WO2024047529A1 - Formulations d'émulsion de cannabinoïdes dispersibles dans l'eau, procédés de fabrication et applications - Google Patents

Formulations d'émulsion de cannabinoïdes dispersibles dans l'eau, procédés de fabrication et applications Download PDF

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WO2024047529A1
WO2024047529A1 PCT/IB2023/058536 IB2023058536W WO2024047529A1 WO 2024047529 A1 WO2024047529 A1 WO 2024047529A1 IB 2023058536 W IB2023058536 W IB 2023058536W WO 2024047529 A1 WO2024047529 A1 WO 2024047529A1
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cannabinoid
water dispersible
emulsion
oil
emulsion composition
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PCT/IB2023/058536
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English (en)
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Justin Frank BINDER
Abhinandan Banerjee
Krunalkumar Kiritbhai PATEL
Ian Scott
John Frederick Trant
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2682130 Ontario Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing six-membered aromatic rings and other rings, with unsaturation outside the aromatic rings
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/38—Other non-alcoholic beverages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/658—Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/286—Carthamus (distaff thistle)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/55—Linaceae (Flax family), e.g. Linum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/889—Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto

Definitions

  • the present invention relates generally to water-dispersible emulsion formulations, and more particularly to water-dispersible emulsion formulations comprising cannabinoids or cannabis-derived compounds for use in beverages and other water-based or water-containing products.
  • Cannabinoids refer to a group of chemicals that that can act on cannabinoid receptors.
  • Cannabinoid receptor ligands include endocannabinoids, which can be found naturally occurring in humans and other animals, phytocannabinoids, which can be found in cannabis and other plants, other plants, and lichens, and synthetic cannabinoids. Cannabinoids also include tetrahydrocannabinol (THC), such as delta-9-tetrahydrocannabinol, and cannabidiol (CBD), which are known to be psychoactive.
  • THC tetrahydrocannabinol
  • CBD cannabidiol
  • cannabinoid stability and oral bioavailability of cannabinoids exist with edible preparations, such as cannabinoid-infused oils and edibles. Being a highly lipophilic and essentially water insoluble, CBD and THC are difficult to formulate in relatively high concentration for consumption without increasing the oily fraction to be consumed. Emulsion and other colloidal formulations are sometimes used to overcome issues with oral bioavailability and 108430-00009 colloidal stability for many lipophilic nutraceutical substances in water-based or water-containing preparations (such as curcumin, lutein, lycopene, vitamins A, D and E, coenzyme Q10, and others).
  • Figure 1A shows intensity weighted particle size distribution profiles of a cannabinoid comprising about 85% w/w THC distillate
  • Figure 1B shows an example of the volume weighted particle size distribution profiles of a cannabinoid comprising about 85% w/w THC distillate
  • Figure 2A shows intensity weighted particle size distribution profiles of a cannabinoid comprising about 80% w/w CBD distillate
  • Figure 2B shows an example of the volume weighted particle size distribution profiles of a cannabinoid comprising about 108430-00009 80% w/w CBD distillate
  • Figure 3A shows intensity weighted particle size distribution profiles of a cannabinoid comprising about 95% w/w CBD distillate
  • Figure 3B shows an example of the volume weighted
  • emulsion formulation that has substantial advantages over general commercially available infusion technologies is described.
  • the formulation includes high dispersibility into water, low to no perceptible off-flavors in the diluted emulsion, remarkably high cannabinoid stability and rapid onset of effects compared to oils and other edible preparations.
  • Described herein is a formulation for a water-dispersible cannabinoid emulsion.
  • the composition of a water-dispersible cannabinoid base emulsion includes a cannabinoid, cannabis-derived compounds, or compounds found in cannabis, an edible oil or partially-hydrolyzed or alcoholized edible oil, and an emulsifier.
  • a cannabinoid may include cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabidivarol (CBDV), tetrahydrocannabidiol (THCBD), tetrahydrocannabigerol (THCBG), tetrahydrocannabichromene (THCBC), tetrahydrocannabidivarol (THCBDV), or derivatives thereof.
