Process and apparatus for production of a granular cannabinoid material essentially soluble in aqueous medium

Abstract

The invention relates to a process and to an apparatus (1) for production of a granular cannabinoid material essentially soluble in aqueous medium, wherein a matrix liquid composed of a first liquid that dissolves a cannabinoid or composed of a first liquid that dissolves a cannabinoid and a second liquid that forms an emulsion with the first liquid and a cannabinoid dissolved in the first liquid or emulsion is produced, wherein the matrix liquid is dried by convection, and wherein the apparatus (1) has a vessel system (2) having an inlet (5, 6, 11, 12) and a matrix liquid outlet (14) for production of the matrix liquid and a drying apparatus fluidically connected to the matrix liquid outlet (14) of the vessel system (2).

Description

[0001] ADD Advanced Drug Delivery Technologies Ltd.,

[0002] Kraftwerkstrasse 6, 4133 Pratteln, Switzerland

[0003] Method and apparatus for the production of a cannabinoid granule that is essentially soluble in an aqueous environment

[0004] The invention relates to a method for producing a cannabinoid granule that is essentially soluble in an aqueous environment, wherein a matrix liquid is produced from a first liquid dissolving a cannabinoid or from a first liquid dissolving a cannabinoid and a second liquid forming an emulsion with the first liquid and a cannabinoid dissolved in the first liquid or the emulsion.

[0005] Furthermore, the invention relates to a device for the production of a cannabinoid granule that is essentially soluble in an aqueous environment.

[0006] Methods and devices for the production of, in particular, oral dosage forms of a cannabinoid have long been part of the prior art. WO 02 / 064109 A2 discloses pharmaceutical formulations for use in the administration of lipophilic drugs via mucosal surfaces. In particular, pharmaceutical formulations are provided for use in the administration of a lipophilic drug via a mucosal surface, which, upon hydration, form an emulsion containing the lipophilic drug, especially drugs containing as active ingredients certain combinations of cannabinoids in predefined ratios, wherein the drug is able to adhere to a mucosal surface and enable a controlled release of the drug.US Patent 2016 / 0143972 discloses a process for producing a solid dosage form of a cannabinoid, wherein the solid dosage form of the cannabinoid is essentially soluble in an aqueous solution. The process comprises dissolving a cannabinoid and one or more emulsifiers in one or more solvents to obtain one or more combined solutions, and further comprising drying the one or more solvents from the combination solutions comprising the one or more solvents to obtain the solid dosage form of the cannabinoid.

[0007] A disadvantage is that the solid dosage forms of a cannabinoid mentioned in the prior art exhibit insufficient systemic absorption and therefore the bioavailability of the cannabinoids is low, since the particle size distributions of the solid dosage forms are not very homogeneous and, in addition, the orally administered solid dosage forms may have poor flowability.

[0008] The object of the invention is therefore to expand the application areas for consumers and to increase the systemic absorption of the cannabinoids, so that the bioavailability of the cannabinoids is improved and at the same time the flowability of the solid dosage form of the cannabinoids is improved.

[0009] This problem is solved in a process of the type mentioned above by drying the matrix fluid convectively. Preferably, the matrix fluid is spray-dried or dried convectively in a fluidization apparatus by spray granulation, spray agglomeration, or spray encapsulation to form cannabinoid granules. Surprisingly, it was found that when the matrix fluid containing the cannabinoid is convectively dried in a fluidization apparatus, in particular a jet or fluidized bed apparatus, by spray granulation, spray agglomeration, or spray encapsulation, a stable emulsion of the first and second fluids is formed after the cannabinoid granules are redissolved in the aqueous environment. This significantly improves the absorbability of the cannabinoids and thus ensures optimal bioavailability.The improved absorbability and optimal bioavailability of the cannabinoids result from more homogeneous and smaller emulsion particles (oil droplets in water) after the cannabinoid granules are redissolved in the aqueous environment, compared to the emulsion particles (oil droplets in water) contained in the matrix liquid before convective drying in the fluidization apparatus. The dissolution behavior of the granules in the aqueous environment is also improved compared to conventional products, such as...

[0010] Pressed pellets. Furthermore, a surprising reduction in the mean diameter x and the equivalent diameter was observed after convective drying in the fluidization apparatus. The cannabinoid granules can be very well filled into stick packs, pressed into tablets, or further processed into capsules.

