DK202300252A1

DK202300252A1 - Carrier systems for cannabinoids

Info

Publication number: DK202300252A1
Application number: DKPA202300252A
Authority: DK
Inventors: Blaaholm Rasmus; Skov Jensen Sanne; Nykjær Nikolajsen Gitte; Laursen Simon; Boesen Dorte
Original assignee: Fertin Pharma As
Priority date: 2023-03-21
Filing date: 2023-03-21
Publication date: 2024-10-18
Also published as: DK181701B1

Abstract

The present invention relates to an orally dissolvable or chewable tableted powder formulation, comprising one or more mesoporous silica carriers loaded with a liquid cannabinoid suspension or solution; one or more water-soluble agents in an amount of 20-80% by weight of the tableted powder formulation; and one or more flavors, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10.

Description

DK 2023 00252 A1 1

CARRIER SYSTEMS FOR CANNABINOIDS

FIELD OF THE INVENTION

The invention relates to the field of cannabinoids. In particular, the invention relates to carrier systems for cannabinoids.

BACKGROUND OF THE INVENTION

Administration of medication to patients in need of alleviation with respect to various indications has traditionally applied the gastrointestinal route, such as in the form of pills to swallow for dissolution in the stomach and absorption of the active ingredient in the intestines. Particularly, this applies for active ingredients with a bitter taste in a high dose considered to cause inconvenience if for instance delivered in the oral cavity for oral uptake.

Although oral administration of cannabinoids is a common route of administration, less attention has been given in the prior art to carrier systems that may allow a high amount of cannabinoids to be administered to patients in need thereof. Particularly, less attention has been given to carrier systems for cannabinoids that allow a high load of cannabinoids and at the same time provides convenience during oral administration. Typically, carrier systems may be expected to provide an inconvenient mouthfeel in oral formulations that are to be dissolved or disintegrated in the oral cavity.

Cannabinoids are highly lipophilic, meaning that they are soluble in lipids and some organic solvents while being substantially insoluble or only sparsely soluble in water.

Cannabinoids are soluble in highly non-polar solvents. Some of these solvents are pharmaceutically unacceptable, and the pharmaceutically acceptable solvents need to beused in high concentrations to produce solutions.

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Various solutions have been suggested in the prior art with respect to oral formulations for delivery of cannabinoids. Among these solutions, solid dosage forms, lozenges, chewing gums and pouches have been proposed. While these solutions may have certain benefits with respect to oral delivery of cannabinoids, such as CBD or THC, these solutions have been mainly focused on either release from the application forms or certain components that allow effective absorption of the cannabinoids in the mucosa.

However, less attention has been given to administration of high doses of cannabinoids and the associated mouthfeel during or after partly dissolution or partly disintegration in the oral cavity of the application form. Typically, when carrier systems are present it may be expected that the carrier systems as such will accommodate an unsuitable mouthfeel, such as a sandy feeling or even a creaking sound upon mastication of the application form with a content of the carrier system.

The challenges of carrier systems may particularly be the case if a high load of cannabinoids are to be present and accordingly a high load of the carrier system is present in the formulation. At the same time, homogeneity and/or release of the cannabinoid in the application form is of importance which in some cases may be a — challenge if the cannabinoids are applied in a carrier system.

It is a desire in the prior art with improved homogeneity but hitherto provided solutions have traditionally been considered less suitable also partly in view of the desire to provide fast releasing products. Already available means for providing improved homogeneity have shown to be associated with drawbacks while at the same time being required to provide fast release of the cannabinoids.

In formulating solid dosage forms, various challenges are associated with obtaining a homogenous mixture where variations are avoided and a safe and convenient delivery may be obtained. Also, the general formulation of the tablets offering

DK 2023 00252 A1 3 convenience to the user need not be compromised which is often the case if conventional delivery means are applied.

Furthermore, it is preferable that a formulation is provided that may also help in obtaining improved sensorics properties of oral cannabinoid delivery. Here, important sensorics properties include texture, flavor perception, sweetness perception and off-notes associated with cannabinoids. These properties are both relevant from a convenience perspective in solid dosage forms, but certainly also in order to support an appropriate delivery of cannabinoids from the tablets and avoid adverse side effects of cannabinoids.

Another challenge is that cannabinoids tend to be associated with off-notes if delivered in the oral cavity due to the specific physiochemical properties of the compounds. The taste masking challenge is more profound when a higher release of cannabinoids are delivered. If off-notes are the predominant sensation during administration, convenience may be affected and even more critically, the delivery of cannabinoids may also be affected.

A special challenge applies in case the carrier systems are to be released in the oral cavity, such as when the oral application form is partly dissolved or partly disintegrated in the oral cavity, but the carrier systems containing the cannabinoids are to be delivered in the gastrointestinal tract for absorption of the cannabinoids.

Under these circumstances, it may be critical to provide a special carrier system which may allow the cannabinoids to be contained in the carrier for a relatively long time in order for the carrier system to be delivered in the gastrointestinal tract with a high load of cannabinoids.

Additionally, it may be critical that the carrier system may withstand the conditions in the stomach, such as a low pH value, without being critically effected by such conditions and allowing effective delivery of the cannabinoids in the gastrointestinal tract, such as in the intestines.

DK 2023 00252 A1 4

Hence, there is a need in the prior art for powders and formulations that solve the above-referenced challenges and problems of the prior art. In particular, there is a need in the prior art for powders to be applied in various administration form, such as tablets, pouches, chewing gums and lozenges, that are both associated with a suitable uniformity of content of the cannabinoids and offer suitable sensorial properties.

More particularly, it is a desire that these formulations are also acceptable or improved with respect to taste masking and give a desired release of the carrier — systems in the oral cavity and a desired release of cannabinoids for gastrointestinal absorption.

SUMMARY OF THE INVENTION

Accordingly, there is provided an orally dissolvable or chewable tableted powder formulation, comprising one or more mesoporous silica carriers loaded with a liquid cannabinoid suspension or solution; one or more water-soluble agents in an amount of 20-80% by weight of the tableted powder formulation; and one or more flavors, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10.

One of the advantages of the present invention is that a relatively high load of cannabinoids may be accomplished and at the same time the invention may provide convenience during oral administration, such as an improved mouthfeel during and/or after the tableted powder formulation is dissolved and/or chewed. Typically, when carrier systems are present it may be expected that the carrier systems as such will accommodate an unsuitable mouthfeel, such as a sandy feeling or even a creaking sound upon mastication of the application form with a content of the carrier system. However, it was seen that the carrier system according to the invention may provide improvements to known carrier systems.

DK 2023 00252 A1

A special advantage of the present invention is that the system is especially suitable for release of the carrier system in the oral cavity, such as when the oral application form is partly dissolved or partly disintegrated in the oral cavity, and subsequent delivery of the carrier system in the gastrointestinal tract for absorption of the 5 cannabinoids. Under these circumstances, it was seen that the carrier system may allow the cannabinoids to be contained in the carrier for a relatively long time in order for the carrier system to be delivered in the gastrointestinal tract with a high load of cannabinoids.

Additionally, it was seen that the carrier system may withstand the conditions in the stomach, such as a low pH value, without being critically effected by such conditions and allowing effective delivery of the cannabinoids in the gastrointestinal tract, such as in the intestines.

In accordance with the invention, it was not expected that a high load of cannabinoids could be obtained and at the same time that the tableted powder formulation could serve to deliver the cannabinoids to the gastrointestinal target without the challenges disclosed in the prior art. The challenges of carrier systems is particularly the case if a high load of cannabinoids are to be present and accordingly a high load of the carrier system is present in the formulation.

At the same time, homogeneity of the cannabinoid in the application form is of importance which in some cases may be a challenge if the cannabinoids are applied in a carrier system. These challenges may also be overcome by the present invention.

Accordingly, variations may be avoided and a safe and convenient delivery may be obtained.

Furthermore, a formulation is provided that may also help in obtaining improved sensorics properties of oral cannabinoid delivery. Here, important sensorics properties include texture, flavor perception, sweetness perception and off-notes associated with cannabinoids. These properties are both relevant from a convenience perspective in solid dosage forms, but certainly also in order to support an appropriate delivery of cannabinoids from the tablets and avoid adverse side effects of cannabinoids. — Another challenge is that cannabinoids tend to be associated with off-notes during administration due to the specific physiochemical properties of the compounds. Since the cannabinoids may be contained in one or more mesoporous silica carriers according to the invention, this challenge off-notes are less predominant during administration according to the invention.

In some embodiments of the invention, the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:5.

In some embodiments of the invention, the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 8:1 to 1:2.

In some embodiments of the invention, the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 5:1 to 1:2.

In some embodiments of the invention, the one or more mesoporous silica carriers comprises the liquid cannabinoid suspension or solution in a weight ratio of silica — carrier to liquid cannabinoid suspension or solution of 2:8 to 8:2.

In some embodiments of the invention, the one or more mesoporous silica carriers comprises the liquid cannabinoid suspension or solution in a weight ratio of silica carrier to liquid cannabinoid suspension or solution of 3:7 to 7:3.

In some embodiments of the invention, the one or more mesoporous silica carriers comprises the liquid cannabinoid suspension or solution in a weight ratio of silica carrier to liquid cannabinoid suspension or solution of 4:6 to 6:4. n some embodiments of the invention, the one or more mesoporous silica carriers having an average particle size of 20 to 200 microns.

In some embodiments of the invention, the one or more mesoporous silica carriers having an average particle size of 30 to 180 microns.

In some embodiments of the invention, the one or more mesoporous silica carriers having an average particle size of 40 to 180 microns.

In some embodiments of the invention, the one or more mesoporous silica carriers — having an average particle size of 40 to 170 microns.

In some embodiments of the invention, the one or more mesoporous silica carriers having an average particle size of 30 to 100 microns.

In some embodiments of the invention, the one or more mesoporous silica carriers having an average particle size of 30 to 80 microns.

In some embodiments of the invention, the one or more mesoporous silica carriers having an average particle size of 80 to 200 microns.

In some embodiments of the invention, the one or more mesoporous silica carriers having an average particle size of 80 to 170 microns.

In some embodiments of the invention, the one or more mesoporous silica carriers having an average particle size of 80 to 120 microns.

DK 2023 00252 A1 8

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount of above 5% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount of above 10% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount of above 20% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount up to 60% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount up to 50% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount up to 40% by weight of the orally dissolvable or chewable tableted powder formulation.

DK 2023 00252 A1 9

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount up to 30% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount up to 25% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount up to 20% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount up to 15% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount up to 10% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of 30 to 600 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of 30 to 300 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of above 30 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is — present in an amount of above 40 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of above 50 mg in the orally dissolvable or chewable tableted — powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of above 60 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of above 70 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of above 80 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of above 90 mg in the orally dissolvable or chewable tableted powder formulation.

DK 2023 00252 A1 11

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of above 100 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of below 500 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of below 400 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of below 300 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of below 250 mg in the orally dissolvable or chewable tableted — powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of below 200 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of below 150 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more mesoporous silica carriers is present in an amount of below 100 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, an average pore volume of the one or more mesoporous silica carriers is above 1.0 cm”/g.

In some embodiments of the invention, an average pore volume of the one or more mesoporous silica carriers is above 1.5 cm”/g.

In some embodiments of the invention, an average pore volume of the one or more mesoporous silica carriers is from 1.5 to 3.0 cm”/g.

In some embodiments of the invention, an average density of the one or more mesoporous silica carriers is above 50 g/L.

In some embodiments of the invention, an average density of the one or more mesoporous silica carriers is from 50 to 400 g/L.

In some embodiments of the invention, an average density of the one or more mesoporous silica carriers is from 150 to 400 g/L.

In some embodiments of the invention, the moisture adsorption capacity of the one or more mesoporous silica carriers is above 10% by weight of the one or more mesoporous silica carriers at a relative humidity of 50%.

In some embodiments of the invention, the moisture adsorption capacity of the one or more mesoporous silica carriers is above 20% by weight of the one or more mesoporous silica carriers at a relative humidity of 50%.

In some embodiments of the invention, the one or more mesoporous silica carriers is not characterized as a powder flow promotor.

In some embodiments of the invention, the one or more mesoporous silica carriers — does not comprise fumed colloidal silica.

In some embodiments of the invention, the surface of the one or more mesoporous silica carriers is characterized by having an average surface hydrophilicity of 3 to 7

OH/nm'?.

In some embodiments of the invention, the one or more mesoporous silica carriers comprises at least two types of mesoporous silica carriers.

In some embodiments of the invention, the one or more mesoporous silica carriers comprises magnesium aluminometasilicate.

In some embodiments of the invention, the one or more mesoporous silica carriers is essentially consisting of magnesium aluminometasilicate.

In some embodiments of the invention, the one or more mesoporous silica carriers is consisting of magnesium aluminometasilicate.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation is associated with an improved mouthfeel.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation is associated with an improved mouthfeel comprising a less sandy mouthfeel.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation is associated with an improved mouthfeel comprising a less

DK 2023 00252 A1 14 creaking sound upon mastication of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation is associated with an improved mouthfeel by the presence of the one or more mesoporous silica carriers loaded with a liquid cannabinoid suspension or solution compared to separately added silica.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation is associated with an improved mouthfeel by the presence of the one or more water-soluble agents compared to separately added silica.

In some embodiments of the invention, at least a part of the liquid cannabinoid suspension or solution is separate from the one or more mesoporous silica carriers.

In some embodiments of the invention, the one or more cannabinoids is fully contained in the liquid cannabinoid suspension or solution.

In some embodiments of the invention, the orally dissolvable or chewable tableted — powder formulation comprises one or more cannabinoids separate from the liquid cannabinoid suspension or solution.

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

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

DK 2023 00252 A1 15

In some embodiments of the invention, the one or more cannabinoids comprises cannabidiol (CBD).

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

In some embodiments of the invention, the one or more cannabinoids is an isolated cannabinoid.

In some embodiments of the invention, the one or more cannabinoids is a synthetic cannabinoid.

