METHOD AND DEVICE FOR THE PRODUCTION OF A CANNABINOID GRANULES ESSENTIALLY SOLUBLE IN AQUEOUS ENVIRONMENT

Description

[0001] The invention relates to a method for producing cannabinoid granules which are essentially soluble in an aqueous medium, wherein a matrix liquid is produced from a first liquid which dissolves a cannabinoid or from a first liquid which dissolves a cannabinoid and a second liquid which forms an emulsion with the first liquid and a cannabinoid dissolved in the first liquid or the emulsion.

[0002] Processes for the production of, in particular, oral dosage forms of a cannabinoid have long been part of the state of the art.

[0003] WO 02 / 064109 A2 discloses pharmaceutical formulations for use in administering lipophilic drugs via mucosal surfaces. In particular, pharmaceutical formulations for use in administering a lipophilic drug via a mucosal surface are provided which, upon hydration, form an emulsion containing the lipophilic drug, in particular drugs containing, as active ingredients, specific combinations of cannabinoids in predefined ratios, wherein the drug is capable of adhering to a mucosal surface and enabling controlled release of the drug.

[0004] US 2016 / 0143972 A1 discloses a method for producing a solid dosage form of a cannabinoid, wherein the solid dosage form of the cannabinoid is substantially soluble in an aqueous solution. The method comprises dissolving a cannabinoid and one or more emulsifiers in one or more solvents to obtain one or more combined solutions, and further drying the one or more solvents from the combined solutions comprising the one or more solvents to obtain the solid dosage form of the cannabinoid.

[0005] A disadvantage is that the solid dosage forms of a cannabinoid mentioned in the prior art have 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, there is poor flowability of the orally administered, possibly solid, dosage forms.

[0006] AT 509 000 A1 discloses preparations and methods for solubilizing cannabis preparations, as well as natural and synthetic cannabinoids, using surfactants, so that they are completely dissolved in water and miscible with it in any ratio. This significantly increases their bioavailability, allowing dosages for therapeutic use to be significantly reduced. This makes it possible to produce a wide variety of pharmaceutical products and stimulants with water-soluble cannabinoids.

[0007] WO 1999 / 32107 A1 provides a composition for nasal administration of a cannabinoid, which discloses a cannabinoid in a biphasic delivery system or a cannabinoid in a microsphere delivery system. The biphasic oil-in-water emulsion is spray-dried.

[0008] EP 2 298 284 A1 discloses pharmaceutical formulations for use in administering lipophilic drugs across mucous membranes and, more particularly, relates to pharmaceutical compositions for use in administering a lipophilic drug across a mucosal surface which, upon hydration, form an emulsion containing the lipophilic drug capable of adhering to a mucosal surface and enabling controlled release of the drug. EP 2 298 284 A1 further discloses pharmaceutical formulations containing, as active ingredients, specific combinations of cannabinoids in predefined ratios.

[0009] The object of the invention is therefore to expand the areas of application for consumers and increase the systemic absorption of cannabinoids, thereby improving the bioavailability of the cannabinoids and simultaneously improving the flowability of the solid dosage form of the cannabinoids. This object is achieved in a method of the type mentioned above by convectively drying the matrix liquid in a fluidization apparatus to form cannabinoid granules by spray granulation, spray agglomeration, or spray encapsulation.Surprisingly, it was discovered that during convective drying of the cannabinoid-containing matrix liquid in a fluidization apparatus, particularly a jet or fluidized bed apparatus, by spray granulation, spray agglomeration, or spray encapsulation, a stable emulsion of the first and second liquid forms after redissolution of the cannabinoid granules in an aqueous medium. This significantly improves the absorbability of the cannabinoids, thus ensuring optimal bioavailability. The improved absorbability and optimal bioavailability of the cannabinoids result from more homogeneous and smaller emulsion particles (oil droplets in water) after redissolution of the cannabinoid granules in the aqueous medium 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 an aqueous environment is also improved compared to conventional products, such as pellets. Furthermore, a surprising reduction in the average diameter x and the equivalent diameter was observed after convective drying in the fluidization apparatus. The cannabinoid granules can be easily filled into stick packs, compressed into tablets, or further processed into capsules.

