surfactants having a chemical structure including a PEG portion are present in an amount of 25 to 75% by mass of one or more liquid or solid self-emulsifying systems.

[0042] In some embodiments of the present invention, one or more surfactants having a chemical structure including a PEG portion are present in an amount of 30 to 75% by mass of one or more liquid or solid self-emulsifying systems.

[0043] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in relatively high amounts relative to the mass of one or more liquid or solid self-emulsifying systems. This relatively high amount has been found to be preferable for balancing high uptake in terms of plasma concentration with the need for the self-emulsifying system to function optimally. In addition, the relatively high abundance of cannabinoids such as CBD in SEDDS may be important for limiting the SEDDS content in oral formulations.

[0044] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 15% by mass of one or more liquid or solid self-emulsifying systems.

[0045] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 20% by mass of one or more liquid or solid self-emulsifying systems.

[0046] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 25% by mass of one or more liquid or solid self-emulsifying systems.

[0047] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 30% by mass of one or more liquid or solid self-emulsifying systems.

[0048] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 35% by mass of one or more liquid or solid self-emulsifying systems.

[0049] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 40% by mass of one or more liquid or solid self-emulsifying systems.

[0050] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of 15 to 50% by mass of one or more liquid or solid self-emulsifying systems.

[0051] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of 20-40% by mass of one or more liquid or solid self-emulsifying systems.

[0052] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of 25-35% by mass of one or more liquid or solid self-emulsifying systems.

[0053] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of 10 to 30% by mass of the tablet powder formulation.

[0054] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of 10 to 20% by mass of the tablet powder formulation.

[0055] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 5% by mass of the tablet powder formulation.

[0056] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 10% by mass of the tablet powder formulation.

[0057] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 15% by mass of the tablet powder formulation.

[0058] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 20% by mass of the tablet powder formulation.

[0059] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 25% by mass of the tablet powder formulation.

[0060] In some embodiments of the present invention, one or more carrier systems are released in the oral cavity from an orally soluble or chewable tablet powder formulation.

[0061] In some embodiments of the present invention, at least 90% of one or more carrier systems are released from an orally soluble or chewable tablet powder formulation in the oral cavity within 5 minutes after oral administration.

[0062] In some embodiments of the present invention, up to 50% of one or more isolated or synthetic cannabinoids are released from one or more carrier systems 10 minutes after oral administration.

[0063] In some embodiments of the present invention, up to 20% of one or more isolated or synthetic cannabinoids are released from one or more carrier systems 10 minutes after oral administration.

[0064] In some embodiments of the present invention, the self-emulsifying system, when hydrated, forms an emulsion for the delivery of one or more cannabinoids to the mucosal surface within the gastrointestinal tract.

[0065] In some embodiments of the present invention, the self-emulsifying system, when hydrated, forms an emulsion for the delivery of one or more cannabinoids to the mucosal surface in the small intestine of the gastrointestinal tract.

[0066] In some embodiments of the present invention, the self-emulsifying system, when hydrated, forms an emulsion for the delivery of one or more cannabinoids to the mucosal surface within the colon of the gastrointestinal tract.

[0067] In some embodiments of the present invention, one or more carrier systems provide a stable state for the delivery of one or more cannabinoids to the mucosal surface in the gastrointestinal tract.

[0068] In some embodiments of the present invention, one or more self-emulsifying systems include one or more liquid self-emulsifying systems.

[0069] In some embodiments of the present invention, one or more lipids include one or more oils.

[0070] In some embodiments of the present invention, one or more lipids include one or more oils, including orange oil.

[0071] In some embodiments of the present invention, one or more lipids comprise one or more triglycerides.

[0072] In some embodiments of the present invention, one or more lipids comprise one or more triglycerides of plant origin.

[0073] In some embodiments of the present invention, one or more lipids include one or more oils selected from the group consisting of almond oil, castor oil, coconut oil, corn oil, cottonseed oil, flaxseed oil, olive oil, palm oil, peanut oil, rapeseed oil, safflower oil, sesame oil, soybean oil, sunflower oil, and combinations thereof.

[0074] In some embodiments of the present invention, one or more lipids comprise one or more triglycerides selected from one or more C4-C14 triglycerides.

[0075] In some embodiments of the present invention, one or more lipids comprise one or more triglycerides, including partially hydrogenated vegetable oil.

[0076] In some embodiments of the present invention, one or more lipids comprise one or more triglycerides, including fully hydrogenated vegetable oil.

[0077] In some embodiments of the present invention, one or more lipids comprise one or more triglycerides containing caprylic acid in an amount of 50 to 80% by mass.

[0078] In some embodiments of the present invention, one or more lipids comprise one or more triglycerides containing capric acid in an amount of 20 to 45% by mass.

[0079] In some embodiments of the present invention, one or more lipids do not contain flavoring oils.

[0080] In some embodiments of the present invention, one or more lipids include one or more lipophilic compounds selected from the group consisting of glyceryl caprylate, glyceryl caprate, glyceryl monocaprylate, glyceryl monooleate, glyceryl monostearate, glyceryl monolinoleate, polyglyceryl-3 dioleate, propylene glycol dicaprylate, propylene glycol dilaurate, benzyl alcohol, alpha-tocopherol, isopropyl myristate, glycerol monocaprylate, and combinations thereof.

[0081] In some embodiments of the present invention, one or more lipids include one or more lipophilic compounds selected from the group consisting of glyceryl caprylate (Type I) mixed with glyceryl caprate, glyceryl caprylate (Type II) mixed with glyceryl caprate, glyceryl monocaprylate (Type I), glyceryl monooleate (Type 40), glyceryl monooleate (Type 60), glyceryl monooleate (Type 90), glyceryl monostearate, glyceryl monolinoleate, polyglyceryl-3 dioleate, propylene glycol dicaprylate, propylene glycol dilaurate, benzyl alcohol, alpha-tocopherol, isopropyl myristate, glycerol monocaprylate, and combinations thereof.

[0082] In some embodiments of the present invention, one or more lipids comprise one or more lipophilic compounds having an HLB value of less than 6.

[0083] In some embodiments of the present invention, one or more lipids comprise one or more lipophilic compounds other than triglycerides.

[0084] In some embodiments of the present invention, one or more lipids are present in an amount of 1 to 30% by mass of the orally soluble or chewable tablet powder formulation.

[0085] In some embodiments of the present invention, one or more lipids are present in an amount of 5 to 30% by mass of the orally soluble or chewable tablet powder formulation.

[0086] In some embodiments of the present invention, one or more lipids are present in an amount of 10 to 30% by mass of the orally soluble or chewable tablet powder formulation.

[0087] In some embodiments of the present invention, one or more lipids are present in an amount of 5 to 40% by mass of one or more self-emulsifying systems.

[0088] In some embodiments of the present invention, one or more lipids are present in an amount of 10 to 40% by mass of one or more self-emulsifying systems.

[0089] In some embodiments of the present invention, one or more lipids improve the homogeneity of one or more cannabinoids in an orally soluble or chewable tablet powder formulation.

[0090] In some embodiments of the present invention, one or more lipids are present in an amount of 10 to 300 mg in an orally soluble or chewable tablet powder formulation.

[0091] In some embodiments of the present invention, one or more lipids are present in an amount of 50 to 300 mg in an orally soluble or chewable tablet powder formulation.

[0092] In some embodiments of the present invention, one or more self-emulsifying systems include one or more solid self-emulsifying systems.

[0093] In some embodiments of the present invention, one or more waxes comprise a substance that is solid and / or semi-solid at 25 degrees Celsius. In some embodiments, one or more waxes comprise a solid and / or semi-solid lipid.

[0094] Generally, the term "solid self-emulsifying system" is intended to mean a self-emulsifying system that is solid and / or semi-solid at 25 degrees Celsius, while the term "liquid self-emulsifying system" is intended to mean a self-emulsifying system that is liquid and / or semi-liquid at 25 degrees Celsius.

[0095] In some embodiments of the present invention, one or more waxes are present in an amount of 1 to 30% by mass of the orally soluble or chewable tablet powder formulation.

[0096] In some embodiments of the present invention, one or more waxes improve the homogeneity of one or more cannabinoids in an orally soluble or chewable tablet powder formulation.

[0097] In some embodiments of the present invention, one or more waxes are present in an amount of 10 to 300 mg in an orally soluble or chewable tablet powder formulation.

[0098] In some embodiments of the present invention, one or more waxes are present in an amount of 50 to 300 mg in an orally soluble or chewable tablet powder formulation.

[0099] In some embodiments of the present invention, one or more surfactants have an HLB value greater than 6.

[0100] In some embodiments of the present invention, the surfactant comprises one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, selected from the group consisting of PEG-modified glycosphingolipid-based surfactants, PEG-containing polymer-based surfactants, PEGylated emulsifiers, and combinations thereof.

[0101] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure containing a polyethylene glycol (PEG) moiety, which are PEG-modified glycosphingolipid-based surfactants selected from the group consisting of polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan trioleate, and combinations thereof.

[0102] In some embodiments of the present invention, one or more surfactants are PEG-containing polymer-based surfactants selected from the group consisting of poloxamer 124, poloxamer 188, poloxamer 338, poloxamer 407 and combinations thereof, and each surfactant has a chemical structure including a polyethylene glycol (PEG) moiety. All are triblock copolymers of polyoxyethylene and polyoxypropylene glycol.

[0103] In some embodiments of the present invention, one or more surfactants have a chemical structure containing a polyethylene glycol (PEG) moiety, and are PEGylated emulsifiers selected from the group consisting of d-alpha-tocopheryl polyethylene glycol succinate, d-alpha-tocopheryl PEG-1000 succinate, PEG-15 hydroxystearate, PEG-30 castor oil, PEG-32 lauroyl glyceride, PEG-32 stearoyl glyceride, PEG-35 castor oil, PEG-40 hydrogenated castor oil, PEG-6 lauroyl glyceride, PEG-6 linoleoyl glyceride, PEG-6 oleoyl glyceride, PEG-8 caprylic / capric acid glyceride, polyoxyl 20 cetostearyl ether, polyoxyethylene-laurylether, polyoxyethylene-23-lauryl ether, and combinations thereof. In this context, the abbreviation "PEG-15" is intended to mean that there are 15 units of PEG. The same numbering applies to other abbreviations, where the number after PEG indicates the number of "PEG" units in the molecule if the number is 100 or less. If the number after PEG is greater than 100, the number indicates the average molecular weight of the "PEG" chains in the molecule.

[0104] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure comprising a polyethylene glycol (PEG) moiety, comprising d-alpha-tocopheryl polyethylene glycol succinate.

[0105] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure comprising a polyethylene glycol (PEG) moiety, which comprises polyoxyethylene-lauryl ether.

[0106] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure comprising a polyethylene glycol (PEG) moiety, which comprises polyoxyethylene-23-lauryl ether.

[0107] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure comprising a polyethylene glycol (PEG) moiety, which includes poloxamer 188.

[0108] In some embodiments of the present invention, one or more surfactants have an average HLB value greater than 6.

[0109] In some embodiments of the present invention, one or more surfactants have an average HLB value greater than 9.

[0110] In some embodiments of the present invention, one or more surfactants are 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 glycerides, stearoyl polyoxyl-32 glyceride, polyoxyl-32 stearate, propylene glycol monolaurate, propylene glycol dilaurate, and mixtures and combinations thereof.

[0111] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more cosolvents.

[0112] In some embodiments of the present invention, one or more self-emulsifying systems further comprise 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.

[0113] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more hydrophilic solvents.

[0114] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more hydrophilic solvents in an amount of at least 5% by mass of the mass of one or more liquid or solid self-emulsifying systems.

[0115] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more hydrophilic solvents in an amount of at least 10% by mass of the mass of one or more liquid or solid self-emulsifying systems.

[0116] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more hydrophilic solvents in an amount of at least 20% by mass of the mass of one or more liquid or solid self-emulsifying systems.

[0117] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more hydrophilic solvents in an amount of 10 to 50% by mass of the mass of one or more liquid or solid self-emulsifying systems.

[0118] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more hydrophilic solvents in an amount of 10 to 40% by mass of the mass of one or more liquid or solid self-emulsifying systems.

[0119] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more hydrophilic solvents in an amount of 10 to 30% by mass of the mass of one or more liquid or solid self-emulsifying systems.

[0120] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more hydrophilic solvents selected from the group consisting of propylene glycol, acetyl tributyl citrate, acetyl triethyl citrate, dimethyl sulfoxide, ethanol, ethyl oleate, glycerol triacetate (high-purity versions preferred), diethylene glycol monoethyl ether, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, propan-2-ol, glycerol, triethyl citrate, and combinations thereof.

[0121] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more hydrophilic solvents containing propylene glycol.

[0122] In some embodiments of the present invention, one or more emulsifying systems further comprise one or more solubilizing agents.

[0123] In some embodiments of the present invention, one or more self-emulsifying systems further comprise one or more solubilizers selected from the group consisting of lauroyl polyoxyl-32 glycerides; stearoyl polyoxyl-32 glycerides; polyoxyl-32 stearates; synthetic copolymers of ethylene oxide (80) and propylene oxide (27); polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymers; alpha-, beta-, or gamma cyclodextrins and their derivatives; pea proteins (globulins, albumin, glutelin proteins); and mixtures and combinations thereof.

[0124] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation further comprises one or more penetration enhancers.

[0125] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation further comprises an antioxidant.

[0126] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation further comprises a preservative.

[0127] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure that does not contain a polyethylene glycol (PEG) moiety. These may also be referred to as "non-PEG" surfactants.

[0128] In this context, “part” is as it is commonly understood in organic chemistry; that is, the polyethylene glycol part is a part of a molecule and can be identified as the polyethylene glycol part within a molecule. This may exist as the tail of a surfactant, a side chain group of a surfactant, or a part of a chain within a surfactant. In this context, the expression “one or more surfactants include one or more surfactants having a chemical structure that does not contain a polyethylene glycol (PEG) part” specifically indicates that the “PEG” part is not present within the molecule.

[0129] One advantage of including one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety as a self-emulsifying system component according to the present invention is that in vivo uptake of cannabinoids was observed to increase remarkably after in vivo administration in rats, particularly on long-term scales such as over 240 minutes. This was highly unexpected, as it was theoretically expected that the low PEG content in the surfactant would lead to significant degradation of the surfactant, which in turn was expected to result in lower cellular uptake due to the lower surfactant content after degradation. In fact, degradation was observed to increase as expected. Nevertheless, in vivo uptake was very high on long-term scales, as was observed for high plasma concentrations of cannabinoids in rats relatively long after ingestion.

[0130] Specifically, when applied in an in vivo test setting in rats, cannabinoid plasma concentrations remained at a very high level as a function of time compared to other surfactants, such as surfactants containing a PEG portion. Therefore, in vivo cannabinoid uptake by including a surfactant without a polyethylene glycol (PEG) portion as part of the self-emulsifying system was particularly remarkable on a long-term scale. Furthermore, plasma concentrations were at the same level as the standard Epidiolex® in terms of cannabinoid uptake on a long-term scale.

[0131] However, it wasn't just the surprisingly high acquisitions observed on long-term scales that were noteworthy. Even on short-term scales, high initial acquisitions, significantly higher than those of Epidiolex®, were also observed.

[0132] In addition, overall cannabinoid uptake was observed to be very high as a function of time by including surfactants without a polyethylene glycol (PEG) moiety as part of the self-emulsifying system. Compared to the baseline Epidiolex®, overall cannabinoid uptake, including uptake on both short-term and long-term scales, was significantly higher on average. Furthermore, compared to PEG-containing surfactants, including surfactants without a polyethylene glycol (PEG) moiety as part of the self-emulsifying system (i.e., "non-PEG" surfactants), the overall level of uptake, including uptake on both short-term and long-term scales, was significantly higher. This was quite surprising.

[0133] In some embodiments of the present invention, the surfactant comprises one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety, and the one or more surfactants having a chemical structure that does not include a PEG moiety are present in an amount of 0.1 to 20% by mass of one or more liquid or solid self-emulsifying systems.

[0134] In some embodiments of the present invention, the surfactant comprises one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety, and the one or more surfactants having a chemical structure that does not include a PEG moiety are present in an amount of 0.1 to 10% by mass of one or more liquid or solid self-emulsifying systems.

