Cannabinoid pouch

Abstract

A pouch designed for administration of an active ingredient in the oral cavity is disclosed, the pouch containing a matrix composition having a combination of an amount of one or more cannabinoids and a water-insoluble composition. Also, pouches for use as a medicament, for use in alleviation of pain, and for use in mitigation of appetite deficiency are disclosed. Further, a method of alleviation of pain and a method of mitigation of appetite deficiency using the pouch are disclosed.

Claims

1. A pouch designed for administration of an active ingredient in the oral cavity, the pouch containing a matrix composition comprising: powdered granules comprising a combination of an amount of one or more cannabinoids; and a water-insoluble composition comprising microcrystalline cellulose (MCC), wherein the matrix composition further comprises a water-soluble composition comprising one or more sugar alcohols, and wherein the pouch comprises a water-permeable membrane.

2. The pouch according to claim 1, wherein the matrix composition comprises said water-insoluble composition in an amount of between 1 and 80 percent by weight of said matrix composition.

3. The pouch according to claim 1, wherein the water-insoluble composition further comprises an ion-exchange resin.

4. The pouch according to claim 3, wherein the ion-exchange resin is present in an amount of 5 to 60 percent of said matrix composition.

5. The pouch according to claim 1, wherein the matrix composition further comprises a release controlling composition.

6. The pouch according to claim 5, wherein said release controlling composition is hydrophobic.

7. The pouch according to claim 5 wherein said release controlling composition comprises one or more metallic stearates.

8. The pouch according to claim 5, wherein the matrix composition comprises said release controlling composition in an amount of between 1 and 20 percent by weight of said matrix composition.

9. The pouch according to claim 1, wherein the one or more cannabinoids is physically or chemically bound to at least a part of the matrix composition acting as a carrier.

10. The pouch according to claim 1, wherein the one or more cannabinoids comprises cannabidiol.

11. The pouch according to claim 1, wherein the one or more cannabinoids comprises tetrahydrocannabinol.

12. The pouch according to claim 1, wherein the pouch further comprises a humectant.

13. A pouch designed for administration of an active ingredient in the oral cavity, the pouch containing a matrix composition comprising: a powder composition comprising an amount of one or more cannabinoids; a water-soluble composition comprising one or more sugar alcohols; and a water-insoluble composition comprising microcrystalline cellulose (MCC), wherein the pouch comprises a water-permeable membrane.

14. A pouch designed for administration of an active ingredient in the oral cavity, the pouch containing a powdered matrix composition comprising: an amount of one or more cannabinoids; a water-soluble composition comprising one or more sugar alcohols; and a water-insoluble composition comprising microcrystalline cellulose (MCC), wherein the one or more cannabinoids is physically or chemically bound to at least a part of the powdered matrix composition acting as a carrier, and wherein the pouch comprises a water-permeable membrane.

15. The pouch according to claim 13, wherein the water-permeable membrane is a woven fabric.

16. The pouch according to claim 13, wherein the water-permeable membrane is a non-woven fabric.

17. The pouch according to claim 13, wherein the matrix composition comprises said one or more cannabinoids in an amount of 0.25 to 500 milligrams.

18. The pouch according to claim 13, wherein the one or more cannabinoids is physically or chemically bound to at least a part of the matrix composition acting as a carrier.

19. The pouch according to claim 13, wherein the matrix composition comprises said water-insoluble composition in an amount of between 1 and 80 percent by weight of said matrix composition.

20. The pouch according to claim 14, wherein the one or more cannabinoids comprises cannabidiol and/or tetrahydrocannabinol.

21. The pouch according to claim 14, wherein the pouch further comprises a humectant.

22. The pouch according to claim 14, wherein the powdered matrix composition has an average particle size between 1 and 1200 micrometers.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) Definitions

(2) As used herein the term “pouch” is intended to mean a container typically formed by a web of a fibrous material enclosing a cavity. The pouch is pouch designed for administration of an active ingredient in the oral cavity, and thus it is adapted for oral use, it is non-toxic and not water-soluble. The fibrous material may e.g. form a woven or non-woven web or fabric. The pouch may for example be sealed by bonding two corresponding pieces of web or fabric to each other along their edges to form a cavity for the one or more cannabinoids and the water-insoluble composition. In order to release the one or more cannabinoids, the pouch is made water-permeable so as to allow saliva from the oral cavity to penetrate the pouch and enter the cavity, where the saliva can come into contact with the one or more cannabinoids, whereby the one or more cannabinoids are released from the oral pouch.

(3) As used herein the term “carrier” is intended to mean a substance that binds, physically or chemically an active ingredient. Unless otherwise stated, the term “carrier” refers to a carrier for said one or more cannabinoids. Examples of carriers include ion exchange resins, and cellulose, e.g. microcrystalline cellulose. The one or more cannabinoids may for example be granulated with the cellulose, when using cellulose as the water-insoluble composition. When using ion-exchange resin as the water-insoluble composition, the one or more cannabinoids are bound to the ion-exchange resin.

