Oral solid dosage form comprising cannabinoid

Abstract

The present disclosure relates to drug-containing particles comprising one or more cannabinoids and a porous solid carrier. In embodiments, the one or more cannabinoids are adsorbed onto and / or into the porous solid support. In embodiments, the drug-containing particles exhibit improved solubility and bioavailability, as well as other beneficial properties. Methods of preparation and pharmaceutical compositions are also described.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 371,292, filed on August 12, 2022, the entire contents of which are incorporated herein by reference and are relied upon. Background Art

[0002] Contemporary uses of cannabinoids in medicine have necessitated the need to find more effective methods of delivering these poorly soluble compounds. In addition to poor water solubility, cannabinoids are also known to have limited bioavailability and poor stability in various formulations.

[0003] Oral delivery remains the preferred route of drug administration due to high patient compliance and ease of administration. However, most cannabinoids are highly lipophilic and poorly water soluble, which can result in oral formulations exhibiting poor pharmacokinetics (e.g., low and highly variable bioavailability) and undesirable side effects. These suboptimal properties often result in unpredictable and inconsistent efficacy (e.g., variable onset and / or peak of observed effects) and potential safety issues (e.g., overdosing, especially in use by the elderly) following oral administration.

[0004] Although some progress has been made recently using self-emulsifying drug delivery systems, oil-based excipients, and / or ethanol as a co-solvent, oral formulations that provide suitable bioavailability and can reliably deliver sufficient amounts of cannabinoids in a patient-friendly formulation remain challenging.

[0005] The present disclosure addresses these and other unmet needs. Summary of the invention

[0006] In some embodiments, the present disclosure provides a drug-containing particle comprising: (a) one or more cannabinoids; and (b) a porous solid carrier. In an embodiment, the one or more cannabinoids are adsorbed onto the porous solid carrier. As used herein, "absorbed onto a porous solid carrier" covers the situation where the cannabinoid is present on the surface of the solid carrier and / or in the pores of the porous solid carrier. The term "absorbed onto a porous solid carrier" can be used interchangeably with "absorbed onto and / or in a porous solid carrier". In some embodiments, the present disclosure provides a drug-containing particle comprising: (a) one or more cannabinoids; (b) a porous solid carrier; and (c) one or more lipophilic materials. In an embodiment, the one or more cannabinoids are adsorbed onto the porous solid carrier and / or into the pores of the porous solid carrier (e.g., adsorbed onto and / or in the porous solid carrier). In some embodiments, the present disclosure provides a drug-containing particle comprising: (a) one or more cannabinoids; (b) a porous solid carrier; (c) one or more lipophilic materials; and (d) an antioxidant. In embodiments, the one or more cannabinoids are adsorbed onto the porous solid support and / or into the pores of the porous solid support (e.g., adsorbed onto and / or into the porous solid support). In embodiments, the porous solid support has one or more of the following properties: (i) an average pore volume of 1-2 cm3 / g; (ii) an average surface area of ​​250 to 375; or (iii) a pore size of about 2-50 nm. In embodiments, the porous solid support has two or more of the following properties: (i) an average pore volume of 1-2 cm3 / g; (ii) an average surface area of ​​250 to 375; or (iii) a pore size of about 2-50 nm. In embodiments, the porous solid support has: (i) an average pore volume of 1-2 cm3 / g; (ii) an average surface area of ​​250 to 375; or (iii) a pore size of about 2-50 nm. In embodiments, the one or more cannabinoids may be part of a bulk drug containing additional components such as terpenes, triglycerides and / or sterols. In some embodiments, the porous solid carrier is present as microparticles. In some embodiments, the porous solid carrier has an average particle size in the range of about 1 μm to about 250 μm (e.g., about 50 μm to about 150 μm). In certain embodiments, the porous solid carrier may be highly microporous.

[0007] In some embodiments, the porous solid support has a porosity in a range from about 75% to about 99%.

[0008] In some embodiments, the porous solid support has an oil absorbing capacity of about 1 mL / g to about 10 mL / g.

[0009] In some embodiments, the porous solid support comprises silicon dioxide (SiO2), microcrystalline cellulose, silicified microcrystalline cellulose, chitosan, isomalt, or a silicate (e.g., magnesium silicate, aluminum magnesium silicate, or calcium-magnesium silicate). In certain embodiments, the porous solid support comprises ordered mesoporous silica. In some embodiments, the porous solid support comprises silicon dioxide (SiO2) or a silicate. In some embodiments, the silicon dioxide is mesoporous silicon dioxide or amorphous silicon dioxide. In some embodiments, the silicon dioxide is mesoporous silicon dioxide. In some embodiments, the mesoporous silicon dioxide is or Fujisil TM (It can be manufactured according to cGMP guidelines). In some embodiments, the mesoporous silica is XDP (which is available in 3050 and 3150 grades and manufactured under cGMP guidelines).

[0010] In some embodiments, the mesoporous silica has an average pore size in a range from about 5 nm to about 100 nm (eg, about 2 nm to about 50 nm).

[0011] In some embodiments, the porous solid support comprises a silicate. In some embodiments, the silicate comprises a magnesium silicate, an aluminum magnesium silicate, or a calcium-magnesium silicate. In some embodiments, the silicate is an aluminum silicate, such as a magnesium aluminum silicate. In some embodiments, the silicate is

[0012] In some embodiments, the porous solid carrier is present in an amount ranging from about 20 weight % to about 80 weight % based on the total weight of the drug-containing particle.

[0013] In some embodiments, the drug-containing particles comprise one or more cannabinoids, wherein the one or more cannabinoids are cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic ...varinic acid (THCA), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic acid (THCA), tetrahydrocannabivarinic acid (THCA), tetrahydrocannabivarinic acid (THCA), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic acid (THCA), tetrahydrocannabivarinic acid (THCA), tetrahydrocannabivarinic acid (THCA), tetrahydrocannabivarinic acid (THCA), tetrahydrocannabi acid, THCVA), OH-CBD, CBD-C4, 6-OH-CBD, 7-OH-CBD, 7-COOH-CBD, 11-COOH-THC or 11-OH-THC or a combination thereof. In some embodiments, the one or more cannabinoids are nabilone. In some embodiments, the drug-containing particles comprise metabolites of one or more cannabinoids disclosed herein.

[0014] In some embodiments, the one or more cannabinoids are present in an amount ranging from about 5 to about 75 weight percent based on the total weight of the drug-containing particle.

[0015] In some embodiments, the one or more cannabinoids are present in an amorphous form.

[0016] In some embodiments, adsorption of the one or more cannabinoids onto and / or into the porous solid support is determined by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and / or X-ray powder diffraction (XRPD).

[0017] In some embodiments, substantially all of the one or more cannabinoids are present in the pores and / or surface of the porous solid support. In some embodiments, substantially all of the one or more cannabinoids are present in the pores of the porous solid support.

[0018] In some embodiments, the drug-containing particles further comprise a chelating agent. In some embodiments, the chelating agent is EDTA, citric acid, or a polyphenolic substance (eg, curcumin).

[0019] In some embodiments, the amount of the chelating agent in the drug-containing particle ranges from about 0.05% to about 3% by weight. In some embodiments, the amount of the chelating agent in the drug-containing particle ranges from about 0.05% to about 0.5% by weight.

[0020] In some embodiments, the drug-containing particles further comprise one or more antioxidants. In some embodiments, the one or more antioxidants are tocopherol derivatives (e.g., alpha tocopherol), carotenoids (e.g., lutein or beta-carotene), tocotrienols, ascorbic acid, ascorbyl palmitate, lecithin, butylated hydroxyanisole, butylated hydroxytoluene (BHT), monothioglycerol, propyl gallate, curcumin, or a combination thereof. In some embodiments, the one or more antioxidants are alpha-tocopherol, beta-carotene, ascorbic acid, ascorbyl palmitate, lecithin, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, propyl gallate, curcumin, or a combination thereof.

[0021] In some embodiments, the amount of the one or more antioxidants in the drug-containing particle ranges from about 0.05 weight percent to about 3 weight percent.

[0022] In some embodiments, the drug-containing particles further comprise a chelating agent and one or more antioxidants disclosed herein.

[0023] In some embodiments, the drug-containing particles further comprise one or more lipophilic materials. In embodiments, the drug substance is dissolved or suspended in a lipophilic material and then the drug substance is adsorbed onto the porous carrier. In embodiments, the lipophilic material comprises fatty acid esters containing polyethylene oxide, polyethylene oxide glycerides, polypropylene glycol fatty acid esters, PEG, monoglycerol fatty acid esters, diglycerol fatty acid esters, triglycerol fatty acid esters, propylene glycol diglycerides, polyethylene oxide vegetable oils or combinations thereof. In embodiments, the lipophilic material comprises fatty acid esters containing polyethylene oxide. In some embodiments, the one or more lipophilic materials comprise fatty acid esters containing polyethylene oxide. In some embodiments, the one or more lipophilic materials comprise polyethylene oxide glycerides. In some embodiments, the lipophilic material comprises plant seed oil, fruit seed oil, kernel oil, monoglycerides, diglycerides and triglycerides of palmitic (C16) acid and stearic (C18) acid, and PEG-32 (MW 1500) monoesters and diesters of palmitic (C16) acid and stearic (C18) acid; monoglycerides, diglycerides and triglycerides of fatty acids (C8 to C18); monoglycerides, diglycerides and triglycerides of lauric (C12) acid and stearic (C18) acid, and PEG-6 (MW 300) monoesters and diesters of lauric (C12) acid and stearic (C18) acid; monoglycerides, diglycerides and triglycerides of oleic (C18:1) acid, and PEG-6 (MW 500) monoesters and diesters of oleic (C18:1) acid. 300) and monoesters and diesters; mixtures of monoesters and diesters of 12-hydroxystearic acid and polyethylene glycol glycerides; PEG-40 hydrogenated castor oil; propylene glycol monocaprylate; propylene glycol monolaurate; medium chain triglycerides; propylene glycol dicaproate / dicaprate; PEG-8 (MW400) monoesters and diesters of caprylic (C8) and capric (C10) acids; or combinations thereof. In an embodiment, the lipophilic material is monoglycerides, diglycerides and triglycerides of fatty acids (C8 to C18); monoglycerides, diglycerides and triglycerides of lauric (C12) and stearic (C18) acids and PEG-6 (MW 300) monoesters and diesters of lauric (C12) and stearic (C18) acids; or propylene glycol monocaprylate. In some embodiments, the lipophilic material comprises sesame seed oil, medium chain triglyceride (MCT) oil, oleic acid, pumpkin seed oil, or any other plant or fruit seed oil, and combinations thereof.

[0024] In some embodiments, the one or more lipophilic materials (eg, 2 or 3 lipophilic materials) are present in an amount of about 10 weight percent to about 75 weight percent based on the total weight of the drug-containing particle.

[0025] In some embodiments, the drug-containing particles further comprise one or more polymers. In some embodiments, the polymer has a Tg of about 50° C. to about 130° C. In some embodiments, the polymer comprises carboxymethyl cellulose, polyvinyl pyrrolidone (kollidon VA64), cross-linked polyvinyl N-pyrrolidone (crospovidone), hydroxypropyl methylcellulose phthalate (HPMCP 50), polyvinyl alcohol-polyethylene glycol copolymer (kollicoat), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (soluplus), polyvinyl alcohol, or a combination thereof.

[0026] In some embodiments, the one or more polymers are present in an amount of about 10 wt% to about 50 wt% based on the total weight of the drug-containing particle. In some embodiments, the polymer is provided as a coating on the drug-containing particle.

[0027] In some embodiments, the drug-containing particles disclosed herein release 50-90% of the one or more cannabinoids within about 1-16 hours. In some embodiments, the drug-containing particles disclosed herein release 50-90% of the one or more cannabinoids within about 3-12 hours. In some embodiments, the drug-containing particles disclosed herein release greater than about 70% of the one or more cannabinoids by about 6 hours. In some embodiments, the drug-containing particles disclosed herein release greater than about 80% of the one or more cannabinoids by about 12 hours.

[0028] In some embodiments, the drug-containing particles are substantially free of cannabidiorcol (CBD-C1), cannabidiol (CBDV) and / or butyl-cannabidiol (cannabidibutol, CBD-C4). In some embodiments, the drug-containing particles contain no more than about 0.2% by weight of CBD-C1 actives. In some embodiments, the drug-containing particles contain no more than about 0.8% by weight of CBDV actives. In some embodiments, the drug-containing particles contain about 0.15 to about 0.8% by weight of CBDV actives. In some embodiments, the drug-containing particles contain no more than about 0.5% by weight of CBD-C4 actives.

[0029] In some embodiments, the present disclosure provides a pharmaceutical composition comprising the drug-containing particles disclosed herein. In some embodiments, the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients and / or carriers. In some embodiments, the pharmaceutical composition is in the form of tablets, capsules or granules.

[0030] In some embodiments, the pharmaceutical composition is prepared by a process comprising mixing / blending (eg, high or low shear mixing / blending), spray drying, or hot melt extrusion. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 An overview of formulation techniques used to prepare the drug-containing particles of the present disclosure is provided.

[0032] Figure 2 A schematic diagram showing the impregnation and release of drugs from the porous solid carrier of the present disclosure is provided.

[0033] Figure 3 is a graph showing that a drug can be released from a porous solid carrier of the present disclosure after contact with gastric fluid.

[0034] Figure 4 Schematic diagram showing aspects comparing lipid loading and solvent mediated approaches for adsorption of drugs into mesoporous silica.

[0035] Figure 5 A flow chart describing the laboratory-scale preparation of drug-containing particles of the present disclosure via a solvent-mediated method is provided.

[0036] Figure 6 Provided from loading 50% w / w drug and Fujisil TM Graph of CBD release.

[0037] Figure 7 A flow chart is provided describing the laboratory-scale preparation of drug-containing particles of the present disclosure by a formulation method comprising spray drying.

[0038] Figure 8 An exemplary spray drying apparatus that can be used to prepare the drug-containing particles of the present disclosure is shown.

[0039] Fig. 9A A flow chart is provided describing the CBD / sesame oil loaded mesoporous silica drug particle formulations 1-6 of Table 5 manufacturing methods for preparing the drug-containing particles of the present disclosure.

[0040] Fig. 9B A flow chart is provided describing a manufacturing method for CBD / lipid-loaded mesoporous silica drug particle formulations 7-10 for preparing the drug-containing particles of the present disclosure.

[0041] Fig. 9C A flow chart is provided describing the CBD / lipid-loaded mesoporous silica drug particle formulations 1-10 of the manufacturing method of Table 8 for preparing the drug-containing particles of the present disclosure.

[0042] Fig.10A graph of CBD release from lipid-loaded mesoporous silica samples of the present disclosure is provided.

[0043] Fig.11 A flow chart is provided describing the laboratory-scale preparation of drug-containing particles of the present disclosure via a solvent-mediated polymer formulation method.