[0135] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety, and the one or more surfactants having a chemical structure that does not include a PEG moiety are present in an amount of less than 10% by mass of one or more liquid or solid self-emulsifying systems.

[0136] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety, and the one or more surfactants having a chemical structure that does not include a PEG moiety are present in an amount of less than 5% by mass of one or more liquid or solid self-emulsifying systems.

[0137] In some embodiments of the present invention, the surfactant comprises one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety, and the one or more surfactants having a chemical structure that does not include a PEG moiety are present in an amount of less than 2% by mass of one or more liquid or solid self-emulsifying systems.

[0138] In some embodiments of the present invention, the surfactant comprises one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety, and the one or more surfactants having a chemical structure that does not include a PEG moiety are present in an amount of less than 1% by mass of one or more liquid or solid self-emulsifying systems.

[0139] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure that does not contain a polyethylene glycol (PEG) moiety, selected from the group consisting of monoglycerides, sugar-lipid-based surfactants, and combinations thereof.

[0140] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure that does not contain a polyethylene glycol (PEG) moiety, selected from the group consisting of decaglycerol mono and dioleates, hexaglycerol octastearate, polyglycerol esters of oleic acid, propylene glycol monocaprylate, propylene glycol monolaurate, triglycerol monooleate, polyglyceryl-4 oleyl ether olivate, polyglyceryl-4 laurate / sebacate, polyglyceryl-4 caprylate / caprate, and combinations thereof.

[0141] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a polyethylene glycol (PEG) moiety-free chemical structure, selected from the group consisting of decaglycerol mono and dioleates, hexaglycerol octastearate, polyglycerol esters of oleic acid, propylene glycol monocaprylate (Type I), propylene glycol monocaprylate (Type II), propylene glycol monolaurate (Type I), propylene glycol monolaurate (Type II), triglycerol monooleate, polyglyceryl-4 oleyl ether olive, polyglyceryl-4 laurate / sebacate, polyglyceryl-4 caprylate / caprate, and combinations thereof.

[0142] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure that does not contain a polyethylene glycol (PEG) moiety, selected from the group consisting of sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, sorbitan trioleate, sucrose palmitate, sucrose stearate, and combinations thereof.

[0143] In some embodiments of the present invention, one or more surfactants comprise one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety, comprising polyglyceryl-4 laurate / sebacate and / or polyglyceryl-4 caprylate / caprate. In some embodiments, polyglyceryl-4 laurate / sebacate and / or polyglyceryl-4 caprylate / caprate may contain water.

[0144] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety, and which includes ascorbic acid palmitate.

[0145] In some embodiments of the present invention, one or more surfactants include one or more surfactants having a chemical structure that contains sodium lauryl sulfate and does not include a polyethylene glycol (PEG) moiety.

[0146] In some embodiments of the present invention, the surfactant comprises one or more surfactants having a chemical structure that includes soy phosphatidylcholine and does not contain a polyethylene glycol (PEG) moiety.

[0147] In some embodiments of the present invention, one or more surfactants substantially do not include one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety.

[0148] In some embodiments of the present invention, one or more surfactants do not include one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety.

[0149] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), and combinations thereof.

[0150] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are selected from the group consisting of tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and combinations thereof.

[0151] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids include cannabidiol (CBD).

[0152] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), cannabielsoin (CBE), isotetrahydrocannabinol (iso-THC), cannabicyclol (CBL), cannabicitran (CBT), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), and combinations thereof.

[0153] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are isolated cannabinoids.

[0154] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are synthetic cannabinoids.

[0155] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are not cannabinoid distillates having a cannabinoid purity of more than 80%.

[0156] In some embodiments of the present invention, the purity of the isolated cannabinoid exceeds 95%. In some embodiments of the present invention, the purity of the isolated cannabinoid exceeds 98%. In some embodiments of the present invention, the purity of the isolated cannabinoid exceeds 99%.

[0157] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are not cannabinoid extracts having a cannabinoid purity of less than 80%.

[0158] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 10 mg in an orally soluble or chewable tablet powder formulation.

[0159] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 20 mg in an orally soluble or chewable tablet powder formulation.

[0160] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 30 mg in an orally soluble or chewable tablet powder formulation.

[0161] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 40 mg in an orally soluble or chewable tablet powder formulation.

[0162] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 60 mg in an orally soluble or chewable tablet powder formulation.

[0163] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 75 mg in an orally soluble or chewable tablet powder formulation.

[0164] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 100 mg in an orally soluble or chewable tablet powder formulation.

[0165] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 150 mg in an orally soluble or chewable tablet powder formulation.

[0166] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 200 mg in an orally soluble or chewable tablet powder formulation.

[0167] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 250 mg in an orally soluble or chewable tablet powder formulation.

[0168] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 300 mg in an orally soluble or chewable tablet powder formulation.

[0169] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 400 mg in an orally soluble or chewable tablet powder formulation.

[0170] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 500 mg in an orally soluble or chewable tablet powder formulation.

[0171] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 600 mg in an orally soluble or chewable tablet powder formulation.

[0172] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are present in an amount of at least 300 mg in an orally soluble or chewable tablet powder formulation.

[0173] In some embodiments of the present invention, one or more carrier systems include one or more solid carriers selected from the group consisting of silica, microcrystalline cellulose, cellulose, silicified microcrystalline cellulose, clay, talc, starch, pregelatinized starch, calcium carbonate, dicalcium phosphate, modified calcium carbonate, magnesium carbonate, magnesium aluminometasilicate, hyperporous silica, and mixtures thereof.

[0174] In some embodiments of the present invention, one or more carrier systems include one or more microcrystalline cellulose carriers.

[0175] In some embodiments of the present invention, one or more carrier systems include one or more modified calcium carbonate carriers.

[0176] In some embodiments of the present invention, one or more carrier systems include one or more silica carriers.

[0177] In some embodiments of the present invention, one or more carrier systems include one or more mesoporous silica carriers.

[0178] In some embodiments of the present invention, one or more carrier systems include one or more mesoporous silica carriers comprising magnesium aluminometasilicate.

[0179] In some embodiments of the present invention, one or more carrier systems include one or more mesoporous silica carriers containing dicalcium phosphate.

[0180] In some embodiments of the present invention, one or more carrier systems include one or more solid carriers having an average particle size of 20 to 200 microns.

[0181] In some embodiments of the present invention, one or more carrier systems include one or more solid carriers having an average particle size of 30 to 150 microns.

[0182] In some embodiments of the present invention, one or more carrier systems are present in an amount exceeding 10% by mass of the orally soluble or chewable tablet powder formulation.

[0183] In some embodiments of the present invention, one or more carrier systems are present in an amount exceeding 20% ​​by mass of the orally soluble or chewable tablet powder formulation.

[0184] In some embodiments of the present invention, one or more carrier systems are present in an amount of 30 to 1500 mg in an orally soluble or chewable tablet powder formulation.

[0185] In some embodiments of the present invention, one or more carrier systems are 1.0 cm 3 It comprises one or more solid carriers having an average pore volume exceeding / g.

[0186] In some embodiments of the present invention, one or more carrier systems are 1.5 cm 3It comprises one or more solid carriers having an average pore volume exceeding / g.

[0187] In some embodiments of the present invention, one or more carrier systems include one or more solid carriers having an average density of more than 50 g / L.

[0188] In some embodiments of the present invention, one or more carrier systems include one or more solid carriers having an average density of 50 to 400 g / L.

[0189] In some embodiments of the present invention, one or more carrier systems include one or more solid carriers having an average density of 150 to 400 g / L.

[0190] In some embodiments of the present invention, one or more carrier systems include one or more solid carriers not characterized as powder flow promoters.

[0191] In some embodiments of the present invention, one or more liquid or solid self-emulsifying systems are present in an amount of 30 to 800 mg in an orally soluble or chewable tablet powder formulation.

[0192] In some embodiments of the present invention, one or more liquid or solid self-emulsifying systems are present in an amount of 30 to 300 mg in an orally soluble or chewable tablet powder formulation.

[0193] In some embodiments of the present invention, one or more isolated or synthetic cannabinoids are contained entirely in one or more liquid or solid self-emulsifying systems.

[0194] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation comprises one or more cannabinoids, in addition to one or more liquid or solid self-emulsifying systems.

[0195] In some embodiments of the present invention, one or more water-soluble agents are present in an amount of 30 to 80% by mass of the tablet powder formulation.

[0196] In some embodiments of the present invention, one or more water-soluble agents are present in an amount of 40 to 80% by mass of the tablet powder formulation.

[0197] In some embodiments of the present invention, one or more water-soluble agents comprise one or more sugar alcohol particles.

[0198] In some embodiments of the present invention, one or more water-soluble agents comprise one or more sugar alcohol particles selected from the group consisting of sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, isomalt, and combinations thereof.

[0199] In some embodiments of the present invention, one or more water-soluble agents comprise one or more sugar alcohol particles, including non-directly compressible (non-DC) sugar alcohol particles and directly compressible (DC) sugar alcohol particles.

[0200] In some embodiments of the present invention, one or more water-soluble agents comprise one or more sugar alcohol particles, including non-directly compressible (non-DC) sugar alcohol particles and directly compressible (DC) sugar alcohol particles, in a ratio of 0.2 to 1.2 non-DC to DC.

[0201] In some embodiments of the present invention, one or more water-soluble agents comprise one or more sugar alcohol particles, including non-directly compressible (non-DC) sugar alcohol particles and directly compressible (DC) sugar alcohol particles, in a ratio of 0.3 to 0.7 of non-DC to DC.

[0202] In some embodiments of the present invention, orally soluble or chewable tablet powder formulations are associated with improved mouthfeel.

[0203] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation is associated with an improved mouthfeel, including a less gritty texture.

[0204] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation is associated with an improved mouthfeel, including less grittiness when the orally soluble or chewable tablet powder formulation is chewed.

[0205] In some embodiments of the present invention, orally soluble or chewable tablet powder formulations are associated with improved mouthfeel due to one or more carrier systems compared to separately added carriers that do not contain one or more liquid or solid self-emulsifying systems.

[0206] In some embodiments of the present invention, orally soluble or chewable tablet powder formulations are associated with improved mouthfeel due to the presence of one or more water-soluble agents.

[0207] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation further comprises one or more disintegrants.

[0208] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation further comprises one or more disintegrants selected from the group consisting of croscarmellose sodium, crospovidone, sodium starch glycolate, and combinations thereof.

[0209] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation further comprises at least one solubilizer selected from the group consisting of acacia, agar, alginic acid or its salts, carbomer, carboxymethylcellulose, carrageenan, cellulose, chitosan, copovidone, cyclodextrin, ethylcellulose, gelatin, guar gum, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, hypromellose, inulin, methylcellulose, pectin, polycarbophil or its salts, polyvinyl alcohol, pullulan, starch, tragacanth, trehalose, xanthan gum, and mixtures thereof.

[0210] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation further comprises at least one dissolving agent in an amount of 3 to 20% by mass of the orally soluble or chewable tablet powder formulation.

[0211] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation further comprises one or more organic acids.

[0212] In some embodiments of the present invention, the powder formulation further comprises one or more organic fruit acids. The organic fruit acids according to the present invention may support the flavor of fruit. Furthermore, the organic fruit acids according to the present invention may support the flavor of sweeteners.

[0213] In some embodiments of the present invention, one or more flavoring agents are present in an amount of 0.1 to 10% by mass of the orally soluble or chewable tablet powder formulation.

[0214] In some embodiments of the present invention, one or more self-emulsifying systems comprise one or more isolated or synthetic cannabinoids and one or more lipids in a mass ratio of cannabinoids to lipids of 10:1 to 1:10.

[0215] In some embodiments of the present invention, one or more self-emulsifying systems comprise one or more isolated or synthetic cannabinoids and one or more lipids in a mass ratio of cannabinoids to lipids of 10:1 to 1:5.

[0216] In some embodiments of the present invention, one or more self-emulsifying systems comprise one or more isolated or synthetic cannabinoids and one or more lipids in a mass ratio of cannabinoids to lipids of 8:1 to 1:2.

[0217] In some embodiments of the present invention, one or more self-emulsifying systems comprise one or more isolated or synthetic cannabinoids and one or more lipids in a mass ratio of cannabinoids to lipids of 4:1 to 1:2.

[0218] In some embodiments of the present invention, one or more self-emulsifying systems comprise one or more isolated or synthetic cannabinoids and one or more lipids in a mass ratio of cannabinoids to lipids of 3:1 to 1:1.

[0219] In some embodiments of the present invention, one or more self-emulsifying systems comprise one or more isolated or synthetic cannabinoids and one or more waxes in a mass ratio of 10:1 to 1:10 of cannabinoids to wax.

[0220] In some embodiments of the present invention, one or more self-emulsifying systems comprise one or more isolated or synthetic cannabinoids and one or more waxes in a mass ratio of 10:1 to 1:5 of cannabinoids to wax.

[0221] In some embodiments of the present invention, one or more self-emulsifying systems comprise one or more isolated or synthetic cannabinoids and one or more waxes in a mass ratio of 8:1 to 1:2 of cannabinoids to wax.

[0222] In some embodiments of the present invention, one or more self-emulsifying systems comprise one or more isolated or synthetic cannabinoids and one or more waxes in a mass ratio of 4:1 to 1:2 of cannabinoids to wax.

[0223] In some embodiments of the present invention, one or more self-emulsifying systems comprise one or more isolated or synthetic cannabinoids and one or more waxes in a mass ratio of 3:1 to 1:1 of cannabinoids to wax.

[0224] In some embodiments of the present invention, one or more carrier systems include one or more solid carriers, and one or more carrier systems include one or more liquid or solid self-emulsifying systems in a mass ratio of solid carriers to liquid or solid self-emulsifying systems of 2:8 to 8:2.

[0225] In some embodiments of the present invention, one or more carrier systems comprise one or more solid carriers, and each carrier system comprises one or more liquid or solid self-emulsifying systems in a mass ratio of 4:6 to 6:4 of solid carriers to liquid or solid self-emulsifying systems.

[0226] In some embodiments of the present invention, one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids in a tablet powder formulation comprises at least two separate liquid or solid self-emulsifying systems.

[0227] In some embodiments of the present invention, the first liquid or solid self-emulsifying system comprises one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, and the second liquid or solid self-emulsifying system comprises one or more surfactants having a chemical structure not including a polyethylene glycol (PEG) moiety.

[0228] In some embodiments of the present invention, one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety are present in the first liquid or solid self-emulsifying system in an amount of at least 20% by mass of the first liquid or solid self-emulsifying system.

[0229] In some embodiments of the present invention, one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) moiety are present in the second liquid or solid self-emulsifying system in an amount of at least 5% by mass of the second liquid or solid self-emulsifying system.

[0230] In some embodiments of the present invention, a first liquid or solid self-emulsifying system is located in a first compartment or module of an orally soluble or chewable tablet powder formulation, and a second compartment or module of the orally soluble or chewable tablet powder formulation includes a second liquid or solid self-emulsifying system.

[0231] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation is an orally soluble tablet.

[0232] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation is an orally soluble tablet that disintegrates in the oral cavity within 2 minutes after oral administration.

[0233] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation is a chewable tablet.

[0234] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation is a lozenge containing a fine particle component.

[0235] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation comprises a gum base.

[0236] In some embodiments of the present invention, the orally soluble or chewable tablet powder formulation is a compressed chewing gum tablet.

[0237] In some embodiments of the present invention, the unit volume mass of the orally soluble or chewable tablet powder formulation is 400 to 2000 mg.

[0238] In another embodiment of the present invention, an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids in a powder formulation, wherein one or more self-emulsifying systems i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) If the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble drugs in an amount of 20-80% by mass of the powder formulation, One or more flavorings and Includes, An oral-soluble or chewable powder formulation is provided, comprising one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety.

[0239] In another embodiment of the present invention, an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids in a powder formulation, wherein one or more self-emulsifying systems i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) If the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble drugs in an amount of 20-80% by mass of the powder formulation, One or more flavorings and Includes, One or more of the self-emulsifying systems are stable at a pH of approximately 1 to 4, and when one or more carrier systems are released in the oral cavity, they are activating for the gastrointestinal delivery of one or more cannabinoids. An orally soluble or chewable powder formulation is provided.

[0240] In this embodiment of the present invention, an orally soluble or chewable powder formulation may be further defined according to any of the above embodiments.