  • CBD cannabidiol
  • CBN cannabinol
  • CBG cannabigerol
  • CBC cannabichromene
  • CBD cannabidivarol
  • THCBD tetrahydrocannabidiol
  • THCBG tetrahydrocannabigerol
  • THCBC tetrahydrocannabichromene
  • THCBDV tetrahydrocannabidivarol
  • Cannabis-derived compounds may include cannabinoids, cannabinoid 108430-00009 acids, terpenoids (such as alpha-bisabolol, alpha-cedrene, alpha-humulene, alpha- phellandrene, alpha-pinene, alpha-terpinene, alpha-terpineol, beta-caryophyllene, beta-myrcene, beta-ocimene, beta-pinene, borneol, camphene, camphor, caryophyllene oxide, cedrol, cis-nerolidol, d-limonene, delta-3-carene, e-beta- farnesene, eucalyptol, fenchol, fenchone, gamma-terpinene, geraniol, geranyl acetate, guaiol, isoborneol, isopulegol, linalool
  • the emulsifier may be any chemical or natural additive that encourages the suspension of a liquid in another liquid where the two liquids are not soluble in each other.
  • an emulsifier may include phospholipids, saponins, pectin, gum arabic, gum acacia, modified acacia gum, chitosan, sucrose esters of fatty acids, polysorbates, sorbitan esters of fatty acids, cholesterol, acetylated monoglycerides, agar, algin, carrageenan, arabino-galactan, carob bean gum, carboxymethyl cellulose, citric acid esters of mono and diglycerides, gellan gum, guar gum, hydroxylated phospholipids, lactylated mono and diglycerides, polyglycerol esters of fatty acids, propylene glycol alginate and other propylene glycol esters.
  • the composition of a water-dispersible cannabinoid base emulsion may include an acidulant and/or a pH adjusting agent.
  • acidulants or pH adjusting agents may include acetic acid, adipic acid, ammonium aluminum sulphate, ammonium bicarbonate, ammonium carbonate, ammonium citrate, ammonium hydroxide, ammonium phosphate, calcium acetate, 108430-00009 calcium acid pyrophosphate, calcium carbonate, calcium chloride, calcium citrate, calcium fumarate, calcium gluconate, calcium hydroxide, calcium lactate, calcium oxide, calcium phosphate, calcium sulphate, citric acid, cream of tartar, fumaric acid, gluconic acid, hydrochloric acid, lactic acid, magnesium carbonate, magnesium citrate, magnesium fumarate, magnesium hydroxide, magnesium oxide, magnesium sulphate, magnesium phosphate, malic acid, manganese sulphate, metatartaric acid,
  • the composition of a water-dispersible cannabinoid base emulsion may include a citrus oil or other flavoring agents.
  • citrus oils may include lemon oil, orange oil, grapefruit oil, sweet orange oil, bitter orange oil, blood orange oil, lime oil, bergamot oil, mandarin oil, tangerine oil, yuzu oil, petitgrain oil, neroli oil, and others.
  • the amount of citrus oil that may be added may depend on various factors such as the citrus oil used and desired flavor.
  • flavoring agents may include other essential oils, for example; anise oil, basil oil, black pepper oil, cannabis flower essential oil, caraway seed oil, lavender oil, peppermint oil, the chemical equivalents of those essential oils or 108430-00009 combinations of essential oils, and artificial flavoring agents that are of synthetic origin but formulated to imitate an essential oil, combination of essential oils, or a produce a perceived flavor when consumed.
  • the amount of flavoring agents that may be added may depend on various factors such as the desired flavor.
  • the composition may include one or more of: a) Polysorbate 80 at between about 0.1% to about 5% by weight; preferably, between about 0.5% and about 2% by weight. b) Sorbitan monostearate at between about 0.1% to about 5% by weight; preferably, between about 0.5% and about 2% by weight. c) Corn oil mono and diglycerides at between about 0.1% to about 15% by weight; preferably, between about 1% and about 10% by weight.
  • Cannabinoid such as tetrahydrocannabinol (THC) or cannabidiol (CBD) at between about 0.1% to about 5% by weight; preferably, between about 0.5% and about 3% by weight, or alternatively, between about 0.5% and about 5% by weight.
  • Lemon oil at between about 0.1% to about 6% by weight; preferably, between about 0.5% and about 3% by weight.
  • Citric acid at between about 0.1% to about 8% by weight; preferably, between about 0.5% and about 2% by weight.
  • Potassium citrate at between about 0.1% to about 6% by weight; preferably, between about 0.5% and about 3% by weight.
  • Water at between about 20% to about 95% by weight.
  • Polysorbate 80 is a non-ionic surfactant that is used as an excipient in drug formulation and as an emulsifier in food and cosmetic products (E433). It is commercially available from suppliers such as BASF (trade name Kolliphor PS 80), Croda (trade name Tween 80), and others. 108430-00009 [0031] Sorbitan monostearate is a non-ionic surfactant that is used as an excipient in food and healthcare products for the purpose of thickening, emulsifying, dispersing, and wetting (E491). It is commercially available from suppliers such as Croda (Span 60) and others.