[0044] Fig.12 is a chart showing classes of polymers suitable for use in the drug-containing particles of the present disclosure.

[0045] Fig.13A The variation of the CBD content in the lipid-loaded formulations described in Table 6 of Example 3, prepared with the mesoporous silica described herein and in addition containing 0.2% alpha-tocopherol, is shown.

[0046] Fig. 13B Shown is the variation in CBD content in the same lipid loaded formulation prepared without alpha-tocopherol.

[0047] Fig.14A Shown is the variation in CBE I content in the lipid-loaded formulations described herein containing 0.2% alpha-tocopherol.

[0048] Fig. 14B Shown is the change in CBE I content in the same lipid loading formulation prepared without 0.2% α-tocopherol.

[0049] Fig.15A Shown is the variation in CBE II content in the lipid-loaded formulations described herein containing 0.2% alpha-tocopherol.

[0050] Fig. 15B Shown is the change in CBE II content in the same lipid loading formulation prepared without 0.2% α-tocopherol.

[0051] Fig.16A Shown is the variation in OH-CBD content in the lipid-loaded formulations described herein containing 0.2% alpha-tocopherol.

[0052] Fig. 16B Shown is the change in OH-CBD content in the same lipid-loaded formulation prepared without 0.2% α-tocopherol.

[0053] Fig.17A Shown is the variation in OH-CBD content in the lipid-loaded formulations described herein containing 0.2% alpha-tocopherol.

[0054] Fig. 17B Shown is the change in OH-CBD content in the same lipid-loaded formulation prepared without 0.2% α-tocopherol.

[0055] Fig.18A Shown is the CBE I content in the hard fat loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0056] Fig.18B Shown is the CBE II content in the hard fat loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0057] Fig.18C Shown is the OH-CBD content in the hard fat loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0058] Fig.18D Shown are additional unknown degradant levels in the hard fat loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0059] Fig.19A Shown is the CBE I content in lauroyl polyoxyl-6 glyceride loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0060] Fig.19B Shown is the CBE II content in lauroyl polyoxyl-6 glyceride loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0061] Fig.19C Shown is the OH-CBD content in lauroyl polyoxyl-6 glyceride loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0062] Fig.19D Shown are additional unknown degradant levels in lauroyl polyoxyl-6 glyceride loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0063] Fig. 20A Shown is the CBE I content in the propylene glycol monocaprylate loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0064] Fig. 20B Shown is the CBE II content in the propylene glycol monocaprylate loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0065] Fig. 20C Shown is the OH-CBD content in propylene glycol monocaprylate loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0066] Fig.20D The additional unknown degradant levels are shown in the propylene glycol monocaprylate loaded formulations described herein containing 0.2%, 0.6% and 1% alpha-tocopherol at 40°C / 75%RH.

[0067] Fig.21A Shown is the relative bioavailability (in Frel %) of formulations containing different ratios of CBD to lipophilic material, as measured in beagle dogs.

[0068] Fig. 21B Shown is the relative bioavailability (in Frel %) of formulations containing different ratios of CBD to lipophilic material, as measured in beagle dogs.

[0069] Fig. 21C The relative bioavailability (in % Frel) of formulations containing different ratios of CBD to lipophilic material, as measured in beagle dogs, is shown. The Y axis is reported as % Frel, which measures the % of the mean plasma concentration (AUC) relative to the mean plasma concentration of CBD dissolved in sesame oil and prepared into capsules ("CBD OS in capsules").

[0070] Fig.22A The relative bioavailability (in Frel %) of formulations containing different ratios of CBD to lipophilic material in rats, as described in Example 8, is shown.

[0071] Fig. 22B The relative bioavailability (in Frel %) of formulations containing different ratios of CBD to lipophilic material in rats, as described in Example 8, is shown.

[0072] Fig. 22C The relative bioavailability (in Frel %) of formulations containing different ratios of CBD to lipophilic material in rats, as described in Example 8, is shown.

[0073] Fig.23A Shown is the x-ray diffraction pattern (XRPD) of solvent loaded drug-containing particles at time point 0.

[0074] Fig. 23B Shown is the x-ray diffraction pattern (XRPD) of solvent loaded drug-containing particles after 1 week.

[0075] Fig.24An x-ray diffraction pattern (XRPD) showing the non-crystalline nature of CBD when absorbed onto and / or into a porous carrier using the lipid loading process described herein is shown. definition

[0076] The term "cannabinoid" as used herein generally refers to one of a class of diverse chemical compounds that act on cannabinoid receptors in cells that inhibit the release of neurotransmitters in the brain. Ligands for these receptor proteins include endogenous cannabinoids (produced naturally in the body by humans and animals), phytocannabinoids (found in cannabis and some other plants), and synthetic cannabinoids (manufactured artificially). Thus, the term "cannabinoid" encompasses both endogenous cannabinoids and phytocannabinoids.

[0077] "Endocannabinoids" are endogenous cannabinoids that are high affinity ligands for the CB1 and CB2 receptors.

[0078] "Phytocannabinoids" are cannabinoids that originate in nature and can be found in the cannabis plant. The phytocannabinoids may be present in extracts including botanical raw materials, isolated, or synthetically produced.

[0079] A "synthetic cannabinoid" is a cannabinoid that has been produced by chemical synthesis. This term may include the modification of an isolated phytocannabinoid, for example by forming a pharmaceutically acceptable salt thereof.

[0080] A "substantially pure" cannabinoid is defined as a cannabinoid that is greater than 95% (w / w) pure. In some embodiments, "substantially pure" refers to greater than 96% (w / w), greater than 97% (w / w), greater than 98% (w / w), or greater than 99% (w / w) pure.

[0081] "Botanical drug substance" or "BDS" is defined in the Guidance for Industry Botanical Drug Products Draft Guidance, August 2000, US Department of Health and Human Services, Food and Drug Administration Centre for Drug Evaluation and Research as: "A drug derived from one or more plants, algae or microscopic fungi. It is prepared from botanical raw materials by one or more of the following processes: comminution, decoction, expression, aqueous extraction, ethanol extraction or other similar processes."

[0082] The term "pharmaceutically acceptable" means biologically or pharmacologically suitable for use in vivo in animals or humans, and may mean approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia (e.g., the European Pharmacopoeia, the British Pharmacopoeia, and the Japanese Pharmacopoeia) for use in animals, and more particularly in humans.

[0083] The terms "lipophilic material" and "lipophilic materials" and the like may refer to materials that are soluble in non-polar materials such as fats, oils, and lipids. General examples of lipophilic materials include fatty acids, fatty alcohols, oils, lipids, butters, and fats. As used herein, a lipophilic material may be a class of lipophilic materials such as fatty acid esters containing polyethylene oxide, or a lipophilic material such as polyethylene oxide esters of C8 fatty acids. Additional lipophilic materials are described in U.S. Pat. No. 6,294,192, which is incorporated by reference in its entirety.

[0084] For example, in an embodiment, the lipophilic material of the present application comprises MCT oil; oleic acid oil; monoglycerides, diglycerides and triglycerides of palmitic acid (C16) and stearic acid and PEG-32 (MW 1500) monoesters and diesters of palmitic acid (C16) and stearic acid (C18); monoglycerides, diglycerides and triglycerides of fatty acids (C8 to C18); monoglycerides, diglycerides and triglycerides of lauric (C12) acid and stearic (C18) acid and PEG-6 (MW 300) monoesters and diesters of lauric (C12) acid and stearic (C18) acid; monoglycerides, diglycerides and triglycerides of oleic (C18:1) acid and PEG-6 (MW 300) monoesters and diesters. 300) and mono- and diesters; mixtures of mono- and diesters of 12-hydroxystearic acid with polyethylene glycol glycerides; PEG-40 hydrogenated castor oil; propylene glycol monocaprylate; propylene glycol monolaurate; medium chain triglycerides; propylene glycol dicaproate / dicaprate; PEG-8 (MW 400) mono- and diesters of caprylic (C8) and capric (C10) acids; or combinations thereof.

[0085] The term "lipid loading" refers to a composition in which a cannabinoid and a lipophilic material are present on a porous solid carrier. In embodiments, the cannabinoid is dissolved or suspended in a lipophilic material and the resulting solution is then combined with a porous solid carrier such that the cannabinoid is absorbed onto the porous solid carrier. This results in an amorphous form of the cannabinoid.

[0086] Throughout this specification, the term "about" and / or "approximately" can be used in conjunction with numerical values ​​and / or ranges. The term "about" should be understood to mean those values ​​close to the listed values ​​and within the range of variation levels recognized in the field. For example, "about 40 [units]" can mean within ± 25% (e.g., 30 to 50) of 40, within ± 20%, ± 15%, ± 10%, ± 9%, ± 8%, ± 7%, ± 6%, ± 5%, ± 4%, ± 3%, ± 2%, ± 1%, less than ± 1% or any other value or the range of values ​​therebetween. In addition, the phrase "less than about [a value]" or "greater than about [a value]" should be understood to be in view of the definition of the term "about" provided herein. The terms "about" and "approximately" can be used interchangeably. In an embodiment, approximately can mean within ± 10% of a value.

[0087] Unless expressly stated to the contrary, all ranges cited herein are inclusive; that is, the range includes the value of the upper and lower limit of the range and all values ​​therebetween. DETAILED DESCRIPTION Solid dosage form

[0088] Described herein are oral solid dosage forms comprising cannabinoid-containing drug particles, which when prepared according to the method generally described in Figure 1 When manufactured using the formulation techniques in the invention, the drug-containing particles of the present invention provide improved solubility and oral bioavailability compared to formulations manufactured by other methods known in the art. Among its beneficial properties, the drug-containing particles of the present invention are found to be stable free-flowing powders that can exhibit high oil adsorption capacity and rapid drug release upon contact with gastric fluid.

[0089] In some embodiments, the present disclosure provides a drug-containing particle comprising: (a) one or more cannabinoids, terpenes, triglycerides and / or sterols; and (b) a porous solid carrier. In some embodiments, the present disclosure provides a drug-containing particle comprising: (a) one or more cannabinoids and one or more terpenes, triglycerides and / or sterols; and (b) a porous solid carrier. In an embodiment, the one or more cannabinoids are present on the surface and / or in the pores of the porous solid carrier. In an embodiment, the one or more cannabinoids are present in the pores of the porous solid carrier. The association of the cannabinoids on the surface of the porous solid carrier or in the pores of the solid carrier may be referred to herein as "adsorption". Therefore, in some embodiments, the one or more cannabinoids are adsorbed onto and / or in the porous solid carrier.

[0090] In some embodiments, the present disclosure provides a drug-containing particle comprising: (a) one or more cannabinoids and terpenes, and / or sterols; and (b) a porous solid carrier. In embodiments, the one or more cannabinoids are present (adsorbed) on the surface and / or in the pores of the porous solid carrier. In embodiments, the one or more cannabinoids are present in the pores of the porous solid carrier. In some embodiments, the present disclosure provides a drug-containing particle comprising: (a) one or more cannabinoids; and (b) a porous solid carrier. In embodiments, the one or more cannabinoids are present (adsorbed) on the surface and / or in the pores of the porous solid carrier. In embodiments, the one or more cannabinoids are present in the pores of the porous solid carrier.

[0091] In some embodiments, the drug-containing particle has a composition provided in Table 11, Table 12, or Table 15. Porous solid support

[0092] The porous solid carrier of the present disclosure can be any porous material onto or into which one or more cannabinoids can be adsorbed to provide suitable bioavailability and drug release.

[0093] In some embodiments, the porous solid carrier comprises silicon dioxide (SiO2), microcrystalline cellulose (MCC; e.g., Pharmacel 102), silicified microcrystalline cellulose (SMCC; e.g., Pharmacel SMCC90), chitosan, isomalt (e.g., Galen IQ 721), florite, or a silicate. In some embodiments, the porous solid carrier comprises microcrystalline sodium carboxymethyl cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, chitosan, or isomalt. In some embodiments, the porous solid carrier comprises silicon dioxide, microcrystalline cellulose, silicified microcrystalline cellulose, chitosan, isomalt, or a silicate. In some embodiments, the porous solid carrier comprises silicon dioxide or a silicate. In some embodiments, the porous solid carrier is mesoporous silica or amorphous silica.

[0094] In some embodiments, the porous solid carrier disclosed herein is present as microparticles. In some embodiments, the porous solid carrier has an average particle size of about 1 μm to about 1000 μm, for example, about 1 μm, about 10 μm, about 20 μm, about 30 μm, about 40 μm, about 50 μm, about 60 μm, about 70 μm, about 80 μm, about 90 μm, about 100 μm, about 150 μm, about 200 μm, about 250 μm, about 300 μm, about 350 μm, about 400 μm, about 450 μm, about 500 μm, about 550 μm, about 600 μm, about 650 μm, about 700 μm, about 750 μm, about 800 μm, about 850 μm, about 900 μm, about 950 μm or about 1000 μm (including all ranges and values ​​therebetween). In some embodiments, the porous solid carrier has an average particle size in the range of about 1 μm to about 250 μm. In some embodiments, the porous solid carrier has an average particle size in the range of about 25 μm to about 250 μm. In some embodiments, the porous solid carrier has an average particle size in the range of about 50 μm to about 150 μm. In some embodiments, the porous solid carrier has an average particle size in the range of about 40 μm to about 100 μm. In some embodiments, the porous solid carrier has an average particle size in the range of about 40 μm to about 85 μm. In some embodiments, the porous solid carrier has an average particle size in the range of about 50 μm to about 80 μm. In some embodiments, the porous solid carrier has an average particle size in the range of about 50 μm to about 70 μm. In some embodiments, the porous solid carrier has an average particle size in the range of about 10 μm to about 75 μm. In some embodiments, the porous solid carrier has an average particle size in the range of about 20 μm to about 70 μm. In some embodiments, the porous solid support has an average particle size in a range from about 25 μm to about 65 μm.

[0095] In some embodiments, the porous solid carrier has a porosity in the range of about 25% to about 99%, for example, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95% or about 99% (including all ranges and values ​​therebetween). In some embodiments, the porous solid carrier has a porosity in the range of about 50% to about 99%. In some embodiments, the porous solid carrier has a porosity in the range of about 75% to about 99%. In some embodiments, the porous solid carrier has a porosity in the range of about 25% to about 95%. In some embodiments, the porous solid carrier has a porosity in the range of about 50% to about 95%. In some embodiments, the porous solid carrier has a porosity in the range of about 75% to about 95%. In some embodiments, the porous solid support has a porosity in the range of about 85% to about 95%. In some embodiments, the porous solid support has a porosity greater than about 50%, greater than about 55%, greater than about 60%, greater than about 65%, greater than about 70%, greater than about 75%, greater than about 80%, greater than about 85%, greater than about 90%, or greater than about 95%.

