Cannabinoid lipid premixes

Abstract

The present invention relates to a powder pre-mix for oral administration of cannabinoids, the powder pre-mix comprising: a cannabinoid powder composition comprising one or more isolated cannabinoids in an amount of at least 2% by weight of the powder pre-mix; a lipid 5 composition comprising one or more triglycerides in an amount of at least 1.0% by weight of the powder pre-mix; and a sweetener powder composition comprising one or more sweeteners, wherein the weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1: 50 to 1: 1.

Description

Technical Field

[0001] The present invention relates to the field of cannabinoids. In particular, the present invention relates to powder premixes for oral administration of cannabinoids. Background Art

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

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

[0004] Oral administration of cannabinoids is a common route of administration. Cannabinoids are highly lipophilic, meaning they are soluble in lipids and some organic solvents, but essentially insoluble or only slightly soluble in water. Cannabinoids are soluble in highly non-polar solvents. Some of these solvents are not pharmaceutically acceptable, and pharmaceutically acceptable solvents need to be used in high concentrations to produce a solution.

[0005] A variety of solutions have been proposed in the prior art for oral formulations for the delivery of cannabinoids. Among these solutions, solid dosage forms, lozenges, chewing gums and pouches have been proposed. Although these solutions may have certain benefits for the oral delivery of cannabinoids (e.g., CBD or THC), these solutions mainly focus on the release from the application form or certain components that allow for effective absorption of the cannabinoids in the mucosa.

[0006] Typically, little attention has been paid to the accurate dosing and reliability of cannabinoids (e.g., CBD or THC) in oral formulations. For example, a homogenous product would be beneficial, but this is offset to some extent by the highly lipophilic nature of cannabinoids and the resulting potential for interaction with the remaining components in the oral formulation.

[0007] Improved homogeneity is desirable in the prior art, but the solutions provided to date have traditionally been considered less than suitable, also in part due to the desire to provide a fast-release product. Already available approaches for providing improved homogeneity have been shown to be associated with disadvantages, while at the same time providing a fast release of the cannabinoid is desired.

[0008] In formulating solid dosage forms, several challenges are associated with obtaining a homogenous mixture in which variations are avoided and safe and convenient delivery is achieved. Furthermore, a general tablet formulation that provides convenience to the user need not compromise, which is often the case if conventional modes of delivery are applied.

[0009] Furthermore, it is preferred to provide a formulation that may also contribute to the improved organoleptic properties of oral cannabinoid delivery. Important organoleptic properties here include crispness, texture, flavor perception, sweetness perception, and off-notes associated with the cannabinoids. These properties are not only relevant from the perspective of the convenience of the solid dosage form, but of course also in order to support the proper delivery of the cannabinoids from the tablet and avoid adverse side effects of the cannabinoids.

[0010] Another challenge is that cannabinoids tend to be associated with an off-note during administration due to their unique physicochemical properties. The taste masking challenge is even more significant when delivering higher release cannabinoids. If the off-note during administration is primarily sensory, it may affect convenience and, even more seriously, may also affect the delivery of the cannabinoid.

[0011] Therefore, there is a need in the art for powders and formulations that address the above challenges and problems in the prior art. In particular, there is a need in the art for powders that can be applied in a variety of application forms, such as tablets, sachets, chewing gums, and lozenges, that are both associated with adequate uniformity of cannabinoid content and provide appropriate organoleptic properties. More specifically, it is desirable that these formulations also be acceptable or improved with respect to taste masking and give the desired release during administration. Summary of the invention

[0012] Thus, there is provided a powder premix for oral administration of cannabinoids, the powder premix comprising: a cannabinoid powder composition comprising one or more isolated cannabinoids in an amount of at least 2% by weight of the powder premix; a lipid composition comprising one or more triglycerides in an amount of at least 1.0% by weight of the powder premix; and a sweetener powder composition comprising one or more sweeteners, wherein the weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:1.

[0013] In another aspect of the present invention, an oral administration form in which the powder is incorporated, for example, an oral administration form in which the powder is partially or completely incorporated, is provided.

[0014] In yet another aspect, a method of preparing a powder premix for oral administration of a cannabinoid is provided.

[0015] One of the advantages of the present invention is that it can provide accurate dosing of cannabinoids in oral formulations and reliability of formulation of cannabinoids (e.g., CBD or THC). For example, a homogenous product would be beneficial, but is offset to some extent by the highly lipophilic nature of the cannabinoids and the potential for interaction with the remaining components in the oral formulation.

[0016] Traditionally, the solutions provided to date have been considered less than suitable, partly due to the desire to provide a fast-release product. Already available approaches for providing improved homogeneity have been shown to be associated with disadvantages, while at the same time providing a fast release of the cannabinoid is required.

[0017] One of the prejudices in the prior art is that highly lipophilic cannabinoids may not be properly formulated into powder or solid dosage forms with other ingredients without damaging the other ingredients and interacting with each other in the system.

[0018] Another advantage is that the formulations according to the invention may also contribute to obtaining improved organoleptic properties for oral cannabinoid delivery. Important organoleptic properties here include crispness, texture, flavor perception, sweetness perception and cannabinoid-related anomalies. These properties are relevant not only from the perspective of the convenience of the solid dosage form, but also of course in order to support the proper delivery of the cannabinoid from the solid dosage form and avoid adverse side effects of the cannabinoid.

[0019] Yet another advantage is that the present invention can help address the off-characteristics during administration. When delivering higher release cannabinoids via such solid dosage forms, the taste masking challenge is even more profound. If the off-characteristics during administration are primarily sensory, this may affect convenience and, even more seriously, may also affect the delivery of the cannabinoids.

[0020] Unexpected results were observed in terms of improved content uniformity. Typically, the method for sample content uniformity is determined according to Ph. Eur. 10.8 when using test method 2.9.40. Uniformity of dosage units. Depending on the dose and proportion of the drug substance, the acceptance value (AV) is calculated using mass variation (MV) or content uniformity (CU). An appropriate analytical method is selected for content uniformity, for example using standard HPLC techniques.

[0021] When trying to obtain a highly uniform distribution, insufficient mixing can lead to uneven distribution, such as undesirable particle agglomeration in certain parts of the solid dosage form. In addition, even if these ingredients are mixed very thoroughly, undesirable processing of the mixture from mixing to the tablet press can also lead to segregation. For example, smaller particles can usually be segregated to the bottom of the container, resulting in different particle distributions of different solid dosage forms. Particularly when different ingredients have different particle sizes, segregation can lead to different contents in different solid dosage forms.

[0022] Compared to powders in formulations containing cannabinoid powder compositions where no lipid composition according to the invention was applied, the content uniformity was poor. This was highly unexpected for the inventors of the present invention and was not expected given the prior art attempts to provide a suitable solution.

[0023] In some embodiments of the invention, a series of at least 5 samples, each having the same fixed weight in the range of 0.25 to 2 g and taken from the powder mixture to be analyzed, vary with a relative standard deviation (RSD) of less than 10% with respect to the content of one or more cannabinoids.

[0024] In some embodiments of the invention, a series of at least 5 samples, each having the same fixed weight in the range of 0.25 to 2 g and taken from the powder mixture to be analyzed, vary with a relative standard deviation (RSD) of less than 5% with respect to the content of one or more cannabinoids.

[0025] In some embodiments of the invention, a series of at least 5 samples, each having the same fixed weight in the range of 0.25 to 2 g and taken from the powder mixture to be analyzed, vary with a relative standard deviation (RSD) of less than 2% with respect to the content of one or more cannabinoids.

[0026] In some embodiments of the present invention, the weight ratio of one or more triglycerides to one or more sweeteners is in the range of 1:50 to 1:2. In some embodiments of the present invention, the weight ratio of one or more triglycerides to one or more sweeteners is in the range of 1:50 to 1:3. In some embodiments of the present invention, the weight ratio of one or more triglycerides to one or more sweeteners is in the range of 1:50 to 1:4. In some embodiments of the present invention, the weight ratio of one or more triglycerides to one or more sweeteners is in the range of 1:50 to 1:5. In some embodiments of the present invention, the weight ratio of one or more triglycerides to one or more sweeteners is in the range of 1:50 to 1:6. In some embodiments of the present invention, the weight ratio of one or more triglycerides to one or more sweeteners is in the range of 1:50 to 1:7.

[0027] In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:10.

[0028] In some embodiments of the invention, the weight ratio of one or more triglycerides to one or more sweeteners is in the range of 1:40 to 1:10. In some embodiments of the invention, the weight ratio of one or more triglycerides to one or more sweeteners is in the range of 1:40 to 1:12. In some embodiments of the invention, the weight ratio of one or more triglycerides to one or more sweeteners is in the range of 1:40 to 1:15. In some embodiments of the invention, the weight ratio of one or more triglycerides to one or more sweeteners is in the range of 1:40 to 1:20.

[0029] In some embodiments of the invention, the one or more triglycerides are of plant origin. In some embodiments of the invention, the one or more triglycerides are free of triglycerides of animal origin.

[0030] In some embodiments of the present invention, one or more triglycerides are selected from one or more C4 to C14 triglycerides. In some embodiments of the present invention, one or more triglycerides are selected from one or more C4 to C12 triglycerides. In some embodiments of the present invention, one or more triglycerides are selected from one or more C6 to C14 triglycerides. In some embodiments of the present invention, one or more triglycerides are selected from one or more C6 to C12 triglycerides. In some embodiments of the present invention, one or more triglycerides are selected from one or more C6 to C10 triglycerides. In some embodiments of the present invention, one or more triglycerides are selected from one or more C8 to C12 triglycerides. In some embodiments of the present invention, one or more triglycerides are selected from one or more C8 to C10 triglycerides.

[0031] In some embodiments of the present invention, the one or more triglycerides comprise partially hydrogenated vegetable oil. In some embodiments of the present invention, the one or more triglycerides comprise fully hydrogenated vegetable oil (HVO).

[0032] In some embodiments of the invention, the one or more triglycerides are selected from triglycerides that are liquid at or above 0 degrees Celsius.

[0033] In some embodiments of the invention, the one or more triglycerides are a blend of triglycerides, such as a blend of corn oil and oleic acid, such as a blend of corn oil and oleic acid in a ratio of 1:3 to 3:1.

[0034] In some embodiments of the invention, one or more triglycerides are heated to a temperature above ambient temperature prior to addition to the premix.

[0035] In some embodiments of the present invention, one or more triglycerides are heated to a temperature of 50 to 80 degrees Celsius before being added to the premix. In some embodiments of the present invention, one or more triglycerides are heated to a temperature of 50 to 70 degrees Celsius before being added to the premix. In some embodiments of the present invention, one or more triglycerides are heated to a temperature of 50 to 60 degrees Celsius before being added to the premix. In some embodiments of the present invention, one or more triglycerides are heated to a temperature of 60 to 70 degrees Celsius before being added to the premix. In some embodiments of the present invention, one or more triglycerides are heated to a temperature of 40 to 80 degrees Celsius before being added to the premix. In some embodiments of the present invention, one or more triglycerides are heated to a temperature of 40 to 70 degrees Celsius before being added to the premix.

[0036] In some embodiments of the invention, one or more triglycerides are selected from triglycerides that are liquid at 20 degrees Celsius or above. In some embodiments of the invention, one or more triglycerides are selected from triglycerides that are liquid at 25 degrees Celsius or above. In some embodiments of the invention, one or more triglycerides are selected from triglycerides that are liquid at 30 degrees Celsius or above. In some embodiments of the invention, one or more triglycerides are selected from triglycerides that are liquid at 40 degrees Celsius or above.

[0037] In some embodiments of the invention, the one or more triglycerides are selected from triglycerides having a melting temperature of 25 to 50 degrees Celsius. In some embodiments of the invention, the one or more triglycerides are selected from triglycerides having a melting temperature of 25 to 40 degrees Celsius. In some embodiments of the invention, the one or more triglycerides are selected from triglycerides having a melting temperature of 30 to 40 degrees Celsius. In some embodiments of the invention, the one or more triglycerides are selected from triglycerides having a melting temperature of 30 to 50 degrees Celsius.

[0038] In some embodiments of the present invention, one or more triglycerides include caprylic acid in an amount of 50% to 80% by weight. In some embodiments of the present invention, one or more triglycerides include caprylic acid in an amount of 50% to 70% by weight. In some embodiments of the present invention, one or more triglycerides include caprylic acid in an amount of 50% to 90% by weight. In some embodiments of the present invention, one or more triglycerides include caprylic acid in an amount of 60% to 90% by weight. In some embodiments of the present invention, one or more triglycerides include caprylic acid in an amount of 65% to 80% by weight.

[0039] In some embodiments of the present invention, one or more triglycerides include capric acid in an amount of 20% to 45% by weight. In some embodiments of the present invention, one or more triglycerides include capric acid in an amount of 20% to 50% by weight. In some embodiments of the present invention, one or more triglycerides include capric acid in an amount of 20% to 40% by weight. In some embodiments of the present invention, one or more triglycerides include capric acid in an amount of 20% to 35% by weight. In some embodiments of the present invention, one or more triglycerides include capric acid in an amount of 25% to 50% by weight. In some embodiments of the present invention, one or more triglycerides include capric acid in an amount of 25% to 40% by weight. In some embodiments of the present invention, one or more triglycerides include capric acid in an amount of 30% to 50% by weight. In some embodiments of the present invention, one or more triglycerides include capric acid in an amount of 30% to 45% by weight. In some embodiments of the present invention, one or more triglycerides include capric acid in an amount of 20% to 30% by weight.

[0040] In some embodiments of the invention, the one or more triglycerides comprise caprylic acid in an amount of 65 wt % to 80 wt % and capric acid in an amount of 20 wt % to 35 wt %.

[0041] In some embodiments of the invention, the one or more triglycerides comprise caprylic acid in an amount of 50% to 65% by weight and capric acid in an amount of 30% to 45% by weight.

[0042] In some embodiments of the invention, one or more triglycerides comprise coconut oil and / or corn oil and / or oleic acid. In some embodiments of the invention, one or more triglycerides consist essentially of coconut oil and / or corn oil and / or oleic acid. In some embodiments of the invention, one or more triglycerides are coconut oil and / or corn oil and / or oleic acid.

[0043] In some embodiments of the invention, the one or more triglycerides are present in an amount of at least 1.5% by weight of the powder premix.

[0044] In some embodiments of the invention, the one or more triglycerides are present in an amount of at least 2.0% by weight of the powder premix.

[0045] In some embodiments of the invention, the one or more triglycerides are present in an amount of at least 2.5% by weight of the powder premix.

[0046] In some embodiments of the invention, the one or more triglycerides are present in an amount of at least 3.0% by weight of the powder premix.

[0047] In some embodiments of the invention, the one or more triglycerides are present in an amount of at least 4.0% by weight of the powder premix.

[0048] In some embodiments of the present invention, one or more triglycerides are present in an amount of at least 5.0% by weight of a powder premix. In some embodiments of the present invention, one or more triglycerides are present in an amount of at least 6.0% by weight of a powder premix. In some embodiments of the present invention, one or more triglycerides are present in an amount of at least 7.0% by weight of a powder premix. In some embodiments of the present invention, one or more triglycerides are present in an amount of at least 8.0% by weight of a powder premix. In some embodiments of the present invention, one or more triglycerides are present in an amount of at least 9.0% by weight of a powder premix. In some embodiments of the present invention, one or more triglycerides are present in an amount of at least 10.0% by weight of a powder premix.

[0049] In some embodiments of the present invention, one or more triglycerides are present in an amount of at least 15.0% by weight of a powder premix. In some embodiments of the present invention, one or more triglycerides are present in an amount of at least 20.0% by weight of a powder premix. In some embodiments of the present invention, one or more triglycerides are present in an amount of at least 25.0% by weight of a powder premix. In some embodiments of the present invention, one or more triglycerides are present in an amount of at least 30.0% by weight of a powder premix.

[0050] In some embodiments of the invention, one or more triglycerides are present in an amount of 1% to 30.0% by weight of a powder premix. In some embodiments of the invention, one or more triglycerides are present in an amount of 1% to 25.0% by weight of a powder premix. In some embodiments of the invention, one or more triglycerides are present in an amount of 1% to 20.0% by weight of a powder premix.

[0051] In some embodiments of the invention, one or more triglycerides are present in an amount of 2% to 30.0% by weight of a powder premix. In some embodiments of the invention, one or more triglycerides are present in an amount of 2% to 25.0% by weight of a powder premix. In some embodiments of the invention, one or more triglycerides are present in an amount of 2% to 20.0% by weight of a powder premix.

[0052] In some embodiments of the invention, one or more triglycerides are present in an amount of 5% to 30.0% by weight of a powder premix. In some embodiments of the invention, one or more triglycerides are present in an amount of 5% to 25.0% by weight of a powder premix. In some embodiments of the invention, one or more triglycerides are present in an amount of 5% to 20.0% by weight of a powder premix.

[0053] In some embodiments of the invention, the one or more sweeteners are present in an amount of at least 40% by weight of the powder premix.

[0054] In some embodiments of the invention, the one or more sweeteners are present in an amount of at least 50% by weight of the powder premix.

[0055] In some embodiments of the invention, the one or more sweeteners are present in an amount of at least 60% by weight of the powder premix.

[0056] In some embodiments of the invention, the one or more sweeteners are present in an amount of at least 70% by weight of the powder premix.

[0057] In some embodiments of the invention, the one or more sweeteners are present in an amount of at least 75% by weight of the powder premix.

[0058] In some embodiments of the present invention, one or more sweeteners are present in an amount of at least 80 % by weight of a powder premix. In some embodiments of the present invention, one or more sweeteners are present in an amount of at least 90 % by weight of a powder premix. In some embodiments of the present invention, one or more sweeteners are present in an amount of at least 95 % by weight of a powder premix.

[0059] In some embodiments of the present invention, one or more sweeteners are selected from sugar-containing components, alone or in combination, such as sucrose, dextrose, maltose, saccharose, lactose, sorbitol, dextrin, trehalose, D-tagatose, dried invert sugar, fructose, levulose, galactose, corn syrup solids, glucose syrup, etc. These sugar sweeteners may also be included as wetting agents.

[0060] In some embodiments of the invention, the one or more sweeteners comprises dextrose. In some embodiments of the invention, the one or more sweeteners is dextrose.

[0061] In some embodiments of the invention, the one or more sweeteners comprise dextrin. In some embodiments of the invention, the one or more sweeteners are dextrins.

[0062] In some embodiments of the invention, the one or more sweeteners comprises sucrose. In some embodiments of the invention, the one or more sweeteners is sucrose.