[0241] In another embodiment of the present invention, a stick package containing an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids in a powder formulation, wherein one or more self-emulsifying systems i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) If the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble drugs in an amount of 20-80% by mass of the powder formulation, One or more flavorings and Includes, A stick package is provided containing an oral-soluble or chewable powder formulation, wherein one or more surfactants have a chemical structure including a polyethylene glycol (PEG) moiety.

[0242] In another embodiment of the present invention, a stick package containing an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids in a powder formulation, wherein one or more self-emulsifying systems i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) If the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble drugs in an amount of 20-80% by mass of the powder formulation, One or more flavorings and Includes, One or more of the self-emulsifying systems are stable at a pH of approximately 1 to 4, and when one or more carrier systems are released in the oral cavity, they are activating for the gastrointestinal delivery of one or more cannabinoids. A stick package containing an orally soluble or chewable powder formulation is provided.

[0243] In this embodiment of the present invention, the unit volume mass of the orally soluble or chewable powder formulation is 400 to 2000 mg.

[0244] Furthermore, in this embodiment of the present invention, stick packaging may be further defined according to any of the above embodiments.

[0245] In another embodiment of the present invention, a sachet comprising an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids in a powder formulation, wherein one or more self-emulsifying systems i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) If the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble drugs in an amount of 20-80% by mass of the powder formulation, One or more flavorings and Includes, A sachet is provided containing an oral-soluble or chewable powder formulation, comprising one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety.

[0246] In another embodiment of the present invention, a sachet comprising an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids in a powder formulation, wherein one or more self-emulsifying systems i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) If the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble drugs in an amount of 20-80% by mass of the powder formulation, One or more flavorings and Includes, One or more of the self-emulsifying systems are stable at a pH of approximately 1 to 4, and when one or more carrier systems are released in the oral cavity, they are activating for the gastrointestinal delivery of one or more cannabinoids. A sachet containing an orally soluble or chewable powder formulation is provided.

[0247] In this embodiment of the present invention, the unit volume mass of the orally soluble or chewable powder formulation is 400 to 2000 mg.

[0248] Furthermore, in this embodiment of the present invention, the sachet may be further defined according to any of the above embodiments.

[0249] In another embodiment of the present invention, a pouch containing an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids in a powder formulation, wherein one or more self-emulsifying systems i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) If the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble drugs in an amount of 20-80% by mass of the powder formulation, One or more flavorings and Includes, A pouch is provided containing an oral-soluble or chewable powder formulation, wherein one or more surfactants have a chemical structure including a polyethylene glycol (PEG) moiety.

[0250] In another embodiment of the present invention, a pouch containing an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids in a powder formulation, wherein one or more self-emulsifying systems i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) If the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble drugs in an amount of 20-80% by mass of the powder formulation, One or more flavorings and Includes, One or more of the self-emulsifying systems are stable at a pH of approximately 1 to 4, and when one or more carrier systems are released in the oral cavity, they are activating for the gastrointestinal delivery of one or more cannabinoids. A pouch containing an orally soluble or chewable powder formulation is provided.

[0251] In this embodiment of the present invention, the unit volume mass of the orally soluble or chewable powder formulation is 400 to 2000 mg.

[0252] Furthermore, in this embodiment of the present invention, the pouch may be further defined according to any of the above embodiments.

[0253] In another embodiment of the present invention, a capsule formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids, wherein one or more self-emulsifying systems i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) If the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble agents in an amount of 20-80% by mass of the formulation, One or more flavorings and Includes, A capsule formulation is provided, comprising one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety.

[0254] In another embodiment of the present invention, a capsule formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids, wherein one or more self-emulsifying systems i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) If the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble agents in an amount of 20-80% by mass of the formulation, One or more flavorings and Includes, One or more of the self-emulsifying systems are stable at a pH of approximately 1 to 4, and when one or more carrier systems are released in the oral cavity, they are activating for the gastrointestinal delivery of one or more cannabinoids. A capsule formulation is provided.

[0255] In some embodiments of the present invention, the capsule includes an orally soluble or chewable powder formulation. [Modes for carrying out the invention]

[0256] As used in this description and claims, the verb “including” and its conjugations are used in their non-restrictive sense to mean that the items following the word are included, but not excluded from items not specifically mentioned. In addition, references to elements with the indefinite article “a” or “an” do not exclude the possibility of two or more of the elements being present unless the context clearly requires that only one or one of the elements be present. Thus, the indefinite article “a” or “an” usually means “at least one.” In addition, when the words “a” and “an” are used in this document in relation to the words “including” or “containing,” they indicate “one or more.” The expression “one or more” is intended to mean one, two, three or more.

[0257] When used herein, the terms “approximately” or “about” in reference to numerical values ​​are generally interpreted to include numerical values ​​that fall within a range of 5%, 10%, 15%, or 20% (greater than or less than) either direction of the numerical value, unless otherwise indicated or the context makes it clear otherwise (unless such numerical values ​​could be less than 0% or greater than 100% of the possible value).

[0258] As used herein, the terms "%" and "percent" refer to mass percentages unless otherwise indicated.

[0259] The term "particle size" relates to the ability of a particle to pass through or be held by a sieve hole of a particular size. As used herein, unless otherwise specifically referred to, the term "particle size" refers to the average particle size as determined when using the particle size distribution estimation method 2.9.38 by analytical sieving in accordance with European Pharmacopoeia 9.1.

[0260] The term "particle" or similar expression is intended to refer to a single, distinct composition of solid matter having a certain size which can deviate considerably, such as individual elements in granules or powder.

[0261] In this context, the term “release” refers to a released substance or a released carrier system that is released from a solid dosage form. In some embodiments, the process of releasing a substance corresponds to the substance dissolving in saliva or mucous membranes. In this context, the term “release” is intended to mean being tested under “in vivo” conditions unless otherwise indicated. In this context, where a solid dosage form is chewed, “in vivo” conditions are intended to mean that the sample is chewed for a specific period of time at a chewing frequency of 60 chews per minute by a test panel of eight testers, unless otherwise indicated. These testers refrain from eating or drinking for at least 30 minutes prior to the start of any test. Testers are healthy individuals designated on an objectivity basis in accordance with specific requirements.

[0262] The term "texture" refers to the quality measurement of the properties of a solid dosage form, as well as the overall mouthfeel quality experienced by the user during use. Therefore, the term "texture" encompasses both measurable quantities such as hardness, and more subjective parameters related to sensations such as grittiness experienced by the user during or after chewing the product.

[0263] The terms “sustained-release” or “long-term release” are intended herein to mean release that is extended over time. The terms “immediate-release” or “rapid-release” or “high-release” are intended herein to mean a higher content released over a given period of time. The term “controlled-release” is intended to mean release of a substance or carrier system from a solid dosage form, aided by the active use of the solid dosage form in the oral cavity of a subject, where the active use controls the amount of substance or carrier system released.

[0264] An "auto - emulsifier" is an agent that forms an emulsion with a minimum amount of required energy when present in an interaction phase. In contrast, an emulsifier, as opposed to an auto - emulsifier, requires additional energy to form an emulsion.

[0265] Due to the poor solubility of certain active ingredients in physiological fluids, solubilizing cannabinoids to promote bio - absorption when mixed with physiological body fluids is still an unaddressed requirement. To overcome low bio - availability, various lipid - based drug delivery systems and self - emulsifying systems have been developed. Lipid - based delivery systems and especially self - emulsifying drug delivery systems (SEDDS) have been demonstrated to increase the solubility, dissolution, and bio - availability of many insoluble active ingredients.

[0266] In formulating solid dosage forms with SEDDS, certain difficulties may arise. For example, difficulties may occur in obtaining a homogeneous mixture where variability is avoided and safe and convenient delivery can be achieved. Also, it is necessary that the overall formulation of the solid dosage form that provides convenience to the user is not impaired. Without taking preventive measures, for example, when a high - dose active ingredient is required, the overall formulation is often impaired.

[0267] Particularly for SEDDS, the formulations of the present invention can provide some obvious advantages that enable higher - dose active ingredients and at the same time provide improved organoleptic properties of the formulations during use. There are also other advantages.

[0268] Importantly, the presence of SEDDS or at least one auto - emulsifier was found to act synergistically with the formulations of the present invention. The presence of SEDDS or at least one auto - emulsifier was found to further increase the uptake of the active ingredient through mucosal surfaces such as the gastrointestinal tract. In this regard, the gastrointestinal tract is not considered to include the oral cavity.

[0269] The administration route in this context is thought to be as follows. First, the carrier system is at least partially or completely released in the oral cavity, and then immediately, the carrier system containing a substantial amount of cannabinoid is ingested for delivery in the gastrointestinal tract by the generated saliva. Without being bound by theory, relatively more responsive or faster release of the cannabinoid-containing carrier system in the oral cavity, and relatively long release of the cannabinoid from the carrier in the oral cavity are thought to contribute to more accurate delivery of the cannabinoid in the gastrointestinal tract. Thus, the system of the present invention provides a synergistic effect for various advantages for delivery of cannabinoid in the gastrointestinal tract.

[0270] Therefore, the synergistic effect between the presence of SEDDS or at least one self-emulsifier and the cannabinoid was surprising to the inventors. In particular, the potential of SEDDS, for example in the carrier system according to the present invention, to have a high formulation of the active ingredient further contributes to the synergistic effect of the solid dosage form according to the present invention.

[0271] In this context, SEDDS is a solid or liquid dosage form containing at least one surfactant and optionally one co-surfactant, which is mainly characterized in that the dosage form can spontaneously form an oil-in-water emulsion in the oral cavity or at room temperature (generally referring to body temperature, i.e., 37 °C). When SEDDS enters the gastrointestinal tract, it first self-emulsifies as emulsion droplets and rapidly disperses. The resulting microparticles at the micrometer or nanometer level can penetrate the mucosa of the gastrointestinal tract, and the absorbed oil droplets enter the blood circulation, thereby significantly improving the bioavailability of the active ingredient.

[0272] The term "non-DC sugar alcohol particles" refers to particles of non-directly compressible (non-DC) sugar alcohols. It should be noted that the terms "non-DC sugar alcohol particles" and "non-DC particles" are used interchangeably. In this context, non-DC sugar alcohol particles refer to particles that have not been pre-treated by granulation, for example, with other sugar alcohols or binders, for the purpose of obtaining so-called directly compressible particles (DC). In this context, non-DC sugar alcohol particles include particles obtained by crystallization and subsequent milling without other sugar alcohols or binders. Therefore, non-DC sugar alcohol particles are considered to be particles consisting of non-DC sugar alcohols.

[0273] The term "DC sugar alcohol particles" refers to particles of directly compressible (DC) sugar alcohols. It should be noted that the terms "DC sugar alcohol particles" and "DC particles" are used interchangeably. DC sugar alcohol particles can be obtained, for example, as particles of a sugar alcohol that inherently possesses DC grade, such as sorbitol, or by granulation of a non-DC sugar alcohol, for example with another sugar alcohol or binder, for the purpose of obtaining so-called directly compressible (DC) particles. Furthermore, granulation of a non-DC sugar alcohol with water as a binder is considered to produce "DC sugar alcohol particles" in this context.

[0274] The terms “tablet,” “tablet,” or “compressed” are intended to mean that a tablet composition is pressurized in a tableting apparatus and consists primarily of particulate matter. While this term describes a process in this context, it is intended to mean that the resulting tablet is obtained by tableting some of the particles. It should be noted that any tablet or tablet composition mentioned as ultimately containing particles should be understood as particles pressurized together in the tableting process.

[0275] The following description outlines how the tablets of the present invention may be produced and provides further details on what may be added to the composition of the present invention.

[0276] Typically, the tablet manufacturing method of the present invention can be carried out in a single compression, such as by rotary compression. However, applying separate compressions may be beneficial in some circumstances.

[0277] Preferably, the upper punch is a convex surface that gives a concave shape to the upper surface of the tablet being pressed.

[0278] Of course, it should be noted that the shape of the punch may vary depending on the desired tablet shape.

[0279] In some embodiments of the present invention, the tablets are pressurized with a force of 20 to 50 kN.

[0280] In one embodiment of the present invention, the “tablet” is a “rapidly disintegrating tablet” (“FDT”), for example, an “orally disintegrating tablet” (“ODT”). In some embodiments, if such a tablet is manufactured as a single module rather than two or more modules, the tablet is intended to be an FDT tablet. On the other hand, if the tablet consists of two or more modules, for example two modules, such additional modules may be “lozenge” modules that provide a longer disintegration time compared to the FDT modules. A combination of “FDT” modules and “lozenge” modules contributes to another embodiment of the present invention. The “lozenge” modules may also contain elements from the “FDT” modules, but generally have a different composition and provide a longer disintegration time.

[0281] The term “lozenge” is intended to include the fact that the “lozenge composition” is “compressed” into a “lozenge module.” In this context, “lozenge module” or similar expression is intended to mean that the module in use in the oral cavity is intended to be sucked or licked. The term “lozenge” has its usual meaning in the field of lozenges. The intention is that the lozenge module does not need to be chewed. The intention is also that FDT modules do not need to be chewed. Generally, unlike the few seconds for orally disintegrating tablets (ODTs) or rapidly disintegrating tablets (FDTs), the “lozenge modules” of the present invention may disintegrate when sucked or licked for several minutes. Therefore, if a tablet is manufactured as a combination of two modules, the intention is that the “lozenge module” is intended to deliver one or more cannabinoids over a longer period than an FDT module.

[0282] The term “module” is generally intended to refer to a composition of substances having substantially the same characteristics throughout the module. Therefore, if two modules are present, the two modules have different compositions and generally have two different characteristics throughout each module. In this context, if two modules are present, a tablet consists of two modules fused together. The term “fused together” is intended to mean that the tablet is assembled together by means of compressive force. A tablet may consist of two or more modules. One module may, in a particular embodiment, be a gum-based module. In this context, even when cannabinoid delivery is “single-phase,” the present invention provides an attractive two-phase masking delivery.

[0283] In the context of the present invention, "chewable tablet" is intended to mean an oral tablet that is chewed when administered orally, having the characteristic of enabling convenient chewing without the adverse side effects associated with the texture of oral tablets.

[0284] In particular, little attention has been paid to the advantages of chewable tablet formulations, which can help obtain cannabinoid release characteristics that offer high convenience and efficacy. One of these release characteristics is increased saliva production during chewing. The experience of increased saliva production, and especially increased saliva production upon administration, may have some significant advantages for the delivery of cannabinoids to the mucosal surface.

[0285] One advantage of chewable tablets containing non-DC sugar alcohol particles is their remarkably strong saliva production compared to conventional chewable tablets and lozenges. In particular, non-DC particles can remarkably induce significant saliva production. Increased saliva production can have a remarkably high impact on the administration of carrier systems for mucosal delivery of cannabinoids in the gastrointestinal tract. Specifically, increased saliva production can enable increased release of carrier systems from oral formulations, so as soon as possible, the carrier systems can be swallowed more quickly and easily. More specifically, this allows the carrier systems to access the gastrointestinal tract with a higher concentration of cannabinoids, thereby providing higher uptake of one or more cannabinoids onto the mucosal surface in the gastrointestinal tract. Therefore, the synergistic effect of cannabinoid uptake in the gastrointestinal tract and increased saliva production can be seen in the present invention.

[0286] Having a combination of non-DC particles and DC particles can further enhance tablet stability, sufficient mechanical strength, tablet disintegration during chewing, and saliva production induced during chewing.

[0287] One unexpected advantage over prior art is the remarkable sustained saliva production, even after the user has swallowed the bulk portion of the non-DC sugar alcohol. This sustained saliva production can be beneficial for many applications of oral tablets, affecting mouthfeel, taste, and flavor perception.

[0288] In this context, non-DC sugar alcohol particles are understood and defined by those skilled in the art in terms of their typical commercial grades.

[0289] In one embodiment of the present invention, the non-DC sugar alcohol particles are not granulated before tableting. Thus, the non-DC sugar alcohol particles are provided as non-granulated particles. These are typically particles that are not pretreated by granulation with other sugar alcohols or binders for the purpose of obtaining so-called direct compressible particles (DC) based on sugar alcohol particles that are not suitable for direct compression by themselves. They can be used in the non-DC type of the relevant sugar alcohol as particles that have not been pretreated by granulation with other sugar alcohols or binders for the purpose of obtaining so-called direct compressible particles (DC) based on sugar alcohol particles that are not suitable for direct compression by themselves. Such non-DC particles of sugar alcohol can typically consist of sugar alcohol. Therefore, the non-DC sugar alcohol particles can typically be particles consisting of a sugar alcohol that is non-direct compressible in its pure form.

