GELLED OIL-IN-WATER EMULSION COMPRISING AT LEAST ONE CANNABINOID

Abstract

The invention relates to compositions for oral administration which contain at least one cannabinoid, to methods for their preparation and to their use as pharmaceuticals or nutraceuticals. In particular, it relates to orally administrable, gelled oil-in-water emulsions which are self-supporting, viscoelastic solids having a gelled aqueous phase and an oil phase which comprises one or more physiologically tolerable lipids and at least one cannabinoid.

Claims

1. An orally administrable, gelled oil-in-water emulsion which is a self-supporting, viscoelastic solid having a gelled aqueous phase and an oil phase which comprises one or more physiologically tolerable lipids and at least one cannabinoid.

2. An orally administrable, gelled oil-in-water emulsion as claimed in claim 1, wherein said at least one cannabinoid is selected from tetrahydrocannabinols, tetrahydrocannabinolic acids, cannabidiol, cannabidiolic acid, cannabigerol, cannabigerolic acid, cannabigerovarin, cannabigerovarinic acid, cannabichromene, cannabichromenic acid, cannabidivarin, cannabidivarinic acid, cannabivarin, cannabivarinic acid, tetrahydrocannabivarin, tetrahydrocannabivarinic acid, cannabinol, cannabinolic acid, cannabinodiol, cannabielsoin, cannabicyclol, cannabicitran, isomers thereof, and mixtures thereof.

3. An orally administrable, gelled oil-in-water emulsion as claimed in claim 1 or claim 2, wherein said at least one cannabinoid is selected from a tetrahydrocannabinol (e.g. a delta-9-tetrahydrocannabinol) and/or a cannabidiol.

4. An orally administrable, gelled oil-in-water emulsion as claimed in any one of the preceding claims, wherein said one or more physiologically tolerable lipids are derived from rapeseed oil, sunflower oil, corn oil, olive oil, sesame oil, palm kernel oil, coconut oil, a nut oil, or hemp oil.

5. An orally administrable, gelled oil-in-water emulsion as claimed in any one of the preceding claims, wherein said one or more physiologically tolerable lipids are fatty acids or derivatives thereof, e.g. the carboxylic esters, carboxylic anhydrides, glycerides (i.e. mono-, di-, or triglycerides) and phospholipids.

6. An orally administrable, gelled oil-in-water emulsion as claimed in claim 5, wherein said fatty acids or derivatives thereof have a saturated or unsaturated hydrocarbon chain comprising from 4 to 28 carbon atoms, preferably from 6 to 12 carbons.

7. An orally administrable, gelled oil-in-water emulsion as claimed in claim 6, wherein said fatty acids or derivatives thereof have a saturated hydrocarbon chain.

8. An orally administrable, gelled oil-in-water emulsion as claimed in claim 7, wherein said fatty acids or derivatives thereof have from 8 to 12, e.g. 8, 10 or 12, carbon atoms in the hydrocarbon chain.

9. An orally administrable, gelled oil-in-water emulsion as claimed in claim 5 or claim 6, wherein said fatty acids or derivatives thereof have an unsaturated hydrocarbon chain.

10. An orally administrable, gelled oil-in-water emulsion as claimed in claim 9, wherein said fatty acids are ω-3, ω-6 or ω-9 fatty acids, or derivatives thereof.

11. An orally administrable, gelled oil-in-water emulsion as claimed in any one of claims 5 to 10, wherein said fatty acid derivatives are glycerides, preferably triglycerides.

12. An orally administrable, gelled oil-in-water emulsion as claimed in claim 11, wherein said fatty acid derivatives are medium-chain triglycerides having two or three medium-chain fatty acids which may be identical or different, preferably fatty acids having 6 to 12 carbon atoms, e.g. 8 or 10 carbons.

13. An orally administrable, gelled oil-in-water emulsion as claimed in any one of the preceding claims, wherein said oil phase constitutes from 5 to 85 wt. %, preferably from 20 to 50 wt. % of the emulsion.

