Cannabinoid emulsions and complexes and related methods of manufacture

Abstract

The invention described herein relates to dried cannabinoid emulsions (DCEs), dried cannabinoid complexes, and related systems and methods. One example of a method for forming a DCE includes obtaining an aqueous phase, obtaining an oil phase containing a cannabinoid, forming a water-in-oil emulsion in which the oil phase is suspended as particles in the aqueous phase, and drying the emulsion in a refractance window dryer. One example of a method for forming a dried cannabinoid-cyclodextrin complex includes obtaining an aqueous solution containing cyclodextrin, adding a mixture of ethanol and cannabinoid to the aqueous solution to form a cannabinoid-cyclodextrin complex, and drying the cannabinoid-cyclodextrin complex in a refractance window dryer.

Description

[Technical Field]

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 398,693, filed August 17, 2022, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates generally to the field of cannabinoid products, and more particularly to systems and methods for producing products containing cannabinoid emulsions and / or cannabinoid complexes. [Background technology]

[0003] An oil-in-water (O / W) emulsion is a homogeneous dispersion of fine oil droplets within water or another aqueous matrix. The oil can act as a carrier for hydrophobic substances, which may include active ingredients ("actives"). Emulsifiers, surfactants, stabilizers, carriers, and other ingredients can be added to improve emulsion stability or modify flow properties.

[0004] Cannabinoids can include over 100 naturally occurring cannabinoids (e.g., cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), isomers of tetrahydrocannabinol (THC)), endocannabinoids or their analogs (e.g., anandamide), synthetic cannabinoids (e.g., HU-210), and mixtures thereof. Cannabinoids are used to treat chronic pain, chemotherapy-induced nausea, multiple sclerosis (MS)-related spasticity, and other medical conditions. Summary of the Invention

[0005] While certain processes for producing cannabinoid emulsions and cannabinoid-cyclodextrin complexes are known, these emulsions and complexes are typically spray-dried. This method produces powder-like materials with high surface area and poor flowability. Described herein is a method utilizing Refractance Window Drying (RWD) technology to provide glassy solids or "crystals" of emulsified cannabinoids and / or dried cannabinoid-cyclodextrin complexes. These products produced using RWD can be more flowable, stable, and easily dispersible in aqueous media. Spray-dried powders, on the other hand, can be prone to agglomeration and require time to fully disperse.

[0006] The systems and methods described herein can use RWD technology to produce dry cannabinoid emulsions (DCEs) (e.g., water-in-oil emulsions that are dry to the touch). DCEs may be physically and chemically more stable than typical liquid emulsions. Such cannabinoid products may be more fluid, better dispersible, and have a glossier appearance than products produced by other drying techniques, such as spray drying. RWD-produced products may have reduced surface area and / or larger particle size (e.g., lower surface area-to-volume ratio), which may improve resistance to degradation compared to spray-dried materials.

[0007] In some embodiments, the systems and methods described herein can use RWD to produce dried cannabinoid-gamma cyclodextrin (DC-GCD) complexes. Gamma cyclodextrin can encapsulate CBD or other active ingredients, and the use of RWD can minimize loss of the active ingredient during the drying process. Alternatively, other cyclodextrins (e.g., delta cyclodextrin) can be used to encapsulate the active ingredient.

[0008] In one aspect of the disclosure, there is provided a method of forming a dried cannabinoid emulsion (DCE), the method comprising obtaining an aqueous phase, obtaining an oil phase containing a cannabinoid, forming a water-in-oil emulsion in which the oil phase is dispersed as particles in the aqueous phase, and drying the emulsion in a refractance window dryer to form the DCE.

[0009] In another aspect, a dry cannabinoid emulsion (DCE) composition is provided. The composition comprises a matrix phase comprising a bulking agent and water, and particles of an oil phase comprising a cannabinoid, the particles being dispersed within the matrix phase. The particle size ranges from about 10 nm to about 400 nm.

[0010] In yet another aspect, there is provided a method of forming a dried cannabinoid-cyclodextrin complex, the method comprising the steps of forming an aqueous solution containing cyclodextrin, adding a mixture of ethanol and a cannabinoid to the aqueous solution to form a cannabinoid-cyclodextrin complex, and drying the cannabinoid-cyclodextrin complex in a refractance window dryer to form a dried cannabinoid-cyclodextrin complex.

[0011] Additionally, in another aspect of the present disclosure, there is provided a composition comprising a dried cannabinoid-cyclodextrin complex and at least one of an amylase enzyme, an excipient, or a bulking agent.

[0012] Objects, advantages, and features of various embodiments of the present disclosure will become more apparent with reference to the following description, drawings, and claims. Also, the features of each embodiment described herein are not mutually exclusive and can be combined and modified in various ways. [Brief explanation of the drawings]

[0013] In the drawings, like reference characters generally refer to the same parts throughout the different views. Also, the drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. In the following description, various embodiments of the present invention are described with reference to the following drawings:

[0014] [Figure 1] 1 is a schematic diagram of a method for manufacturing a DCE according to embodiments described herein.