[0290] In order to obtain the mouthfeel and taste obtained through the present invention, it has been proven that the mass ratio of non-DC sugar alcohol particles to DC sugar alcohol particles is important according to one embodiment of the present invention in the sense that a relatively high amount of non-DC sugar alcohol particles must be present. However, this taste and mouthfeel also exist in the DC sugar alcohol particles. An example of such DC sugar alcohol particles is DC-grade xylitol, which can provide a unique and very attractive mouthfeel to the test panel together with the non-DC sugar alcohol particles.

[0291] The mass ratio of non-DC sugar alcohol particles to DC sugar alcohol particles is important for the purpose of obtaining a beneficial taste and mouthfeel. By having an upper limit of this mass ratio, the chewer can also experience a desirable crunchiness sensation when chewing the tablet, and the crunchiness sensation is obtained through the use of a substantial amount of DC sugar alcohol particles and non-DC sugar alcohol particles.

[0292] In one embodiment of the present invention, the non-DC sugar alcohol particles are selected from non-DC particles of erythritol, maltitol, xylitol, isomalt, lactitol, mannitol and combinations thereof. One advantage of the above embodiment may be that desirable saliva production induction can be obtained. According to one embodiment of the present invention, the non-DC sugar alcohol particles consist of sugar alcohols selected from erythritol, maltitol, xylitol, isomalt, lactitol, mannitol and combinations thereof.

[0293] In one embodiment of the present invention, the non-DC sugar alcohol particles are selected from non-DC particles of erythritol, maltitol, xylitol, isomalt, and combinations thereof. One advantage of the above embodiment may be that desirable saliva production can be induced.

[0294] In one embodiment of the present invention, the non-DC sugar alcohol particles are selected from non-DC particles of erythritol, maltitol, xylitol, and combinations thereof. In one embodiment of the present invention, the non-DC sugar alcohol particles are non-DC erythritol particles. One advantage of the above embodiment may be that a cooling sensation is obtained along with the induction of desirable saliva production. In one embodiment of the present invention, the non-DC sugar alcohol particles are non-DC xylitol particles. One advantage of the above embodiment may be that a cooling sensation is obtained along with the induction of desirable saliva production.

[0295] In one embodiment of the present invention, the DC sugar alcohol particles include a sugar alcohol selected from DC particles of sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, isomalt, and combinations thereof.

[0296] Sorbitol is an example of a sugar alcohol, and when provided as particles consisting of sorbitol, i.e., in its pure form, it is considered DC grade. On the other hand, some other sugar alcohols are considered non-DC grade when provided as particles consisting of a particular sugar alcohol. Therefore, such non-DC sugar alcohols are conventionally processed into DC grade sugar alcohols, for example, by granulation with a binder.

[0297] Examples of commercially available DC sugar alcohols include sorbitol particles provided as Neosorb® P 300 SD by Roquette, mannitol particles provided as Pearlitol® 300DC or Pearlitol 200 SD by Roquette, maltitol provided as SweetPearl® P 300 DC, and xylitol provided as Xylisorb® XTAB 400 DC or Xylitab 200 by Dupont.

[0298] In one embodiment of the present invention, an oral tablet comprises at least two modules. A module is typically assembled from a plurality of compressed particles and may have a mass greater than 0.1 grams and less than 10 grams. In one embodiment of the present invention, a module is defined as a plurality of particles that are compressed together to form a module of aggregated particles.

[0299] In one embodiment of the present invention, an oral tablet comprises a plurality of oral tablet modules. In this context, the application of, for example, two modules is particularly beneficial if non-DC sugar alcohol particles are mainly present in one module, thereby optimizing the desired salivary secretion and sensory experience from that module and the tablet itself, while the other module may mainly contain DC sugar alcohol particles that act as support to ensure that the desired stability and crushability of the complete tablet are obtained.

[0300] The term "cannabinoid composition" is intended to mean a certain amount of a substance containing one or more cannabinoids. A cannabinoid composition may contain components other than cannabinoids. A cannabinoid composition may constitute cannabinoids. A cannabinoid composition may constitute one type of cannabinoid. A cannabinoid composition may constitute two types of cannabinoids. A cannabinoid composition may constitute two or more types of cannabinoids.

[0301] The terms "water-insoluble gum base," "gum base," or "gum base matrix," or similar expressions, primarily refer to water-insoluble components and hydrophobic gum base components. "Gum base" may contain gum base polymers, natural resins, elastomer plasticizers, waxes, emulsifiers, fats, and / or fillers.

[0302] As used herein, the term "natural resin" means a resin compound that is either a polyterpene derived from a naturally occurring terpene, or a resin compound derived from gum rosin, wood rosin, or tall oil rosin.

[0303] Elastomers provide gum with rubbery, elastomeric, and bouncy properties, which vary depending on the chemical structure of the component and how it can combine with other components. Suitable elastomers for use in gum bases and gums according to the present invention may include natural or synthetic types. Polyvinyl acetate elastomer plasticizers are not considered elastomers according to the present invention.

[0304] The elastomer may be selected from the group consisting of styrene-butadiene copolymer, polyisobutylene, isobutylene-isoprene copolymer, polyethylene, polyurethane, or any combination thereof. Preferred elastomers are styrene-butadiene copolymer (SBR), polyisobutylene, and isobutylene-isoprene copolymer (BR).

[0305] Styrene-butadiene type elastomers, sometimes called SBRs, are typically copolymers of styrene:butadiene monomers in a ratio of approximately 20:80 to 60:40. The ratio of these monomers affects the elasticity of SBR, which is assessed by its Mooney viscosity. As the styrene:butadiene ratio decreases, the Mooney viscosity decreases.

[0306] SBR typically consists of a linear 1,3-butadiene copolymerized with phenylethylene (styrene). The average molecular weight of SBR is less than 600,000 g / mol.

[0307] Isobutylene-isoprene type elastomers, sometimes called butyl, have isoprene molar percentage levels ranging from 0.2 to 4.0. Similar to SBR, as the isoprene:isobutylene ratio decreases, the elasticity, as measured by Mooney viscosity, decreases.

[0308] The structure of butyl rubber typically consists of branched 2-methyl-1,3-butadiene (isoprene) copolymerized with branched 2-methylpropene (isobutylene). The average molecular weight of BR is in the range of 150,000 g / mol to 1,000,000 g / mol.

[0309] Polyisobutylene, sometimes called PIB, is an elastomer type that is a polymer of 2-methylpropene. Low molecular weight elastomers provide a soft chewing characteristic to gum bases while still offering elastic properties similar to other elastomers. Average molecular weight can range from approximately 30,000 to 120,000 g / mol, and penetration can range from approximately 4 to 20 millimeters. The higher the penetration, the softer the PIB. Similar to SBR and butyl, high molecular weight elastomers provide elasticity to gum. Average molecular weight can range from 120,000 to 1,000,000 g / mol.

[0310] Polybutenes have an average molecular weight ranging from approximately 5,000 g / mol to approximately 30,000 g / mol.

[0311] Useful natural elastomers include natural rubbers, such as smoked or liquid latex and guayule, and natural gums, such as Jelutong, lechi caspi, perillo, sorva, massaranduba balata, massaranduba chocolate, nispero, rosidinha, chicle, gutta perka, gutta kataiu, niger gutta, tunu, chilte, chiquibul, and gutta hang kang. Natural elastomers can also be applied in embodiments of the present invention.

[0312] Elastomer plasticizers alter the hardness of the gum base. Their specificity for elastomer intermolecular chain severance (plasticization) and their various softening points result in varying degrees of hardness and compatibility of the finished gum when used in a substrate. Polyvinyl acetate elastomer plasticizers are an example of elastomer plasticizers in this invention.

[0313] Natural resins may be selected from, for example, ester gums including glycerol esters of partially hydrogenated rosin, glycerol esters of polymerized rosin, glycerol esters of partially dimerized rosin, glycerol esters of tally oil rosin, pentaerythritol esters of partially hydrogenated rosin, methyl esters of rosin, partially hydrogenated methyl esters of rosin, and pentaerythritol esters of rosin; synthetic resins, for example, terpene resins derived from alpha-pinene, beta-pinene and / or d-limonene; and natural terpene resins.

[0314] In one embodiment of the present invention, the solid dosage form comprises further components selected from the group consisting of flavoring agents, drying binders, tableting aids, anticaking agents, emulsifiers, antioxidants, enhancers, mucosal adhesives, absorption enhancers, high-strength sweeteners, softeners, colorants, active ingredients, water-soluble indigestible polysaccharides, water-insoluble polysaccharides, or any combination thereof.

[0315] The solid dosage form according to the present invention is manufactured by applying pressure to particles as contents using a suitable compression means. The particles or powder are then pressurized to form a dense, coherent tablet. The particles may include, for example, so-called primary particles or aggregated primary particles. When they are pressurized, bonds are established between the particles or granules, thereby giving the pressurized tablet a certain mechanical strength.

[0316] It should be noted that the terms introduced above—powder, primary particles, and aggregated primary particles—can be somewhat misleading in that the difference between primary particles and aggregated primary particles can very often be perceived differently depending on the user's background. For example, some people might consider sweeteners, such as sorbitol, to be primary particles, despite the fact that they should rather be considered a kind of aggregated primary particle due to the pretreatment typically performed on sorbitol when delivered to customers. In the definitions adopted in this description, aggregated primary particles refer to large particles that include some pretreated primary particles.

[0317] When pressure is applied to particles, the bulk volume is reduced, and the amount of air is decreased. Energy is consumed during this process. During the volume reduction process, if particles are in close proximity to each other, bonds may be established between particles or granules. The formation of bonds is associated with a reduction in the energy of the system as energy is released. Volume reduction occurs by various mechanisms, and different types of bonds can be established between particles or granules depending on the pressure applied and the properties of the particles or granules. The first thing that happens when powder is pressurized is that the particles are rearranged under low compression pressure to form a more densely packed structure. Particles with a regular shape appear to rearrange more easily than particles with an irregular shape. As the pressure increases, further rearrangement is prevented, and the next volume reduction is obtained by the plasticity and elastic deformation and / or fragmentation of the tablet particles. Brittle particles appear to be more prone to fragmentation, i.e., the original particles break down into smaller units. Plastic deformation is an irreversible process that results in a permanent change in particle shape, while after elastic deformation, the particles regain their original shape. Clearly, when a solid dosage form is compressed, both plasticity and elastic deformation can occur.

[0318] Several studies on binding types in pressurized tablets have been conducted over many years, typically in the pharmaceutical field, and several techniques have been offered to obtain pressurized tablets based on available powders. Such studies have focused quite a bit on what happens when volume reduction is made and how the final product can be optimized for a given purpose. Several refinements have been made to the tablet raw materials, for example, in addition to binders, for the purpose of obtaining sufficient strength of the final pressurized tablet while maintaining acceptable properties, such as properties with respect to release, for the pressurized tablet.

[0319] Unlike tableted chewing gum, conventional chewing gum can be produced by sequentially adding various chewing gum components to a commercially available mixer known in the art, in which a finished gum base already exists. After the first components are completely mixed, the gum mass is discharged from the mixer and shaped into the desired form, for example, by being rolled into a sheet and cut into sticks, extruded into a large mass, or molded into pellets. Generally, the components of conventional chewing gum can be mixed by first melting the gum base and adding it to a working mixer. Colorants, activators, and / or emulsifiers may also be added at this time. Softeners such as glycerin may also be added at this time, along with syrup and some bulking agents / sweeteners. Further portions of the bulking agents / sweeteners may then be added to the mixer. Flavoring agents are typically added together with the final portion of the bulking agents / sweeteners. High-strength sweeteners are preferably added after the bulking agent and flavoring agent have been added. The entire mixing procedure typically takes 30-40 minutes, but sometimes a longer mixing time may be required. Those skilled in the art will recognize that many variations of the procedure described above can be made.

[0320] In some embodiments of the present invention, the solid dosage form does not include conventional chewing gum, i.e., so-called extruded chewing gum.

[0321] In accordance with the present invention, the tablet solid dosage form according to the present invention may include an external coating of about 0.1 to about 75% by mass applied to the center of the solid dosage form. Accordingly, suitable coating types include hard coatings, film coatings, and soft coatings of any composition, including those currently used in coatings for tablet solid dosage forms.

[0322] One currently preferred type of external coating is hard coating, and this term is used in its conventional sense, including sugar coatings and sugar-free (or sugarless) coatings and combinations thereof. The purpose of hard coating is to obtain a sweet, crunchy layer that is highly valued by consumers, and it may further protect the solid dosage form center for various reasons. In a typical process of providing a protective sugar coating to a solid dosage form center, the solid dosage form center is continuously treated with an aqueous solution of an easily crystalline sugar such as sucrose or dextrose in a suitable coating facility, and the aqueous solution may contain other functional components, such as fillers, binders, colorants, etc., depending on the coating stage reached. In this context, the sugar coating may contain further functional or active compounds, including flavor compounds and / or active compounds.

[0323] As will be described in detail below, in a typical hard coating process, a suspension containing easily crystalline sugars and / or polyols is applied to the center of a solid dosage form, and the water contained in the suspension is evaporated by blowing air onto it. To reach the required thickening, this cycle must be repeated several times, typically 3 to 80 times. The term "thickening" refers to the increase in mass or thickness of the product considered at the end compared to the beginning of the coating operation, and relates to the final mass or thickness of the coated product. According to the present invention, the coating layer constitutes about 10 to about 60% by mass, for example, about 0.1 to about 75% by mass of the finished solid dosage form element, including about 15 to about 50% by mass.

[0324] In one embodiment of the present invention, the product is a pouch.

[0325] In one embodiment of the present invention, the aggregate of particles used for tableting may also be present in the pouch as a powder. Therefore, this aspect of the present invention includes aggregates of particles in a pouch as a powder or part of a powder, without tableting, but with other powders or powder components. This means that the directly compressible (DC) and indirectly compressible (non-DC) sugar alcohol particles of the present invention may be contained in the pouch according to the present invention. Furthermore, additional embodiments relating to aggregates of particles of the present invention are applicable when contained in a pouch. It should be noted that additional components, such as water-soluble or water-insoluble fibers, including microcrystalline cellulose, may be present in the pouch.

[0326] According to an advantageous embodiment of the present invention, the pouch comprises a water-permeable membrane, such as a woven or nonwoven fabric.

[0327] The pouch according to the present invention includes an opening, the characteristic dimensions of which are adapted to the characteristic dimensions of a particle cluster in order to hold the matrix composition in the pouch before use and / or to hold a portion of the contents in the pouch during use.

[0328] In other words, according to various embodiments, the pouch forms a membrane that allows saliva to pass through and prevents or inhibits the passage of at least a portion of the contents. The membrane of the pouch may be made of any suitable material, such as woven or nonwoven fabrics (e.g., cotton, fleece, etc.), heat-sealable nonwoven cellulose, or other polymeric materials, such as synthetic, semi-synthetic, or natural polymeric materials. An example of a suitable pouch material is paper made from pulp and a small amount of wet-strengthening agent. A suitable material for use must provide a semipermeable membrane layer to prevent the powder or composition from separating from the bag or pouch during use. A suitable material is also one that does not have a significant effect on the release of the active ingredient from the pouch.

[0329] The powder is filled into a pouch and kept inside by sealing. An ideal pouch is chemically and physically stable, pharmaceutically acceptable, insoluble in water, easy to fill with powder and seal, and provides a semipermeable membrane layer that prevents the powder from escaping the bag but allows components from the powder in the pouch, dissolved in saliva or suspended in sufficiently small sizes, to pass through the pouch.

[0330] The pouch can be placed in the mouth by the user. Saliva then enters the pouch, and the active ingredients and other components, which are soluble in saliva, begin to dissolve and are transported out of the pouch and into the mouth with the saliva. In some embodiments of the present invention, the pouch can be chewed in a manner similar to chewing gum. This is particularly beneficial if the aggregate of particles contains a gum base. Therefore, the pouch can be chewed to become a coherent residue containing water-insoluble components.