14. An orally administrable, gelled oil-in-water emulsion as claimed in any one of the preceding claims, wherein the oil phase is dispersed in the gelled aqueous phase in the form of oil droplets having a diameter in the range from 10 nm to 100 μm.

15. An orally administrable, gelled oil-in-water emulsion as claimed in claim 14, wherein the oil droplets have an average diameter in the range from 100 nm to 1 μm.

16. An orally administrable, gelled oil-in-water emulsion as claimed in any one of the preceding claims, wherein said aqueous phase comprises a physiologically tolerable gelling agent selected from alginates, pectins, carrageenans, gelatin, gellan gum and agar.

17. An orally administrable, gelled oil-in-water emulsion as claimed in claim 16, wherein the gelling agent is gelatin.

18. An orally administrable, gelled oil-in-water emulsion as claimed in claim 17, wherein the gelatin is present in the aqueous phase at a concentration of 5 to 25 wt. % based on the weight of the aqueous phase.

19. An orally administrable, gelled oil-in-water emulsion as claimed in any one of the preceding claims, wherein the aqueous phase constitutes from 15 to 95 wt. %, preferably from 50 to 80 wt. %, of the emulsion.

20. An orally administrable, gelled oil-in-water emulsion as claimed in any one of the preceding claims, wherein the aqueous phase further comprises one or more bulking agents, for example sugar alcohols.

21. An orally administrable, gelled oil-in-water emulsion as claimed in claim 20, wherein said bulking agents are present at a concentration of from 45 to 70 wt. %, preferably 50 to 65 wt. %, e.g. 55 to 60 wt. %, based on the aqueous phase.

22. An orally administrable, gelled oil-in-water emulsion as claimed in any one of the preceding claims which further comprises an oromucosal uptake enhancer.

23. An orally administrable, gelled oil-in-water emulsion as claimed in claim 22, wherein said oromucosal uptake enhancer is a cationic polymer, preferably chitosan or a chitosan derivative.

24. An orally administrable, gelled oil-in-water emulsion as claimed in any one of the preceding claims which is provided in unit dose form.

25. An orally administrable, gelled oil-in-water emulsion as claimed in claim 24, wherein said unit dose form is uncoated.

26. A package comprising an air-tight and light-tight compartment containing one dose unit of the gelled oil-in-water emulsion as claimed in claim 24 or claim 25.

27. A method for the preparation of an orally administrable, gelled oil-in-water emulsion as claimed in any one of claims 1 to 25, said method comprising the steps of: forming an oil phase which comprises one or more physiologically tolerable lipids and at least one cannabinoid; forming an aqueous phase comprising a physiologically tolerable gelling agent; combining said oil phase and said aqueous phase to form an oil-in-water emulsion; and allowing said emulsion to gel.

28. A method for the preparation of an orally administrable, gelled oil-in-water emulsion as claimed in any one of claims 1 to 25, said method comprising the steps of: forming an oil phase which comprises one or more physiologically tolerable lipids; forming an aqueous phase comprising a physiologically tolerable gelling agent; combining said oil phase, said aqueous phase and at least one cannabinoid to form an oil-in-water emulsion; and allowing said emulsion to gel.

29. A gelled oil-in-water emulsion as claimed in any one of claims 1 to 25 for oral use as a medicament or for oral use in therapy.

30. A gelled oil-in-water emulsion as claimed in any one of claims 1 to 25 for oral use in the treatment of a condition responsive to a cannabinoid.

31. A gelled oil-in-water emulsion for use as claimed in claim 30, wherein said condition is selected from pain (e.g. cancer pain, arthritis pain), inflammation, neurological disorders, mood disorders (e.g. anxiety), epilepsy, sleep disorders, the symptoms of multiple sclerosis, anorexia, schizophrenia, inflammatory bowel disease (e.g. Crohn's disease and ulcerative colitis), and chemotherapy-induced nausea.

32. A gelled oil-in-water emulsion for use as claimed in claim 30, wherein said condition is selected from chronic pain (e.g. musculoskeletal pain) and chronic inflammatory diseases (e.g. rheumatoid arthritis and osteoarthritis).