In some embodiments of the invention, the one or more cannabinoids is a cannabinoid distillate with a cannabinoid purity of more than 80%.

In some embodiments of the invention, the one or more cannabinoids is not a cannabinoid extract with a cannabinoid purity of less than 80%.

In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 10 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 20 mg in the orally dissolvable or chewable tableted powder formulation.

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In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 30 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 40 mg in the orally dissolvable or chewable tableted powder formulation. — In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 50 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 75 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 100 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 150 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 200 mg in the orally dissolvable or chewable tableted powder formulation.

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In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 250 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least 300 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more cannabinoids is present in an — amount of at least 400 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more cannabinoids is present in an amount of at least S00 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more water-soluble agents is present in an amount of 30-80% by weight of the tableted powder formulation.

In some embodiments of the invention, the one or more water-soluble agents is present in an amount of 40-80% by weight of the tableted powder formulation.

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In some embodiments of the invention, the one or more water-soluble agents comprises one or more sugar alcohol particles.

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

In some embodiments of the invention, the one or more water-soluble agents comprises one or more sugar alcohol particles comprising non-directly compressible (non-DC) sugar alcohol particles and directly compressible (DC) sugar alcohol particles.

In some embodiments of the invention, the one or more water-soluble agents comprises one or more sugar alcohol particles comprising non-directly compressible (non-DC) sugar alcohol particles and directly compressible (DC) sugar alcohol particles in a ratio of non-DC to DC between 0.2 and 1.2.

In some embodiments of the invention, the one or more water-soluble agents comprises one or more sugar alcohol particles comprising non-directly compressible (non-DC) sugar alcohol particles and directly compressible (DC) sugar alcohol particles in a ratio of non-DC to DC between 0.3 and 0.7.

In some embodiments of the invention, the powder formulation further comprises one or more disintegrants.

In some embodiments of the invention, the powder formulation further comprises one or more disintegrants selected from the group consisting of sodium croscarmellose, crospovidone, sodium starch glycolate, and combinations thereof.

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In some embodiments of the invention, the powder formulation further comprises at least one dissolution modifier selected from the group consisting of acacia, agar, alginic acid or a salt thereof, carbomer, carboxymethylcellulose, carrageenan, cellulose, chitosan, copovidone, cyclodextrins, ethylcellulose, gelatin, guar gum, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl cellulose, hypromellose, inulin, methylcellulose, pectin, polycarbophil or a salt thereof, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, pullulan, starch, tragacanth, trehalose, xanthan gum and mixtures thereof. — In some embodiments of the invention, the powder formulation further comprises at least one dissolution modifier in an amount of 3 to 20% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the powder formulation further comprises at least one microcrystalline cellulose dissolution modifier.

In some embodiments of the invention, the powder formulation further comprises one or more organic acids.

In some embodiments of the invention, the powder formulation further comprises one or more organic fruit acids. The organic fruit acids according to the invention may support fruit taste. The organic fruit acids according to the invention may also support sweetener taste.

In some embodiments of the invention, the one or more flavors is present in an amount of 0.1 to 10% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more non-volatile solvents comprises one or more oils.

In some embodiments of the invention, the one or more non-volatile solvents comprises one or more triglycerides.

In some embodiments of the invention, the one or more non-volatile solvents comprises one or more triglycerides of vegetable origin.

In some embodiments of the invention, the one or more non-volatile solvents comprises one or more triglycerides selected from one or more C4 to C14 triglycerides.

In some embodiments of the invention, the one or more non-volatile solvents comprises one or more triglycerides comprising a partially hydrogenated vegetable oil.

In some embodiments of the invention, the one or more non-volatile solvents comprises one or more triglycerides comprising a fully hydrogenated vegetable oil.

In some embodiments of the invention, the one or more non-volatile solvents comprises one or more triglycerides comprising caprylic acid in an amount of 50 to — 80% by weight.

In some embodiments of the invention, the one or more non-volatile solvents comprises one or more triglycerides comprising capric acid in an amount of 20 to 45% by weight.

In some embodiments of the invention, the one or more non-volatile solvents comprises propylene glycol.

In some embodiments of the invention, the one or more non-volatile solvents does — not comprise an alcohol.

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In some embodiments of the invention, the one or more non-volatile solvents does not comprise a flavor oil.

In some embodiments of the invention, the one or more non-volatile solvents is present in an amount of 1 to 20% by weight of the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more non-volatile solvents improves homogeneity of the one or more cannabinoids in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more non-volatile solvents is present in an amount of 10 to 500 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the one or more non-volatile solvents is present in an amount of 50 to 300 mg in the orally dissolvable or chewable tableted powder formulation.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system that when hydrated forms an emulsion for delivery of the one or more cannabinoids.

In some embodiments of the invention, the orally dissolvable or chewable tableted — powder formulation comprises a self-emulsifying system that when hydrated forms an emulsion for delivery of the one or more cannabinoids to mucosal surfaces in the gastrointestinal tract.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system loaded in the one or more mesoporous silica carriers.

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In some embodiments of the invention, the liquid cannabinoid suspension or solution comprises a self-emulsifying system.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system loaded in a solid matrix.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more waxes.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more surfactants.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more surfactants having an HLB-value of more than 6.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more surfactants having a mean HLB-value of more than 6.

In some embodiments of the invention, the orally dissolvable or chewable tableted — powder formulation comprises a self-emulsifying system comprising one or more surfactants selected from the group consisting of PEG-35 castor oil, PEG-6 oleoyl glycerides, PEG-6 linoleoyl glycerides, PEG-8 caprylic/capric glyceride, sorbitan monolaurate, sorbitan monooleate, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (60) sorbitan monostearate, polyoxyethylene (80) sorbitan monooleate, lauroylpoloxyl-32 glycerides, stearoyl polyoxyl-32 glycerides,

DK 2023 00252 A1 23 polyoxyl-32 stearate, propylene glycol mono laurate , propylene glycol di laurate, and mixtures and combinations thereof.

In some embodiments of the invention, the orally dissolvable or chewable tableted — powder formulation comprises a self-emulsifying system comprising one or more co- solvents.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more co- solvents selected from the group consisting of polyglyceryl-3 dioleate, 1,2- propandiol, polyethylene glycol 300, polyethylene glycol 400, diethylene glycol monoethyl ether, and mixtures and combinations thereof.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more solubilizers.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more — solubilizers selected from the group consisting of lauroylpoloxyl-32 glycerides; stearoyl polyoxyl-32 glycerides; Polyoxyl-32 stearate; synthetic copolymer of ethylene oxide (80) and propylene oxide (27); polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer; alpha-, beta- or gamma cyclodextrins and derivatives thereof, pea proteins (globulins, albumins, glutelins proteins); and mixtures and combinations thereof.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises one or more permeation enhancers.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation is an orally dissolvable tablet.

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In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation is an orally dissolvable tablet disintegrating in the oral cavity within 2 minutes upon oral administration.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation is an orally dissolvable tablet disintegrating in the oral cavity within 1 minute upon oral administration.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation is a chewable tablet.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation is a lozenge comprising particulate ingredients.

In some embodiments of the invention, the orally dissolvable or chewable tableted powder formulation comprises gum base.

In some embodiments of the invention, the orally dissolvable or chewable tableted — powder formulation is a compressed chewing gum tablet.

In some embodiments of the invention, the ingredients of the orally dissolvable or chewable tableted powder formulation is released in the oral cavity.

In some embodiments of the invention, the unit weight of the orally dissolvable or chewable tableted powder formulation is from 400 to 2000 mg.

In some embodiments of the invention, the unit weight of the orally dissolvable or chewable tableted powder formulation is from 500 to 1800 mg.

DK 2023 00252 A1 25

In another aspect of the invention, there is provided an orally dissolvable or chewable powder formulation comprising one or more mesoporous silica carriers loaded with a liquid cannabinoid suspension or solution; one or more water-soluble agents in an amount of 20-80% by weight of the powder formulation; and one or — more flavors, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10.

In this aspect of the invention, the orally dissolvable or chewable powder formulation may be further defined according to any of the preceding embodiments.

In another aspect of the invention, there is provided a stick pack comprising an orally dissolvable or chewable powder formulation comprising one or more mesoporous silica carriers loaded with a liquid cannabinoid suspension or solution; one or more water-soluble agents in an amount of 20-80% by weight of the powder formulation; and one or more flavors, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10. — In this aspect of the invention, the unit weight of the orally dissolvable or chewable powder formulation is from 400 to 2000 mg.

Also, in this aspect of the invention, the stick pack may be further defined according to any of the preceding embodiments.

In another aspect of the invention, there is provided a sachet comprising an orally dissolvable or chewable powder formulation comprising one or more mesoporous silica carriers loaded with a liquid cannabinoid suspension or solution; one or more water-soluble agents in an amount of 20-80% by weight of the powder formulation; and one or more flavors, wherein the liquid cannabinoid suspension or solution

DK 2023 00252 A1 26 comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10.

In this aspect of the invention, the unit weight of the orally dissolvable or chewable — powder formulation is from 400 to 2000 mg.

Also, in this aspect of the invention, the sachet may be further defined according to any of the preceding embodiments. — In another aspect of the invention, there is provided a pouch comprising an orally dissolvable or chewable powder formulation comprising one or more mesoporous silica carriers loaded with a liquid cannabinoid suspension or solution; one or more water-soluble agents in an amount of 20-80% by weight of the powder formulation; and one or more flavors, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10.

In this aspect of the invention, the unit weight of the orally dissolvable or chewable powder formulation is from 400 to 2000 mg.

Also, in this aspect of the invention, the pouch may be further defined according to any of the preceding embodiments.

DETAILED DESCRIPTION OF THE INVENTION

The verb "to comprise" as is used in this description and in the claims and its conjugations are used in its non-limiting sense to mean that items following the word are included, but items not specifically mentioned are not excluded. In addition, reference to an element by the indefinite article "a" or "an" does not exclude the — possibility that more than one of the elements are present, unless the context clearly requires that there is one and only one of the elements. The indefinite article "a" or

DK 2023 00252 A1 27 "an" thus usually means "at least one". Additionally, the words "a" and "an" when used in the present document in connection with the word comprising or containing denote "one or more." The expression "one or more” is intended to mean one, two, three or more.

As used herein, the term "approximately" or "about" in reference to a number are generally taken to include numbers that fall within a range of 5%, 10%, 15%, or 20% in either direction (greater than or less than) of the number unless otherwise stated or otherwise evident from the context (except where such number would be less than 0% or exceed 100% of a possible value).

As used herein, the term ”%” and “percent” refers to percent by weight, unless otherwise is stated. — The term "particle size" relates to the ability of the particles to move through or be retained by sieve holes of a specific size. As used herein, the term “particle size” refers to the average particle size as determined according to European

Pharmacopoeia 9.1 when using test method 2.9.38 particle size distribution estimation by analytical sieving, unless otherwise specifically is mentioned.

The term “particle” or similar wording is intended to denote a single, discrete composition of solid matter, such as a granule or individual elements in powder, having a certain size that may deviate considerable.

Inthe present context the term “release” refers to the released substance being liberated from the solid dosage form or the released carrier system being liberated from the solid dosage form. In some embodiments, the process of releasing a substance corresponds to the substance being dissolved in saliva or mucosa. The term “release” in the present context is intended to mean tested under “in vivo” conditions, if not stated otherwise. In the present context, when the solid dosage form is masticated, “in vivo” conditions is intended to mean that a sample is masticated

DK 2023 00252 A1 28 with a chewing frequency of 60 chews pr. minute for a certain period of time in a test panel of 8 test persons, if not stated otherwise. These test persons abstain from eating and drinking at least 30 minutes before initiation of any test. The test persons are healthy persons appointed on an objective basis according to specified requirements.

By the phrase “texture” is meant a qualitative measure of the properties of the solid dosage form and of the overall mouthfeel experienced by the user during use. Thus, the term “texture” encompasses measurable quantities such as hardness as well as more subjective parameters related to the feel experienced by a user, such as a sandy — feeling upon or after mastication of the product.

The term “sustained release” or "extended release” is herein intended to mean prolonged release over time. The term "rapid release” or "quick release” or "high release” is herein intended to mean a higher content released for a given period of time. The term “controlled release” is intended to mean a release of a substance or the carrier system from a solid dosage form by the aid of active use of the solid dosage form in the oral cavity of the subject, whereby the active use is controlling the amount of substance or carrier system released.

A “self-emulsifying agent” is an agent which will form an emulsion when presented with an alternate phase with a minimum energy requirement. In contrast, an emulsifying agent, as opposed to a self-emulsifying agent, is one requiring additional energy to form an emulsion.

Due to the poor solubility of certain active ingredients in physiological fluids, it is an unmet need to solubilize cannabinoids upon mixture with the body physiological fluids to facilitate bio-absorption. To overcome low bioavailability, various lipid- based drug delivery systems and self-emulsifying systems have been developed.

Lipid-based delivery systems and particularly self-emulsifying drug delivery systems —(SEDDS) have been demonstrated to increase the solubility, dissolution and bioavailability of many insoluble active ingredients. However, lipid based and

DK 2023 00252 A1 29

SEDDS delivery systems are very limited by the amount of active ingredient loading.

Higher concentration of active ingredients are obtained using co-solvents, which enable loads of up to 30% in specific cases.

Particular challenges are considered to arise in formulating solid dosage forms with

SEDDS. For instance, challenges may arise with obtaining a homogenous mixture where variations are avoided and a safe and convenient delivery may be obtained.

Also, the general formulation of the solid dosage forms offering convenience to the user need not be compromised which is often the case if precaution is not taken, such asin cases where a high load of active ingredients is needed.

Particularly with respect to SEDDS, the formulation of the present invention may provide some clear benefits, both allowing a higher load of active ingredients and at the same time offer improved sensorics properties of the formulation during use. — Other advantages are also present.

Importantly, the presence of SEDDS or at least a self-emulsifying agent was seen to act in synergy with the formulation of the present invention. The presence of SEDDS or at least a self-emulsifying agent was seen to further increase the uptake of the active ingredients through mucosal surfaces, such as the gastrointestinal tract. In this respect, the gastrointestinal tract is not considered to include the oral cavity.