[0063] In some embodiments of the invention, the one or more sweeteners comprises fructose. In some embodiments of the invention, the one or more sweeteners is fructose.

[0064] In some embodiments of the invention, the one or more sweeteners comprise one or more sugar alcohols.

[0065] In some embodiments of the present invention, the one or more sugar alcohols are selected from sorbitol, xylitol, maltitol, isomalt, mannitol, erythritol, lactitol, and combinations thereof.

[0066] In some embodiments of the present invention, the one or more sugar alcohols are selected from the group consisting of xylitol, erythritol, maltitol, mannitol, and combinations thereof.

[0067] In some embodiments of the invention, the one or more sugar alcohols comprises xylitol. In some embodiments of the invention, the one or more sugar alcohols is xylitol.

[0068] In some embodiments of the invention, the one or more sugar alcohols comprises erythritol. In some embodiments of the invention, the one or more sugar alcohols is erythritol.

[0069] In some embodiments of the invention, the one or more sugar alcohols comprise mannitol. In some embodiments of the invention, the one or more sugar alcohols are mannitol.

[0070] In some embodiments of the invention, the one or more sugar alcohols comprises maltitol. In some embodiments of the invention, the one or more sugar alcohols is maltitol.

[0071] In some embodiments of the invention, the one or more sugar alcohols comprise granulated sugar alcohol particles.

[0072] In some embodiments of the invention, the one or more sugar alcohols comprise non-direct (non-DC) sugar alcohol particles.

[0073] In some embodiments of the invention, the one or more sweeteners comprise one or more sugars.

[0074] In some embodiments of the invention, the one or more sweeteners comprise at least two types of sweetener particles.

[0075] In some embodiments of the invention, one or more sweeteners include sweetener particles with a particle size of less than 250 microns of particles exceeding 50%. In some embodiments of the invention, one or more sweeteners include sweetener particles with a particle size of less than 250 microns of particles exceeding 60%. In some embodiments of the invention, one or more sweeteners include sweetener particles with a particle size of less than 250 microns of particles exceeding 70%. In some embodiments of the invention, one or more sweeteners include sweetener particles with a particle size of less than 250 microns of particles exceeding 80%.

[0076] In some embodiments of the invention, one or more sweeteners include sweetener particles having a particle size greater than 500 microns of particles exceeding 20%. In some embodiments of the invention, one or more sweeteners include sweetener particles having a particle size greater than 500 microns of particles exceeding 30%. In some embodiments of the invention, one or more sweeteners include sweetener particles having a particle size greater than 500 microns of particles exceeding 50%.

[0077] In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:40 to 1: 1. In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:30 to 1: 1. In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:20 to 1: 1. In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:15 to 1: 1.

[0078] In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:10 to 1:1. In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:10 to 1:2. In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:8 to 1:2. In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:7 to 1:2. In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:6 to 1:2. In some embodiments of the invention, the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:5 to 1:2.

[0079] In some embodiments of the invention, the weight ratio of one or more triglycerides to one or more isolated cannabinoids is in the range of 1:40 to 1:5, such as 1:40 to 1:4, such as 1:40 to 1:3, such as 1:40 to 1:2, such as 1:40 to 1:1.

[0080] In some embodiments of the invention, the weight ratio of one or more triglycerides to one or more isolated cannabinoids is in the range of 1:20 to 1:5, such as 1:20 to 1:4, such as 1:20 to 1:3, such as 1:20 to 1:2, such as 1:20 to 1:1.

[0081] In some embodiments of the invention, the weight ratio of one or more triglycerides to one or more isolated cannabinoids is in the range of 1:10 to 1:5, such as 1:10 to 1:4, such as 1:10 to 1:3, such as 1:10 to 1:2, such as 1:10 to 1:1.

[0082] In some embodiments of the invention, the weight ratio of one or more triglycerides to one or more isolated cannabinoids is in the range of 1:5 to 1:4, such as 1:5 to 1:3, such as 1:5 to 1:2.

[0083] In some embodiments of the invention, the weight ratio of one or more triglycerides to one or more isolated cannabinoids is in the range of 1:4 to 4:1, such as 1:4 to 3:1, such as 1:4 to 2:1, such as 1:4 to 1:1, such as 1:4 to 1:2.

[0084] In some embodiments of the invention, the weight ratio of one or more triglycerides to one or more isolated cannabinoids is in the range of 1:3 to 4:1, such as 1:2 to 4:1, such as 1:1 to 4:1, such as 2:1 to 4:1.

[0085] In some embodiments of the invention, the one or more isolated cannabinoids are present in an amount of at least 5% by weight of the powder premix. In some embodiments of the invention, the one or more isolated cannabinoids are present in an amount of at least 7% by weight of the powder premix.

[0086] In some embodiments of the invention, the one or more isolated cannabinoids are present in an amount of at least 10% by weight of the powder premix. In some embodiments of the invention, the one or more isolated cannabinoids are present in an amount of at least 15% by weight of the powder premix.

[0087] In some embodiments of the invention, the one or more isolated cannabinoids are present in an amount of at least 20% by weight of the powder premix. In some embodiments of the invention, the one or more isolated cannabinoids are present in an amount of at least 25% by weight of the powder premix.

[0088] In some embodiments of the invention, the one or more isolated cannabinoids are present in an amount of at least 30% by weight of the powder premix. In some embodiments of the invention, the one or more isolated cannabinoids are present in an amount of at least 35% by weight of the powder premix. In some embodiments of the invention, the one or more isolated cannabinoids are present in an amount of at least 40% by weight of the powder premix.

[0089] In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder mixture in an amount of 0.1 to 400 mg. In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder mixture in an amount of 0.1 to 300 mg. In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder mixture in an amount of 0.1 to 250 mg.

[0090] In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder premix in an amount of 1 to 200 mg. In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder premix in an amount of 1 to 150 mg. In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder premix in an amount of 1 to 100 mg.

[0091] In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder premix in an amount of 5 to 200 mg. In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder premix in an amount of 5 to 100 mg.

[0092] In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder premix in an amount of 3 to 200 mg. In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder premix in an amount of 3 to 100 mg.

[0093] In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder premix in an amount of 2 to 200 mg. In some embodiments of the invention, the one or more isolated cannabinoids are present in the powder premix in an amount of 2 to 100 mg.

[0094] In some embodiments of the invention, one or more isolated cannabinoids are present in the powder pre-mix in an amount of 10 to 100 mg.

[0095] In some embodiments of the present invention, the one or more isolated cannabinoids are selected from cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), and combinations thereof.

[0096] In some embodiments of the invention, the one or more isolated cannabinoids are selected from tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and combinations thereof.

[0097] In some embodiments of the invention, the one or more isolated cannabinoids comprises cannabigerol (CBG).

[0098] In one embodiment of the invention, the one or more cannabinoids comprise cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), salts and derivatives thereof.

[0099] In one embodiment of the invention, the one or more cannabinoids comprise tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabinolic acid (THCV), salts and derivatives thereof.

[0100] In one embodiment of the invention, the one or more cannabinoids comprises cannabigerol (CBG), its salts and derivatives.

[0101] In some embodiments of the present invention, the cannabinoid is selected from cannabidiol (CBD), cannabidiolic acid (CBDA), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), cannabielsoin (CBE), iso-tetrahydrocannabinol (iso-THC), cannabicyclol (CBL), cannabidipyran cycloalkane (CBT), cannabivarin (CBV), tetrahydrocannabinol (THCV), cannabidiol (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethylether (CBGM), salts thereof, derivatives thereof, and mixtures of cannabinoids.

[0102] In one embodiment of the invention, the one or more cannabinoids include cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidiol (CBDV), salts and derivatives thereof. In one embodiment of the invention, the one or more cannabinoids include CBD, salts and derivatives thereof (including analogs and homologues). In one embodiment of the invention, the one or more cannabinoids include CBD. In one embodiment of the invention, the one or more cannabinoids are CBD.

[0103] In one embodiment of the invention, the one or more cannabinoids comprise tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabinolic acid (THCV), salts and derivatives thereof. In one embodiment of the invention, the one or more cannabinoids comprise tetrahydrocannabinol (THC). Preferably, THC is intended to mean (-)-trans-Δ 9 -tetrahydrocannabinol, i.e. (6aR,10aR)-Δ-9-tetrahydrocannabinol). In one embodiment of the invention, the one or more cannabinoids is THC.

[0104] In one embodiment of the invention, wherein the one or more cannabinoids comprises at least two cannabinoids. In one embodiment of the invention, the one or more cannabinoids comprises a combination of several cannabinoids (e.g., THC and CBD). In one embodiment of the invention, the one or more cannabinoids is a combination of THC and CBD.

[0105] In some embodiments of the invention, the one or more isolated cannabinoids are present in a purity of at least 90% (w / w).

[0106] In some embodiments of the invention, the one or more isolated cannabinoids are present in a purity of at least 95% (w / w).

[0107] In some embodiments of the invention, the one or more isolated cannabinoids are present in a purity of at least 98% (w / w).

[0108] In some embodiments of the invention, the one or more isolated cannabinoids do not comprise a cannabinoid distillate.

[0109] In some embodiments of the invention, the one or more isolated cannabinoids do not comprise a cannabinoid extract.

[0110] In some embodiments of the invention, the one or more isolated cannabinoids does not comprise the one or more isolated cannabinoids at a purity of less than 90% (w / w).

[0111] In some embodiments of the invention, one or more isolated cannabinoids are dissolved in one or more triglycerides prior to mixing with the sweetener powder composition.

[0112] In some embodiments of the invention, one or more isolated cannabinoids are added to a sweetener powder composition prior to mixing with one or more triglycerides.

[0113] In some embodiments of the invention, one or more triglycerides are added to the sweetener powder composition prior to mixing with the one or more isolated cannabinoids.

[0114] In some embodiments of the invention, additional ingredients are added to the premix.

[0115] Generally speaking, when reference is made to "adding" additional ingredients to a premix or similar expressions, it is intended to mean that these ingredients are added to the total mixture. Thus, depending on the operations and amounts involved, a premix may also be added to additional ingredients. Generally, "premix" or "premix" are expressions that are used interchangeably. Additional ingredients combined with a premix are often referred to as a "powder blend" or similar expressions. A "powder blend" may contain additional ingredients.

[0116] In some embodiments of the present invention, additional ingredients are added to the premix or powder blend, and the additional ingredients are selected from flavors, dry binders, tableting aids, anti-caking agents, surfactants, emulsifiers, antioxidants, enhancers, mucoadhesives, absorption enhancers, high intensity sweeteners, softeners, colorants, additional active ingredients, water-soluble indigestible polysaccharides, water-insoluble polysaccharides, and any combination thereof.

[0117] In some embodiments of the invention, one or more flavoring agents are added to the premix or powder blend.

[0118] In some embodiments of the invention, a high intensity sweetener is added to a premix or powder blend.

[0119] In some embodiments of the invention, the premix is ​​a ready-to-use premix.

[0120] In some embodiments of the invention, the premix is ​​used in combination with additional ingredients in an amount of 10% to 99.9% by weight.

[0121] In some embodiments of the invention, the premix is ​​used in an amount of 10% to 99.9% by weight in combination with additional ingredients such as oral care agents.

[0122] In one embodiment of the invention, the oral care agent comprises one or more antiplaque agents.

[0123] Antiplaque agents include a fluoride ion source. An antiplaque agent is any substance that acts by itself to inhibit the accumulation of bacterial deposits on oral surfaces. Examples include xylitol and other antimicrobial agents. When used in combination with an extract, the inhibitory effect of xylitol on oral microorganisms may have a greater effect because the extract also acts to disable the microorganisms.

[0124] Typical examples of particularly desirable active ingredients in view of anti-plaque effectiveness, safety and formulation are: naficillin, oxacillin, vancomycin, clindamycin, erythromycin, trimethoprim-sulfamethoxazole, trimethoprim-sulphamethoxazole, rifampin, ciprofloxacin, broad-spectrum penicillins, amoxicillin, gentamicin, ceftriazoxone, cefotaxime, chloramphenicol, clavunate, sulbactam, probenecid, doxycycline, spectinomycin, cefixime, penicillin G, minocycline, β-lactamase inhibitors; meziocillin, piperacillin, aztreonam, norfloxacin, trimethoprim, ceftazidime, dapsone. Halogenated diphenyl ethers, for example 2',4,4'-trichloro-2-hydroxydiphenyl ether (triclosan), 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether. Halogenated salicylanilides, for example 4',5-dibromo-salicylicylanilide, 3,4',5-trichloro-salicylicylanilide, 3,4',5-tribromo-salicylicylanilide, 2,3,3',5-tetrachloro-salicylicylanilide, 3,3,3',5-tetrachloro-salicylicylanilide, 3,5-dibromo-3'-trifluoromethyl-salicylicylanilide, 5-n-octanoyl-3'-trifluoromethyl-salicylicylanilide, 3,5-dibromo-4'-trifluoromethyl-salicylicylanilide, 3,5-dibromo-3'-trifluoromethyl-salicylicylanilide (Flurophene). Benzoates, for example methylparaben, ethylparaben, propylparaben, butylparaben. Halogenated carbanilide, for example 3,4,4'-trichlorocarbanilide, 3-trifluoromethyl-4,4'-dichlorocarbanilide or 3,3,4'-trichlorocarbanilide.Phenolic compounds (including phenol and its homologues, monoalkyl and polyalkyl and aromatic halogenated-phenols and their homologues), such as phenol, 2-methyl-phenol, 3-methyl-phenol, 4-methyl-phenol, 4-ethyl-phenol, 2,4-dimethyl-phenol, 2,5-dimethyl-phenol, 3,4-dimethyl-phenol, 2,6-dimethyl-phenol, 4-n-propyl-phenol, 4-n-butyl-phenol, 4-n-pentyl-phenol, 4-tert-pentyl-phenol, 4-n-hexyl-phenol, 4-n-heptyl-phenol, 2-methoxy-4-(2-propenyl)-phenol (eugenol), 2-isopropyl-5-methyl-phenol (thymol), monoalkyl-halogenated phenols and polyalkyl-halogenated phenols substituted phenols and aralkyl-halogenated phenols, methyl-p-chlorophenol, ethyl-p-chlorophenol, n-propyl-p-chlorophenol, n-butyl-p-chlorophenol, n-pentyl-p-chlorophenol, sec-pentyl-p-chlorophenol, n-hexyl-p-chlorophenol, cyclohexyl-p-chlorophenol, n-heptyl-p-chlorophenol, n-octyl-p-chlorophenol, o-chlorophenol, methyl-o-chlorophenol, ethyl-o-chlorophenol, n-propyl-o-chlorophenol, n-butyl-o-chlorophenol, n-pentyl-o-chlorophenol, tert-pentyl-o-chlorophenol, n-hexyl-o-chlorophenol, n-heptyl-o-chlorophenol, p-chlorophenol, o-benzyl-p-chlorophenol, o-benzyl-m-methyl-p-chlorophenol, o-benzyl-m-, m-dimethyl-p-chlorophenol, o-phenylethyl-p-chlorophenol, o-phenylethyl 6-isopropyl-3-methyl-p-chlorophenol, 2-ethyl-3,5-dimethyl-p-chlorophenol, 6-sec-butyl-3-methyl-p-chlorophenol, 2-isopropyl-3,5-dimethyl-p-chlorophenol, 6-diethylmethyl-3-methyl-p-chlorophenol, 6-isopropyl-2-ethyl-3-methyl-p-chlorophenol, 2-sec-pentyl-3,5-dimethyl-p-chlorophenol, 2-diethylmethyl-3,5-dimethyl-p-chlorophenol, 6-sec-octyl-3-methyl-p-chlorophenol, 4-bromobenzene Phenol, methyl-p-bromophenol, ethyl-p-bromophenol, n-propyl-p-bromophenol, n-butyl-p-bromophenol, n-pentyl-p-bromophenol, sec-pentyl-p-bromophenol, n-hexyl-p-bromophenol, cyclohexyl-p-bromophenol, o-bromophenol, tert-amyl-o-bromophenol, n-hexyl-o-bromophenol, n-propyl-m-, m-dimethyl-o-bromophenol, 2-phenyl-phenol, 4-chloro-2-methyl-phenol, 4-chloro-3-methyl-phenol, 4-chloro-3,5-dimethyl-phenol, 2,4-dichloro-3,5-dimethyl-phenol, 3,4,5,6-tetrabromo-2-methylphenol, 5-methyl-2-pentylphenol 4-isopropyl-3-methylphenol 5-chloro-2-hydroxydiphenyl-methane.Resorcinol and its derivatives, such as resorcinol, methyl-resorcinol, ethyl-resorcinol, n-propyl-resorcinol, n-butyl-resorcinol, n-pentyl-resorcinol, n-hexyl-resorcinol, n-heptyl-resorcinol, n-octyl-resorcinol, n-nonyl-resorcinol, phenyl-resorcinol, benzyl-resorcinol, phenethyl-resorcinol, phenylpropyl-resorcinol, p-chlorobenzyl-resorcinol, 5-chloro-2,4-dihydroxydiphenyl-methane, 4'-chloro-2,4-dihydroxy bisphenol compounds, such as bisphenol A, 2,2'-methylene-bis-(4-chlorophenol), 2,2'-methylene-bis-(3,4,6-trichlorophenol) (hexachlorophenol), 2,2'-methylene-bis-(4-chloro-6-bromophenol), bis-(2-hydroxy-3,5-dichlorophenyl)-sulfide, bis-(2-hydroxy-5-chlorobenzyl)-sulfide.

[0125] Exemplary polyphosphate compounds having plaque inhibiting properties are dialkali metal pyrophosphates and tetraalkali metal pyrophosphates in hydrated or non-hydrated form and mixtures thereof. Exemplary pyrophosphates are Na2H2P2O7, Na4P2O7 and K4P2O7. Other suitable polyphosphates include hydrated or non-hydrated alkali metal tripolyphosphates, such as Na5P3O10 and K5P3O10.

[0126] In one embodiment of the invention, the active ingredient comprises one or more anti-gingivitis agents.

[0127] The anti-gingivitis agent can be an anti-inflammatory agent, such as salicylic acid derivatives (e.g., aspirin), para-aminophenol derivatives (e.g., acetaminophen), indole and indene acetic acids (indo-methacin, sulindac, and etodalac), heteroaryl acetic acids (tolmetin, diclofenac, and ketorolac), aryl propionic acid derivatives (ibuprofen, naproxen, ketoprofen, fenopren, promazine), anthranilic acid-(mefenamic acid, meclofenamic acid), enolic acid (piroxicam, tenoxicam, phenylbutazone, and oxyphenthatrazone), lactic acid bacteria (LAB), osteopontin (ONP), IG-Lyt, hexefene, Aloe Vera, chlorhexidine, myrrh, or sage.