[0015] [Figure 2] FIG. 1 is a schematic diagram of a method for producing a cannabinoid complex formulation according to embodiments described herein. DETAILED DESCRIPTION OF THE INVENTION

[0016] The devices, systems, methods, and processes claimed in the present invention are intended to encompass various variations and improvements developed in light of the embodiments described herein. Adaptations and modifications of the devices, systems, methods, and processes described herein can be made by one of ordinary skill in the art.

[0017] In the present invention, the order in which certain steps or actions are performed is not necessarily important so long as the invention functions. Moreover, two or more steps or actions may be performed simultaneously.

[0018] Disclosed herein are techniques relating to dried cannabinoid emulsions (DCEs), cannabinoid complexes (e.g., DC-GCD complexes), and systems and methods for producing DCEs and cannabinoid complexes.

[0019] As used herein, a "dry cannabinoid emulsion (DCE)" or "DCE" is a composition in which particles of an oil phase containing a cannabinoid (e.g., CBD) are dispersed within a matrix phase comprising water and a filler or bulking agent (e.g., maltodextrin). The DCE itself may be in the form of particles, with each DCE particle containing both an oil phase and a matrix phase.

[0020] As used herein, the term "cannabinoid complex" refers to a molecular structure in which a cannabinoid molecule (e.g., a CBD molecule) is encapsulated or enclosed within another molecule (e.g., a cyclodextrin). For example, a cyclodextrin molecule has a hydrophilic surface and a hydrophobic cavity, and a cannabinoid molecule can be enclosed within the hydrophobic cavity to form a "cannabinoid-cyclodextrin complex."

[0021] Figure 1 shows a schematic diagram of a process 100 for producing DCE. Generally, the process 100 uses a high-speed mixer to produce a coarse water-in-oil emulsion, a high-pressure homogenizer to produce a fine water-in-oil emulsion, and a RWD process to dry the emulsion to produce the DCE.

[0022] In step 102, an aqueous phase is produced by mixing an emulsifier with water. The emulsifier can be dissolved in the water by heating (e.g., to about 50° C.), allowing it to stand for a period of time (e.g., about 2 hours), and / or cooling the mixture. Emulsifiers can include, for example, biosurfactants (e.g., surfactants derived from bacteria, yeast, or fungi, such as rhamnolipids or sophorolipids), sucrose esters (e.g., sucrose laurate), phospholipids (e.g., soybean, canola, and / or sunflower lecithin), proteins (e.g., gelatin, pea protein, or potato protein), polysaccharides (e.g., potato starch or gums), and / or saponins (e.g., yucca saponin, yam saponin, ginseng saponin, legume saponin, tea saponin, glycyrrhizin saponin, licorice root saponin, red beet saponin, oat bran saponin, or quillaja saponin (e.g., O-NATURALE from INGREDION, or quillaja extract powder from GURADA)). Similar to sucrose esters, O-alkylated organic acid or fatty acid esters derived from synthetic and / or natural sources can produce effective emulsifiers (e.g., propylene glycol fatty acid esters, ethoxylated jojoba esters, or esters of citric acid, tartaric acid, ascorbic acid, and other organic acids). Amide analogs of esters, proteins, and peptides can also function as emulsifiers. Sucrose esters are colorless, odorless, tasteless, and non-allergenic, imparting these favorable properties to DCE and / or the final products produced with DCE. The use of saponin (a surface-active compound) or quillaja extract as an emulsifier can be advantageous in promoting emulsion stability, especially when the emulsion is mixed with acidic substances (e.g., acidic beverage bases). Saponin or quillaja extract emulsifiers fulfill the need for natural ingredients and can achieve high loadings of active ingredients in emulsions (e.g., 10% or more on a dry basis).Compared to other emulsifiers, saponins (e.g., quillaja extract) are generally hypoallergenic and less likely to cause allergic reactions in consumers of DCE or related products. The emulsifier and water can be combined in a weight ratio of about 1:150 (e.g., about 0.7% emulsifier), although other ratios (e.g., about 1:15 to about 1:1500) can also be used. In various examples, the emulsifier can include one or more surfactants that impart short-term stability by reducing the oil-water interfacial tension and / or forming a protective film around the emulsion droplets.