[0011] Cannabinoids are transformation products and synthetic analogs of some terpene phenols. Endogenous substances with similar pharmacological properties to cannabinoids, known as endocannabinoids, and substances from plants other than hemp that have a similar or identical effect to cannabinoids, known as phytocannabinoids, are also referred to as cannabinoids in this context. For example, a cannabinoid may contain one or more of cannabidiol (CBD), cannabinol (CBN), Δ9-tetrahydrocannabinol (THC), or others. According to a further development of the process, a cannabinoid is first dissolved in the first liquid, and then the first liquid is mixed with the second liquid to form the emulsion.

[0012] Furthermore, in one particular embodiment of the process, the first liquid is first mixed with the second liquid to form the emulsion, and then a cannabinoid is dissolved in the emulsion.

[0013] Preferably, the first liquid consists of lipids, alcohols, oils, and / or any mixture thereof. The choice of the first liquid is of great importance, for example, for the absorbability of cannabinoids in the human gastrointestinal tract. At the same time, the choice of the first liquid is also significant with regard to potential flavor masking. Oils, such as orange oil, are particularly suitable for this purpose.

[0014] The second liquid is preferably an aqueous solution or water.

[0015] In a particularly advantageous embodiment of the process, the first liquid is an oil or a mixture of different oils, in particular rapeseed, orange, or coconut oil, and / or an alcohol or a mixture of different alcohols, especially ethanol, preferably with a purity of > 80%, and the second liquid is water, and thus an oil-in-water emulsion or an alcoholic solution. Emulsifiers are auxiliary substances used for the production and stabilization of emulsions. These are preferably surfactants that serve to mix two immiscible liquids, such as oil and water, into a finely dispersed mixture, the so-called emulsion, and to stabilize it.

[0016] According to an advantageous embodiment of the process, an emulsifier is added to the second liquid before mixing it with the first liquid. According to a further advantageous embodiment of the process, an emulsifier is added to the emulsion before convective drying.

[0017] Furthermore, an emulsifier is preferably added to the matrix liquid before convective drying. The addition of one or more emulsifiers has the advantage that the first and second liquids are more finely dispersed in the emulsion, thus producing a matrix liquid that is better suited for convective drying in a convective drying apparatus, e.g., a drum dryer, a vacuum dryer, or, in particular, in a fluidization apparatus, preferably a jet or fluidized bed apparatus. The addition of one or more emulsifiers, such as Hi-Cap 100 (modified starch) or the like, is preferably carried out with stirring, preferably by means of a stirring device or the like, and / or the application of temperature, i.e., the supply or removal of heat.

[0018] Furthermore, according to an additional advantageous embodiment of the process, the matrix liquid is homogenized before convective drying. Preferably, the emulsion is homogenized under high pressure, particularly preferably at pressures between 50 bar and 250 bar, very preferably at pressures between 100 bar and 200 bar, and most preferably at pressures between 125 bar and 175 bar. Homogenization significantly reduces the mean diameter of the droplets of the first liquid present in the emulsion, so that the mixture of the first and second liquids, which are immiscible, becomes more homogeneous, i.e., more uniform. Due to the homogenization, especially high-pressure homogenization, an optimized matrix liquid is produced for convective drying, particularly in a fluidizing apparatus.

[0019] Advantageously, the matrix liquid is applied to one or more carrier materials before convective drying, particularly in a fluidization apparatus. Applying the matrix liquid to one or more carrier materials before convective drying preferably produces wet granules containing the cannabinoid while simultaneously compacting the carrier materials. Preferably, the matrix liquid is extruded after application to one or more carrier materials, or it is pelletized after application to one or more carrier materials. According to a further advantageous embodiment of the process, carrier particles are placed in the fluidization apparatus. The carrier particles, in particular, for example, maltodextrin, mannitol, cellulose, lactose, xylitol, or a mixture thereof, serve as nuclei for the formation of the cannabinoid granules.The matrix liquid partially evaporates, resulting in spray-dried granule nuclei from the matrix liquid itself. Advantageously, additives are added to the solution, emulsion, or matrix liquid before convective drying. By adding additives, such as carbohydrates (e.g., maltodextrin), starch, sugars (e.g., fructose or sucrose), salts (e.g., magnesium stearate), flavorings, or similar substances, the odor and taste of the cannabinoid granules can be masked. Additives can also be used, for example, to adjust the compressibility of the cannabinoid granules during tablet production or to modify the release profile of the cannabinoids.