[0128] Antigingivitis agents also include psychotherapeutic agents such as thorazine, serentil, mellaril, millazine, tindal, permitil, prolixin, trilafon, stelazine, suprazine, taractan, navan, clozaril, haldol, halperon, loxitane, moban, orap, risperdal, alprazolam, chlordiaepoxide, clonazepam, clorezepate, diazepam, halazepam, lorazepam, razepam, oxazepam, prazepam, buspirone, elvavil, anafranil, adapin, sinequan, tofranil, surmontil, asendin, norpramin, pertofrane, ludiomil, pamelor, vivactil, prozac, luvox, paxil, zoloft, effexor, welibutrin, serzone, desyrel, nardil, parnate, or eldepryl.

[0129] In one embodiment of the present invention, the oral care agent comprises one or more dental cosmetic ingredients.

[0130] Dental cosmetic ingredients include whitening agents. These are conveniently selected from the tooth color modifying substances that can be considered among the oral care active substances that can be used in the tablets according to the present invention. These substances are suitable for modifying the color of teeth to satisfy consumers, such as those listed in CTFA Cosmetic Ingredient Handbook, 3.sup.rd Edition, Cosmetic and Fragrances Association Inc., Washington D.C. (1982), which is incorporated herein by reference. Specific examples include talc, mica, magnesium carbonate, calcium carbonate, calcium pyrophosphate, baking soda, Icelandic moss, bamboo, sodium hexametaphosphate, magnesium silicate, magnesium aluminum carbonate, silicon dioxide, titanium dioxide, zinc oxide, iron oxide red, iron oxide brown, iron oxide yellow, iron oxide black, ferric ammonium ferrocyanide, manganese violet, ultramarine, nylon powder, polyethylene powder, methacrylate powder, polystyrene powder, silk powder, crystalline cellulose, starch, titanium mica, titanium oxide mica, bismuth oxychloride, and mixtures thereof. Typical levels are from about 0.05% to about 20% by weight of the composition, preferably from about 0.1% to about 15% by weight, and most preferably from about 0.25% to about 10% by weight.

[0131] Whitening agents for use herein may also include substances that remove or bleach intrinsic or exogenous coloration on or in the tooth surface. Such substances are selected from peroxides, metal chlorites, perborates, percarbonates, peroxyacids, persulfates, and combinations thereof. Suitable peroxide compounds include hydrogen peroxide, urea peroxide, calcium peroxide, carbamide peroxide, and mixtures thereof. Suitable metal chlorites include calcium chlorite, barium chlorite, magnesium chlorite, lithium chlorite, sodium chlorite, and potassium chlorite. Additional bleaching substances may be hypochlorites and chlorine dioxide. Preferred percarbonates are sodium percarbonate. Preferred persulfates are oxones. The amounts of these substances depend on the available oxygen or chlorine.

[0132] In one embodiment of the present invention, the oral care agent comprises one or more abrasives.

[0133] In the scope of the present invention, oral tablets may contain abrasives. Typical materials include silica gel and precipitates, alumina, phosphates, and mixtures thereof. Specific examples include dicalcium orthophosphate dihydrate, calcium pyrophosphate, bamboo, tricalcium phosphate, hydrated alumina, beta calcium pyrophosphate, calcium carbonate, sodium polymetaphosphate, sodium hexametaphosphate, Calgen, Giltex, Quadrafos, Hagan phosphate, micromet, monocalcium phosphate, monocalcium phosphate, dicalcium orthophosphate dibasic calcium phosphate, calcium carbonate salts, cacti, calcichew, calcidia, citrical, aragonite, calcite, valerite, aluminum oxide, alumina, silicon dioxide, silica, silicic anhydride, and resin abrasive materials, such as granular condensation products of urea and formaldehyde, etc., such as disclosed in U.S. Patent No. 3,070,510. A mixture of polishing agents can also be used.

[0134] The average particle size of the silica polishing material is generally about 0.1 to about 30 microns; and preferably about 5 to about 15 microns. The polishing agent can be precipitated silica or silica gel, such as the silica dry gel described in U.S. Patent No. 3,538,230 or U.S. Patent No. 3,862,307. Preferred is the silica dry gel sold by WR Grace and Company, Davison Chemical Division under the name "Syloid". Precipitated silica materials are also preferred, such as those sold by JM Huber Corporation under the trade name "Zeodent", especially silica with the name "Zeodent 119". The types of silica tooth polishing agents that can be used in the tablets of the present invention are described in more detail in U.S. Patent No. 4,340,583. In the tablets according to the present invention, the polishing agent is generally present in the range of about 6% to about 70% by weight of the tablet, preferably about 10% to about 50% by weight. In one aspect of the present invention, a solid dosage form for oral administration of cannabinoids is provided, which comprises a premix according to the present invention.

[0135] In some embodiments of the invention, the premix is ​​present in an amount of 10% to 100% by weight of the solid dosage form. In some embodiments of the invention, the premix is ​​present in an amount of about 100% by weight of the solid dosage form. In some embodiments of the invention, the premix is ​​present in an amount of substantially 100% by weight of the solid dosage form. In some embodiments of the invention, the premix is ​​present in an amount of 10% to 90% by weight of the solid dosage form.

[0136] In some embodiments of the present invention, the premix is ​​present in an amount of 15% to 75% by weight of the solid dosage form. In some embodiments of the present invention, the premix is ​​present in an amount of 20% to 70% by weight of the solid dosage form. In some embodiments of the present invention, the premix is ​​present in an amount of 25% to 60% by weight of the solid dosage form. In some embodiments of the present invention, the premix is ​​present in an amount of 30% to 50% by weight of the solid dosage form.

[0137] In some embodiments of the invention, a series of at least 10 solid dosage forms comprises one or more cannabinoids, the amount of the one or more cannabinoids varying by a relative standard deviation (RSD) of less than 5%.

[0138] Typically, the method used for sample content uniformity is determined according to Ph. Eur. 10.8 using Test Method 2.9.40. Uniformity of Dosage Units. Depending on the dose and proportion of the drug substance, the Acceptable Value (AV) is calculated using either Mass Variation (MV) or Content Uniformity (CU). Select the appropriate analytical method for content uniformity.

[0139] In some embodiments of the invention, a series of at least 10 solid dosage forms comprises one or more cannabinoids in amounts that vary with a relative standard deviation (RSD) of less than 2%.

[0140] In one aspect of the invention there is provided a tablet for oral administration of a cannabinoid comprising a pre-mix according to the invention.

[0141] In some embodiments of the invention, the premix is ​​present in an amount of 10% to 100% by weight of the tablet.

[0142] In some embodiments of the invention, the premix is ​​present in an amount of 15% to 75% by weight of the tablet.

[0143] In some embodiments of the invention, the tablet comprises, in addition to the one or more sweeteners in the premix, one or more sugar alcohols selected from the group consisting of sorbitol, erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof.

[0144] In some embodiments of the invention, the tablet comprises one or more sweeteners in addition to the one or more sweeteners in the premix in an amount of 20% to 80% by weight of the tablet.

[0145] In some embodiments of the invention, a series of at least 10 tablets comprises one or more active pharmaceutical ingredients in amounts that vary with a relative standard deviation (RSD) of less than 5%.

[0146] Typically, methods for tablet content uniformity are determined according to Ph. Eur. 10.8 using test method 2.9.40. Uniformity of dosage units. Depending on the dose and proportion of the drug substance, the acceptable value (AV) is calculated using either mass variation (MV) or content uniformity (CU). An appropriate analytical method is selected for content uniformity.

[0147] In some embodiments of the invention, a series of at least 10 tablets comprises one or more cannabinoids in amounts that vary with a relative standard deviation (RSD) of less than 2%.

[0148] In some embodiments of the present invention, the tablet comprises directly compressible (DC) sugar alcohol granules and non-directly compressible (non-DC) sugar alcohol granules.

[0149] In some embodiments of the present invention, the weight ratio of the non-DC sugar alcohol particles to the DC sugar alcohol particles in the tablet is 0.2 to 1.2.

[0150] In some embodiments of the present invention, the weight ratio of the non-DC sugar alcohol particles to the DC sugar alcohol particles in the tablet is 0.3 to 0.7.

[0151] In some embodiments of the invention, the tablet comprises one or more insoluble components selected from the group consisting of silicon dioxide, microcrystalline cellulose, cellulose, silicified microcrystalline cellulose, clay, talc, starch, pregelatinized starch, calcium carbonate, dicalcium phosphate, magnesium carbonate, magnesium aluminum metasilicate, hyper porous silica, and mixtures thereof.

[0152] In some embodiments of the invention, the tablet comprises one or more binders in an amount of 0.1% to 6% by weight of the tablet.

[0153] In some embodiments of the invention, the tablet comprises one or more binders in an amount of 0.1% to 8% by weight of the tablet, such as 0.1% to 7% by weight, such as 1% to 7% by weight, such as 2% to 7% by weight, such as 0.1% to 6% by weight, such as 1% to 6% by weight.

[0154] In some embodiments of the invention, the tablet comprises at least two modules, and wherein the premix is ​​contained in at least one module of the tablet.

[0155] In some embodiments of the invention, the tablet comprises additional ingredients selected from the group consisting of flavors, dry binders, tableting aids, anti-caking agents, surfactants, emulsifiers, antioxidants, enhancers, mucoadhesives, absorption enhancers, high intensity sweeteners, softeners, colorants, additional active ingredients, water-soluble indigestible polysaccharides, water-insoluble polysaccharides, and any combination thereof.

[0156] In one aspect of the invention there is provided a chewing gum for oral administration of cannabinoids comprising a pre-mix according to the invention.

[0157] In some embodiments of the invention, the premix is ​​present in an amount of 15% to 75% by weight of the chewing gum.

[0158] In some embodiments of the invention, a series of at least 10 chewing gums comprises one or more cannabinoids in amounts varying by a relative standard deviation (RSD) of less than 5%.

[0159] Typically, methods for cannabinoid content uniformity in chewing gum are determined using Test Method 2.9.40. Uniformity of Dosage Units according to European Pharmacopoeia 10.8. Depending on the dose and proportion of the drug substance, the Acceptable Value (AV) is calculated using either Mass Variation (MV) or Content Uniformity (CU). An appropriate analytical method is selected for content uniformity.

[0160] In some embodiments of the invention, a series of at least 10 chewing gums comprises one or more cannabinoids in amounts varying by a relative standard deviation (RSD) of less than 2%.

[0161] In some embodiments of the present invention, the chewing gum comprises a gum base in an amount of 20% to 40% by weight of the chewing gum, and wherein the chewing gum is designed to be chewed into a coherent residual containing a water-insoluble component.

[0162] In some embodiments of the present invention, the chewing gum comprises a gum base, and wherein the gum base comprises an elastomer selected from the group consisting of styrene-butadiene rubber (SBR), butyl rubber, polyisobutylene (PIB), and combinations thereof.

[0163] In some embodiments of the present invention, the chewing gum comprises a gum base, and wherein the gum base comprises at least 5% by weight of an elastomer.

[0164] In some embodiments of the present invention, the chewing gum comprises a gum base, and wherein the gum base comprises a gum base resin selected from natural resins and / or synthetic resins.

[0165] In some embodiments of the present invention, the chewing gum comprises a gum base, and wherein the gum base comprises at least 5% by weight of a gum base resin.

[0166] In some embodiments of the present invention, the chewing gum comprises a gum base, and wherein the gum base comprises gum base particles having an average particle size of 400 μm to 1400 μm.

[0167] In some embodiments of the present invention, the chewing gum comprises, in addition to the one or more sweeteners in the premix, one or more sugar alcohols selected from the group consisting of sorbitol, erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof.

[0168] In some embodiments of the invention, the chewing gum comprises one or more sweeteners in addition to the one or more sweeteners in the premix in an amount of 20% to 60% by weight of the chewing gum.

[0169] In some embodiments of the invention, a series of at least 10 compressed chewing gums comprises one or more cannabinoids in amounts varying by a relative standard deviation (RSD) of less than 5%.

[0170] Typically, methods for cannabinoid content uniformity in compressed chewing gum are determined according to European Pharmacopoeia 10.8 using Test Method 2.9.40. Uniformity of Dosage Units. Depending on the dose and proportion of the drug substance, the acceptable value (AV) is calculated using either mass variation (MV) or content uniformity (CU). An appropriate analytical method is selected for content uniformity.

[0171] In some embodiments of the invention, a series of at least 10 compressed chewing gums comprises one or more cannabinoids in amounts varying by a relative standard deviation (RSD) of less than 2%.

[0172] In some embodiments of the invention, the chewing gum comprises at least two compressed modules, and wherein the premix is ​​contained in at least one of the two compressed modules.

[0173] In some embodiments of the present invention, the chewing gum comprises at least two compressed modules, and wherein the two modules are different in composition.

[0174] In some embodiments of the present invention, the chewing gum comprises at least two compressed modules, and wherein at least one of the two compressed modules does not comprise a gum base.

[0175] In some embodiments of the present invention, the chewing gum comprises additional ingredients selected from the group consisting of flavors, dry binders, tableting aids, anti-caking agents, surfactants, emulsifiers, antioxidants, enhancers, mucoadhesives, absorption enhancers, high intensity sweeteners, softeners, colorants, additional active ingredients, water-soluble indigestible polysaccharides, water-insoluble polysaccharides, and any combination thereof.

[0176] In one aspect of the invention there is provided a lozenge for oral administration of a cannabinoid comprising a pre-mix according to the invention.

[0177] In some embodiments of the invention, the premix is ​​present in an amount of 10% to 100% by weight of the tablet.

[0178] In some embodiments of the invention, the premix is ​​present in an amount of 15% to 75% by weight of the tablet.

[0179] In some embodiments of the invention, a series of at least 10 lozenges comprises one or more cannabinoids in amounts that vary with a relative standard deviation (RSD) of less than 5%.

[0180] Typically, methods for tablet content uniformity are determined according to Ph. Eur. 10.8 using test method 2.9.40. Uniformity of dosage units. Depending on the dose and proportion of the drug substance, the acceptable value (AV) is calculated using either mass variation (MV) or content uniformity (CU). An appropriate analytical method is selected for content uniformity.

[0181] In some embodiments of the invention, a series of at least 10 lozenges comprises one or more cannabinoids in amounts that vary with a relative standard deviation (RSD) of less than 2%.

[0182] In some embodiments of the invention, the lozenge comprises, in addition to the one or more sweeteners in the premix, one or more sugar alcohols selected from the group consisting of sorbitol, erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof.

[0183] In some embodiments of the invention, the lozenge contains one or more sweeteners in addition to the one or more sweeteners in the premix in an amount of 20% to 60% by weight of the lozenge.

[0184] In some embodiments of the invention, the lozenge comprises one or more insoluble components selected from the group consisting of silicon dioxide, microcrystalline cellulose, cellulose, silicified microcrystalline cellulose, clay, talc, starch, pregelatinized starch, calcium carbonate, dicalcium phosphate, magnesium carbonate, magnesium aluminum metasilicate, superporous silica, and mixtures thereof.

[0185] In some embodiments of the invention, the lozenge comprises one or more disintegrants operable to disintegrate the lozenge within 1 minute or less of contact with oral saliva.

[0186] In some embodiments of the invention, the tablet comprises one or more disintegrants selected from the group consisting of croscarmellose sodium, crospovidone, sodium starch glycolate, and combinations thereof.

[0187] In some embodiments of the invention, the tablet comprises one or more disintegrants in an amount of 0.5% to 25% by weight of the tablet.

[0188] In some embodiments of the invention, the lozenges comprise additional ingredients selected from the group consisting of flavors, dry binders, tableting aids, anti-caking agents, surfactants, emulsifiers, antioxidants, enhancers, mucoadhesives, absorption enhancers, high intensity sweeteners, softeners, colorants, additional active ingredients, water-soluble indigestible polysaccharides, water-insoluble polysaccharides, and any combination thereof.

[0189] In one aspect of the invention there is provided a sachet for oral administration of a cannabinoid comprising a pre-mix according to the invention.

[0190] In some embodiments of the invention, the premix is ​​present in an amount of 10% to 100% by weight of the sachet.

[0191] In some embodiments of the invention, the premix is ​​present in an amount of 15% to 75% by weight of the sachet.

[0192] In some embodiments of the invention, a series of at least 10 pouches comprises one or more cannabinoids in amounts varying by a relative standard deviation (RSD) of less than 5%.

[0193] Typically, the method for uniformity of the contents of a sachet is determined according to Ph. Eur. 10.8 using Test Method 2.9.40. Uniformity of Dosage Units. Depending on the dose and proportion of the drug substance, the Acceptable Value (AV) is calculated using either Mass Variation (MV) or Content Uniformity (CU). For Content Uniformity select the appropriate analytical method.

[0194] In some embodiments of the invention, a series of at least 10 pouches comprises one or more cannabinoids in amounts varying by a relative standard deviation (RSD) of less than 2%.

[0195] In some embodiments of the present invention, the pouch comprises one or more insoluble components selected from the group consisting of silicon dioxide, clay, talc, starch, pregelatinized starch, calcium carbonate, dicalcium phosphate, magnesium carbonate, magnesium aluminum metasilicate, superporous silica, and mixtures thereof.

[0196] In some embodiments of the invention, the sachets comprise one or more insoluble fibers.

[0197] In some embodiments of the invention, the pouch comprises one or more insoluble fibers selected from the group consisting of wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, bran fiber, bamboo fiber, powdered cellulose, microcrystalline cellulose, and combinations thereof.

[0198] In some embodiments of the invention, the pouch comprises, in addition to the one or more sweeteners in the premix, one or more sugar alcohols selected from the group consisting of sorbitol, erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof.

[0199] In some embodiments of the invention, the sachet comprises one or more sweeteners in addition to the one or more sweeteners in the premix in an amount of 20% to 60% by weight of the sachet.

[0200] In some embodiments of the invention, the pouch comprises additional ingredients selected from the group consisting of flavors, dry binders, anti-caking agents, surfactants, emulsifiers, antioxidants, enhancers, mucoadhesives, absorption enhancers, high intensity sweeteners, softeners, colorants, additional active ingredients, water-soluble indigestible polysaccharides, water-insoluble polysaccharides, and any combination thereof.