[0010] Cannabinoids are transformation products and synthetic analogues of some terpene phenols. Endogenous substances that exhibit similar pharmacological properties to cannabinoids, so-called endocannabinoids, and substances from plants other than the hemp plant that exhibit similar or identical effects to cannabinoids, so-called phytocannabinoids, are also referred to herein as cannabinoids. For example, the cannabinoid can include one or more of cannabidiol (CBD), cannabinol (CBN), and Δ9-tetrahydrocannabinol (THC), among others.

[0011] According to a related development of the method, a cannabinoid is first dissolved in the first liquid, then the first liquid is mixed with the second liquid to form the emulsion.

[0012] In addition, in a corresponding embodiment of the method, 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 selection of the first liquid is of great importance, for example, for the absorption of cannabinoids in the human gastrointestinal tract. At the same time, the selection of the first liquid is also important with regard to possible taste masking. Oils such as orange oil are particularly suitable for this purpose.

[0014] More preferably, the second liquid is an aqueous solution or water.

[0015] In a very advantageous embodiment of the method, the first liquid is an oil or a mixture of different oils, in particular a rapeseed, orange or coconut oil, and / or an alcohol or a mixture of different alcohols, in particular ethanol, preferably with a purity of > 80%, and the second liquid is water and thus an oil-in-water emulsion or an alcoholic solution.

[0016] Emulsifiers are additives used to produce and stabilize emulsions. These are typically surfactants that blend two immiscible liquids, such as oil and water, into a finely dispersed mixture, known as an emulsion, and stabilize it.

[0017] According to an advantageous development of the method, an emulsifier is added to the second liquid before mixing with the first liquid.

[0018] According to a further advantageous development of the process, an emulsifier is added to the emulsion before convective drying.

[0019] In addition, an emulsifier is preferably added to the matrix liquid before convective drying.

[0020] The addition of one or more emulsifiers has the advantage that the first and second liquids are more finely distributed in the emulsion, which also allows the production of a matrix liquid that is more suitable 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, for example, 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 with the influence of temperature, i.e., the addition or removal of heat.

[0021] Furthermore, according to an additional advantageous embodiment of the method, the matrix liquid is homogenized before convective drying. The emulsion is preferably homogenized under high pressure, particularly preferably at pressures between 50 bar and 250 bar, very particularly preferably at pressures between 100 bar and 200 bar, and most preferably at pressures between 125 bar and 175 bar. The homogenization greatly reduces the average diameter of the droplets of the first liquid present in the emulsion, so that the mixture of first and second liquid, which are not soluble in one another, becomes more homogeneous, i.e. more uniform. Due to the homogenization, in particular high-pressure homogenization, an optimized matrix liquid for convective drying, in particular in the fluidization apparatus, is produced.

[0022] Advantageously, the matrix liquid is applied to one or more carriers prior to convective drying, particularly in the fluidization apparatus. By applying the matrix liquid to one or more carriers prior to convective drying, wet granules containing the cannabinoid are preferably produced while simultaneously compacting the carriers. Preferably, the matrix liquid is extruded after application to one or more carriers, or the matrix liquid is pelletized after application to one or more carriers.

[0023] According to an additional advantageous embodiment of the process, carrier particles are introduced into 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. Part of the matrix liquid evaporates, and spray-dried granule nuclei are formed from the matrix liquid itself.

[0024] Advantageously, additives are added to the solution, emulsion, or matrix liquid prior to convective drying. By adding additives, such as carbohydrates (e.g., maltodextrin), starch, sugar (e.g., fructose or sucrose), salts (e.g., magnesium stearate), flavorings, or the like, odor and taste masking of the cannabinoid granules can be achieved. Additives can also be used, for example, if the compressibility of the cannabinoid granules needs to be adjusted during tablet production or if the release profile of the cannabinoids needs to be adjusted.

[0025] According to a preferred 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.

[0026] To carry out the method, a device is preferably used, wherein the device has a container system for producing the matrix liquid, which container system has one or more containers and which has a cannabinoid inlet, a liquid inlet for a first liquid from the group of lipids, alcohols, oils and / or any mixture thereof, a liquid inlet for a second liquid and a matrix liquid outlet, and wherein the device further has a convective drying apparatus fluidically connected to the matrix liquid outlet of the container system as a fluidization apparatus.Surprisingly, it was discovered that convective drying of the cannabinoid-containing matrix liquid in a fluidization apparatus, particularly a jet or fluidized bed apparatus, by spray granulation, spray agglomeration, or spray encapsulation, after redissolution of the cannabinoid granules in an aqueous environment, forms a stable emulsion of the first and second liquids. 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, are smaller.by spraying and drying, in particular film drying, the matrix liquid onto carrier particles, after redissolving the cannabinoid granules in an aqueous medium 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 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 easily filled into stick packs and administered directly into the oral cavity or added to a glass of liquid, or pressed into tablets or processed into capsules.