33. Use of a gelled oil-in-water emulsion as claimed in any one of claims 1 to 25 as a nutraceutical.

34. Use of a gelled oil-in-water emulsion as claimed in claim 33 to reduce the symptoms of anxiety, to reduce menopause symptoms, to treat insomnia, to reduce menstrual symptoms (e.g. menstrual cramps), to prevent or treat nausea, to stimulate appetite, or for use as a muscle relaxant.

Description

[0156] The invention will now be described further with reference to the following non-limiting Examples and the accompanying figures in which:

[0157] FIG. 1: Droplet size distribution for the emulsions prepared in Examples 24 to 27.

[0158] FIG. 2: Droplet size distribution for the emulsions of Examples 24 and 27. These have the same composition but differ only in mixing speed used in their preparation.

[0159] FIG. 3: Influence of mixing speed of the Ultra-turrax® unit on the average volume-based (D[4,3]) droplet size for the emulsions in Examples 24 to 27.

EXAMPLES

[0160] Materials:

[0161] Unless otherwise specified, the gelatin is a Type A or Type B gelatin. Unless otherwise specified, it may have a bloom value of 150.

[0162] The MCT oil is based on coconut oil from Cocos nucifera supplied Henry Lamotte Oils GmbH, and has the following fatty acid composition (% given by weight):

TABLE-US-00001 Caproic acid (C 6:0) 0.1% Caprylic acid (C 8:0) 55.0% Capric acid (C 10:0) 44.8% Lauric acid (C 12:0) 0.1% Myristic acid (C 14:0) 0.0%

[0163] “Hemp oil” is CBD standardised hemp oil containing 3.832 wt. % CBD, 99.5% pure by HPLC (THC content <0.25) supplied by Hempro Int. GmbH & Co. KG.

Examples 1 to 4

Gelled Oil-in-Water Emulsions Containing CBD

[0164] Gelled oil-in-water emulsions having the compositions set out in Table 1 were made by adding the gelatin to the water and heating the solution to 70° C. with stirring for 10 minutes. The sorbitol and xylitol were added stepwise to the mixture, followed by the sodium citrate. Heating and stirring was continued between each addition to ensure full dissolution and the temperature was maintained between 50-75° C. After approx. 15 minutes, the resultant solution was degassed under vacuum to remove air bubbles. At a temperature of about 55° C. the malic acid was added and dissolved in the mixture. Colour and flavouring agents and the oil containing the CBD was added to the resulting aqueous phase with stirring and homogenized into the mixture using a commercially available Ultra-Turrax® unit. The resulting emulsion was once again degassed under vacuum to remove air bubbles. Whilst still liquid, the warm emulsion was filled into pre-formed cavities in a suitable packing material, sealed and allowed to set to form a gel at room temperature.

TABLE-US-00002 TABLE 1 Composition of gelled oil-in-water emulsions containing CBD Example 1 Example 2 Example 3 Example 4 Dose size (mg) 1500 1500 1500 1500 wt. % wt. % wt. % wt. % Oil Hemp oil 16.6 16.6 Sunflower oil 16.6 10 25.867 25.867 Active/dose CBD 0.733 0.733 mg/dose 9.54 9.54 10 10 Water 18.6 20.6 20.6 20.6 Gelatin Bovine type B 7.07 7.4 7.4 7.4 Fish 195 bloom type A Sugar Sorbitol 11.01 12.5 12.5 12.5 alcohols Xylitol 26 28.78 28.68 28.73 Buffer salts Sodium citrate 1.8 1.8 1.8 1.8 Malic acid 0.92 0.92 0.92 0.92 Colour Betacarotene 0.5 0.5 0.5 0.5 Flavour Lemon 0.9 0.9 0.9 Lemon/Lime 0.9 Peppermint 0.1 0.05 Total 100 100 100 100 Mixing conditions “Normal” “Normal” “Normal” “Normal” Ultra-turrax ® setting/minutes 2/7 2/7 2/7 2/7