[0201] In one aspect of the invention, there is provided a method of preparing a powder premix for oral administration of a cannabinoid, the method comprising the steps of:

[0202] i) dissolving or dispersing a cannabinoid powder composition comprising one or more isolated cannabinoids in a lipid composition comprising one or more triglycerides, and then

[0203] ii) mixing a sweetener powder composition comprising one or more sweeteners with the mixture obtained in i) to obtain a powder premix,

[0204] The weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:1.

[0205] In some embodiments of the invention, one or more triglycerides are heated to a temperature above ambient temperature prior to addition to the premix.

[0206] In one aspect of the invention, there is provided a powder premix for oral administration of a cannabinoid, the method comprising the steps of:

[0207] i) mixing a sweetener powder composition comprising one or more sweeteners with a cannabinoid powder composition comprising one or more isolated cannabinoids, and then

[0208] ii) mixing a lipid composition comprising one or more triglycerides with the mixture obtained in i) to obtain a powder premix,

[0209] The weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:1.

[0210] In some embodiments of the invention, one or more triglycerides are heated to a temperature above ambient temperature prior to addition to the premix.

[0211] In one aspect of the invention, there is provided a powder premix for oral administration of a cannabinoid comprising the steps of:

[0212] i) mixing a sweetener powder composition comprising one or more sweeteners with a lipid composition comprising one or more triglycerides, and then

[0213] ii) mixing a cannabinoid powder composition comprising one or more isolated cannabinoids with the mixture obtained in i) to obtain a powder pre-mix,

[0214] The weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:1.

[0215] In some embodiments of the invention, one or more triglycerides are heated to a temperature above ambient temperature prior to addition to the premix. DETAILED DESCRIPTION

[0216] The verb "comprise / include" and its variations as used in this specification and claims are used in their non-restrictive sense, meaning the items included after the word, but not excluding items not specifically mentioned. In addition, unless the context clearly requires the presence of one and only one element, the possibility of more than one element is not excluded by mentioning the element by a noun not defined by a quantifier. Therefore, the noun not defined by a quantifier usually means "at least one / kind". In addition, the noun not defined by a quantifier means "one / kind or more / kind" when used in conjunction with the word include or contain in this article. The expression "one / kind or more / kind" is intended to mean one / kind, two / kinds, three / kinds or more / kinds.

[0217] Unless otherwise stated or otherwise apparent from the context, the terms "about" or "approximately" as used herein in reference to numbers are generally considered to include numbers that fall within 5%, 10%, 15%, or 20% in either direction (greater or less than) of that number (unless such a number is less than 0% or more than 100% of the possible value).

[0218] Unless otherwise specified, the terms "%" and "percentage" used herein refer to percentage by weight.

[0219] The term "particle size" relates to the ability of a particle to move through or be retained by a sieve opening of a particular size. Unless specifically mentioned otherwise, the term "particle size" as used herein refers to the average particle size as determined by particle size distribution estimation by analytical sieving according to European Pharmacopoeia 9.1 when using test method 2.9.38.

[0220] The term "particle" or similar expressions is intended to denote a single discrete component of a solid substance, such as a granulate or individual elements in a powder, having a certain size which may deviate significantly.

[0221] In this article, the term "release" refers to the released material released from the solid dosage form. In some embodiments, the process of releasing the material corresponds to the dissolution of the material in saliva. In the context of the present invention, unless otherwise stated, the term "release" is intended to mean testing under "in vivo" conditions. In this article, when chewing a solid dosage form, unless otherwise stated, "in vivo" conditions are intended to mean chewing samples with a chewing frequency of 60 chews / minute in a specific time period in a test group of 8 subjects. These subjects must not eat and drink water at least 30 minutes before starting any test. Subjects are healthy people arranged on an objective basis according to specified requirements.

[0222] The term "sustained release" or "extended release" is intended herein to mean extended release over time. The term "rapid release" or "fast release" or "high release" is intended herein to mean release of a higher level in a given period of time.

[0223] The phrase "texture" refers to the characteristics of a solid dosage form and a qualitative measure of the overall mouthfeel perceived by a user during use. Thus, the term "texture" encompasses measurable quantities, such as hardness, as well as more subjective parameters related to the sensation experienced by the user.

[0224] The term "sustained release" or "extended release" is intended herein to mean extended release over time. The term "rapid release" or "fast release" or "high release" is intended herein to mean release of a higher content in a given period of time. The term "controlled release" is intended to mean release of a substance from a solid dosage form by active use of the solid dosage form in the oral cavity of a subject, whereby the amount of the substance released is controlled by active use.

[0225] A "self-emulsifier" is an agent that will form an emulsion with minimal energy requirements when present with an alternating phase. In contrast, an emulsifier is an agent that requires additional energy to form an emulsion, as opposed to a self-emulsifier.

[0226] Due to the poor solubility of some active ingredients in physiological fluids, the demand for dissolving cannabinoids to promote bioabsorption when mixed with body physiological fluids is not met. In order to overcome low oral bioavailability, a variety of lipid-based drug delivery systems and self-emulsifying systems have been developed. It has been shown that lipid-based delivery systems and especially self-emulsifying drug delivery systems (self-emulsifying drug delivery system, SEDDS) have improved the solubility, dissolution and bioavailability of many insoluble active ingredients. However, lipid-based delivery systems and SEDDS delivery systems are greatly restricted by the active ingredient loading that must be dissolved in the carrier composition. Using cosolvents has obtained a higher concentration of active ingredients, which can achieve up to 30% load in certain cases.

[0227] It is believed that special challenges may arise in formulating solid dosage forms containing SEDDS. For example, challenges may arise in obtaining a homogenous mixture in which variations are avoided and safe and convenient delivery can be obtained. In addition, the general formulation of a solid dosage form that provides convenience to the user need not be compromised, which is often the case if precautions are not taken, such as where high loads of active ingredient are required.

[0228] Particularly for SEDDS, the formulations of the present invention may offer some significant benefits, both allowing for higher active ingredient loadings and at the same time providing improved organoleptic properties of the formulation during use. Additional advantages also exist.

[0229] Importantly, it is found that the presence of SEDDS or at least a self-emulsifier and the saliva production of improvement work synergistically. Although it is found that the saliva production of improvement makes some active ingredients dispersed and distributes the active ingredients of higher load to, for example, mucosal surfaces, it is found that the presence of SEDDS or at least a self-emulsifier further improves the intake of these active ingredients by the oral surface. Therefore, the synergy between the presence of SEDDS or at least a self-emulsifier and the saliva production of improvement according to the present invention makes the inventor feel unexpected. In some embodiments, the saliva production of improvement can cause the active ingredient to be exposed to mucosal surfaces higher. The presence of SEDDS can contribute to improving the affinity of the active ingredient from the saliva to the mucosa. Especially, SEDDS has the potential of high active ingredient load, which further contributes to the synergistic effect of the solid dosage form according to the present invention and the saliva production combination of improvement.

[0230] In the present context, SEDDS is a solid or liquid dosage form comprising an oil phase, a surfactant and optionally a 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 ambient temperature (usually body temperature, i.e., 37° C.). When SEDDS enters the oral cavity, it initially self-emulsifies into emulsion droplets and quickly disperses throughout the oral cavity, thereby reducing the irritation caused by direct contact of the active ingredient with the mucous membrane in the oral cavity, and thus helps to mask the taste of the active ingredient. In the oral cavity, the structure of the emulsion particles will be changed or destroyed. The resulting micron or nanometer-level particles can penetrate into the mucous membrane of the oral cavity, for example, and the absorbed oil droplets enter the blood circulation, thereby significantly improving the bioavailability of the active ingredient.

[0231] In one embodiment of the present invention, the self-emulsifying system comprises one or more emulsifiers and one or more oil carriers.

[0232] In one embodiment of the present invention, the self-emulsifying system comprises one or more emulsifiers, one or more oil carriers, and one or more solubilizing agents.

[0233] In one embodiment of the present invention, the self-emulsifying system comprises one or more emulsifiers, one or more oil carriers, one or more solubilizers, and one or more solvents.

[0234] In one embodiment of the present invention, the self-emulsifying system comprises one or more emulsifiers and one or more solvents.

[0235] In one embodiment of the invention, the self-emulsifying system comprises one or more emulsifiers having both emulsifying and solubilizing properties.

[0236] In one embodiment of the present invention, the self-emulsifying system comprises one or more emulsifiers that act as both an emulsifier and a carrier.

[0237] In one embodiment of the present invention, the self-emulsifying system comprises one or more emulsifiers that simultaneously act as emulsifier, carrier and solubilizer.

[0238] In one embodiment of the invention, the self-emulsifying system comprises one or more fatty acids, one or more glycerols, one or more waxes, one or more flavonoids and one or more terpenes.

[0239] In one embodiment of the present invention, the self-emulsifying system comprises one or more emulsifiers having an HLB value greater than 6, preferably from 8 to 18.

[0240] In one embodiment of the present invention, the one or more emulsifiers are selected from PEG-35 castor oil, PEG-6 oleoyl glyceride, PEG-6 linoleoyl glyceride, PEG-8 caprylic / capric glyceride, sorbitan monolaurate, sorbitan monooleate, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (60) sorbitan monostearate, polyoxyethylene (80) sorbitan monooleate, lauroyl polyoxyl-32 glyceride, stearoyl polyoxyl-32 glyceride, polyoxyl-32 stearate, propylene glycol monolaurate, propylene glycol dilaurate, and mixtures and combinations thereof.

[0241] In one embodiment of the present invention, the one or more emulsifiers include PEG-35 castor oil.

[0242] In one embodiment of the present invention, the oil carrier is selected from: natural fatty acids, medium chain triglycerides of caprylic acid (C8) and capric acid (C10), propylene glycol esters of caprylic acid (C8) and capric acid (C10), mono-, di- and triglycerides of primarily linoleic acid (C18:2) and oleic acid (C18:1), 18:1 cis-9 fatty acids, natural fatty acids, mono-, di- and triglycerides of oleic acid (C18:1), and mixtures and combinations thereof.

[0243] In one embodiment of the present invention, the one or more solvents are selected from the group consisting of: polyglyceryl-3 dioleate, 1,2-propylene glycol, polyethylene glycol 300, polyethylene glycol 400, diethylene glycol monoethyl ether, and mixtures and combinations thereof.

[0244] In one embodiment of the present invention, the oil carrier is selected from the group consisting of: corn oil, Labrafac lipophilic WL1349, Labrafac PG, Maisine CC, oleic acid, olive oil, Peceol, and mixtures and combinations thereof.

[0245] In one embodiment of the present invention, the one or more solvents are selected from polyglyceryl-3 dioleate, 1,2-propylene glycol, polyethylene glycol 300, polyethylene glycol 400, diethylene glycol monoethyl ether, and mixtures and combinations thereof.

[0246] In one embodiment of the present invention, the one or more solubilizing agents are selected from: lauroyl polyoxyl-32 glyceride; stearoyl polyoxyl-32 glyceride; polyoxyl-32 stearate; synthetic copolymers of ethylene oxide (80) and propylene oxide (27); polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; alpha-cyclodextrin, beta-cyclodextrin or gamma-cyclodextrin and their derivatives; pea proteins (globulin, albumin, gluten); and mixtures and combinations thereof.

[0247] In one embodiment of the invention, the formulation further comprises one or more lipids in addition to the lipid composition according to the invention.

[0248] The term "non-DC sugar alcohol granules" refers to non-directly compressible (non-DC) sugar alcohol granules. Note that the terms "non-DC sugar alcohol granules" and "non-DC granules" are used interchangeably. In this context, non-DC sugar alcohol granules refer to such granules: it is not pre-treated by granulating with, for example, other sugar alcohols or binders for the purpose of obtaining so-called directly compressible granules (DC). In this context, non-DC sugar alcohol granules include granules obtained by crystallization and then grinding, which do not involve other sugar alcohols or binders. Therefore, non-DC sugar alcohol granules are considered to be granules consisting of non-DC sugar alcohols.

[0249] The term "DC sugar alcohol granules" refers to direct compressible (DC) sugar alcohol granules. Note that the terms "DC sugar alcohol granules" and "DC granules" are used interchangeably. DC sugar alcohol granules can be obtained, for example, as granules of sugar alcohols (e.g., sorbitol) naturally having a DC grade, or by granulating non-DC sugar alcohols with, for example, other sugar alcohols or binders for the purpose of obtaining so-called direct compressible granules (DC). In addition, in the context of the present invention, granulation of non-DC sugar alcohols with water as a binder is considered to produce "DC sugar alcohol granules".

[0250] The term "compressed" or "tablet" or "compressed" is intended to mean that the tablet composition is compressed in a tableting device and consists mainly of granular material. Although the term implies a process step, in the present context, these terms are intended to mean the resulting tablet obtained when a portion of the granules is tableted. It should be noted that references to tablets or compressed compositions that ultimately contain granules are to be understood as granules that have been compressed together in a tableting step.

[0251] The following description outlines instructions for how the tablets of the invention may be produced as well as further details of the materials that may be added to the compositions of the invention.

[0252] Typically, the manufacturing process of the tablets of the present invention can be carried out in a single tablet press, such as a rotary tablet press. However, in some cases it may be beneficial to use a separate tablet press.

[0253] Preferably, the upper punch is convex, which gives the upper surface of the compressed tablet a concave shape.

[0254] It should of course be noted that the shape of the punch may vary depending on the desired tablet shape.

[0255] In some embodiments of the invention, compression of the tablet is performed with a force of 20 kN to 50 kN.

[0256] In one aspect of the invention, "tablet" is intended to mean a "fast disintegrating tablet" ("FDT") or similar wording, such as an "orally disintegrating tablet" ("ODT"). If not otherwise stated, a tablet according to the invention is intended to be a FDT tablet if it is made as one module, as opposed to two or more modules. If on the other hand, the tablet is made from more than one module, such as two modules, such additional modules are intended to be "lozenge" modules, which provide a longer disintegration time compared to the FDT modules according to the invention. The combination of an "FDT" module and a "lozenge" module contributes to another aspect of the invention. A "lozenge" module according to the invention may also contain elements from a "FDT" module, but typically differs in composition, thereby providing an extended disintegration time.

[0257] The term "lozenge" is intended to encompass that a "lozenge composition" has been "compressed" into a "lozenge module". In this context, a "lozenge module" or similar wording is intended to mean that the module is intended to be sucked or licked during use in the oral cavity. The term "lozenge" has the ordinary meaning in the lozenge field. The purpose is that the lozenge module may not be chewed. The purpose is also that the FDT module may not be chewed. Generally, the "lozenge module" of the present invention can disintegrate within minutes when sucked or licked, as opposed to the seconds of an orally disintegrating tablet (ODT) or a rapidly disintegrating tablet (FDT). Therefore, if the tablet is made as a combination of two modules, the purpose is that the "lozenge module" delivers one or more cannabinoids over a longer period of time than the FDT module.

[0258] The term "module" is generally intended to be composed of a composition of materials having substantially the same characteristics throughout the module. Therefore, if there are two modules, the two modules are different in composition and generally have two different characteristics throughout each module. In this context, if there is only one module, the module is considered to be an FDT tablet. On the other hand, if there are two modules, the tablet is composed of an FDT tablet module or an FDT tablet fused with a lozenge tablet or lozenge module. The term "fusion" is intended to mean that the tablet is gathered together by compression force. Generally, if there are two modules, the lozenge module is made into a first module and the FDT module is made into a second module. The tablet can be composed of more than two modules. The lozenge module can be replaced by a gum base module in certain embodiments. In this context, the present invention provides an attractive dual-phase masked delivery, even if the delivery of nicotine is "single-phase".

[0259] The term "cannabinoid composition" is intended to mean a number of substances that contain one or more cannabinoids. A cannabinoid composition may contain other components in addition to cannabinoids. A cannabinoid composition may consist of cannabinoids. A cannabinoid composition may consist of one type of cannabinoid. A cannabinoid composition may consist of two types of cannabinoids. A cannabinoid composition may consist of two or more types of cannabinoids.

[0260] The term "water insoluble gum base" or "gum base" or "gum base matrix" or similar expressions means the main water insoluble ingredients and hydrophobic gum base ingredients. "Gum base" may include gum base polymers as well as plasticizers, waxes, emulsifiers, fats and / or fillers.

[0261] The term "natural resin" as used herein means a resin compound which is a polyterpene derived from a natural source terpene or a resin compound derived from gum rosin, wood rosin or tall oil rosin.

[0262] Elastomers provide rubber-like, elastic and resilient properties to chewing gums, which vary depending on the chemical structure of the ingredient and how it can be mixed with other ingredients. Elastomers suitable for use in the gum bases and chewing gums of the present invention may include natural or synthetic types. According to the present invention, polyvinyl acetate elastomer plasticizers are not considered elastomers.

[0263] The elastomer may be selected from 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).

[0264] Styrene-butadiene elastomers, or SBRs, are typically copolymers of styrene:butadiene monomers in a ratio of about 20:80 to 60:40. The ratio of these monomers affects the elasticity of SBR as evaluated by Mooney viscosity. As the styrene:butadiene ratio decreases, the Mooney viscosity decreases.

[0265] The structure of SBR is usually composed of linear 1,3-butadiene copolymerized with phenylethylene or styrene. The average molecular weight of SBR is <600,000 g / mole.

[0266] Isobutylene-isoprene type elastomers, or butyl rubbers as they may be called, have isoprene mole percentage levels ranging from 0.2 to 4.0. Similar to SBR, as the isoprene:isobutylene ratio decreases, the elasticity measured by Mooney viscosity also decreases.

[0267] The structure of butyl rubber is usually composed of branched 2-methyl-1,3-butadiene (isoprene) copolymerized with branched 2-methylpropylene (isobutylene). The average molecular weight of BR is in the range of 150,000 g / mole to 1,000,000 g / mole.

[0268] Polyisobutylene (or PIB) type elastomer is a polymer of 2-methyl propylene. Low molecular weight elastomer provides soft chewing properties for gum base, and still provides elastic quality like other elastomers. The range of average molecular weight can be about 30,000g / mole to 120,000g / mole, and the range of needle penetration can be about 4 mm to 20 mm. The higher the needle penetration, the softer PIB. Similar to SBR and butyl rubber, high molecular weight elastomer provides elasticity for chewing gum. The range of average molecular weight can be 120,000g / mole to 1,000,000g / mole.

[0269] The average molecular weight of the polybutene ranges from about 5.000 g / mole to about 30.000 g / mole.

[0270] Useful natural elastomers include natural rubbers such as smoked or liquid latex and guayule, natural gums such as jelutong, lechi caspi, perillo, sorva, massaranduba balata, massaranduba chocolate, nispero, rosidinha, chicle, gutta percha, gutta kataiu, niger gutta, tunu, chilte, chiquibul, gutta hangkang. Natural elastomers may also be used in some aspects of the present invention.