[0096] In some embodiments, the porous solid support has an average surface area in the range of about 100 m2 / g to about 1000 m2 / g, for example, about 100 m2 / g, about 200 m2 / g, about 300 m2 / g, about 400 m2 / g, about 500 m2 / g, about 600 m2 / g, about 700 m2 / g, about 800 m2 / g, about 900 m2 / g, or about 1000 m2 / g, including all ranges and values ​​therebetween. In some embodiments, the porous solid support has an average surface area in the range of about 100 m2 / g to about 800 m2 / g, about 200 m2 / g to about 800 m2 / g, about 200 m2 / g to about 600 m2 / g, about 200 m2 / g to about 500 m2 / g, about 200 m2 / g to about 400 m2 / g, about 300 m2 / g to about 400 m2 / g, or about 250 m2 / g to about 350 m2 / g, including all ranges and values ​​therebetween.

[0097] In some embodiments, the porous solid carrier has an average pore volume in the range of about 0.1 mL / g to about 5 mL / g, such as about 0.1 mL / g, about 0.5 mL / g, about 1 mL / g, about 1.25 mL / g, about 1.5 mL / g, about 1.75 mL / g, about 2 mL / g, about 2.25 mL / g, about 2.25 mL / g, about 2.5 mL / g, about 2.75 mL / g, about 3 mL / g, about 3.25 mL / g, about 3.5 mL / g, about 3.75 mL / g, about 4 mL / g, about 4.25 mL / g, about 4.5 mL / g, about 4.75 mL / g or about 5 mL / g (including all ranges and values ​​therebetween). In some embodiments, the porous solid carrier has an average pore volume in the range of about 1 mL / g to about 5 mL / g. In some embodiments, the porous solid carrier has an average pore volume in the range of about 1.5mL / g to about 5mL / g. In some embodiments, the porous solid carrier has an average pore volume in the range of about 1.5mL / g to about 4mL / g. In some embodiments, the porous solid carrier has an average pore volume in the range of about 1.5mL / g to about 3mL / g. In some embodiments, the porous solid carrier has an average pore volume in the range of about 1.5mL / g to 2.0mL / g. In some embodiments, the porous solid carrier has an average pore volume in the range of about 1mL / g to 2mL / g. In some embodiments, the porous solid carrier has an average pore volume in the range of about 1mL / g to 1.9mL / g.

[0098] In some embodiments, the porous solid carrier has an average pore size in the range of about 1nm to about 100nm, for example, about 1nm, about 2nm, about 3nm, about 4nm, about 5nm, about 10nm, about 15nm, about 20nm, about 25nm, about 30nm, about 35nm, about 40nm, about 45nm, about 50nm, about 55nm, about 60nm, about 65nm, about 70nm, about 80nm, about 85nm, about 90nm, about 95nm or about 100nm (including all ranges and values ​​therebetween). In some embodiments, the porous solid carrier has an average pore size in the range of about 2nm to about 60nm. In some embodiments, the porous solid carrier has an average pore size in the range of about 2nm to about 50nm. In some embodiments, the porous solid carrier has an average pore size in the range of about 10nm to about 50nm. In some embodiments, the porous solid carrier has an average pore size in the range of about 15nm to about 30nm. In some embodiments, the porous solid support has an average pore size in the range of about 20 nm to about 30 nm. In some embodiments, the porous solid support has an average pore size in the range of about 15 nm to about 25 nm.

[0099] In some embodiments, the porous solid carrier has an oil absorption of about 1 mL / g to about 10 mL / g, for example, about 1 mL / g, about 1.5 mL / g, about 2 mL / g, about 2.5 mL / g, about 3 mL / g, about 3.5 mL / g, about 4 mL / g, about 4.5 mL / g, about 5 mL / g, about 5.5 mL / g, about 6 mL / g, about 6.5 mL / g, about 7 mL / g, about 7.5 mL / g, about 8 mL / g, about 8.5 mL / g, about 9 mL / g, about 9.5 mL / g or about 10 mL / g (including all ranges and values ​​therebetween). In some embodiments, the porous solid carrier has an oil absorption of about 1 mL / g to about 5 mL / g. In some embodiments, the porous solid carrier has an oil absorption of about 1 mL / g to about 4 mL / g. In some embodiments, the porous solid carrier has an oil absorption of about 2 mL / g to about 5 mL / g.

[0100] Without being bound by any particular theory, based on the properties disclosed herein, the internal mesopores of the porous solid support (e.g., the silica material described herein) may be impregnated with a concentrated drug solution comprising one or more cannabinoids. Figure 2 ). A stable amorphous phase may then be generated due to the drug being confined to pores of subcritical size and / or the strength of the absorptive interactions (e.g., H-bonding). Upon contact with gastric fluid, the confined amorphous drug may be rapidly released ( Figure 3 ).

[0101] In some embodiments, the porous solid carrier is present in an amount ranging from about 10% by weight to about 90% by weight (e.g., about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, or about 90%, including all ranges and values ​​therebetween) based on the total weight of the drug-containing particle. In some embodiments, the porous solid carrier is about 20% to about 80% by weight, about 25% to about 80% by weight, about 30% to about 80% by weight, about 35% to about 80% by weight, about 40% to about 80% by weight, about 45% to about 80% by weight, about 50% to about 80% by weight, about 55% to about 80%, about 60% to about 80% by weight, about 20% to about 75%, about 50% to about 80% by weight, about 55% to about 80%, about 60% to about 80% by weight, about 20% to about 75%, about 25% to about 20% by weight, about 20% to about 30% by weight, about 25% to about 3 ... In some embodiments, the porous solid carrier is present in an amount ranging from about 30% by weight to about 50% by weight, about 20% by weight to about 65% by weight, about 20% by weight to about 60% by weight, about 20% by weight to about 55%, about 20% by weight to about 50% by weight, about 20% by weight to about 45% by weight, about 25% by weight to about 55% by weight, about 25% by weight to about 50% by weight, about 30% by weight to about 60% by weight, about 30% by weight to about 55% by weight, about 30% by weight to about 50% by weight, or about 35% by weight to about 50%. In some embodiments, the porous solid carrier is present in an amount ranging from about 30% by weight to about 50% by weight based on the total weight of the drug-containing particles.

[0102] In some embodiments, the porous solid support is mesoporous silica. In some embodiments, the mesoporous silica is or Fujisil TM or In some embodiments, the mesoporous silica is XDP or FP. In some embodiments, the mesoporous silica is In some embodiments, the mesoporous silica is

[0103] In some embodiments, the porous solid support has a Fujisil TM or In some embodiments, the porous solid support has XDP or In some embodiments, the porous solid support has In some embodiments, the porous solid support has In an embodiment, the porous solid support has XDP or In an embodiment, the solid support has a XDP or In an embodiment, the solid support has a pore volume corresponding to XDP or In an embodiment, the solid support has a surface area corresponding to XDP or The aperture of the aperture.

[0104] XDP is a commercially available silica-based product (WR Grace & Co.-Conn, Columbia, Maryland) that can be used as a porous solid carrier containing drug particles as described herein. XDP is used to prepare solid dosage forms (e.g., liquid-solid formulations) from liquid ingredients. In some embodiments, the porous solid carrier has one or more of the following properties: *All values ​​are presented as mean values; values ​​may range from ±20% or ±10%

[0105] Fujisil TM is a commercially available silica-based product (Fuji Chemical Industries Co., Ltd.) and can be used as a porous solid carrier in the drug-containing particles described herein. TM For preparing solid dosage forms (e.g., liquid-solid formulations) from liquid ingredients. In some embodiments, the porous solid carrier has one or more of the following properties: form Amorphous Average particle size (μm) 80 Bulk density (g / mL) 0.17 Tap density (g / mL) 0.20 <![CDATA[Specific surface area (m 2 / g)]]> 400 Oil absorption (mL / g) 3.3 <![CDATA[Pore volume (cm 3 / g)]]> 2.1 Angle of repose(°) 30 pH (USP method) 4.0-8.0 *All values ​​are presented as mean values; value ranges may be ±20% or ±10%

[0106] is a commercially available silica-based product (WR Grace & Co.-Conn, Columbia, Maryland) that can be used as a porous solid carrier containing drug particles as described herein. For preparing solid dosage forms (e.g., liquid-solid formulations) from liquid ingredients. In some embodiments, the porous solid carrier has one or more of the following properties: Specific surface area (BET) m2 / g 260-320 pH, in slurry 3.5-5.5 Tap density (g / l) 280 Average particle size (μm) 30 Pore ​​volume (ml / g) 1.5-1.9 Average pore size 22.9 *All values ​​are presented as mean values; values ​​may range from ±20% or ±10%

[0107] In some embodiments, the porous solid support is a silicate. In some embodiments, the silicate comprises a magnesium silicate, an aluminum magnesium silicate, or a calcium-magnesium silicate. In some embodiments, the silicate is an aluminum silicate, such as a magnesium silicate. In some embodiments, the silicate is is a commercially available magnesium aluminum silicate product having the chemical formula Al2O3·MgO·1.7SiO2·xH2O (Fuji Chemical Industries Co., Ltd.), which can be used as a porous solid carrier in the drug-containing particles described herein. In some embodiments, the present disclosure For preparing solid dosage forms (e.g., liquid-solid formulations) from liquid ingredients. In one embodiment, the porous solid carrier has one or more of the following characteristics: *The value range can be ±20% or ±10% Cannabinoids and other active agents

[0108] The term "drug substance" is used herein to refer to an active agent or a mixture of active agents absorbed onto a porous solid carrier. In an embodiment, the active agent is a cannabinoid. There are many cannabinoids known to be suitable for use in the drug-containing particles disclosed herein. In some embodiments, the cannabinoid is a natural cannabinoid. In some embodiments, the cannabinoid is a natural cannabinoid found in the cannabis plant. In some embodiments, the cannabinoid is a synthetic cannabinoid. In some embodiments, the cannabinoid is a mixture of natural cannabinoids. In some embodiments, the cannabinoid is a mixture of synthetic cannabinoids. In some embodiments, the cannabinoid is a mixture of natural and synthetic cannabinoids. In some embodiments, the cannabinoids suitable for use in drug-containing particles are phytocannabinoids, endogenous cannabinoids, synthetic cannabinoids, or a combination thereof. In some embodiments, the drug-containing particles contain one or more metabolites or synthetically produced derivatives of one or more cannabinoids disclosed herein.

[0109] In some embodiments, the drug-containing particles comprise one or more cannabinoids, wherein the one or more cannabinoids are cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabichromene (CBL), cannabinol (CBN), cannabigerol propyl variant (CBNV), dihydroxycannabinol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabinol (THCV), tetrahydrocannabinolic acid (THCVA), OH-CBD, CBD-C4, 6-OH-CBD, 7-OH-CBD, 7-COOH-CBD, 11-COOH-THC, 11-OH-THC, metabolites thereof, combinations thereof, or mixtures thereof.

[0110] In some embodiments, the drug-containing particles include one or more cannabinoids, wherein the one or more cannabinoids are cannabichromene (CBC), cannabichromene acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidiol (CBDV), cannabigerol (CBG), cannabidiolic acid propyl variant (CBGV), cannabicycline (CBL), cannabinol (CBN), cannabidiolic acid propyl variant (CBNV), dihydroxycannabinol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabinol (THCV), tetrahydrocannabinolic acid (THCVA), CBD-C4, combinations thereof or mixtures thereof. In some embodiments, the one or more cannabinoids are cannabidiol (CBD), cannabidiol (CBDV), tetrahydrocannabinol (THCV), cannabigerol (CBG), cannabidiolic acid (CBDA), combinations thereof or mixtures thereof. In some embodiments, the one or more cannabinoids are CBD.

[0111] The drug-containing particles of the present disclosure may also include at least one selected from those disclosed in Handbook of Cannabis, Cannabinoids in Cannabinoids by Roger Pertwee, Chapter 1, pages 3-15.

[0112] In some embodiments, the one or more cannabinoids are extracted from a cannabis plant, and the resulting extract may include additional components extracted from the cannabis plant. Such components may include, but are not limited to, terpenes and sterols.

[0113] In some embodiments, the drug-containing particles comprise one or more terpenes. In embodiments, the terpenes comprise one or more sesquiterpenes. Non-limiting examples of terpenes and sesquiterpenes include, but are not limited to, beta-farnesene, selina-3,7(11)-diene, guaia-3,9-diene, trans-caryophyllene, alpha-caryophyllene, trans-nerolidol, myrcene, trans-phytol, squalene, alpha-bisabolol, alpha-tocopherol, or a combination thereof.

[0114] In some embodiments, the drug-containing particles comprise one or more sterols including, but not limited to, beta-sitosterol, beta-amyrin, campesterol, lupeol, or a combination thereof.

[0115] Thus, in embodiments, the drug-containing particles described herein comprise CBD, THC, CBDA, CBDV, CBN, CBC, monomethylated CBG (CBG MME), CBD-C1, CBD-C4, THCV, CBG, OH-CBD, CBL, DHC, and / or various terpenes and sterols described herein (e.g., alpha-bergmatone, alpha-bisabolol, β-farnesene, 3,7(11)-diene, 3,9-diene, trans-caryophyllene, α-caryophyllene, trans-nerolidol, myrcene, trans-phytol, squalene, alpha-tocopherol, β-myristol, β-amyrin, phytosterol, lupeol, or a combination thereof.

[0116] In some embodiments, the drug-containing particles include a bulk drug comprising a mixture of CBD, trans-THC, CBC, CBG, CBDV, CBD-C4, cis-THC, terpenes, triglycerides, and sterols. In some embodiments, the bulk drug comprises 70-100% w / w cannabinoids, 1.0-3.0% w / w terpenes, 0.8-3.0% w / w triglycerides, and / or 0.5-2.0% w / w sterols based on the total weight of the bulk drug.

[0117] In some embodiments, the mixture comprises the following cannabinoids:

[0118] In some embodiments, the drug-containing particles comprise a drug substance comprising a mixture of the following cannabinoids based on the total weight of the drug substance: CBD 99%w / w CBDA NMT 0.15%w / w CBDV NMT 1.0%w / w <![CDATA[Δ 9 THC]]> NMT 0.15%w / w CBD-C4 NMT 0.5%w / w

[0119] In some embodiments, the drug-containing particles include nabilone. Nabilone (sold under the trade name Cesamet) consists of a racemic mixture of the following two compounds:

[0120] In some embodiments, the drug-containing particles comprise:

[0121] or a salt thereof. This compound and its therapeutic utility are described in WO 2022 / 129908, which is incorporated herein by reference in its entirety.

[0122] The drug-containing particles of the present disclosure may include one or more cannabinoid-containing plant extracts (e.g., nabiximols), which are described in WO 2007 / 083098, which is incorporated herein by reference in its entirety. In some embodiments, the drug-containing particles include nabiximols. Nabiximols (also known by its trade name Sativex) is available as an oromucosal spray containing 27 mg THC, 25 mg CBD, and lesser amounts of other cannabinoids per ml. Nabiximols has been used to treat spasticity, neuropathic pain, and other symptoms of multiple sclerosis.