[0020] Depending on a preferred further development of the process, the process is carried out batchwise or continuously. By varying the plant and process parameters, the desired end product properties, such as particle size distribution, dissolution rate, bulk density, or residual moisture, can be individually and optimally adjusted.

[0021] Furthermore, the problem is solved in a device of the type mentioned above by the fact that the device comprises a container system with an inlet and a matrix liquid outlet for producing the matrix liquid and a convective drying apparatus fluidically connected to the matrix liquid outlet of the container system. Preferably, the convective drying apparatus is designed as a spray dryer, a drum dryer, a vacuum dryer, or a fluidization apparatus.Surprisingly, it was discovered that convective drying of the cannabinoid-containing matrix fluid in a fluidization apparatus, particularly a jet or vortex layer apparatus, through spray granulation, spray agglomeration, or spray encapsulation, results in a stable emulsion of the first and second liquids after the cannabinoid granules are redissolved in an aqueous environment. This significantly improves the absorbability of the cannabinoids and thus ensures optimal bioavailability. The improved absorbability and optimal bioavailability of the cannabinoids result from more homogeneous and smaller emulsion particles (oil droplets in water), which, for example,The cannabinoid granules are obtained by spraying and drying, in particular film drying, of the matrix liquid onto carrier particles, after re-dissolving the cannabinoid granules in an aqueous environment compared to the emulsion particles (oil droplets in water) contained in the matrix liquid prior to convective drying, preferably in a fluidization apparatus. Furthermore, a reduction in the mean diameter x and the equivalent diameter was surprisingly observed after convective drying in the fluidization apparatus. The cannabinoid granules can be readily filled into stick packs and applied directly into the oral cavity, added to a glass of liquid, compressed into tablets, or further processed in capsules. According to an advantageous embodiment of the device, the fluidization apparatus is designed as a jet bed apparatus or a fluidized bed apparatus.In comparison to fluidized bed apparatuses, ejection bed apparatuses allow, for example, atomization at very low fill volumes, and furthermore, on the one hand, the high shear forces in the atomization area support a uniform liquid film formation and, on the other hand, minimize tendencies towards agglomeration.

[0022] Advantageously, the container system comprises one or more containers. Preferably, the multiple containers are at least partially fluidically connected to one another. Particularly preferably, the device comprises a first container for the first liquid, a second container for the second liquid, and a container for the emulsion. Most preferably, the container for the emulsion corresponds to the first or second container. This ensures simple production of the matrix liquid while simultaneously processing the starting materials separately.

[0023] According to a further advantageous embodiment of the preferred device, the convective drying apparatus, preferably the fluidization apparatus, has a nozzle for atomizing the emulsion or solution. Preferably, the nozzle, preferably a two-fluid nozzle, is configured to spray droplets with a droplet size of 1 mpi to 200 mth, preferably from 10 mpi to 100 mh, and most preferably between 20 mpi and 60 mh. Most preferably, the sprayed droplets have a droplet size of 25 mpi to 40 mh, and most preferably 30 mpi. By adjusting the droplet size using the nozzle and the compressed air supplied to the nozzle, the shear forces occurring during spraying can be precisely controlled, so that a very homogeneous droplet size of the emulsion or solution to be sprayed can be achieved.The droplets adhere to the carrier particles, such as cellulose, lactose, or xylitol, and film evaporation preferentially occurs. This film evaporation results in very uniform evaporation of the emulsion or solution on the carrier particles.

[0024] According to an advantageous embodiment of the device, a homogenizer for homogenizing the matrix liquid is arranged between the container system and the drying apparatus, preferably the fluidization apparatus. Homogenization reduces the mean diameter of the particles in the

[0025] The emulsion of the first liquid is greatly reduced, so that the mixture of the first and second liquids, which are not mutually soluble, becomes more homogeneous, i.e., more uniform. Due to this homogenization, particularly high-pressure homogenization, an optimized matrix liquid is produced for convective drying, especially in fluidizing apparatus.