(4) As used herein the term “cannabinoids” refers to cannabinoids derived from cannabis plants and synthetic cannabinoids. Examples of cannabinoids include cannabidiol, tetrahydrocannabinol, cannabinol, etc.

(5) As used herein the terms “cannabidiol” and “CBD” both refer to Cannabidiol (IUPAC: 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol).

(6) As used herein the terms “tetrahydrocannabinol” and “THC” both refer to Tetrahydrocannabinol, (−)-trans-Δ.sup.9-tetrahydrocannabinol (IUPAC: (−)-(6aR,10aR)-6,6,9-Trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol).

(7) As used herein the term “powder composition” refers to composition in the form of powder, i.e. as a particulate material having a relatively small average particle size, for example between 1 and 1200 micrometer.

(8) As used herein the term “humectant” is understood as a moistening agent used to attract moisture or water in the form of saliva. Humectants may typically include suitably hygroscopic compositions. In some cases, humectants may also be described as moistening agents, due to their role in attraction of moisture. Examples of humectants include cellulose, such as microcrystalline cellulose and other cellulose types disclosed herein, sugar alcohols, such as those disclosed herein, alginate, cellulose, such as microcrystalline cellulose, pectin, xanthan gum, etc.

(9) As used herein the term “water-insoluble composition” refers to a composition having a relatively low water-solubility, for example consisting of water-soluble substances having a water-solubility of less than 1 gram of water-insoluble composition per 100 mL of water measured at 25 degrees Celsius and pH of 7.0. When referring to an “insoluble” composition or substance, water-insoluble is meant, unless otherwise stated. Likewise, when referring to “soluble”, water-soluble is meant unless otherwise stated. The water-insoluble composition is part of the matrix composition. In some embodiments, water-soluble composition is part of a carrier or forms such carrier.

(10) As used herein the term “matrix composition” is used as reference to the total content of the pouch, i.e. the entire composition enclosed by the pouch. Typically, it therefore corresponds to the pouch excluding the outer membrane of the pouch.

(11) Typically, the pouches comprise openings, where the characteristic opening dimension is adapted to a characteristic dimension of the matrix composition so as to retain the matrix composition inside the pouch before use and/or to retain a part of the matrix composition, such as an insoluble composition, inside the pouch during use.

(12) In order to obtain a pouch having suitable opening dimensions in view of the matrix composition to be used, the material for the pouch may be selected accordingly, e.g. comprising e.g. wowen or non-wowen fabric.

(13) In other words, according to the various embodiments, the pouch forms a membrane allowing passage of saliva and prevents or inhibits passage of said water-insoluble composition. The membrane of the pouch may be of any suitable material e.g. wowen or non-wowen fabric (e.g. cotton, fleece etc.), heat sealable non-wowen 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 cannabinoids from the pouch.

(14) 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 suspended components from the powder in the pouch, such as cannabinoids, to pass through said pouch.

(15) The pouch may be placed in the oral cavity by the user. Saliva then enters into the pouch, and the one or more cannabinoids 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, where the cannabinoid may be absorbed.

(16) According to an embodiment of the invention, the matrix composition may further comprise one or more enhancers.

(17) In an embodiment of the invention, said enhancers are selected from the group consisting of bile salts, cetomacrogols, chelating agents, citrates, cyclodextrins, detergents, enamine derivatives, fatty acids, labrasol, lecithins, phospholipids, syntetic and natural surfactants, nonionic surfactants, cell envelope disordering compounds, solvents, steroidal detergents, chelators, solubilization agents, charge modifying agents, pH control agents, degradative enzyme inhibitors, mucolytic or mucus clearing agents, membrane penetration-enhancing agents, modulatory agents of epithelial junction physiology, vasodilator agents, selective transport-enhancing agents, or any combination thereof. pH control agents include buffers.