Example 5

Gelled Oil-in-Water Emulsion with 10 wt. % Oil Phase

[0165] Water: 25.35 wt. %

[0166] Gelatin: 9 wt. %

[0167] Sorbitol: 15 wt. %

[0168] Xylitol: 36.57 wt. %

[0169] Trisodium citrate: 2.7 wt. %

[0170] Malic acid: 1.38 wt. %

[0171] MCT oil containing 10 mg CBD: 10 wt. %

[0172] The gelatin is added to the water and the solution is then heated to about 70° C. with stirring for 10 minutes. The sorbitol and xylitol are then added stepwise to the mixture, followed by the trisodium citrate. Heating and stirring is continued between each addition to ensure full dissolution and the temperature is maintained between 50-75° C. The resultant solution is degassed under vacuum to remove air bubbles. At a temperature of about 55° C. the malic acid is added and dissolved in the mixture.

[0173] The MCT oil containing the CBD is added to the resulting aqueous phase with stirring, and homogenized into the mixture using a commercially available Ultra-Turrax unit. The resulting emulsion is once again degassed under vacuum to remove air bubbles.

[0174] Whilst still liquid, the warm emulsion is filled into pre-formed cavities in a suitable packing material, sealed and allowed to set to form a gel at room temperature.

Example 6

Gelled Oil-in-Water Emulsion with 20 wt. % Oil Phase

[0175] A gelled oil-in-water emulsion with the following composition is prepared analogously to Example 5:

[0176] Water: 22.53 wt. %

[0177] Gelatin: 8 wt. %

[0178] Sorbitol: 13.33 wt. %

[0179] Xylitol: 32.51 wt. %

[0180] Trisodium citrate: 2.4 wt. %

[0181] Malic acid: 1.23 wt. %

[0182] MCT oil containing 10 mg CBD: 20 wt. %

Example 7

Gelled Oil-in-Water Emulsion with 30 wt. % Oil Phase

[0183] A gelled oil-in-water emulsion with the following composition is prepared analogously to Example 5:

[0184] Water: 19.72 wt. %

[0185] Gelatin: 7 wt. %

[0186] Sorbitol: 11.67 wt. %

[0187] Xylitol: 28.44 wt. %

[0188] Trisodium citrate: 2.1 wt. %

[0189] Malic acid: 1.07 wt. %

[0190] MCT oil containing 10 mg CBD: 30 wt. %

Example 8

Gelled Oil-in-Water Emulsion with 40 wt. % Oil Phase

[0191] A gelled oil-in-water emulsion with the following composition is prepared analogously to Example 5:

[0192] Water: 16.9 wt. %

[0193] Gelatin: 6 wt. %

[0194] Sorbitol: 10 wt. %

[0195] Xylitol: 24.38 wt. %

[0196] Trisodium citrate: 1.8 wt. %

[0197] Malic acid: 0.92 wt. %

[0198] MCT oil containing 10 mg CBD: 40 wt. %

Example 9

Gelled Oil-in-Water Emulsion with 50 wt. % Oil Phase

[0199] A gelled oil-in-water emulsion with the following composition is prepared analogously to Example 5:

[0200] Water: 14.08 wt. %

[0201] Gelatin: 5 wt. %

[0202] Sorbitol: 8.33 wt. %

[0203] Xylitol: 20.32 wt. %

[0204] Trisodium citrate: 1.5 wt. %

[0205] Malic acid: 0.77 wt. %

[0206] MCT oil containing 10 mg CBD: 50 wt. %

Example 10

Gelled Oil-in-Water Emulsion with 50 wt. % Oil Phase and Higher Loading of CBD

[0207] Gelled oil-in-water emulsions with the following composition may be prepared analogously to Example 5:

[0208] Water: 14.08 wt. %

[0209] Gelatin: 5 wt. %

[0210] Sorbitol: 8.33 wt. %

[0211] Xylitol: 20.32 wt. %

[0212] Trisodium citrate: 1.5 wt. %

[0213] Malic acid: 0.77 wt. %

[0214] MCT oil containing 20-300 mg CBD.sup.1: 50 wt. % .sup.1The amount of CBD may be varied between 20 to 300 mg depending on the intended use of the composition.