[0023] In step 104, an oil phase is generated by mixing the CBD or other cannabinoid with a carrier oil (e.g., by applying heat and / or cooling). The carrier oil can include, for example, medium-chain triglyceride (MCT) oil, palm oil, coconut oil, hemp seed oil, omega-3 fatty acids (e.g., flaxseed oil or fish oil), long-chain triglyceride (LCT), glycerin, or any combination thereof. MCT oil is odorless, colorless, tasteless, and non-allergenic, imparting these properties to the final product. Compared to other carrier oils, MCT oil is more stable, less susceptible to oxidative degradation and off-flavors, and may be more easily absorbed by the body. In some examples, the carrier oil may contain one or more antioxidants, such as tocopherol (e.g., about 0.1-0.4% by weight), diterpenes (e.g., carnosic acid), fatty acid esters of flavonoids (e.g., palmitoylated catechin), or alkyl esters of phenolic acids (e.g., pentyl gallate). The type or combination of carrier oils selected and used may affect emulsion stability and / or absorption into the body or bloodstream. In some examples, the carrier oil may provide nutritional or health benefits. CBD or other cannabinoids may include isolates (e.g., crystalline solid forms of pure CBD) and / or oils (e.g., CBD oil, distillates, concentrates, or other cannabinoid oils). CBD isolates or other cannabinoid isolates are colorless and generally odorless. In general, it may be desirable to use ingredients that do not impart color, odor, or taste to DCE or the final product produced using DCE. The carrier oil and CBD (or other cannabinoid) can be combined in a weight ratio of about 1:1, although other ratios (e.g., about 1:0.1 to about 1:10) can also be used.

[0024] In step 106, the aqueous phase and the oil phase are mixed in a high-speed mixer to generate a shear effect, thereby producing a coarse emulsion 107 (e.g., an O / W emulsion with relatively large particles and / or a wide variation in particle size). Heating and / or cooling can be applied during this process. The high-speed mixer can be, for example, a Silverson shear mixer (or other suitable device) or can be operated at one or more speeds (e.g., about 10,000 to about 20,000 RPM) for about 5 to 10 minutes. In some cases, the aqueous phase can be introduced into the mixer first, and the oil phase can be added (e.g., dropwise) while the mixer is running. The coarse emulsion 107 can have an oil particle size of about 2,000 nm to 200,000 nm. The ratio of oil phase to water phase in crude emulsion 107 can be about 1:40 by weight (e.g., about 2.4% oil), although other ratios (e.g., about 1:4 to about 1:400) can also be used.

[0025] In step 108, the coarse emulsion 107 can be converted into a fine emulsion 109 (e.g., an oil-in-water emulsion having a relatively small particle size and / or a narrow particle size distribution) using an ultrasonic homogenizer, membrane, microfluidizer, emulsifier, or high-pressure homogenizer (or other suitable device), such as a STANSTED high-pressure homogenizer (manufactured by HOMOGENISING SYSTEMS LTD., Essex, UK). Particle size reduction is typically achieved through a shear mechanism. The high-pressure homogenizer can include, for example, a heat exchanger, a piston, a nozzle, a microchannel, an interaction zone, and / or a mixing chamber. The oil and water phases can be subjected to pressures of about 10,000 psi to about 60,000 psi and / or temperatures of about 25°C to about 65°C in the high-pressure homogenizer. In some formulations, higher temperatures (e.g., about 45°C to about 65°C) can help promote the formation and size reduction of emulsion particles. The oil and water phases can be passed through a high-pressure homogenizer multiple times (e.g., about 10 times) to obtain an emulsion of appropriate quality or desired particle size. The fine emulsion 109 can have an oil particle size of about 10 nm to about 400 nm, or about 20 nm to about 200 nm, for example, an average size of about 100 nm, or a polydispersity index (PDI) of less than about 20. The small particle size and / or narrow particle size distribution of the fine emulsion 109 can promote emulsion stability and facilitate absorption into the body or bloodstream.

[0026] In some examples, the coarse emulsion 107 and / or the fine emulsion 109 can include one or more stabilizers, such as polysaccharides (e.g., gum arabic). While stabilizers may not be surface active, they can impart long-term emulsion stability by resisting interfacial interactions. For example, stabilizers can enhance emulsion stability by promoting emulsion formation or preventing or minimizing phase separation. Various natural or synthetic stabilizers and / or emulsifiers can be used alone or in combination. Additionally or alternatively, the fine emulsion 109 can include one or more natural or synthetic preservatives, such as NAGARDO (glycolipid), ascorbic acid, ascorbyl palmitate, sodium benzoate, BHT, TBHQ, and / or sorbic acid. These preservatives can enhance chemical, physical, and / or microbiological stability.

[0027] In step 110, the microemulsion 109 can be mixed with a bulking agent or filler. The bulking agent can act as a carrier and aid in the drying process described below. Bulking agents can include, for example, maltodextrin, maltodextrin substitutes, starch (e.g., simple and complex sugars), protein (e.g., animal, whey, vegetable, pea, potato, hemp, etc.), fiber (e.g., chitin, cellulose, hemicellulose, inulin, fructan, gums, polyuronides, raffinose, polydextrose, etc.), and / or modified forms and derivatives thereof. For example, maltodextrin can be dissolved in the microemulsion 109 (in the aqueous phase) in small portions or by allowing it to stand for a period of time (e.g., about 12 hours). The ratio of filler to aqueous phase can be about 1:10 by weight (e.g., the aqueous or matrix phase contains about 9% filler), although other ratios (e.g., about 1:5 to about 1:20) can be used. By adding a bulking agent after the microemulsion 109 is formed, the desired particle size can be formed in step 108, which can then be coated or further encapsulated with the bulking agent in step 110. In contrast, adding a bulking agent before step 108 can interfere with the emulsification process, making it difficult or impossible to achieve the desired particle size.