[0026] Furthermore, in a preferred embodiment of the device, a granulation unit, preferably a wet mixer, particularly preferably a high-shear granulator, a vertical granulator, a rotor disc granulator, or the like, is arranged between the container system and the drying apparatus for granulating the matrix liquid. According to a further embodiment of the device, an extruder for extruding the granules is arranged downstream of the granulation unit. Preferably, the homogenizer and / or the granulation unit and / or the extruder are fluidically connected to one another.

[0027] According to a further advantageous embodiment of the device, the inlet and the matrix fluid outlet are designed as a single opening in the container system. The advantage of such a design for the inlet and matrix fluid outlet lies in the simpler construction and the easier sealing.

[0028] The invention will now be explained in more detail with reference to the accompanying drawing, which shows

[0029] Figure 1 schematic representation of a first embodiment of a preferred device for producing a cannabinoid granule that is essentially soluble in aqueous media, Figure 2 schematic representation of a second embodiment of a preferred device for producing a cannabinoid granule that is essentially soluble in aqueous media, Figure 3 a cumulative distribution curve and a density distribution curve of oil droplets of an oil-in-water emulsion (with rapeseed oil) before drying in the jet bed apparatus.

[0030] Figure 4 shows a cumulative distribution curve and a density distribution curve for oil droplets in an oil-in-water emulsion.

[0031] (with rapeseed oil) after dissolving the cannabinoid granules dried in the blast furnace in water,

[0032] Figure 5 shows a cumulative distribution curve and a density distribution curve of oil droplets of an oil-in-water emulsion (with coconut oil) before drying in the jet bed apparatus.

[0033] Figure 6 shows a cumulative distribution curve and a density distribution curve of oil droplets of an oil-in-water emulsion (with coconut oil) after dissolution of the cannabinoid granules dried in the jet bed apparatus in water.

[0034] Fig. 1 shows a schematic representation of a first embodiment of a preferred device 1 for producing a cannabinoid granule that is essentially soluble in aqueous media.

[0035] The device 1 comprises a container system 2 for producing the matrix fluid. In the embodiment according to Fig. 1, the container system 2 has three containers 3, which are fluidically connected to one another. The fluidic connection of the containers 3 is realized by means of pipes 4.

[0036] The first container 3a of the container system 2, which is double-walled for heating or cooling, has a cannabinoid inlet 5 and a liquid inlet 6 for a first liquid consisting of lipids, alcohols, oils, and / or any mixture thereof, but preferably rapeseed, orange, or coconut oil. The first container 3a can be temperature-controlled by means of a heating medium flowing through the container jacket space 9, which is located between the inner wall 7 and the outer wall 8. Preferably, the container 3a is heated to improve the solubility of a cannabinoid that may not be readily soluble in the first liquid. The temperature control device is not strictly necessary.

[0037] Furthermore, the first container 3a has a motor-driven stirring device 10 for stirring the first liquid. The stirring device is not strictly necessary. For a second liquid, in particular an aqueous solution or water, the container system 2 comprises a second container 3b having a liquid inlet 11.

[0038] The first and second containers 3a, 3b are each connected via a pipe 4 to inlets 12 of a third container 3c. The first liquid containing the cannabinoid and the second liquid are conveyed into the third container 3c via pipes 4, e.g., by means of pumps. In the third container 3c, the matrix liquid is produced by mixing the first liquid containing the cannabinoid and the second liquid, whereby the first and second liquids form an emulsion. Preferably, this is produced in the third container 3c by stirring with a motor-driven stirring device 13. The produced matrix liquid leaves the container system 2 via a matrix liquid outlet 14. The matrix liquid can also be produced in other partial steps, e.g., by simply mixing all components together in a single container.

[0039] The matrix fluid is conveyed via a pipe 15 into a homogenizer 16 for homogenization, preferably a high-pressure homogenizer, e.g., by means of a pump. The homogenized matrix fluid is then conveyed from the homogenizer 16 via the pipe 17 into the fluidization apparatus 18, e.g., by means of a pump. In the embodiment shown in Fig. 1, the drying apparatus is designed as a fluidization apparatus 18 for the production of a cannabinoid granule that is essentially soluble in aqueous media, wherein the fluidization apparatus 18 is designed here as a jet bed apparatus 19. The structure of the

[0040] The jet layer apparatus 19 comprises, from bottom to top, a

[0041] Distribution chamber 20, a process room 21, an expansion zone 22 and an exhaust air section 23.