[0123] Table A below provides the structures of certain cannabinoids, terpenes and sterols that may be included in the drug-containing particles disclosed herein, as well as their standard abbreviations. The following table is not exhaustive and only details the cannabinoids and other potential components of the drug-containing particles, which are identified in this application for reference. Table A. Non-limiting examples of cannabinoids, sterols, and terpenes, and their abbreviations.

[0124] All metabolites and prodrugs of THC, CBD and the remaining cannabinoids are contemplated as being included in the present disclosure. Table B shows the structures of certain metabolites of CBD and THC. Table B. Structures of 11-COOH-THC, 11-OH-THC, 7-OH-CBD, 6-OH-CBD, and 7-COOH-CBD.

[0125] In an embodiment, the drug-containing particle comprises one of the compositions from Table C or Table D: Table C Table D Components DS-C DS-D DS-E DS-F CBD 75.3%w / w 73.62%w / w 78.06%w / w 69.5-83.6%w / w Trans-THC 1.6%w / w 1.55%w / w 0.89%w / w 1.3-1.9% w / w CBC 1.9%w / w 1.72%w / w 1.86%w / w 1.5-2.3% w / w CBG 0.9%w / w 0.74%w / w 1.02%w / w 0.5-1.5% w / w CBDV 0.4%w / w 0.36%w / w 0.63%w / w 0.4-0.7% w / w CBD-C4 0.2%w / w 0.20%w / w 0.28%w / w 0.3-0.4% w / w Total cannabinoids 82.6%w / w 80.13%w / w 85.08%w / w 76.9-92.0%w / w

[0126] When a combination or mixture of cannabinoids is present in the drug-containing particles of the present disclosure, the combination or mixture may include the cannabinoids in any suitable ratio. For example, in some embodiments, the drug-containing particles include about 100:1, 90:1, 80:1, 70:1, 60:1, 50:1, 45:1, 40:1, 35:1, 30:1, 25:1, 20:1, 15:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1 or 1:1 ratios of two cannabinoids disclosed herein.

[0127] The one or more cannabinoids may be present in any amount that allows the cannabinoids to be amorphous when adsorbed onto the porous solid carrier. In some embodiments, the one or more cannabinoids are present in an amount ranging from about 1% to about 75% by weight based on the total weight of the drug-containing particle (e.g., about 1%, about 2.5%, about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, about 20%, about 22.5%, about 25%, about 27.5%, about 30%, about 32.5%, about 33%, about 34%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%. %, about 35% by weight, about 37.5% by weight, about 40% by weight, about 42.5% by weight, about 45% by weight, about 47.5% by weight, about 50% by weight, about 52.5% by weight, about 55% by weight, about 57.5% by weight, about 60% by weight, about 62.5% by weight, about 65% by weight, about 67.5% by weight, about 70% by weight, about 72.5% by weight or about 75% by weight, including all ranges and values ​​therebetween). In some embodiments, the one or more cannabinoids are present in an amount of about 5% to about 75% by weight, about 5% to about 60% by weight, about 5% to about 50% by weight, about 10% to about 75% by weight, about 10% to about 60% by weight, about 10% to about 50% by weight, about 15% to about 75% by weight, about 15% to about 60% by weight, about 15% to about 50% by weight, about 20% to about 75% by weight, about 20% to about 60% by weight, about 20% to about 50% by weight, based on the total weight of the drug-containing particle. 0% by weight; about 25% by weight to about 75% by weight, about 25% by weight to about 60% by weight, about 25% by weight to about 50% by weight; about 30% by weight to about 75% by weight, about 30% by weight to about 60% by weight, about 30% by weight to about 50% by weight, about 35% by weight to about 75% by weight, about 35% by weight to about 60% by weight, about 35% by weight to about 50% by weight, about 40% by weight to about 75% by weight, about 40% by weight to about 60% by weight, or about 40% by weight to about 50% by weight (including all ranges and values ​​therebetween). In some embodiments, the one or more cannabinoids are present in an amount ranging from about 5% by weight to about 75% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more cannabinoids are present in an amount ranging from about 10% by weight to about 60% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more cannabinoids are present in an amount ranging from about 25% by weight to about 50% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more cannabinoids are present in an amount ranging from about 15 weight percent to about 40 weight percent based on the total weight of the drug-containing particle.

[0128] In some embodiments, substantially all of the one or more cannabinoids are present in the pores and / or surface of the porous solid carrier. In some embodiments, substantially all of the one or more cannabinoids are present in the pores of the porous solid carrier. Substantially in this context may mean that about 70%, about 75%, about 80%, about 85%, about 90%, about 95 or about 99% of the one or more cannabinoids are present in the pores and / or surface of the porous solid carrier. In some embodiments, greater than about 70%, greater than about 75%, greater than about 80%, greater than about 85%, greater than about 90%, greater than about 95% or greater than about 99% of the one or more cannabinoids are present in the pores of the porous solid carrier.

[0129] In some embodiments, the one or more cannabinoids are present in an amorphous form. In some embodiments, adsorption of the amorphous form of the one or more cannabinoids onto and / or in the porous solid support is determined by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and / or x-ray powder diffraction (XRPD). Without being bound by any particular theory, the porous solid support of the present disclosure may be optimized to stabilize the amorphous form of the one or more cannabinoids with the pores, which is desirable to achieve a targeted drug release profile.

[0130] In some embodiments, the drug-containing particles comprising the one or more cannabinoids are substantially free of cannabidiol (CBD-C1), cannabidiol (CBDV), and / or butyl-cannabidiol (CBD-C4). In some embodiments, the drug-containing particles contain no more than about 0.5% by weight of CBD-C1 actives. In some embodiments, the drug-containing particles contain no more than about 0.5% by weight of CBDV actives. In some embodiments, the drug-containing particles contain no more than about 0.2% by weight of CBD-C4 actives. Lipophilic materials

[0131] In some embodiments, the drug-containing particles further comprise one or more lipophilic materials. In embodiments, the drug-containing particles comprise one lipophilic material. In embodiments, the drug-containing particles comprise a combination of two lipophilic materials. In embodiments, the drug-containing particles comprise a combination of three lipophilic materials.

[0132] In embodiments wherein the drug-containing particles comprise two lipophilic materials, the ratio of the first lipophilic material to the second lipophilic material is in the range of about 90:10 to about 10:90, including about 90:10, about 85:15, about 80:20, about 75:25, about 70:30, about 65:35, about 60:40, about 55:45, about 50:50, about 45:55, about 40:60, about 35:65, about 30:70, about 25:75, about 20:80, about 15:85, or about 10:90, including all values ​​and ranges therebetween.

[0133] In embodiments where the drug-containing particles comprise three lipophilic materials, the ratio of the first lipophilic material to the second lipophilic material to the third lipophilic material is in the range of about 98:1:1 to 1:1:98, including 90:1:9, 85:1:14, 80:10:10, 70:15:15; 70:10:20, 60:20:20, 50:25:25; 40:30:30; 30:20:40; 20:10:70; 10:10:80 and 9:1:90, including all ranges and subranges therebetween.

[0134] The hydrophilic-lipophilic balance ("HLB") value refers to the balance of the size and strength of the hydrophilic and lipophilic portions of the surfactant molecule. The HLB value is reported based on a scale ranging from 0 to 20. A lower HLB value indicates a high oil affinity (lipophilicity). A high HLB value indicates a high water solubility (hydrophilicity). In embodiments, the lipophilic material has an HLB of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In embodiments, the lipophilic material has an HLB value in the range of 1-10 or 10-20. In embodiments, the lipophilic material has an HLB value in the range of 1-3, 4-6, 7-10, 11-14, 15-20. In embodiments, the lipophilic material has an HLB value in the range of 11-15.

[0135] Non-limiting examples of lipophilic materials suitable for use in the drug-containing particles disclosed herein include pharmaceutically acceptable fats, fatty substances, oils (including seed / kernel oils of plant and fruit origin), phospholipids, sterols, and waxes. Fats generally refer to esters of glycerol (e.g., monoesters, diesters, or triesters of glycerol and saturated and unsaturated fatty acids). Suitable fats and fatty substances include, but are not limited to, fatty alcohols, including short, medium, and long chain fatty alcohols (e.g., lauryl, myristyl, stearyl, cetyl, or cetearyl alcohol, etc.), fatty acids and derivatives, including, but not limited to, fatty acid esters, fatty acid glycerides (monoglycerides, diglycerides, and triglycerides), and hydrogenated fats. Fats can be solid or liquid at normal room temperature, depending on their structure and composition.

[0136] Suitable oils include pharmaceutically acceptable animals (e.g., fatty acid esters), minerals (e.g., paraffin oil), plants (e.g., plant and fruit oils), or synthetic hydrocarbons that are liquid at room temperature. Examples of pharmaceutically acceptable oils include, but are not limited to: mineral oils, such as paraffin oil; vegetable oils, such as castor oil, hydrogenated vegetable oils, sesame oil, nuclear oil, soybean oil, safflower oil, corn oil, olive oil, cottonseed oil, peanut oil (arachis oil), sunflower seed oil, palm oil, pumpkin seed oil, rapeseed oil, and peanut oil (peanut oil); and animal oils and fats, such as triglycerides and butter. Partially hydrogenated vegetable oils are mixtures of glycerides derived from natural products and typically contain C14-20 fatty acids (e.g., palmitic acid and stearic acid). Suitable examples of partially hydrogenated vegetable oils include partially hydrogenated cottonseed oil, soybean oil, corn oil, peanut oil, palm oil, sunflower seed oil, or mixtures thereof. Chemical equivalents of the partially hydrogenated vegetable oils include synthetically produced glycerides of C14-20 fatty acids having the same properties as the naturally derived products as described above.

[0137] Suitable phospholipids include pharmaceutically acceptable plant, animal and synthetic phospholipids. Examples of pharmaceutically acceptable phospholipids include egg lecithin, soybean lecithin, vegetable lecithin, choline, phosphatidylethanolamine, and phosphatidylglycerol, such as (but not limited to) phosphatidylcholine, 1,2-dierucylphosphatidylcholine, 1,2-dimyristoylphosphatidylcholine, 1,2-dioleoylphosphatidylcholine, 1,2-dioleoylphosphatidylserine, 1,2-distearoylphosphatidyl-glycerol, 1,2-dipalmitoylphosphatidylcholine, 1,2-dipalmitoylphosphatidylcholine, 1,2-dioleoylphosphatidylserine, 1,2-distearoylphosphatidyl-glycerol, 1,2-dipalmitoylphosphatidylcholine, 1,2-dipalmitoylphosphatidylcholine, 1,2-dioleoylphosphatidylcholine, 1,2-dioleoylphosphatidylserine, 1,2-distearoylphosphatidyl-glycerol, 1,2-dipalmitoylphosphatidylcholine ... Palmitoylphosphatidylcholine, 1,2-distearoylphosphatidylcholine, 1,2-distearoylphosphatidylglycerol, egg phosphatidylcholine, egg phosphatidylglycerol, soybean phosphatidylcholine, glycerophosphocholine, hydrogenated soybean phosphatidylcholine, lysophosphatidylcholine, lysophosphatidylethanolamine, N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoylphosphatidylethanolamine sodium salt, cell wall tripeptide-phosphatidylethanolamine, 1-palmitoylphosphatidylcholine, 1,2-distearoylphosphatidylcholine, 1,2-distearoylphosphatidylethanolamine, 1,2-distearoylphosphatidylcholine ... Palmitoyl-2-linoleoylphosphatidylcholine, 1-palmitoyl-2-linoleoylphosphatidylglycerol, 1-palmitoyl-2-oleoylphosphatidylcholine, 1-palmitoyl-2-oleoylphosphatidylglycerol, polyenylphosphatidylcholine, 1-palmitoyl-2-stearoylphosphatidylcholine, 1-palmitoyl-2-stearoylphosphatidylglycerol, 1-stearoyl-2-linoleoylphosphatidylcholine, 1-stearoyl-2-linoleoylphosphatidylcholine, 1-stearoyl-2-linoleoylphosphatidylglycerol Oleylphosphatidylglycerol, sphingomyelin, 1-stearoyl-2-oleoylphosphatidylcholine, 1-stearoyl-2-oleoylphosphatidylglycerol, sodium taurocholate, 1,2-diacyl-sn-glycero-3-phosphocholine, 2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphocholine, 1-palmitoyl-2-stearoyl-sn-glycero-3-phosphocholine, etc.

[0138] Suitable waxes include animal waxes, vegetable waxes, mineral waxes, and petroleum waxes. Examples of waxes include, but are not limited to, glyceryl behenate, glyceryl monostearate, stearic acid, palmitic acid, lauric acid, carnauba wax, cetyl alcohol, glyceryl stearate beeswax, paraffin wax, ozokerite, candelilla wax, cetyl alcohol, stearyl alcohol, spermaceti, carnauba wax, bayberry wax, lignite, ceresin, and microcrystalline wax.

[0139] In some embodiments, lipophilic materials suitable for use in the drug-containing particles disclosed herein include fatty acid glycerides, polyethylene oxide-containing fatty acid esters, and combinations thereof.

[0140] In some embodiments, the drug-containing particles of the present disclosure include one or more fatty acid glycerides. As used herein, the term "fatty acid glyceride" refers to esters formed between glycerol and one or more fatty acids, including monoesters, diesters, and triesters (i.e., glycerides). Suitable fatty acids include saturated and unsaturated fatty acids having eight (8) to twenty-two (22) carbon atoms (i.e., C8-C22 fatty acids). In certain embodiments, suitable fatty acids include C12-C18 fatty acids. Fatty acid glycerides suitable for use in formulations can be provided by commercially available sources. A representative source of fatty acid glycerides is what may be generally referred to as "olein" or "monoolein." (Gattefosse, Saint Priest Cedex, France) to obtain a mixture of monoesters, diesters and triesters. In some embodiments, when using When the fatty acid glyceride in the preparation is used as the source, the fatty acid glyceride includes about 32% weight to about 52% weight of fatty acid monoglyceride, about 30% weight to about 50% weight of fatty acid diglyceride and about 5% weight to about 20% weight of fatty acid triglyceride. The fatty acid glyceride includes oleic acid (C18:1) monoglyceride, diglyceride and triglyceride greater than about 60% weight. Other fatty acid glycerides include palmitic acid (C16) (less than about 12%), stearic acid (C18) (less than about 6%), linolenic acid (C18:2) (less than about 35%), linolenic acid (C18:3) (less than about 2%), arachidic acid (C20) (less than about 2%) and arachidic acid (C20:1) (less than about 2%) esters. Free glycerol (usually about 1%) may also be included. In one embodiment, the fatty acid glycerides include about 44% by weight of fatty acid monoglycerides, about 45% by weight of fatty acid diglycerides, and about 9% by weight of fatty acid triglycerides, and the fatty acid glycerides include about 75% by weight of oleic acid (C18:1) monoglycerides, diglycerides, and triglycerides. Other fatty acid glycerides include esters of palmitic acid (C16) (about 4%), stearic acid (C18:0) (about 2%), linolenic acid (C18:2) (about 12%), linolenic acid (C18:3) (less than 1%), arachidic acid (C20) (less than 1%), and eicosanoic acid (C20:1) (less than 1%).