[0027] In step 112, the mixture can be pasteurized (e.g., by ultraviolet light, heat, or gamma irradiation) if desired. In some instances, flash sterilization or high-temperature, short-time (HTST) sterilization may be preferred. Other suitable sterilization techniques may include retorting, autoclaving, using a plate-and-frame heat exchanger, or refractance window drying.

[0028] Finally, in step 114, the mixture can be dried using a refractance window drying (RWD) process. In a specific example, the dryer can include a drying chamber containing a heating medium (e.g., a hot water bath), a moving belt (e.g., a PET belt) suspended above or above the heating medium, an air supply (e.g., an air manifold) for supplying dry air, and an air exhaust (e.g., an air manifold) for removing moisture. In the RWD process, the heating medium heats the belt and the mixture by spreading the mixture evenly (e.g., using a spreader or applicator) onto the moving belt. As the belt and mixture are heated and move through the dryer, moisture evaporates from the mixture. The dried mixture is then collected at the exit of the dryer (e.g., using a scraper, blade, etc.). Details of RWD technology are described in U.S. Patent No. 11,221,179, issued January 11, 2022, the entire disclosure of which is incorporated herein by reference. The RWD process described herein can convert the wet mixture into DCE115, which can take the form of glassy, ​​dry flakes. It may also be used in combination with other drying techniques such as spray drying, drum drying, or freeze drying.

[0029] Referring to Table 1, an example of DCE115 produced by the method 100 described herein is shown. DCE115 may include cannabinoids, a bulking agent, water, a carrier oil, and an emulsifier. Each component shown in the table may be present within a range of "low" and "high" values, with "typical" indicating the average observed value. [Table 1]

[0030] In some embodiments, the DCE (e.g., DCE115) or compositions comprising DCE described herein can contain cannabinoids (or other active ingredients) in a range of about 1% to about 40% by weight. In certain embodiments, the cannabinoid (or other active ingredient) may be present in the DCE in an amount greater than, less than, or equal to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, or about 40% by weight.

[0031] In other embodiments, the DCE or compositions comprising DCE described herein can comprise a bulking agent in a range of about 10% to about 80% by weight. In certain embodiments, the bulking agent can be about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, or about 45% by weight of the DCE. , about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, or about 80%.

[0032] In yet another embodiment, the DCE or compositions comprising DCE described herein can contain water in the range of about 0% to about 6% by weight. In certain embodiments, water can be present in the DCE in an amount greater than, less than, or equal to about 0.005%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, or about 6% by weight.

[0033] In some embodiments, the DCE or compositions comprising DCE described herein can include a carrier oil in the range of about 1% to about 40% by weight. In certain embodiments, the carrier oil may be present in the DCE in an amount greater than, less than, or equal to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, or about 40% by weight.

[0034] Additionally, in some embodiments, the DCE or compositions comprising DCE described herein can comprise an emulsifier in the range of about 1% to about 20% by weight. In certain embodiments, the emulsifier can be present in the DCE in an amount greater than, less than, or equal to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% by weight.

[0035] In some embodiments, the DCE or compositions comprising the DCE described herein can include emulsion particles encapsulated within a matrix phase. This matrix phase can include water and / or a filler or bulking agent (e.g., maltodextrin). The DCE described herein can have a water content of less than about 6%, less than about 5%, less than about 4%, less than about 3%, or less than about 2% by weight. In some aspects, the water content of the DCE can be about 3% by weight. The water activity of the DCE can range from about 0.1 to about 0.7, or from about 0.3 to about 0.5, and in certain examples, can be about 0.4. The DCE described herein can feel dry to the touch. The content of the active ingredient (e.g., CBD or other cannabinoid) in the DCE can be about 40% or less, about 30% or less, about 20% or less, about 15% or less, about 10% or less, or about 5% or less by weight. Also, in some aspects, the active ingredient may be present in the DCE in a range of about 8% to about 12% by weight.

