WO2020028897A1

WO2020028897A1 - CONSTRUCT OF β-CYCLODEXTRIN AND CANNABINOID GUEST COMPLEX AND PROCESSES FOR PRODUCING A PASTE COMPRISING THE SAME

Info

Publication number: WO2020028897A1
Application number: PCT/US2019/045086
Authority: WO
Inventors: Mason Alexander LEGRANGE; Tiffany Lynnan COLEMAN; Thomas GUEL; Chuck CIANCANELLI; Lyle O'BRIEN
Original assignee: Lilu's Garden, Ltd.
Priority date: 2018-08-03
Filing date: 2019-08-05
Publication date: 2020-02-06

Abstract

Provided herein are water-soluble cannabinoid compositions wherein a cannabinoid is complexed with a cyclodextrin. For example, provided herein is a unique and previously undescribed encapsulation of β-cyclodextrin and CBD (a two hydroxyl group- containing cannabinoid). Also provided herein are methods of preparing water-soluble cannabinoid complexes, wherein a reaction mixture comprising a cannabinoid component and a cyclodextrin component uniformly dispersed in a polar solvent is heated to a temperature just below the melting point of the cannabinoid component.

Description

CONSTRUCT OF b-C Y CLODEXTRIN AND C ANNABIN OID GUEST COMPLEX AND PROCESSES FOR PRODUCING A PASTE COMPRISING THE SAME

BACKGROUND

[0001] There is a rapidly increasing demand for edible food products that contain cannabinoids, such as cannabidiol (CBD). Particularly of interest are water-based products, such as beverages and water-based pharmaceuticals, that include cannabinoids.

[0002] Unfortunately, the majority of cannabinoids are hydrophobic, and they demonstrate limited solubility in water. Although some progress has been made in producing water-soluble cannabinoid products, current practices have multiple significant drawbacks.

[0003] For example, because most cannabinoids have flavor profiles that are undesirable, it is attractive to develop a method that masks the bitter aftertaste and other adverse taste properties of cannabinoids in a beverage product. However, many current methods for incorporating cannabinoids into beverage products fail to adequately address adverse flavor problems. Additionally, known methods for increasing the water-solubility of cannabinoids frequently require high concentrations of sugar and salts. Unfortunately, cannabinoid compositions prepared with large weight percentages of sugars significantly increase the caloric content of the final product, and such products are also often

characterized by undesirable taste.

[0004] Current methods for incorporating cannabinoids into beverage products also have many drawbacks with respect to their manufacturing processes. For example, known methods generally require high volumes of additives to increase cannabinoid solubility, which dilute the concentration of the active cannabinoid in the formulation. This is undesirable for two main reasons. First, the manufacturer of the final food product or pharmaceutical composition must use higher concentrations of the final water-soluble formulation to achieve desired amounts of the active cannabinoid in the end product, and that can lead to problems with taste, product consistency, or other critical product quality attributes. Second, many known methods can alter the chemistry of the cannabinoid molecule, which can result in a reduced efficacy of the formulation or, worse, the formation of undesirous side products that may have unknown adverse effects.

[0005] For example, in a widely used method of preparing water-soluble cannabinoid compositions, the cannabinoid is sonicated in water with a series of additives, resulting in a product wherein a portion of the cannabinoid has been microencapsulated. In addition to suffering from many or all the drawbacks listed above, these processes are complicated and time consuming to execute, and they are not easy to commute to an industrial scale.

[0006] It is therefore desirable to develop alternatives to existing techniques for incorporating cannabinoids into aqueous formulations. Particularly, it is attractive to develop a process for producing a water-soluble cannabinoid composition that is efficient, scalable, and which results in a product with a high concentration of the cannabinoid active ingredient. It is also desirous to develop a water-soluble cannabinoid composition that is edible, that masks the taste of the cannabinoid, that does not have a significant caloric content, and that can easily be introduced into downstream product formulations.

SUMMARY

[0007] Provided herein is a method of preparing a water-soluble cannabinoid composition, the method comprising combining a cannabinoid component and a cyclodextrin component in the presence of a polar solvent, thereby forming a uniform formulation; and heating the formulation to a temperature within about 10 °C of the melting point of the cannabinoid component.