[0331] According to embodiments of the present invention, the flavoring agent may be selected from the group consisting of coconut, coffee, chocolate, vanilla, grapefruit, orange, lime, menthol, licorice, caramel aroma, honey aroma, peanut, walnut, cashew nut, hazelnut, almond, pineapple, strawberry, raspberry, tropical fruit, cherry, cinnamon, peppermint, wintergreen, spearmint, eucalyptus, and mint; and fruit extracts such as apple, pear, peach, strawberry, apricot, raspberry, cherry, pineapple, and plum extract. The essential oils include peppermint, spearmint, menthol, eucalyptus, clove oil, bay oil, anise, thyme, cedar leaf oil, nutmeg, and the fruit oils listed above.

[0332] Suitable antioxidants for use include butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), beta-carotene, tocopherol, acidulants such as vitamin C (ascorbic acid or its corresponding salt (ascorbate)), propyl gallate, catechin, green tea extract, and other synthetic and natural types or mixtures thereof.

[0333] Furthermore, high-strength sweeteners may be used according to preferred embodiments of the present invention. Preferred high-strength sweeteners include, but are not limited to, sucralose, aspartame, acesulfame salts, alitame, neotame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, monellin, monk fruit extract, advantame, stevioside, etc., either alone or in combination.

[0334] To provide a longer-lasting sweetness and flavor perception, it may be desirable to encapsulate at least a portion of the high-intensity sweetener or to control its release by other means.

[0335] Techniques such as wet granulation, wax granulation, spray drying, spray cooling, fluidized bed coating, preservation, encapsulation with yeast cells, and fiber extrusion molding may be used to achieve desired release characteristics. Furthermore, encapsulation of the sweetener may be provided using other formulation components such as resinous compounds.

[0336] The level of use of high-strength sweeteners varies considerably and depends on factors such as the strength of the sweetener, its release rate, the desired sweetness of the product, the level and type of flavoring agent used, and cost considerations. Therefore, the activity level of artificial sweeteners can vary from about 0.001% to about 8% by mass (preferably about 0.02% to about 8% by mass). If a carrier is used for encapsulation, the level of use of the encapsulated high-strength sweetener is proportionally higher.

[0337] If desired, the present invention may include one or more texturers, for example, magnesium carbonate and calcium carbonate, sodium sulfate, crushed limestone, silicate compounds such as magnesium silicate and aluminum silicate, kaolin and clay, aluminum oxide, silicon oxide, talc, titanium dioxide, monocalcium phosphate, dicalcium phosphate and tricalcium phosphate, cellulose polymers, such as wood, and combinations thereof. According to one embodiment of the present invention, one preferred texturer is calcium carbonate.

[0338] In accordance with the present invention, one or more cannabinoids may be selected from a variety of cannabinoids.

[0339] "Cannabinoids" is a group of compounds that include endocannabinoids, phytocannabinoids, and, hereafter referred to as "syntho-cannabinoids," which are cannabinoids that are neither endocannabinoids nor phytocannabinoids.

[0340] "Endocannabinoids" are endogenous cannabinoids that may have high-affinity ligands for CB1 and CB2 receptors.

[0341] Phytocannabinoids are cannabinoids of natural origin that can be found in the cannabis plant. Phytocannabinoids can be present in extracts containing plant-derived medicinal substances, isolated, or synthesized.

[0342] "Synto-cannabinoids" are compounds capable of interacting with cannabinoid receptors (CB1 and / or CB2), but are not found endogenously or in cannabis plants. Examples include WIN55212 and limonabane.

[0343] "Isolated phytocannabinoids" or "isolated cannabinoids" are cannabinoids extracted from the cannabis plant and purified until additional components such as secondary cannabinoids and trace amounts of cannabinoids, as well as non-cannabinoid fractions, are substantially removed.

[0344] "Synthetic cannabinoids" are cannabinoids produced by chemical synthesis. This term includes modifying isolated phytocannabinoids, for example, by forming pharmaceutically acceptable salts thereof.

[0345] "Substantially pure" cannabinoids are defined as cannabinoids that exist in a pure state of more than 95% (w / w). More preferably, they are greater than 96% (w / w), 97% (w / w), 98% (w / w), 99% (w / w), and above.

[0346] In some embodiments, a purity of more than 80% (w / w) may be applicable.

[0347] "Highly purified" cannabinoids are defined as cannabinoids extracted from the cannabis plant and purified to the extent that other cannabinoids and non-cannabinoid components extracted with the cannabinoids are substantially removed. Therefore, highly purified cannabinoids are more than 95% (w / w) pure or equal to 95% (w / w) pure.

[0348] "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 exudates, and includes materials that fall under the definition of "plant-derived raw materials" 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.

[0349] 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 macroscopic fungi, which is prepared from botanical raw materials by one or more of the following processes: grinding, decoction, pressing, aqueous extraction, ethanol extraction or other similar processes.” Botanical drug substances do not include highly purified or chemically modified substances derived from natural sources. Therefore, in the case of cannabis, “botanical drug substances” derived from the cannabis plant do not include highly purified pharmacopoeia-grade cannabinoids.

[0350] The term "cannabis plant" encompasses wild-type Cannabis sativa, which includes chemical varieties of Cannabis containing different amounts of individual cannabinoids in nature, and also its variants, including the variant variety Indica and the variety Kafiristanica, as well as Cannabis sativa subspecies such as Cannabis indica, Cannabis indica, Cannabis ruderalis, and also plants resulting from genetic hybridization, self-hybridization, or hybrids thereof. Therefore, the term "cannabis plant material" should be interpreted as encompassing plant material derived from one or more Cannabis plants. To avoid ambiguity, this indicates that "cannabis plant material" includes dried cannabis biomass.

[0351] 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 (THCVA). More preferably, one or more cannabinoids are CBD or THC. This list is not exhaustive and is merely a detail of the cannabinoids specified in this application for reference purposes only.

[0352] To date, more than 120 different phytocannabinoids have been identified, and these fall within the scope of this invention.

[0353] Cannabinoids can be divided into three distinct groups: phytocannabinoids, endocannabinoids, and synthetic cannabinoids.

[0354] Cannabinoid receptors, for the purposes of the present invention and whether or not they are explicitly named in this specification, are naturally lipophilic and can be activated by agonist ligands of three main groups, classified as endocannabinoids (endogenously produced by mammalian cells), phytocannabinoids (e.g., cannabidiol produced by the cannabis plant), and synthetic cannabinoids (e.g., HU-210), respectively.

[0355] 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, heating the carboxylic acid form will cause most of it to decarboxylate.

[0356] Furthermore, phytocannabinoids can exist 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 that they have almost opposite effects.

[0357] 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 (THCVA). More preferably, one or more cannabinoids are CBD or THC.

[0358] Furthermore, the formulation according to the present invention may contain at least one cannabinoid selected from the cannabinoids disclosed in A. Douglas Kinghorn et al., Phytocannabinoids, Vol. 103, Chapter 1, pp. 1-30.

[0359] 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 have been identified that share similar structural features but exhibit weak or no activity to cannabinoid receptors, yet are still called endocannabinoids. Examples of these endocannabinoid lipids include 2-acylglycerols, alkyl or alkenylglyceryl ethers, acyldopamine, and N-acylethanolamide, which contain 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 neuromodulatory and affect short-term memory, appetite, stress response, anxiety, immune function, and analgesia.

[0360] In one embodiment, the cannabinoid is palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the class of nuclear factor agonists.

[0361] Synthetic cannabinoids encompass a variety of distinct chemical classes: structurally related cannabinoids to THC; non-THC related cannabinoids, including aminoalkylindoles, 1,5-diallylpyrazole, quinoline, and allylsulfonamides (cannabimimetics); and endocannabinoid-related eicosanoids. All or any of these cannabinoids may be used in the present invention.

[0362] 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.

[0363] Preferably, the solid dosage form of the present invention may be used to treat or alleviate pain, epilepsy, cancer, nausea, inflammation, congenital disorders, neurological disorders, oral infections, toothache, sleep apnea, mental disorders, gastrointestinal disorders, inflammatory bowel disease, loss of appetite, diabetes, and fibromyalgia.

[0364] In a further embodiment of the present invention, oral cannabinoid formulations are suitable for use in the treatment of conditions requiring the administration of neuroprotective agents or anticonvulsant drug therapy.

[0365] Oral cannabinoid preparations may be used for the treatment of seizures.

[0366] Oral cannabinoid preparations may be used in the treatment of Dravet syndrome, Lennox-Gastaut syndrome, myoclonic seizures, juvenile myoclonic epilepsy, refractory epilepsy, schizophrenia, juvenile convulsions, West syndrome, infantile spasms, refractory infantile spasms, tuberous sclerosis, brain tumors, neuropathic pain, cannabis use disorder, post-traumatic stress disorder, anxiety, early psychosis, Alzheimer's disease, and autism.

[0367] The following non-limiting examples illustrate different variations of the present invention. The examples are intended to provide an overview of the invention, and therefore, the examples mentioned should not be understood as exhaustive. In particular, while CBD is used as the example compound, other cannabinoids may also be used. [Examples]

[0368] (Example 1) Premix: Hydrogenated vegetable oil (HVO) added to a mixture of isolated CBD and a mesoporous carrier. Approximately 1000g of mesoporous silica carrier (Syloid XDP 3050) provided by Grace was added to a Lodige high-shear mixer. Then, approximately 500g of cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600 micron sieve and added to the silica carrier composition. This mixture was mixed in the mixer at a speed of approximately 80 rpm for approximately 5 minutes. After activating the chopper (approximately 600 rpm) of the Lodige mixer, approximately 500g of HVO provided by AAK under the trademark Akocrem NT 76-33, which has a melting temperature of 30-35 degrees Celsius, was melted at a temperature of approximately 55 degrees Celsius and added to the mixture. After adding the lipid composition, the temperature in the mixer was approximately 49 degrees Celsius, and the mixture was mixed for a further 10 minutes. After 10 minutes, the temperature of the final mixture was approximately 51 degrees Celsius. A total of 2 kg of mixed powder premix was produced with a CBD content of approximately 250 mg / g.

[0369] Unless otherwise specified, in all examples, [%] refers to "mass%" and is also referred to as "wt%".

[0370] [Table 1]

[0371] [Table 2]

[0372] [Table 3]

[0373] (Example 2) Premix: Miglyol added to a mixture of isolated CBD and a mesoporous carrier. Approximately 1000g of mesoporous silica carrier (Syloid XDP 3050) provided by Grace was added to a Lodige high-shear mixer. Then, approximately 500g of cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600-micron sieve and added to the silica carrier composition. This mixture was mixed in the mixer at a speed of approximately 80 rpm for approximately 5 minutes. After activating the chopper (approximately 600 rpm) of the Lodige mixer, approximately 500g of Miglyol 812, a medium-chain triglyceride (MCT) provided by Sasol, was added to the mixture for a period of approximately 3 minutes. After adding Miglyol 812, the mixture was heated and mixed for a further 10 minutes. After 10 minutes, the temperature of the final mixture was approximately 51 degrees Celsius. A total of 2 kg of mixed powder premix was produced with a CBD content of approximately 250 mg / g.

[0374] [Table 4]

[0375] [Table 5]

[0376] [Table 6]

[0377] [Table 7]

[0378] (Example 3) Premix: High concentration - Hydrogenated vegetable oil (HVO) added to a mixture of isolated CBD and a mesoporous carrier. Approximately 1000g of mesoporous silica carrier (Syloid XDP 3050) provided by Grace was added to a Lodige high-shear mixer and heated to approximately 55 degrees Celsius. Then, approximately 750g of cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600-micron sieve and added to the silica carrier composition. This mixture was mixed in the mixer at a speed of approximately 80 rpm for approximately 5 minutes. After activating the chopper (approximately 600 rpm) of the Lodige mixer, approximately 250g of HVO provided by AAK under the trademark Akocrem NT 76-33, which has a melting temperature of 30-35 degrees Celsius, was melted at approximately 55 degrees Celsius and added to the mixture. After adding the lipid composition, the temperature in the mixer was approximately 49 degrees Celsius, and the mixture was mixed for a further 10 minutes. After 10 minutes, the temperature of the final mixture was approximately 51 degrees Celsius. A total of 2 kg of mixed powder premix was produced with a CBD content of approximately 375 mg / g.

[0379] [Table 8]

[0380] [Table 9]

[0381] [Table 10]

[0382] (Example 4) Premix: A mixture of hydrogenated vegetable oil (HVO) with isolated CBD added to a mesoporous carrier. Approximately 1000g of mesoporous silica support (Syloid XDP 3050) provided by Grace was added to a Lodige high-shear mixer. Then, approximately 500g of a cannabinoid powder composition (batch number MH B18592) containing 99% CBD isolate (phytocannabinoid) from cannabis plant tissue, provided by Medical Hemp, was mixed with approximately 500g of HVO provided by AAK under the trademark Akocrem NT 76-33, which has a melting temperature of 30-35 degrees Celsius. While stirring, the CBD-HVO mixture was heated to approximately 60 degrees Celsius to form a liquid solution of CBD in HVO. The CBD-HVO mixture was then added to the silica support. After adding the lipid composition, the mixture was mixed for approximately 10 minutes. A total of 2000g of mixed powder premix was produced.

[0383] [Table 11]

[0384] [Table 12]

[0385] [Table 13]

[0386] (Example 5) Premix: Miglyol mixture with isolated CBD added to a mesoporous carrier. Approximately 1000g of mesoporous silica carrier (Syloid XDP 3050) provided by Grace was added to a Lodige high-shear mixer. Then, approximately 500g of a cannabinoid powder composition (batch number MH B18592) containing 99% CBD isolate (phytocannabinoid) from cannabis plant tissue, provided by Medical Hemp, was mixed with approximately 500g of Miglyol 812, a medium-chain triglyceride (MCT), provided by Sasol. While stirring, the CBD-MCT mixture was heated to approximately 70 degrees Celsius to form a liquid solution of CBD in the MCT. The mixture of CBD and Miglyol 812 was then added to approximately 1000g of the silica carrier powder composition. After adding the lipid composition, the mixture was mixed for approximately 10 minutes. A total of 2000g of mixed powder premix was produced.

[0387] [Table 14]

[0388] [Table 15]

[0389] [Table 16]

[0390] (Example 6) Premix: Comparative sample - without non-volatile solvent A mesoporous silica carrier (Syloid XDP 3050) provided by Grace was added to a Lodige high-shear mixer. Then, a cannabinoid powder composition containing CBD isolate (phytocannabinoid) from cannabis plant tissue with approximately 99% CBD purity, provided by either Medical Hemp (batch number MH18592) or Valens (batch number BVA032013), was sieved through a 600-micron sieve and added to the silica carrier powder composition. This mixture was mixed at a speed of approximately 80 rpm for approximately 10 minutes. No solvent was used.

[0391] [Table 17]

[0392] (Example 7) Premix: Liquid self-emulsifying system with isolated CBD and mesoporous carrier Approximately 1000 g of mesoporous silica support (Syloid XDP 3050) provided by Grace was added to a Lodige high-shear mixer. Then, approximately 500 g of a cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600 micron sieve. The CBD was added to approximately 500 g of a composition containing lipids and surfactants (SEDDS composition). After activation of the Lodige mixer's chopper (approximately 600 rpm), the CBD-containing SEDDS composition was added to the mixture. A total of 2 kg of mixed powder premix with a CBD content of approximately 250 mg / g was prepared. Co-solvents and / or permeation enhancers may be added optionally. Additionally, one or more hydrophilic solvents may be added optionally.

[0393] [Table 18]

[0394] [Table 19]

[0395] [Table 20]

[0396] (Example 8) Premix: Solid self-emulsifying system with isolated CBD and mesoporous carrier Approximately 1000 g of mesoporous silica support (Syloid XDP 3050) provided by Grace was added to a Lodige high-shear mixer. Then, approximately 500 g of a cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600 micron sieve. The CBD was added to approximately 500 g of a composition containing wax and surfactant (SEDDS composition). After activation of the Lodige mixer's chopper (approximately 600 rpm), the CBD-containing SEDDS composition was added to the mixture. A total of 2 kg of mixed powder premix with a CBD content of approximately 250 mg / g was prepared. Co-solvents and / or permeation enhancers may be added optionally.