[0141] In other embodiments, the formulation may include a mixture fatty acid glyceride, such as any one of those disclosed herein. In other embodiments, one or more fatty acid glycerides may be used in combination with other lipophilic materials as described herein (e.g., one or more fatty acid esters containing polyethylene oxide as described herein).

[0142] In some embodiments, the drug-containing particles described herein include at least one lipophilic material containing polyethylene oxide, such as a fatty acid ester containing polyethylene oxide. As used herein, the term "fatty acid ester containing polyethylene oxide" refers to a fatty acid ester comprising a polyethylene oxide group (i.e., also referred to as a polyethylene glycol group) covalently coupled to a fatty acid by an ester bond. Fatty acid esters containing polyethylene oxide include mono- and di-fatty acid esters of polyethylene glycol (PEG). Suitable fatty acid esters containing polyethylene oxide are derived from fatty acids, including saturated and unsaturated fatty acids (i.e., polyethylene oxide esters of C8-C22 fatty acids) having eight (8) to twenty-two (22) carbon atoms. In certain embodiments, suitable fatty acid esters containing polyethylene oxide are derived from fatty acids, including saturated and unsaturated fatty acids (i.e., polyethylene oxide esters of C12-C18 fatty acids) having twelve (12) to eighteen (18) carbon atoms. Representative polyethylene oxide-containing fatty acid esters include saturated C8-C22 fatty acid esters. In certain embodiments, suitable polyethylene oxide-containing fatty acid esters include saturated C12-C18 fatty acids.

[0143] The molecular weight of the polyethylene oxide group of the polyethylene oxide-containing fatty acid ester can be varied to optimize the solubility of the therapeutic agent in the drug-containing particles. The representative average molecular weight of the polyethylene oxide group can be from about 350 to about 6000. In one embodiment, the average molecular weight of the polyethylene oxide group is about 1500, about 2000, about 4000, about 6000, including any value or range therebetween. In one embodiment, the average molecular weight of the polyethylene oxide group is about 1500.

[0144] In some embodiments, when the drug-containing particles include a fatty acid containing polyethylene oxide contained in the lipophilic material, the lipophilic material may include only one type of fatty acid containing polyethylene oxide. In other embodiments, the fatty acid containing polyethylene oxide in the lipophilic material may include a mixture of fatty acid esters containing polyethylene oxide (mono- and di-fatty acid esters of PEG). In embodiments, the fatty acid ester containing polyethylene oxide is an ester of caproic acid (C6), caprylic acid (C8), capric acid (C10), lauric acid (C12), palmitic acid (C16), stearic acid (C18), oleic acid (C18:1), linolenic acid (C18:2), linolenic acid (C18:3), arachidic acid (C20), eicosenoic acid (C20:1) or behenic acid (behenic acid) (C22). In embodiments, the polyethylene oxide-containing fatty acid ester is a laurate, palmitate, or stearate (ie, monolaurate and dilaurate of polyethylene glycol, monopalmitate and dipalmitate of PEG, monostearate and distearate of PEG). Mixtures of these esters may also be used.

[0145] Polyethylene oxide-containing fatty acid esters suitable for use in the formulations of the present disclosure can be provided by commercial sources. Representative polyethylene oxide-containing fatty acid esters (mixtures of monoesters and diesters) can be found under the names (Gattefosse, Saint Priest Cedex, France) purchased.

[0146] In an embodiment, the lipophilic material of the present disclosure comprises polyethylene oxide-containing fatty acid esters, polyethylene oxide glycerides, polypropylene glycol fatty acid esters, PEG, monoglycerol fatty acid esters, diglycerol fatty acid esters, triglycerol fatty acid esters, propylene glycol diglycerides, polyethylene oxide vegetable oils, or combinations thereof.

[0147] In some embodiments, the lipophilic material comprises: 1) saturated or unsaturated C8-C22 fatty acid monoglyceride; 2) saturated or unsaturated C8-C22 fatty acid diglyceride; 3) saturated or unsaturated C8-C22 fatty acid triglyceride; 4) polyethylene glycol (PEG); 5) PEG-fatty acid (C8-C22) monoester; 6) PEG-fatty acid (C8-C22) diester or any combination thereof. In some embodiments, the lipophilic material comprises monoglyceride, diglyceride and / or triglyceride of C6-C18 fatty acid. In some embodiments, the lipophilic material comprises polyethylene glycol (e.g., PEG-4, PEG-6, PEG-7, PEG-8, PEG-32, PEG-75, PEG-100, PEG-150, PEG-14M or PEG-20M). In some embodiments, the lipophilic material comprises C8-C22 fatty acids containing polyethylene glycol. In some embodiments, the lipophilic material comprises a C8-C22 fatty acid monoester containing polyethylene glycol. In some embodiments, the lipophilic material comprises a C8-C22 fatty acid diester containing polyethylene glycol. In some embodiments, the lipophilic material comprises monoglycerides, diglycerides or triglycerides and polyethylene glycol as described herein. In some embodiments, the lipophilic material comprises monoglycerides, diglycerides and triglycerides as described herein and fatty acid monoesters containing polyethylene oxide. In some embodiments, the lipophilic material comprises monoglycerides, diglycerides and triglycerides as described herein and fatty acid diesters containing polyethylene oxide. In an embodiment, the lipophilic material comprises any combination of the components described in this paragraph.

[0148] In some embodiments, the one or more lipophilic materials in the drug-containing particles include one or more fatty acid esters containing polyethylene oxide. In some embodiments, the one or more lipophilic materials in the drug-containing particles include one or more glycerol fatty acid esters. In some embodiments, the fatty acid ester containing polyethylene oxide or glycerol fatty acid ester includes one or more fatty acid residues. In embodiments, the fatty acid residue includes C6-C22 fatty acids, such as C6-C20 fatty acids, C8-C20 fatty acids, C8-C18 fatty acids, C8-C16 fatty acids, C8-C14 fatty acids, C8-12 fatty acids, C8-C10 fatty acids (including any value or range therebetween). In embodiments, the fatty acid residue includes the residue of C8-C20 fatty acids. In some embodiments, the C6-C20 fatty acid comprises a residue of caproic acid (C6), caprylic acid (C8), capric acid (C10), lauric acid (C12), palmitic acid (C16), stearic acid (C18), oleic acid (C18:1), linoleic acid (C18:2), linolenic acid (C18:3), arachidic acid (C20), eicosenoic acid (C20:1), or behenic acid (C22). In some embodiments, the C8-C20 fatty acid comprises a residue of caprylic acid (C8), capric acid (C10), lauric acid (C12), palmitic acid (C16), stearic acid (C18), or arachidic acid (C20). In some embodiments, the one or more lipophilic materials in the drug-containing particles comprise a polyethylene glycol derivative of a vegetable oil. In some embodiments, the one or more lipophilic materials in the drug-containing particles comprise a C8-C20 monoglyceride. In some embodiments, the one or more lipophilic materials in the drug-containing particles comprise C8-C20 diglycerides. In some embodiments, the one or more lipophilic materials in the drug-containing particles comprise C8-C20 triglycerides.

[0149] In some embodiments, the lipophilic material comprises stearoyl polyoxyglyceride, stearoyl polyethylene oxide, lauroyl polyoxyglyceride, oleyl polyoxyglyceride, mono / diester of hydroxystearic acid and polyethylene glycol, PEG-hydrogenated castor oil, propylene glycol monocaprylate, propylene glycol monolaurate, medium chain triglycerides, propylene glycol dicaproate / dicaprate, caprylocaproyl polyoxyglyceride, or a combination thereof.

[0150] In some embodiments, the lipophilic material comprises mono-, di- and tri-glycerides of fatty acids and PEG-32 (MW 1500) mono- and di-glycerides of palmitic acid (C16) and stearic acid (C18); mono-, di- and tri-glycerides of fatty acids (C8 to C18); mono-, di- and tri-glycerides of lauric (C12) and stearic (C18) acids and PEG-6 (MW 1500). 300) mono- and diesters; mono-, di- and tri-glycerides of oleic (C18:1) acid and PEG-6 (MW 300) and mono- and diesters; a mixture of mono- and diesters of 12-hydroxystearic acid and polyethylene glycol glycerides; PEG-40 hydrogenated castor oil; propylene glycol monocaprylate; propylene glycol monolaurate; medium chain triglycerides; propylene glycol dicaproate / dicaprate; PEG-8 (MW 400) mono- and diesters of caprylic (C8) and capric (C10) acids; or combinations thereof.

[0151] In some embodiments, the lipophilic material comprises a mixture of mono-, di-, and triglycerides of palmitic (C16) and stearic (C18) acids and PEG-32 (MW 1500) mono- and diesters of palmitic (C16) and stearic (C18) acids (e.g., stearoyl polyoxyl-32 glycerides: 50 / 13); mono-, di- and triglycerides of fatty acids (C8 to C18) (e.g. hard fats: 43 / 01); mono-, di- and triglycerides of lauric (C12) and stearic (C18) acids and PEG-6 (MW 300) mono- and diesters of lauric (C12) and stearic (C18) acids (e.g. lauroyl polyoxyl-6-glyceride: M 2130); mono-, di- and tri-glycerides of oleic (C18:1) acid and PEG-6 (MW 300) mono- and di-esters of oleic (C18:1) acid (e.g. oleoyl polyoxyl-6-glyceride: 1944); polyethylene glycol monoesters and diesters of 12-hydroxystearic acid (e.g. CRODASOL TM HS); PEG-40 hydrogenated castor oil (such as CRODURET TM 40), propylene glycol monocaprylate (e.g. 90); Propylene glycol monolaurate (e.g. 90); medium chain triglycerides (such as LABRAFAC TM lipophile WL1349, 810N); Propylene glycol dicaprylate / dicaprate (e.g. LABRAFAC TMPG); PEG-8 (MW400) monoesters and diesters of caprylic (C8) and capric (C10) acids (e.g. caprylocaproyl polyoxyl-8-glyceride: ALF) or a combination thereof.

[0152] In some embodiments, one or more lipophilic materials of the present disclosure comprise a fatty acid ester containing polyethylene oxide. (For example 44 / 14, 50 / 13, 53 / 10, and 48 / 16). The numbers in these names refer to the melting point and hydrophile / lipophile balance (HLB) of these materials, respectively. 44 / 14, 50 / 13, 53 / 10, 43 / 01 is a mixture of (a) monoesters, diesters and triesters of glycerol (glycerides) and (b) monoesters and diesters of polyethylene glycol (polyethylene glycol / macrogol). In some embodiments, the lipophilic material comprising a fatty acid ester containing polyethylene oxide also includes free polyethylene glycol (e.g., PEG 1500). In an embodiment, one or more lipophilic materials of the present disclosure comprise polyglycolyzed glycerides prepared by alcoholysis of natural oils with polyethylene glycol (PEG).

[0153] 44 / 14 is lauroyl polyoxyl / polyethylene glycol 32 glyceride NF / EP and contains a portion of the mono-, di- and tri-glycerides of lauric acid (C12) and a major portion of the mono- and di-esters of PEG-32 (MW 1500). 50 / 13 is stearoyl polyoxyl / polyethylene glycol 32 glyceride according to the National formulary (NF) / European Pharmacopoeia (EP) and contains mono-, di- and tri-glycerides of palmitic acid (C16) and stearic acid (C18) and PEG-32 (MW 1500) mono- and diesters.

[0154] 43 / 01 is a hard fat consisting of mono-, di- and triglycerides of fatty acids (C8 to C18) according to the European Pharmacopoeia (EP) and the National Formulary (NF).

[0155] 48 / 16 is a pure PEG ester. In some embodiments, the lipophilic material of the present disclosure comprises mono-, di- and tri-glycerides of palmitic acid (C16) and stearic acid (C18) and mono- and di-glycerides of PEG-32 (MW 1500) ( In some embodiments, the lipophilic material comprises monoglycerides, diglycerides and triglycerides of fatty acids (C8 to C18) 43 / 01).

[0156] Lauric acid (C12) The main fatty acid components of glycerides and polyethylene glycol esters in 44 / 14. 44 / 14 is known as a mixture of glyceryl dilaurate (lauric acid diester with glycerol) and PEG dilaurate (lauric acid diester with polyethylene glycol) and is commonly known as PEG-32 glyceryl laurate (Gattefosse) lauroyl macrogol-32 glyceride EP or lauroyl polyoxyglycerol USP / NF. 44 / 14 includes lauric acid (C12) ester (30% to 50%), myristic acid (C14) ester (5% to 25%), palmitic acid (C16) ester (4% to 25%), stearic acid (C18) ester (5% to 35%), caprylic acid (C8) ester (less than 15%) and capric acid (C10) ester (less than 12%). 44 / 14 may also include free glycerol (usually less than about 1%). In a representative formulation, 44 / 14 includes lauric acid (C12) ester (about 47%), myristic acid (C14) ester (about 18%), palmitic acid (C16) ester (about 10%), stearic acid (C18) ester (about 11%), caprylic acid (C8) ester (about 8%) and capric acid (C10) ester (about 12%). 44 / 14 is prepared by the reaction of hydrogenated palm kernel oil with polyethylene glycol (average molecular weight 1500). 44 / 14 contains about 20% of mono-, di-, and tri-glycerides of polyethylene glycol 1500, about 72% of mono- and di-fatty acid esters of polyethylene glycol 1500, and about 8% polyethylene glycol 1500.

[0157] Palmitic acid (C16) (40-50%) and stearic acid (C18) (48-58%) are The main fatty acid components of glycerides and polyethylene glycol esters in 50 / 13. 50 / 13 is known as PEG-32 Glyceryl Stearate Palmitate (Gattefosse), Stearoyl Macrogol Glycerides EP or Stearoyl Polyoxyglycerides USP / NF). 50 / 13 includes C16 palmitic acid (40% to 50%), C18 stearic acid (48% to 58%) (greater than about 90% stearic acid and palmitic acid), C12 lauric acid (less than 5%), C14 myristic acid (less than 5%), C8 caprylic acid (less than 3%), and C10 capric acid (less than 3%). 50 / 13 may also include free glycerin (usually less than about 1%). In a representative formulation, 50 / 13 includes palmitic acid (C16) ester (about 43%), stearic acid (CIS) ester (about 54%) (stearate and palmitate about 97%), lauric acid (C12) ester (less than 1%), myristic acid (C14) ester (about 1%), caprylic acid (C8) ester (less than 1%) and capric acid (C10) ester (less than 1%). 50 / 13 is known as PEG-32 Glyceryl Stearate (Gattefosse).