  • Corn oil mono and diglycerides are mixtures of mono, di, and triglycerides of long chain fatty acids derived by partial hydrolysis or alcoholysis of corn oil. It is commercially available from suppliers such as Gattefosse (Maisine CC) or others.
  • Cannabinoids are molecules found in the cannabis plant (or synthetic equivalents) that interact with the endocannabinoid system, a biological system composed of cannabinoid receptors (e.g. CB1 and CB2) that are expressed throughout the central and peripheral nervous systems of vertebrates. Some of these compounds are extracted or physically separated from Cannabis Sativa and can be purified by distillation to produce a cannabinoid distillate (e.g.
  • Lemon oil is an essential oil extracted from Citrus Limon. It is widely used as a flavoring agent in food and beverage products, as a fragrance in personal care products and consumer products more generally.
  • the primary compound in lemon oil is limonene, a monoterpene that may be derived from natural sources (e.g.
  • Citric acid is an organic acid found naturally in many fruits and vegetables, especially in citrus fruits. Citric acid is also produced industrially through the fermentation of sugars in the presence of various strains of aspergillus 108430-00009 niger. It is used as an acidulant, preservative, emulsifying agent, and chelating agent, among other applications, in food products, beverage products, topical products, cosmetic products, and consumer goods in general.
  • the composition may include one or more of: a) Polysorbate 80 at about 1.00% by weight; b) Sorbitan monostearate at about 1.00% by weight; c) Corn oil mono and diglycerides at about 1.95% by weight; d) Cannabinoid, such as tetrahydrocannabinol (THC) or cannabidiol (CBD) at about 2.00% by weight; e) Lemon oil at about 0.50% by weight; f) Citric acid at about 0.26% by weight; g) Potassium citrate at about 0.26% by weight; and h) Water at about 93.03% by weight.
  • THC tetrahydrocannabinol
  • CBD cannabidiol
  • Lemon oil at about 0.50% by weight
  • Citric acid at about 0.26% by weight
  • g) Potassium citrate at about 0.26% by weight
  • Water at about 93.03% by weight.
  • the composition of the water-dispersible cannabinoid base emulsion may be modified to include additional preservatives.
  • the amount and type of preservatives that may be added may depend on various factors such as the intended use of the emulsion and the desired shelf life under various conditions as well as other factors. It is to be appreciated by a person of skill in the art with the benefit of this description that the acidulants and preservative concentrations may be adjusted in tandem to achieve a target pH range and to enhance microbial resistance.
  • the increased microbial resistance may be useful in non-sterile manufacturing environments or food processing plants where microbes may be encountered.
  • Increased microbial resistance may also be useful in applications where products are stored and consumed in resealable or reusable containers or bags.
  • the composition may include one or more of: a) Polysorbate 80 at about 1.00% by weight; b) Sorbitan monostearate at about 1.00% by weight; 108430-00009 c) Corn oil mono and diglycerides at about 1.95% by weight; d) Cannabinoid, such as tetrahydrocannabinol (THC) or cannabidiol (CBD) at about 2.00% by weight; e) Lemon oil at about 0.50% by weight; f) Citric acid at about 0.50% by weight; g) Potassium citrate at about 0.10% by weight; h) Potassium sorbate at about 0.04% by weight; and i) Water at about 93% by weight.
  • THC tetrahydrocannabinol
  • CBD cannabidiol
  • the amount of cannabinoid added to achieve a desired therapeutic or recreational result is influenced by, and will therefore vary based on, a number of factors, including for example and without limitation, the age, sex, and weight of the subject, factors that influence the metabolic rate, and other characteristics of the subject.
  • concentration of at least one cannabinoid in compositions provided herein is between about 0.1% to about 5%.
  • the cannabinoid concentrations of the water- dispersible cannabinoid base emulsion may be increased proportionally with surfactants and oils to maintain consistent emulsion colloidal properties and flavor.
  • the composition may include one or more of: a) Polysorbate 80 at about 2.00% by weight; b) Sorbitan monostearate at about 2.00% by weight; c) Corn oil mono and diglycerides at about 3.90% by weight; d) Cannabinoid, such as tetrahydrocannabinol (THC) or cannabidiol (CBD) at about 4.00% by weight; e) Lemon oil at about 1.00% by weight; f) Citric acid at about 0.50% by weight; g) Potassium citrate at about 0.10% by weight; h) Potassium sorbate at about 0.04% by weight; and i) Water at about 86% by weight.