[0042] The process gas 24 required for drying the cannabinoid granules to be produced is fed to the distribution chamber 20, where the process gas 24 is distributed and enters a process chamber 21 preferably as a kind of free jet via a slot opening 25 and a process gas deflection part 26.

[0043] Furthermore, the cross-sectional area of ​​the apparatus can optionally increase in the expansion zone 22, so that the velocity of the process gas flow decreases steadily upwards. The process gas 24 leaves the jet bed apparatus 19 preferably as exhaust gas 28, which has been cleaned by a dust removal system 27, in particular filter cartridges or textile filter elements.

[0044] Process chamber 21 contains carrier particles designated as starter material, such as mannitol, cellulose, xylitol, or the like, which are carried upwards by the process gas 24 towards the dust removal system 27. In the upper region of process chamber 21 and in the expansion zone 22 above it, the process gas velocity decreases, causing the upward-flowing carrier particles to exit the process gas stream laterally and fall back into process chamber 21. The lower region of process chamber 21 is bounded by inclined side surfaces 28. Due to the inclined side surfaces 28, the carrier particles are transported by gravity across the return zone 29 towards the slot opening 25, where they are subsequently carried back into process chamber 21 by the process gas 24.

[0045] This mechanism creates a very uniform solids circulation 30 of the carrier particles. In the lower region of the process chamber 21, one or more spray devices 31, preferably a spray nozzle or the like, are arranged, which spray upwards in the same direction as the process gas 24 and serve to introduce the matrix liquid. Such introduction of the matrix liquid in the lower region of the process chamber 21 is referred to as bottom spraying. The nozzle, preferably a two-fluid nozzle, is configured to spray droplets with a droplet size of 1 µm to 200 µm, preferably from 10 µm to 100 µm, and most preferably between 20 µm and 60 µm. Most preferably, the sprayed droplets have a droplet size of 25 µm to 40 µm, and most preferably 30 µm.By adjusting the droplet size using the nozzle and the compressed air applied to the nozzle, the shear forces occurring during spraying can be precisely controlled, thus ensuring a highly homogeneous droplet size of the emulsion or solution to be sprayed. The droplets adhere to the carrier particles, such as cellulose, lactose, or xylitol, and film evaporation preferentially occurs.

[0046] Due to the highly advantageous heat and mass transfer, as well as the high carrier particle circulation in the spray zone 32 of the process chamber 21 of the spray bed apparatus 19, the matrix liquid is largely deposited on the carrier particles, thus ensuring uniform wetting of the particle surfaces. This uniform wetting, combined with the high particle circulation between the spray zone 32 and the return zone 29, results in the formation of a very uniform liquid film on the carrier particles. During the drying process, the matrix liquid evaporates and exits the spray bed apparatus 19 with the exhaust gas 28. The cannabinoid contained in the matrix liquid remains on the particle surface of the carrier particles, resulting in very uniform and homogeneous growth of the cannabinoid granules.

[0047] The discharge 33 of the cannabinoid granules can be realized, for example, by an overflow or by a volumetric discharge device, in particular a rotary valve, or also by a gravity classifier, preferably a zigzag classifier supplied with screening gas or a riser tube classifier.

[0048] Mechanical units 34, such as crushers, shredders, etc., can be arranged as required in the process chamber 21, preferably in the return zone 29, in order to produce sufficiently fine particles as granule nuclei for the granule formation process by crushing.

[0049] In the process chamber 21 or in the apparatus components above it, the expansion zone 22 and the exhaust air section 23, one or more spray devices 35 can optionally be arranged, preferably spraying downwards. The liquid matrix fluid can also be injected into the process chamber 21 of the spray bed apparatus 19 via the spray device 35. Alternatively, additives 36 or other components 37 can be sprayed in liquid form via some of the spray devices 31, 35 and thus homogeneously embedded in the granule structure.