[0271] Elastomer plasticizers change the firmness of the gum base. Their specificity for chain cleavage (plasticization) between elastomer molecules and their different softening points result in different degrees of firmness and compatibility of the finished gum when used in a matrix. Polyvinyl acetate elastomer plasticizers are examples of elastomer plasticizers of the present invention.

[0272] The natural resin may be selected from: ester gums including, as examples, glycerol esters of partially hydrogenated rosin, glycerol esters of polymerized rosin, glycerol esters of partially dimerized rosin, glycerol esters of tall oil rosin, pentaerythritol esters of partially hydrogenated rosin, methyl esters of rosin, partially hydrogenated methyl esters of rosin, pentaerythritol esters of rosin; synthetic resins, such as terpene resins derived from α-pinene, β-pinene and / or d-limonene, and natural terpene resins.

[0273] In one embodiment of the invention, the solid dosage form comprises an additional ingredient selected from the group consisting of flavors, dry binders, tableting aids, anti-caking agents, emulsifiers, antioxidants, enhancers, mucoadhesives, absorption enhancers, high intensity sweeteners, softeners, colorants, active ingredients, water-soluble indigestible polysaccharides, water-insoluble polysaccharides, or any combination thereof.

[0274] The solid dosage form according to the present invention is manufactured by applying pressure to the granular contents by suitable compression means. The granules or powders are then pressed into a dense cohesive tablet. The granules may, for example, comprise so-called primary granules or aggregated primary granules. When these granules are compressed, a bond is established between the granules or granules, thereby giving the compressed tablet a certain mechanical strength.

[0275] It should be noted that the terms powder, primary particles and aggregated primary particles introduced above may be somewhat misleading in the following sense: the difference between primary particles and aggregated primary particles may often be viewed differently depending on the context of the user. Some people may, for example, consider sweeteners such as sorbitol as primary particles, despite the fact that sorbitol should be considered as some kind of aggregated primary particles due to the fact that sorbitol is usually pre-processed when delivered to the customer. The definition adopted in the description of the present invention is that aggregated primary particles refer to macroscopic particles containing more or less pre-processed primary particles.

[0276] When pressure is applied to the particles, the total volume (bulk volume) is reduced and the amount of air is reduced. During this process, energy is consumed. As the particles become closer to each other during the volume reduction process, a bond can be established between the particles or granules. As energy is released, the formation of the bond is associated with a reduction in the energy of the system. The volume reduction occurs through a variety of mechanisms, and different types of bonds can be established between the particles or granules depending on the pressure applied and the characteristics of the particles or granules. The first thing that happens when the powder is compressed is that the particles are rearranged under low compaction pressure to form a more compacted structure. Particles with regular shapes show that they are easier to rearrange than those with irregular shapes. As the pressure increases, further rearrangement is prevented, and the volume reduction is then obtained by plastic deformation and elastic deformation and / or crushing of the tablet particles. Brittle particles may undergo crushing, i.e., the original particles are broken into smaller units. Plastic deformation is an irreversible process that causes permanent changes in the shape of the particles, while the particles recover their original shape after elastic deformation. Obviously, when compressing solid dosage forms, both plastic deformation and elastic deformation can occur.

[0277] Several studies have been conducted over the years on the type of bonding in compressed tablets, usually in the context of pharmaceuticals, and several techniques for obtaining compressed tablets based on available powders have been provided. Such studies have focused very much on what happens when volume reduction is performed and how the final product can be optimized for a given purpose. For the purpose of obtaining sufficient strength for the final compressed tablet while maintaining acceptable properties (e.g. with respect to release), for example, several improvements have been made with respect to compressed tablets by adding, for example, binders in the tablet raw materials.

[0278] In contrast to tableted chewing gum, conventional chewing gum can be manufactured by sequentially adding a variety of chewing gum ingredients to commercially available mixers known in the art when the finished gum base already exists. After the initial ingredients are fully mixed, the chewing gum material is discharged from the mixer and shaped into the desired form, for example, by rolling into sheets and cutting into sticks, extruding into blocks or casting into pellets. Usually, the ingredients of conventional chewing gum can be mixed by first melting the gum base and adding it to the mixer in operation. At this point, pigment, activating agent and / or emulsifier can also be added. At this point, a softener such as glycerol can also be added, as well as a part of syrup and filler / sweetener. Then the other part of filler / sweetener can be added to the mixer. Flavorings are usually added together with the last part of filler / sweetener. Preferably, high-intensity sweeteners are added after the last part of filler and spices have been added. The whole mixing process usually takes thirty minutes to forty minutes, but sometimes longer mixing time may be required. Those skilled in the art will recognize that many variations of the above process can be adopted.

[0279] In some embodiments of the invention, the solid dosage form does not comprise conventional chewing gum, ie, so-called extruded chewing gum.

[0280] According to the present invention, the compressed solid dosage form according to the present invention may comprise from about 0.1 wt % to about 75 wt % of an outer coating applied to the center of the solid dosage form. Thus, suitable coating types include: hard coatings, film coatings, and soft coatings comprising any composition currently used for coating compressed solid dosage forms.

[0281] A currently preferred type of outer coating is a hard coating, which term is used in the conventional sense of the term, including sugar coatings and sugarless (or sugar-free) coatings, and combinations thereof. The purpose of the hard coating is to obtain a sweet, crisp layer that consumers like, and in addition it can protect the solid dosage form center for various reasons. In a typical process for providing a solid dosage form center with a protective sugar coating, the solid dosage form center is continuously treated with an aqueous solution of a crystallizable sugar (e.g., sucrose or dextrose) in a suitable coating device, which may contain other functional ingredients, such as fillers, binders, pigments, etc., depending on the coating stage reached. In this context, the sugar coating may contain additional functional or active compounds, including flavoring compounds and / or active compounds.

[0282] In a typical hard coating process as will be described in detail below, a suspension comprising a crystallizable sugar and / or a polyol is applied to the center of the solid dosage form and the water contained therein is evaporated by a gas purge. This cycle must be repeated several times, typically 3 to 80 times, to achieve the desired expansion. The term "expansion" refers to the increase in weight or thickness of the product considered at the end of the coating operation as compared to the beginning and related to the final weight or thickness of the coated product. According to the present invention, the coating layer constitutes about 0.1% to about 75% by weight of the final solid dosage form element, for example, about 10% to about 60% by weight, including about 15% to about 50% by weight.

[0283] In one embodiment of the invention, the product is a sachet.

[0284] In one aspect of the present invention, the particle group for tableting can also be present in the bag as a powder. Therefore, this aspect of the present invention includes a particle group that is not tableted but is a part of a powder or a powder with other powders or powder components in the bag. Therefore, the direct compressible (DC) sugar alcohol particles of the present invention and the non-direct compressible (non-DC) sugar alcohol particles can be included in the bag according to the present invention. When included in the bag, the other embodiments related to the particle group of the present invention will also be applicable. It should be noted that other ingredients, such as water-soluble fiber or water-insoluble fiber, including microcrystalline cellulose, may be present in the bag.

[0285] According to an advantageous embodiment of the invention, the sachet comprises a water-permeable membrane, for example a woven or nonwoven fabric.

[0286] The pouch according to the invention comprises an opening, wherein the characteristic opening size is adapted to the characteristic size of the particle population to retain the matrix composition within the pouch prior to use and / or to retain a portion of the contents within the pouch during use.

[0287] In other words, according to a plurality of embodiments, the bag forms a film that allows saliva to pass through and prevents or inhibits at least a portion of the contents from passing through. The film of the bag can have any suitable material, such as woven or nonwoven fabrics (such as cotton fabrics, fleece fabrics, etc.); heat-sealable nonwoven cellulose or other polymer materials, such as synthetic, semi-synthetic or natural polymer materials. An example of a suitable bag material is paper made of pulp and a small amount of wet strength agent. The material suitable for use must provide a semi-permeable membrane layer to prevent powder or composition from leaving the bag or bag during use. Suitable materials are also materials that do not have a significant impact on the release of active ingredients from the bag.

[0288] The powder is filled into the pouch and is held in the pouch by a seal. An ideal pouch is chemically and physically stable, it is pharmaceutically acceptable, it is insoluble in water, it is easy to fill with powder and seal, and it provides a semi-permeable membrane layer that prevents the powder from leaving the pouch but allows saliva and sufficiently small suspended components dissolved in the saliva or from the powder in the pouch to pass through the pouch.

[0289] The user can place the bag in the oral cavity. Saliva then enters the bag, and the active ingredients and other components that are soluble in saliva begin to dissolve and are transported to the outside of the bag into the oral cavity along with the saliva. In some embodiments of the present invention, the bag can be chewed in a manner similar to chewing chewing gum. This is particularly advantageous when the particle group comprises a gum base. Therefore, the bag can be chewed into a cohesive residue comprising a water-insoluble component.

[0290] According to an embodiment of the present invention, spices can be selected from coconut, coffee, chocolate, vanilla, grapefruit, orange, lemon, menthol, licorice, caramel, honey, peanut, walnut, cashew, hazelnut, almond, pineapple, strawberry, raspberry, tropical fruit, cherry, cinnamon, peppermint, wintergreen, spearmint, eucalyptus and mint, fruit essence (e.g., essence from apple, pear, peach, strawberry, apricot, raspberry, cherry, pineapple and plum). Essential oils include peppermint, spearmint, menthol, eucalyptus, clove oil, bay oil, anise, thyme, cedar leaf oil, nutmeg and oils of the above-mentioned fruits.

[0291] Antioxidants suitable for use include butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), beta carotene, tocopherol, acidulants such as vitamin C (ascorbic acid or the corresponding salt (ascorbate)), propyl gallate, catechins, green tea extract, other synthetic and natural types, or mixtures thereof.

[0292] According to a preferred embodiment of the present invention, high-intensity sweeteners can also be used. Preferred high-intensity sweeteners include, but are not limited to, sucralose, aspartame, salts of acesulfame potassium, alitame, neotame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, tamarind protein, monk fruit extract, adventitium, stevioside, etc., alone or in combination.

[0293] To provide a longer lasting sweetness and flavor perception, it may be desirable to encapsulate or otherwise control the release of at least a portion of the high intensity sweetener.

[0294] Can use for example wet granulation, wax granulation, spray drying, spray cooling, fluidized bed coating, preservation, encapsulation in yeast cells and fiber extrusion technology to achieve the desired release characteristics.Also can use additional formulation components such as resin compounds to provide the encapsulation of sweeteners.

[0295] The use level of high intensity sweetener will vary greatly, and will depend on factors such as the effectiveness of the sweetener, the rate of release, the desired sweetness of the product, the level and type of spices used, and cost considerations. Therefore, the activity level of the artificial sweetener can vary from about 0.001 % by weight to about 8 % by weight (preferably about 0.02 % by weight to about 8 % by weight). When comprising a carrier for encapsulation, the use level of the encapsulated high intensity sweetener will be proportionally higher.

[0296] If desired, the present invention may include one or more fillers / texturizers, including, by way of example, magnesium and calcium carbonates, sodium sulfate, ground limestone, silicate compounds (e.g., magnesium and aluminum silicates, kaolin and clay), aluminum oxide, silicon oxide, talc, titanium oxide, monocalcium phosphate, dicalcium phosphate and tricalcium phosphate, cellulosic polymers (e.g., wood), and combinations thereof. According to one embodiment of the present invention, a preferred filler / texturizer is calcium carbonate.

[0297] According to the present invention, the one or more cannabinoids may be selected from a plurality of cannabinoids.

[0298] "Cannabinoids" are a group of compounds that include endocannabinoids, phytocannabinoids, and those that are neither endocannabinoids nor phytocannabinoids, hereinafter referred to as "synthetic cannabinoids".

[0299] "Endocannabinoids" are endogenous cannabinoids that may have high affinity ligands for both the CB1 and CB2 receptors.

[0300] "Phytocannabinoids" are cannabinoids that are derived from nature and that can be found in plants of the genus Cannabis. Phytocannabinoids may be present in isolated or synthetically reproduced extracts (including botanical drug substances).

[0301] "Synthetic cannabinoids" are compounds that are able to interact with cannabinoid receptors (CB1 and / or CB2) but are not found endogenously or in the cannabis plant. Examples include WIN 55212 and rimonabant.

[0302] An "isolated phytocannabinoid" or "isolated cannabinoid" is a cannabinoid that has been extracted from the cannabis plant and purified to the extent that additional components such as secondary and minor cannabinoids and non-cannabinoid fractions have been substantially removed.

[0303] "Synthetic cannabinoids" are cannabinoids produced by chemical synthesis. The term includes modifications of isolated phytocannabinoids, for example by forming pharmaceutically acceptable salts thereof.

[0304] "Substantially pure" cannabinoids are defined as cannabinoids present in a purity of greater than 95% (w / w), more preferably greater than 96% (w / w) through 97% (w / w) through 98% (w / w) to 99%% (w / w) and greater.

[0305] A "highly purified" cannabinoid is defined as a cannabinoid that has been extracted from the cannabis plant and purified to the extent that other cannabinoids and non-cannabinoid components that were co-extracted with the cannabinoid have been substantially removed, such that the highly purified cannabinoid is greater than or equal to 95% (w / w) pure.

[0306] "Botanical material" is defined as plants or plant parts (e.g., bark, wood, leaves, stems, roots, flowers, fruits, seeds, berries, or parts thereof) and secretions, and includes materials that fall within the definition of "botanical raw materials" in the U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research Guidance for Industry Botanical Drug Products Draft Guidance, August 2000.

[0307] In the context of this application, the terms "cannabinoid extract" or "extract of cannabinoids" are used interchangeably to cover "botanical drug substances" derived from plant material of the genus Cannabis. In the August 2000 Guidance for Industry Botanical Drug Products Draft Guidance of the Center for Drug Evaluation and Research of the U.S. Department of Health and Human Services, Food and Drug Administration, a botanical drug substance is defined as: "a drug substance derived from one or more plants, algae, or macrofungi. It is prepared from plant material by one or more of the following methods: grinding, decoction, expression, aqueous extraction, ethanol extraction, or other similar methods." Botanical drug substances do not include highly purified or chemically modified substances derived from natural sources. Therefore, in the case of cannabis, a "botanical drug substance" derived from a plant of the genus Cannabis does not include highly purified pharmacopeial grade cannabinoids.

[0308] The term "Cannabis plant" includes wild-type Cannabis sativa and also variants thereof, including Cannabis chemovar, Cannabis sativa subspecies indica (including the variants var. Indica and var. Kafiristanica), Indian hemp, Weed Cannabis and also plants that are the result of genetic crosses, self-crosses or hybrids thereof. The term "Cannabis plant material" should accordingly be interpreted as including plant material derived from one or more Cannabis plants. For the avoidance of doubt, it is hereby stated that "Cannabis plant material" comprises dried cannabis biomass.

[0309] Preferably, the one or more cannabinoids are selected from the group consisting of cannabichromene (CBC), cannabichromene (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabichromene (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), dihydroxycannabinol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabinol (THCV) and tetrahydrocannabinolic acid (THCVA). More preferably, the one or more cannabinoids are CBD or THC. This list is not exhaustive, but only details the cannabinoids identified in the present application for reference.

[0310] To date, over 120 different phytocannabinoids have been identified, all of which are within the scope of the present invention.

[0311] Cannabinoids can be divided into different groups: phytocannabinoids, endocannabinoids, and synthetic cannabinoids.

[0312] For the purposes of the present invention and whether or not explicitly designated as such herein, cannabinoid receptors can be activated by three major groups of agonist ligands that are lipophilic in nature and are classified separately as follows: endocannabinoids (produced endogenously by mammalian cells), phytocannabinoids (e.g., cannabidiol produced by plants of the genus Cannabis), and synthetic cannabinoids (e.g., HU-210).

[0313] Depending on the method used to extract the cannabinoids, the phytocannabinoids may exist as a neutral carboxylic acid form or a decarboxylated form. For example, it is known that heating the carboxylic acid form will decarboxylate a large portion of the carboxylic acid form.

[0314] Phytocannabinoids can also occur as pentyl (5 carbon atoms) or propyl (3 carbon atoms) variants. For example, the phytocannabinoid THC is known to be a CB1 receptor agonist, while the propyl variant THCV has been found to be a CB1 receptor antagonist, meaning it has almost the opposite effect.

[0315] According to the present invention, some examples of phytocannabinoids may be cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabichromene (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), dihydroxycannabinol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabinol (THCV) and tetrahydrocannabinolic acid (THCVA). More preferably, the one or more cannabinoids are CBD or THC.

[0316] The formulation according to the invention may also comprise at least one cannabinoid selected from those disclosed in A. Douglas Kinghorn et al., Phytocannabinoids, Vol. 103, Chapter 1, pages 1-30.

[0317] Examples of endocannabinoids are molecules that activate cannabinoid receptors in the body. Some examples include 2-arachidonylglycerol (2AG), 2-arachidonylglycerol ether (2AGE), arachidonyl dopamine and arachidonyl ethanolamide (arachidonylethanolamine, anandamide). Structurally related endogenous molecules have been identified to have similar structural features, but show weak or no activity on cannabinoid receptors, but are also referred to as endocannabinoids. Some examples of these endocannabinoid lipids include: 2-acylglycerol, alkyl glyceryl ether or alkenyl glyceryl ether, acyl dopamine and N-acylethanolamide containing alternative fatty acid or alcohol parts, and other fatty acid amides containing different head groups. These include N-acylserine and many other N-acylated amino acids. Some examples of cannabinoid receptor agonists are neuromodulatory and affect short-term memory, appetite, stress response, anxiety, immune function and analgesia.

[0318] In one embodiment, the cannabinoid is palmitoylethanolamide (PEA), which is an endogenous fatty acid amide belonging to the class of nuclear factor agonists.

[0319] Synthetic cannabinoids cover a variety of different chemical classes: cannabinoids that are structurally related to THC; cannabinoids that are not related to THC, such as (cannabinoid mimetics) including aminoalkyl indoles, 1,5-diaryl pyrazoles, quinolines, and aryl sulfonamides; and dodecanoic acids related to endogenous cannabinoids. All or any of these cannabinoids may be used in the present invention.

[0320] Preferably, the formulation comprises one or two primary cannabinoids, preferably selected from cannabidiol (CBD) or cannabidivarin (CBDV), tetrahydrocannabinol (THC), tetrahydrocannabinol (THCV), tetrahydrocannabinolic acid (THCA), cannabigerol (CBG) and cannabidiolic acid (CBDA), or a combination thereof. Preferably, the formulation comprises cannabidiol and / or tetrahydrocannabinol.