(18) In an embodiment of the invention, said enhancers are selected from the group consisting of cetylpyridinium chloride (CPC), benzalkonium chloride, sodium lauryl sulfate, polysorbate 80, Polysorbate 20, cetyltrimethylammonium bromide, laureth 9, sodium salicylate, sodium EDTA, EDTA, aprotinin, sodium taurocholate, saponins, bile salt derivatives, fatty acids, sucrose esters, azone emulsion, dextran sulphate, linoleic acid, labrafil, transcutol, urea, azone, nonionic surfactants, sulfoxides, sauric acid/PG, POE 23 lauryl ether, methoxysalicylate, dextran sulfate, methanol, ethanol, sodium cholate, Sodium taurocholate, Lysophosphatidyl choline, Alkylglycosides, polysorbates, Sorbitan esters, Poloxamer block copolymers, PEG-35 castor oil, PEG-40 hydrogenated castor oil, Caprocaproyl macrogol-8 glycerides, PEG-8 caprylic/capric, glycerides, Dioctyl sulfosuccinate, Polyethylene lauryl ether, Ethoxydiglycol, Propylene glycol, mono-di-caprylate, Glycerol monocaprylate, Glyceryl fatty acids (C.sub.8-C.sub.18) ethoxylated Oleic acid, Linoleic acid, Glyceryl caprylate/caprate, Glyceryl monooleate, Glyceryl monolaurate, Capryliccapric triglycerides, Ethoxylated nonylphenols, PEG-(8-50) stearates, Olive oil PEG-6, esters, Triolein PEG-6 esters, Lecithin, d-alpha tocopherol polyethylene glycol 1,000 succinate, Citric acid, Sodium citrate, BRIJ, Sodium laurate, 5-methoxysalicylic acid, Bile salts, Acetyl salicylate, ZOT, Docosahexaenoic acid, Alkylglycosides, Sodium glycocholate (GC-Na), Sodium taurocholate (TC-Na), EDTA, Choline salicylate, Sodium caprate (Cap-Na), N-lauryl-beta-D-maltopyranoside (LM), Diethyl maleate, Labrasol, Sodium salicylate, Mentol, Alkali metal alkyl sulphate, Sodium lauryl sulphate, Glycerin, Bile acid, Lecithin, phosphatidylcholine, phosphatidylserine, sphingomyelin, phophatidylethanolamine, cephalin, lysolecithin, Hyaluronic acid: alkalimetal salts, sodium, alkaline earth and aluminum, Octylphenoxypolyethoxyethanol, Glycolic acid, Lactic acid, Chamomile extract, Cucumber extract, Borage oil, Evening primrose oil, Polyglycerin, Lysine, Polylysine, Triolein, Monoolein, Monooleates, Monolaurates, Polydocanol alkyl ethers, Chenodeoxycholate, Deoxycholate, Glycocholic acid, Taurocholic acid, Glycodeoxycholic acid, Taurodeoxycholic acid, Sodium glycocholate, Phosphatidylcholine, Phosphatidylserine, Sphingomyelin, Phosphatidylethanolamine, Cephalin, Lysolecithin, Alkali metal hyaluronates, Chitosan, Poly-L-arginine, Alkyl glucoside, Saccharide alkyl ester, Fusidic acid derivatives, Sodium taurdihydrofusidate (STDHF), L-α-phosphatidylcholine Didecanoyl (DDPC), Nitroglycerine, nitropruside, NOC5 [3-(2-hydroxy-l-(methyl-ethyl)-2-nitrosohydrazino)-l-propanamine], NOC12 [iV-ethyl-2-(l-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine, SNAP [S-nitroso-N-acetyl-DL-penicillamine, NORI, NOR4, deacylmethyl sulfoxide, azone, salicylamide, glyceryl-l,3-diacetoacetate, l,2-isopropylideneglycerine-3-acetoacetate), Amino acids, Amino acid salts, monoaminocarboxlic acids, Glycine, alanine, phenylalanine, proline, hydroxyproline, hydroxyamino acids, serine, acidic amino acids, aspartic acid, Glutamic acid, Basic amino acids, Lysine, N-acetylamino acids, N-acetylalanine, N-acetylphenylalanine, TM-acetylserine, N-acetylglycine, N-acetyllysine, N-acetylglutamic acid, N-acetylproline, N-acetylhydroxyproline, lactic acid, malic acid and citric acid and alkali metal salts thereof, pyrrolidonecarboxylic acids, alkylpyrrolidonecarboxylic acid esters, N-alkylpyrrolidones, proline acyl esters, sodium lauryl phosphate, sodium lauryl sulphate, sodium oleyl phosphate, sodium myristyl sulphate, polyoxyethylene alkyl ethers, polyoxyethylene alkyl esters, and caproic acid, alkylsaccharide, fusidic acid, polyethylene glycol, cetyl alcohol, polyvinylpyrolidone, Polyvinyl alcohol, Lanolin alcohol, Sorbitan monooleate, Ethylene glycol tetraacetic acid, Bile acid conjugate with taurine, Cholanic acid and salts, Cyclodextran, Cyclodextrin, Cyclodextrin (beta), Hydroxypropyl-β-cyclodetran, Sulfobutylether-β-cyclodextran, Methyl-β-cyclodextrin, Chitosan glutamate, Chitosan acetate, Chitosan hydrochloride, Chitosan hydrolactate, 1-O-alkyl-2-hydroxy-sn-glycero-3-phosphocholine, 3-O-alkyl-2-acetoyl-sn-glycero-1-phosphocholine, 1-O-alkyl-2-O-acetyl-sn-glycero-3-phospho(N,N,N-trimethyl)hexanolamine, Propylene glycol, Tetradecylmaltoside (TDM), Sucrose dedecanoate.

(19) According to an embodiment of the invention, the enhancer comprises one or more pH control agent, such as a buffering agent.

(20) In an embodiment of the invention, said pH control agents are selected from the group consisting of Acetic acid, Adipic acid, Citric acid, Fumaric acid, Glucono-δ-lactone, Gluconic acid, Lactic acid, Malic acid, Maleic acid, Tartaric acid, Succinic acid, Propionic acid, Ascorbic acid, Phosphoric acid, Sodium orthophosphate, Potassium orthophosphate, Calcium orthophosphate, Sodium diphosphate, Potassium diphosphate, Calcium diphosphate, Pentasodium triphosphate, Pentapotassium triphosphate, Sodium polyphosphate, Potassium polyphosphate, Carbonic acid, Sodium carbonate, Sodium bicarbonate, Potassium carbonate, Calcium carbonate, Magnesium carbonate, Magnesium oxide, or any combination thereof.