[0036] In some embodiments, the DCE described herein may be composed of or include flakes or particles of an amorphous solid and / or a glassy solid. The flakes or particles may be shiny and transparent, white-transparent, or pale yellow or brown. These flakes can be colored by adding a water-soluble or lipophilic dye (e.g., in steps 102 or 104). In certain embodiments, the RWD process can result in a DCE with a glassy or crystalline appearance, which differs from the dull, powdery appearance (e.g., obtained by other drying techniques, such as spray drying). The DCE may also have a larger particle size than powders obtained by, for example, spray drying. The DCE described herein may have a minimum, maximum, or average particle size ranging from, for example, about 100 μm to about 1000 μm or greater, and may be adjusted so that 90% or more of the particles pass through a 40 mesh (about 400 μm) screen. The large particle size of DCE (e.g., combined with the hydrophilic properties of the matrix phase) improves its dispersibility in water compared to powders, making it more readily wettable and soluble when added to a liquid. For example, when particles of DCE are added to an aqueous liquid, such as water, they may readily contact and / or wet, settle, and dissolve. In contrast, powders may not readily contact or wet aqueous liquids, and therefore may not settle and / or may be difficult to mix with aqueous liquids. Powders may also create dust, pose an inhalation hazard, or even pose an explosion hazard. In some embodiments, flakes or particles of DCE described herein may be milled to obtain a desired particle size, including particle sizes similar to those of powders (e.g., in the range of 20 μm to 80 μm). Additionally or alternatively, DCE may be mixed with other ingredients (e.g., different dry cannabinoid emulsions and / or liquids and / or dry pigments) to alter its composition or properties. In some instances, pigments may be introduced at other stages of method 100.For example, depending on the solubility of the pigment in water or oil, it may be added to the aqueous phase (e.g., containing water and an emulsifier) ​​or the oil phase (e.g., containing a carrier oil and a cannabinoid) (steps 102, 104, and 106). In other examples, the pigment may be added to a filler or bulking agent (e.g., step 110).

[0037] The DCE described herein may have improved bioavailability due to the increased water compatibility of water-insoluble cannabinoids compared to conventional compositions. The DCE can be reconstituted with an aqueous medium and administered orally, dermally, ophthalmically, or via other routes of administration. In some embodiments, the DCE described herein can be reconstituted into a beverage or added to food. It can also be incorporated into cosmetics, topicals, lotions, and the like, making it suitable for human and veterinary use. In certain embodiments, the DCE can be formed into a pill, capsule, or tablet and taken orally. It can also be formulated into a suppository and administered anally or vaginally.

[0038] In various embodiments, a system for producing a DCE described herein can include any of the materials and equipment described in method 100. For example, the system can include a water source, an emulsifier source, and a mixer and / or vessel for performing step 102, a carrier oil source, a cannabinoid (e.g., CBD) source, and a mixer and / or vessel for performing step 104, a high-speed mixer for performing step 106, a homogenizer for performing step 108, a filler or bulking agent source and mixer for performing step 110, a pasteurizer for performing step 112, a refractance window dryer for performing step 114, and a grinder, mixer, or blender for adjusting particle size and / or mixing the DCE with other ingredients.

[0039] Referring to Figure 2, the present disclosure provides a method 200 for producing a cannabinoid-cyclodextrin complex (e.g., DC-GCD). Method 200 may include mixing (combining) (e.g., by dropwise addition) an ethanol solution containing CBD 212 (or other cannabinoid) with an aqueous solution containing cyclodextrin 214 (e.g., step 210). When the ethanol solution 212 is added to the aqueous solution 214, the cyclic cyclodextrin molecules encapsulate the CBD molecules, and the resulting CBD-cyclodextrin complex 216 may precipitate from the solution. The ethanol solution may contain, for example, about 10 mg to about 1000 mg of CBD (or other cannabinoid) in 5 mL of ethanol, or about 100 mg of CBD in 5 mL of ethanol (i.e., about 20 mg of CBD per mL). The ethanol may be a mixture of ethanol and water, and may comprise about 90% to 100% ethanol by volume. In other embodiments, the ethanol in the ethanol solution may be replaced in whole or in part with another solvent (e.g., methanol, propanol, isopropanol, acetone, propylene glycol, dimethyl sulfoxide (DMSO), or a combination thereof). The aqueous solution of cyclodextrin may contain, for example, about 350 mg to about 1400 mg of cyclodextrin in 40 mL of water, or about 700 mg of cyclodextrin in 40 mL of water (i.e., about 17.5 mg of cyclodextrin per mL). The cyclodextrin may be gamma cyclodextrin, which may function to precisely encapsulate CBD molecules or other active ingredients.

[0040] In some embodiments, gamma cyclodextrin can be used in combination with or substituted by alpha cyclodextrin, beta cyclodextrin, and / or delta cyclodextrin, and / or alpha, beta, gamma, or delta forms of hydroxypropyl-cyclodextrin, methylated cyclodextrin, or acetylated cyclodextrin. Alternatively, cannabinoid complexes can be formed with other host-guest chemical systems. For example, cannabinoid complexes can be formed with calixarenes, dendrimers, cyclic peptides, or cyclic condensed tannins rather than cyclodextrins. Cyclic peptides may be more biocompatible and have nutritional value and specific biological benefits compared to cyclic condensed tannins. In some instances, cannabinoids complexed with hydroxypropyl-cyclodextrin may have improved or greater water solubility compared to other cannabinoid complexes.