[0050] In the preferred device 1, a granulation unit (not shown) for granulating the matrix liquid can be arranged between the container system 2 and the fluidization unit 18, which is designed as a jet bed apparatus 19. Furthermore, an extruder for extruding the granules can be arranged downstream of the granulation unit. Preferably, the homogenizer 16 and / or the granulation unit and / or the extruder are fluidically connected to each other.

[0051] Figure 2 shows a schematic representation of a second embodiment of a preferred device 1 for producing a cannabinoid granule that is substantially soluble in aqueous media. The device 1 comprises a container system 2 for producing the matrix liquid. In the second embodiment according to Figure 2, the container system 2 has a single container 3. The container 3 of the container system 2, which is double-walled for heating or cooling, has a cannabinoid inlet 5 and a liquid inlet 6 for a first liquid consisting of lipids, alcohols, oils, and / or any mixture thereof, but particularly preferably rapeseed, orange, or coconut oil, as well as a liquid inlet 11 for a second liquid, in particular an aqueous solution or water.

[0052] The first container 3a can be heated by means of a heating medium flowing through the container jacket space 9, which is enclosed between the inner wall 7 and the outer wall 8. Preferably, the container 3a is heated to improve the solubility of a cannabinoid that may not be readily soluble in the first liquid. The heating device is not strictly necessary. Furthermore, the first container 3a has a motor-driven stirring device 10 for stirring the first liquid. The stirring device is not strictly necessary.

[0053] In container 3, the matrix liquid is produced by mixing the first liquid containing the cannabinoid with the second liquid, whereby the first and second liquids form an emulsion. Preferably, this is produced in container 3 while stirring using a motor-driven stirring device 13. The produced matrix liquid leaves the container system 2 for the production of the matrix liquid via a matrix liquid outlet 14. In the exemplary embodiment, the inlet 5, 6, 11 and the matrix liquid outlet 14 are designed as a container system opening 38.

[0054] The matrix fluid is conveyed via a pipe 15 into a homogenizer 16 for homogenization, preferably a high-pressure homogenizer, e.g. by means of a pump. The homogenized matrix fluid is then conveyed from the homogenizer 16 via the pipe 17 into the fluidization apparatus 18, e.g. by means of a pump.

[0055] The further convective drying process using a fluidization apparatus is carried out according to the first embodiment described in Fig. 1.

[0056] Subsequently, the produced cannabinoid granules can be coated, for example, in a drum coater. This has the advantage that the cannabinoid granules can, for example, receive a gastric juice-resistant coating or a flavor masking.

[0057] The following are examples of the production of a matrix fluid and its further processing in the fluidization apparatus.

[0058] Example 1: The production of the cannabinoid granules in the fluidization apparatus, designed as a jet bed apparatus, was carried out in batch operation using a bottom-spray process. 500 g of mannitol were used as the starting material in the fluidization apparatus. The matrix fluid consisted of 200 g Hi-Cap 100, 200 g maltodextrin, 1365 g water, 5 g cannabidiol (CBD), and 50 g rapeseed oil. The cannabidiol (CBD) was dissolved in rapeseed oil as the first liquid, and the maltodextrin and Hi-Cap 100 were dissolved in water as the second liquid. Subsequently, the CBD-containing rapeseed oil and the water containing the maltodextrin and Hi-Cap 100 were mixed together to form an emulsion, thus producing the matrix fluid. The maltodextrin and Hi-Cap 100 serve as additives to form a matrix structure within the matrix fluid.

[0059] Spray rates were selected between 10 and 15 g / in. The produced cannabinoid granules dissolved well in water, forming a stable oil-in-water emulsion. The residual moisture content of the cannabinoid granules was 1.8%. Following its production, the matrix liquid was analyzed using a Cilas 1190 LD (Quantachrome) laser diffraction system. The particle sizes of the CBD-containing oil droplets in the matrix liquid emulsion are shown in Fig. 3. The cumulative distribution curve, with equivalent diameters xio = 1.17 mpi, xso = 7.97 mth, and xso = 18.37 mh, exhibits a mean diameter of x = 8.87 mth. Furthermore, the density distribution curve, with its two maxima, shows a bimodal distribution.

[0060] After the production of the cannabinoid granules and subsequent dissolution of the cannabinoid granules in water, a stable oil-in-water emulsion has formed in the aqueous environment.