[0008] Also provided herein is a water-soluble cannabinoid composition comprising a cannabinoid component, a cyclodextrin component, and a polar solvent. [0009] Also provided herein is an inclusion complex consisting of a cannabinoid component, a cyclodextrin component, and water, wherein the molar ratio of the cyclodextrin component to the cannabinoid component is about 2:1, and wherein the molar ratio of the cyclodextrin component to water is about 1 : 1.

[0010] Other aspects and features of the present disclosure are provided below.

DETAILED DESCRIPTION

[0011] Provided herein are water-soluble cannabinoid compositions wherein a cannabinoid is complexed with a cyclodextrin. For example, provided herein is a unique and previously undescribed encapsulation of b-cyclodextrin and CBD (a two-hydroxyl group- containing cannabinoid). The processes described herein can be used to prepare a novel guest molecule/ -cyclodextrin complex (e.g., a thick suspension) relative to insoluble guest complexes settled on the bottom of an oversaturated aqueous solution. The aqueous swelling of the hydrated b-cyclodextrin/CBD complex creates a unique form of paste that allows for a more concentrated dose of water-soluble CBD relative to other b-cyclodextrin/CBD complexes.

[0012] As described in further detail below, it is believed that other hydroxyl group containing cannabinoids can be processed in a manner analogous to that outlined herein for CBD. As such, CBD can be considered as a two-hydroxyl group cannabinoid/terpene with - OH groups located on ring carbons G and 3’ in Delta-2-CBD and Delta- 1 -CBD models respectively. It is further believed that the processes described herein can be applied to previously unidentified cannabinoid/terpene compounds containing one or more hydroxyl groups. Cannabinoids [0013] The water-soluble cannabinoid compositions provided herein may comprise one or more cannabinoids. As used herein, the term“cannabinoid” generally refers to a chemical compound that expresses a pharmacodynamic effect in man when bound to a cannabinoid receptor.

[0014] Cannabinoids suitable for use in the compositions provided herein include, for example, endocannabinoids, phytocannabinoids, and synthetic cannabinoids. For example, the cannabinoid may be a phytocannabinoid that is derived from a Cannabis plant. Non- limiting examples of specific cannabinoids that can be incorporated into the compositions provided herein include cannabidiol (CBD),

cannabidiobc acid (CBD A),

CBDA

cannabinol (CBN),

cannabigerol (CBG),

cannabichromene (CBC),

cannabicyclol (CBL),

cannabivarin (CBV),

tetrahydrocannabivarin (THCV),

THCV

cannabidivarin (CBDV),

CBDV

cannabichromevarin (CBCV),

cannabigerovarin (CBGV),

CBGV

cannabielsoin (CBE),

cannabicitran (CBT),

tetrahydrocannabinol (THC),

THC

tetrahydrocannabinol! c acid (THCA),

THCA

and derivatives thereof (e.g., cannabigerol monomethyl ether (CBGM)). For example, the cannabinoid may be selected from the group consisting of CBD and CBDA. In a preferred embodiment, the cannabinoid is CBD.

[0015] Compositions comprising mixtures of two or more cannabinoids are also within the scope of the present disclosure. As a non-limiting example, the cannabinoid component may comprise both CBD and CBDA. As a further example, the cannabinoid component may comprise a full-spectrum or multi-spectrum oil extracted from a Cannabis plant. In a particularly preferred embodiment, the cannabinoid component comprises an oil extracted from a Cannabis plant wherein the oil comprises at least about 50% by weight of CBD.

Cyclodextrins

[0016] The water-soluble cannabinoid compositions provided herein may comprise one or more cyclodextrins. Cyclodextrins are cyclic oligoglucosides containing 5 or more glucose residues, and they have a hydrophilic exterior and a hydrophobic core. It has been discovered that cannabinoids, being hydrophobic, can be received in the center of the cyclodextrin core, which results in the formation of a water-soluble complex (e.g., an inclusion complex).

[0017] The number of glucose residues within the structure of a given cyclodextrin ring determines the diameter of the hydrophobic pocket. Which compounds can be successfully encapsulated and solubilized by a given cyclodextrin is a function of the hydrophobic pocket diameter. Non-limiting examples of cyclodextrins suitable for use in the compositions provided herein include a-cyclodextrins, b-cyclodextrins, g-cyclodextrins, and hydroxypropyl- -cyclodextrins. In preferred embodiments, the cyclodextrin is a b- cyclodextrin or hydroxylpropyl^-cyclodextrin.