[0321] Preferably, the solid dosage form of the present invention can be used to treat or relieve pain, epilepsy, cancer, nausea, inflammation, congenital disorders, neurological disorders, oral infections, toothache, sleep apnea, psychiatric disorders, gastrointestinal disorders, inflammatory bowel disease, loss of appetite, diabetes and fibromyalgia.

[0322] In another aspect of the invention, the oral cannabinoid formulations are useful for treating conditions requiring administration of a neuroprotectant or anticonvulsant drug.

[0323] Oral cannabinoid preparations can be used to treat epileptic seizures.

[0324] Oral cannabinoid preparations can be used to treat Dravet syndrome, Lennox-Gastaut syndrome, myoclonic seizures, juvenile myoclonic epilepsy, refractory epilepsy, schizophrenia, juvenile spasms, West syndrome, infantile spasms, refractory infantile spasms, tuberous sclerosis complex, brain tumors, neuropathic pain, cannabis use disorder, post-traumatic stress disorder, anxiety, early psychosis, Alzheimer's disease, and autism.

[0325] The following non-limiting examples illustrate different variations of the invention. These examples are intended to illustrate the inventive concept; therefore, the examples mentioned should not be understood as being exhaustive of the invention. In particular, CBD is used as an exemplary compound, but other cannabinoids are also possible.

[0326] Example

[0327] Example 1

[0328] Premix: Hydrogenated vegetable oil (HVO) added to a mixture of isolated CBD and sweeteners

[0329] Mannitol (Pearlitol 150SD) in an amount of about 1780 g supplied by Roquette was added to A high shear mixer was added and heated to a temperature of about 55 degrees Celsius. Thereafter, a cannabinoid powder composition comprising CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content provided by Medical Hemp (Batch No. MH B18592) was sieved through a 600 micron sieve in an amount of about 140 g and added to the sweetener powder composition. The mixture was mixed in the mixer at a speed of about 80 rpm for about 5 minutes. Upon activation, After the chopper (about 600rpm) of the mixer, the HVO with a melting temperature of 30 to 35 degrees Celsius provided by AAK under the trade name Akocrem NT 76-33 was melted at a temperature of about 55 degrees Celsius, and added to the mixture in an amount of about 80g. After adding the lipid composition, the temperature in the mixer was made to be about 49 degrees Celsius, and the mixture was further mixed for about 10 minutes. After 10 minutes, the temperature of the final mixture was about 51 degrees Celsius. A total of 2kg of the mixture powder premix was prepared, wherein the CBD content was about 70mg / g.

[0330] Table 1: Hydrogenated vegetable oil (HVO) preheated to a temperature of about 55 degrees Celsius. Differences in the content of CBD isolate (purity 99%). Sample 102 corresponds to the above process, and the other samples are adjusted by the content differences.

[0331]

[0332] Table 2: Hydrogenated vegetable oil (HVO) preheated to a temperature of about 55 degrees Celsius. Differences in the content of HVO. Sample 112 corresponds to the above process, and the other samples are adjusted by the content differences.

[0333]

[0334] Table 3: Hydrogenated vegetable oil (HVO) has been preheated to a temperature of about 55 degrees Celsius. Difference in the type of sweetener. Here mannitol is replaced by other sweeteners. Sample 122 corresponds to the above process.

[0335]

[0336] Example 2

[0337] Premix: Miglyol added to a mixture of isolated CBD and sweetener

[0338] Mannitol (Pearlitol 150SD) in an amount of about 1780 g supplied by Roquette was added to A high shear mixer was added and heated to a temperature of about 55 degrees Celsius. Thereafter, a cannabinoid powder composition comprising CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content provided by Medical Hemp (Batch No. MH B18592) was sieved through a 600 micron sieve in an amount of about 140 g and added to the sweetener powder composition. The mixture was mixed in the mixer at a speed of about 80 rpm for about 5 minutes. Upon activation, After the chopper of the mixer (about 600 rpm), the medium chain triglyceride (MCT) Miglyol 812 provided by Sasol was added to the mixture in an amount of about 80 g during a period of about 3 minutes. After adding Miglyol 812, the mixture was further mixed for about 10 minutes. After 10 minutes, the temperature of the final mixture was made to be about 51 degrees Celsius. A total of 2 kg of the mixture powder premix was prepared, wherein the CBD content was about 70 mg / g.

[0339] Table 4: Miglyol 812 without preheating. Difference in the content of CBD isolate (purity 99%). Sample 202 corresponds to the above process, and the other samples are adjusted by the content difference.

[0340]

[0341] Table 5: Miglyol 812 without preheating. Differences in the content of Miglyol 812. Sample 212 corresponds to the above process, and the other samples are adjusted by the content differences.

[0342]

[0343] Table 6: Miglyol was not preheated unless otherwise stated. Difference in the type of Miglyol. Sample 222 corresponds to the above process. Miglyol 829 in powder premix No. 223 was heated to about 50°C to function. Powder premix No. 224 is a comparative powder.

[0344]

[0345] Table 7: Miglyol 812 without preheating. Difference in the type of sweetener. Here mannitol was replaced by other sweeteners. Sample 232 corresponds to the above process.

[0346]

[0347] Example 3

[0348] Premix: High Load – Hydrogenated Vegetable Oil (HVO) added to a mixture of isolated CBD and sweeteners

[0349] Mannitol (Pearlitol 150SD) in an amount of about 1220 g supplied by Roquette was added to A high shear mixer was added and heated to a temperature of about 55 degrees Celsius. Thereafter, a cannabinoid powder composition comprising CBD isolate (phytocannabinoid) from cannabis plant tissue with a 99% CBD content provided by Medical Hemp (Batch No. MH B18592) was sieved through a 600 micron sieve in an amount of about 700 g and added to the sweetener powder composition. The mixture was mixed in the mixer at a speed of about 80 rpm for about 5 minutes. Upon activation, After the chopper (about 600rpm) of the mixer, the HVO with a melting temperature of 30 to 35 degrees Celsius provided by AAK under the trade name AkocremNT 76-33 is melted at a temperature of about 55 degrees Celsius, and is added to the mixture in an amount of about 80g. After adding the lipid composition, the temperature in the mixer is about 49 degrees Celsius, and the mixture is further mixed for about 10 minutes. After 10 minutes, the temperature of the final mixture is about 51 degrees Celsius. Preparation is a mixture powder premix of 2kg in total, wherein the CBD content is about 350mg / g.

[0350] Table 8: Differences in the content of hydrogenated vegetable oil (HVO) preheated to a temperature of about 55 degrees Celsius. CBD isolate (purity 99%). Sample 302 corresponds to the above process, and the other samples are adjusted by the content differences.

[0351]

[0352] Table 9: Hydrogenated vegetable oil (HVO) preheated to a temperature of about 55 degrees Celsius. Differences in HVO content. Sample 312 corresponds to the above process, and the other samples are adjusted by the content differences.

[0353]

[0354] Table 10: Hydrogenated vegetable oil (HVO) has been preheated to a temperature of about 55 degrees Celsius. Difference in the type of sweetener. Here mannitol is replaced by other sweeteners. Sample 322 corresponds to the above process.

[0355]

[0356] Example 4

[0357] Premix: Hydrogenated vegetable oil (HVO) blend containing isolated CBD added to sweetener

[0358] Mannitol (Pearlitol 150SD) in an amount of about 721 g supplied by Roquette was added to High shear mixer, and heated to a temperature of about 55 degrees Celsius. After this, the cannabinoid powder composition of the CBD isolate (phytocannabinoid) (batch number MH B18592) from the cannabis plant tissue containing 99% CBD content provided by Medical Hemp is mixed with about 91g of about 29g of HVO with a melting temperature of 30 to 35 degrees Celsius provided by AAK under the trade name AkocremNT 76-33. While stirring, the CBD-HVO mixture is heated to a temperature of about 60 degrees Celsius to form a liquid solution of CBD in HVO. Then the CBD and HVO mixture corresponding to about 75 / 25 ratio (hereinafter referred to as 75% CBD mixture) is added to the sweetener powder composition in an amount of about 79g. After adding the lipid composition, the mixture is mixed for about 10 minutes. A total of 800g of mixture powder premixes are prepared.

[0359] Table 11: Hydrogenated vegetable oil (HVO) heated to a temperature of about 60 degrees Celsius after mixing with 99% pure CBD (75% CBD mixture). Differences in the content of CBD (75% CBD mixture). Sample 402 corresponds to the above process, and the other samples are adjusted by the content differences.

[0360]

[0361] Table 12: Hydrogenated vegetable oil (HVO) heated to a temperature of about 60 degrees Celsius after mixing with 99% pure CBD (X% CBD mixture). Differences in the content of CBD mixed with HVO. * indicates the percentage X of CBD in the "X% CBD mixture". Sample 412 corresponds to the above process, and the other samples are adjusted by the content differences.

[0362]

[0363] Table 13: Hydrogenated vegetable oil (HVO) heated to a temperature of about 60 degrees Celsius after mixing with 99% CBD (75% CBD mixture). Difference in the type of sweetener. Here mannitol is replaced by other sweeteners. Sample 422 corresponds to the above process.

[0364]

[0365]

[0366] Example 4A

[0367] Premix: Corn oil and oleic acid blend containing isolated CBD added to sweetener

[0368] Mannitol (Pearlitol 150SD) in an amount of about 666 g supplied by Roquette was added to High shear mixer, and heated to a temperature of about 55 degrees Celsius. After this, the cannabinoid powder composition of the CBD isolate (phytocannabinoid) (batch number MH B18592) from the cannabis plant tissue containing 99% CBD content provided by Medical Hemp is mixed and dissolved with a combination of about 151.6g of liquid corn oil (melting temperature below 0 degrees Celsius) of about 25.0g provided by ADM and about 25.0g of liquid oleic acid (melting temperature of about 13 degrees Celsius) provided by Sigma Aldrich under the trade name W281506. While stirring, the CBD-oil mixture is heated to a temperature of about 60 degrees Celsius to form a liquid solution of CBD in oil. Then the CBD and oil mixture (hereinafter referred to as 75% CBD mixture) corresponding to about 75 / 25 ratio is added to the sweetener powder composition in an amount of about 134g. After adding the lipid composition, the mixture is mixed for about 10 minutes. A total of 800g mixture powder premixes are prepared.

[0369] Table 11A: Differences in CBD (75% CBD blend) content Sample 402A corresponds to the above process, and the other samples are adjusted by differences in content.

[0370]

[0371] Table 12A: Differences in CBD content mixed with oil. * indicates the percentage X of CBD in the "X% CBD mixture". Sample 411A corresponds to the above process, and the other samples are adjusted by the content differences.

[0372]

[0373] Example 5

[0374] Premix: Miglyol blend containing isolated CBD added to sweetener

[0375] Mannitol (Pearlitol 150SD) in an amount of about 721 g supplied by Roquette was added to High shear mixer, and heated to a temperature of about 55 degrees Celsius. After this, the cannabinoid powder composition of the CBD isolate (phytocannabinoid) (batch number MH B18592) from the cannabis plant tissue containing 99% CBD content provided by Medical Hemp is mixed with the medium chain triglyceride (MCT) Miglyol 812 provided by Sasol in an amount of about 91g and about 29g. While stirring, the CBD-MCT mixture is heated to a temperature of about 70 degrees Celsius to form a liquid solution of CBD in MCT. Then, the CBD and Miglyol 812 mixture (hereinafter referred to as 75% CBD mixture) corresponding to about 75 / 25 ratio is added to the sweetener powder composition in an amount of about 79g. After adding the lipid composition, the mixture is mixed for about 10 minutes. A total of 800g mixture powder premixes are prepared.

[0376] Table 14: Miglyol 812 mixed with 99% pure CBD and then heated (75% CBD mixture). Differences in CBD (75% CBD mixture) content. Sample 502 corresponds to the above process, and the other samples are adjusted by the content differences.

[0377]

[0378] Table 15: Miglyol 812 mixed with 99% CBD and then heated (X% CBD mixture). Differences in the content of CBD mixed with Miglyol 812. * indicates the percentage X of CBD in the "X% CBD mixture". Sample 512 corresponds to the above process, and the other samples are adjusted by the content differences.

[0379]

[0380] Table 16: Miglyol 812 mixed with 99% CBD and then heated (75% CBD mixture). Difference in the type of sweetener. Here mannitol was replaced by other sweeteners. Sample 522 corresponds to the above process.

[0381]

[0382] Example 6

[0383] Premix: Comparative sample - without triglyceride lipids

[0384] Mannitol (Pearlitol 150SD) supplied by Roquette was added to The mixture was stirred at room temperature for 2 hours and then stirred for 3 hours. The mixture was stirred for 2 hours and then stirred for 3 hours. The mixture was stirred for 2 hours and then stirred for 3 hours. The mixture was stirred for 3 hours and then stirred for 4 ...

[0385] Table 17: Differences in the content of CBD isolates.

[0386]

[0387] Table 18: Differences in the content of CBD isolates.

[0388]

[0389] Table 19: Differences in the content of CBD isolates. Differences in the source of CBD isolates.

[0390]

[0391] Example 7

[0392] Preparation of tablets with two layers

[0393] Tablets were prepared based on the CBD-containing powder mixture of Examples 1 to 2, with each layer weighing approximately 50% of the total tablet. The total weight of the tablet was 1800 mg. Tablets were prepared using a standard tablet press (3090i, available from Fette GmbH) including a metering device (P 3200C, available from Fette GmbH, Germany). Punch used: 16.00 mm round punch. The rotor speed used was 11 rpm.

[0394] A first layer (denoted as layer 1) comprising the powder mixture containing CBD prepared in Examples 1 to 2 and additional ingredients is prepared and tableted, followed by a layer (denoted as layer 2) comprising a gum base. Layer 1 weighing about 900 mg is compressed at a compression force of about 5 kN. Thereafter, layer 2 weighing about 900 mg and comprising a gum base and additional ingredients is pressed on top of layer 1 at a compression force of 40 kN. The tablet press is debugged by adjusting the filling depth and compression force so that the weight and hardness of the tablets meet the acceptance criteria. A pre-compression force may be included to avoid capping.

[0395] Table 20: In all tablet examples, the amounts of the various ingredients are given as % by weight of the tablet.

[0396]

[0397] Table 21: In all tablet examples, the amounts of the various ingredients are given as % by weight of the tablet.

[0398]

[0399] Table 22: In all tablet examples the amounts of the various ingredients are given in % by weight of the tablet. *Silicon dioxide can optionally be added at the stage of preparing the mixture in Example 2.

[0400]

[0401] Example 8

[0402] Preparation of tablets with two layers

[0403] Tablets were prepared based on the CBD-containing powder mixture of Example 3, with each layer weighing approximately 50% of the total tablet. The total weight of the tablet was 1800 mg. Tablets were prepared using a standard tablet press (3090i, available from Fette GmbH) including a metering device (P 3200C, available from Fette GmbH, Germany). Punch used: 16.00 mm round punch. The rotor speed used was 11 rpm.

[0404] A first layer (denoted as layer 1) comprising the powder mixture containing CBD prepared in Example 3 and additional ingredients is prepared and tableted, followed by a layer (denoted as layer 2) comprising a gum base. Layer 1 is compressed at a compression force of about 5 kN. Thereafter, layer 2 comprising gum base and additional ingredients is pressed on top of layer 1 at a compression force of 40 kN. The tablet press is debugged by adjusting the filling depth and compression force so that the weight and hardness of the tablets meet the acceptance criteria. A pre-compression force may be included to avoid capping.

[0405] Table 23: In all tablet examples the amounts of the various ingredients are given in % by weight of the tablet. *Silicon dioxide can optionally be added at the stage of preparing the mixture in Example 3.

[0406]

[0407] Table 24: In all tablet examples the amounts of the various ingredients are given in % by weight of the tablet. *Silicon dioxide can optionally be added at the stage of preparing the mixture in Example 3.

[0408]

[0409] Example 9

[0410] Preparation of tablets with two layers

[0411] Tablets with two layers were prepared based on the CBD-containing powder mixture of Examples 4 to 5, wherein the weight of one layer was about 45% of the total tablet and the weight of the other layer was about 55% (the layer without CBD). The total weight of the tablet was 1800 mg. The tablets were prepared with a standard tablet press (3090i, available from Fette GmbH) including a metering device (P 3200C, available from Fette GmbH, Germany). Punch used: 16.00 mm round punch. The rotor speed used was 11 rpm.

[0412] A first layer (denoted as layer 1) comprising the powder mixture containing CBD prepared in Examples 1 to 2 and additional ingredients is prepared and tableted, followed by a layer (denoted as layer 2) comprising a gum base. Layer 1 is compressed at a compression force of about 5 kN. Thereafter, layer 2 comprising gum base and additional ingredients is pressed on top of layer 1 at a compression force of 40 kN. The tablet press is debugged by adjusting the filling depth and compression force so that the weight and hardness of the tablets meet the acceptance criteria. A pre-compression force may be included to avoid capping.

[0413] Table 25: In all tablet examples, the amounts of the various ingredients are given as % by weight of the tablet.

[0414]

[0415] Table 26: In all tablet examples, the amounts of the various ingredients are given as % by weight of the tablet.

[0416]

[0417] Example 9A

[0418] Preparation of tablets

[0419] Tablets were prepared based on the CBD-containing powder mixture of Example 4A. Tablets were prepared using a standard tablet press (3090i, available from Fette GmbH) including a metering device (P 3200C, available from Fette GmbH, Germany). Punches used: 16.00 mm round punches. The rotor speed used was 11 rpm.

[0420] Tablets were prepared based on the CBD-containing powder mixture of Example 4A and additional ingredients and compressed at a compression force of about 35 kN. The total weight of the tablets was 1800 mg. The tablet press was debugged by adjusting the filling depth and compression force so that the weight and hardness of the tablets met the acceptance criteria.

[0421] Table 25A: In all tablet examples, the amounts of the various ingredients are given as % by weight of the tablet.

[0422]

[0423] Example 9B

[0424] Preparation of chewable tablets

[0425] Chewable tablets were prepared based on the CBD-containing powder mixture of Example 4A. Chewable tablets were prepared using a standard tablet press (3090i, available from Fette GmbH) including a metering device (P3200C, available from Fette GmbH, Germany). Punch used: 16.00 mm round punch. The rotor speed used was 11 rpm.

[0426] A chewable tablet was prepared based on the CBD-containing powder mixture of Example 4A and additional ingredients and compressed at a compression force of about 30 kN. The total weight of the chewable tablet was 1800 mg. The tablet press was debugged by adjusting the filling depth and compression force so that the weight and hardness of the tablet met the acceptance criteria.