  • THC tetrahydrocannabinol
  • CBD cannabidiol
  • the process may involve preparing a buffer solution with about 0.26% w/w citric acid and about 0.26% w/w potassium citrate in water.
  • An aqueous surfactant solution is then prepared by dispersing about 1.00% w/w polysorbate 80 and about 1.00% w/w sorbitan monostearate in the buffer solution and heating it to about 65°C with continuous stirring.
  • about 1.95% w/w corn oil mono and diglycerides is heated to about 65°C, and about 0.5% w/w lemon oil and about 2% w/w cannabinoid were added and mixed to generate a lipid phase.
  • An oil-in-water pre-emulsion is obtained by combining the hot aqueous surfactant solution and the hot lipid phase by high shear mixing with a rotor-stator mixer.
  • High-pressure homogenization using Microfluidizer® is carried out in a pre-heated system (about 60°C) at about 30 Kpsi for 3 cycles; the outlet temperature was adjusted to about 15°C.
  • the resulting emulsion is then stored at a temperature between about 0 °C to about 4 °C.
  • the creation of the base emulsion may be carried out using other mixing methods.
  • a high-shear homogenization method may be used to generate the water-dispersible cannabinoid base emulsion.
  • the water-dispersible cannabinoid base emulsion may be created using ultrasonication or with ultrasonic processing.
  • the water- dispersible cannabinoid base emulsion may be created using solvent emulsification and/or evaporation methods.
  • 108430-00009 Dynamic light scattering is a widely used method for evaluating the physicochemical properties of colloidal systems, including emulsions. The method involves the measurement of particle-scattered light intensities over time due to diffusion of particles in a sample. Thus, information such as the diffusion coefficients of the particles can be determined and the particle size distributions, and other physicochemical properties can also be determined.
  • DLS measurements of an emulsion over time can provide insights into the colloidal stability of the emulsion.
  • Emulsions that are resistant to instability mechanisms like Ostwald ripening, creaming, sedimentation, flocculation, coalescence, and ultimately phase separation can be selected by visual observation of the sample over time and by measurement of a sample’s particle size distributions over time using dynamic light scattering techniques.
  • dz average particle sizes
  • PDI polydispersity indices
  • zeta potentials DLS also known as photon correlation spectroscopy
  • the measurements were conducted using a Malvern Zetasizer (Nano ZS, Malvern Instruments Ltd., UK).
  • the supplier’s software Zetasizer Software 7.13 was used to analyze the data and derive the average particle sizes, polydispersity indices and zeta potentials for the emulsion samples.
  • the base emulsion formulations produced with slightly different cannabinoid-containing raw materials e.g. distillates or isolates
  • the base emulsion prepared with CBD isolate rather than CBD distillate may have smaller particle sizes if the viscosity of the emulsion’s oil phase more closely matches that of the emulsion’s aqueous phase.
  • the base emulsion produced using the same processing methods but with different cannabinoid-containing raw materials produced slightly different average particle sizes (dz), polydispersity indices (PDI) and zeta potentials.
  • the average particle sizes of the emulsions produced with sufficiently high purity raw materials such as greater than 108430-00009 about 80% pure by weight, may be in the range of about 200 nm to about 800 nm.
  • Table 1 Cannabinoid Average Particle Polydispersity Zeta Potential Raw Material Size (nm) Index (mV) [ ] eerrng to gures an c aracterzatons o a ase emuson created with a cannabinoid comprising about 85% w/w THC distillate.
  • Figure 1A shows an example of the intensity weighted particle size distribution profiles obtained from a dynamic light scattering experiment performed in triplicate using a Malvern Zetasizer.
  • Figure 1B shows an example of the volume weighted particle size distribution profiles obtained from a dynamic light scattering experiment performed in triplicate using a Malvern Zetasizer.
  • the average size of the droplets was determined to be about 674nm ⁇ 14nm and the polydispersity index for this example was determined to be about 0.25.
  • the average zeta potential for this example base emulsion was measured to be about -8.9mV.
  • Figure 2A shows an example of the intensity weighted particle size distribution profiles obtained from a dynamic light scattering experiment performed in triplicate using a Malvern Zetasizer.