[0018] Accordingly, in a preferred embodiment, at least about 50% by weight of the cannabinoid component forms an inclusion complex with the cyclodextrin component. For example, at least about 60%, at least about 70%, at least about 80%, or at least about 90% by weight of the cannabinoid component forms an inclusion complex with the cyclodextrin component.

[0019] In preferred embodiments, the composition comprises the cyclodextrin component in molar excess relative to the cannabinoid component. The molar ratio of the cyclodextrin component to the cannabinoid component may range, for example, from about 1: 1 to about 10: 1, from about 1: 1 to about 5: 1, from about 1 : 1 to about 4: 1, from about 1: 1 to about 3 : 1 , or from about 1.5 : 1 to about 3 : 1. In a particularly preferred embodiment, the molar ratio of the cyclodextrin component to the cannabinoid component is about 2:1.

[0020] Without being bound to any particular theory, it is believed that each cannabinoid molecule can form a complex with two cyclodextrins, which together will fully encapsulate the cannabinoid. This type of complex, in which the cannabinoid is fully encapsulated within a lattice formed by the cyclodextrins, is known in the art as a clathrate. Once the cannabinoid molecule becomes incorporated into the hydrophobic pocket formed by the cyclodextrin molecule(s), the sole interaction between the cannabinoid/cyclodextrin complex and any surrounding water will take place via the hydrophilic interface of the cyclodextrin outer ring hydroxyl groups. This allows the cyclodextrin/cannabinoid complex to exhibit water solubility far greater than that of the cannabinoid molecule in isolation.

[0021] Accordingly, in a preferred embodiment, at least about 50% by weight of the cannabinoid component forms a clathrate with the cyclodextrin component. For example, at least about 60%, at least about 70%, at least about 80%, or at least about 90% by weight of the cannabinoid component can form a clathrate with the cyclodextrin component.

[0022] Additionally, and without being bound to a particular theory, it is believed that the presence of two hydroxyl groups on CBD (and on other cannabinoids having two hydroxyl groups, as generally described herein) allows it to form a complex resulting in a thick paste, rather than the sediment/saturated supernatant mixture that would be obtained using prior art methods of combining cannabinoids and cyclodextrins. At this time, it is also believed that a similar complex and resulting thick paste can be formed by combining a cannabinoid having a single hydroxyl group with a cyclodextrin that has been functionalized to include one or more additional hydroxyl groups. In other words, and again without being bound to a particular theory, it is believed that the addition of additional hydroxyl groups to the cyclodextrin molecule can compensate for the presence of only one hydroxyl group on these cannabinoids (e.g., THC). Accordingly, it is believed that the processes described herein can be generally applied to form a water-soluble paste comprising any cannabinoid having one or more hydroxyl groups, so long as an appropriate cyclodextrin molecule is selected in accordance with the principles described above.

[0023] Therefore, in some embodiments, it is desirable to select a cyclodextrin having an increased concentration of hydroxyl groups relative to b-cyclodextrin. For example, the cyclodextrin component may comprise a functionalized b-cyclodextrin having at least 1, at least 2, at least 3, at least 4, or at least 5 or more additional hydroxyl groups. Non-limiting examples include hydroxypropyl a-cyclodextrin, hydroxypropyl b-cyclodextrin, and hydroxypropyl g-cyclodextrin. In a particularly preferred embodiment, the cyclodextrin comprises hydroxypropyl b-cyclodextrin.

Hydroxypropyl-P-cyclodextrin

[0024] As used herein, the term“hydroxyl” refers to a group of the form -OH.

Polar Solvent

[0025] The water-soluble cannabinoid compositions provided herein may further comprise a polar solvent. Non-limiting examples of polar solvents include water and ethanol. In a preferred embodiment, the polar solvent is water. Without being bound to a particular theory, it is believed that the addition of the polar solvent (e.g., water) drives the hydrophobic molecules into the center of the cyclodextrins, and therefore increases the amount of oil (e.g., the cannabinoid) that makes it to the center of the cyclodextrins.

Methods of Preparing Water-Soluble Cannabinoid Complexes

[0026] Also provided herein are methods of preparing water-soluble cannabinoid complexes.