[0061] The cannabinoid granules dissolved in aqueous solution were reconstituted in water, and the particle size of the CBD-containing oil droplets was again analyzed using the Cilas 1190 LD laser diffraction system (Quantachrome). Figure 4 shows the analysis. The cumulative distribution curve, with equivalent diameters xio = 0.82 mi, xso = 2.33 mi, and xso = 6.26 ma, exhibits a mean diameter of x = 3.01 ma. Furthermore, the density distribution curve shows a monomodal distribution. The oil droplets exhibit a very homogeneous density distribution with significantly smaller diameters. This leads to a considerably improved absorbability of CBD and thus to more optimal bioavailability. This improved absorbability of the cannabinoids results from more homogeneous and smaller emulsion particles.

[0062] Example 2: The production of the cannabinoid granules in the fluidization apparatus designed as a jet bed apparatus was carried out in batch operation as bottom spray.

[0063] The starting material used in the fluidization apparatus was 250 g of mannitol and 250 g of maltrodextrin, i.e. in a ratio of 1:1.

[0064] The matrix liquid contains 200 g Hi-Cap 100, 200 g maltodextrin, 1417 g water, 5.5 g cannabidiol (CBD), and 51 g coconut oil. The cannabidiol (CBD) was dissolved in coconut oil as the first liquid, and the maltodextrin and Hi-Cap 100 were dissolved in water as the second liquid. Subsequently, the CBD-containing coconut oil and the water containing the maltodextrin and Hi-Cap 100 were mixed together to form an emulsion, thus creating the matrix liquid. The maltodextrin and Hi-Cap 100 serve as additives to form a matrix structure within the matrix liquid.

[0065] The spray rates were increased compared to example 1. Additionally, the process air flow rate was reduced to minimize product loss at the filters. The produced cannabinoid granules dissolved well in water, forming a stable oil-in-water emulsion. The residual moisture content of the cannabinoid granules was 3.4%.

[0066] The matrix fluid was analyzed after its preparation using a Cilas 1190 LD (Quantachrome) laser diffraction system. The particle sizes of the CBD-containing oil droplets in the matrix fluid emulsion are shown in Fig. 5. The cumulative distribution curve, with equivalent diameters x0 = 1.18 mth, xso = 6.99 mth, and xso = 15.17 mih, exhibits a mean diameter of x = 7.58 mpi. Furthermore, the density distribution curve, with its two maxima, shows a bimodal distribution.

[0067] After production of the cannabinoid granules and subsequent dissolution in water, a stable oil-in-water emulsion formed in the aqueous environment. The cannabinoid granules dissolved in the aqueous environment were then dissolved in water, and the particle size of the CBD-containing oil droplets was again analyzed using the Cilas 1190 LD laser diffraction system (Quantachrome). Figure 6 shows the analysis. The cumulative distribution curve, with equivalent diameters xio = 0.90 mpi, xso = 2.48 mpi, and xso = 6.24 mpi, exhibits a mean diameter of x = 3.08 mpi. Furthermore, the density distribution curve shows a monomodal distribution. The oil droplets exhibit a very homogeneous density distribution with significantly smaller diameters. This leads to significantly improved CBD absorption and thus to more optimal CBD bioavailability. This improved absorption of the cannabinoids results from more homogeneous and smaller emulsion particles.

Claims

Claims 1. A method for producing a cannabinoid granule that is substantially soluble in aqueous media, wherein a matrix liquid is produced from a first liquid dissolving a cannabinoid or from a first liquid dissolving a cannabinoid and a second liquid forming an emulsion with the first liquid and a cannabinoid dissolved in the first liquid or the emulsion, characterized in that the matrix liquid is dried convectively.

2. The method according to claim 1, characterized in that the matrix liquid is spray-dried or convectively dried to form a cannabinoid granule in a fluidization apparatus (18) by spray granulation, spray agglomeration, or spray encapsulation.

3. The method according to claim 1 or 2, characterized in that a cannabinoid is first dissolved in the first liquid and then the first liquid is mixed with the second liquid to form the emulsion.

4. Method according to claim 1 or 2, characterized in that the first liquid is first mixed with the second liquid to form the emulsion and then a cannabinoid is dissolved in the emulsion.