[0027] The fluidization apparatus is preferably designed as a spouted bed or fluidized bed apparatus. Compared to fluidized bed apparatus, spouted bed apparatuses allow for atomization with very low fill volumes. Furthermore, the high shear forces in the spraying area promote uniform liquid film formation while minimizing agglomeration tendencies.

[0028] Advantageously, the container system comprises one or more containers. Preferably, the plurality of 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.

[0029] According to an advantageous development of the device, the convective drying apparatus, preferably the fluidization apparatus, has a nozzle for atomizing the emulsion or solution. The nozzle, preferably a two-component nozzle, is configured to produce droplets with a droplet size of 1 µm up to 200 µm , preferably from 10 µm up to 100µm , particularly preferably between 20µm and 60 µm Most preferably, the sprayed droplets have a droplet size of 25µm to 40µm, most preferably 30 µ m. 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 adjusted, allowing a very homogeneous droplet size of the emulsion or solution to be sprayed to be achieved. The droplets adhere to the carrier particles, such as cellulose, lactose, or xylitol, and preferential film evaporation occurs. Film evaporation results in a very uniform evaporation of the emulsion or solution on the carrier particles.

[0030] According to an advantageous development of the device, a homogenizer for homogenizing the matrix liquid is arranged between the container system and the drying apparatus, preferably the fluidization apparatus. The homogenization greatly reduces the average diameter of the first liquid present in the emulsion, so that the mixture of the first and second liquids, which are not soluble in each other, becomes more homogeneous, i.e., more uniform. Due to the homogenization, in particular high-pressure homogenization, an optimized matrix liquid for convective drying is produced, especially in the fluidization apparatus.

[0031] Furthermore, a granulation unit, preferably a wet mixer, particularly preferably a high-shear granulator, a vertical granulator, a rotor disc granulator, or the like, for granulating the matrix liquid is advantageously arranged between the container system and the drying apparatus. According to a related development of the device, an extruder for extruding the granules is arranged downstream of the granulation unit.

[0032] Preferably, the homogenizer and / or the gratification unit and / or the extruder are fluidically connected to one another.

[0033] According to an advantageous embodiment of the device, the inlet and the matrix fluid outlet are designed as a single container system opening. The advantage of such a design of the inlet and matrix fluid outlet is the structural simplicity and simplified sealing.

[0034] The invention will be explained in more detail below with reference to the accompanying drawings, which show Figure 1 shows a schematic representation of a first embodiment of a preferred device for producing cannabinoid granules that are essentially soluble in an aqueous medium. Figure 2 shows a schematic representation of a second embodiment of a preferred device for producing cannabinoid granules that are essentially soluble in an aqueous medium. Figure 3 shows 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 spouted bed apparatus. Figure 4 shows a cumulative distribution curve and a density distribution curve of oil droplets of an oil-in-water emulsion (with rapeseed oil) after dissolving the cannabinoid granules dried in the spouted bed apparatus in water.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 a spouted bed apparatus, and 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 a spouted bed apparatus in water.

[0035] Fig. 1 shows a schematic representation of a first embodiment of a preferred device 1 for producing a cannabinoid granulate that is essentially soluble in an aqueous medium.

[0036] The device 1 comprises a container system 2 for producing the matrix liquid. In the embodiment according to Fig. 1 The container system 2 comprises three containers 3, which are fluidically connected to each other. The fluidic connection between the containers 3 is realized by means of pipelines 4.

[0037] 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 the group of lipids, alcohols, oils and / or any mixture thereof, but particularly preferably of a rapeseed, orange or coconut oil.

[0038] Through the container shell space 9 spanned between the container inner wall 7 and the container outer wall 8, the first container 3a can be temperature-controlled by means of a heating medium flowing through the container shell space 9. Preferably, the container 3a is heated to better dissolve a cannabinoid that may not be readily soluble in the first liquid. The temperature control device is not mandatory.