[0158] In some embodiments, one or more lipophilic materials of the present disclosure comprise a fatty acid diester glyceride (e.g., lauroyl polyethylene glycol-6 glyceride, also known as lauroyl polyoxyl-6 glyceride, or M2130). Exemplary fatty acid diglycerides include oleoyl polyethylene glycol-6 glyceride or oleoyl polyoxyl-6 glyceride (e.g. M2130, M1944) and linoleoyl polyethylene glycol 6 glyceride (also known as M2125, corn oil PEG-6 esters or linoleoyl polyoxyl-6 glyceride). M2130 contains mono-, di- and triglycerides PEG-6 (MW 300) and mono- and di-esters of lauric (C12) and stearic (C18) acids. M1944 contains mono-, di-, and tri-glycerides of oleic (C18:1) acid and PEG-6 (MW 300) and mono- and di-esters. M2125 comprises mono-, di- and tri-glycerides of linoleic (C18:2) acid and PEG-6 (MW 300) and mono- and di-esters. In some embodiments, the lipophilic material of the present disclosure comprises lauroyl polyoxyl-6 glyceride ( M2130). In some embodiments, the lipophilic material comprises oleoyl macrogol-6 glyceride ( M1944).

[0159] In some embodiments, one or more lipophilic materials of the present disclosure comprise a mixture of monoesters and diesters of 12-hydroxystearic acid and polyethylene glycol (CRODASOL TMHS HP), a multi-componial mixture of caprylocaproyl macrogol glycerides (CRODASOL TM CCMG 400), polysorbate 20 (and) PEG-25 hydrogenated castor oil and propylene glycol (CRODASOL TM PHC), PEG-6 Caprylic / Capric Glycerides and PEG-60 Almond Glycerides (CRODASOL TM AC) or a combination thereof. In some embodiments, the one or more lipophilic materials are a mixture of a monoester / diester of 12-hydroxystearic acid and polyethylene glycol (CRODASOL TM HS HP).

[0160] In some embodiments, one or more lipophilic materials of the present disclosure include a plant-derived ethoxylated nonionic surfactant (e.g., PEG-40 hydrogenated castor oil, also known as CRODURET TM In an embodiment, the one or more lipophilic materials include PEG-40 hydrogenated castor oil (CRODURET TM 40), PEG-50 hydrogenated castor oil (CRODURET TM 50), PEG-60 hydrogenated castor oil (CRODURET TM 60), PEG-7 hydrogenated castor oil (CRODURET TM 7) or a mixture thereof. In an embodiment, the one or more lipophilic materials comprise PEG-40 hydrogenated castor oil (CRODURET TM 40).

[0161] In some embodiments, one or more lipophilic materials of the present disclosure include propylene glycol monocaprylate (e.g. 90. Propylene glycol ester of (C8) octanoate).

[0162] In some embodiments, one or more lipophilic materials of the present disclosure include propylene glycol laurate (e.g. 90 or LAUROGLYCOL FCC, also known as propylene glycol monolaurate). In an embodiment, the propylene glycol laurate is a mixture of monoesters and diesters of lauric acid. In an embodiment, the propylene glycol laurate comprises a ratio of monoester to ester of about 90:10. In an embodiment, the lipophilic material comprising propylene glycol laurate may further contain esters of caprylic acid, capric acid, myristic acid and / or palmitic acid.

[0163] In some embodiments, one or more lipophilic materials of the present disclosure include caprylocaproyl polyoxyl-8 glyceride (e.g. ALF). In an embodiment, such glycerides include PEG-8 (MW 400) monoesters and diesters of caprylic (C8) and capric (C10) acids. In an embodiment, the glycerides include mono-, di- and tri-glycerides of caprylic (C8) and capric (C10) acids.

[0164] In an embodiment, the drug-containing particles include one or more triglycerides. The triglycerides may be short-chain, medium-chain, long-chain triglycerides, or very long-chain triglycerides, or any combination thereof, or any combination of short-chain triglycerides, or any combination of medium-chain triglycerides, any combination of long-chain triglycerides, or any combination of very long-chain triglycerides. In an embodiment, short-chain triglycerides include fatty acids with a trimer (trial) containing 1-5 carbon atoms. In an embodiment, medium-chain triglycerides include fatty acids with a trimer containing 6-12 carbon atoms. In an embodiment, medium-chain triglycerides include fatty acids with a trimer containing 13-21 carbon atoms. In an embodiment, medium-chain triglycerides include fatty acids with a trimer containing 22 or more carbon atoms. The hydrocarbon chain in the triglyceride may be saturated or unsaturated. When the hydrocarbon chain is unsaturated, it may have any number of double or triple bonds, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[0165] In some embodiments, one or more lipophilic materials of the present disclosure comprise medium chain triglycerides (e.g., LABRAFAC TM In some embodiments, the one or more lipophilic materials include medium chain triglycerides of caprylic acid (C8) and capric acid (C10) (LABRAFAC TM lipophile WT 1349) or triglycerides of caprylic and capric acid ( 810, 812, 829 or 840). In an embodiment, the one or more lipophilic materials comprise caprylic acid (C8) and capric acid (C10) (LABRAFAC TM In an embodiment, the one or more lipophilic materials contain glyceryl monocaprylyl caprate (Type I) (LABRAFAC TM MC60).

[0166] In some embodiments, the lipophilic material comprises one or more plant seed oils, including but not limited to kernel oil, borage oil, coconut oil, cottonseed oil, soybean oil, safflower oil, sunflower oil, castor oil, hydrogenated castor oil, corn oil, olive oil, palm oil, peanut oil, peppermint oil, poppy seed oil, canola oil, soybean oil, hydrogenated soybean oil, pumpkin oil, pumpkin seed oil, medium chain triglyceride (MCT) oil (e.g., MCT oil derived from coconut oil and / or palm oil), oleic acid oil (e.g., derived from olive oil and / or canola oil), fruit seed oil, and sesame oil. In some embodiments, the lipophilic material comprises sesame oil, pumpkin oil, or a combination thereof. In some embodiments, the lipophilic material comprises kernel oil, sesame seed oil, MCT oil, oleic acid, pumpkin seed oil, or a mixture thereof.

[0167] In an embodiment, the lipophilic material comprises one or more vegetable oils. In an embodiment, the vegetable oil comprises one or more vegetable seed oils, fruit seed oils, nuclear oils, sesame seed oils, medium chain triglyceride (MCT) oils, oleic acid oils, pumpkin seed oils, interesterified vegetable oils, polyoxyethylene hydrogenated vegetable oils, PEG-hydrogenated castor oils, or a combination thereof.

[0168] In some embodiments, the one or more lipophilic materials are present in an amount sufficient to provide one or more cannabinoids in an amorphous form. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 1% by weight to about 75% by weight (e.g., about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or 75%, including all values ​​and ranges therein) based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 5% by weight to about 75% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 10% by weight to about 75% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 15% by weight to about 75% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 20% by weight to about 75% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 5% by weight to about 50% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 10% by weight to about 50% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 15% by weight to about 50% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 20% by weight to about 50% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 5% by weight to about 75% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 10% by weight to about 75% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 15% by weight to about 75% by weight based on the total weight of the drug-containing particles. In some embodiments, the one or more lipophilic materials are present in the drug-containing particles in an amount ranging from about 5% by weight, about 10% by weight, about 15% by weight, about 20% by weight, about 25% by weight, about 30% by weight, about 35% by weight, about 40% by weight, about 45% by weight, about 50% by weight, about 55% by weight, about 60% by weight, about 65% by weight, about 70% by weight, or about 75% by weight based on the total weight of the drug-containing particles. polymer

[0169] In some embodiments, the drug-containing particles further comprise one or more polymers. In some embodiments, the polymer has a glass transition temperature (Tg) in the range of about 50°C to about 130°C. g In some embodiments, the polymer comprises polyvinyl pyrrolidone (kollidon VA64), cross-linked polyvinyl N-pyrrolidone (crospovidone), hydroxypropyl methylcellulose phthalate (HPMCP 50), polyvinyl alcohol-polyethylene glycol copolymer (kollicoat), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (soluplus), polyvinyl alcohol, or a combination thereof.

[0170] In some embodiments, the one or more polymers are present in an amount ranging from about 10% by weight to about 50% by weight (e.g., about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%, including all values ​​and ranges therein) based on the total weight of the drug-containing particles. In some embodiments, the polymer is provided as a coating on the drug-containing particles. Chelating Agents (CA) and Antioxidants (AO)

[0171] The drug-containing particles disclosed herein optionally include a chelating agent. In some embodiments, the chelating agent is EDTA, citric acid, or curcumin.

[0172] In some embodiments, the amount of the chelating agent in the drug-containing particles is in the range of about 0.05% by weight to about 3% by weight, for example, about 0.05%, about 0.10%, about 0.20%, about 0.30%, about 0.40%, about 0.50%, about 0.60%, about 0.70%, about 0.80%, about 0.90%, about 1%, about 1.10%, about 1.20%, about 1.30%, about 1.40%, about 1.50%, about 1.60%, about 1.70%, about 1.80%, about 1.90%, about 2%, about 2.10%, about 2.20%, about 2.30%, about 2.40%, about 2.50%, about 2.60%, about 2.70%, about 2.80%, about 2.90% or about 3% (including all ranges and values ​​therebetween). In some embodiments, the amount of the chelating agent in the drug-containing particles is in the range of about 0.05% by weight to about 0.5% by weight. In some embodiments, the amount of the chelating agent in the drug-containing particles is in the range of about 0.05% by weight to about 0.4% by weight, about 0.05% by weight to about 0.35% by weight, about 0.05% by weight to about 0.3% by weight, about 0.05% by weight to about 0.25% by weight, or about 0.05% by weight to about 0.2% by weight.

[0173] The drug-containing particles disclosed herein optionally include one or more antioxidants. In some embodiments, the one or more antioxidants are tocopherol derivatives (e.g., alpha-tocopherol), carotenoids (e.g., lutein or beta-carotene), tocotrienols, ascorbic acid, ascorbyl palmitate, lecithin, butylated hydroxyanisole, butylated hydroxytoluene (BHT), monothioglycerol, propyl gallate, curcumin, or a combination thereof. In some embodiments, the one or more antioxidants are alpha-tocopherol, beta-carotene, ascorbic acid, ascorbyl palmitate, lecithin, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, propyl gallate, curcumin, or a combination thereof. In some embodiments, the one or more antioxidants are alpha-tocopherol, beta-carotene, ascorbic acid, ascorbyl palmitate, lecithin, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, propyl gallate, or a combination thereof. In some embodiments, the one or more antioxidants are alpha-tocopherol.

[0174] In some embodiments, the amount of the one or more antioxidants in the drug-containing particles is in the range of about 0.05% by weight to about 3% by weight, for example, about 0.05%, about 0.10%, about 0.20%, about 0.30%, about 0.40%, about 0.50%, about 0.60%, about 0.70%, about 0.80%, about 0.90%, about 1%, about 1.10%, about 1.2 In some embodiments, the amount of the one or more antioxidants in the drug-containing particles is in the range of about 0.05% by weight to about 2.5% by weight, about 0.05% by weight to about 2.0% by weight, about 0.05% by weight to about 1.5% by weight, about 0.05% by weight to about 1.0% by weight, or about 0.05% by weight to about 0.5% by weight. In some embodiments, the amount of the one or more antioxidants in the drug-containing particles is about 0.05% by weight to about 2.0% by weight. In some embodiments, the amount of the one or more antioxidants in the drug-containing particles is about 0.1% by weight to about 1.5% by weight. In some embodiments, the one or more antioxidants are present in the drug-containing particles at about 0.2%, about 0.6%, or about 1.0%.

[0175] In some embodiments, the drug-containing particles include any combination of chelators disclosed herein and one or more antioxidants. In some embodiments, the chelator is EDTA, citric acid or a polyphenolic substance (e.g., curcumin) and the one or more antioxidants are tocopherol derivatives (e.g., α-tocopherol), carotenoids (e.g., lutein or β-carotene), tocotrienols, ascorbic acid, ascorbyl palmitate, lecithin, butylated hydroxyanisole, butylated hydroxytoluene (BHT), monothioglycerol, propyl gallate, curcumin or a combination thereof. In some embodiments, the drug-containing particles include one of the following combinations of antioxidants and chelators (CA): Drug Release Profile

[0176] Depending on the application, the release of the one or more cannabinoids from the drug-containing particles can be immediate release or regulated release. In some embodiments, the drug-containing particles are formulated for immediate release. In some embodiments, the drug-containing particles are formulated for regulated release, such as delayed or extended release. In some embodiments, the drug-containing particles disclosed herein release 50-90% of the one or more cannabinoids within about 1-16h. In some embodiments, the drug-containing particles disclosed herein release 50-90% of the one or more cannabinoids within about 2-12h. In some embodiments, the drug-containing particles disclosed herein release 50-90% of the one or more cannabinoids within about 3-12h. In some embodiments, the drug-containing particles disclosed herein release at least about 50% of the one or more cannabinoids by about 30min, about 1h, about 2h, about 3h, about 4h, about 5, about 6, about 7, about 8, about 9, about 10, about 11 or about 12h. In some embodiments, the drug-containing particles disclosed herein release at least about 60% of the one or more cannabinoids by about 30 min, about 1 h, about 2 h, about 3 h, about 4 h, about 5, about 6, about 7, about 8, about 9, about 10, about 11, or about 12 h. In some embodiments, the drug-containing particles disclosed herein release at least about 70% of the one or more cannabinoids by about 30 min, about 1 h, about 2 h, about 3 h, about 4 h, about 5, about 6, about 7, about 8, about 9, about 10, about 11, or about 12 h. In some embodiments, the drug-containing particles disclosed herein release at least about 80% of the one or more cannabinoids by about 30 min, about 1 h, about 2 h, about 3 h, about 4 h, about 5, about 6, about 7, about 8, about 9, about 10, about 11, or about 12 h. In some embodiments, the drug-containing particles disclosed herein release at least about 90% of the one or more cannabinoids by about 30 min, about 1 h, about 2 h, about 3 h, about 4 h, about 5, about 6, about 7, about 8, about 9, about 10, about 11, or about 12 h.

[0177] In an embodiment, the drug-containing particles disclosed herein release at least 20% within 10 minutes. In an embodiment, the drug-containing particles disclosed herein release 20-50% within 10 minutes. In an embodiment, the drug-containing particles disclosed herein release at least 30% within 15 minutes. In an embodiment, the drug-containing particles disclosed herein release 30-70% within 15 minutes. In an embodiment, the drug-containing particles disclosed herein release at least 40% within 20 minutes. In an embodiment, the drug-containing particles disclosed herein release 40-80% within 20 minutes. In an embodiment, the drug-containing particles disclosed herein release at least 45% within 30 minutes. In an embodiment, the drug-containing particles disclosed herein release 45-85% within 30 minutes. In an embodiment, the drug-containing particles disclosed herein release at least 50% within 45 minutes. In an embodiment, the drug-containing particles disclosed herein release 50-85% within 50 minutes.