(21) According to an embodiment of the invention, the water-insoluble composition comprises cellulose, e.g. as a carrier.

(22) In an embodiment of the invention the cellulose is or comprises microcrystalline cellulose.

(23) One advantage of the above embodiment may be that microcrystalline cellulose may absorb a relatively high amount of cannabinoid, while also allowing for the one or more cannabinoids to be effectively released from the pouch during use.

(24) The cellulose may be synthetic or semisynthetic celluloses, or it may be derived from natural celluloses. It is normally crystalline such as microcrystalline. Certain specific embodiments may also utilize other forms of carriers, in addition to or including mcc, such as but not limited to fibrous material or carbohydrates including cellulose (including hemicellulose, celluloses with different crystallinities and structures (e.g. varying structures including solid fibers, and addition or including fibers or the like in various structures such as web-like structures and/or other structures), including naturally occurring celluloses including Cladophora sp. Algae cellulose or the like), dextran, agarose, agar, pectin, alginate, xanthan, chitosan, starch (including potato starch, shoti starch) etc. or mixtures thereof.

(25) The microcrystalline cellulose may be selected from the group consisting of AVICEL® grades PH-100, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300, PH-302, VIVACEL® grades 101, 102, 12, 20 and EMOCEL® grades 50M and 90M, and the like, and mixtures thereof.

(26) In an embodiment of the invention said cellulose is provided in the form of particles having an average particle size between 1 and 1000 micrometers, such as between 10 and 250 micrometers, such as between 15 and 200 micrometers, such as between 20 and 150 micrometers, such as between 50 and 100 micrometers, such as about 75 micrometers.

(27) In an embodiment of the invention said cellulose has a specific surface area of between 0.65 and 1.5 m.sup.2/g, such as between 0.75 and 1.25 m.sup.2/g, such as between 0.85 and 1.15 m.sup.2/g, such as between 0.9 and 1.1 m.sup.2/g, such as about 0.95 m.sup.2/g, about 1.00 m.sup.2/g, or such as about 1.05 m.sup.2/g.

(28) In an embodiment of the invention said cellulose has a bulk density between 0.1 and 1.0 grams per cubic centimeter (g/cm.sup.3), such as between 0.25 and 0.5 grams per cubic centimeter, such as between 0.26 and 0.31 grams per cubic centimeter, or such as between 0.28 and 0.33 grams per cubic centimeter.

(29) In the context of the above embodiment it should preferably be understood that the bulk density of the cellulose is understood as the bulk density at about 25 degrees Celsius.

(30) In an embodiment of the invention said cellulose has a porosity characterized by an average specific pore volume between 0.003 cm.sup.3/g and 0.60 cm.sup.3/g, such as between 0.01 and 0.3 cm.sup.3/g.

(31) In an embodiment of the invention said cellulose has a moisture content of less than about 5% by weight, such as between 2 and 5% by weight, such as between 3 and 5% by weight, such as about 4% by weight.

(32) Various types of usable cellulose includes microcrystalline cellulose (MCC); carboxymethylcellulose (CMC), such as sodium carboxymethylcellulose; hydroxypropyl methylcellulose (HPMC); methylcellulose; ethylcellulose (EC); methylethylcellulose (MEC); hydroxyethyl cellulose (HEC); hydroxyethyl methylcellulose (HEMC); and any combination thereof.

(33) In an embodiment of the invention said cellulose has an average fiber size of less than 200 micrometers, such as between 75 and 125 micrometers, or such as below 75 micrometers.

(34) In an embodiment of the invention the cellulose comprises pores, the pores having an average pore size of between about 3 nanometers and about 300 nanometers, such as between 10 nanometers and 200 nanometers, such as between 20 nanometers and 100 nanometers.

(35) In an embodiment of the invention said cellulose is derived from natural sources, such as wood pulp.

(36) Other examples of natural sources of cellulose include sugar beet fiber, cotton fiber, bran fiber, citrus pulp fiber, grass fiber, willow fiber, poplar fiber, bamboo fiber, and combinations thereof, or combinations thereof with wood pulp.

(37) In some embodiments, the cellulose can be chemically treated, e.g. by means of CMC, MPMC, HPC, MCC, and/or other methods.

(38) Alternatively, the cellulose may be semi-synthetic or synthetic cellulose.

(39) According to an embodiment of the invention the water-insoluble composition comprises an ion-exchange resin, such as a basic ion-exchange resin, e.g. a strongly basic ion-exchange resin.

(40) The ion-exchange resin, such as the basic ion-exchange resin, of the water-insoluble composition may be part of the carrier when the matrix composition comprises a carrier.