[0427] Table 25B: In all chewable tablet examples, the amounts of the various ingredients are given as % by weight of the chewable tablet. Non-DC represents a non-directly compressible grade, and DC represents a directly compressible grade.

[0428]

[0429] Example 9C

[0430] Preparation of powder for sachets

[0431] A sachet powder was prepared based on the CBD-containing powder mixture of Example 4A. The total weight of the sachet powder was 1800 mg.

[0432] Table 25C: In all sachet powder examples, the amounts of the various ingredients are given as % by weight of the sachet powder.

[0433]

[0434] Example 10

[0435] Comparative tablet with two layers

[0436] Tablets with two layers were prepared based on the CBD-containing powder mixture of Example 6, wherein the weight of one layer was about 45% of the total tablet and the weight of the other layer was about 55% (the layer without CBD). The total weight of the tablet was 1800 mg. Tablets were prepared using a standard tablet press (3090i, available from Fette GmbH) including a metering device (P 3200C, available from Fette GmbH, Germany). Punch used: 16.00 mm round punch. The rotor speed used was 11 rpm.

[0437] A first layer (denoted as layer 1) comprising the powder mixture containing CBD prepared in Examples 1 to 2 and additional ingredients is prepared and tableted, followed by a layer (denoted as layer 2) comprising a gum base. Layer 1 is compressed at a compression force of about 5 kN. Thereafter, layer 2 comprising gum base and additional ingredients is pressed on top of layer 1 at a compression force of 40 kN. The tablet press is debugged by adjusting the filling depth and compression force so that the weight and hardness of the tablets meet the acceptance criteria. A pre-compression force may be included to avoid capping.

[0438] Table 27: In all tablet examples, the amounts of the various ingredients are given as % by weight of the tablet.

[0439]

[0440] Table 28: In all tablet examples, the amounts of the various ingredients are given as % by weight of the tablet.

[0441]

[0442] Table 29: In all tablet examples, the amounts of the various ingredients are given as % by weight of the tablet.

[0443]

[0444] Example 11A

[0445] Test Methods for Content Uniformity in Powder Premixes and Powder Blends

[0446] Content uniformity (CU), i.e. the homogeneity of the CBD active substance in the powder premix (powder premix sample) and in the powder blend (powder blend) which is a mixture with additional ingredients to be processed into an oral dosage form, was determined according to Ph. Eur. 10.8 using test method 2.9.40 Uniformity of dosage units.

[0447] At least 5 samples were taken from the powder mixture to be analyzed, each sample having the same fixed weight, which ranged from 0.25 to 2 grams. For each sample, the content of CBD active was analyzed by standard HPLC techniques. The content uniformity was then calculated as the relative standard deviation (RSD) of the individual results.

[0448] Example 11B

[0449] Test Methods for Content Uniformity in Solid Dosage Forms

[0450] Content uniformity, i.e. the homogeneity of the CBD active substance in the solid dosage form was determined according to Ph. Eur. 10.8 using test method 2.9.40 Uniformity of dosage units.

[0451] At least 10 samples were taken from the solid dosage form (e.g. tablet) for analysis. For each sample, the content of CBD active was analyzed by standard HPLC techniques. The content uniformity was then calculated as the relative standard deviation (RSD) of the individual results.

[0452] Example 12

[0453] In vivo testing of release from solid dosage forms

[0454] The sample solid dosage form was tested in a test group of 8 test subjects. The test subject was not allowed to eat and drink water at least 30 minutes before any test began. The test subject is a healthy person arranged on an objective basis according to specific requirements. After a specific use time interval such as 0, 0.5, 1, 2, 3, 5 and 10 minutes, the content of CBD in the remaining solid dosage residues is measured. Each of the 8 test subjects is measured in triplicate for solid dosage form, and a total of 24 measurements are obtained for each sample. The average value of 24 measurements is calculated, and the weight % release is calculated based on the initial content of CBD in the sample. The content of CBD (if still present) is measured in the remaining solid dosage form residues.

[0455] The solid dosage form is weighed and placed in the mouth, and the test subject is instructed to place and use the solid dosage form as expected. For chewing gum, the test subject is instructed to chew the sample at a frequency of 60 chews per minute. For lozenges, the test subject is instructed to place the sample between the tongue and the palate, and then suck and flip the solid dosage form every 0.5 minutes. Once the desired test time (0.5, 1, 2, 3, 5 and 10 minutes) is reached, the solid dosage form is taken out and weighed directly in the measuring cup for analyzing CBD content. The in vivo dissolution curve is obtained by analyzing the CBD content in the solid dosage form under different dissolution times.

[0456] The test is performed on tablets, gums and lozenges. In addition, the test is also performed on other cannabinoids, including THC.

[0457] Embodiment 13

[0458] In vitro release testing in solid dosage forms

[0459] The sample solid dosage form is tested. After a specific use time interval such as 0, 0.5, 1, 2, 3, 5 and 10 minutes, the content of CBD in the remaining solid dosage residue is measured. The solid dosage form is measured in triplicate. The average value of the measurement results is calculated, and the weight % release amount is calculated based on the initial content of CBD in the sample. The content of CBD is measured in the remaining solid dosage form residue (if still present).

[0460] 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 content of CBD in the solid dosage form was analyzed. In vitro curves were obtained by analyzing the content of CBD in the solid dose at different dissolution times.

[0461] The test is performed on tablets, gums and lozenges. In addition, the test is performed on other cannabinoids, including THC.

[0462] Embodiment 14

[0463] CBD delivered to the oral mucosa from solid dosage forms

[0464] The sample was used for 1 minute as expected by a test group of 8 test subjects. The test subjects were healthy people arranged on an objective basis according to specific requirements. The test subjects were not allowed to eat and drink water for at least 30 minutes before any test began. During this process, the test subjects were not allowed to swallow. The solid dosage form was weighed and placed in the mouth, and the test subjects were instructed to place and use the solid dosage form as expected. For chewing gum, the test subjects were instructed to chew the sample at a frequency of 60 chews per minute. For lozenges, the test subjects were instructed to place the sample between the tongue and the palate, and then suck and flip the solid dosage form every 10 seconds. After one minute, saliva was obtained from the test subjects and collected in a container for later analysis. In the test of 2 minutes release, the same process was followed until 2 minutes (the last saliva sample was collected at 2 minutes), and added to the same container for aggregation analysis. After 2 minutes, the aggregated saliva samples were collected, and the CBD content in the saliva was measured. The CBD content in the remaining residue was also measured. If the residue still exists, it is placed in a flask, weighed and analyzed. The residue (if still exists) and saliva of each of the 8 subjects were measured in triplicate 3 times, resulting in a total of 24 measurements per sample. The average of the 24 measurements was then calculated. By comparing the amount of CBD in the residue and the amount of CBD in the saliva with the amount of CBD in the solid dosage form before use, the amount of CBD delivered to the oral mucosa can be estimated.

[0465] The test is performed on tablets, gums and lozenges. In addition, the test is performed on other cannabinoids, including THC.

[0466] Embodiment 15

[0467] Sensory Evaluation Test Setup for Solid Dosage Forms

[0468] In addition to in vivo or in vitro release measurements, sensory testing was also performed to reveal the very important features and characteristics of solid dosage forms. These sensory parameters are important as indicators of solid dosage form composition structure. This structure is a basic guide for how solid dosage forms are similar to the structure of comparative solid dosage forms, which are set as the standard in the test series, i.e., in the test series of preferably 5 samples, solid dosage forms are compared with each other. The test setting is composed of 8 test subjects in the test group. All test subjects are healthy individuals arranged on an objective basis according to specific requirements. Sensory analysis is performed according to ISO 4121-2003 following the test conditions of ISO8589. The result is the average value of 8 individual results.

[0469] The test subjects gave a grade from "+" to "+++++", where "+" is poor and "+++++" is excellent, i.e., "+++++" means that the solid dosage form is excellent compared to the standard, "+++" means that the solid dosage form is comparable to the standard, and "+" means that the solid dosage form is far from the standard. "0" means that the test was not performed.

[0470] Four different parameters were tested in the test group:

[0471] friability Flavor Sweetness Abnormal characteristics

[0472] "Texture" - the overall impression of a solid dosage form when placed in the mouth with respect to elements such as hardness, roughness and smoothness.

[0473] "Fragility" - the impression of a solid dosage form when placed in the mouth and when it is used for its intended purpose. For example, a very hard and sticky structure would give a very low rating, while a very brittle structure would also give a very low rating.

[0474] "Flavor" - the overall impression of the solid dosage form regarding flavor during its intended use. For example, a very low flavor experience is given a very low rating, while a flavor experience that is too high and not comparable to the standard is also given a very low rating.

[0475] "Sweetness" - the overall impression of the solid dosage form regarding sweetness during the intended use period. For example, if the sweetness decreases quickly, give it a very low rating, while if the sweetness is too high, giving an unpleasant sensation, also give it a very low rating.

[0476] "Off-notes" - the overall impression of the off-notes of one or more cannabinoids in the composition during the intended use. For example, if off-notes are experienced in the throat (grassy, ​​bitter, throat irritation) a low rating is given, while if other unpleasant sensations are experienced a low rating is also given.

[0477] Example 16

[0478] Results for content uniformity in powder premixes

[0479] The process of Example 11A was used for the above powder premix (Powder Premix Samples) and the results are shown in the table below. The results for the content uniformity of the samples are provided as a single value obtained as the relative standard deviation (RSD) of the CBD content of multiple samples taken at the end of the premix preparation process.

[0480] Table 30: Content uniformity of powder premixes containing hydrogenated vegetable oil (HVO) - HVO added to isolated CBD and sweetener.

[0481]

[0482] Table 31: Content uniformity of powder premixes containing hydrogenated vegetable oil (HVO) - HVO added to isolated CBD and sweetener.

[0483]

[0484] Table 32: Content uniformity of powder premixes containing hydrogenated vegetable oil (HVO) (preheated) - HVO added to isolated CBD and sweetener.

[0485]

[0486] Table 33: Content uniformity of powder premixes containing Miglyol - Miglyol added to isolated CBD and sweetener.

[0487]

[0488] Table 34: Content uniformity of powder premixes containing Miglyol - Miglyol added to isolated CBD and sweetener.

[0489]

[0490] Table 35: Content uniformity of powder premixes containing Miglyol - Miglyol added to isolated CBD and sweetener.

[0491]

[0492] Table 35: Content uniformity of powder premixes containing Miglyol - Miglyol added to isolated CBD and sweetener.

[0493]

[0494] Table 36: Content uniformity of powder premixes containing hydrogenated vegetable oil (HVO) - HVO added to high load of isolated CBD and sweetener.

[0495]

[0496] Table 37: Content uniformity of powder premixes containing hydrogenated vegetable oil (HVO) - HVO added to high load of isolated CBD and sweetener.

[0497]

[0498] Table 38: Content uniformity of powder premixes containing hydrogenated vegetable oil (HVO) - HVO added to high load of isolated CBD and sweetener.

[0499]

[0500] Table 39: Content uniformity of powder premixes containing hydrogenated vegetable oil (HVO) - CBD / HVO blend added to sweetener.

[0501]

[0502] Table 40: Content uniformity of powder premixes containing hydrogenated vegetable oil (HVO) - CBD / HVO blend added to sweetener.

[0503]

[0504] Table 41: Content uniformity of powder premixes containing hydrogenated vegetable oil (HVO) - CBD / HVO blend added to sweetener.

[0505]

[0506] Table 42: Content uniformity of powder premixes containing Miglyol - CBD / Miglyol mixture added to sweetener.

[0507]

[0508] Table 43: Content uniformity of powder premixes containing Miglyol - CBD / Miglyol mixture added to sweetener.

[0509]

[0510] Table 44: Content uniformity of powder premixes containing Miglyol - CBD / Miglyol mixture added to sweetener.

[0511]

[0512] Table 45: Content uniformity of comparative samples - without triglyceride lipids.

[0513]

[0514] Table 46: Content uniformity of powder premix containing Miglyol (without preheating) - Mix added to sweetener.

[0515]

[0516] Table 47: Content uniformity of powder premix containing Miglyol (without preheating) - Mix added to sweetener.

[0517]

[0518] Example 16A

[0519] Results for content uniformity in powder premixes

[0520] The procedure of Example 11A was used for the above powder premix (Powder Premix Samples) and the results are shown in the table below. The results for the content uniformity of the samples are provided as a single value obtained as the relative standard deviation (RSD) of the CBD content of multiple samples taken at the end of the premix preparation procedure.

[0521] Table 47A: Content uniformity of powder premixes.

[0522]

[0523] Embodiment 17

[0524] Results for content uniformity in powder blends and solid dosage forms

[0525] The process of Example 11A was used for powder blends (Powder Blends), which were powder premixes containing additional ingredients as outlined in the formulation of oral dosage forms (Powder Premix Samples). These powder blends were formed into solid dosage forms. The process of Example 11B was used for solid dosage forms. The results are shown in the table below.

[0526] The results of the content uniformity (CU) of the samples are provided as a single value obtained as the relative standard deviation (RSD) of the CBD content of multiple samples taken at the end of the manufacturing process. If individual samples are collected at different stages of the tableting process (e.g., beginning, middle, end), the content uniformity is determined by analyzing the combined samples from the different process stages.

[0527] Table 48: Based on the procedure in Example 11B.

[0528]

[0529] Table 49: Based on the procedure in Example 11B.

[0530]

[0531] Table 50: Based on the procedure in Example 11B.

[0532]

[0533] Table 51: Based on the procedure in Example 11B.

[0534]

[0535] Example 17A

[0536] Results for content uniformity in powder blends and solid dosage forms

[0537] The process of Example 11A was used for powder blends (Powder Blends), which were powder premixes containing additional ingredients as outlined in the formulation of oral dosage forms (Powder Premix Samples). These powder blends were formed into solid dosage forms. The process of Example 11B was used for solid dosage forms. The results are shown in the table below.

[0538] The results of the content uniformity (CU) of the samples are provided as a single value obtained as the relative standard deviation (RSD) of the CBD content of multiple samples taken at the end of the manufacturing process. If individual samples are collected at different stages of the tableting process (e.g., beginning, middle, end), the content uniformity is determined by analyzing the combined samples from the different process stages.

[0539] Table 51A: Based on the procedure in Example 11B.

[0540]

[0541] Table 51B: Based on the procedure in Example 11B.

[0542]

[0543]

[0544] Table 51C: Based on the procedure in Example 11B.

[0545]

[0546] Embodiment 18

[0547] Additional powder premixes and powder blends content uniformity results

[0548] The process of Example 11A was also carried out for additional powder premixes and powder blends for different application forms. For example, the powders provided in the above examples were applied to bags, sachets and flowpacks, where similar good results of content uniformity were observed. See Examples 16A and 17A for some examples.

[0549] Embodiment 19

[0550] Additional Solid Dosage Form Content Uniformity Results

[0551] The process of Example 11B was also performed on additional solid dosage forms. Similar good results were observed for tablets without gum base, FDT tablets, chewing gums and lozenges. See Example 17A for some examples.

Claims

1. A powder premix for oral administration of a cannabinoid, the powder premix comprising: a cannabinoid powder composition comprising one or more isolated cannabinoids in an amount of at least 2% by weight of the powder premix; a lipid composition comprising one or more triglycerides in an amount of at least 1.0% by weight of the powder premix; and A sweetener powder composition comprising one or more sweeteners, wherein a weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:

1.

2. The powder premix according to claim 1, wherein the weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:

2.

3. The powder premix according to any one of claims 1 or 2, wherein the weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:

4.

4. The powder premix according to any one of claims 1 to 3, wherein the weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:

5.

5. The powder premix according to any one of claims 1 to 4, wherein the weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:

10.

6. A powder premix according to any one of claims 1 to 5, wherein the weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:40 to 1:10, such as 1:40 to 1:15, such as 1:40 to 1:

20.

7. A powder premix according to any one of claims 1 to 6, wherein the one or more triglycerides are of vegetable origin.

8. Powder premix according to any one of claims 1 to 7, wherein the one or more triglycerides do not contain triglycerides of animal origin.

9. The powder premix according to any one of claims 1 to 8, wherein the one or more triglycerides are selected from one or more C4 to C14 triglycerides.

10. The powder premix according to any one of claims 1 to 9, wherein the one or more triglycerides are selected from one or more C6 to C12 triglycerides.

11. The powder premix according to any one of claims 1 to 10, wherein the one or more triglycerides are selected from one or more C8 to C12 triglycerides.

12. A powder premix according to any one of claims 1 to 11, wherein the one or more triglycerides comprises a partially hydrogenated vegetable oil.

13. A powder premix according to any one of claims 1 to 11, wherein the one or more triglycerides comprise a fully hydrogenated vegetable oil.

14. A powder premix according to any one of claims 1 to 13, wherein the one or more triglycerides are selected from triglycerides that are liquid at or above 0 degrees Celsius.

15. A powder premix according to any one of claims 1 to 14, wherein the one or more triglycerides is a blend of multiple triglycerides, such as a blend of corn oil and oleic acid, such as a blend of corn oil and oleic acid in a ratio of 1:3 to 3:

1.

16. A powder premix according to any one of claims 1 to 15, wherein the one or more triglycerides are heated to a temperature above ambient temperature before being added to the premix.

17. A powder premix according to any one of claims 1 to 16, wherein the one or more triglycerides are heated to a temperature of 50 to 80 degrees Celsius before being added to the premix.

18. A powder premix according to any one of claims 1 to 17, wherein the one or more triglycerides are heated to a temperature of 60 to 70 degrees Celsius before being added to the premix.

19. A powder premix according to any one of claims 1 to 18, wherein the one or more triglycerides are selected from triglycerides that are liquid at or above 20 degrees Celsius.

20. A powder premix according to any one of claims 1 to 18, wherein the one or more triglycerides are selected from triglycerides that are liquid at or above 25 degrees Celsius.

21. A powder premix according to any one of claims 1 to 20, wherein the one or more triglycerides are selected from triglycerides having a melting temperature of 25 to 50 degrees Celsius.

22. A powder premix according to any one of claims 1 to 21, wherein the one or more triglycerides are selected from triglycerides having a melting temperature of 30 to 40 degrees Celsius.

23. A powder premix according to any one of claims 1 to 18, wherein the one or more triglycerides comprises caprylic acid in an amount of 50% to 80% by weight.

24. A powder premix according to any one of claims 1 to 19, wherein the one or more triglycerides comprises capric acid in an amount of 20% to 45% by weight.