[0027] In a first step of the method, a cannabinoid component and a cyclodextrin component are combined. In preferred embodiments, both materials are introduced at temperatures slightly above the melting point of the desired cannabinoid(s). After the mixture is mixed (as needed) to a uniform state, a polar solvent (e.g., water) is introduced. In preferred embodiments, the polar solvent is also introduced at a temperature above the melting point of the desired cannabinoid(s). The components are then mixed (e.g., by stirring, agitation, mixing, or kneading) as needed to form a homogeneous mixture. The cannabinoid component, cyclodextrin component, and polar solvent may each be selected as described above. Generally, the components may be combined in any order. In preferred embodiments, prior to the combination step, each component is heated to a temperature close to the melting point of the cannabinoid component as described in further detail below.

[0028] In preferred embodiments, the mixture comprises the polar solvent in an amount of greater than about 30% by weight, for example greater than about 40% by weight or greater than about 50% by weight relative to the formulation as a whole, but less than the amount required to maintain a complete suspension of the cyclodextrin and cannabinoid components. [0029] In a further step of the process, the mixture of the cannabinoid component, cyclodextrin component, and polar solvent is maintained at a temperature close to the melting point of the cannabinoid component. For example, the mixture may be heated to a temperature within about 10 °C, within about 5 °C, within about 4 °C, within about 3 °C, within about 2 °C, or even within about 1 °C of the melting point of the cannabinoid component. In preferred embodiments, the formulation is maintained at a temperature just above the melting point of the cannabinoid component. During this step, the mixture will transition from a non-viscous mixture of particulates and solvent to a thick paste.

[0030] Without being bound to theory, it is believed that the process described above facilitates driving the cannabinoid into the central cavity formed by the cyclodextrin, thereby forming an inclusion complex. In embodiments where the polar solvent is water, it is further believed that the process facilitates the formation of a complex wherein the

cannabinoid/cyclodextrin inclusion complex becomes associated with one or more water molecules. In particular, it is believed that the hydroxyl groups present on the outer surface of the cannabinoid facilitate the formation of a complex with the water molecules, and that this step leads to the formation of a thick paste having the desirable properties described herein.

[0031] Prior art methods of combining cyclodextrin, cannabinoids and water that are not heated and prepared as described herein will not form the paste formulation described above. Traditional use of cyclodextrin will reach a solubility limit in water that results in the cyclodextrin dropping out and forming two layers. In contrast, the process described herein allows for the formation of a more concentrated paste than can be achieved using prior art methods.

[0032] In some embodiments, the paste may be dried (e.g, using conventional dehydration techniques) to form a powder. Edible Compositions

[0033] Also provided herein is an edible composition comprising a water-soluble cannabinoid complex. The edible composition may be, for example, a food or a beverage.

[0034] The water-soluble cannabinoid complexes described herein can be formulated, for example, as a concentrated paste or syrup. The paste or syrup advantageously contains a high concentration of the cannabinoid active ingredient, and is appropriate for use in personal dispensing devices, soda stations, large-scale beverage production lines, and more generally any large-scale liquid product botling line.

[0035] Accordingly, the water-soluble cannabinoid complexes described herein may be incorporated into a variety of beverage products. For example, the cannabinoid complexes may be incorporated into flavored water products and soft drinks; alcoholic beverages; and concentrated liquids suitable for sublingual application, as non-limiting examples. That said, we recognize that the inclusion of additional hydroxyl groups described above and defined here as being present on a cannabinoid/terpene structure allows the ability for the B- cyclodextrin/cannabinoid complex to uptake additional water once certain experimental conditions are met(i.e temperature that approximates solid to liquid state transitions of the guest compound in the presence of water).

[0036] The water-soluble cannabinoid complexes described herein provide many advantages that make them desirable to include in food and beverage products. Current methods for increasing the water-solubility of cannabinoids require high concentrations of sugar and salts. As a result, cannabinoid compositions prepared using current methods will significantly increase the caloric content of the final product, and they will also impart an undesirable taste. In contrast, the cannabinoid/cyclodextrin complexes described herein provide minimal calories and impart litle or no detectible taste or odor to the final product. Pharmaceutical Compositions [0037] Also provided herein is a pharmaceutical composition prising a water-soluble cannabinoid complex. The pharmaceutical composition can comprise one or more pharmaceutically acceptable excipients. Suitable excipients are generally known to those skilled in the art.