Example 11

Gelled Oil-in-Water Emulsion with 20 wt. % Oil Phase and a Mucoadhesive Agent

[0215] Gelled oil-in-water emulsions with the following composition may be prepared analogously to Example 5 except for the following initial steps: the chitosan is first dissolved in the weakly acidified water (water plus acetic acid) and, when completely dissolved, the alkaline buffering agent (typically phosphate) is added. The gelatin is then added to the resulting aqueous solution and the temperature is raised to 70° C. with stirring for 10 minutes. The remainder of the procedure from Example 5 is then followed.

[0216] Water: 22.53 wt. %

[0217] Gelatin: 8 wt. %

[0218] Sorbitol: 13.33 wt. %

[0219] Xylitol: 32.51 wt. %

[0220] MCT oil containing 20-300 mg CBD.sup.1: 20 wt. %

[0221] Acetylated chitosan (mucoadhesive agent): 1 wt. %

[0222] Acetic acid: as required

[0223] Alkaline buffering agent (pH 7.5): 2.63 wt. % .sup.1The amount of CBD may be varied between 20 to 300 mg depending on the intended use of the composition.

Example 12

Gelled Oil-in-Water Emulsion Containing Other Oromucosal Uptake Enhancing Agents

[0224] A gelled oil-in-water emulsion having the composition set out in Table 2 may be prepared analogously to Example 5, subject to the following modifications: glycerol is added after the xylitol/sorbitol; citric acid and peppermint essential oil are added before the oil and dissolved; and the lechitin is added towards the end of the homogenisation step. A cannabinoid (e.g. CBD) may be included as part of the oil phase.

TABLE-US-00003 TABLE 2 Composition of gelled oil-in-water emulsions wt. % Oil MCT 47 Water 18 Gelatin Bovine type B 5.5 Sugar Sorbitol 6.95 alcohols Xylitol 16.855 Buffer salts Sodium citrate 2.025 Oromucosal Citric acid 1 uptake Peppermint essential oil, 40% Menthol 0.5 enhancing Glycerol 2 agents Lecithin, 95% 0.1 Colour Betacarotene 30% 0.07 Total 100

Example 13

Gelled Oil-in-Water Emulsion with 20 wt. % Oil Phase Containing CBD+Dronabinol

[0225] Gelled oil-in-water emulsions with the following composition may be prepared analogously to Example 5. The Dronabinol is added to the oil phase together with the CBD.

[0226] Water: 22.53 wt. %

[0227] Gelatin: 8 wt. %

[0228] Sorbitol: 13.33 wt. %

[0229] Xylitol: 32.51 wt. %

[0230] Trisodium citrate: 2.4 wt. %

[0231] Malic acid: 1.23 wt. %

[0232] MCT oil containing 20-300 mg CBD.sup.1 and 2.5-10 mg Dronabinol.sup.2: 20 wt. % .sup.1The amount of CBD may be varied between 20 to 300 mg depending on the intended use of the composition..sup.2The amount of Dronabinol may be varied between 2.5 to 10 mg depending on the intended use of the composition.

Example 14

Gelled Oil-in-Water Emulsion with 20 wt. % Oil Phase Containing CBD+NSAID (Diclofenac)

[0233] Gelled oil-in-water emulsions with the following composition may be prepared analogously to Example 5. Diclofenac may be added to the aqueous phase or to the oil phase prior to mixing of these phases and homogenization.

[0234] Water: 21 wt. %

[0235] Gelatin: 8 wt. %

[0236] Sorbitol: 13 wt. %

[0237] Xylitol: 31.05 wt. %

[0238] Trisodium citrate: 2.4 wt. %

[0239] Malic acid: 1.22 wt. %

[0240] MCT oil containing 20-300 mg CBD.sup.1: 20 wt. %

[0241] Diclofenac (50 mg): 3.33 wt. % .sup.1The amount of CBD may be varied between 20 to 300 mg depending on the intended use of the composition.

Example 15

Gelled Oil-in-Water Emulsion with 20 wt. % Oil Phase Containing CBD+Other Active Agents

[0242] Gelled oil-in-water emulsions based on MCT oil and including CBD plus any of vitamin D, melatonin (0.5 to 5 mg) and magnesium carbonate (40 mg—approx. 10% RDA) may be prepared analogously to Example 14. The gelled emulsions can be used as nutraceuticals.