[0397] [Table 21]

[0398] [Table 22]

[0399] [Table 23]

[0400] (Example 9) Premix: Solid self-emulsifying system with isolated CBD Approximately 400 g of a cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600 micron sieve. The CBD was added to approximately 400 g of a composition containing wax and surfactant (SEDDS composition). A total of 800 g of the mixture, with a CBD content of approximately 500 mg / g, was prepared. Co-solvents and / or permeation enhancers may be added optionally.

[0401] [Table 24]

[0402] (Example 10) Premix: Solid self-emulsifying system with isolated CBD and permeation enhancer Approximately 400g of a cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600 micron sieve. The CBD was added to approximately 400g of a composition (SEDDS composition) containing wax, surfactant, and penetration enhancer. A total of 800g of the mixture was prepared, with a CBD content of approximately 500mg / g.

[0403] [Table 25]

[0404] (Example 11) Premix: Liquid self-emulsifying system with isolated CBD and permeation enhancer. Approximately 400g of a cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600 micron sieve. The CBD was added to approximately 400g of a composition (SEDDS composition) containing lipids, surfactants, and a penetration enhancer. A total of 800g of the mixture was prepared, with a CBD content of approximately 500mg / g.

[0405] [Table 26]

[0406] (Example 11A) Premix: Liquid self-emulsifying system with isolated CBD and PEG and non-PEG surfactants Approximately 300g of a cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600 micron sieve. The CBD was added to approximately 700g of a composition (SEDDS compositions A-Z) containing lipids, surfactants, and hydrophilic solvents. A total of 1000g of mixtures were prepared for each SEDDS composition to produce pre-formulated SEDDS A30-Z30 with a CBD content of approximately 300mg / g.

[0407] The above procedure was repeated by adding CBD to SEDDS compositions A to Z to produce pre-compounded SEDDS A25 to Z25 with a CBD content of approximately 250 mg / g.

[0408] The above procedure was repeated by adding CBD to SEDDS compositions A to Z to produce pre-compounded SEDDS A20 to Z20 with a CBD content of approximately 200 mg / g.

[0409] [Table 27]

[0410] [Table 28]

[0411] [Table 29]

[0412] [Table 30]

[0413] [Table 31]

[0414] [Table 32]

[0415] (Example 11B) SEDDS characterization The following table outlines the characteristic properties of the SEDDS from Example 11A (premix 1141 in Table 26F (Table 32), corresponding to a 20% CBD content), specifically the droplet size and zeta potential of the SEDDS, i.e., the pre-mixed SEDDS containing CBD. Both properties influence the properties of the SEDDS in terms of mucosal penetration.

[0416] The droplet size of pre-compounded SEDDS containing CBD was measured after emulsification at 1:100 (v / v) in deionized water and incubation at 37 degrees Celsius at 300 rpm for over 4 hours. The values ​​are average (n=4). The values ​​were measured after 4 hours.

[0417] Zeta potentials were measured for pre-compounded SEDDS containing CBD, emulsified at 1:100 (v / v) in deionized water and incubated at 37 degrees Celsius at 300 rpm for over 4 hours. The values ​​are averages (n=4). The values ​​were measured after 4 hours.

[0418] [Table 33]

[0419] (Example 12) Premix: Self-emulsifying system with isolated CBD Approximately 400g of a cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600 micron sieve. The CBD was added to approximately 400g of the SEDDS composition described in Table 27 (Table 34). A total of 800g of the mixture with a CBD content of approximately 500mg / g was prepared.

[0420] [Table 34]

[0421] [Table 35]

[0422] (Example 13) Premix: Self-emulsifying system with isolated CBD and carrier Approximately 1000g of mesoporous silica carrier (Syloid XDP 3050) provided by Grace was added to a Lodige high-shear mixer. Subsequently, approximately 500g of cannabinoid powder composition (batch number MH B18592) containing CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content, provided by Medical Hemp, was sieved through a 600 micron sieve. The CBD was added to approximately 500g of the SEDDS composition described in Example 12, Table 27 (Table 34) and Example 11A, Tables 26A-26F (Tables 27-32). After activating the chopper (approximately 600 rpm) of the Lodige mixer, the CBD-containing SEDDS composition was added to the mixture. A total of 2kg of mixed powder premix with a CBD content of approximately 250mg / g was produced. Penetration enhancers may be added as an option.

[0423] [Table 36]

[0424] [Table 37]

[0425] [Table 38]

[0426] (Example 14) Preparation of two-layered chewable tablets based on Examples 1-8 and 13 Tablets were manufactured based on the CBD-containing mixtures of Examples 1-8 and 13, with each layer comprising approximately 50% of the total tablet mass. The total mass of the tablets was 1800 mg. The tablets were manufactured using a standard tablet press (3090i, available from Fette GmbH) including a dispensing device (P 3200 C, available from Fette GmbH, Germany). Punch used: 16.00 mm round punch. Rotor speed used: 11 rpm.

[0427] A first layer (referred to as Layer 1) containing the CBD-containing mixture and additional components prepared in Examples 1-8 and 13 was prepared and tableted, followed by the tableting of a layer containing a gum base (referred to as Layer 2). Layer 1, having a mass of approximately 900 mg, was compressed with a compressive force of approximately 5 kN. Then, Layer 2, having a mass of approximately 900 mg and containing the gum base and additional components, was pressed over Layer 1 with a compressive force of 40 kN. The tablet press was operated by adjusting the filling depth and compression force so that the tablet mass and hardness met the acceptable standards. Pre-compression force may be included to avoid capping.

[0428] [Table 39]

[0429] [Table 40]

[0430] [Table 41]

[0431] (Example 15) Preparation of two-layered chewable tablets based on Examples 9-12 and 11A Tablets were manufactured based on the CBD-containing mixtures of Examples 9-12 and Example 11A, Tablets 26A-26F (Tables 27-32), with each layer comprising approximately 50% of the total tablet mass. The total mass of the tablets was 1800 mg. The tablets were manufactured using a standard tablet press (3090i, available from Fette GmbH) including a dispensing device (P 3200 C, available from Fette GmbH, Germany). Punch used: 16.00 mm round punch. Rotor speed used: 11 rpm.

[0432] A first layer (referred to as Layer 1) containing the CBD-containing mixture and additional components prepared in Examples 9-12 and Example 11A, Tables 26A-26F (Tables 27-32) was prepared and tableted, and then a layer containing a gum base (if present) (referred to as Layer 2) was tableted. Layer 1, having a mass of approximately 900 mg, was compressed with a compressive force of approximately 5 kN. Then, Layer 2, having a mass of approximately 900 mg and containing the gum base and additional components, was pressed on top of Layer 1 with a compressive force of 40 kN. The tablet press was operated by adjusting the filling depth and compression force so that the tablet mass and hardness met the acceptable standards. Pre-compression force may be included to avoid capping.

[0433] [Table 42]

[0434] [Table 43]

[0435] [Table 44]

[0436] (Example 16) Test method for content uniformity in premixtures and powder blends The uniformity (CU) of the CBD active substance in the premixture (premix sample) and the powder blend (powder blend), which is a mixture with additional components for processing into an oral dosage form, is determined using Test Method 2.9.40 "Uniformity of Dosage Units" in accordance with European Pharmacopoeia 10.8.

[0437] At least five samples, each with the same constant mass within the range of 0.25 to 2 grams, are taken from the powder mixture and analyzed. For each sample, the CBD active substance content is analyzed using standard HPLC techniques. Subsequently, the uniformity of content is calculated as the relative standard deviation (RSD) of the individual results.

[0438] This study included testing of powders for pouch, sachet, and stick packaging. The study was also conducted for other cannabinoids, including THC.

[0439] (Example 17) Test method for content uniformity in solid dosage forms The uniformity (CU) of the CBD active substance content in the solid dosage form, i.e., homogeneity, is determined using test method 2.9.40 "Uniformity of Dosage Units" in accordance with European Pharmacopoeia 10.8.

[0440] At least 10 samples are taken from solid dosage forms, such as tablets, and analyzed. For each sample, the content of CBD active substance is analyzed using standard HPLC techniques. Subsequently, the uniformity of content is calculated as the relative standard deviation (RSD) of the individual results.

[0441] This study included testing of chewable tablets, compressed chewing gum, and lozenges containing particulate matter. The study was also conducted for other cannabinoids, including THC.

[0442] (Example 18) In vivo release testing of solid dosage forms The sample solid dosage form was tested in a test panel of eight testers. Testers refrained from eating or drinking for at least 30 minutes before the start of any test. Testers were healthy individuals selected based on objectivity in accordance with specific requirements. The CBD content in the remaining solid dosage form residue was measured at specific usage time intervals, e.g., 0, 0.5, 1, 2, 3, 5, and 10 minutes. For each of the eight testers, a triple measurement was performed for the solid dosage form, resulting in a total of 24 measurements for each sample. The average of the 24 measurements was calculated, and the mass % release was calculated based on the original CBD content in the sample. If still present, the CBD content in the remaining solid dosage form residue was measured.

[0443] The solid dosage forms were weighed, placed in the mouth, and the testers were instructed to position and use the solid dosage form as intended. For chewing gum, the testers were instructed to chew the sample at a rate of 60 chews per minute. For lozenges, the testers were instructed to place the sample between the tongue and palate, then suck on the solid dosage form, turning it over every 0.5 minutes. Once the desired test time was achieved (0.5, 1, 2, 3, 5, and 10 minutes), the solid dosage form was removed and weighed directly in a measuring glass used for CBD content analysis. In vivo dissolution profiles were obtained by analyzing the CBD content in the solid dosage form at different dissolution times.

[0444] This study was conducted on chewable tablets, chewing gum, and lozenges containing particulate matter. It was also conducted on other cannabinoids, including THC.

[0445] (Example 19) In vitro release test of solid dosage form The sample solid dosage form was tested. The CBD content in the remaining solid dosage residue was measured at specific usage time intervals, e.g., 0, 0.5, 1, 2, 3, 5, and 10 minutes. Triple measurements were performed for the solid dosage form. The average of the measurements was calculated, and the mass % release was calculated based on the original CBD content in the sample. If still present, the CBD content in the remaining solid dosage form residue was measured.

[0446] The solid dosage form was weighed. Then, 25 ml of phosphate buffer was added to a 50 ml measuring tube with a screw cap. The solid dosage form was added to the tube. The tube was fixed horizontally on a shaking table. After shaking, the solid dosage form was analyzed for CBD content. In vitro profiles were obtained by analyzing the CBD content in the solid dosage form at different dissolution times.

[0447] This study was conducted on tablets, chewing gum, and lozenges containing particulate matter. It was also conducted on other cannabinoids, including THC.

[0448] (Example 20) In vitro release testing from premixture The corresponding tests were performed for the premixtures of Examples 1-8 and 13, following the outline of the procedure in Example 19.

[0449] (Example 21) In vitro release test from powder blend Corresponding tests were performed for powder blends containing the premixtures of Examples 1-8 and 13, following the general procedure outlined in Example 19.

[0450] The powder blends included testing for powders in pouch, sachet, and stick packaging.

[0451] (Example 22) Setting up sensory organ evaluation tests for solid dosage forms In addition to release measurements, sensory tests were performed either in vivo or in vitro to reveal crucial characteristics and properties of the solid dosage forms and powder blends. These sensory parameters are important indicators of the composition of the solid dosage form compositions. The composition provides underlying guidance on how the solid dosage forms resemble the composition of a comparative solid dosage form set as the baseline for a series of tests; that is, the solid dosage forms are compared to each other in a series of tests of preferably five samples. The test setup consisted of eight testers on the test panel. All testers were healthy individuals selected based on objectivity in accordance with specific requirements. Sensory analysis was performed according to ISO 4121-2003 under test conditions in accordance with ISO 8589. The results are the average of the results of the eight individuals.

[0452] Testers assigned a ranking from "+" to "+++++", where "+" was inferior and "+++++" was superior. That is, "++++++" meant the solid dosage form was superior to the standard, "+++" meant the solid dosage form was at the same level as the standard, and "+" meant the solid dosage form was far below the level of the standard. "0" indicated that it was not tested.

[0453] Four different parameters were tested in the test panel.

[0454] [Table 45]

[0455] "Rough texture" refers to the overall impression of the solid dosage form when placed in the mouth, specifically the impression of coarseness of the particles in the mouth upon administration, i.e., a rough feeling.

[0456] "Flavor" refers to the overall impression of the flavor of the solid dosage form during intended use. For example, a very low flavor experience resulted in a very low rank, and a flavor experience that was too high and not equivalent to the standard also resulted in a very low rank.

[0457] "Sweetness" refers to the overall impression of the taste of the solid dosage form during intended use, specifically regarding sweetness. For example, if the sweetness decreased rapidly, it received a very low rank, and if the sweetness was too strong and unpleasant, it also received a very low rank.

[0458] "Off-flavor" refers to the overall impression of off-flavors from one or more cannabinoids in the intended composition during use. For example, if an off-flavor (grassy, ​​bitter smell, throat irritation) is experienced in the throat, it will receive a low rank, and if any other unpleasant sensations are experienced, it will also receive a low rank.

[0459] "Grinding" refers to the overall impression when chewing a chewable solid dosage form, specifically the grinding sensation produced when it comes into contact with the teeth. For example, if grinding was experienced, it was given a lower rank.

[0460] (Example 23) Results regarding content uniformity in premixtures The procedure of Example 16 was applied to the above premix (premix sample), and the results revealed the remarkably excellent uniformity of content of the sample of the present invention. The results of the uniformity of content for the sample were revealed as a single value obtained as the relative standard deviation (RSD) of the CBD content of a large number of samples taken at the end of the premix preparation procedure.

[0461] (Example 24) Results regarding content uniformity in powder blends and solid dosage forms The procedure of Example 16 was applied to powder blends, which are powder premixes (powder premix samples) with additional components, as outlined in the oral dosage form formulation. The powder blends included testing for powders for pouch, sachet and stick packaging, as well as for use in solid dosage forms, including chewable tablets, chewing gum and lozenges containing the particulate components according to the above examples. The procedure of Example 17 was applied to solid dosage forms.

[0462] The content uniformity (CU) results for the samples are presented as a single value obtained as the relative standard deviation (RSD) of the CBD content of a large number of samples taken at the end of the preparation procedure. Individual samples were collected at different stages of the tableting process (e.g., start, middle, end), and content uniformity was then determined by analysis of pooled samples from the different process stages. The results revealed the remarkably excellent content uniformity of the samples of the present invention.

[0463] (Example 25) Results regarding release from solid dosage forms The procedure of Example 19 was performed on the solid dosage forms according to the above examples. The results revealed remarkably excellent release of the sample of the present invention. Similar excellent results were observed for gum-base-free tablets, FDT tablets, compressed chewing gum, and lozenges.

[0464] (Example 26) Results regarding release from premixture The procedure of Example 20 was performed on the premixture according to the above example. The results revealed the remarkably excellent release of the sample of the present invention.

[0465] (Example 27) Results regarding release from powder blends The procedure of Example 21 was performed on the powder blend according to the above example. The results revealed remarkably excellent release of the sample of the present invention. Excellent results were observed for the powder according to the above example for use in pouches, sachets, stick packaging and flowpacks.

[0466] (Example 28) Results regarding the setting of sensory organ evaluation tests for solid dosage forms To establish the advantages of the sensory properties of the solid samples of this application, the procedure in Example 22 was performed. Surprisingly good results were observed for chewable tablets, FDT tablets, compressed chewing gum, and lozenges, with or without a gum base.

[0467] (Example 29) Degradability of selected SEDDS To establish the degradability effect of selected SEDDS from Example 11A and Tables 26A-26F (Tables 27-32), efficacy studies were conducted. For SEDDS A, G, and P, the amount of CBD in the SEDDS was 20% by mass of the SEDDS (synthesized in Table 26F (Table 32) in Example 11A). For SEDDS C, E, I, and M, the amount of CBD in the SEDDS was 30% by mass of the SEDDS (synthesized in Table 26F (Table 32) in Example 11A).

[0468] In vitro studies were conducted based on the release of fatty acids (millimoles) from SEDDS formulations after 60 minutes (incubation time) of treatment with lipase. The amount of released fatty acids served as an indicator of degradability. Blank samples were prepared for assessment of the results.