[0041] Additionally or alternatively, the DC-GCD complex (or other cannabinoid complex) may be formulated with one or more other ingredients or additives to facilitate degradation in the body, such as by including an encapsulated amylase enzyme (step 218). The cannabinoid complex formulation may include excipients (e.g., antioxidants) to improve stability and / or bulking agents (e.g., maltodextrin, cellulose, sugars, sugar alcohols, etc.) to increase volume.

[0042] Additionally or alternatively, the cannabinoid complex formulation can include (e.g., instead of or in addition to amylase enzyme) other enzymes (e.g., amyloglucosidase enzyme, amylolytic enzymes, commercial enzyme preparations, probiotics (e.g., those containing Lactobacillus), etc.). In some embodiments, the enzyme activity level of the cannabinoid complex formulation can range from about 1,000 U to about 1,000,000 U.

[0043] After the DC-GCD complex (or other cannabinoid complex) is formed, it can be removed from the aqueous solution (e.g., as a precipitate) and dried. In certain embodiments, the cannabinoid complex can be separated from the aqueous solution using, for example, a filter, centrifuge, sedimentation device, other separation device, or a combination thereof. Additionally or alternatively, the cannabinoid complex can be dried in a refractance window dryer or other suitable dryer (e.g., a spray dryer, drum dryer, or freeze dryer) (step 220). Before or after drying, the cannabinoid complex can be mixed with enzymes (e.g., amylase enzymes), excipients, bulking agents, and / or other additives using a mill, blender, V-mixer, or the like to obtain the cannabinoid complex formulation 222 described herein.

[0044] Referring to Table 2, an example of a cannabinoid complex formulation (e.g., cannabinoid complex formulation 222) produced by the method 200 described herein is shown. The cannabinoid complex formulation may include one or more cannabinoid complexes, enzymes, excipients, bulking agents, and water. Each component shown in the table may be present within a range of "low" and "high" values, with "typical" indicating the observed average value. [Table 2]

[0045] In some embodiments, a cannabinoid complex formulation described herein (e.g., cannabinoid complex formulation 222) may contain one or more cannabinoid complexes (e.g., DC-GCD complexes) in a range of about 5% to about 20% by weight. In certain embodiments, one or more cyclodextrin complexes may be present in an amount greater than, less than, or equal to about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% by weight.

[0046] In some embodiments, the cannabinoid complex formulations described herein may include one or more enzymes (e.g., amylase enzymes) in the range of about 0% to about 10% by weight. In certain embodiments, the enzyme may be present in an amount greater than, less than, or equal to about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% by weight.

[0047] In some embodiments, the cannabinoid complex formulations described herein may include one or more excipients in the range of about 0% to about 50% by weight. In certain embodiments, the excipient may be present in an amount greater than, less than, or equal to about 0.05%, about 0.1%, about 0.5%, about 1%, about 5%, about 10%, about 15%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, or about 50% by weight.

[0048] In some embodiments, the cannabinoid complex formulations described herein may include a bulking agent in the range of about 0% to about 50% by weight. In certain embodiments, the bulking agent may be present in an amount greater than, less than, or equal to about 0.05%, about 0.1%, about 0.5%, about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, or about 50% by weight.

[0049] In some embodiments, the cannabinoid complex formulations described herein may contain water in the range of about 0% to about 6% by weight. In certain embodiments, water may be present in an amount greater than, less than, or equal to about 0.005%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, or about 6% by weight.

[0050] The dried cannabinoid complexes and / or cannabinoid complex formulations can be used in a variety of applications, such as beverages, food products, cosmetics, topicals, lotions, pills, capsules, and / or tablets, which are provided for human and / or animal consumption. In particular, complexation can reduce the bitter taste sometimes associated with cannabinoids.

[0051] In some instances, the dried cannabinoid complexes described herein are insoluble in water and therefore may be absorbed by the body in a manner different from DCE. For example, the oligosaccharide portion of the cannabinoid complex may be degraded by pancreatic enzymes in the intestinal lumen, releasing the free cannabinoids. This allows the cannabinoids to be readily absorbed into the bloodstream. Alternatively, the cannabinoid complexes may dissociate in the oral cavity, releasing the free cannabinoids, which can then be absorbed through the oral mucosa. The cannabinoid complexes may be used in a variety of oral applications, such as lozenges, edible films, hard candies, chewing gum, and chewable products.

[0052] In some instances, DC-GCD (or other cannabinoid complexes) can be combined with DCE in various ratios (e.g., co-dried using RWD) to create hybrid cannabinoid compositions that utilize the respective absorption pathways of DCE and DC-GCD. Complementary absorption of the active ingredients in the body may promote a more rapid effect or result in more consistent or reproducible effects. Combining DCE and DC-GCD can also help compensate for differences in absorption between individuals. For example, using a blend of DCE and DC-GCD may result in less variability in response between different individuals and a more uniform effect.