5. A method according to any one of the preceding claims, characterized in that the first liquid consists of the group consisting of lipids, alcohols, oils and / or any mixture thereof.

6. A method according to any one of the preceding claims, characterized in that the second liquid is an aqueous solution or water.

7. Method according to one of the preceding claims, characterized in that an emulsifier is added to the second liquid before mixing it with the first liquid.

8. A method according to any one of claims 1 to 7, characterized in that an emulsifier is added to the emulsion before convective drying.

9. A method according to any one of claims 1 to 7, characterized in that an emulsifier is added to the matrix liquid before convective drying.

10. Method according to one of the preceding claims, characterized in that the matrix liquid is homogenized before convective drying.

11. Method according to claim 10, characterized in that the emulsion is homogenized under high pressure, preferably at pressures between 50 bar and 250 bar, particularly preferably at pressures between 100 bar and 200 bar, and most particularly preferably at pressures between 125 bar and 175 bar.

12. Method according to one of the preceding claims, characterized in that the matrix fluid is removed before the is applied to one or more carrier materials by convective drying in a fluidization apparatus (18).

13. Method according to claim 12, characterized in that the matrix liquid is extruded after being applied to one or more carrier materials.

14. Method according to claim 12, characterized in that the matrix liquid is pelletized after being applied to one or more carrier materials.

15. Method according to one of the preceding 1 to 11, characterized in that carrier particles are placed in the fluidization apparatus (18).

16. Method according to one of the preceding claims, characterized in that additives (36) are added to the solution, emulsion or matrix liquid before convective drying.

17. Method according to one of the preceding claims, characterized in that the method is carried out batchwise or continuously.

18. Device (1) for producing a cannabinoid granule that is substantially soluble in an aqueous environment according to one of the preceding claims, characterized in that the device (1) comprises a container system (2) having an inlet (5, 6, 11, 12) and a matrix liquid outlet (14) for producing the matrix liquid and a convective drying apparatus fluidically connected to the matrix liquid outlet (14) of the container system (2).

19. Device (1) according to claim 18, characterized in that the convective drying apparatus is configured as a spray dryer, a drum dryer, a vacuum dryer, or a fluidization apparatus (18).

20. Device (1) according to claim 18 or 19, characterized in that the fluidization apparatus (18) is configured as a jet bed dryer (19) or as a fluidized bed dryer.

21. Device (1) according to one of claims 18 to 20, characterized in that the container system (2) has one or more containers (3, 3a, 3b, 3c).

22. Device (1) according to claim 21, characterized in that the multiple containers (3, 3a, 3b, 3c) are at least partially fluidically connected to one another.

23. Device (1) according to one of claims 21 or 22, characterized in that the device comprises a first container (3a) for the first liquid, a second container (3b) for the second liquid, and a container (3c) for the emulsion.

24. Device (1) according to claim 23, characterized in that the container (3c) for the emulsion corresponds to the first or second container (3a, 3b).

25. Device (1) according to one of claims 18 to 24, characterized in that the fluidizing apparatus (18) has a nozzle for atomizing the emulsion or solution.

26. Device (1) according to claim 25, characterized in that the nozzle, preferably a two-fluid nozzle, is configurable is designed to spray droplets with a droplet size of 1 mta to 200 mth, preferably from 10 mpi to 100 mih, particularly preferably between 20 mih and 60 mpi.

27. Device (1) according to one of claims 18 to 26, characterized in that a homogenizer (16) for homogenizing the matrix fluid is arranged between the container system (2) and the fluidization apparatus (18).

28. Device (1) according to one of claims 18 to 27, characterized in that a granulation unit, preferably a high shear granulator, a vertical granulator or a rotor disc granulator, is arranged between the container system (2) and the drying apparatus (18) for granulating the matrix liquid.

29. Device (1) according to claim 28, characterized in that an extruder is provided after the granulation unit for The extrusion of the granules is arranged.

30. Device (1) according to one of claims 27 to 29, characterized in that the homogenizer (16) and / or the grating unit and / or the extruder are fluidically connected to each other.

31. Device (1) according to one of claims 18 to 30, characterized in that the inlet (5, 6, 11, 12) and the matrix fluid outlet (14) are designed as a container system opening (38).

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