The route of administration in the present context is considered to be as follows.

First, the carrier system is at least partly or fully released in the oral cavity, whereupon saliva generated accomplishes that the carrier system containing a substantial amount of the cannabinoids are swallowed for delivery in the gastrointestinal tract. Without being bound by theory it is believed that the relatively more responsive or quicker release of the carrier system containing the cannabinoid in the oral cavity and the relatively prolonged release of cannabinoids from the — carrier in the oral cavity contributes to the cannabinoids being delivered more accurately in the gastrointestinal tract. Accordingly, the system of the present

DK 2023 00252 A1 30 invention provides a synergy with respect to various advantages for delivery of cannabinoids in the gastrointestinal tract.

Accordingly, the synergy between the presence of SEDDS or at least a self- emulsifying agent and cannabinoids was a surprise to the inventors. Particularly, the potential of SEDDS to have a high load of active ingredients, such as in the carrier system according to the invention, further contributes to the synergy of the solid dosage form according to the invention.

In the present context, SEDDS is a solid or liquid dosage form comprising at least a surfactant and optionally a co-surfactant, characterized primarily in that said dosage form can form oil-in-water emulsion spontaneously in the oral cavity or at ambient temperature (referring generally to body temperature, namely 37° C.). When a

SEDDS enters the gastrointestinal tract, it is initially self-emulsified as emulsion droplets and rapidly dispersed. The resulting microparticulate of micrometer or nanometer level can penetrate into the mucous membrane of the gastrointestinal tract, and the absorbed oil droplets enter the blood circulation, thereby significantly improving the bioavailability of the active ingredient. — The term “non-DC sugar alcohol particles” refers to particles of non-directly compressible (non-DC) sugar alcohol. It is noted that the terms “non-DC sugar alcohol particles” and “non-DC particles” are used interchangeably. In the present context, the non-DC sugar alcohol particles refer to particles which have not been preprocessed by granulation with e.g. other sugar alcohols or binders for the purpose of obtaining so-called direct compressible particles (DC). In the present context, non-

DC sugar alcohol particles include particles obtained by crystallization followed by milling which does not involve other sugar alcohols or binders. Thus, non-DC sugar alcohol particles are considered as particles consisting of non-DC sugar alcohol. — The term “DC sugar alcohol particles” refers to particles of direct compressible (DC) sugar alcohol. It is noted that the terms “DC sugar alcohol particles” and “DC

DK 2023 00252 A1 31 particles” are used interchangeably. DC sugar alcohol particles may be obtained e.g. as particles of sugar alcohols having DC grade by nature, e.g. sorbitol, or by granulating non-DC sugar alcohol with e.g. other sugar alcohols or binders for the purpose of obtaining so-called direct compressible particles (DC). Also, granulation of non-DC sugar alcohol with water as binder is considered to result in “DC sugar alcohol particles” in the present context.

The term “tableted” or “tablet” or “compressed” is intended to mean that the tablet composition is pressed in a tableting apparatus and mainly being composed of particulate matter. Although the terms imply a method step, in the present context, the terms are intended to mean the resulting tablet obtained in tableting a portion of particles. It is noted that a tablet or tableted composition that is mentioned to comprise particles eventually is to be understood as particles that have been pressed together in a tableting step.

The following description outlines explanations of how the tablet of the invention may be produced and further details of what may be added to the inventive composition.

Typically, the process of manufacture of the inventive tablet may be performed in a single tablet press, such as a rotary tablet press. But it may be a benefit under some circumstances to apply a separate tablet press.

Preferably, the upper punch is convex which gives the upper face of the pressed — tablet a concave form.

It should of course be noted that the shape of the punches may vary depending of the desired tablet shape.

In some embodiments of the invention, pressing of the tablets are performed at a force of 20 to 50 kN.

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In one embodiment of the invention, the “tablet” is a “fast disintegrating tablet” (“FDT”), such as an “orally disintegrating tablet” (“ODT”). In some embodiments, if such a tablet is made as one module, contrary to two or more modules, then the tablet is intended to be an FDT tablet. If on the other hand, the tablet is made of more than one module, such as two modules, such additional module may be a “lozenge” module, which provides a longer disintegration time compared to a FDT module.

The combination of an “FDT” module and a “lozenge” module contributes to another embodiment of the invention. A “lozenge” module may also comprise elements from — the “FDT” modules but is generally different in composition, providing an extended disintegration time.

The term “lozenge” is intended to cover that a “lozenge composition” has been “compressed” into a “lozenge module”. In the present context, a “lozenge module” or similar wording is intended to mean that the module during use in the oral cavity is intended to be sucked or licked on. The term “lozenge” is given the ordinary meaning in the art of lozenges. The intention is that the lozenge module may not be chewed. The intention is also that the FDT module may not be chewed. Generally, the “lozenge module” of the present invention may disintegrate upon sucking or licked in minutes, contrary to seconds for orally disintegrating tablets (ODT) or fast disintegrating tablets (FDT) tablets. Hence, the intention is that the “lozenge module” is to deliver the one or more cannabinoids over a longer period of time than the FDT module, if the tablet is made as a combination of the two modules.

The term “module” is generally intended to be composed of a composition of matter with substantially the same characteristics throughout the module. Hence, if two module are present, then the two modules are different in composition and generally have two different characteristics throughout each module. In the present context, if two modules are present, then the tablet is composed of two modules fused together.

The term “fused” is intended to mean that the tablet is gathered together by means of compression force. The tablet may be composed of more than two modules. One

DK 2023 00252 A1 33 module may in certain embodiments be a gum base containing module. In the present context, the invention provides an attractive bi-phasic delivery of masking, even if the delivery of cannabinoids is “single-phased”.

In context of the present invention, a “chewable tablet” is intended to mean an oral tablet that is chewed upon oral administration, having characteristics allowing convenient chewing without adverse side effects associated with the texture of the oral tablet.

Particularly, less attention is given on the benefits of chewable tablet formulations that may help in obtaining a release characteristic of cannabinoids that offers increased convenience and effectiveness. One of these release characteristics is increased generation of saliva upon chewing. Increased saliva generation and particularly an experience of increased saliva generation upon administration may have some pronounced benefits for delivery of cannabinoids to mucosal surfaces.

One advantage of a chewable tablet with a content of non-DC sugar alcohol particles is a surprisingly strong saliva generation compared to conventional chewable tablets and lozenges. Particularly, the non-DC particles may surprisingly induce a — remarkable generation of saliva. Increased generation of saliva may have a surprisingly high impact on the administration of the carrier systems for mucosal delivery of cannabinoids in the gastrointestinal tract. Specifically, increased generation of saliva may allow an increased release of the carrier systems from the oral formulation, whereupon the carrier systems may be more quickly and more — easily swallowed. More specifically, this allows the carrier systems to access the gastrointestinal tract with a higher load of cannabinoids and thereby provide a higher uptake of the one or more cannabinoids to mucosal surfaces in the gastrointestinal tract. Hence, a synergy between uptake of cannabinoids in the gastrointestinal tract and increased saliva generation may be seen according to the invention.

DK 2023 00252 A1 34

Having a combination of non-DC particles and DC particles may further facilitate sufficient mechanical strength combined with stability of the tablet, disintegrability of the tablet upon chewing, and induced saliva generation upon chewing.

One unexpected advantage over the prior art is that the saliva generation is surprisingly sustained even after a user has swallowed the bulk-portion of the non-

DC sugar alcohols. This sustaining of the salivation generation may be advantageous in relation to many applications of an oral tablet ranging from mouthfeel, taste, flavor perception, etc.

In the present context, the non-DC sugar alcohol particles are understood and defined by the skilled person with reference to their typical commercial trade grade.

In an embodiment of the invention, the non-DC sugar alcohol particles have not been granulated prior to tableting. Thus, the non-DC sugar alcohol particles are provided as non-granulated particles. These are typically available in a non-DC form of the relevant sugar alcohol as particles which have not been preprocessed by granulation with other sugar alcohols or binders for the purpose of obtaining so-called direct compressible particles (DC) on the basis of sugar alcohol particles which are by themselves not suitable for direct compression. Such non-DC particles of sugar alcohol may typically consist of the sugar alcohol. Therefore, non-DC sugar alcohol particles may typically be particles consisting of sugar alcohol, which is non-directly compressible in its pure form.

The weight ratio between non-DC sugar alcohol particles and DC sugar alcohol particles have proven significant according to an embodiment of the invention in the sense that a relatively high amount of non-DC sugar alcohol particles must be present in order to obtain the mouthfeel and taste obtained through the invention. However, this taste and mouthfeel also resides in the DC sugar alcohol particles. An example of — such DC sugar alcohol particle is DC grade xylitol, which, together with the non-DC

DK 2023 00252 A1 35 sugar alcohol particles may provide a mouthfeel which is unique and very attractive to test panels.

The weight ratio between non-DC sugar alcohol particles and DC sugar alcohol particles is important for the purpose of obtaining an advantageous taste and mouthfeel. By having an upper limit of this weight ratio, the chewer will moreover also experience a desirable crunch sensation when masticating the tablet, the crunch being obtained through the use of substantial amounts of DC sugar alcohol particles and the non-DC sugar alcohol particles.

In an embodiment of the invention, the non-DC sugar alcohol particles are selected from non-DC particles of erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof. One advantage of the above embodiment may be that a desirable induced saliva generation is obtained. According to an embodiment of the invention, the non-DC sugar alcohol particles consist of sugar alcohols selected from erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof.

In an embodiment of the invention, the non-DC sugar alcohol particles are selected from non-DC particles of erythritol, maltitol, xylitol, isomalt, and combinations thereof. One advantage of the above embodiment may be that a desirable induced saliva generation is obtained.

In an embodiment of the invention, the non-DC sugar alcohol particles are selected from non-DC particles of erythritol, maltitol, xylitol, and combinations thereof. In an embodiment of the invention, the non-DC sugar alcohol particles are non-DC erythritol particles. One advantage of the above embodiment may be that a desirable induced saliva generation is obtained, together with a cooling sensation. In an embodiment of the invention, the non-DC sugar alcohol particles are non-DC xylitol particles. One advantage of the above embodiment may be that a desirable induced saliva generation is obtained, together with a cooling sensation.

DK 2023 00252 A1 36

In an embodiment of the invention, said DC sugar alcohol particles comprises sugar alcohols selected from DC particles of sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, isomalt, and combinations thereof.

Sorbitol is an example of a sugar alcohol, which is considered DC grade, when provided as particles consisting of sorbitol, i.e. in its pure form. On the other hand, several other sugar alcohols are considered non-DC grade if providing them as particles consisting of the specific sugar alcohol. Therefore, such non-DC sugar alcohols are conventionally processed into DC grade sugar alcohols, e.g. by granulating them with e.g. a binder.

Examples of trade grades of DC sugar alcohols include sorbitol particles provided as e.g. Neosorb ® P 300 SD from Roquette, mannitol particles provided as e.g. Pearlitol ® 300DC or Pearlitol 200 SD from Roquette, maltitol provided as e.g. SweetPearl ®

P 300 DC, xylitol provided as e.g. Xylisorb ® XTAB 400 or Xylitab 200 from

Dupont.

In an embodiment of the invention, the oral tablet comprises at least two modules.

The module may typically be gathered from a plurality of compressed particles and have a weight which is greater than 0.1 gram and less than 10 grams. In an embodiment of the invention, a module is defined as a plurality of particles being compressed together to form a gathered module of particles.

In an embodiment of the invention, the oral tablet comprises a plurality of oral tablet modules. In the present context the application of e.g. two modules are in particular advantageous when non-DC sugar alcohol particles are present primarily in one module thereby optimizing the desired salivation and sensory experience from the module and the tablet as such, whereas another module may primarily comprise DC sugar alcohol particles that serve as a support ensuring that the desired stability and — friability of the complete tablet is obtained.

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The term “cannabinoid composition” is intended to mean a volume of matter comprising one or more cannabinoids. The cannabinoid composition may contain other components than cannabinoids. The cannabinoid composition may constitute cannabinoids. The cannabinoid composition may constitute one type of cannabinoids. The cannabinoid composition may constitute two types of cannabinoids. The cannabinoid composition may constitute two or more types of cannabinoids.

By the terms “ water-insoluble gum base” or “gum base” or "gum base matrix” or similar wording is meant the mainly water-insoluble ingredients and hydrophobic gum base ingredients. The “gum base” may contain gum base polymers, natural resins, elastomer plasticizers, waxes, emulsifiers, fats and/or fillers.

The term “natural resin”, as used herein, means resinous compounds being either polyterpene derived from terpenes of natural origin or resinous compounds derived from gum rosin, wood rosin or tall-oil rosin.

Elastomers provide the rubbery, elastomeric and bouncing nature to the gum, which varies depending on this ingredient's chemical structure and how it may be compounded with other ingredients. Elastomers suitable for use in the gum base and gum of the present invention may include natural or synthetic types. Polyvinyl acetate elastomer plasticizers are not considered elastomers according to the invention.

Elastomers may be selected from the group consisting of styrene-butadiene copolymers, polyisobutylene, isobutylene-isoprene copolymers, polyethylene, polyurethane or any combination thereof. Preferred elastomers are styrene-butadiene copolymers (SBR), polyisobutylene and isobutylene-isoprene copolymers (BR).

Styrene-butadiene type elastomers, or SBR as they may be called, typically are copolymers of from about 20:80 to 60:40 styrenes:butadiene monomers. The ratio of

DK 2023 00252 A1 38 these monomers affects the elasticity of the SBR as evaluated by mooney viscosity.

As the styrene:butadiene ratio decreases, the mooney viscosity decreases.

The structure of SBR typically consists of straight chain 1,3-butadiene copolymerized with phenylethylene (styrene). The average molecular weight of SBR is <600,000 g/mole.

Isobutylene-isoprene type elastomers, or butyl as they may be called, have molar percent levels of isoprene ranging from 0.2 to 4.0. Similar to SBR, as the isoprene:isobutylene ratio decreases, so does the elasticity, measured by mooney viscosity.