[0053] In certain cases, the hybrid composition may comprise a mixture of a cannabinoid complex (e.g., DC-GCD) and a DCE (e.g., DCE115). The cannabinoid complex and DCE may be included in the hybrid composition in any ratio and may be blended with one or more other ingredients (e.g., flavors, colors, bulking agents, etc.). In some examples, the weight ratio of cannabinoid complex to DCE in the hybrid composition may range from about 1:99 to about 99:1, or from about 10:90 to about 90:10, or from about 25:75 to about 75:25, or about 50:50.

[0054] In various embodiments, a system for producing a dried cannabinoid complex or dried cannabinoid complex formulation can include the materials and equipment described in method 200. For example, the system can include any or a combination of the following: a source of an ethanolic solution of cannabinoid, a source of an aqueous solution of cyclodextrin, and mixing equipment and / or vessel for performing step 210, a source of additives and mixing equipment for performing step 218, and a refractance window dryer for performing step 220.

[0055] While much of the description herein relates to cannabinoid-containing products, and more specifically, to products containing CBD, the materials and products described herein can include other active ingredients ("actives") in place of or in addition to CBD or other cannabinoids. Other possible active ingredients include, for example, plant oils, plant extracts, pigments, vitamins, alkaloids (e.g., psilocybin, nicotine, caffeine), flavorings, enzymes, prebiotics, probiotics, postbiotics, pharmaceuticals, dietary supplements, and / or cosmetic materials.

[0056] As used in the specification and claims, expressions such as "about" and "approximately equal" (e.g., "X is about Y" or "X is approximately equal to Y") should be understood to mean that one value (X) is within a given range of another value (Y). This given range may be any of ±20%, ±10%, ±5%, ±3%, ±1%, ±0.1%, or less than 0.1%, unless otherwise indicated.

[0057] The indefinite articles "a" and "an" used in this specification and claims should be understood to mean "at least one" unless a clear contrary intention is indicated. The term "and / or" used in this specification and claims should be understood to mean "either or both" of the associated elements, i.e., including the presence of both in some instances and the presence of only one in other instances. Multiple elements connected by "and / or" should be interpreted similarly to refer to "one or more elements." Furthermore, "and / or" does not exclude the presence of other elements besides the elements identified. Thus, as a non-limiting example, when a phrase such as "A and / or B" is used in conjunction with an open expression such as "comprising," it should be interpreted as referring, in one embodiment, to only A (optionally including elements other than B), in another embodiment to only B (optionally including elements other than A), and in yet another embodiment to both A and B (optionally including other elements).

[0058] As used in the specification and claims, "or" should be understood to have the same meaning as "and / or" above. For example, when separating items in a list, "or" or "and / or" should be interpreted to indicate the possibility of including one or more elements from the list, and may include additional, unlisted items. However, the explicit phrases "only one of" or "exactly one of," or the use of "consisting of" in the claims, refer to the inclusion of exactly one element from the list. Generally, "or" will be interpreted as indicating exclusive alternatives (i.e., "one or the other, but not both") only when preceded by language indicating exclusivity, such as "either," "one of," or "exactly one of." The phrase "consisting essentially of" shall have its meaning as commonly used in the field of patent law.

[0059] In this specification and claims, the phrase "at least one," when referring to a list of one or more elements, should be understood to mean the inclusion of any one or more elements in the list, but not necessarily all elements in the list, and does not exclude any combination of elements in the list. This definition does not exclude the optional inclusion of other elements, related or not, in addition to the specific elements in the list to which "at least one" refers. Thus, by way of example, "at least one of A and B," or the equivalent phrases "at least one of A or B," "at least one of A and / or B," in one embodiment, refers to the presence of at least one or more A's and the absence of B (which may include elements other than B). In another embodiment, refers to the presence of at least one or more B's and the absence of A (which may include elements other than A). In yet another embodiment, refers to the presence of at least one or more A's and at least one or more B's (which may include elements other than A).

[0060] The terms "including," "including," "having," "containing," "involving," and variations thereof are intended to encompass not only the items listed after these terms, but also additional items.

[0061] The use of ordinal numbers such as "first," "second," "third," etc. in the claims does not in itself indicate a priority, precedence, or chronological order of the claim elements or method steps. The ordinal numbers are merely used as labels to distinguish a claim element from other similarly named elements.

[0062] Each numerical value set forth in this specification (e.g., a numerical value shown in a table, chart, or graph) is considered to represent the minimum or maximum value in the range of the corresponding parameter. Therefore, when a numerical value is added to a claim, the numerical value will follow the guidance of this specification and clearly support a range extending up and down based on the numerical value. However, unless included in a claim, each numerical value set forth in this specification should not be construed as limiting in any sense.