[0469] [Table 46]

[0470] The results revealed that certain SEDDS containing relatively low amounts of PEG-containing surfactants, such as samples A20, C30, and E30, degraded relatively quickly. On the other hand, SEDDS containing relatively high amounts of PEG-containing surfactants degraded to a lesser degree. This trend was expected, as the PEG portion in the surfactant was expected to protect the SEDDS from degradation.

[0471] (Example 30) Effectiveness study Efficacy studies were conducted to establish the plasma pharmacokinetic (PK) profiles of selected SEDDSs in Sprague Dawley rats, based on Example 11A and Tables 26A-26F (Tables 27-32). The amount of CBD in the SEDDSs was approximately 20% by mass (synthesized in Table 26F (Table 32) in Example 11A).

[0472] Samples containing pre-formulated SEDDS with CBD (in deionized water) were administered to rats using standard oral gastric tube feeding techniques, i.e., by means of a tube that delivers SEDDS to the rat's stomach.

[0473] The study involved orally administering 6.643 mg of CBD per kg to rats, equivalent to the dose given to a human (70 kg) consuming 75 mg of CBD. Plasma CBD concentrations (mg / mL) were measured at specific time intervals to reveal in vivo CBD uptake. Values ​​are mean (n=7). The Epidiolex® standard was applied.

[0474] Area under the curve (AUC) was established for the 0–240 minute period and the 0–1440 minute period, which corresponds to the entire study period. Values ​​were applied to establish rat uptake at short-term scales (0–240 minutes) and long-term scales (240–1440 minutes), and to measure total CBD uptake in rats over the entire period.

[0475] In addition, the maximum plasma concentration (Cmax) was determined.

[0476] [Table 47]

[0477] As the AUC results show, G20 (containing a high content of PEG-containing surfactant) demonstrated significantly faster uptake within 240 minutes, representing 53.5% of total uptake at 1440 minutes, compared to 40.2% of A20 (without PEG-containing surfactant), and faster uptake than P20 (containing a lower content of PEG-containing surfactant than G20), which represented 43.2% of oral uptake at 1440 minutes. This was quite surprising, as it was theoretically expected that PEG-containing surfactants could pose a steric hindrance to cellular uptake. However, the exact opposite occurred when comparing SEDDS containing less or no PEG-containing surfactant.

[0478] Furthermore, the results were even more striking compared to Epidiolex®, as the uptake of Epidiolex® within 240 minutes accounted for 23.6% of the total oral uptake at 1440 minutes. Therefore, even for SEDDS without PEG-containing surfactants (here, 40.2% of the A20 value), uptake on a short-term scale was higher than that of the baseline Epidiolex®.

[0479] Since uptake on a short-term scale (0-240 minutes) is quite high for SEDDS containing PEG-containing surfactants, one prospect is to apply these SEDDS to accelerate the uptake of cannabinoids such as CBD, for example, in combination with SEDDS systems that provide sustained uptake.

[0480] Furthermore, as can be seen from the AUC results, total uptake (0-1440 min) was significantly higher for A20 than for all other SEDDS and Epidiolex®, specifically a value of 10337 min*ng / mL was observed for SEDDS A20 containing surfactants without a PEG moiety, which was considerably higher than SEDDS with high concentrations of surfactants containing PEG (8482 for G20 and 8575 for P20), and even higher than Epidiolex®. This was highly unexpected and surprising, as the degradation studies revealed in Example 29 showed that these SEDDS (containing surfactants without a PEG moiety) were degraded. Contrary to expectations, despite this degradation, the uptake was very high, considerably higher than that of the non-degraded SEDDS as revealed in Example 29. Therefore, total uptake (on both short-term and long-term scales) was unexpectedly high for SEDDS containing surfactants without a PEG moiety.

[0481] Furthermore, as can be seen from the AUC results, and also over longer time scales (within 240 minutes to 1440 minutes), the uptake was significantly higher for SEDDS with surfactants that do not contain the PEG portion (6185 min*ng / mL) compared to the values ​​of SEDDS with surfactants containing the PEG portion (4869 and 3947 min*ng / mL). This is evidence of higher uptake for these SEDDS over longer time scales compared to other SEDDS in the test. Also, the degradation test in Example 29 revealed degradation of these SEDDS, which was very surprising. Although this was very unexpected, the uptake was higher over longer time scales despite this fact and was comparable to the baseline Epidiolex®. One prospect is to apply these SEDDS for more sustained uptake of cannabinoids such as CBD, for example, in combination with SEDDS systems that provide faster uptake.

[0482] [Table 48]

[0483] As can be seen from the Cmax results, the maximum concentrations of A20, G20, and P20 were considerably higher than that of the baseline Epidiolex®. Therefore, these SEDDSs were superior to the baseline in terms of peak concentration, i.e., the maximum possible plasma concentration levels that can be obtained are higher. For SEDDSs (G20 and P20) with surfactants containing a PEG moiety, this was quite surprising, as it was expected that steric hindrance due to the PEG moiety might negatively affect uptake. However, the results prove otherwise. For SEDDS (A20) with surfactants without a PEG moiety, this was also unexpected, as in light of the degradation study revealed in Example 29, where it was shown that these SEDDSs were significantly degraded.

Claims

1. Orally soluble or chewable tablet powder formulations, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids in the aforementioned tablet powder formulation, wherein one or more of the self-emulsifying systems are i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) When the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble agents in an amount of 20 to 80% by mass of the aforementioned compressed powder tablet preparation, One or more flavorings and Includes, An orally soluble or chewable tablet powder formulation comprising one or more surfactants having a chemical structure including a polyethylene glycol (PEG) portion.

2. The oral-soluble or chewable tablet powder formulation according to claim 1, wherein one or more of the self-emulsifying systems are stable at a pH of about 1 to 4.

3. An orally soluble or chewable tablet powder formulation according to claim 1 or 2, wherein one or more of the self-emulsifying systems are stable at a pH of about 1 to 4, and when one or more of the carrier systems are released in the oral cavity, they are activatable for the gastrointestinal delivery of one or more of the cannabinoids.

4. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 3, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, and one or more of the surfactants having a chemical structure including a PEG moiety are present in at least 20% by mass of one or more of the liquid or solid self-emulsifying systems.

5. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 4, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, and one or more of the surfactants having a chemical structure including a PEG moiety are present in at least 25% by mass of one or more of the liquid or solid self-emulsifying systems.

6. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 5, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, and one or more of the surfactants having a chemical structure including a PEG moiety are present in an amount of at least 30% by mass of one or more of the liquid or solid self-emulsifying systems.

7. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 6, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, and one or more of the surfactants having a chemical structure including a PEG moiety are present in an amount of at least 35% by mass of one or more of the liquid or solid self-emulsifying systems.

8. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 7, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, and one or more of the surfactants having a chemical structure including a PEG moiety are present in an amount of at least 40% by mass of one or more of the liquid or solid self-emulsifying systems.

9. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 8, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, and one or more of the surfactants having a chemical structure including a PEG moiety are present in an amount of at least 50% by mass of one or more of the liquid or solid self-emulsifying systems.

10. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 9, wherein one or more of the isolated or synthetic cannabinoids are present in an amount of at least 20% by mass of one or more of the liquid or solid self-emulsifying systems.

11. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 10, wherein one or more of the isolated or synthetic cannabinoids are present in an amount of at least 30% by mass of one or more of the liquid or solid self-emulsifying systems.

12. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 11, wherein one or more of the isolated or synthetic cannabinoids are present in an amount of 10 to 30% by mass of the tablet powder formulation.

13. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 12, wherein one or more of the isolated or synthetic cannabinoids are present in an amount of 10 to 20% by mass of the tablet powder formulation.

14. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 13, wherein one or more of the isolated or synthetic cannabinoids are present in an amount of at least 15% by mass of the tablet powder formulation.

15. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 14, wherein one or more of the carrier systems are released from the oral-soluble or chewable tablet powder formulation in the oral cavity.

16. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 15, wherein at least 90% of one or more of the carrier systems are released from the oral cavity within 5 minutes after oral administration.

17. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 16, wherein up to 50% of one or more of the isolated or synthetic cannabinoids are released from one or more of the carrier systems 10 minutes after oral administration.

18. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 17, wherein up to 20% of one or more of the isolated or synthetic cannabinoids are released from one or more of the carrier systems 10 minutes after oral administration.

19. The orally soluble or chewable tablet powder formulation according to any one of claims 1 to 18, wherein the self-emulsifying system, when hydrated, forms an emulsion for the delivery of one or more cannabinoids to the mucosal surface in the gastrointestinal tract.

20. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 19, wherein the self-emulsifying system, when hydrated, forms an emulsion for the delivery of one or more cannabinoids to the mucosal surface in the small intestine of the gastrointestinal tract.

21. The orally soluble or chewable tablet powder formulation according to any one of claims 1 to 20, wherein the self-emulsifying system, when hydrated, forms an emulsion for the delivery of one or more cannabinoids to the mucosal surface in the colon of the gastrointestinal tract.

22. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 21, wherein one or more of the carrier systems provide a stable state for delivery of one or more of the cannabinoids to the mucosal surface in the stomach of the gastrointestinal tract.

23. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 22, wherein one or more of the self-emulsifying systems comprises one or more liquid self-emulsifying systems.

24. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 23, wherein one or more of the lipids comprises one or more oils.

25. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 24, wherein one or more of the lipids comprises one or more triglycerides.

26. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 25, wherein one or more of the lipids comprises one or more triglycerides of plant origin.

27. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 26, wherein one or more of the lipids comprises one or more oils selected from the group consisting of almond oil, castor oil, coconut oil, corn oil, cottonseed oil, flaxseed oil, olive oil, palm oil, peanut oil, rapeseed oil, safflower oil, sesame oil, soybean oil, sunflower oil, and combinations thereof.

28. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 27, wherein one or more of the lipids comprises one or more triglycerides selected from one or more C4 to C14 triglycerides.

29. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 28, wherein one or more of the lipids comprises one or more triglycerides including partially hydrogenated vegetable oil.

30. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 29, wherein one or more of the lipids comprises one or more triglycerides including fully hydrogenated vegetable oil.

31. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 30, wherein one or more of the lipids comprises one or more triglycerides containing caprylic acid in an amount of 50 to 80% by mass.

32. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 31, wherein one or more of the lipids comprises one or more triglycerides containing capric acid in an amount of 20 to 45% by mass.

33. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 32, wherein one or more of the lipids comprises one or more lipophilic compounds selected from the group consisting of glyceryl caprylate, glyceryl caprate, glyceryl monocaprylate, glyceryl monooleate, glyceryl monostearate, glyceryl monolinoleate, polyglyceryl-3 dioleate, propylene glycol dicaprylate, propylene glycol dilaurate, benzyl alcohol, alpha-tocopherol, isopropyl myristate, glycerol monocaprylate, and combinations thereof.

34. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 33, wherein one or more of the lipids do not contain flavoring oils.

35. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 34, wherein one or more of the lipids are present in an amount of 1 to 30% by mass of the oral-soluble or chewable tablet powder formulation.

36. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 35, wherein one or more of the lipids are present in an amount of 5 to 40% by mass of one or more of the self-emulsifying systems.

37. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 36, wherein one or more of the lipids improve the homogeneity of one or more of the cannabinoids in the oral-soluble or chewable tablet powder formulation.

38. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 37, wherein one or more of the lipids are present in an amount of 10 to 300 mg in the oral-soluble or chewable tablet powder formulation.

39. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 38, wherein one or more of the lipids are present in an amount of 50 to 300 mg in the oral-soluble or chewable tablet powder formulation.

40. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 39, wherein one or more of the self-emulsifying systems comprises one or more solid self-emulsifying systems.

41. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 40, wherein one or more of the waxes comprise a substance that is solid and / or semi-solid at 25 degrees Celsius.

42. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 41, wherein one or more of the waxes are present in an amount of 1 to 30% by mass of the oral-soluble or chewable tablet powder formulation.

43. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 42, wherein one or more of the waxes improve the homogeneity of one or more of the cannabinoids in the orally soluble or chewable tablet powder formulation.

44. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 43, wherein one or more of the waxes are present in the oral-soluble or chewable tablet powder formulation in an amount of 10 to 300 mg.

45. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 44, wherein one or more of the waxes are present in an amount of 50 to 300 mg in the oral-soluble or chewable tablet powder formulation.

46. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 45, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, selected from the group consisting of PEG-modified glycosphingolipid-based surfactants, PEG-containing polymer-based surfactants, PEGylated emulsifiers, and combinations thereof.

47. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 46, comprising one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, which are PEG-modified glycosphingolipid-based surfactants selected from the group consisting of polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan trioleate and combinations thereof.

48. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 47, comprising one or more surfactants having a chemical structure including a polyethylene glycol (PEG) portion, wherein one or more of the surfactants are PEG-containing polymer-based surfactants selected from the group consisting of poloxamer 124, poloxamer 188, poloxamer 338, poloxamer 407 and combinations thereof.

49. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 48, comprising one or more surfactants having a chemical structure including a polyethylene glycol (PEG) portion, wherein one or more of the surfactants is a PEGylated emulsifier selected from the group consisting of d-alpha-tocopheryl polyethylene glycol succinate, d-alpha-tocopheryl PEG-1000 succinate, PEG-15 hydroxystearate, PEG-30 castor oil, PEG-32 lauroyl glyceride, PEG-32 stearoyl glyceride, PEG-35 castor oil, PEG-40 hydrogenated castor oil, PEG-6 lauroyl glyceride, PEG-6 linoleoyl glyceride, PEG-6 oleoyl glyceride, PEG-8 caprylic / capric acid glyceride, polyoxyl 20 cetostearyl ether, polyoxyethylene-lauryl ether, polyoxyethylene-23-lauryl ether, and combinations thereof.

50. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 49, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure comprising a polyethylene glycol (PEG) moiety, wherein the surfactant comprises d-alpha-tocopheryl polyethylene glycol succinate.

51. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 50, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure comprising a polyethylene glycol (PEG) moiety containing polyoxyethylene-lauryl ether.

52. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 51, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure comprising a polyethylene glycol (PEG) moiety containing polyoxyethylene-23-lauryl ether.

53. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 52, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure comprising a polyethylene glycol (PEG) moiety containing poloxamer 188.

54. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 53, wherein one or more of the surfactants have an average HLB value greater than 6.

55. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 54, wherein one or more of the self-emulsifying systems further comprises one or more hydrophilic solvents.

56. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 55, wherein one or more of the self-emulsifying systems further comprises one or more hydrophilic solvents in an amount of at least 5% by mass of the mass of one or more of the liquid or solid self-emulsifying systems.

57. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 56, wherein one or more of the self-emulsifying systems further comprises one or more hydrophilic solvents in an amount of at least 10% by mass of the mass of one or more of the liquid or solid self-emulsifying systems.

58. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 57, wherein one or more of the self-emulsifying systems further comprises one or more hydrophilic solvents in an amount of at least 20% by mass of the mass of one or more of the liquid or solid self-emulsifying systems.

59. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 58, wherein one or more of the self-emulsifying systems further comprises one or more hydrophilic solvents selected from the group consisting of propylene glycol, acetyl tributyl citrate, acetyl triethyl citrate, dimethyl sulfoxide, ethanol, ethyl oleate, glycerol triacetate, diethylene glycol monoethyl ether, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, propan-2-ol, glycerol, triethyl citrate, and combinations thereof.

60. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 59, wherein one or more of the self-emulsifying systems further comprises one or more hydrophilic solvents containing propylene glycol.

61. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 60, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) portion.

62. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 61, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) portion, and one or more of the surfactants having a chemical structure that does not include a PEG portion are present in an amount of 0.1 to 20% by mass of one or more of the liquid or solid self-emulsifying systems.

63. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 62, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) portion, and one or more of the surfactants having a chemical structure that does not include a PEG portion are present in an amount of 0.1 to 10% by mass of one or more of the liquid or solid self-emulsifying systems.

64. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 63, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) portion, and one or more of the surfactants having a chemical structure that does not include a PEG portion are present in an amount of less than 5% by mass of one or more of the liquid or solid self-emulsifying systems.

65. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 64, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure that does not contain a polyethylene glycol (PEG) moiety, selected from the group consisting of monoglycerides, sugar-lipid based surfactants and combinations thereof.

66. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 65, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure that includes a polyglycerol ester of a fatty acid and does not include a polyethylene glycol (PEG) portion.

67. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 66, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure that does not contain a polyethylene glycol (PEG) portion, selected from the group consisting of decaglycerol mono and dioleate, hexaglycerol octastearate, polyglycerol ester of oleic acid, propylene glycol monocaprylate, propylene glycol monolaurate, triglycerol monooleate, polyglyceryl-4 oleyl ether olive, polyglyceryl-4 laurate / sebacate, polyglyceryl-4 caprylate / caprate, and combinations thereof.

68. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 67, comprising one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) portion, selected from the group consisting of sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, sorbitan trioleate, sucrose palmitate, sucrose stearate, and combinations thereof.

69. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 68, comprising one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) portion, wherein one or more of the surfactants include polyglyceryl-4 laurate / sevacate and / or polyglyceryl-4 caprylate / caprate.

70. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 69, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure that includes ascorbic acid palmitate and does not include a polyethylene glycol (PEG) portion.

71. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 70, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure that includes sodium lauryl sulfate and does not include a polyethylene glycol (PEG) portion.

72. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 71, wherein one or more of the surfactants comprises one or more surfactants having a chemical structure that contains soy phosphatidylcholine and does not contain a polyethylene glycol (PEG) moiety.

73. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 72, wherein one or more of the surfactants do not include one or more surfactants having a chemical structure that does not include a polyethylene glycol (PEG) portion.

74. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 73, wherein one or more of the isolated or synthetic cannabinoids are selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), and combinations thereof.

75. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 74, wherein one or more of the isolated or synthetic cannabinoids are selected from the group consisting of tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and combinations thereof.

76. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 75, wherein one or more of the isolated or synthetic cannabinoids comprises cannabidiol (CBD).

77. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 76, wherein one or more of the isolated or synthetic 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), cannabigerovalin (CBGV), cannabigerol monomethyl ether (CBGM), and combinations thereof.

78. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 77, wherein one or more of the isolated or synthetic cannabinoids are isolated cannabinoids.

79. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 78, wherein one or more of the isolated or synthetic cannabinoids are synthetic cannabinoids.

80. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 79, wherein one or more of the isolated or synthetic cannabinoids are not cannabinoid distillates having a cannabinoid purity of more than 80%.

81. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 80, wherein one or more of the isolated or synthetic cannabinoids are not cannabinoid extracts having a cannabinoid purity of less than 80%.

82. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 81, wherein one or more of the isolated or synthetic cannabinoids are present in an amount of at least 40 mg in the oral-soluble or chewable tablet powder formulation.

83. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 82, wherein one or more of the isolated or synthetic cannabinoids are present in an amount of at least 75 mg in the oral-soluble or chewable tablet powder formulation.

84. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 83, wherein one or more of the isolated or synthetic cannabinoids are present in an amount of at least 150 mg in the oral-soluble or chewable tablet powder formulation.

85. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 84, wherein one or more of the isolated or synthetic cannabinoids are present in an amount of at least 300 mg in the oral-soluble or chewable tablet powder formulation.

86. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 85, wherein one or more of the carrier systems comprises one or more solid carriers selected from the group consisting of silica, microcrystalline cellulose, cellulose, silicified microcrystalline cellulose, clay, talc, starch, pregelatinized starch, calcium carbonate, dicalcium phosphate, modified calcium carbonate, magnesium carbonate, magnesium aluminometasilicate, superporous silica, and mixtures thereof.

87. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 86, wherein one or more of the carrier systems comprises one or more microcrystalline cellulose carriers.

88. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 87, wherein one or more of the carrier systems comprises one or more modified calcium carbonate carriers.

89. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 88, wherein one or more of the carrier systems comprise one or more silica carriers.

90. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 89, wherein one or more of the carrier systems comprise one or more mesoporous silica carriers.

91. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 90, wherein one or more of the carrier systems comprise one or more mesoporous silica carriers comprising magnesium aluminometasilicate.

92. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 91, wherein one or more of the carrier systems comprise one or more mesoporous silica carriers comprising dicalcium phosphate.

93. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 92, wherein one or more of the carrier systems comprises one or more solid carriers having an average particle size of 20 to 200 microns.

94. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 93, wherein one or more of the carrier systems comprise one or more solid carriers having an average particle size of 30 to 150 microns.

95. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 94, wherein one or more of the carrier systems are present in an amount exceeding 10% by mass of the oral-soluble or chewable tablet powder formulation.

96. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 95, wherein one or more of the carrier systems are present in an amount exceeding 20% ​​by mass of the oral-soluble or chewable tablet powder formulation.

97. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 96, wherein one or more of the carrier systems are present in the oral-soluble or chewable tablet powder formulation in an amount of 30 to 1500 mg.

98. One or more of the carrier systems are 1.0 cm 3 An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 97, comprising one or more solid carriers having an average pore volume greater than / g.

99. One or more of the carrier systems are 1.5 cm 3 An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 98, comprising one or more solid carriers having an average pore volume greater than / g.

100. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 99, wherein one or more of the carrier systems comprises one or more solid carriers having an average density of 50 g / L or more.

101. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 100, wherein one or more of the carrier systems comprise one or more solid carriers having an average density of 50 to 400 g / L.

102. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 101, wherein one or more of the carrier systems comprise one or more solid carriers having an average density of 150 to 400 g / L.

103. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 102, wherein one or more of the carrier systems comprises one or more solid carriers not characterized as powder flow promoters.

104. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 103, wherein one or more of the liquid or solid self-emulsifying systems are present in the oral-soluble or chewable tablet powder formulation in an amount of 30 to 800 mg.

105. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 104, wherein one or more of the liquid or solid self-emulsifying systems are present in the oral-soluble or chewable tablet powder formulation in an amount of 30 to 300 mg.

106. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 105, wherein one or more of the isolated or synthetic cannabinoids are completely contained in one or more of the liquid or solid self-emulsifying systems.

107. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 106, comprising one or more cannabinoids separately from one or more of the liquid or solid self-emulsifying systems.

108. The orally soluble or chewable tablet powder formulation according to any one of claims 1 to 107, wherein one or more of the water-soluble agents are present in an amount of 30 to 80% by mass of the tablet powder formulation.

109. The orally soluble or chewable tablet powder formulation according to any one of claims 1 to 108, wherein one or more of the water-soluble agents are present in an amount of 40 to 80% by mass of the tablet powder formulation.

110. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 109, wherein one or more of the water-soluble agents comprise one or more sugar alcohol particles.

111. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 110, wherein one or more of the water-soluble agents comprises one or more sugar alcohol particles selected from the group consisting of sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, isomalt, and combinations thereof.

112. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 111, wherein one or more of the water-soluble agents comprises one or more sugar alcohol particles including non-directly compressible (non-DC) sugar alcohol particles and directly compressible (DC) sugar alcohol particles.

113. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 112, wherein one or more of the water-soluble agents comprises one or more sugar alcohol particles, including non-directly compressible (non-DC) sugar alcohol particles and directly compressible (DC) sugar alcohol particles, in a ratio of 0.2 to 1.2 non-DC to DC.

114. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 113, relating to an improved mouthfeel.

115. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 114, relating to an improved mouthfeel, including a less gritty texture.

116. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 115, relating to an improved mouthfeel, including less crunching noise when the oral-soluble or chewable tablet powder formulation is chewed.

117. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 116, associated with an improved mouthfeel due to one or more carrier systems compared to separately added carriers that do not contain one or more liquid or solid self-emulsifying systems.

118. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 117, relating to an improved mouthfeel due to the presence of one or more of the water-soluble agents.

119. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 118, further comprising one or more disintegrants.

120. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 119, further comprising one or more disintegrants selected from the group consisting of croscarmellose sodium, crospovidone, sodium starch glycolate, and combinations thereof.

121. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 120, further comprising at least one solubilizer selected from the group consisting of acacia, agar, alginic acid or a salt thereof, carbomer, carboxymethylcellulose, carrageenan, cellulose, chitosan, copovidone, cyclodextrin, ethylcellulose, gelatin, guar gum, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, hypromellose, inulin, methylcellulose, pectin, polycarbophil or a salt thereof, polyvinyl alcohol, pullulan, starch, tragacanth, trehalose, xanthan gum, and mixtures thereof.

122. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 121, further comprising at least one dissolving agent in an amount of 3 to 20% by mass of the oral-soluble or chewable tablet powder formulation.

123. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 122, further comprising one or more organic acids.

124. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 123, wherein one or more of the flavoring agents are present in an amount of 0.1 to 10% by mass of the oral-soluble or chewable tablet powder formulation.

125. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 124, wherein one or more of the self-emulsifying systems comprises one or more of the isolated or synthetic cannabinoids and one or more lipids in a mass ratio of cannabinoids to lipids of 10:1 to 1:

10.

126. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 125, wherein one or more of the self-emulsifying systems comprises one or more of the isolated or synthetic cannabinoids and one or more lipids in a mass ratio of cannabinoids to lipids of 10:1 to 1:

5.

127. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 126, wherein one or more of the self-emulsifying systems comprises one or more of the isolated or synthetic cannabinoids and one or more lipids in a mass ratio of cannabinoids to lipids of 8:1 to 1:

2.

128. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 127, wherein one or more of the self-emulsifying systems comprises one or more of the isolated or synthetic cannabinoids and one or more lipids in a mass ratio of cannabinoids to lipids of 4:1 to 1:

2.

129. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 128, wherein one or more of the self-emulsifying systems comprises one or more of the isolated or synthetic cannabinoids and one or more lipids in a mass ratio of cannabinoids to lipids of 3:1 to 1:

1.

130. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 129, wherein one or more of the self-emulsifying systems comprises one or more of the isolated or synthetic cannabinoids and one or more waxes in a mass ratio of 10:1 to 1:10 of cannabinoids to wax.

131. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 130, wherein one or more of the self-emulsifying systems comprises one or more of the isolated or synthetic cannabinoids and one or more waxes in a mass ratio of 10:1 to 1:5 of cannabinoids to wax.

132. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 131, wherein one or more of the self-emulsifying systems comprises one or more of the isolated or synthetic cannabinoids and one or more waxes in a mass ratio of 8:1 to 1:2 for cannabinoids to wax.

133. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 132, wherein one or more of the self-emulsifying systems comprises one or more of the isolated or synthetic cannabinoids and one or more waxes in a mass ratio of 4:1 to 1:2 of cannabinoids to wax.

134. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 133, wherein one or more of the self-emulsifying systems comprises one or more of the isolated or synthetic cannabinoids and one or more waxes in a mass ratio of 3:1 to 1:1 for cannabinoids to wax.

135. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 134, wherein one or more of the carrier systems comprises one or more solid carriers, and one or more of the carrier systems comprises one or more of the liquid or solid self-emulsifying systems in a mass ratio of 2:8 to 8:2 of solid carriers to liquid or solid self-emulsifying systems.

136. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 135, wherein one or more of the carrier systems comprises one or more solid carriers, and one or more of the carrier systems comprises one or more of the liquid or solid self-emulsifying systems in a mass ratio of 4:6 to 6:4 of solid carriers to liquid or solid self-emulsifying systems.

137. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 136, wherein one or more liquid or solid self-emulsifying systems, each containing at least 10% by mass of cannabinoids in the tablet powder formulation, comprises at least two separate liquid or solid self-emulsifying systems.

138. The orally soluble or chewable tablet powder formulation according to claim 137, wherein the first liquid or solid self-emulsifying system comprises one or more surfactants having a chemical structure including a polyethylene glycol (PEG) moiety, and the second liquid or solid self-emulsifying system comprises one or more surfactants having a chemical structure not including a polyethylene glycol (PEG) moiety.

139. The oral-soluble or chewable tablet powder formulation according to claim 138, wherein one or more surfactants having a chemical structure including a polyethylene glycol (PEG) portion are present in the first liquid or solid self-emulsifying system in an amount of at least 20% by mass of the first liquid or solid self-emulsifying system.

140. The oral-soluble or chewable tablet powder formulation according to claim 138 or 139, wherein one or more of the surfactants having a chemical structure that does not include a polyethylene glycol (PEG) portion are present in the second liquid or solid self-emulsifying system in an amount of at least 5% by mass of the second liquid or solid self-emulsifying system.

141. The oral-soluble or chewable tablet powder formulation according to any one of claims 138 to 140, wherein the first liquid or solid self-emulsifying system is located in a first compartment or module of the oral-soluble or chewable tablet powder formulation, and the second compartment or module of the oral-soluble or chewable tablet powder formulation comprises the second liquid or solid self-emulsifying system.

142. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 141, wherein the tablet is an orally soluble tablet.

143. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 142, which is an orally soluble tablet that disintegrates in the oral cavity within 2 minutes after oral administration.

144. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 143, which is a chewable tablet.

145. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 144, which is a lozenge containing a particulate component.

146. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 145, comprising a gum base.

147. An orally soluble or chewable tablet powder formulation according to any one of claims 1 to 146, wherein the compressed chewing gum tablet is a compressed chewing gum tablet.

148. The oral-soluble or chewable tablet powder formulation according to any one of claims 1 to 147, wherein the unit weight of the oral-soluble or chewable tablet powder formulation is 400 to 2000 mg.

149. Orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids of the aforementioned powder formulation, wherein one or more of the self-emulsifying systems are i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) When the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble agents in an amount of 20 to 80% by mass of the aforementioned powder formulation, One or more flavorings and Includes, An oral-soluble or chewable powder formulation comprising one or more surfactants having a chemical structure including a polyethylene glycol (PEG) portion.

150. The oral-soluble or chewable powder formulation according to claim 149, as further defined in any one of claims 2 to 141.

151. A stick package containing an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids of the aforementioned powder formulation, wherein one or more of the self-emulsifying systems are i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) When the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble agents in an amount of 20 to 80% by mass of the aforementioned powder formulation, One or more flavorings and Includes, A stick package containing an oral-soluble or chewable powder formulation, wherein one or more of the surfactants have a chemical structure including a polyethylene glycol (PEG) portion.

152. The stick packaging according to claim 151, wherein the unit volume mass of the oral-soluble or chewable powder formulation is 400 to 2000 mg.

153. The stick packaging according to claim 151 or 152, as defined in any one of claims 2 to 141.

154. A sachet containing an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids of the aforementioned powder formulation, wherein one or more of the self-emulsifying systems are i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) When the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble agents in an amount of 20 to 80% by mass of the aforementioned powder formulation, One or more flavorings and Includes, A sachet comprising an orally soluble or chewable powder formulation, wherein one or more of the surfactants have a chemical structure including a polyethylene glycol (PEG) portion.

155. The sachet according to claim 154, wherein the unit volume mass of the oral-soluble or chewable powder formulation is 400 to 2000 mg.

156. The sachet according to claim 154 or 155, as defined in any one of claims 2 to 141.

157. A pouch containing an orally soluble or chewable powder formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids of the aforementioned powder formulation, wherein one or more of the self-emulsifying systems are i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) When the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble agents in an amount of 20 to 80% by mass of the aforementioned powder formulation, One or more flavorings and Includes, A pouch containing an orally soluble or chewable powder formulation, wherein one or more of the surfactants have a chemical structure including a polyethylene glycol (PEG) portion.

158. The pouch according to claim 157, wherein the unit volume mass of the oral-soluble or chewable powder formulation is 400 to 2000 mg.

159. A pouch as defined in any one of claims 2 to 141, according to claim 157 or 158.

160. A capsule formulation, One or more carrier systems comprising one or more liquid or solid self-emulsifying systems containing at least 10% by mass of cannabinoids of the formulation, wherein one or more of the self-emulsifying systems are i) If the self-emulsifying system is a liquid self-emulsifying system, it comprises at least one or more surfactants, one or more lipids, and one or more isolated or synthetic cannabinoids, ii) When the self-emulsifying system is a solid self-emulsifying system, a carrier system comprising at least one or more surfactants, one or more waxes, and one or more isolated or synthetic cannabinoids, One or more water-soluble agents in an amount of 20 to 80% by mass of the aforementioned preparation, One or more flavorings and Includes, A capsule formulation comprising one or more surfactants having a chemical structure including a polyethylene glycol (PEG) portion.

161. The capsule according to claim 160, wherein the unit volume mass of the preparation is 400 to 2000 mg.

162. A capsule according to claim 160 or 161, comprising an orally soluble or chewable powder formulation.

163. A capsule as defined in any one of claims 2 to 141, according to any one of claims 160 to 162.

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