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

Polyisobutylene, or PIB as they may be called, type elastomers are polymers of 2- methylpropene. The low molecular weight elastomers provide soft chew characteristics to the gum base and still provide the elastic qualities as do the other elastomers. Average molecular weights may range from about 30,000 to 120,000 g/mole and the penetration may range from about 4 millimeters to 20 millimeters.

The higher the penetration, the softer the PIB. Similar to the SBR and butyl, the high molecular weight elastomers provide elasticity to the gum. Average molecular weight may range from 120,000 to 1,000,000 g/mole.

Polybutene range in average molecular weight from about 5.000 g/mole to about 30.000 g/mole.

Useful natural elastomers include natural rubber 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,

DK 2023 00252 A1 39 niger gutta, tunu, chilte, chiquibul, gutta hang kang. Natural elastomers may also be applied in aspects of the present invention.

Elastomer plasticizers vary the firmness of the gum base. Their specificity on elastomer inter-molecular chain breaking (plasticizing) along with their varying softening points cause varying degrees of finished gum firmness and compatibility when used in base. Polyvinyl acetate elastomers plasticizers are examples of elastomer plasticizers of the present invention.

Natural resins may be selected from ester gums including as examples glycerol esters of partially hydrogenated rosins, glycerol esters of polymerized rosins, glycerol es- ters of partially dimerized rosins, glycerol esters of tally oil rosins, pentaerythritol esters of partially hydrogenated rosins, methyl esters of rosins, partially hydrogenated methyl esters of rosins, pentaerythritol esters of rosins, synthetic resins — such as terpene resins derived from alpha-pinene, beta-pinene, and/or d-limonene, and natural terpene resins.

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

The solid dosage form according to the invention is manufactured by applying pressure to a content of particles by suitable compression means. The particles or powder is then pressed into a compact coherent tablet. The particles may for example comprise so-called primary particles or aggregated primary particles. When these are pressed, bonds are established between the particles or granules, thereby conferring a certain mechanical strength to the pressed tablet.

DK 2023 00252 A1 40

It should be noted that the above-introduced terms: powder, primary particles and aggregated primary particles may be somewhat misleading in the sense that the difference between primary particles and aggregated primary particles may very often be looked upon differently depending on the background of the user. Some may for instance regard a sweetener, such as sorbitol, as a primary particle in spite of the fact that sorbitol due to the typically preprocessing performed on sorbitol when delivered to the customer should rather be regarded as some sort of aggregated primary particles. The definition adopted in the description of this invention is that aggregated primary particles refer to macro-particles comprising more or less preprocessed primary particles.

When pressure is applied to the particles, the bulk volume is reduced, and the amount of air is decreased. During this process energy is consumed. As the particles come into closer proximity to each other during the volume reduction process, bonds may be established between the particles or granules. The formation of bonds is associated with a reduction in the energy of the system as energy is released. Volume reduction takes place by various mechanisms and different types of bonds may be established between the particles or granules depending on the pressure applied and the properties of the particles or granules. The first thing that happens when a powder 1s pressed is that the particles are rearranged under low compaction pressures to form a closer packing structure. Particles with a regular shape appear to undergo rearrangement more easily than those of irregular shape. As the pressure increases, further rearrangement is prevented, and subsequent volume reduction is obtained by plastic and elastic deformation and/or fragmentation of the tablet particles. Brittle particles are likely to undergo fragmentation, i.e. breakage of the original particles into smaller units. Plastic deformation is an irreversible process resulting in a permanent change of particle shape, whereas the particles resume their original shape after elastic deformation. Evidently, both plastic and elastic deformation may occur, when compressing an solid dosage form.

DK 2023 00252 A1 41

Several studies of the bond types in pressed tablets have been made over the years, typically in the context of pharmaceuticals and several techniques of obtaining pressed tablets on the basis of available powders has been provided. Such studies have been quite focused on what happens when the volume reduction is performed and how the end-product may be optimized for the given purpose. Several refinements with respect to pressed tablets has for instance been made in the addition of for example binders in the tablet raw materials for the purpose of obtaining a sufficient strength to the final pressed tablet while maintaining acceptable properties, e.g. with respect to release.

Contrary to tableted chewing gum, conventional chewing gum may be manufactured by sequentially adding the various chewing gum ingredients to a commercially available mixer known in the art where the finished gum base is already present.

After the initial ingredients have been thoroughly mixed, the gum mass is discharged from the mixer and shaped into the desired form such as by rolling into sheets and cutting into sticks, extruded into chunks or casting into pellets. Generally, the ingredients of conventional chewing gum may be mixed by first melting the gum base and adding it to the running mixer. Colors, active agents and/or emulsifiers may also be added at this time. A softener such as glycerin may also be added at this time, along with syrup and a portion of the bulking agent/sweetener. Further portions of the bulking agent/sweetener may then be added to the mixer. A flavoring agent is typically added with the final portion of the bulking agent/sweetener. A high- intensity sweetener is preferably added after the final portion of bulking agent and flavor have been added. The entire mixing procedure typically takes from thirty to forty minutes, but longer mixing times may sometimes be required. Those skilled in the art will recognize that many variations of the above described procedure may be followed.

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

DK 2023 00252 A1 42

In accordance with the invention, the tableted solid dosage form according to the invention may comprise about 0.1 to about 75% by weight of an outer coating applied onto the solid dosage form centre. Thus, suitable coating types include hard coatings, film coatings and soft coatings of any composition including those currently used in coating of tableted solid dosage form.

One presently preferred outer coating type is a hard coating, which term is used in the conventional meaning of that term including sugar coatings and sugar-free (or sugarless) coatings and combinations thereof. The object of hard coating is to obtain a sweet, crunchy layer, which is appreciated by the consumer and it may moreover protect the solid dosage form centres for various reasons. In a typical process of providing the solid dosage form centres with a protective sugar coating, the solid dosage form centres are successively treated in suitable coating equipment with aqueous solutions of crystallisable sugar such as sucrose or dextrose, which, depending on the stage of coating reached, may contain other functional ingredients, e.g. fillers, binding agents, colours, etc. In the present context, the sugar coating may contain further functional or active compounds including flavour compounds and/or active compounds.

In atypical hard coating process as it will be described in detail in the following, a suspension containing crystallisable sugar and/or polyol is applied onto the solid dosage form centres and the water it contains is evaporated off by blowing with air.

This cycle must be repeated several times, typically 3 to 80 times, in order to reach the swelling required. The term “swelling” refers to the increase in weight or — thickness of the products, as considered at the end of the coating operation by comparison with the beginning, and in relation to the final weight or thickness of the coated products. In accordance with the present invention, the coating layer constitutes about 0.1 to about 75% by weight of the finished solid dosage form element, such as about 10 to about 60% by weight, including about 15 to about 50% by weight.

DK 2023 00252 A1 43

In an embodiment of the invention, the product is a pouch.

In one aspect of the invention, the population of particles used for tableting may also be present in a pouch as a powder. Hence, this aspect of the invention includes the population of particles in a pouch without tableting, but as a powder or part of a powder with other powders or powder ingredients. It follows that the directly compressible (DC) and non-directly compressible (non-DC) sugar alcohol particles of the invention may be included in the pouch according to the invention. Additional embodiments pertaining to the population of particles of the invention will also be applicable when included in a pouch. It is noted that additional ingredients may be present in the pouch, such as water-soluble fibers or water-insoluble fibers, including microcrystalline cellulose.

According to an advantageous embodiment of the invention the pouch comprises a water-permeable membrane, such as a woven or non-woven fabric.

The pouches according to the invention comprise openings, where the characteristic opening dimension is adapted to a characteristic dimension of the population of particles so as to retain the matrix composition inside the pouch before use and/or to retain a part of the content inside the pouch during use.

In other words, according to the various embodiments, the pouch forms a membrane allowing passage of saliva and prevents or inhibits passage of at least a part of the content. The membrane of the pouch may be of any suitable material e.g. woven or non-woven fabric (e.g. cotton, fleece etc.), heat sealable non-woven cellulose or other polymeric materials such as a synthetic, semi-synthetic or natural polymeric material. An example of suitable pouch material is paper made of pulp and a small amount of wet strength agent. A material suitable for use must provide a semi- permeable membrane layer to prevent the powder or composition from leaving the bag or pouch during use. Suitable materials are also those that do not have a significant impact on the release of the active ingredients from the pouch.

DK 2023 00252 A1 44

The powder is filled into pouches and is maintained in the pouch by a sealing. 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 which prevent the powder from leaving the bag but permit saliva and therein dissolved or sufficiently small-sized suspended components from the powder in the pouch to pass through said pouch.

The pouch may be placed in the oral cavity by the user. Saliva then enters into the pouch, and the active ingredient and other components, which are soluble in saliva, start to dissolve and are transported with the saliva out of the pouch into the oral cavity. In some embodiments of the invention, the pouch may be masticated in a similar way as chewing a gum. This is particularly advantageous when the population of particles comprise gum base. Hence, the pouch may be masticated into a coherent residual containing water-insoluble components.

According to embodiments of the invention, flavors may be selected from the group consisting of coconut, coffee, chocolate, vanilla, grape fruit, orange, lime, menthol, liquorice, caramel aroma, honey aroma, peanut, walnut, cashew, hazelnut, almonds, pineapple, strawberry, raspberry, tropical fruits, cherries, cinnamon, peppermint, wintergreen, spearmint, eucalyptus, and mint, fruit essence such as from apple, pear, peach, strawberry, apricot, raspberry, cherry, pineapple, and plum essence. The essential oils include peppermint, spearmint, menthol, eucalyptus, clove oil, bay oil, anise, thyme, cedar leaf oil, nutmeg, and oils of the fruits mentioned above.

Antioxidants suitable for use include butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), betacarotenes, tocopherols, acidulants such as Vitamin C (ascorbic acid or corresponding salts (ascorbates)), propyl gallate, catechins, green tea extract other synthetic and natural types or mixtures thereof.

DK 2023 00252 A1 45

High intensity sweetening agents can also be used according to preferred embodiments of the invention. Preferred high intensity sweeteners include, but are not limited to sucralose, aspartame, salts of acesulfame, alitame, neotame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, monk fruit extract, advantame, stevioside and the like, alone or in combination.

In order to provide 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 sweeteners.

Techniques such as wet granulation, wax granulation, spray drying, spray chilling, fluid bed coating, conservation, encapsulation in yeast cells and fiber extrusion may be used to achieve desired release characteristics. Encapsulation of sweetening — agents can also be provided using another formulation component such as a resinous compound.

Usage level of the high-intensity sweetener will vary considerably and will depend on factors such as potency of the sweetener, rate of release, desired sweetness of the — product, level and type of flavor used and cost considerations. Thus, the active level of artificial sweetener may vary from about 0.001 to about 8% by weight (preferably from about 0.02 to about 8% by weight). When carriers used for encapsulation are included, the usage level of the encapsulated high-intensity sweetener will be proportionately higher.

The invention, if desired, may include one or more fillers/texturizers including as examples, magnesium- and calcium carbonate, sodium sulphate, ground limestone, silicate compounds such as magnesium- and aluminum silicate, kaolin and clay, aluminum oxide, silicium oxide, talc, titanium oxide, mono-, di- and tri-calcium phosphates, cellulose polymers, such as wood, and combinations thereof. According

DK 2023 00252 A1 46 to an embodiment of the invention, one preferred filler/texturizer is calcium carbonate.

According to the invention, the one or more cannabinoids may be selected from — various cannabinoids. "Cannabinoids" are a group of compounds including the endocannabinoids, the phytocannabinoids and those which are neither endocannabinoids or phytocannabinoids, hereinafter "syntho-cannabinoids". "Endocannabinoids" are endogenous cannabinoids, which may have high affinity ligands of CB1 and CB2 receptors. "Phytocannabinoids" are cannabinoids that originate in nature and can be found in — the cannabis plant. The phytocannabinoids can be present in an extract including a botanical drug substance, isolated, or reproduced synthetically. "Syntho-cannabinoids" are those compounds capable of interacting with the cannabinoid receptors (CB1 and/or CB2) but are not found endogenously or in the — cannabis plant. Examples include WIN 55212 and rimonabant.

An "isolated phytocannabinoid" or “isolated cannabinoid” is one which has been extracted from the cannabis plant and purified to such an extent that the additional components such as secondary and minor cannabinoids and the non-cannabinoid fraction have been substantially removed.

A "synthetic cannabinoid" is one which has been produced by chemical synthesis.

This term includes modifying an isolated phytocannabinoid, by, for example, forming a pharmaceutically acceptable salt thereof.

DK 2023 00252 A1 47

A "substantially pure" cannabinoid is defined as a cannabinoid which is present at greater than 95% (w/w) pure. More preferably greater than 96% (w/w) through 97% (w/w) thorough 98% (w/w) to 99% % (w/w) and greater.

In some embodiments, a purity of above 80% (w/w) may be applied.

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 are co-extracted with the cannabinoids have been substantially removed, such that the highly purified cannabinoid is greater than or equal to 95% (w/w) pure. “Plant material” is defined as a plant or plant part (e.g. bark, wood, leaves, stems, roots, flowers, fruits, seeds, berries or parts thereof) as well as exudates, and includes — material falling within the definition of “botanical raw material” in the Guidance for

Industry Botanical Drug Products Draft Guidance, August 2000, US Department of

Health and Human Services, Food and Drug Administration Center for Drug

Evaluation and Research.

In the context of this application the terms "cannabinoid extract" or "extract of cannabinoids", which are used interchangeably, encompass "Botanical Drug

Substances" derived from cannabis plant material. A Botanical Drug Substance is defined in the Guidance for Industry Botanical Drug Products Draft Guidance,

August 2000, US Department of Health and Human Services, Food and Drug

Administration Centre for Drug Evaluation and Research as: "A drug substance derived from one or more plants, algae, or macroscopic fungi. It is prepared from botanical raw materials by one or more of the following processes: pulverisation, decoction, expression, aqueous extraction, ethanolic extraction, or other similar processes." A botanical drug substance does not include a highly purified or chemically modified substance derived from natural sources. Thus, in the

DK 2023 00252 A1 48 case of cannabis, "botanical drug substances" derived from cannabis plants do not include highly purified, Pharmacopoeial grade cannabinoids.