(41) The one or more cannabinoids may, especially when using a basic ion-exchange resin, be selected from the cannabinoids having at least one phenolic moiety. By using cannabinoid(s) having at least one phenolic moiety, the basic group of the basic ion exchange resin has one or more groups on the cannabinoid(s) to bind with. The cannabinoid(s) may in some embodiment optionally comprise one or more carboxylic groups, thus adding to the potential binding sites for the basic ion exchange resin.

(42) In an embodiment of the invention the ion exchange resin(s) acts as a stabilization agent.

(43) One very important advantage of the above embodiment may be that the amount of cannabinoid(s) available for body uptake is advantageously preserved due to the stabilization of the cannabinoid(s).

(44) In an advantageous embodiment of the invention the basic ion exchange resin comprises strongly basic ion exchange resin.

(45) One advantage of the above embodiment may be that a relatively effective stabilization of the cannabinoid(s) may be achieved, while synchronized release of the cannabinoid(s) from the complex, i.e. synchronized with the intended time of delivery to the body may be achieved, e.g. in one embodiment by adding an acid to the pouch.

(46) In an advantageous embodiment of the invention the basic ion exchange resin is strongly basic ion exchange resin.

(47) One advantage of the above embodiment may be that a relatively effective stabilization of the cannabinoid(s) may be achieved, while synchronized release of the cannabinoid(s) from the complex, i.e. synchronized with the intended time of delivery to the body may be achieved, e.g. in one embodiment by adding an acid to the pouch.

(48) In an advantageous embodiment of the invention the basic ion exchange resin comprises weakly basic ion exchange resin.

(49) One advantage of the above embodiment may be that a relatively effective release of the cannabinoid(s) from the complex may be obtained, in some embodiments without using any agents, such as acids, for facilitating release of the cannabinoid(s) from the complex.

(50) In an advantageous embodiment of the invention said basic ion exchange resin is a strongly basic ion exchange resin comprising one or more quaternary amino groups.

(51) Examples of strongly basic ion exchange resins include for example commercially available products, such as Ambersep® 900, Cholestyramine, and Duolite AP143.

(52) In an advantageous embodiment of the invention the basic ion exchange resin are selected from the group consisting of Ambersep 900, Cholestyramine, Duolite AP143, Amberlite CG-400, Amberlite IRA-400, Amberlite IRA-401, Amberlite IRA-410, Amberlite IRA-900, and Amberlite IRA-904.

(53) In an advantageous embodiment of the invention the basic ion exchange resin comprises cross-linked polystyrene.

(54) In an advantageous embodiment of the invention the basic ion exchange resin comprises cross-linked polystyrene, wherein the cross-linking agent comprises or is divinylbenzene.

(55) In an advantageous embodiment of the invention the basic ion exchange resin comprises a styrene-divinylbenzene copolymer.

(56) According to an embodiment of the invention, the basic ion exchange resin is a styrene-divinylbenzene copolymer functionalized by basic groups, such as amine groups. If a strongly basic ion exchange resin is desirable, strongly basic functional groups, such as quaternary amines, are used; whereas if a weakly basic ion exchange resin is desirable, weakly basic functional groups, such a primary, secondary, or tertiary amine groups, are used.

(57) In an advantageous embodiment of the invention the basic ion exchange resin has a counter ion selected from the group consisting of hydroxide, chloride, and bromide, before reaction with the one or more cannabinoids.

(58) According to various embodiments of the invention, sugar alcohols may be included in the pouch as a matrix composition or part thereof as a humectant, or as a sweetener. Suitable sugar alcohols include sugar alcohols selected from the group of sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, hydrogenated starch hydrolyzates, isomalt, or any combination thereof.

(59) In an embodiment of the invention the pouch comprises high intensity sweetener.

(60) Preferred high intensity sweeteners include, but are not limited to sucralose, aspartame, salts of acesulfame, such as acesulfame potassium, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, stevioside and the like, alone or in combination.

(61) In an embodiment of the invention, the pouch comprises bulk sweeteners including sugar and/or sugarless components.

(62) In an embodiment of the invention, the pouch comprises bulk sweetener in the amount of 5 to about 95% by weight of the pouch, more typically constitute 20 to about 80% by weight of the pouch, and more commonly, 30 to 60% by weight of the pouch. Bulk sweeteners may function both as a sweetener and also as a humectant.

(63) The sweeteners may often support the flavor profile of the pouch.

(64) Sugar sweeteners generally include, but are not limited to saccharide-containing components commonly known in the art of pouches, such as sucrose, dextrose, maltose, saccharose, lactose, sorbose, dextrin, trehalose, D-tagatose, dried invert sugar, fructose, levulose, galactose, corn syrup solids, glucose syrup, hydrogenated glucose syrup, and the like, alone or in combination. These sugar sweeteners may also be included as a humectant.

(65) The sweetener can be used in combination with sugarless sweeteners. Generally, sugarless sweeteners include components with sweetening characteristics but which are devoid of the commonly known sugars and comprise, but are not limited to, sugar alcohols, such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolyzates, maltitol, isomalt, erythritol, lactitol and the like, alone or in combination. These sugarless sweeteners may also be included as a humectant.