[0039] In addition, the first container 3a has a motor-driven stirring device 10 for stirring the first liquid. The stirring device is not mandatory.

[0040] 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.

[0041] The first and second containers 3a, 3b are each connected to inlets 12 of a third container 3c via a pipeline 4. The first liquid containing the cannabinoid and the second liquid are conveyed into the third container 3c via pipelines 4, for example, by means of pumps.

[0042] 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. This is preferably produced by stirring by means of a motor-driven stirring device 13 in the third container 3c. The produced matrix liquid leaves the container system 2 for producing the matrix liquid via a matrix liquid outlet 14.

[0043] The matrix fluid can also be produced through other sub-steps, for example, by simply mixing all components together in a single container.

[0044] The matrix liquid is conveyed via a pipeline 15 into a homogenizer 16 for homogenizing the matrix liquid, preferably a high-pressure homogenizer, for example, by means of a pump. The homogenized matrix liquid is then conveyed from the homogenizer 16 via pipeline 17 into the fluidization apparatus 18, for example, by means of a pump.

[0045] In the embodiment of the Fig. 1 The drying apparatus is designed as a fluidization apparatus 18 for producing cannabinoid granules that are essentially soluble in an aqueous medium, with the fluidization apparatus 18 being designed here as a spouted bed apparatus 19. The structure of the spouted bed apparatus 19 comprises, from bottom to top, a distribution chamber 20, a process chamber 21, an expansion zone 22, and an exhaust air section 23.

[0046] 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 via a gap opening 25 and a process gas deflection part 26, preferably as a type of free jet.

[0047] Furthermore, the apparatus cross-section can optionally be enlarged in the expansion zone 22, so that the velocity of the process gas flow decreases steadily upwards. The process gas 24 preferably leaves the spouted bed apparatus 19 as exhaust gas 28 purified by a dedusting system 27, in particular filter cartridges or textile filter elements.

[0048] The process chamber 21 contains carrier particles referred to as starter material, such as mannitol, cellulose, xylitol, or the like, which are entrained upwards by the process gas 24 toward the dedusting system 27. In the upper region of the process chamber 21 and in the expansion zone 22 located above, the process gas velocity decreases, so that the upward-flowing carrier particles exit the process gas stream laterally and fall back into the process chamber 21. The lower region of the process chamber 21 is delimited by inclined side surfaces 28. Due to the inclined side surfaces 28, the carrier particles are transported under the effect of gravity via the return zone 29 toward the gap opening 25, where they are then entrained again by the process gas 24 into the process chamber 21.

[0049] 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.

[0050] Such introduction of the matrix liquid in the lower area of ​​the process chamber 21 is referred to as bottom spray.

[0051] The nozzle, preferably a two-fluid nozzle, is configured to produce droplets with a droplet size of 1 µm up to 200 µm , preferably from 10 µm up to 100 µm , particularly preferably between 20µm and 60 µmto spray. The sprayed droplets particularly preferably have a droplet size of 25 µm to 40 µm, 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 adjusted, 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 preferably occurs.

[0052] Due to the highly advantageous heat and mass transfer, as well as the high carrier particle circulation in the spray area 32 of the process chamber 21 of the spouted bed apparatus 19, the matrix liquid is largely deposited on the carrier particles, thus uniformly wetting the particle surfaces. The uniform wetting combined with the high particle circulation between the spray area 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 leaves the spouted bed apparatus 19 with the exhaust gas 28. The cannabinoid contained in the matrix liquid remains on the particle surface of the carrier particles, so that the resulting cannabinoid granules grow very uniformly and homogeneously.

[0053] 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 sifter, preferably a zigzag sifter pressurized with sifting gas or a riser sifter.

[0054] Mechanical units 34, such as shredders, choppers, 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 granulate nuclei for the granulate formation process by shredding.

[0055] One or more spray devices 35, which preferably spray downwards, can optionally be arranged in the process chamber 21 or in the apparatus sections above it, the expansion zone 22 and the exhaust air section 23. The liquid matrix fluid can also be injected into the process chamber 21 of the spouted 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 into the granulate structure.