The term “Cannabis plant(s)” encompasses wild type Cannabis sativa and also variants thereof, including cannabis chemovars which naturally contain different amounts of the individual cannabinoids, Cannabis sativa subspecies indica including the variants var. indica and var. kafiristanica, Cannabis indica, Cannabis ruderalis and also plants which are the result of genetic crosses, self-crosses or hybrids thereof.

The term “Cannabis plant material” is to be interpreted accordingly as encompassing — plant material derived from one or more cannabis plants. For the avoidance of doubt it is hereby stated that “cannabis plant material” includes dried cannabis biomass.

Preferably the one or more cannabinoids are selected from: cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV) and tetrahydrocannabivarinic acid (THCV

A). More preferably the one or more cannabinoid is CBD or THC. This list is not exhaustive and merely details the cannabinoids which are identified in the present application for reference.

So far, more than 120 different phytocannabinoids have been identified which are within the scope of the present invention.

Cannabinoids can be split into different groups as follows: Phytocannabinoids;

Endocannabinoids; and Synthetic cannabinoids.

Cannabinoid receptors can be activated by three major groups of agonist ligands, for — the purposes of the present invention and whether or not explicitly denominated as such herein, lipophilic in nature and classed respectively as: endocannabinoids

DK 2023 00252 A1 49 (produced endogenously by mammalian cells); phytocannabinoids (such as cannabidiol, produced by the cannabis plant); and, synthetic cannabinoids (such as

HU-210). — Phytocannabinoids can be found as either the neutral carboxylic acid form or the decarboxylated form depending on the method used to extract the cannabinoids. For example, it is known that heating the carboxylic acid form will cause most of the carboxylic acid form to decarboxylate.

Phytocannabinoids can also occur as either the pentyl (5 carbon atoms) or propyl (3 carbon atoms) variant. For example, the phytocannabinoid THC is known to be a

CBI receptor agonist whereas the propyl variant THCV has been discovered to be a

CBI receptor antagonist meaning that it has almost opposite effects.

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

The formulation according to the present 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.

Examples of endocannabinoids are molecules that activate the cannabinoid receptors within the body. Examples include 2-arachidonyl glycerol (2AG), 2-arachidonyl glyceryl ether (2AGE), arachidonyl dopamine, and arachidonyl ethanolamide (anandamide). Structurally related endogenous molecules have been identified that

DK 2023 00252 A1 50 share similar structural features, but that display weak or no activity towards the cannabinoid receptors but are also termed endocannabinoids. Examples of these endocannabinoid lipids include 2-acyl glycerols, alkyl or alkenyl glyceryl ethers, acyl dopamines and N-acylethanolamides that contain alternative fatty acid or alcohol moieties, as well as other fatty acid amides containing different head groups.

These include N-acylserines as well as many other N-acylated amino acids.

Examples of cannabinoid receptor agonists are neuromodulatory and affect short- term memory, appetite, stress response, anxiety, immune function and analgesia. — In one embodiment the cannabinoid is palmitoylethanolamide (PEA) which is an endogenous fatty acid amide belonging to the class of nuclear factor agonists.

Synthetic cannabinoids encompass a variety of distinct chemical classes: the cannabinoids structurally related to THC, the cannabinoids not related to THC, such as (cannabimimetics) including the aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulfonamides, and eicosanoids related to the endocannabinoids.

All or any of these cannabinoids can be used in the present invention.

It is preferred that the formulation comprises one or two primary cannabinoids, which are preferably selected from the group consisting of, cannabidiol (CBD) or cannabidivarin (CBDV), tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), tetrahydrocannabinolic acid (THCA), cannabigerol (CBG) and cannabidiolic acid (CBDA) or a combination thereof. It is preferred that the formulation comprises cannabidiol and/or tetrahydrocannabinol.

Preferably, the solid dosage form of the present invention may be used for the treatment or alleviation of pain, epilepsy, cancer, nausea, inflammation, congenital disorders, neurological disorders, oral infections, dental pain, sleep apnea, psychiatric disorders, gastrointestinal disorders, inflammatory bowel disease, appetite loss, diabetes and fibromyalgia.

DK 2023 00252 A1 51

In a further aspect of the present invention, the oral cannabinoid formulation is suitable for use in the treatment of conditions requiring the administration of a neuroprotectant or anti-convulsive medication.

The oral cannabinoid formulation may be for use in the treatment of seizures.

The oral cannabinoid formulation may be for use in the treatment of 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 tumours, neuropathic pain, cannabis use disorder, post-traumatic stress disorder, anxiety, early psychosis, Alzheimer's disease, and autism.

The following non-limiting examples illustrate different variations of the present invention. The examples are meant for indicating the inventive concept; hence the mentioned examples should not be understood as exhaustive for the present. In particular, CBD is used as an exemplary compound, but may also be another cannabinoid.

EXAMPLES

Example 1

Premix: Hydrogenated Vegetable Oil (HVO) added to a mixture of isolated

CBD and mesoporous carriers

A mesoporous silica carrier (Syloid XDP 3050) provided from Grace in an amount of about 1000 g was added to a Lodige high shear mixer. Thereafter, a cannabinoid powder composition comprising CBD isolate from cannabis plant tissues (phytocannabinoid) with a 99% content of CBD provided by Medical Hemp (batch number MH B18592) in an amount of about 500 g was sieved through a 600 microns sieve and added to the silica carrier composition. This mixture was mixed in the

DK 2023 00252 A1 52 mixer at a speed of about 80 rpm for about 5 minutes. After activation of the chopper (about 600 rpm) of the Lodige mixer, HVO provided from AAK under the tradename

Akocrem NT 76-33 with a melting temperature of 30-35 Degree Celsius was melted at a temperature of about 55 Degree Celsius and added to the mixture in an amount of about 500 g. After adding the lipid composition, the temperature in the mixer was about 49 Degree Celsius, and the mixture was further mixed for about 10 minutes.

After 10 minutes, the temperature of the final mixture was about 51 Degree Celsius.

A total of 2 kg mixture powder premix was made in which the CBD content was about 250 mg/g. [%] [M] [%] [%] [%] [%] [%] [sun | PT | | [wo ar | mo | wo

CBD isolate (purity

Table 1: Hydrogenated Vegetable Oil (HVO) having been preheated to a temperature of about 55

Degree Celsius. Variation in the content of CBD isolate (purity 99%). Sample 103 corresponds to the procedure above, the other samples are adjusted to the variation in contents. [%] [%] [%] [%] [%]

Table 2: Hydrogenated Vegetable Oil (HVO) having been preheated to a temperature of about 55

Degree Celsius. Variation in the content of HVO. The samples are prepared according to the procedure above but adjusted to the variation in contents.

DK 2023 00252 A1

Raw material name

Pål [Få] £26} [Så] el see | 1 1 TT penne | wo [en tom | Ter oner | Two [1 meme

Table 3: Fydrogenateg Fegetadle QF (HFO) having been prefiected to a temperature of about 53

Degree Celsius, Førtation iu the tyve of carrier. Here Sylatd XDP 3030 was replaced by other carriers,

The samples ave prepared according fo the procedure above but odiøsted fo the variation in contents.

S > Example 2

Premix: Miglyol added to a mixture of isolated UBD and mesoporous carriers

A mesoporous silica carrier {Syloid XDP 3050) provided from Grace in an amount of about 1000 g was added to a Lødige high shear nuxer. Thereafter, a cannabinoid powder composition comprising UBD isolate from cannabis plant tissues (phytocannabinoid) with a 99% content of CBD provided by Medical Hemp (batch munber MH BI8592) in an amount of about 300 g was sieved through a 600 microns sieve and added io the silica carner composition. This mixture was mixed in the mixer at a speed of about 80 rpm for about 5 minutes. After activation of the chopper (about 600 rpm) of the Lédige mixer, Medium Chain Triglveenide (MCT), Miglvol 18 812, provided from Sasol was added to the nuxture during a period of about 3 minutes in an amount of about S00 ae. After adding the Miglvol 812, the mixture was heated and further mixed for about 10 minutes. After 10 minutes, the temperature of the final mixture was about 31 Degree Celsius. A total of 2 kg nuxture powder prenux was made m which the CBD content was about 250 mg/g.

DK 2023 00252 A1 34

Raw material Content | Content | Content | Content | Content | Content | Content name [26] [94] f%al [8] [2a] 1941 [98] mm | 90 [0 oe fn en pe 0 Å 40.0 35.0 30.0 23.0 20.0 150 10.0 {parity 99%}

Table 4: Miglva! 817 having not been preheated. Variation in the content of CBD isolate (purity 9975),

Sample 203 corresponds to the procedure above, the ofher semples are adjusted to the variation in contents. mee |S lm

Raw material name fj [98] fe] {od {oa}

Table 5: Miglvol 817 having not been prehented. Variation in the content of Mighol 812, The samples are prepared accerding fo the procedure above But adfusted fo the variation in contents, meer]

Raw material name på | på | på | på | på

KOR UI AU Ad ef pr em ej jeg me” I

Table 6: Mielvol having not bean prehøeated unless specifically denoted. Variation in the type of

Mighvol, Sample 222 corresponds to the procedure above, Mielyol 829 in Powder Premix Number 223 19 is heated fo abort 30°C in order fo work.

DK 2023 00252 A1 55

Raw material name få på] få [så] så]

Sne | 0 1 (fronten | wo [1 [FR |r ommromoma | Two | 1 sy I 1 1

Table 7: Miglvol S12 having not been preheated. Variation in the fype of carrier, Here Xylotd XDF 038 was replaced by other carriers. The samples ave prepared according fo the procedure above but adtusted to the variation fr contents,

Example 3

Premix: High load - Hydrogenated Vegetable Oil (HVO) added to a mixture of isolated CBD and mesoporous carriers

A mesoporous silica carrier (Syloid XDP 3050) provided from Grace in an amount of about 1000 g was added to a Lodige high shear mixer and heated to a temperature of 1G about 55 Degree Celsius. Thereafter, a cannabinoid powder composition comprising

CBD isolate from cannabis plant tissues (phytocannabmoid) with a 99% content of

UBD provided by Medical Hemp (batch munber MH BI8592) in an amount of abont 750 g was sieved through a 600 microns steve and added to the silica carrier composition. This mixture was niuxed in the mixer at a speed of about 80 rpm for about 5 minutes. After activation of the chopper {about 600 rpm) of the Lådige mixer, HVO provided from AAK under the tradename Akocrem NT 76-33 with a melting temperature of 30-35 Degree Celsius was melted at a temperature of about 55 Degree Celsius and added io the mixture in an amount of about 250 g. After adding the lipid composttion, the temperature in the nuxer was about 49 Degree

Celsius, and the mixture was further mixed for about 10 nunutes. After 10 minutes,

DK 2023 00252 A1 36 the temperature of the final mixture was about 51 Degree Celsius. A total of 2 kg puxture powder prenux was made in wlich the CBD content was about 375 mg/e. mere mm

Raw material name ps] fi] 4] [9] [2]

Table 8: Hudrogenated Fegetable ON (HFON having been preheoted fo a temperature of about 33

Derrse Celsius. Variation in the content of CBD isolate (purity 9925), Sample 202 corresponds fo the procedure nbove, fhe offer samples are adjusted fo the variation in covients, eee

Raw material name {9a} [24] 23] fa] foe]

Table 9: Fhdrogenated Vegetable Oil (EVO) having heen prehøoted to a temperature of about 55

Degree Celsius, Variation fn the content of HV. The samples are prepared according to the procedure above but adfested fo the variation in confenis.

Raw material name fe] [8] fe] ft] [98] eee |] 1 wo ET ene | 0 [1 rem | 1 1 1 oe | wo |p mmm | wo

DK 2023 00252 A1 57

Table 10: Hydrogenated Vegetable Oil (HVO) having been preheated to a temperature of about 55

Degree Celsius. Variation in the type of carrier. Here Syloid XDP 3050 was replaced by other carriers.

The samples are prepared according to the procedure above but adjusted to the variation in contents.

Example 4

Premix: Hydrogenated Vegetable Oil (HVO) mixture with isolated CBD added to mesoporous carriers

A mesoporous silica carrier (Syloid XDP 3050) provided from Grace in an amount of about 1000 g was added to a Lodige high shear mixer. Thereafter, a cannabinoid powder composition comprising CBD isolate from cannabis plant tissues (phytocannabinoid) with a 99% content of CBD provided by Medical Hemp (batch number MH B18592 ) in an amount of about 500 g was mixed with HVO provided from AAK under the tradename Akocrem NT 76-33 with a melting temperature of 30-35 Degree Celsius in an amount of about 500 g. While stirring, the CBD-HVO mixture was heated to a temperature of about 60 Degree Celsius to form a liquid solution of CBD in HVO. The mixture of CBD and HVO was then added to the silica carrier. After adding the lipid composition, the mixture was mixed for about 10 minutes. A total of 2000 g mixture powder premix was made. [%] [%] [%] [%] [%] [%] [%]

SDP wo | | a0 | wo | wo | 00 | wo

CBD isolate (50% 20.0 pl A dE

Table 11: Hydrogenated Vegetable Oil (HVO) having been heated to a temperature of about 60 Degree

Celsius after mixing with 99% purity CBD (50% CBD mixture). Sample 403 corresponds to the procedure above, the other samples are adjusted to the variation in contents.

DK 2023 00252 A1 38

Raw material name

[2] [2] på] ps] [94] {BD isolate (X% CBD 54.0 S00 50.0 30.0 50.0

Table 12: Hvdrogenated Fegetable Oil (VO) having been heated fo a femperaturs of about 60 Degres

Celsius after mixing with 00% purity CED (X% CBD mixture). Variation in the confent of CBD in mixture with HVO. ¥denotes the percentage X of CBD in “X%: CBD mixture”. Romple £12 corresponds to the procedure above, the offter sampler are adjusted to the variation in conten, præmie? il Hmm]

Raw matenal name sa] [9] fo] fa] [98] eee | md (fm | 1

PoP] we [ner | Two [1 erm] wo

Table 13: Fydrogenated Vegetable Oi (HV 0) having been heated fo a tfømperature of abort 60 Degree

Celsius after mixing with 90% UBD (73% CBD mixture), Variation in the type of carrier. Here Svloid

XDP 3030 vas replaced by other carriers. The samples ave prepared according fo the procedure above but adiusied fo the variation in confents.