25. A powder premix according to any one of claims 1 to 23, wherein the one or more triglycerides comprises coconut oil and / or corn oil and / or oleic acid.

26. A powder premix according to claim 25, wherein the one or more triglycerides consist essentially of coconut oil and / or corn oil and / or oleic acid.

27. A powder premix according to any one of claims 25 to 26, wherein the one or more triglycerides form part of, or are, a self-emulsifying drug delivery system (SEDDS).

28. A powder premix according to any one of claims 1 to 27, wherein the one or more triglycerides are present in an amount of at least 1.5% by weight of the powder premix.

29. A powder premix according to any one of claims 1 to 28, wherein the one or more triglycerides are present in an amount of at least 2.0% by weight of the powder premix.

30. A powder premix according to any one of claims 1 to 29, wherein the one or more triglycerides are present in an amount of at least 3.0% by weight of the powder premix.

31. A powder premix according to any one of claims 1 to 30, wherein the one or more triglycerides are present in an amount of at least 5.0% by weight of the powder premix.

32. A powder premix according to any one of claims 1 to 31 , wherein the one or more triglycerides are present in an amount of at least 10.0% by weight of the powder premix.

33. A powder premix according to any one of claims 1 to 32, wherein the one or more triglycerides are present in an amount of at least 20.0% by weight of the powder premix.

34. A powder premix according to any one of claims 1 to 33, wherein the one or more sweeteners are present in an amount of at least 50% by weight of the powder premix.

35. A powder premix according to any one of claims 1 to 34, wherein the one or more sweeteners are present in an amount of at least 60% by weight of the powder premix.

36. A powder premix according to any one of claims 1 to 35, wherein the one or more sweeteners are present in an amount of at least 70% by weight of the powder premix.

37. A powder premix according to any one of claims 1 to 36, wherein the one or more sweeteners are present in an amount of at least 75% by weight of the powder premix.

38. A powder premix according to any one of claims 1 to 37, wherein the one or more sweeteners are present in an amount of at least 80% by weight of the powder premix.

39. A powder premix according to any one of claims 1 to 38, wherein the one or more sweeteners comprises one or more sugar alcohols.

40. The powder premix according to any one of claims 1 to 39, wherein the one or more sugar alcohols are selected from sorbitol, xylitol, maltitol, isomalt, mannitol, erythritol, lactitol, and combinations thereof.

41. The powder premix according to any one of claims 1 to 40, wherein the one or more sugar alcohols are selected from xylitol, erythritol, maltitol, mannitol, and combinations thereof.

42. A powder premix according to any one of claims 1 to 41, wherein the one or more sugar alcohols comprises xylitol.

43. A powder premix according to any one of claims 1 to 42, wherein the one or more sugar alcohols comprises erythritol.

44. A powder premix according to any one of claims 1 to 43, wherein the one or more sugar alcohols comprises mannitol.

45. A powder premix according to any one of claims 1 to 44, wherein the one or more sugar alcohols comprises maltitol.

46. ​​A powder premix according to any one of claims 1 to 45, wherein the one or more sugar alcohols comprise granulated sugar alcohol particles.

47. A powder premix according to any one of claims 1 to 46, wherein the one or more sugar alcohols comprise non-direct (non-DC) sugar alcohol particles.

48. A powder premix according to any one of claims 1 to 38, wherein the one or more sweeteners comprises one or more sugars.

49. A powder premix according to any one of claims 1 to 48, wherein the one or more sweeteners comprises at least two types of sweetener particles.

50. A powder premix according to any one of claims 1 to 49, wherein the one or more sweeteners comprises sweetener particles having more than 50% of the particles having a particle size of less than 250 microns.

51. A powder premix according to any one of claims 1 to 50, wherein the one or more sweeteners comprises sweetener particles having a particle size greater than 20% of the particles being greater than 500 microns.

52. A powder pre-mix according to any one of claims 1 to 51 wherein the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:40 to 1:5, such as 1:40 to 1:4, such as 1:40 to 1:3, such as 1:40 to 1:2, such as 1:40 to 1:

1.

53. A powder pre-mix according to any one of claims 1 to 52, wherein the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:20 to 1:5, such as 1:20 to 1:4, such as 1:20 to 1:3, such as 1:20 to 1:2, such as 1:20 to 1:

1.

54. A powder pre-mix according to any one of claims 1 to 53 wherein the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:10 to 1:5, such as 1:10 to 1:4, such as 1:10 to 1:3, such as 1:10 to 1:2, such as 1:10 to 1:

1.

55. A powder pre-mix according to any one of claims 1 to 54 wherein the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:5 to 1:4, such as 1:5 to 1:3, such as 1:5 to 1:

2.

56. A powder pre-mix according to any one of claims 1 to 55 wherein the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:4 to 4:1, such as 1:4 to 3:1, such as 1:4 to 2:1, such as 1:4 to 1:1, such as 1:4 to 1:

2.

57. A powder pre-mix according to any one of claims 1 to 56 wherein the weight ratio of the one or more triglycerides to the one or more isolated cannabinoids is in the range of 1:3 to 4:1, such as 1:2 to 4:1, such as 1:1 to 4:1, such as 2:1 to 4:

1.

58. A powder premix according to any one of claims 1 to 57 wherein the one or more isolated cannabinoids are present in an amount of at least 5% by weight of the powder premix.

59. A powder premix according to any one of claims 1 to 58 wherein the one or more isolated cannabinoids are present in an amount of at least 10% by weight of the powder premix.

60. A powder premix according to any one of claims 1 to 59 wherein the one or more isolated cannabinoids are present in an amount of at least 20% by weight of the powder premix.

61. A powder premix according to any one of claims 1 to 60 wherein the one or more isolated cannabinoids are present in an amount of at least 30% by weight of the powder premix.

62. A powder premix according to any one of claims 1 to 61 wherein the one or more isolated cannabinoids are present in the powder mix in an amount of 0.1 to 400 mg.

63. A powder premix according to any one of claims 1 to 62, wherein the one or more isolated cannabinoids are present in the powder premix in an amount of 1 to 200 mg.

64. A powder premix according to any one of claims 1 to 63 wherein the one or more isolated cannabinoids are present in the powder premix in an amount of 10 to 100 mg.

65. A powder premix according to any one of claims 1 to 64, wherein the one or more isolated cannabinoids are selected from cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidiol (CBDV), and combinations thereof.

66. A powder premix according to any one of claims 1 to 64, wherein the one or more isolated cannabinoids are selected from tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and combinations thereof.

67. A powder pre-mix according to any one of claims 1 to 64, wherein the one or more isolated cannabinoids comprises cannabigerol (CBG).

68. A powder pre-mix according to any one of claims 1 to 67 wherein the one or more isolated cannabinoids are present in a purity of at least 90% (w / w).

69. A powder pre-mix according to any one of claims 1 to 68 wherein the one or more isolated cannabinoids are present in a purity of at least 95% (w / w).

70. A powder pre-mix according to any one of claims 1 to 69 wherein the one or more isolated cannabinoids are present in a purity of at least 98% (w / w).

71. A powder premix according to any one of claims 1 to 70, wherein the one or more isolated cannabinoids does not comprise a cannabinoid distillate.

72. A powder pre-mix according to any one of claims 1 to 71 wherein the one or more isolated cannabinoids does not comprise a cannabinoid extract.

73. A powder pre-mix according to any one of claims 1 to 68 wherein the one or more isolated cannabinoids does not comprise the one or more isolated cannabinoids in a purity of less than 90% (w / w).

74. A powder premix according to any one of claims 1 to 73 wherein the one or more isolated cannabinoids are dissolved in the one or more triglycerides prior to mixing with the sweetener powder composition.

75. A powder premix according to any one of claims 1 to 73 wherein the one or more isolated cannabinoids are added to the sweetener powder composition prior to mixing with the one or more triglycerides.

76. A powder premix according to any one of claims 1 to 73 wherein the one or more triglycerides are added to the sweetener powder composition prior to mixing with the one or more isolated cannabinoids.

77. A powder premix according to any one of claims 1 to 76, wherein further ingredients are added to the premix.

78. A powder premix according to any one of claims 1 to 77, wherein additional ingredients selected from the group consisting of flavors, dry binders, tableting aids, anti-caking agents, surfactants, emulsifiers, antioxidants, enhancers, mucoadhesives, absorption enhancers, high intensity sweeteners, softeners, colorants, additional active ingredients, water soluble indigestible polysaccharides, water insoluble polysaccharides, and any combination thereof are added to the premix.

79. A powder premix according to any one of claims 1 to 78, wherein one or more flavouring agents are added to the premix.

80. A powder premix according to any one of claims 1 to 79, wherein a high intensity sweetener is added to the premix.

81. A powder premix according to any one of claims 1 to 80, wherein the premix is ​​a ready-to-use premix.

82. A powder premix according to any one of claims 1 to 80, wherein the premix is ​​applied in an amount of 10% to 99.9% by weight in combination with further ingredients, such as oral care agents.

83. A solid dosage form for oral administration of a cannabinoid comprising a premix according to any one of claims 1 to 80.

84. The solid dosage form of claim 83, wherein the premix is ​​present in an amount of 10% to 100% by weight of the solid dosage form.

85. The solid dosage form of any one of claims 83 or 84, wherein the premix is ​​present in an amount of 15% to 75% by weight of the solid dosage form.

86. A tablet for oral administration of cannabinoids comprising a premix according to any one of claims 1 to 80.

87. The tablet of claim 86, wherein the premix is ​​present in an amount of 10% to 100% by weight of the tablet.

88. A tablet according to any one of claims 86 or 87, wherein the premix is ​​present in an amount of 15% to 75% by weight of the tablet.

89. A tablet according to any one of claims 86 to 88, wherein the tablet comprises one or more sugar alcohols in addition to the one or more sweeteners in the premix, the sugar alcohols being selected from sorbitol, erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof.

90. A tablet according to any one of claims 86 to 89, wherein the tablet comprises one or more sweeteners in addition to the one or more sweeteners in the premix in an amount of 20% to 80% by weight of the tablet.

91. The tablet of any one of claims 86 to 90, wherein the tablet comprises directly compressible (DC) sugar alcohol granules and non-directly compressible (non-DC) sugar alcohol granules.

92. The tablet of claim 91, wherein the tablet has a weight ratio of the non-DC sugar alcohol particles to the DC sugar alcohol particles of 0.2 to 1.

2.

93. The tablet of any one of claims 91 to 92, wherein the tablet has a weight ratio of the non-DC sugar alcohol particles to the DC sugar alcohol particles of 0.3 to 0.

7.

94. A tablet according to any one of claims 86 to 93, wherein the tablet comprises one or more insoluble components selected from the group consisting of silicon dioxide, microcrystalline cellulose, cellulose, silicified microcrystalline cellulose, clay, talc, starch, pregelatinized starch, calcium carbonate, dicalcium phosphate, magnesium carbonate, magnesium aluminum metasilicate, superporous silica, and mixtures thereof.

95. A tablet according to any one of claims 86 to 94, wherein the tablet comprises one or more binders in an amount of 0.1 to 8 wt % of the tablet, such as 0.1 to 7 wt %, such as 1 to 7 wt %, such as 2 to 7 wt %, such as 0.1 to 6 wt %, such as 1 to 6 wt % of the tablet.

96. The tablet according to any one of claims 86 to 95, wherein the tablet comprises at least two modules, and wherein the premix is ​​contained in at least one module of the tablet.

97. A chewing gum for oral administration of cannabinoids comprising a pre-mix according to any one of claims 1 to 80.

98. The chewing gum according to claim 97, wherein the premix is ​​present in an amount of 15% to 75% by weight of the chewing gum.

99. A chewing gum according to any one of claims 97 or 98, wherein the chewing gum comprises gum base in an amount of 20% to 40% by weight of the chewing gum, and wherein the chewing gum is designed to be chewed into a cohesive residue containing a water-insoluble component.

100. The chewing gum according to any one of claims 97 to 99, wherein the chewing gum comprises a gum base, and wherein the gum base comprises an elastomer selected from the group consisting of styrene butadiene rubber (SBR), butyl rubber, polyisobutylene (PIB), and combinations thereof.

101. A chewing gum according to any one of claims 97 to 100, wherein the chewing gum comprises a gum base, and wherein the gum base comprises at least 5% by weight of an elastomer.

102. The chewing gum according to any one of claims 97 to 101, wherein the chewing gum comprises a gum base, and wherein the gum base comprises a gum base resin selected from natural resins and / or synthetic resins.

103. The chewing gum according to any one of claims 97 to 102, wherein the chewing gum comprises a gum base, and wherein the gum base comprises at least 5% by weight of gum base resin.

104. A chewing gum according to any one of claims 97 to 103, wherein the chewing gum comprises a gum base, and wherein the gum base comprises gum base particles having an average particle size of 400 μm to 1400 μm.

105. A chewing gum according to any one of claims 97 to 104, wherein the chewing gum comprises one or more sugar alcohols in addition to the one or more sweeteners in the premix, the sugar alcohols being selected from sorbitol, erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof.

106. A chewing gum according to any one of claims 97 to 105, wherein the chewing gum comprises one or more sweeteners in addition to the one or more sweeteners in the premix in an amount of 20% to 60% by weight of the chewing gum.

107. The chewing gum according to any one of claims 97 to 106, wherein the chewing gum comprises at least two compressed modules, and wherein the premix is ​​contained in at least one of the two compressed modules.

108. The chewing gum according to any one of claims 97 to 107, wherein the chewing gum comprises at least two compressed modules, and wherein the composition of the two modules is different.

109. The chewing gum according to any one of claims 97 to 108, wherein the chewing gum comprises at least two compressed modules, and wherein at least one of the two compressed modules does not comprise gum base.

110. A lozenge for oral administration of a cannabinoid comprising a premix according to any one of claims 1 to 80.

111. The tablet of claim 110, wherein the premix is ​​present in an amount of 10% to 100% by weight of the tablet.

112. The tablet of any one of claims 110 or 111, wherein the premix is ​​present in an amount of 15% to 75% by weight of the tablet.

113. The lozenge of any one of claims 110 to 112, wherein the lozenge comprises one or more sugar alcohols selected from sorbitol, erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof in addition to the one or more sweeteners in the premix.

114. The lozenge of any one of claims 110 to 113, wherein the lozenge comprises one or more sweeteners in addition to the one or more sweeteners in the premix in an amount of 20% to 60% by weight of the lozenge.

115. The tablet of any one of claims 110 to 114, wherein the tablet comprises one or more insoluble components selected from the group consisting of silicon dioxide, microcrystalline cellulose, cellulose, silicified microcrystalline cellulose, clay, talc, starch, pregelatinized starch, calcium carbonate, dicalcium phosphate, magnesium carbonate, magnesium aluminum metasilicate, superporous silica, and mixtures thereof.

116. The lozenge of any one of claims 110 to 115, wherein the lozenge comprises one or more disintegrants operable to disintegrate the lozenge within 1 minute or less of contact with oral saliva.

117. The lozenge of any one of claims 110 to 116, wherein the lozenge comprises one or more disintegrants selected from the group consisting of croscarmellose sodium, crospovidone, sodium starch glycolate, and combinations thereof.

118. The tablet of any one of claims 110 to 117, wherein the tablet comprises one or more disintegrants in an amount of 0.5% to 25% by weight of the tablet.

119. A sachet for oral administration of a cannabinoid comprising a premix according to any one of claims 1 to 80.

120. The sachet according to claim 119, wherein the premix is ​​present in an amount of 10% to 100% by weight of the sachet.

121. The sachet according to any one of claims 119 or 120, wherein the premix is ​​present in an amount of 15% to 75% by weight of the sachet.

122. The sachet according to any one of claims 120 to 121, wherein the sachet comprises one or more insoluble components selected from the group consisting of silicon dioxide, clay, talc, starch, pregelatinized starch, calcium carbonate, dicalcium phosphate, magnesium carbonate, magnesium aluminum metasilicate, superporous silica, and mixtures thereof.

123. The sachet according to any one of claims 120 to 122, wherein the sachet comprises one or more insoluble fibers.

124. The sachet according to any one of claims 120 to 123, wherein the sachet comprises one or more insoluble fibers selected from the group consisting of wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, cellulose fiber, bran fiber, bamboo fiber, powdered cellulose, microcrystalline cellulose, and combinations thereof.

125. The sachet according to any one of claims 120 to 124, wherein the sachet comprises one or more sugar alcohols selected from sorbitol, erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof in addition to the one or more sweeteners in the premix.

126. The sachet according to any one of claims 120 to 125, wherein the sachet comprises one or more sweeteners in addition to the one or more sweeteners in the premix in an amount of 20% to 60% by weight of the sachet.

127. A method of preparing a powder premix of cannabinoids for oral administration, the method comprising the steps of: i) dissolving or dispersing a cannabinoid powder composition comprising one or more isolated cannabinoids in a lipid composition comprising one or more triglycerides, and then ii) mixing a sweetener powder composition comprising one or more sweeteners with the mixture obtained in i) to obtain a powder premix, Wherein a weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:

1.

128. The method of claim 127, wherein the one or more triglycerides are heated to a temperature above ambient temperature prior to addition to the premix.

129. A method according to any one of claims 127 or 128, wherein the powder premix is ​​defined according to any one of claims 1 to 80.

130. A method of preparing a powder premix of cannabinoids for oral administration, the method comprising the steps of: i) mixing a sweetener powder composition comprising one or more sweeteners with a cannabinoid powder composition comprising one or more isolated cannabinoids, and then ii) mixing a lipid composition comprising one or more triglycerides with the mixture obtained in i) to obtain a powder premix, wherein a weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:

1.

131. The method of claim 130, wherein the one or more triglycerides are heated to a temperature above ambient temperature prior to addition to the premix.

132. A method according to any one of claims 130 or 131, wherein the powder premix is ​​defined according to any one of claims 1 to 80.

133. A method of preparing a powder premix of cannabinoids for oral administration, the method comprising the steps of: i) mixing a sweetener powder composition comprising one or more sweeteners with a lipid composition comprising one or more triglycerides, and then ii) mixing a cannabinoid powder composition comprising one or more isolated cannabinoids with the mixture obtained in i) to obtain a powder pre-mix, wherein a weight ratio of the one or more triglycerides to the one or more sweeteners is in the range of 1:50 to 1:

1.

134. The method of claim 133, wherein the one or more triglycerides are heated to a temperature above ambient temperature prior to addition to the premix.

135. A method according to any one of claims 133 or 134, wherein the powder premix is ​​defined according to any one of claims 1 to 80.

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