[0056] 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 apparatus 18, designed as a spouted bed apparatus 19. Furthermore, it is possible to arrange an extruder for extruding the granules downstream of the granulation unit. Preferably, the homogenizer 16 and / or the granulation unit and / or the extruder are fluidically connected to one another.

[0057] In the Fig. 2 a schematic representation of a second embodiment of a preferred device 1 for producing a cannabinoid granulate that is essentially soluble in an aqueous medium is shown.

[0058] The device 1 comprises a container system 2 for producing the matrix liquid. In the second embodiment according to Fig. 2 the container system 2 has a single container 3.

[0059] The container 3 of the container system 2, which is designed with a double wall for heating or cooling, has a cannabinoid inlet 5 and a liquid inlet 6 for a first liquid consisting of the group of lipids, alcohols, oils and / or any mixture thereof, but particularly preferably of a rapeseed, orange or coconut oil, as well as a liquid inlet 11 for a second liquid, in particular an aqueous solution or water.

[0060] Through the container shell space 9 spanned between the container inner wall 7 and the container outer wall 8, the first container 3a can be temperature-controlled by means of a heating medium flowing through the container shell space 9. Preferably, the container 3a is heated to better dissolve a cannabinoid that may not be readily soluble in the first liquid. The temperature control device is not mandatory.

[0061] In addition, the first container 3a has a motor-driven stirring device 10 for stirring the first liquid. The stirring device is not mandatory.

[0062] In container 3, 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. This is preferably produced in container 3 by 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.

[0063] The matrix liquid is conveyed via a pipeline 15 into a homogenizer 16 for homogenizing the matrix liquid, preferably a high-pressure homogenizer, for example, by means of a pump. The homogenized matrix liquid is then conveyed from the homogenizer 16 via pipeline 17 into the fluidization apparatus 18, for example, by means of a pump.

[0064] The further convective drying process using a fluidization device is carried out according to the first in Fig. 1 described embodiment.

[0065] The resulting cannabinoid granules can then be coated, for example, in a drum coater. This has the advantage of allowing the cannabinoid granules to be given an enteric coating or a flavor masking agent, for example.

[0066] Examples of the production of a matrix liquid and its further processing in the fluidization apparatus are shown below.

[0067] Example 1: The production of the cannabinoid granules in the fluidization apparatus designed as a spouted bed apparatus was carried out in batch operation as bottom spray.

[0068] 500 g of mannitol was used as starting material in the fluidization apparatus.

[0069] The matrix fluid consists of 200 g of Hi-Cap 100, 200 g of maltodextrin, 1365 g of water, 5 g of cannabidiol (CBD), and 50 g of rapeseed oil. The cannabidiol (CBD) was dissolved in rapeseed oil as the first fluid, and the maltodextrin and Hi-Cap 100 were dissolved in water as the second fluid. The rapeseed oil containing CBD and the water containing maltodextrin and Hi-Cap 100 were then mixed together to form an emulsion, thus producing the matrix fluid. Maltodextrin and Hi-Cap 100 serve as additives to form a matrix structure in the matrix fluid.

[0070] The spray rates were set between 10 and 15 g / min. The resulting cannabinoid granules dissolved well in water, forming a stable oil-in-water emulsion. The residual moisture content of the cannabinoid granules was 1.8%.

[0071] After preparation, the matrix fluid was analyzed using a Cilas 1190 LD laser diffraction system (Quantachrome). The particle size of the CBD oil droplets present in the matrix fluid emulsion was determined in Fig. 3 The cumulative distribution curve shows equivalent diameters x 10 = 1.17 µ m , x 50 = 7.97 µ m and x 90 = 18.37 µ m has an average diameter of x = 8.87 µm In addition, the density distribution curve with its two maxima shows a bimodal distribution.

[0072] After the cannabinoid granules have been produced and redissolved in water, a stable oil-in-water emulsion has formed in the aqueous environment.

[0073] The cannabinoid granules dissolved in the aqueous medium were dissolved in water, and the grain size of the CBD-containing oil droplets was again analyzed using the Cilas 1190 LD laser diffraction system (Quantachrome). Fig. 4 shows the analysis. The cumulative distribution curve with equivalent diameters x 10 = 0.82 µ m, x 50 = 2.33 µm and x 90 = 6.26 µ m has an average diameter of x = 3.01 µm. 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 absorbability of CBD and thus to optimal bioavailability. This improved absorbability of the cannabinoids results from more homogeneous and smaller emulsion particles.