Example 5

Premix: Miglvol mixture with isolated CBD added fo mesoporous carriers

A mesoporous silica carrier {Svloid XDP 3050) provided from Grace in an amount of about 1000 g was added to a Lådige high shear mixer. Thereafter, a cannabinoid powder composition comprising CBD isolate from cannabis plant issues {phviccannabinoid) with a 99% content of CBD provided by Medical Hemp (batch number MH B18592 ) in an amount of about 500 g was mixed with Medium Cham

Triglyveride {MCT}, Miglyol 812, provided from Sasol in an amount of about 300 g.

DK 2023 00252 A1 39

While stirring, the CBD-MCT mixture was heated to a temperature of about 70

Degree Celsius to form a hgmd solution of CBD m MCT. The mixture of CBD and

Miglyol 812 was then added to the silica carrer powder composition in an amount of about 1000 g. After adding the lipid composition, the puxture was mixed for about minutes. A total of 2000 g mixture powder prenux was made.

Raw material name prem [GG] | | rå — 76.0 60.0 50.0 40.0 30.0

CBD mixtnre)

Table 14: Aielvaj §12 mixed with 9995 purity CBD followed by heating (30% CBD mixture). Variation in the content of CBD (50% CBD mixture). Sample S03 corresponds fo the procedure above, the other samples gre adivsted fo the variation in confents, 10

Content Content Content Content Content

Raw material name fem rd red red rel rel

CED isolate (X% CED 56.0 50.0 50.0 50.0 50.0

Table 15: Migho! 812 mixed with 09% CBI followed bv heating iX% CBD mixta). Variation in the content of CBD im mixtures with Migho! 812. "denotes the percentage X of CRE in ”X% CBD mixture”.

Sample 32 corresponds fo the procedure above, the sther samples are adjusted to the veriation in

CoRienis. ree | VS

Raw material name på | på | på | på | på ene | Two 1 [fn | 1

DK 2023 00252 A1 60

FAR | TTT rr re

Table 16: Miglvol 8123 mixed with 99% CBD follmved hy henting (30% CBD mixtures). Variaffon in the hve af carrier. Here Syfoid XDF 3030 was replaced bv other carriers. The samples ave prepared according fo the procedure above but adfusted fo the variation i contents. > Example 6

Premix: Comparative samples — without non-volatile solvent

A mesoporous silica camer (Sylotd XDP 3050) provided from Grace was added to a

Ledige high shear mixer. Thereafter, a cannabinoid powder composition comprisine

CBD isolate from cannabis plant tissues (phytocannabinoid) with a purity about 99% of CBD provided by either Medical Hemp (batch munber MH18392) or Valens (batch number BVA032013) was steved through a 600 microns sieve and added to the silica camer powder composition. This mixture was mixed at a speed of about 80 rpm for about 10 minutes. No solvent was present. pos | [SS

Kaw material name

Ps] [Sd ej [9%] [2%]

Table 17: Variation in the content of CBR isolnte,

Example 7

Premix: Liquid self-emulsifving systems with isolated UBD and mesoporous carriers

DK 2023 00252 A1 61

A mesoporous silica carrier (Syloid XDP 3050) provided from Grace in an amount of about 1000 g was added to a Lodige high shear mixer. Thereafter, a cannabinoid powder composition comprising CBD isolate from cannabis plant tissues (phytocannabinoid) with a 99% content of CBD provided by Medical Hemp (batch number MH B18592) in an amount of about 500 g was sieved through a 600 microns sieve. The CBD was added to about 500 g of a composition comprising lipid and surfactant (SEDDS composition). After activation of the chopper (about 600 rpm) of the Lodige mixer, the SEDDS composition containing the CBD was added to the mixture. A total of 2 kg mixture powder premix was made in which the CBD content was about 250 mg/g. A co-solvent and/or a permeation enhancer could optionally be added. [%] [%] [%] [%] [%] [%] [%]

Shasors | wo | ou | wo | so | wo | oo | wo

CBD isolate (purity 40.0 10.0 = [Pffefofefp

Table 18: Variation in the content of CBD isolate (purity 99%). Sample 703 corresponds to the procedure above, the other samples are adjusted to the variation in contents. [%] [%] [%] [%] [%]

Table 19: Variation in the content of HVO. The samples are adjusted to the variation in contents.

DK 2023 00252 A1 62

Raw material name

Table 28: Foriation in the tvpe of carrier. Here Syiotd XDP 2030 was replaced by ather carriers. The sampler are prepared according to fæ procedure above but adiusted fø the variation fn COMERES.

Example 8 3 Premix: Solid self emulsifving systems with isolated CBD and mesoporous carriers

A mesoporous silica carrier {Syloid XDP 3050) provided from Grace in an amount of about 1000 ¢ was added to a Lådige high shear mixer. Thereafter, a cannabinoid powder composition comprising CBD isolate from cannabis plant tissues {phytocannabinoid) with a 99% content of CBD provided by Medical Hemp (batch number MH B18592) in an amount of about 500 g was sieved through a 600 microns sieve. The CBD was added to about 500 g of a composition comprising wax and surfactant (SEDDS composition). After activation of the chopper (about 600 rpm) of the Lodige mixer, the SEDDS composition contammg the CBD was added to the — mixture. A total of 2 kg nuxture powder premix was made in which the CBD content was about 230 mg/g. A co-solvent andor a permeation enhancer could optionally be added.

Raw material name

[2] på] [så] 94] ps] [3] ps]

DK 2023 00252 A1 63

PL Jn Jn [en fee [ee 35.0 30.0 2380 20.0 15.0 999) em NE EE EE 350 30.0 2548 20.0 15.8

COmposiiion

Table 21: Furtation ir the content af CBD isolate {purity 20%), Sample 80 corresponds fo the frocedure above, the other samples are adjusted to Hie variation in contents.

Content Content Content Content Content

Kaw material name prone | LW

Table 22: Pariation in the content of SEDDS. The samples are adjusted to the variation fr contents.

S

Raw material name fol [98] fa] 19%] [98]

Same] we 1 (ne | oe [1

Prt oon Bot]

Ovrom | [wo bts

Table 23: Variation in the nyve of carrier. Here Svlord XDP 3030 was replaced by other omriers. The samples are prepaved aererding fo the procedure gåove Sut adfusted ta the variation in contents.

Example 9 13 Premix: Solid self-emulsifving systems with isolated CBD

DK 2023 00252 A1 64

A cannabinoid powder composition comprising CBD isolate from cannabis plant tissues (phytocannabinoid) with a 99% content of CBD provided by Medical Hemp (batch number MH B18592) in an amount of about 400 g was sieved through a 600 microns sieve. The CBD was added to about 400 g of a composition comprising wax and surfactant (SEDDS composition). A total of 800 g mixture was made in which the CBD content was about 500 mg/g. A co-solvent and/or a permeation enhancer could optionally be added.

Femme | wo [or | ow [ww | oo [we

CBD isolate 20.0 80.0 pe ee Te composition

Table 24: Variation in the content of CBD isolate (purity 99%). Sample 903 corresponds to the procedure above, the other samples are adjusted to the variation in contents.

Example 10

Premix: Solid self-emulsifying systems with isolated CBD and permeation enhancer

A cannabinoid powder composition comprising CBD isolate from cannabis plant tissues (phytocannabinoid) with a 99% content of CBD provided by Medical Hemp (batch number MH B18592) in an amount of about 400 g was sieved through a 600 microns sieve. The CBD was added to about 400 g of a composition comprising wax, surfactant, and a permeation enhancer (SEDDS composition). A total of 800 g mixture was made in which the CBD content was about 500 mg/g.

[mW [Pa [ea [Pa [0 [a]

CBD isolate (purity 20.0 80.0 30.0 40.0 50.0 70.0 99%)

Table 25: Variation in the content of CBD isolate (purity 99%). Sample 1003 corresponds to the procedure above, the other samples are adjusted to the variation in contents.

Example 11 — Premix: Liquid self-emulsifying systems with isolated CBD and permeation enhancer

A cannabinoid powder composition comprising CBD isolate from cannabis plant tissues (phytocannabinoid) with a 99% content of CBD provided by Medical Hemp (batch number MH B18592) in an amount of about 400 g was sieved through a 600 microns sieve. The CBD was added to about 400 g of a composition comprising lipid, surfactant, and a permeation enhancer (SEDDS composition). A total of 800 g mixture was made in which the CBD content was about 500 mg/g. 1100 1101 1102 1103 1104 1105 1106

Raw material name [%] [%] [%] [%] [%] [%] [%]

CBD isolate (purity 20.0 80.0 30.0 40.0 50.0 70.0 99%)

Table 26: Variation in the content of CBD isolate (purity 99%). Sample 1103 corresponds to the procedure above, the other samples are adjusted to the variation in contents.

Example 12

Premix: Self-emulsifying systems with isolated CBD

A cannabinoid powder composition comprising CBD isolate from cannabis plant tissues (phytocannabinoid) with a 99% content of CBD provided by Medical Hemp

(batch number MH B18592) in an amount of about 400 g was sieved through a 600 microns sieve. The CBD was added to about 400 g of a SEDDS composition according to Table 27. A total of 800 g mixture was made in which the CBD content was about 500 mg/g. . Content Content Content | Content | Content

Raw material name [vol. %] [vol. %] [vol. %] | [vol. %] | [vol. %]

Labrafil M 1944 CS (from 34 26 20

Gattefossé)

Oleic acid (from Acme Synthetic 50 40

Chemicals)

Raw material name [%] [%] [%] [%] [%] [%] [%]

CBD isolate (purity 20.0 80.0 30.0 40.0 50.0 70.0 99%)

SEDDS composition 80.0 20.0 70.0 50.0 40.0 30.0 (Table 27)

Table 28: Variation in the content of CBD isolate (purity 99%). Sample 1203 corresponds to the procedure above, the other samples are adjusted to the variation in contents.

Example 13

Premix: Self-emulsifying systems with isolated CBD and carriers

A mesoporous silica carrier (Syloid XDP 3050) provided from Grace in an amount of about 1000 g was added to a Lodige high shear mixer. Thereafter, a cannabinoid

DK 2023 00252 A1 67 powder composition comprising CBD isolate from cannabis plant tissues (phytocannabinoid) with a 99% content of CBD provided by Medical Hemp (batch number MH B18592) in an amount of about 500 g was sieved through a 600 microns sieve. The CBD was added to about 500 g of a SEDDS composition according to

Example 12, Table 27. After activation of the chopper (about 600 rpm) of the Lodige mixer, the SEDDS composition containing the CBD was added to the mixture. A total of 2 kg mixture powder premix was made in which the CBD content was about 250 mg/g. A permeation enhancer could optionally be added. [%] [%] [%] [%] [%] [%] [%] a | wo | wo | woo | wo | wo | wo

CBD isolate (purity 40.0 10.0 po | ee fe ae fae

Table 29: Variation in the content of CBD isolate (purity 99%). Sample 1303 corresponds to the procedure above, the other samples are adjusted to the variation in contents. [%] [%] [%] [%] [%]

Table 30: Variation in the content of SEDDS and CBD. The samples are adjusted to the variation in contents. [%] [%] [%] [%] [%]

DK 2023 00252 A1 68 ene | TIT TT (ferm | | FT er Tee

Oto we [FT re 1 1

Table 31: Variation in fhe fype of carrier. Here Syloid XDP 3030 was replaced by other carriers. The samples are prepøred according fo the procedure above buf adjusted To Bie variation in cowtenis,

Example 14 35 Preparation of chewable tablets with two layers based on Examples I to 8 and 13

Tablets were made based on the CBD containmme mixtures of Examples 1-8 and 13 with each layer having a weight of about 50% of the total tablet. The total weight of the tables were 1800 mg. The tablets were made with a standard tablet pressing machine (30901, available from Fette GmbH) comprising dosing apparatus (P 3200 C, available from Fetie GmbH, Germany). Punch used: 16.00 min round punches. Rotor speed used was 11 mpm.

A first laver (denoted layer 1} comprising the CBD containing mixture made in

Fxamples 1-8 and 13 and additional ingredients was prepared and tableted before

IS tableting the layer comprising gum base (denoted laver 2). Layer I with a weight of about 900 me was compressed at a compression force of about 3 KN. Hereafter, laver 2 with a weight of about 900 me and comprising sum base and additional ingredients was pressed on top of laver 1 af a compression force of 40 KN, The tablet machine was comnussionied by adjusting the fill depth and compression force so the weight and hardness of tablets match the acceptance criteria. A pre-compresston force could be included to avoid capping. pe] Content fS] Content [9]

Premix Sample from one af 18.1

Examples I to 8 and 13

SE

Table 32: fu aff of the tablet examples, He omount af the various gradients is given av S by weight of the taler,

Content {36} Content [98]

Raw material name

Layer I — 900 mg layer 2 — 900 mg

Premix Sample from one af 24.2

Examples I to Band 13 fe

Table 33: fy af? of rhe foblet axconpler, the amount of fre various ingredients is given as Så åyv weight of the tablet.

Content {3} Content [95]

Raw material name

Layer I — 900 mg Layer 2 — 900 mg

Premix Sample from one af 24.2 16.1

Examples I to & and 13

DK 2023 00252 A1 70 ww

AR I feer or

Table 34: In alf of the tablet examples. the amount of the vartous ingredients is given as %5 dy weigh of the tablet.