(66) In an embodiment of the invention the pouch comprises flavor. Flavor may typically be present in amounts between 0.01 and 10% by weight of the total composition of the pouch, such as between 0.01 and 5% by weight of the total composition.

(67) Non-exhaustive examples of flavors suitable in embodiments of the present invention are 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.

(68) In various embodiments of the invention, the matrix composition comprises a release controlling composition for controlling the release of the matrix composition and/or parts thereof, especially the one or more cannabinoids.

(69) The release controlling composition may, according to various embodiments, be selected group consisting of metallic stearates, modified calcium carbonate, hydrogenated vegetable oils, partially hydrogenated vegetable oils, polyethylene glycols, polyoxyethylene monostearates, animal fats, silicates, silicates dioxide, talc, magnesium stearates, calcium stearates, fumed silica, powdered hydrogenated cottonseed oils, hydrogenated vegetable oils, hydrogenated soya oil and mixtures thereof. Particularly, metallic stearates, such as magnesium stearate may be advantageous.

(70) According to an embodiment of the invention said modified calcium carbonate is made according to US patent application US 2012/0039981 A1, hereby incorporated by reference, particularly as in the examples therein.

(71) The release controlling composition may be added to the matrix composition in various ways.

(72) For example, the release controlling composition may be added by full powder mixture during the last few minutes of the final mixing.

(73) Alternatively, the release controlling composition may be added after the granulation steps on a granulation premix.

(74) Still further, the release controlling composition may be added only as a fraction of the matrix composition so two different release profiles of cannabinoids are achieved. Even further two or more fractions of the matrix composition may comprise different amounts of the release controlling composition, if any, thereby providing a more complex and tailored release profile of cannabinoids.

(75) The release controlling composition, such as magnesium stearate, may have a sealing effect and can be used to control the release of the one or more cannabinoids and the solubility of the matrix composition.

(76) According to an embodiment of the invention, the pouch comprises polyvinylpyrrolidone (PVP).

(77) One advantage of the above embodiment may be that a more uniform composition may be obtained.

EXAMPLES

(78) The following examples are illustrative of the present invention and should not be considered as limiting the scope of the invention.

(79) Examples 1-3 illustrate various raw materials and methods for preparing intermediate ingredients.

(80) Examples 4-8 discloses a number of different pouches and their respective compositions.

Example 1

(81) Preparation of Cannabinoid Powder Composition

(82) Cannabinoids come in different grades and form from pasta, oil and crystals and in different concentrations. Depending on the form of cannabinoids the manufacturing steps will vary.

(83) As illustrated in the following examples, cannabinoids can be added as powder or sorbed, mixed or granulated on different carriers as microcrystalline cellulose (MCC) or sugar alcohols etc.

Example 2

(84) Preparation of Pouches Designed for Administration of Cannabinoids

(85) The material of the pouches is heat sealable non-wowen cellulose.

(86) The powder is filled into pouches and is maintained in the pouch by a sealing.

Example 3

(87) Preparation of Pouches with Water-Insoluble Composition

(88) Cannabinoids used in example 3 are obtained in accordance with example 1, The pouches described in example 2 are used.

(89) Herein, target fill weight 400 mg powder per pouch. Alternatively, target fill weights of e.g. 250 mg or 800 mg could be used.

Example 3.1

(90) The cannabinoids are dissolved in ethanol with a weight ratio of about 1:1 to form a homogeneous granulation solution. The granulation solution is slowly added to the microcrystalline cellulose under stirring (Kitchenaid mixer operated at about 30 RPM in about 30 minutes). The resulting granulate is sieved and placed on a tray. The resulting powder is dried at ambient temperature overnight and is thereafter sieved.

(91) A fine-grained powder of cannabinoids-microcrystalline cellulose carrier complex was obtained.

(92) The obtained cannabinoids-microcrystalline cellulose carrier complex is mixed with the remaining ingredients to obtain a final powder composition.

(93) The final powder composition is manually filled into pouches (target fill weight 400 mg powder per pouch). The pouch of example 2, made from long fiber paper, is used.

(94) Magnesium stearate, if any, is added by full powder mixture during the last few minutes of the final mixing. When including smaller amounts of further humectants, apart from e.g. MCC and/or sugar alcohols, these further humectants are added in the same manner as magnesium stearate.

Example 3.2

(95) The cannabinoids are dissolved in ethanol with a weight ratio of about 1:1 and the Kollidon 25 (polyvinylpyrrolidone) is added together with the liquid flavor to form a homogeneous granulation solution.

(96) The following solid components are mixed and sieved to form a powder mixture: mannitol, MCC, high intensive sweetener and flavors.

(97) The granulation solution is slowly added to the powder mixture under stirring (Kitchenaid mixer operated at about 30 RPM in about 30 minutes). The resulting granulate is sieved and placed on a tray. The resulting powder is dried at ambient temperature overnight and is thereafter sieved to obtain a final powder composition.

(98) The final powder composition is manually filled into pouches (target fill weight 400 mg powder per pouch). The pouch of example 2, made from long fiber paper, is used.