Example 16

Gelled Oil-in-Water Emulsion with Agar as Gelling Agent

[0243] Gelled oil-in-water emulsions with the following composition may be prepared analogously to Example 5 except for the following initial steps: agar is added to the water and the solution is then heated to about 90° C. with stirring for 30 minutes or until fully dissolved. The temperature is then lowered to 70° C. and the procedure from Example 5 is followed in which the citric acid ester (emulsifying agent) is added together with the sugar alcohols.

[0244] Water: 26 wt.

[0245] Agar: 2 wt. %

[0246] Citric acid ester (Grinsted Citrem N 12): 1 wt. %

[0247] Sorbitol: 14 wt. %

[0248] Xylitol: 28 wt. %

[0249] Trisodium citrate: 2.4 wt. %

[0250] Malic acid: 1.6 wt. %

[0251] MCT oil containing 10 mg CBD: 25 wt. %

Example 17

Gelled Oil-in-Water Emulsion with Agar as Gelling Agent

[0252] Gelled oil-in-water emulsions with the following composition may be prepared analogously to Example 5 except for the following initial steps: agar and locust bean gum are added to the water and the solution is then heated to about 90° C. with stirring for 30 minutes or until fully dissolved. The temperature is then lowered to 70° C. and the procedure from Example 5 is followed in which the citric acid ester is added together with the sugar alcohols.

[0253] Water: 26 wt. %

[0254] Agar: 1.8 wt. %

[0255] Citric acid ester (Grinsted Citrem N 12): 1 wt. %

[0256] Locust Bean Gum: 0.2 wt. %

[0257] Sorbitol: 14 wt. %

[0258] Xylitol: 28 wt. %

[0259] Trisodium citrate: 2.4 wt. %

[0260] Malic acid: 1.6 wt. %

[0261] MCT oil containing 10 mg CBD: 25 wt. %

Example 18

Gelled Oil-in-Water Emulsion with κ-Carrageenan as Gelling Agent

[0262] Gelled oil-in-water emulsions with the following composition may be prepared analogously to Example 5 except for the following initial steps: κ-Carrageenan is added to the water and the solution is heated to about 80° C. with stirring for 15 minutes or until fully dissolved. The temperature is then lowered to 70° C. and the procedure from Example 5 is followed in which the soy protein and potassium salt are added together with the sugar alcohols.

[0263] Water: 26 wt. %

[0264] κ-Carrageenan: 1.5 wt. %

[0265] KCl: 0.4 wt. %

[0266] Citric acid ester (Grinsted Citrem N 12): 1 wt. %

[0267] Sorbitol: 14 wt. %

[0268] Xylitol: 28 wt. %

[0269] Trisodium citrate: 2.5 wt. %

[0270] Malic acid: 1.6 wt. %

[0271] MCT oil containing 10 mg CBD: 25 wt. %

Example 19

Gelled Oil-in-Water Emulsion with I-carrageenan as Gelling Agent

[0272] Gelled oil-in-water emulsions with the following composition may be prepared analogously to Example 5 except for the following initial steps: I-Carrageenan is added to the water and the solution is heated to about 80° C. with stirring for 15 minutes or until fully dissolved. The temperature is then lowered to 70° C. and the procedure from Example 5 is followed in which the soy protein and calcium salt are added together with the sugar alcohols.