[0038] The pharmaceutical composition can generally comprise any dosage form known in the art. For example, the composition can be in the form of a tablet, capsule, granulated powder, or gel (e.g., a gel capsule). As further non-limiting examples, the composition can be in the form of a liquid suspension, emulsion, or aqueous solution.

[0039] Other objects and features will be in part apparent and in part pointed out hereinafter.

EXAMPLES

[0040] The following non-limiting examples are provided to further illustrate the present disclosure. Example 1

[0041] An experiment was conducted using the following materials: a hot plate with magnetic stir bar; two 500 mL beakers; a 250 mL beaker; a 100 mL graduated cylinder; oven; analytical scale; infrared thermometer; 15.00 g 99+% CBD isolate; 75.00 g beta-cyclodextrin; and 225 mL distilled water.

[0042] An oven was heated to 71 °C, within range of the melting point of CBD. CBD isolate, beta-cyclodextrin, and water were placed in the oven to reach a temperature of 71 °C. The temperature of the components was measured with an infrared thermometer until the desired temperature was reached. [0043] The CBD isolate was melted to an oil, and beta-cyclodextrin was heated to 71

°C. The formulation was pulled out of oven, and the beta-cyclodextrin was poured into a 500 mL beaker containing melted CBD isolate. Using a lab spatula, the two components were mixed together as thoroughly as possible. The mixture was then placed back in the oven to regain temperature of 71 °C. This was to make sure the CBD was melted as much as possible to drive more of the oil into the hydrophobic pocket of beta-cyclodextrin. This step was repeated three times to reach a uniform mixture not containing clumps.

[0044] Once both the beta-cyclodextrin/CBD mixture and distilled water reached 71

°C (using infrared thermometer), the mixture was slowly stirred with approximately 115 mL (roughly half) of the distilled water in the 500 mL beaker containing powder. The mixture was then placed back in oven to regain the desired temperature of 71 °C.

[0045] After reaching temperature, the beaker was placed on a hot plate set at 115 °C.

The rest of the water was poured in, and the magnetic stir bar was turned on. At this point, the top layer of container with 115 mL water + beta-cyclodextrin/CBD powder had a layer of paste already forming by the time it reached 71 °C in the oven.

[0046] The stir bar continued to move until the material thickened to a consistency that rendered it motionless. This occurred 8 minutes after the last half of water was mixed in and the material was agitated/heated on the hot plate.

[0047] The temperature of the slurry in the beaker was between 71 °C and 74 °C until the mixture transitioned to paste. Post-transition, the material had decreased in temperature to 68 °C. Without being bound to any particular theory, the temperature decrease may have been due to the inability of the stir bar to continue stirring the material after it transitioned to a paste. Example 2

[0048] An experiment was conducted using the following materials: a hot plate with magnetic stir bar; two 500 mL beakers; a 250 mL beaker; a 100 mL graduated cylinder; oven; analytical scale; infrared thermometer; 15.00 g 99+% CBD isolate; 75.00 g beta-cyclodextrin; and 225 mL distilled water.

[0049] An oven was heated to 71 °C, within range of the melting point of CBD. CBD isolate, beta-cyclodextrin, and water were placed in the oven to reach a temperature of 71 °C. The temperature of the components was measured with an infrared thermometer until the desired temperature was reached.

[0050] The CBD isolate was melted to an oil, and beta-cyclodextrin was heated to 71

°C. The formulation was pulled out of oven, and the beta-cyclodextrin was poured into a 500 mL beaker containing melted CBD isolate. Using a lab spatula, the two components were mixed together as thoroughly as possible. The mixture was then placed back in the oven to regain temperature of 71 °C. This was to make sure the CBD was melted as much as possible to drive more of the oil into the hydrophobic pocket of beta-cyclodextrin. This step was repeated two times to reach a uniform mixture not containing clumps.

[0051] The beta-cyclodextrin/CBD mixture and distilled water were at different temperatures, both below 71 °C, 65 °C and 61 °C respectively (measured with an infrared thermometer). The beaker was again placed on the hot plate set to 115 °C, and then 225 mL of distilled water was charged into the 500 mL beaker containing the powder. The stir bar was turned on for further agitation until the mixture turned to paste.