[0178] In embodiments, drug release (dissolution) is measured according to the U.S. Pharmacopeia (USP) dissolution test (711). In embodiments, drug release (dissolution) is measured using apparatus I or apparatus II. In embodiments, dissolution (release) rate is tested in 900 mL of suitable buffer using USP apparatus II (paddle, 75 rpm) at 37 ± 0.5 ° C. In some embodiments, the buffer has a pH in the range of about 1 to about 7 (e.g., 1, about 1.5, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 6.8, and about 7, including all values ​​and sub-ranges therebetween). The pH of the buffer can be selected based on the approximate pH in the digestive tract where the release is measured. For example, a pH of 1 can be used to measure dissolution in the stomach, while a higher pH (e.g., 4.5, 5, 5.5, etc.) up to pH 7.4 can be used to measure dissolution in the intestine. Test conditions (e.g., running time, medium, running time, speed, volume, etc.) can be changed.

[0179] In embodiments, drug release (dissolution) is measured under the dissolution test conditions described in Table A1. Table A1. Dissolution test parameters

[0180] In embodiments, drug release (dissolution) is measured under the dissolution test conditions described in Tables AB. Table AB. Dissolution Test Parameters

[0181] In embodiments, for immediate release, the dissolution test is performed for 30 minutes. In embodiments, for delayed release, the dissolution test is performed for at least 3 hours (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more hours). In some embodiments, the buffer is 0.1M HCl (pH 1), 0.01M HCl (pH 2) or acetate buffer (pH 4.5).

[0182] For the enteric coating component, dissolution testing was performed using USP Apparatus II (paddle, 75 rpm) at 37±0.5°C for 3 hours in 900 mL of the first buffer (pH 4.5) followed by testing in 900 mL of the second buffer (pH 6.8).

[0183] In some embodiments, the drug-containing particles disclosed herein are formulated to be bioequivalent to conventional formulations that do not include, for example, a porous solid carrier. In some embodiments, the conventional formulation comprises one or more cannabinoids (e.g., CBD) dissolved in sesame oil. That is, in some embodiments, when applied to humans or animals (e.g., in a mouse model, a rat model, a beagle model, or a minipig model), the drug-containing particles have an average maximum blood plasma concentration (Cmax), average AUC, and / or average Tmax within about 80% to about 125% of the average Cmax, average AUC, and average Tmax of conventional oil-based cannabinoid drugs, respectively. Cmax, AUC, and Tmax as used herein refer to the average or median values ​​measured for a subject population.

[0184] In some embodiments, the drug-containing particles disclosed herein are formulated to have improved pharmacokinetic properties compared to conventional formulations that do not include a porous solid carrier, for example. That is, in some embodiments, when administered to humans or animals (e.g., in a mouse model, a rat model, a beagle model, or a miniature pig model), the drug-containing particles have an average maximum blood plasma concentration (Cmax) or average AUC greater than about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% of the average Cmax or average AUC of conventional oil-based cannabinoid drug products. Cmax or AUC as used herein refers to the average or median value measured for a population of subjects.

[0185] In some embodiments, administration of the drug-containing particles provides an AUC in the range of about 80% to about 125% of about 722 ng*hr / mL when administered at a dose equivalent to 10 mg / kg. In such embodiments, the AUC is about 550 ng*hr / mL to about 950 ng*hr / mL, for example, about 550 ng*hr / mL, about 570 ng*hr / mL, about 590 ng*hr / mL, about 610 ng*hr / mL, about 630 ng*hr / mL, about 650 ng*hr / mL, about 670 ng*hr / mL, about 690 ng*hr / mL, about 710 ng*hr / mL, about 730 ng*hr / mL, about 750 ng*hr / mL, about 770 ng*hr / mL, about 790 ng*hr / mL, about 810 ng*hr / mL, about 830 ng*hr / mL, about 850 ng*hr / mL, about 870 ng*hr / mL, about 890 ng*hr / mL, about 910 ng*hr / mL, about 930 ng*hr / mL or about 950 ng*hr / mL, including all values ​​and ranges therebetween.

[0186] In some embodiments, the drug-containing particles provide a Cmax of about 80% to about 125% of about 150 ng / mL at a dose equivalent to 10 mg / kg. In such embodiments, the subject has a Cmax of about 50 ng / mL to about 190 ng / mL, such as about 50 ng / mL, about 60 ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, about 120 ng / mL, about 140 ng / mL, about 160 ng / mL, about 180 ng / mL, to about 190 ng / mL (including all values ​​and ranges therebetween).

[0187] In some embodiments, administration of the drug-containing particles provides about 30% to about 600% (e.g., about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 100%, about 110%, about 120%, about 140%, about 160%, about 180%, about 200%, about 220%, about 240%, about 260%, about 280%, about 300%, about 320%, about 330%, about 340%, about 350%, about 360%, about 370%, about 380%, about 390%, about 400%, about 410%, about 420%, about 430%, about 440%, about 450%, about 460%, about 470%, about 480%, about 490%, about 500%, about 510%, about 520%, about 530%, about 540%, about 550%, about 560%, about 570%, about 580%, about 590%, about 600%, about 610%, about 620%, about 630%, about 640%, about 650%, about 660%, about 670%, about 680%, about 690%, about 700%, about 710%, about 720%, about 730%, about 740%, about 750%, about 760%, about 770%, about 780%, about 790%, about 800%, about 810%, about 810%, about 820%, about 830%, about 840%, about 850%, about 860%, about 870%, about 880%, about 8 In some embodiments, the drug-containing particles are administered in a formulation of the present invention to provide a relative bioavailability (Frel%) of about 100% to about 600% compared to CBD dissolved in sesame oil containing the same dose of CBD. In some embodiments, the drug-containing particles are administered in a formulation of the present invention to provide a relative bioavailability (Frel%) of about 30% to about 100% compared to CBD dissolved in sesame oil containing the same dose of CBD. Drug-containing particles

[0188] In some embodiments, the pharmaceutical composition comprises about 10-60% of the drug substance described herein and about 20%-80% of the porous solid carrier. In some embodiments, the pharmaceutical composition comprises about 15-40% of the drug substance described herein and about 40%-60% of the porous solid carrier.

[0189] In some embodiments, the pharmaceutical composition comprises about 10-60% of the raw material drug described herein, about 20%-80% of the porous solid carrier, and about 10-50% of one or more lipophilic materials. In some embodiments, the pharmaceutical composition comprises about 15-40% of the raw material drug described herein, about 40%-60% of the porous solid carrier, and about 15-35% of one or more lipophilic materials.

[0190] In some embodiments, the pharmaceutical composition comprises about 10-60% of the raw material drug described herein, about 20%-80% of the porous solid carrier, and about 10-50% of one or more lipophilic materials, and about 0.1-2% of antioxidants. In some embodiments, the pharmaceutical composition comprises about 15-40% of the raw material drug described herein, about 40%-60% of the porous solid carrier, about 15-35% of one or more lipophilic materials, and about 0.2-1% of antioxidants. Method for producing drug-containing particles

[0191] In some embodiments, the drug-containing particles of the present disclosure are manufactured according to a solvent-mediated process, wherein the one or more cannabinoids are loaded from a solution onto a porous solid support (e.g., mesoporous silica) (see Figure 4 In some embodiments, the solvent-mediated method is provided in Figure 5In some embodiments, the drug-containing particles manufactured according to the solvent-mediated methods disclosed herein are free-flowing powders. In some embodiments, the free-flowing powder is stable at elevated temperatures (e.g., 25° C. or 40° C.) for a period of longer than 1 week, longer than 2 weeks, longer than 3 weeks, longer than 4 weeks, longer than 5 weeks, longer than 6 weeks, longer than 7 weeks, longer than 8 weeks, longer than 9 weeks, longer than 10 weeks, longer than 11 weeks, or longer than 12 weeks.

[0192] In some embodiments, the drug-containing particles of the present disclosure are made according to a solvent-mediated process, wherein the one or more cannabinoids, one or more polymers disclosed herein, and one or more optional antioxidants disclosed herein are loaded from a solution onto a porous solid support (e.g., mesoporous silica). In some embodiments, the solvent-mediated process is made according to the method provided in Figure 8 Follow the steps in .

[0193] In some embodiments, the solvent-mediated process disclosed herein comprises spray drying or freeze drying a solution of the one or more cannabinoids or derivatives, the one or more polymers disclosed herein, and the one or more optional antioxidants disclosed herein onto a porous solid support. In some embodiments, the solvent-mediated process comprising spray drying is according to the method provided in 9A to 9C or Fig.10 Follow the steps in .

[0194] In some embodiments, the method of preparing the drug-containing particles of the present disclosure comprises:

[0195] (a) combining a porous solid carrier, one or more cannabinoids, an optional polymer, one or more optional antioxidants, and an optional chelating agent to form a mixture;

[0196] (b) adding a solvent to the mixture, optionally under heating, to form a slurry;

[0197] (c) sonicating and / or agitating the slurry for a period of time; and

[0198] (d) evaporating the solvent to obtain a dry powder.

[0199] In some embodiments, the agitation of step (c) comprises low shear or high shear powder mixing techniques, such as manual mixing or use of a mechanically driven paddle, blade mixer, or twin-screw mixer.

[0200] The evaporation of step (d) can be carried out according to any suitable method known in the art. In some embodiments, the evaporation of step (d) is carried out under reduced pressure. In some embodiments, the evaporation of step (d) is carried out under reduced pressure and / or high temperature. In certain embodiments, the evaporation can be carried out by removing the solvent at a suitable temperature, by spray drying, by freeze drying or a combination thereof. In some embodiments, the evaporation includes secondary drying, which can be carried out in a vacuum oven, for example, until the residual solvent is within the ICH limit.

[0201] In some embodiments, the drug-containing particles of the present disclosure are manufactured according to a lipid loading method, wherein the one or more cannabinoids are combined with a lipophilic material disclosed herein and mixed with a porous solid carrier to facilitate loading (see Figure 4 In some embodiments, the lipid loading method is according to the method provided in Fig.12 In some embodiments, the drug-containing particles manufactured according to the lipid loading method disclosed herein are free-flowing powders. In some embodiments, the free-flowing powder is stable at high temperature (e.g., 25° C. or 40° C.) for a period of longer than 1 week, longer than 2 weeks, longer than 3 weeks, longer than 4 weeks, longer than 5 weeks, longer than 6 weeks, longer than 7 weeks, longer than 8 weeks, longer than 9 weeks, longer than 10 weeks, longer than 11 weeks, or longer than 12 weeks.

[0202] In some embodiments, the method of preparing the drug-containing particles of the present disclosure comprises:

[0203] (a) combining one or more cannabinoids, one or more lipophilic materials, one or more optional antioxidants, and an optional chelating agent to form a mixture;

[0204] (b) stirring the mixture of step (a) for a period of time until it is homogeneous;

[0205] (c) adding the homogenous mixture of step (b) to a porous solid support; and

[0206] (d) stirring the mixture of step (c) for a period of time until homogeneous. Pharmaceutical composition

[0207] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a plurality of drug-containing particles disclosed herein. In some embodiments, the pharmaceutical composition comprises one or more pharmaceutically acceptable excipients and / or carriers. In some embodiments, the pharmaceutical composition is in the form of tablets, capsules or particles. In embodiments, the drug-coated particles can be filled into capsules or compressed, optionally combined into tablets with various excipients as described herein. The pharmaceutical composition disclosed herein can be prepared by any suitable method known in the art. In some embodiments, the method includes blending the drug-containing particles with the one or more pharmaceutically acceptable excipients and / or carriers. In some embodiments, the method includes a dry granulation (roller compaction) process.

[0208] Pharmaceutically acceptable excipients include fillers, diluents, glidants, disintegrants, binders and lubricants. Other pharmaceutically acceptable excipients include acidulants, alkalizers, preservatives, antioxidants, buffers, chelating agents, colorants, complexing agents, emulsifiers and / or solubilizers, flavors, perfumes, humectants, sweeteners and wetting agents.

[0209] Flavoring agents and flavor enhancers make the dosage form more palatable to the patient. Common flavoring agents and flavor enhancers for pharmaceutical products that may be included in the compositions and / or combinations of the present disclosure include fruit flavors, sucrose, maltol, vanillin, ethyl vanillin, menthol, citric acid, fumaric acid, ethyl maltol, and tartaric acid.

[0210] In some embodiments, the drug-containing particles disclosed herein are prepared as a formulation having one of the following non-limiting compositions: Implementation

[0211] 1. A drug-containing particle, comprising:

[0212] (a) one or more cannabinoids; and

[0213] (b) a porous solid support,

[0214] wherein the one or more cannabinoids are adsorbed onto and / or into the porous solid carrier.

[0215] 2. The drug-containing particles according to embodiment 1, wherein the porous solid carrier is a microparticle.

[0216] 3. The drug-containing particle according to embodiment 1 or 2, wherein the porous solid carrier has an average particle size ranging from about 1 μm to about 250 μm.

[0217] 4. The drug-containing particle of any one of embodiments 1-3, wherein the porous solid carrier has an average particle size in the range of about 50 μm to about 150 μm or about 40 μm to 100 μm.

[0218] 5. The drug-containing particle of any one of embodiments 1-4, wherein the porous solid carrier has a porosity ranging from about 75% to about 99%.

[0219] 6. The drug-containing particle of any one of embodiments 1-5, wherein the porous solid carrier has an average surface area in the range of about 100 m2 / g to about 1000 m2 / g.

[0220] 7. The drug-containing particle of any one of embodiments 1-6, wherein the porous solid carrier has an average pore volume in the range of about 0.1 mL / g to about 5 mL / g.

[0221] 8. The drug-containing particle of any one of embodiments 1-7, wherein the porous solid carrier has an average pore volume in the range of about 1 mL / g to about 2 mL / g.

[0222] 9. The drug-containing particle of any one of embodiments 1-7, wherein the porous solid carrier has an average pore size in the range of about 1 nm to about 100 nm.

[0223] 10. The drug-containing particle of any one of embodiments 1-9, wherein the porous solid carrier has an average pore size in the range of about 2 nm to about 60 nm.

[0224] 11. The drug-containing particle of any one of embodiments 1-9, wherein the porous solid carrier has an average pore size in the range of about 10 nm to about 50 nm.

[0225] 12. The drug-containing particle of any one of embodiments 1-11, wherein the porous solid carrier has an average pore size in the range of about 15 nm to about 30 nm.

[0226] 13. The drug-containing particle of any one of embodiments 1-12, wherein the porous solid carrier has one or more of the following properties:

[0227] (i) an average pore volume in the range of 1-2 cm3 / g;

[0228] (ii) an average surface area within the range of 250 to 375; or

[0229] (iii) Pore diameter in the range of about 2-50 nm.