(99) Magnesium stearate, if any, is added by full powder mixture during the last few minutes of the final mixing. When including smaller amounts of further humectants, apart from e.g. MCC and/or sugar alcohols, these further humectants are added in the same manner as magnesium stearate.

Example 3.3

(100) The ion exchange resin complex is made by dissolving the cannabinoids (882 g CBD) in 88 L ethanol to form a homogeneous solution, NaOH can be added to make the binding of the cannabinoid(s) and the ion-exchange resin better.

(101) 5 kg of ion exchange resin (Ambersep 900 on OH-form) is added. When all the CBD solution has been bound by the ion exchange resin the pressure is reduced and the obtained mixture is concentrated in vacuo at elevated temperature affording the desired complex as a powder.

(102) The obtained powder is mixed with the remaining ingredients to obtain a final powder composition. An acid like citric acid can be added to increase the release of the cannabinoid(s) from the resin during usage.

(103) The final powder composition is manually filled into pouches (target fill weight 400 mg powder per pouch). The pouch of example 2, made from long fiber paper, is used.

(104) Magnesium stearate, if any, is added by full powder mixture during the last few minutes of the final mixing. When including smaller amounts of further humectants, apart from e.g. sugar alcohols, these further humectants are added in the same manner as magnesium stearate.

(105) Glycerin may also be added, for example in amounts giving a ratio of glycerin to ion exchange resin of about 1 to 3.4.

Example 3.4

(106) A powder composition obtained the same way as the final powder competition in example 3.3. Thereafter, polyvinylpyrrolidone (Kollidon 25) is added to form a granulation solution. The resulting granulate is sieved and placed on a tray. The resulting powder is dried at ambient temperature overnight and is thereafter sieved to obtain a final powder composition.

(107) The final powder composition manually filled into pouches (target fill weight 400 mg powder per pouch). The pouch of example 2, made from long fiber paper, is used.

(108) Magnesium stearate, if any, is added by full powder mixture during the last few minutes of the final mixing. When including smaller amounts of further humectants, apart from e.g. sugar alcohols, these further humectants are added in the same manner as magnesium stearate.

Example 4

(109) Preparation of Pouches with Water-Insoluble Composition

(110) TABLE-US-00001 TABLE 1 Cannabinoid pouch; CBD used is a 50% extract. Pouch no. 101 102 103 104 105 106 107 Method cf. example 3.1 3.1 3.2 3.3 3.3 3.4  3.4** Raw material Content in weight percent CBD extract 5.00* 5.00* 5.00* 5.00* 5.00* 5.00*  5.00* NaOH — — — — — — 0.60 Citric acid — — — — — — 0.70 Mannitol 43.45 73.45 65.45 43.45 73.45 65.45 64.15  MCC 50.00 20.00 20.00 — — — — Ion exchange resin — — — 50.00 20.00 20.00 20.00  Flavor 1.50 1.50 1.50 1.50 1.50 1.50 1.50 HIS 0.05 0.05 0.05 0.05 0.05 0.05 0.05 PVP — — 8.00 — — 8.00 8.00 Total 100 100 100 100 100 100 100    *5% CBD corresponds to 10 mg CBD/pouch. Pouches contain 400 mg per piece. MCC is microcrystalline cellulose. Ion exchange resin is an Ambersep 900 on OH-form. HIS = High intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. PVP = polyvinylpyrrolidone, Kollidon 25.

(111) As shown in table 1, different water-insoluble compositions may be used, including MCC and ion-exchange resin, and in different amounts. Possible inclusion of PVP is also shown, as well as inclusion of base (here NaOH) and acid (here citric acid) when using ion exchange resin.

Example 5

(112) Preparation of Pouched with Magnesium Stearate

(113) TABLE-US-00002 TABLE 2 Cannabinoid pouch; CBD used is a 50% extract. Pouch no. 108 109 110 Method cf. example 3.1 3.3 3.4 Raw material Content in weight percent CBD extract 5.00* 5.00* 5.00* Mannitol 63.45 63.45 55.45 MCC 20.00 — — Ion exchange resin — 20.00 20.00 Flavor 1.50 1.50 1.50 HIS 0.05 0.05 0.05 PVP — — 8.00 MgSt 10.00 10.00 10.00 Total 100 100 100 *5% CBD corresponds to 10 mg CBD/pouch. Pouches contain 400 mg per piece. MCC is microcrystalline cellulose. Ion exchange resin is an Ambersep 900 on OH— form. HIS = High intense sweetener may for example be sucralose. Flavor may for example be peppermint flavor. PVP = polyvinylpyrrolidone, Koliidon 25. MgSt is magnesium stearate and is added as a release controlling composition.

(114) As shown in table 2, magnesium stearate (MgSt) can be included in the pouch in combination with both MCC and ion exchange resin. Magnesium stearate has a sealing effect and can be used to control the release of CBD and the solubility of the matrix composition. PVP may also be included.