[0074] Example 2: The production of the cannabinoid granules in the fluidization apparatus designed as a spouted bed apparatus was carried out in batch operation as bottom spray.

[0075] As starting material in the fluidization apparatus, 250 g of mannitol and 250 g of maltodextrin were used, i.e. in a ratio of 1:1.

[0076] The matrix fluid consists of 200 g of Hi-Cap 100, 200 g of maltodextrin, 1417 g of water, 5.5 g of cannabidiol (CBD), and 51 g of coconut oil. The cannabidiol (CBD) was dissolved in coconut oil as the first fluid, and maltodextrin and Hi-Cap 100 were dissolved in water as the second fluid. The CBD-containing coconut oil and the water containing maltodextrin and Hi-Cap 100 were then mixed together to form an emulsion, thus producing the matrix fluid. Maltodextrin and Hi-Cap 100 serve as additives to form a matrix structure in the matrix fluid.

[0077] The spray rates were increased compared to Example 1. In addition, 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%.

[0078] After preparation, the matrix fluid was analyzed using a Cilas 1190 LD laser diffraction system (Quantachrome). The particle size of the CBD oil droplets present in the matrix fluid emulsion was determined in Fig. 5 The cumulative distribution curve shows equivalent diameters x 10 = 1.18 µ m , x 50 = 6.99 µ m and x 90 = 15.17 µ m has an average diameter of x = 7.58 µ m. In addition, the density distribution curve with its two maxima shows a bimodal distribution.

[0079] After the cannabinoid granules have been produced and redissolved in water, a stable oil-in-water emulsion has formed in the aqueous environment.

[0080] The cannabinoid granules dissolved in the aqueous medium were dissolved in water, and the grain size of the CBD-containing oil droplets was again analyzed using the Cilas 1190 LD laser diffraction system (Quantachrome). Fig. 6 shows the analysis. The cumulative distribution curve with equivalent diameters x 10 = 0.90 µ m , x 50 = 2.48 µ m and x 90 = 6.24 µ m has an average diameter of x = 3.08 µ m. 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 absorbability of CBD and thus to optimal bioavailability. This improved absorbability of the cannabinoids results from more homogeneous and smaller emulsion particles.

Claims

1. A method for manufacturing a cannabinoid granulate which is essentially soluble in an aqueous environment, wherein a matrix liquid is manufactured from a first liquid which dissolves a cannabinoid or from a first liquid which dissolves a cannabinoid and a second fluid which with the first liquid forms an emulsion and from a cannabinoid which is dissolved in the first liquid or in the emulsion, characterised in that the matrix liquid is convectively dried in a fluidisation apparatus (18) by way of spray granulation, spray agglomeration or spray encapsulation, into a cannabinoid granulate.

2. The method according to claim 1, characterised in that firstly a cannabinoid is dissolved in a first liquid and the first liquid subsequently mixed with the second liquid for forming the emulsion or the first liquid is firstly mixed with the second liquid for forming the emulsion and a cannabinoid is subsequently dissolved in the emulsion.

3. The method according to claim 1 or 2, characterised in that the first liquid consists of the group of lipids, alcohols, oils and / or an arbitrary mixture of these and / or the second liquid is an aqueous solution or water.

4. The method according to one of the preceding claims, characterised in that an emulsifier is added to the second liquid before the mixing with the first liquid, wherein expediently an emulsifier is added to the emulsion or to the matrix liquid before the convective drying.

5. The method according to one of the preceding claims, characterised in that the matrix liquid is homogenised before the convective drying, wherein expediently the emulsion is high-pressure homogenised, particular preferably at pressures between 50 bar and 250 bar, very particularly preferably at pressures between 100 bar and 200 bar, most preferably at pressures between 125 bar and 175 bar.

6. The method according to one of the preceding claims, characterised in that the matrix liquid is deposited onto one or more carrier substances before the convective drying in a fluidisation apparatus (18), wherein the matrix liquid is extruded or pelleted after the deposition onto one or more carrier substances.

7. The method according to one of the preceding claims 1 to 5, characterised in that carrier particles are provided in the fluidisation apparatus (18).

8. The method according to one of the preceding claims, characterised in that additives (36) are added to the solution, emulsion or matrix liquid before the convective drying.