[0063] The terms and expressions used herein are for the purpose of description and not limitation. The use of these terms and expressions is not intended to exclude equivalents of the features shown and described, or portions thereof. Furthermore, while specific embodiments of the present invention have been described, it will be apparent to those skilled in the art that other embodiments incorporating the concepts disclosed herein may be utilized without departing from the spirit and scope of the present invention. The features and functions of the various embodiments may be configured in various combinations and variations, all of which are considered to be within the scope of the present invention. The described embodiments, therefore, are to be considered in all respects as illustrative and not restrictive. Furthermore, the configurations, materials, and dimensions set forth herein are illustrative and not intended to be limiting in any respect. Similarly, while physical descriptions are provided for illustrative purposes, there is no intention to be bound by any particular theory or mechanism, nor is there any intention to limit the scope of the claims thereto.

Claims

1. 1. A method for producing a dried cannabinoid emulsion (DCE), comprising: obtaining an aqueous phase; obtaining an oil phase containing cannabinoids; forming a water-in-oil (O / W) emulsion in which the oil phase is suspended as particles in the aqueous phase; and drying the emulsion using a refractance window dryer to form a dried cannabinoid emulsion (DCE).

2. 10. The method of claim 1, wherein the aqueous phase comprises water and at least one emulsifier, the at least one emulsifier comprising at least one of a sucrose ester or a saponin.

3. The method of claim 1 , wherein the oil phase comprises a carrier oil comprising a medium chain triglyceride (MCT) oil.

4. 10. The method of claim 1, wherein the cannabinoid comprises CBD isolate.

5. 10. The method of claim 1, wherein the step of forming the water-in-oil emulsion comprises using a high-pressure homogenizer.

6. The method of claim 1 , wherein the particles comprise a size ranging from about 10 nm to about 400 nm.

7. 10. The method of claim 1, further comprising mixing the water-in-oil emulsion with a weighting agent.

8. 1. A dry cannabinoid emulsion (DCE) composition comprising: a matrix phase comprising a bulking agent and water; and Particles of an oil phase containing cannabinoids dispersed within said matrix phase, the particle size of which ranges from about 10 nm to about 400 nm. A composition comprising:

9. the composition comprises the bulking agent in the range of about 10% to about 80% by weight; said water in the range of about 0% to about 6% by weight; containing the cannabinoid in the range of about 1% to about 40% by weight, Carrier oil in the range of about 1% to about 40% by weight, 9. The composition of claim 8, comprising an emulsifier in the range of about 1% to about 20% by weight.

10. 9. The composition of claim 8, further comprising an emulsifier comprising at least one of the sucrose ester or a saponin.

11. 9. The composition of claim 8, wherein the oil phase comprises a carrier oil comprising a medium chain triglyceride (MCT) oil.

12. 9. The composition of claim 8, wherein the cannabinoid comprises CBD isolate.

13. 10. The composition of claim 8, further comprising a dried cannabinoid complex.

14. 1. A method for producing a dried cannabinoid-cyclodextrin complex, comprising: obtaining an aqueous solution containing cyclodextrin; adding a mixture of ethanol and cannabinoid to the aqueous solution to form a cannabinoid-cyclodextrin complex; drying the cannabinoid-cyclodextrin complex in a refractance window dryer to form a dried cannabinoid-cyclodextrin complex; A method comprising:

15. 15. The method of claim 14, wherein the cyclodextrin comprises at least one of gamma cyclodextrin, alpha cyclodextrin, beta cyclodextrin, or hydroxypropyl-cyclodextrin.

16. 15. The method of claim 14, further comprising mixing the cannabinoid-cyclodextrin complex with at least one of an amylase enzyme, an excipient, or a bulking agent.

17. a dried cannabinoid-cyclodextrin complex; at least one of an amylase enzyme, an excipient, or a bulking agent mixed with the dried cannabinoid-cyclodextrin complex; A composition comprising:

18. the composition comprises the dried cannabinoid-cyclodextrin complex in the range of about 5% to about 20% by weight; the amylase enzyme in the range of about 0% to about 10% by weight; the excipients in the range of about 0% to about 50% by weight, 18. The composition of claim 17, comprising the bulking agent in the range of about 0% to about 50% by weight.

19. 18. The composition of claim 17, wherein the dried cannabinoid-cyclodextrin complex comprises at least one of alpha cyclodextrin, beta cyclodextrin, gamma cyclodextrin, delta cyclodextrin, alpha hydroxypropyl cyclodextrin, beta hydroxypropyl cyclodextrin, gamma hydroxypropyl cyclodextrin, delta hydroxypropyl cyclodextrin, a methylated cyclodextrin, or an acetylated cyclodextrin.

20. 18. The composition of claim 17, further comprising a dry cannabinoid emulsion (DCE).

Images