Example 6

(115) Preparation of Pouched with Different Cannabinoids and Different Purifications

(116) TABLE-US-00003 TABLE 3 Cannabinoid pouch; CBD used corresponds to 10 mg CBD/pouch. Pouch no. 111 112 113 114 115 Method cf. example 3.1 3.1 3.1 3.1 3.1 Raw material Content in weight percent CBD pure (99.5%) 2.51 — — — 2.51 CDB extract (50%) — 5.00 — — — CDB extract (10%) — — 25.00 — — THC pure (99.5%) — — — 2.51 2.51 Mannitol 75.94 73.45 53.45 75.94 68.43 MCC 20.00 20.00 20.00 20.00 20.00 Flavor 1.50 1.50 1.50 1.50 1.50 HIS 0.05 0.05 0.05 0.05 0.05 MgSt — — — — 5 Total 100 100 100 100 100 THC used corresponds to 10 mg THC/pouch. Pouches contain 400 mg per piece. MCC is microcrystalline cellulose. HIS = High intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. MgSt is magnesium stearate and is added as a releasing agent.

(117) As shown in table 3, different cannabinoids, CBD and THC, may be used. Also, different concentrations of the cannabinoids may be used, here illustrated as 10% extract, 50% extract, or 99.5% pure cannabinoids. Finally, different cannabinoids may be combined, here shown by a combination of CBD and THC.

Example 7

(118) Preparation of Pouches with Different Concentrations of Cannabinoids when Using Pure CBD (99.5%):

(119) TABLE-US-00004 TABLE 4 Cannabinoid pouch; CBD is used in different dosage from 5-100 mg CBD/pouch - CBD extract of 99.5% has been used. Pouch no. 116 117 118 119 120 Method cf. example 3.2 3.2 3.2 3.2 3.2 Amount of cannabinoids 5 mg 10 mg 20 mg 50 mg 100 mg Raw material Content in weight percent CDB 1.26 2.51 5.03 12.56 25.13 Isomalt 64.19 62.94 60.42 42.89 30.32 MCC 20.00 20.00 20.00 30.00 30.00 Flavor 1.50 1.50 1.50 1.50 1.50 HIS 0.05 0.05 0.05 0.05 0.05 PVP 8.00 8.00 8.00 8.00 8.00 MgSt 5.00 5.00 5.00 5.00 5.00 Total 100 100 100 100 100 Pouches contain 400 mg per piece. MCC is microcrystalline cellulose. HIS = High intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. MgSt is magnesium stearate and is added as a releasing agent. PVP = polyvinylpyrrolidone, Kollidon 25. CBD could be replaced with THC or be in combination with THC.
When Using CBD (50% Pure):

(120) TABLE-US-00005 TABLE 5 Cannabinoid pouch; CBD is used in different dosage from 5-100 mg CBD/pouch - CBD extract of 50% has been used. Pouch no. 121 122 123 124 125 Method cf. example 3.2 3.2 3.2 3.2 3.2 Amount of cannabinoids 5 mg 10 mg 20 mg 50 mg 100 mg Raw material Content in weight percent CDB 2.50 5.00 10.00 25.00 50.00 Isomalt 62.95 60.45 55.45 30.45 5.45 MCC 20.00 20.00 20.00 30.00 30.00 Flavor 1.50 1.50 1.50 1.50 1.50 HIS 0.05 0.05 0.05 0.05 0.05 PVP 8.00 8.00 8.00 8.00 8.00 MgSt 5.00 5.00 5.00 5.00 5.00 Total 100 100 100 100 100 Pouches contain 400 mg per piece. MCC is microcrystalline cellulose. HIS = High intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. MgSt is magnesium stearate and is added as a releasing agent. PVP = polyvinylpyrrolidone, Kollidon 25. CBD could be replaced with THC or be in combination with THC.

(121) As shown in tables 4-5, different total amounts of cannabinoids (here CBD) may be used in the pouch, regardless of using relatively pure cannabinoids or if using an extract comprising other components.

Example 8

(122) Preparation of Pouches with Different Humectants

(123) TABLE-US-00006 TABLE 6 Cannabinoid pouch; CBD used is a 50% extract. Pouch no. 126 127 128 129 Method cf. example 3.1 3.1 3.1 3.1 Raw material Content in weight percent CBD extract 5.00* 5.00* 5.00* 5.00* Isomalt 73.45 71.45 71.45 71.45 MCC 20.0 20.0 20.0 20.0 Flavor 1.50 1.50 1.50 1.50 HIS 0.05 0.05 0.05 0.05 Glycerol — 2.00 — — Sodium alginate — — 2.00 — Pectin — — — 2.00 Total 100 100 100 100 *5% CBD corresponds to 10 mg CBD/pouch. Pouches contain 400 mg per piece. MCC is microcrystalline cellulose. HIS = High intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. Glycerol, sodium alginate and pectin are action as moistening or lubricant agent.

(124) As shown in table 6, different further humectants may be added. Humectants attract the saliva from the mouth and make sure that water is available in the pouch. Increased water increase the release.

Example 9

(125) Evaluation

(126) The pouches produced were evaluated and found highly suitable as delivery vehicles for cannabinoids.