[0273] Water: 26 wt. %

[0274] I-Carrageenan: 1.5 wt. %

[0275] CaCl.sub.2: 0.4 wt. %

[0276] Citric acid ester (Grinsted Citrem N 12): 1 wt. %

[0277] Sorbitol: 14 wt. %

[0278] Xylitol: 28 wt. %

[0279] Trisodium citrate: 2.5 wt. %

[0280] Malic acid: 1.6 wt. %

[0281] MCT oil containing 10 mg CBD: 25 wt. %

Example 20

Gelled Oil-in-Water Emulsion with HM Pectin as Gelling Agent

[0282] Water: 27 wt. %

[0283] HM Pectin: 1.5 wt. %

[0284] Sorbitol: 16.75 wt. %

[0285] Xylitol: 29.75 wt. %

[0286] 50% citric acid solution: As required (dependent on required pH)

[0287] MCT oil containing 10 mg CBD: 25 wt. %

[0288] pH 3.0-3.1

[0289] A dry mix of HM pectin and sugar alcohols is prepared and dispersed in water. The resulting solution is brought to the boil under stirring until the pectin is fully dissolved. Still at a temperature 95° C., the MCT oil containing the CBD is added with stirring. The mixture is homogenized using a commercially available Ultra-Turrax unit to produce the emulsion. Citric acid is added as required to obtain the recommended pH range. Whilst still liquid, the warm emulsion is filled into pre-formed cavities in a suitable packing material, sealed and allowed to set to form a gel at room temperature.

Example 21

Gelled Oil-in-Water Emulsion with LM Pectin as Gelling Agent

[0290] Water: 26 wt. %

[0291] LM Pectin: 1.5 wt. %

[0292] Calcium citrate: 0.2 wt. %

[0293] Citric acid ester (Grinsted Citrem N 12): 1 wt. %

[0294] Trisodium citrate: 0.25 wt. %

[0295] Sorbitol: 16.75 wt. %

[0296] Xylitol: 29.3 wt. %

[0297] 50% citric acid solution: As required (dependent on desired pH)

[0298] MCT oil containing 10 mg CBD: 25 wt. %

[0299] pH 3.4-3.7

[0300] A dry mix of LM pectin, sugar alcohols and calcium citrate is prepared and dispersed in water. The resulting solution is brought to the boil under stirring until the pectin is fully dissolved. Still at a temperature 95° C., the MCT oil containing the CBD is added with stirring. The mixture is homogenized using a commercially available Ultra-Turrax unit to produce the emulsion. Citric acid is added as required to obtain the recommended pH range. Whilst still liquid, the warm emulsion is filled into pre-formed cavities in a suitable packing material, sealed and allowed to set to form a gel at room temperature.

Example 22

Gelled Oil-in-Water Emulsion with Alginate as Gelling Agent

[0301] Water: 26 wt. %

[0302] Alginate: 1.5 wt. %

[0303] Calcium sulphate: 0.3 wt. %

[0304] Sodium pyrophosphate: 0.03 wt. %

[0305] Citric acid ester (Grinsted Citrem N 12): 1 wt. %

[0306] Sorbitol: 16.75 wt. %

[0307] Xylitol: 29.4 wt. %

[0308] MCT oil containing 10 mg CBD: 25 wt. %

[0309] A dry mix of alginate, sugar alcohols, soy protein and sodium pyrophosphate is prepared and dispersed in water at 20° C. until dissolved. Still at room temperature, the MCT oil containing the CBD is added with stirring. The mixture is homogenized using a commercially available Ultra-Turrax unit to produce the emulsion. Calcium sulphate is then added under vigorous stirring. Whilst still liquid, the emulsion is filled into pre-formed cavities in a suitable packing material, sealed and allowed to set to form a gel at room temperature.

Example 23

Gelled Oil-in-Water Emulsion with Alginate as Gelling Agent

[0310] Water: 26 wt. %

[0311] Alginate: 1.5 wt. %

[0312] Calcium carbonate: 0.06 wt. %

[0313] Glucono-δ-lactone: 0.2 wt. %

[0314] Citric acid ester (Grinsted Citrem N 12): 1 wt. %

[0315] Sorbitol: 16.75 wt. %

[0316] Xylitol: 29.4 wt. %

[0317] MCT oil containing 10 mg CBD: 25 wt. %

[0318] A dry mix of alginate, sugar alcohols, soy protein and calcium carbonate is prepared and dispersed in water at 20° C. Still at room temperature, the MCT oil containing the CBD is added with stirring. The mixture is homogenized using a commercially available Ultra-Turrax unit to produce the emulsion. Glucono-δ-lactone is then added under vigorous stirring. Whilst still liquid, the emulsion is filled into pre-formed cavities in a suitable packing material, sealed and allowed to set to form a gel at room temperature.