  • Figure 2B shows an example of the volume weighted particle size distribution profiles obtained from a dynamic light scattering experiment performed in triplicate using a Malvern Zetasizer. 108430-00009
  • the average size of the droplets was determined to be about 202nm ⁇ 3nm and the polydispersity index for this example was calculated to be about 0.18.
  • the average zeta potential for this example base emulsion was measured to be about -8.4mV.
  • Figure 3A shows an example of the intensity weighted particle size distribution profiles obtained from a dynamic light scattering experiment performed in triplicate using a Malvern Zetasizer.
  • Figure 3B shows an example of the volume weighted particle size distribution profiles obtained from a dynamic light scattering experiment performed in triplicate using a Malvern Zetasizer.
  • the average size of the droplets was determined to be about 591nm ⁇ 6.7nm and the polydispersity index for this example was calculated to be about 0.391.
  • the average zeta potential for this example base emulsion was measured to be about -12.3mV.
  • the stability of the base emulsion formulation with about 80% CBD distillate was assessed by subjecting the emulsion to several stress tests. These tests mimic some potential conditions that the emulsion or products 108430-00009 produced using the emulsion as an ingredient might face during the production of a cannabis infused product, for example, a cannabis infused beverage.
  • FIGS 4A and 4B results from a stress test of the base emulsion measured in triplicate is shown.
  • the stress test is carried out with a cannabinoid base emulsion comprising about 80% w/w CBD distillate.
  • the base emulsion described in association with figures 2A and 2B was flash heated to test its stability.
  • the stress test involved placing about 1g of the base emulsion in a preheated water bath. The water bath was maintained at about 80°C to hold the internal temperature of the nanoemulsion at about 80°C for about 1 minute.
  • This protocol is a more extreme version of the high-temperature short-time (HTST) pasteurization process that fruit juices and milk beverages are subjected to in the beverage industry, which may involve maintaining a sample at about 71.5°C for about 15s.
  • HTST high-temperature short-time
  • the base emulsion was then allowed to cool to about 23°C and a part of the base emulsion was diluted about 1:50 for dynamic light scattering analysis to generate the graphs in figures 4A and 4B.
  • the pasteurized base emulsion showed no visible signs of creaming, flocculation, sedimentation or coalescence.
  • the average size of the droplets was increased to about 378nm ⁇ 3.4nm.
  • the polydispersity index for this example is calculated to be about 0.18, which remained relatively unchanged.
  • the average zeta potential for this example base emulsion dropped to about -18.3mV.
  • results from another stress test of the base emulsion measured again in triplicate is shown.
  • the stress test is carried out with a cannabinoid base emulsion comprising about 80% w/w CBD distillate.
  • the base emulsion described in association with figures 2A and 2B was subjected to a freeze-thaw cycle to test its stability.
  • the average zeta potential for this example base emulsion was measured to be about -16.7mV.
  • results from another freeze-thaw cycle of the base emulsion shown in figures 5A and 5B measured in triplicate is shown.
  • the freeze-thaw cycle involved placing the emulsion in a freezer at a temperature of about -20°C for about 1 hour.
  • the sample of the base emulsion was removed from the freezer and allowed to revert to about 23°C. Accordingly the results shown in figures 6A and 6B have been subjected to two substantially similar freeze-thaw cycles.
  • the average size of the droplets was determined to be about 377nm ⁇ 2.6nm and the polydispersity index for this example was calculated to be about 0.20.
  • the average zeta potential for this example was measured to be about -16.6mV. Accordingly, the second freeze-thaw cycle did not significantly change the properties of the base emulsion.
  • Referring to figures 7A and 7B results from another freeze-thaw cycle of the base emulsion shown in figures 6A and 6B measured in triplicate is shown. In the present example, the freeze-thaw cycle involved placing the emulsion in a freezer at a temperature of about -20°C for about 1 hour.
  • the base emulsion described in association with figures 2A and 2B was subjected to dilution and carbonation to test its stability for use in some beverages.
  • about 1 mL of the base emulsion was diluted into about 355 mL of carbonated water.
  • the diluted emulsion was then subjected to dynamic light scattering measurements.
  • the diluted and carbonated emulsion showed no signs of creaming, flocculation, sedimentation or coalescence.
  • the average size of the droplets was determined to be about 669nm ⁇ 19.8nm by DLS.
  • the polydispersity index for this example was calculated to be about 0.15.
  • the average zeta potential for this example was measured to be about -26.7mV. There was substantially no change to the particle size distributions upon dilution and carbonation.