[0052] After 30 minutes, the solution had been maintaining temperatures around 71

°C, but not transitioning over to paste. The temperature of the hot plate was increased to try to speed up transition. The mixture was held at 74 °C for another 30 minutes before transitioning to paste. The stir bar continued to move until the formulation thickened to a consistency that rendered it motionless. This happened approximately 60 minutes after the water was mixed in on the hot plate.

[0053] Post-transition the material had decreased in temperature to 68 °C. Without being bound to any particular theory, the temperature decrease may have been due to the inability of the stir bar to continue stirring the material after it transitioned to a paste.

[0054] The extended time to transition, relative to Example 1, is believed to be related to the material not being at the same temperature of 71 °C, the melting point of CBD. This did not prevent the paste from being achieved, but is noted to provide data for increasing efficiency in conversion to as little time as possible. Example 3

[0055] An experiment was conducted using the following materials: a hot plate with magnetic stir bar; two 500 mL beakers; a 250 mL beaker; a 100 mL graduated cylinder; oven; analytical scale; infrared thermometer; 15.00 g Full-Spectrum Cannabis Oil/Crumble (FSO); 75.00 g beta-cyclodextrin; and 225 mL distilled water. The FSO was a composition of cannabinoids and terpenes, and contained 84% CBD.

[0056] An oven was heated to 71 °C, within range of the melting point of CBD. FSO, beta-cyclodextrin, and water were placed in the oven to reach a temperature of 71 °C. The temperature of the components was measured with an infrared thermometer until the desired temperature was reached.

[0057] The FSO was melted to an oil, and beta-cyclodextrin was heated to 71 °C. The formulation was pulled out of oven, and the beta-cyclodextrin was poured into a 500 mL beaker containing melted FSO. Using a lab spatula, the two components were mixed together as thoroughly as possible. The mixture was then placed back in the oven to regain temperature of 71 °C. This was to make sure the CBD was melted as much as possible to drive more of the oil into the hydrophobic pocket of beta-cyclodextrin. This step was repeated three times to reach a uniform mixture not containing clumps.

[0058] Once the beta-cyclodextrin/FSO mixture and distilled water reached 71 °C

(using an infrared thermometer), 115 mL (roughly half) of the distilled water was charged into the 500 mL beaker containing the powder. The mixture was then placed back in the oven to regain a desired temperature of 71 °C.

[0059] After reaching the desired temperature, the beaker was placed on a hot plate and set at a temperature of 115 °C. The rest of the water was poured in and the magnetic stir bar was turned on. The stir bar continued to move until the material thickened to a consistency that rendered it motionless. This occurred 10 minutes after the last half of the water was mixed in, and the material was agitated/heated on the hot plate. The temperature of the slurry in the beaker was between 71 °C and 74 °C until the mixture transitioned to a paste.

Example 4

[0060] The batch size of water-soluble cannabinoid paste produced 330.00 grams following this procedure. 15.004 grams of CBD testing at 99.9wt% with a molecular weight of 314.64 g/mol was prepared for this procedure. 132.375 grams of beta-cyclodextrin with a moisture content of 10% and a molecular weight of 1134.987 g/mol was weighed out. The third and final ingredient, deionized water, was weighed out to 187.676 grams. Beta- Cyclodextrin calculation for 2: 1 (molar basis) ratio of beta-cyclodextrin: CBD was calculated using the following equation, accounting for moisture content: 15.004 g CBD*(l 134.987 g/mol / 314.464 g/mol) * 2/0.9 * 1.1 = 132.375 grams of beta-cyclodextrin. Combine 150 grams of water and beta-cyclodextrin. Heat the mixture to 72 degrees centigrade while agitating using a SILVERS ON mixer at 2000RPM. Melt the CBD at 70 degrees centigrade in its own beaker. Liquid CBD was added to the 72 degrees centigrade mixture of water and beta-cyclodextrin under the SILVERSON mixer, still at 2000RPM. This resulted in a homogenized mixture that turned into a thick paste after 35 seconds of the solutions being introduced under agitation. The resulting batch weight was 292.324 grams. 37.676 grams of deionized water was added to the paste as a Quantum Satis (Q.S.) to achieve a final batch weight of 330.000 grams.