Examples 24-27

Effect of Mixing Speed on Oil Droplet Size

[0319] The compositions set out in Table 3 are made analogously to those of Examples 1 to 4.

TABLE-US-00004 TABLE 3 Compositions of MCT-based emulsions Example Example Example Example 24 25 26 27 wt. % wt. % wt. % wt. % Oil MCT 25 40 55 25 Water 19.1 17 16.7 19.1 Gelatin Bovine type B (2350) 6 4.7 Fish 195 bloom type 6.2 6.2 A (2751) Sugar Sorbitol 14.5 10 14.5 alcohols Xylitol 29.56 22.86 16.25 29.56 Glycerine 4 Buffer salts Sodium citrate 1.8 1.8 1.6 1.8 Citric acid Malic acid 0.92 0.92 0.7 0.92 Thickeners Gum Arabic 1.5 1.5 Colour Carmine 0.05 0.05 0.05 0.05 Flavour Lemon/Lime 1 1 0.7 1 Raspberry 0.37 0.37 0.3 0.37 Total 100 100 100 100 Mixing conditions “Normal” “Medium” “Low” “High” Ultra-turrax ® setting/minutes 2/7 1.75/7 1.25/7 3.5/10 aw 0.694

[0320] Droplet sizes and size distributions were measured using a Malvern Mastersizer 3000 (Worcestershire, UK) connected to a Hydro MV, wet dispersion unit (Malvern, Worcestershire, UK). Analysis of the data was performed using the manufacturer's software (Mastersizer 3000, v1.0.1). Testing was carried out by dissolving and diluting the gelled emulsion in a 10% (v/v) HCl solution (1:100) at 50° C. The refractive index of water and corn oil was set to 1.33 (solvent) and 1.47 (dispersed phase), respectively, and the absorption index of the dispersed droplets set to 0.01. To avoid multiple scattering or low intensity of the scattered light, each dissolved emulsion was added to the dispersion unit (containing ˜125 mL water), until an obscuration of approximately 10% was obtained.

[0321] Droplet size distributions for the different emulsions are shown in FIGS. 1-3. FIG. 1 shows the droplet size distributions achieved by varying the mixing speed: High—Normal—Medium—Low corresponds to the setting of the Ultra-turrax® unit and mixing time given in table 3. FIG. 2 compares the droplet size distribution results for the emulsions of Examples 24 and 27 which have the same composition and differ only in mixing speed. FIG. 3 shows the influence of mixing speed of the Ultra-turrax® unit on the average volume-based (D[4,3]) droplet size.

Example 28

Packaging

[0322] Blister Packs:

[0323] Prior to setting, the emulsions produced in any of Examples 1 to 23 may be filled into blister trays made from a metal/plastic laminate over which a plastic/metal foil laminate is heat sealed.

[0324] Strips:

[0325] Prior to setting, the emulsions produced in any of Examples 1 to 23 may be extruded into individual strips which, once set, are then sealed into individual plastic/metal foil laminate sachets. Alternatively, a single extruded strip, once set, may be cut into individual strips according to need prior to packaging.

Example 29

Coated Gelled Emulsions

[0326] The set emulsions produced in any of Examples 1 to 23 may be coated with a sorbitol solution comprising sorbitol (80 wt. %), lemon flavour (0.15 wt. %), yellow colour (0.5 wt. %) and water (ad 100 wt. %). The coating solution may be cured at 99-95° C. for 4-5 hours before application. Coating is carried out by dipping or panning at 20-45° C. Several layers of coating material may be added with drying between each layer until the final composite layer is hard.

[0327] Alternatively, prior to setting, the liquid emulsion prepared in any of Examples 1 to 23 may be filled into soft capsule shells, for example commercially available gelatin capsule shells). This may be done using a conventional soft-gel machine. Typically such capsule shells comprise gelatin (40 wt. %), glycerol (30 wt. %), lemon flavour (0.15 wt. %), yellow colour (0.5 wt. %) and water (ad 100 wt. %).