  • FIGS 9A and 9B results from another stress test of the base emulsion measured in triplicate is shown. The stress test is carried out with a cannabinoid base emulsion comprising about 80% w/w CBD distillate.
  • the base emulsion described in association with figures 2A and 2B was subjected to acidulation to test its stability. In particular, dilute hydrochloric acid (0.1 mM) was added dropwise to about 1 mL of emulsion until the pH reached about 3.0.
  • Dilution for dynamic light scattering analysis was performed with a pH 3 108430-00009 buffer solution.
  • the acidulated emulsion showed no visible signs of creaming, flocculation, sedimentation or coalescence.
  • the average size of the droplets was determined to be about 483nm ⁇ 4.1nm and the polydispersity index for this example was calculated to be about 0.27.
  • the average zeta potential for this example was measured to be about -16.1mV. There was substantially no change to the particle size distributions occur upon acidulation.
  • Referring to table 2 observations of certain properties of the emulsions comprising various cannabinoid-containing input materials were tracked over time after manufacturing.
  • the emulsions were stored in a dark fridge at about 4 °C in sealed HDPE containers and sampled periodically as outlined in table 2.
  • the appearance, cannabinoid concentrations, and pH were measured and recorded over time to demonstrate that the emulsions are chemically stable.
  • a microbiological scan was carried out by a third- party lab periodically over the course of several months. The microbiological scan tested for the presence of bacteria, yeast and moulds in the samples which may indicate spoilage.
  • Table 2 Cannabinoid Time THC CBD pH Micro Appearance Ingredient Potency Potency Scan 108430-00009 1 Month 18.9 0 4.03 None Unchanged detected 2 M h 1 2 [ ] seres o vara ons o e ase ormua on were prepare o e er understand the relationship between ingredient ratios, and emulsion physicochemical properties produced under the same or similar processing conditions [0077] Referring to table 3, Var 9 displayed visually detectable colloidal destabilization after manufacturing. In particular, creaming of the emulsion was detected where oil builds up on the surface of the emulsion.
  • the results indicate that certain variations of the base formulation may produce emulsions with acceptable stability for use in manufacturing of cannabinoid- containing products.

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Abstract

L'invention concerne un exemple d'émulsion dispersible dans l'eau. L'émulsion dispersible dans l'eau comprend un cannabinoïde à environ 0,1-5,0 % (p/p) collectivement. De plus, l'émulsion dispersible dans l'eau comprend une huile comestible à environ 0,1 à 15,0 % (p/p). En outre, l'émulsion dispersible dans l'eau comprend un agent émulsifiant à environ 0,1-10,0 % (p/p).
PCT/IB2023/058536 2022-08-30 2023-08-29 Formulations d'émulsion de cannabinoïdes dispersibles dans l'eau, procédés de fabrication et applications WO2024047529A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070104741A1 (en) * 2005-11-07 2007-05-10 Murty Pharmaceuticals, Inc. Delivery of tetrahydrocannabinol
WO2021030913A1 (fr) * 2019-08-20 2021-02-25 Hexo Operations Inc. Compositions de cannabinoïdes, procédés de fabrication et utilisations de celles-ci
WO2021119844A1 (fr) * 2019-12-20 2021-06-24 Organigram Inc. Formulations émulsifiantes de cannabinoïdes et/ou d'extraits de cannabinoïdes
WO2023028708A1 (fr) * 2021-09-02 2023-03-09 Canopy Growth Corporation Compositions de cannabinoïdes solubles dans l'eau, procédés de préparation et d'utilisation
WO2023189305A1 (fr) * 2022-03-30 2023-10-05 第一工業製薬株式会社 Composition d'émulsion huile-dans-détergent

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070104741A1 (en) * 2005-11-07 2007-05-10 Murty Pharmaceuticals, Inc. Delivery of tetrahydrocannabinol
WO2021030913A1 (fr) * 2019-08-20 2021-02-25 Hexo Operations Inc. Compositions de cannabinoïdes, procédés de fabrication et utilisations de celles-ci
WO2021119844A1 (fr) * 2019-12-20 2021-06-24 Organigram Inc. Formulations émulsifiantes de cannabinoïdes et/ou d'extraits de cannabinoïdes
WO2023028708A1 (fr) * 2021-09-02 2023-03-09 Canopy Growth Corporation Compositions de cannabinoïdes solubles dans l'eau, procédés de préparation et d'utilisation
WO2023189305A1 (fr) * 2022-03-30 2023-10-05 第一工業製薬株式会社 Composition d'émulsion huile-dans-détergent

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