Example IS

Preparation of chewable tablets with two lavers based on Examples 9 to 12

Tablets were made based on the UBD contamimng mixtures of Examples 9-12 with each layer having a weight of about 50% of the total tablet. The total weight of the tablets were 1800 mø. The tablets were made with a standard tablet pressing machine (3090, available from Fette GmbH) comprising dosing apparatus (P 3200 C, available from

Fette GmbH, Germany). Punch used: 16.00 mm round punches. Rotor speed used was 11 pm.

A first laver (denoted laver D) comprising the CBD containing mixture made in

Examples 9-12 and additional ingredients was prepared and tableted before tableting

IS the laver comprising gum base {denoted laver 2). Laver 1 with a weight of about 900 ing was compressed af a compression force of about 5 KN. Hereafter, layer 2 with a weight of about 900 mg and comprising grun base and additional ingredients was pressed on top of laver I at a compression force of 40 EN, The tablet machine wax commissioned by adjusting the fill depth and compression force so the weight and hardness of tablets match the acceptance ortteria. A pre-compression force could be melded to avoid capping. pe] Content {35} Content [98] oe 20.0

Examples S to 12

DK 2023 00252 A1

Fi gy ew

CC

[omme ew

Table 35: fy af? of rhe foblet axconpler, the amount of fre various ingredients is given as % by weight af the tabla, ree | urene | me

Raw material name

Layer 1 — XD mg layer 2 — 900 mg røn — | 9 Lt 20 10

Examples 810 12 pore. | ws FL

Ra ee a ee free

Table 36: In ofl of the foblet exconples, the amount of fhe various ingredients is given as % by weight af the tallet reste] were | em

Raw material name

Layer I — 800 mg Layer 2 -— 900 mg snøren — | 9 LO 24.2 16.1

Examples 9 to 12 wo wm

DK 2023 00252 A1 72

EEE ere

Table 37: fr aft of the fablet exconples, the amount of the vartous ingredients is given as Så by weight of the tbls,

Example 16

Test method for content uniformity in premixtures and powder blends

Content Uniformity {CU}, je. homogenetty of the UBD active substance in presuxtures (Premix Samples) as well as powder blends which are mixtures with additional ingredients to be processed info the oral dosage form (Powder Blends), is determined according to European Pharmacopoeia 10.8 using test method 2.9.40 Unifornuty of dosage wuts.

At least 5 samples each havine the same fixed weight in the range of 0.25-2 gram are taken from the powder mixture to be analyzed. For each sample, the content of CBD active 1s analyzed by means of standard HPLC techniques. Content Uniformly is then 18 calculated as the relative standard deviation (RSD) of the individual results.

This test meluded tests on powders for pouches, sachets, and stick packs. Also, this test was made to other cannabinoids, melading THC.

Example 17

Test method for content uniformity in solid dosage forms

Content Unifornuty (CT), tie. homogeneity of the CBD active substance in solid dosage forms, is determined according to European Pharmacopoeia 10.8 using test method 2.9.40 Unmfornmty of dosage units.

At least 10 samples are taken from the solid dosage form, eg. tablets, to be analyzed.

For each sample, the content of CBD active is analyzed by means of standard HPLC techniques. Content Umfornuty is then calculated as the relative standard deviation (RSD) of the individual results.

DK 2023 00252 A1 73

This test was included tests on chewable tablets, compressed chewing gums, and lozenges comprising particulate ingredients. Also, this test was made to other cannabinoids, including THC.

Example 18

In vivo testing of release in solid dosage forms

A sample solid dosage form was tested in a test panel of 8 test persons. Test subjects abstain from eating and drinking at least 30 minutes before initiation of any test. The test person was a healthy person appointed on an objective basis according to specified requirements. After specific time intervals of use, eg. 0, 0.5, 1, 2, 3, 5 and 10 minutes, the content of CBD was measured in the remaining solid dosage residue.

The solid dosage form was subject to triple measurements for each of the 8 test persons, giving a total of 24 measurements for each sample. An average of the 24 measurements was calculated and the weight % release was calculated based on the original content of CBD in the sample. The content of CBD was measured in the remaining solid dosage form residue, if still present.

The solid dosage form was weighted and placed in the mouth, and the test persons — were instructed to place and use the solid dosage form as intended. For chewing gum, the test persons were instructed to chew the sample at a frequency of 60 chews per minute. For lozenges the test persons were instructed to place the sample between the tongue and the palate, and then the solid dosage form was sucked and turned every 0.5 minute. Once the desired test time was achieved (0.5, 1, 2, 3, 5 and > 10 min.), the solid dosage form was taken out and weighed directly into a measuring glass to be used for analysis of CBD content. An in vivo dissolution profile was obtained by analyzing the content of CBD in the solid dosage form at different dissolution times.

DK 2023 00252 A1 74

This test was made to chewable tablets, chewing gums, and lozenges comprising particulate ingredients. Also, this test was made to other cannabinoids, including

THC.

Example 19

In vitro testing of release in solid dosage forms

A sample solid dosage form was tested. After specific time intervals of use, eg 0, 0.5, 1, 2, 3, 5 and 10 minutes, the content of CBD was measured in the remaining solid dosage residue. The solid dosage form was subject to triple measurements. An average of the measurements was calculated and the weight % release was calculated based on the original content of CBD in the sample. The content of CBD was measured in the remaining solid dosage form residue, if still present.

The solid dosage form was weighted. Then 25 ml of phosphate buffer was added into a 50 ml measuring tube with screw cap. The solid dosage form was added to the tube. The tube was fixed horizontally on a shaking table. After shaking, the solid dosage form was analyzed for content of CBD. An in vitro profile was obtained by analyzing the content of the CBD in the solid dosage at different dissolution times.

This test was made to tablets, chewing gum, and lozenges comprising particulate ingredients. Also, this test was made to other cannabinoids, including THC.

Example 20

Invitro testing of release from premixtures

Corresponding tests were made on premixtures of Examples 1-8 and 13 in accordance with the procedure outline in Example 19.

Example 21

In vitro testing of release from powder blends

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Corresponding tests were made on powder blends comprising premixtures of

Examples 1-8 and 13 in accordance with the procedure outline in Example 19.

The powder blends included tests on powders for pouches, sachets, and stick packs.

Example 22

Sensoric evaluation test set-up of solid dosage forms

In addition to release measurements, either in vivo or in vitro, sensoric tests were performed to reveal very important characteristics and properties of the solid dosage form and powder blends. These sensoric parameters are important as indicators of the structure of the solid dosage form composition. The structure is the underlying guidance as to how the solid dosage form resembles the structure of a comparative solid dosage form, which is set as the standard in the test series, i.e. the solid dosage forms are compared to each other in the test series of preferably 5 samples. The test set-up was composed of 8 test persons in a test panel. All of the test persons were healthy individuals appointed on an objective basis according to specified requirements. The sensory analysis was performed according to ISO 4121-2003 in testing conditions following ISO 8589. The result is an average of the results of the 8 individuals.

The test persons gave a rating from “+” to +4+4+”, where “+” is poor and +44447 is excellent, i.e. "+4++1+” means that the solid dosage form was excellent compared to the standard, “+++” means that the solid dosage form was comparable to the standard and “+” means that the solid dosage form was very far from comparable to — the standard. "0" indicated that it was not tested.

Four different parameters were tested in a test panel:

DK 2023 00252 A1 76 “Sandy Texture” - the general impression of the solid dosage form when placed in the mouth with respect to the impression of particulate roughness, i.e., a sandy feeling in the mouth upon administration. “Flavor” — the overall impression of the solid dosage form during intended use with respect to flavor. For instance, a very low flavor experience gave a very low rating and a too high flavor experience that was not comparable to the standard also gave a very low rating. “Sweetness” — the overall impression of the taste of the solid dosage form during intended use with respect to sweetness. For instance, if the sweetness was decreasing rapidly, a very low rating was given and if the sweetness was too high giving an uncomfortable feeling, a very low rating was also given. “Off-notes” — the overall impression of the off-note from the one or more cannabinoids in the composition during intended use. For instance, if off-notes (grass, bitter notes, irritation in the throat) were experienced in the throat, a low rating was given and if other uncomfortable sensations was experienced, a low rating was also given. “Creaking sound” — the overall impression upon mastication of a chewable solid dosage form with respect to invoking a creaking feeling upon contact with the teeth.

For instance, if a creaking sound was experienced, a low rating was given.

Example 23

Results on content uniformity in premixtures

The procedures of Example 16 was used for the premixes (Premix Samples) above and the results revealed a surprisingly good content of uniformity of the inventive samples.

The result of content uniformity for a sample was revealed as a single value obtained as the relative standard deviation (RSD) of CBD content of multiple samples taken at the end of the premix preparation procedures.

DK 2023 00252 A1 77

Example 24

Results on content uniformity in powder blends and solid dosage forms — The procedures of Example 16 was used for powder blends (Powder Blends) which are powder premixes (Powder Premix Samples) with additional ingredients as outlined in the formulations of the oral dosage forms. The powder blends included tests on powders for pouches, sachets, and stick packs as well as powder blends for use in the solid dosage forms, including chewable tablets, chewing gums, and lozenges comprising particulate ingredients according to the previous examples. The procedure of Example 17 was used for the solid dosage forms.

The result of content uniformity (CU) for a sample is provided as a single value obtained as the relative standard deviation (RSD) of CBD content of multiple samples taken at the end of the preparation procedures. If individual samples have been collected at different stages of a tableting process (eg. start, middle, end) then content uniformity is determined by analysis of pooled samples from the different process stages. The results revealed a surprisingly good content of uniformity of the inventive samples.

Example 25

Results on release from solid dosage forms

The procedures of Example 19 was made on solid dosage forms according to the previous examples. The results revealed a surprisingly good release of the inventive samples. Similar good results were seen for tablets without gum base, FDT tablets, compressed chewing gums, and lozenges.

Example 26

Results on release from premixtures

The procedures of Example 20 was made on premixtures according to the previous examples. The results revealed a surprisingly good release of the inventive samples.

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Example 27

Results on release from powder blends

The procedures of Example 21 was made on powder blends according to the previous examples. The results revealed a surprisingly good release of the inventive samples.

Good results were seen for powders according to the previous examples for use in pouches, sachets, stick packs, and flowpacks.

Example 28

Results on sensoric evaluation test set-up of solid dosage forms

The procedures of Example 22 was made in order to establish benefits of the sensory properties of the solid samples of the instant application. Surprisingly good results were seen for chewable tablets with or without gum base, FDT tablets, compressed chewing gums, and lozenges.

Claims

DK 2023 00252 A1 79 CLAIMS

1. An orally dissolvable or chewable tableted powder formulation, comprising: one or more mesoporous silica carriers loaded with a liquid cannabinoid — suspension or solution; one or more water-soluble agents in an amount of 20-80% by weight of the tableted powder formulation; and one or more flavors, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10.

2. The orally dissolvable or chewable tableted powder formulation according to claim 1, wherein the liquid cannabinoid suspension or solution comprises one or — more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:5.

3. The orally dissolvable or chewable tableted powder formulation according to any one of claim 1 or 2, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 8:1 to 1:2.

4. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 5:1 to 1:2.

5. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers comprises the liquid cannabinoid suspension or solution in a weight ratio of silica carrier to liquid cannabinoid suspension or solution of 2:8 to 8:2.

DK 2023 00252 A1 80

6. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers comprises the liquid cannabinoid suspension or solution in a weight ratio of silica — carrier to liquid cannabinoid suspension or solution of 3:7 to 7:3.

7. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers comprises the liquid cannabinoid suspension or solution in a weight ratio of silica — carrier to liquid cannabinoid suspension or solution of 4:6 to 6:4.

8. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers having an average particle size of 20 to 200 microns.

9. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers having an average particle size of 30 to 170 microns. —

10. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount of above 5% by weight of the orally dissolvable or chewable tableted powder formulation.

11. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount of above 10% by weight of the orally dissolvable or chewable tableted powder formulation.

DK 2023 00252 A1 81

12. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount of above 20% by weight of the orally dissolvable or chewable tableted powder formulation.

13. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises the one or more mesoporous silica carriers in an amount up to 60% by weight of the orally dissolvable or chewable tableted powder formulation.

14. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers is present in an amount of 30 to 600 mg in the orally dissolvable or chewable tableted — powder formulation.

15. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers is present in an amount of 30 to 300 mg in the orally dissolvable or chewable tableted — powder formulation.

16. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein an average pore volume of the one or more mesoporous silica carriers is above 1.0 cm”/g.

17. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein an average pore volume of the one or more mesoporous silica carriers is above 1.5 cm”/g.

DK 2023 00252 A1 82

18. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein an average pore volume of the one or more mesoporous silica carriers is from 1.5 to 3.0 cm”/g.

19. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein an average density of the one or more mesoporous silica carriers is above 50 g/L.

20. The orally dissolvable or chewable tableted powder formulation according to any — ofthe preceding claims, wherein an average density of the one or more mesoporous silica carriers is from 50 to 400 g/L.

21. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein an average density of the one or more mesoporous silica carriers is from 150 to 400 g/L.

22. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the moisture adsorption capacity of the one or more mesoporous silica carriers is above 10% by weight of the one or more mesoporous silica carriers at a relative humidity of 50%.

23. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the moisture adsorption capacity of the one or more mesoporous silica carriers is above 20% by weight of the one or more mesoporous — silica carriers at a relative humidity of 50%.

24. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers is not characterized as a powder flow promotor.

DK 2023 00252 A1 83

25. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers does not comprise fumed colloidal silica.

26. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the surface of the one or more mesoporous silica carriers is characterized by having an average surface hydrophilicity of 3 to 7 OH/nm?.

27. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers comprises at least two types of mesoporous silica carriers.

28. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers comprises magnesium aluminometasilicate.

29. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is associated with an improved mouthfeel.

30. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is associated with an improved mouthfeel comprising a less sandy mouthfeel.

31. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is associated with an improved mouthfeel comprising a less creaking — sound upon mastication of the orally dissolvable or chewable tableted powder formulation.

DK 2023 00252 A1 84

32. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is associated with an improved mouthfeel by the presence of the one or more mesoporous silica carriers loaded with a liquid cannabinoid suspension or solution compared to separately added silica.

33. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is associated with an improved mouthfeel by the presence of the one or more water-soluble agents compared to separately added silica.

34. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein at least a part of the liquid cannabinoid suspension — or solution is separate from the one or more mesoporous silica carriers.

35. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is fully contained in the liquid cannabinoid suspension or solution.

36. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises one or more cannabinoids separate from the liquid cannabinoid suspension or solution.

37. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), and combinations thereof.

DK 2023 00252 A1 85

38. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is selected from the group consisting of tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and combinations thereof.

39. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids comprises cannabidiol (CBD).

40. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), cannabielsoin (CBE), iso- — tetrahydrocannabinol (iso-THC), cannabicyclol (CBL), cannabicitran (CBT), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), and combinations thereof. —

41. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is an isolated cannabinoid.

42. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is a synthetic cannabinoid.

43. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is a cannabinoid distillate with a cannabinoid purity of more than 80%.

DK 2023 00252 A1 86

44. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is not a cannabinoid extract with a cannabinoid purity of less than 80%.

45. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is present in an amount of at least 40 mg in the orally dissolvable or chewable tableted powder formulation.

46. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is present in an amount of at least 75 mg in the orally dissolvable or chewable tableted powder formulation.

47. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is present in an amount of at least 100 mg in the orally dissolvable or chewable tableted powder formulation.

48. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is present in an amount of at least 150 mg in the orally dissolvable or chewable tableted powder formulation.

49. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more cannabinoids is present in an amount of at least 300 mg in the orally dissolvable or chewable tableted powder formulation.

50. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers is

DK 2023 00252 A1 87 present in an amount of 30 to 600 mg in the orally dissolvable or chewable tableted powder formulation.

51. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more mesoporous silica carriers is present in an amount of 30 to 300 mg in the orally dissolvable or chewable tableted powder formulation.

52. The orally dissolvable or chewable tableted powder formulation according to any — ofthe preceding claims, wherein the one or more water-soluble agents is present in an amount of 30-80% by weight of the tableted powder formulation.

53. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more water-soluble agents is present in an amount of 40-80% by weight of the tableted powder formulation.

54. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more water-soluble agents comprises one or more sugar alcohol particles.

55. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more water-soluble agents comprises one or more sugar alcohol particles selected from the group consisting of sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, isomalt, and combinations thereof.

56. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more water-soluble agents comprises one or more sugar alcohol particles comprising non-directly compressible (non-DC) sugar alcohol particles and directly compressible (DC) sugar alcohol particles.

DK 2023 00252 A1 88

57. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more water-soluble agents comprises one or more sugar alcohol particles comprising non-directly compressible (non-DC) sugar alcohol particles and directly compressible (DC) sugar alcohol particles in a ratio of non-DC to DC between 0.2 and 1.2.

58. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, further comprising one or more disintegrants.

59. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, further comprising one or more disintegrants selected from the group consisting of sodium croscarmellose, crospovidone, sodium starch glycolate, and combinations thereof. —

60. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, further comprising at least one dissolution modifier selected from the group consisting of acacia, agar, alginic acid or a salt thereof, carbomer, carboxymethylcellulose, carrageenan, cellulose, chitosan, copovidone, cyclodextrins, ethylcellulose, gelatin, guar gum, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl cellulose, hypromellose, inulin, methylcellulose, pectin, polycarbophil or a salt thereof, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, pullulan, starch, tragacanth, trehalose, xanthan gum and mixtures thereof.

61. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, further comprising at least one dissolution modifier in an amount of 3 to 20% by weight of the orally dissolvable or chewable tableted powder formulation.

DK 2023 00252 A1 89

62. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, further comprising at least one microcrystalline cellulose dissolution modifier. 3563.

The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, further comprising one or more organic acids.

64. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more flavors is present in an amount of

0.1 to 10% by weight of the orally dissolvable or chewable tableted powder formulation.

65. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents comprises one — or more oils.

66. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents comprises one or more triglycerides.

67. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents comprises one or more triglycerides of vegetable origin.

68. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents comprises one or more triglycerides selected from one or more C4 to C14 triglycerides.

69. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents comprises one or more triglycerides comprising a partially hydrogenated vegetable oil.

DK 2023 00252 A1 90

70. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents comprises one or more triglycerides comprising a fully hydrogenated vegetable oil.

71. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents comprises one or more triglycerides comprising caprylic acid in an amount of 50 to 80% by weight.

72. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents comprises one or more triglycerides comprising capric acid in an amount of 20 to 45% by weight.

73. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents comprises propylene glycol.

74. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents does not comprise an alcohol.

75. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents does not comprise a flavor oil.

76. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents is present in an amount of 1 to 20% by weight of the orally dissolvable or chewable tableted powder formulation.

DK 2023 00252 A1 91

77. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents improves homogeneity of the one or more cannabinoids in the orally dissolvable or chewable tableted powder formulation.

78. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents is present in an amount of 10 to 500 mg in the orally dissolvable or chewable tableted powder formulation.

79. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the one or more non-volatile solvents is present in an amount of 50 to 300 mg in the orally dissolvable or chewable tableted powder formulation.

80. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system that when hydrated forms an emulsion for delivery of the one or more cannabinoids.

81. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system that when hydrated forms an emulsion for delivery of the one or more cannabinoids to mucosal surfaces in the gastrointestinal tract.

82. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system loaded in the one or more mesoporous silica carriers.

DK 2023 00252 A1 92

83. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the liquid cannabinoid suspension or solution comprises a self-emulsifying system.

84. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system loaded in a solid matrix.

85. The orally dissolvable or chewable tableted powder formulation according to any — ofthe preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more waxes.

86. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more surfactants.

87. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more surfactants — having an HLB-value of more than 6.

88. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more surfactants selected from the group consisting of PEG-35 castor oil, PEG-6 oleoyl glycerides, PEG-6 linoleoyl glycerides, PEG-8 caprylic/capric glyceride, sorbitan monolaurate, sorbitan monooleate, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (60) sorbitan monostearate, polyoxyethylene (80) sorbitan monooleate, lauroylpoloxyl-32 glycerides, stearoyl polyoxyl-32 glycerides, polyoxyl-32 stearate, propylene glycol mono laurate , propylene glycol di laurate, and mixtures and combinations thereof.

DK 2023 00252 A1 93

89. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more co- solvents.

90. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more co-solvents — selected from the group consisting of polyglyceryl-3 dioleate, 1,2-propandiol, polyethylene glycol 300, polyethylene glycol 400, diethylene glycol monoethyl ether, and mixtures and combinations thereof.

91. The orally dissolvable or chewable tableted powder formulation according to any — ofthe preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more solubilizers.

92. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises a self-emulsifying system comprising one or more solubilizers selected from the group consisting of lauroylpoloxyl-32 glycerides; stearoyl polyoxyl-32 glycerides; Polyoxyl-32 stearate; synthetic copolymer of ethylene oxide (80) and propylene oxide (27); polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer; alpha-, beta- or gamma cyclodextrins and derivatives thereof; pea proteins (globulins, albumins, glutelins proteins); and mixtures and combinations thereof.

93. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises one or more permeation enhancers.

DK 2023 00252 A1 94

94. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is an orally dissolvable tablet.

95. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is an orally dissolvable tablet disintegrating in the oral cavity within 2 minutes upon oral administration.

96. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is an orally dissolvable tablet disintegrating in the oral cavity within 1 minute upon oral administration.

97. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is a chewable tablet. —

98. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is a lozenge comprising particulate ingredients.

99. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation comprises gum base.

100. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the orally dissolvable or chewable tableted powder formulation is a compressed chewing gum tablet.

DK 2023 00252 A1 95

101. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the ingredients of the orally dissolvable or chewable tableted powder formulation is released in the oral cavity.

102. The orally dissolvable or chewable tableted powder formulation according to any of the preceding claims, wherein the unit weight of the orally dissolvable or chewable tableted powder formulation is from 400 to 2000 mg.

103. The orally dissolvable or chewable tableted powder formulation according to — any of the preceding claims, wherein the unit weight of the orally dissolvable or chewable tableted powder formulation is from 500 to 1800 mg.

104. An orally dissolvable or chewable powder formulation comprising: one or more mesoporous silica carriers loaded with a liquid cannabinoid — suspension or solution; one or more water-soluble agents in an amount of 20-80% by weight of the powder formulation; and one or more flavors, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10.

105. The orally dissolvable or chewable powder formulation according to claim 104 as further defined in any of claims 2-93.

106. A stick pack comprising an orally dissolvable or chewable powder formulation comprising: one or more mesoporous silica carriers loaded with a liquid cannabinoid suspension or solution; one or more water-soluble agents in an amount of 20-80% by weight of the powder formulation; and

DK 2023 00252 A1 96 one or more flavors, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10.

107. The stick pack according to claim 106, wherein the unit weight of the orally dissolvable or chewable powder formulation is from 400 to 2000 mg.

108. The stick pack according to claim 106 or 107 as defined in any of claims 2-93.

109. A sachet comprising an orally dissolvable or chewable powder formulation comprising: one or more mesoporous silica carriers loaded with a liquid cannabinoid suspension or solution; one or more water-soluble agents in an amount of 20-80% by weight of the powder formulation; and one or more flavors, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10.

110. The sachet according to claim 109, wherein the unit weight of the orally dissolvable or chewable powder formulation is from 400 to 2000 mg.

111. The sachet according to claim 109 or 110 as defined in any of claims 2-93.

112. A pouch comprising an orally dissolvable or chewable powder formulation comprising: one or more mesoporous silica carriers loaded with a liquid cannabinoid — suspension or solution;

DK 2023 00252 A1 97 one or more water-soluble agents in an amount of 20-80% by weight of the powder formulation; and one or more flavors, wherein the liquid cannabinoid suspension or solution comprises one or more cannabinoids and one or more non-volatile solvents in a weight ratio of cannabinoid to solvent of 10:1 to 1:10.

113. The pouch according to claim 112, wherein the unit weight of the orally dissolvable or chewable powder formulation is from 400 to 2000 mg.

114. The pouch according to claim 112 or 113 as defined in any of claims 2-93.

g TY DANISH PATENT AND 335 mee TRADEMARK OFFKE Application No. Search report - patent PA 2023 00252

1. [] Certain claims were found unsearchable (See Box No. I).

2. [1] Lack of unity of invention was found prior to search (See Box No. II).

A. Classification A61K 31/05 (2006.01)i, CO8K 3/36 (2006.01)a. According to International Patent Classification (IPC)

B. Fields searched PCT-minimum documentation searched (classification system followed by classification symbols) IPC&CPC A61K, A23L Documentation searched other than PCT-minimum documentation DK, NO, SE, FI: IPC-classes as specified in Box A above Electronic database consulted during the search (name of database and, where practicable, search terms used) WPI, EPODOC, FULL TEXT: ENGLISH.

C. Documents considered to be relevant Citation of document, with indication, where appropriate, of the relevant passages Y US 2020/0345684 Al (VIALPANDO MONICA MARIE et al.) 05/11/2020 1-7 and 10 A Paragraphs [0078], [0084], [0115], [0120], [0129]-[0131], [0177]-[0178] 8-9 and [0194]. Y GB 2614634 A (GREENWAY HERBAL PRODUCTS LLC) 12/07/2023 1-7 and 10 A Paragraphs [0057], [0061]. 8-9 Y US 2021/0126775 AL (KAROLCHYK SCOTT) 01/07/2021 17 and 10 A Claims 6, 13, paragraphs [0005]-[0006], [0008], [0015] and [0018]. i A WE 2020/181715 AL (CANNASOUL ANALYTICS LTD) 13/08/2020 1-10 Claims 1 to 6. A WE 2020/01885% A2 (GLATT GMBH) 23/01/2020 1-10 Paragraph [0006], [0012], [0056], [0069]-[0070], [0094] and [00103]. [] Further documents are listed in the continuation of Box C * Special categories of cited documents: "P" Document published prior to the filing date but later than the priority date claimed. "A" Document defining the general state of the art which is not un | | Å considered to be of particular relevance. T" Document not in conflict with the application but cited to understand the principle or theory underlying the invention. "D" Document cited in the application. " "X" Document of particular relevance; the claimed invention cannot be "E" Earlier application or patent but published on or after the filing considered novel or cannot be considered to involve an essential date. difference when the document is taken alone. m Document which may throw doubt on priority claim(s) or which is "Y" Document of particular relevance; the claimed invention cannot be cited to establish the publication date of another citation or other considered to involve an essential difference when the document is special reason (as specified). combined with one or more other such documents, such combination "0" Document referring to an oral disclosure, use, exhibition, or other being obvious to a person skilled in the art. means. "&" Document member of the same patent family. Danish Patent and Trademark Office Date of completion of the search report Helgeshgj Allé 81 03/10/2023 DK-2630 Taastrup Authorized officer Denmark i Erik Lund

Tel.: +45 43 50 80 00 Tel.: +45 43 50 81 40 Page 1 of 4 v. 03.23 g TY DANISH PATENT AND vYVVK mee — TRADEMARK OFFICE Application No. Search report - patent PA 2023 00252

C. Documents considered to be relevant (continuation) Page 2 of 4 v. 03.23 g TY DANISH PATENT AND 335 ze — TRADEMARK OFFICE Application No. Search report - patent PA 2023 00252 Box No. I Certain claims were found unsearchable This search report has not been established in respect of certain claims for the following reasons:

1. O Claims Nos.: because they relate to subject matter not required to be searched. Specifically:

2. [J Claims Nos.: because they relate to parts of the patent application that do not comply with the prescribed requirements to such an extent that no meaningful search can be carried out. Specifically:

3. O Claims Nos.: because of other matters. Specifically: Box No. II Lack of unity of invention was found prior to search Prior to search, multiple independent inventions were found in the patent application. Specifically: Page 3 of 4 v. 03.23 tå Danisk PATENT AND vYVVK mee — TRADEMARK OFFICE Application No.

Search report - patent PA 2023 00252 Supplemental Box Continuation of Box [.] Page 4 of 4 v. 03.23