Example 5

[0061] The batch size produced was 330.00 grams subsequent to the following procedure. 15.004 grams of CBD testing at 99.9wt% with a molecular weight of 314.64 g/mol was prepared for this procedure. 132.375 grams of beta-cyclodextrin with a moisture content of 10% and a molecular weight of 1134.987 g/mol was weighed out. The third and final ingredient, deionized water, was weighed out to 188.886 grams. Beta-Cyclodextrin calculation for 2: 1 (molar basis) ratio of beta-cyclodextrin: CBD was calculated using the following equation, accounting for moisture content: 15.004 g CBD*(l 134.987 g/mol / 314.464 g/mol) * 2/0.9 * 1.1 = 132.375 grams of beta-cyclodextrin. Combine 150 grams of water and beta-cyclodextrin. Heat the mixture to 72 degrees centigrade while agitating using a SILVERSON mixer at 2000RPM. Melt the CBD at 72 degrees centigrade in its own beaker. Liquid CBD was added to the 72 degrees centigrade mixture of water and beta-cyclodextrin under the SILVERSON mixer, still at 2000RPM. This resulted in a homogenized mixture that turned into a thick paste after 32 seconds of the solutions being introduced under agitation. The resulting batch weight was 291.114 grams. 37.886 grams of deionized water was added to the paste as a Quantum Satis (Q.S.) to achieve a final batch weight of 330.000 grams.

Example 6

[0062] The batch size produced was 330.00 grams subsequent to the following procedure. 15.004 grams of CBD testing at 99.9wt% with a molecular weight of 314.64 g/mol was prepared for this procedure. 132.375 grams of beta-cyclodextrin with a moisture content of 10% and a molecular weight of 1134.987 g/mol was weighed out. The third and final ingredient, deionized water, was weighed out to 186.578 grams. Beta-Cyclodextrin calculation for 2: 1 (molar basis) ratio of beta-cyclodextrin: CBD was calculated using the following equation, accounting for moisture content: 15.004 g CBD*(l 134.987 g/mol / 314.464 g/mol) * 2/0.9 * 1.1 = 132.375 grams of beta-cyclodextrin. Combine 150 grams of water and beta-cyclodextrin. Heat the mixture to 72 degrees centigrade while agitating using a SILVERSON mixer at 2000RPM. Melt the CBD at 72 degrees centigrade in its own beaker. Liquid CBD was added to the 72 degrees centigrade mixture of water and beta-cyclodextrin under the SILVERSON mixer, still at 2000RPM. This resulted in a homogenized mixture that turned into a thick paste after 32 seconds of the solutions being introduced under agitation. The resulting weight was 288.321 grams. 41.679 grams of deionized water was added to the paste as a Quantum Satis (Q.S.) to achieve a final batch weight of 330.000 grams. An additional 5.101 grams of deionized water were added to account for loss of weight due to evaporation. This keeps the batch size consistent for all three components of the formulation.

[0063] When introducing elements of the present disclosure or the preferred embodiment(s) thereof, the articles“a”,“an”,“the”, and“said” are intended to mean that there are one or more of the elements. The terms“comprising”,“including”, and“having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.

[0064] In view of the above, it will be seen that the several objects of the disclosure are achieved and that other advantageous results are attained.

[0065] As various changes could be made in the above products and methods without departing from the scope of the disclosure, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

Claims

CLAIMS What is claimed is:

1. A method of preparing a water-soluble cannabinoid composition, the method comprising:

combining a cannabinoid component and a cyclodextrin component in the presence of a polar solvent, thereby forming a uniform formulation;

and heating the formulation to a temperature within about 10 °C, within about 5 °C, within about 4 °C, within about 3 °C, within about 2 °C, or within about 1 °C of the melting point of the cannabinoid component.

2. The method of claim 1 wherein the formulation comprises the polar solvent in an amount of greater than about 30% by weight, about 40% by weight, or about 50% by weight, relative to the formulation as a whole, but less than the amount required to maintain a dispersion of the cyclodextrin and cannabinoid components.

3. The method of claim 1 wherein the polar solvent comprises water.

4. The method of claim 1 wherein the cannabinoid component comprises a cannabinoid having two hydroxyl groups.

5. The method of claim 4 wherein the cannabinoid component comprises CBD.

6. The method of claim 1 wherein the cyclodextrin component comprises a cyclodextrin selected from the group consisting of a-cyclodextrins, b-cyclodextrins, g- cyclodextrins, and derivatives thereof.

7. The method of claim 6 wherein the cyclodextrin component comprises a b- cyclodextrin.

8. The method of claim 6 wherein the cyclodextrin component comprises a cyclodextrin derivative that comprises one or more additional hydroxyl-containing functional groups.

9. The method of claim 8 wherein the cyclodextrin component comprises a hydroxypropyl b-cyclodextrin.

10. The method of claim 1 wherein the reaction mixture comprises the cyclodextrin component in molar excess relative to the cannabinoid component.

11. The method of claim 10 wherein the formulation comprises the cyclodextrin component and the cannabinoid component in a molar ratio of from about 1 : 1 to about 10: 1, from about 1 : 1 to about 5: 1, from about 1 : 1 to about 4: 1, from about 1 : 1 to about 3: 1, or from about 1.5: 1 to about 3: 1.

12. The method of claim 10 wherein the formulation comprises the cyclodextrin component and the cannabinoid component in a molar ratio of about 2: 1.

13. A water-soluble cannabinoid composition produced by the method of claim 1.

14. An edible food composition comprising the water-soluble cannabinoid composition of claim 13.

15. A beverage composition comprising the water-soluble cannabinoid composition of claim 13.

16. A water-soluble cannabinoid composition comprising:

(a) a cannabinoid component;

(b) a cyclodextrin component; and

(c) a polar solvent.

17. The composition of claim 16 wherein the polar solvent comprises water.

18. The composition of claim 16 wherein the cannabinoid component comprises a phytocannabinoid.

19. The composition of claim 18 wherein the cannabinoid component comprises a phytocannabinoid that is derived from a Cannabis plant.

20. The composition of claim 16 wherein the cannabinoid component comprises a cannabinoid selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabielsoin (CBE), cannabicitran (CBT), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA).

21. The composition of claim 20 wherein the cannabinoid component comprises a cannabinoid having two hydroxyl groups.

22. The composition of claim 20 wherein the cannabinoid component comprises

CBD.

23. The composition of claim 14 wherein the cyclodextrin component comprises a cyclodextrin selected from the group consisting of a-cyclodextrins, b-cyclodextrins, g- cyclodextrins, and derivatives thereof.

24. The composition of claim 21 wherein the cyclodextrin component comprises a b-cyclodextrin.

25. The method of claim 21 wherein the cyclodextrin component comprises a cyclodextrin derivative that comprises one or more additional hydroxyl-containing functional groups.

26. The method of claim 23 wherein the cyclodextrin component comprises a hydroxypropyl b-cyclodextrin.

27. The composition of claim 16 wherein the composition comprises the cyclodextrin component in molar excess relative to the cannabinoid component.

28. The composition of claim 25 wherein the composition comprises the cyclodextrin component and the cannabinoid component in a molar ratio of from about 1: 1 to about 10: 1, from about 1 : 1 to about 5: 1, from about 1: 1 to about 4: 1, from about 1 : 1 to about 3: 1, or from about 1.5: 1 to about 3: 1.

29. The composition of claim 25 wherein the composition comprises the cyclodextrin component and the cannabinoid component in a molar ratio of about 2: 1.

30. The composition of claim 16 wherein at least about at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% by weight of the cannabinoid component forms an inclusion complex with the cyclodextrin component.

31. The composition of claim 16 wherein at least about at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% by weight of the cannabinoid component forms a clathrate with the cyclodextrin component.

32. An inclusion complex consisting of:

(a) a cannabinoid component

(b) a cyclodextrin component; and

(c) water,

wherein the molar ratio of the cyclodextrin component to the cannabinoid component is about 2: 1, and wherein the molar ratio of the cyclodextrin component to water is about 1 : 1.

33. The composition of claim 1 wherein the water-soluble cannabinoid composition is in the form of a paste.

34. The composition of claim 33 wherein the water-soluble cannabinoid composition is dried to form a powder.

35. A pharmaceutical composition comprising the water-soluble cannabinoid composition of claim 1.

36. A pharmaceutical composition comprising the water-soluble cannabinoid composition of claim 32.

37. The pharmaceutical composition of claim 34, wherein the composition is in the form of a tablet.

38. The pharmaceutical composition of claim 34, wherein the composition is in the form of a gel capsule.