[0230] 14. The drug-containing particle of any one of embodiments 1-13, wherein the porous solid carrier has two or more of the following properties:

[0231] (i) an average pore volume in the range of 1-2 cm3 / g;

[0232] (ii) an average surface area within the range of 250 to 375; or

[0233] (iii) Pore diameter in the range of about 2-50 nm.

[0234] 15. The drug-containing particle according to any one of embodiments 1 to 14, wherein the porous solid carrier has:

[0235] (i) an average pore volume in the range of 1-2 cm3 / g;

[0236] (ii) an average surface area in the range of 250 to 375; and

[0237] (iii) Pore diameter in the range of about 2-50 nm.

[0238] 16. The drug-containing particle of any one of embodiments 1-14, wherein the porous solid carrier comprises silicon dioxide (SiO2), microcrystalline cellulose, silicified microcrystalline cellulose, chitosan, isomalt, or a silicate.

[0239] 17. The drug-containing particle of any one of embodiments 1-16, wherein the porous solid carrier comprises silicon dioxide or a silicate.

[0240] 18. The drug-containing particle of any one of embodiments 1-17, wherein the porous solid carrier comprises silicon dioxide.

[0241] 19. The drug-containing particle of any one of embodiments 16-18, wherein the silica comprises mesoporous silica or amorphous silica.

[0242] 20. The drug-containing particle of any one of embodiments 16-19, wherein the silica comprises mesoporous silica.

[0243] 21. The drug-containing particle of any one of embodiments 1-11, wherein the porous solid carrier comprises a silicate.

[0244] 22. The drug-containing particle of embodiment 21, wherein the silicate comprises an aluminosilicate.

[0245] 23. The drug-containing particle of embodiment 22, wherein the silicate comprises magnesium aluminum silicate.

[0246] 24. The drug-containing particle of any one of embodiments 1-23, wherein the porous solid carrier is present in an amount ranging from about 20 wt% to about 80 wt% based on the total weight of the drug-containing particle.

[0247] 25. The drug-containing particle of any one of embodiments 1-24, wherein the solid carrier is present in an amount ranging from about 30 wt% to about 50 wt% based on the total weight of the drug-containing particle.

[0248] 26. The drug-containing particle of any one of embodiments 1-25, wherein the one or more cannabinoids comprises cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabichromene (CBL), cannabinol (CBN), cannabigerol propyl variant (CBNV), dihydroxycannabinol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabinol (THCV), tetrahydrocannabinolic acid (THCVA), CBD-C4, OH-CBD, CBD-C4, 6-OH-CBD, 7-OH-CBD, 7-COOH-CBD, 11-COOH-THC, or 11-OH-THC.

[0249] 27. The drug-containing particle of any one of embodiments 1-26, wherein the one or more cannabinoids comprises CBD.

[0250] 28. The drug-containing particle of any one of embodiments 1-27, wherein the one or more cannabinoids are present in an amount ranging from about 5 weight % to about 75 weight % based on the total weight of the drug-containing particle.

[0251] 29. The drug-containing particle of any one of embodiments 1-28, wherein the one or more cannabinoids are present in an amount ranging from about 10 weight % to about 60 weight % based on the total weight of the drug-containing particle.

[0252] 30. The drug-containing particle of any one of embodiments 1-29, wherein the one or more cannabinoids are present in an amount ranging from about 15 weight % to about 40 weight % based on the total weight of the drug-containing particle.

[0253] 31. The drug-containing particle according to any one of embodiments 1-30, wherein the ratio of the porous solid carrier to the drug substance is 10:1 to 1:5.

[0254] 32. The drug-containing particle of any one of embodiments 1-30, wherein the ratio of the porous solid carrier to the drug substance is 2:1 to 1:2.

[0255] 33. The drug-containing particle of any one of embodiments 1-32, wherein the one or more cannabinoids are present in an amorphous form.

[0256] 34. The drug-containing particle of any one of embodiments 1-33, wherein adsorption is determined by SEM, DSC and / or XRPD.

[0257] 35. The drug-containing particle of any one of embodiments 1-34, wherein substantially all of the one or more cannabinoids are adsorbed into the pores of the porous solid carrier.

[0258] 36. The drug-containing particle of any one of embodiments 1-35, wherein the one or more cannabinoids are adsorbed into the pores of the porous solid carrier.

[0259] 37. The drug-containing particle of any one of embodiments 1-36, comprising a lipophilic material.

[0260] 38. The drug-containing particles of embodiment 39, wherein the lipophilic material comprises a stabilizer, a viscosity modifier and / or a processability enhancer.

[0261] 39. The drug-containing particles of embodiment 37 or 38, wherein the lipophilic material comprises one or more non-ionic surfactants.

[0262] 40. The drug-containing particles of embodiment 39, wherein the one or more nonionic surfactants comprise polyoxyethylene sorbitan fatty acid esters (polysorbates, ), polyoxyethylene 15 hydroxystearate (polyethylene glycol 15 hydroxystearate, solutol )、Polyoxyethylene castor oil derivatives ( EL, ELP, RH40), polyoxyethylene stearate Sorbitan fatty acid esters Polyoxyethylene alkyl ether Polyoxyethylene nonylphenol ether or a combination thereof.

[0263] 41. The drug-containing particle of embodiment 39 or 40, wherein the lipophilic material comprises one or more polyoxyglycerides.

[0264] 42. The drug-containing particles of any one of embodiments 39-41, wherein the lipophilic material comprises one or more fatty acid esters containing polyethylene oxide, one or more fatty acid glycerides, one or more

[0265] 43. The drug-containing particles of embodiment 33 or 34, wherein the lipophilic material comprises one or more of stearoyl polyoxyl-32 glyceride (gelucire 50 / 13, gelucire 43 / 01), lauroyl polyoxyl-6-glyceride (labrafil M2130), oleoyl polyoxyl-6-glyceride (labrafil 1944), mono / diester of 12-hydroxystearic acid and polyethylene glycol (crodasol HS), PEG-40 hydrogenated castor oil (croduret 40), propylene glycol monocaprylate (capryol 90), medium chain triglycerides (labrafac 1349), propylene glycol dicaprylate / dicaprate (labrafac PG), caprylocaproyl polyoxyl-8-glyceride (labrasol ALF), or a combination thereof.

[0266] 39. The drug-containing particle of any one of embodiments 32-38, wherein the lipophilic material is present in an amount of about 1 wt% to about 75 wt% based on the total weight of the drug-containing particle.

[0267] 40. The drug-containing particle of any one of embodiments 32-38, wherein the lipophilic material is present in an amount of about 25 wt% to about 35 wt% based on the total weight of the drug-containing particle.

[0268] 41. The drug-containing particle of any one of embodiments 1-23, wherein the weight ratio of the solid carrier to the combined weight of the drug substance and the lipophilic material is in the range of 3:1 to 1:1.

[0269] 42. The drug-containing particle of embodiment 33 or 34, wherein the lipophilic material is sesame seed oil or pumpkin seed oil.

[0270] 43. The drug-containing particle of embodiment 42, wherein the lipophilic material is present in an amount of about 25 wt% to about 75 wt% based on the total weight of the drug-containing particle.

[0271] 44. The drug-containing particle according to embodiment 42, wherein the sesame oil is present in an amount of about 45% by weight to about 60% by weight based on the total weight of the drug-containing particle.

[0272] 45. The drug-containing particle of any one of embodiments 1-44, comprising a polymer.

[0273] 46. ​​The drug-containing particle of embodiment 45, wherein the polymer has a Tg of about 50°C to about 130°C.

[0274] 47. The drug-containing particles of embodiment 45 or 46, wherein the polymer comprises polyvinyl pyrrolidone (kollidon VA64), cross-linked polyvinyl N-pyrrolidone (crospovidone), hydroxypropyl methylcellulose phthalate (HPMCP 50), polyvinyl alcohol-polyethylene glycol copolymer (kollicoat), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (soluplus), polyvinyl alcohol, or a combination thereof.

[0275] 48. The drug-containing particle of any one of embodiments 45-47, wherein the polymer is present in an amount of about 1 wt% to about 75 wt% based on the total weight of the drug-containing particle.

[0276] 49. The drug-containing particle of any one of embodiments 45-47, wherein the polymer is present in an amount of about 10 wt% to about 50 wt% based on the total weight of the drug-containing particle.

[0277] 50. The drug-containing particle of any one of embodiments 45-49, wherein the polymer is provided as a coating on the drug-containing particle.

[0278] 51. The drug-containing particle of any one of embodiments 1-50, further comprising a chelating agent.

[0279] 52. The drug-containing particle of embodiment 51, wherein the chelating agent comprises EDTA, citric acid, or curcumin.

[0280] 53. The drug-containing particle of embodiment 51, wherein the chelating agent comprises citric acid or curcumin.

[0281] 54. The drug-containing particle of any one of embodiments 51-53, wherein the amount of the chelating agent is in the range of about 0.05 wt% to about 3 wt% based on the total weight of the drug-containing particle.

[0282] 55. The drug-containing particle of any one of embodiments 51-53, wherein the amount of the chelating agent ranges from about 0.05 wt% to about 0.1 wt% based on the total weight of the drug-containing particle.

[0283] 56. The drug-containing particle of any one of embodiments 1-55, comprising one or more antioxidants.

[0284] 57. The drug-containing particle of embodiment 56, wherein the one or more antioxidants comprise α-tocopherol, β-carotene, ascorbic acid, ascorbyl palmitate, lecithin, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, propyl gallate, or a combination thereof.

[0285] 58. The drug-containing particle of embodiment 56 or 57, wherein the antioxidant comprises α-tocopherol.

[0286] 59. The drug-containing particle of any one of embodiments 56-58, wherein the amount of the one or more antioxidants ranges from about 0.05 wt% to about 3 wt% based on the total weight of the drug-containing particle.

[0287] 60. The drug-containing particle of embodiment 59, wherein the amount of the one or more antioxidants is in the range of about 0.2-1% by weight based on the total weight of the drug-containing particle.

[0288] 61. The drug-containing particle of any one of claims 1-60, wherein about 30-90% of the one or more cannabinoids are released in about 3-12 hours.

[0289] 62. The drug-containing particle of any one of claims 1-60, wherein about 50-90% of the one or more cannabinoids are released within about 3-12 hours.

[0290] 63. The drug-containing particle of any one of claims 1-60, wherein greater than about 80% of the one or more cannabinoids are released by about 12 hours.

[0291] 64. The drug-containing particle of any one of claims 1-61, comprising no greater than about 0.2% by weight cannabidiolic acid (CBD-C1).

[0292] 65. The drug-containing particle of any one of claims 1-64, comprising no greater than about 0.8% cannabidiol (CBDV) by weight.

[0293] 66. The drug-containing particle of any one of claims 1-65, comprising less than about 0.5% by weight butyl-cannabidiol (CBD-C4).

[0294] 67. A pharmaceutical composition comprising a plurality of drug-containing particles according to any one of claims 1 to 66 or a combination thereof and at least one pharmaceutically acceptable excipient.

[0295] 68. The pharmaceutical composition of claim 67, wherein the pharmaceutical composition is a tablet, a capsule or a granule.

[0296] 69. The pharmaceutical composition of any one of claims 1-68, wherein the drug-containing particles are prepared by a process comprising spray drying or hot melt extrusion.

[0297] 70. A method for preparing the drug-containing particles of any one of claims 1-32 and 45-66, the method comprising:

[0298] (a) combining a porous solid carrier, one or more cannabinoids, and optionally a polymer to form a mixture;

[0299] (b) adding a solvent to the mixture to form a slurry;

[0300] (c) sonicating and / or agitating the slurry; and

[0301] (d) evaporating the solvent to obtain a dry powder.

[0302] 71. A method for preparing the drug-containing particles of any one of claims 1-44 and 51-66, the method comprising:

[0303] (a) combining one or more cannabinoids and one or more lipophilic materials to form a mixture;

[0304] (b) stirring the mixture of step (a) until homogeneous;

[0305] (c) adding the homogenous mixture of step (b) to a porous solid support; and

[0306] (d) stirring the mixture of step (c) until homogeneous. Example Example 1: Evaluation of solvent-mediated drug loading on mesoporous silica

[0307] The drug-containing particles having the compositions provided in Table 1 were prepared according to the method described in Figure 5 The solvent-mediated manufacturing method is used to prepare the Table 1. Compositions of CBD-containing particles prepared by solvent-mediated manufacturing. Porous solid support (% w / w) Cannabinoids (%w / w) Fujisil 71.4 CBD 28.6 Fujisil 50.0 CBD 50.0 Fujisil 25.1 CBD 74.9 Syloid 71.3 CBD 28.7 Syloid 50.2 CBD 49.8 Syloid 25.1 CBD 74.9

[0308] Stability Test: The stability of the CBD-containing drug particles in Table 1 was evaluated under accelerated temperature conditions of 60° C. after 7 days. The stability success criteria are shown in Table 2A. The amounts of CBD degraders CBE I, CBE II, and OH-CBD, and THC are provided as percentages of active ingredients and are shown in Table 2B. Table 2A. Stability criteria Table 2B. Stability of drug granules after 7 days at 60°C. ND = Not Detected; CBE 1, CBE II, OH-CBD, THC and total unknowns are given as % weight of CBD.

[0309] The formulations were stored at 60°C and amorphous properties were assessed by XRPD at 0 and 7 days. The XRPD diffractograms at the initial time point and 1 week time point are shown in Fig.23A and Fig. 23B The diffractograms indicated that all 25% w / w and 50% w / w batches were amorphous by XRPD. The 75% w / w Fujisil batch was not amorphous and showed peaks indicative of crystalline CBD. There was no change in the amorphous state of any batch after storage at 60°C for 7 days.

[0310] Table 2 Drug release profile: Drug release from Syloid granules containing 50% w / w CBD and Fujisil granules containing 50% w / w CBD was evaluated. Figure 6 As shown in Figure 2, CBD was effectively released from Syloid silica, reaching 80% at the 60-minute time point. In addition, Syloid exhibited superior flow properties after API loading compared to Fukisil. Therefore, Syloid was selected for further development. Example 2: Evaluation of CBD-loaded mesoporous silica drug particles prepared by spray drying

[0311] The properties of the spray-dried drug-containing particles provided in Tables 3 and 4 were evaluated. These particles were prepared according to the method described in Figure 7 An exemplary spray drying apparatus is described in Figure 8 middle. Table 3. CBD-containing Composition of particles Table 4. CBD-containing Composition of particles.

[0312] The spray drying process was carried out on a Buchi B-290 apparatus using the following parameters:

[0313] Inlet temperature: 60℃(Syloid) / 80℃(Neusilin)

[0314] Cooling machine temperature: -20℃

[0315] Air Extractor: 100%

[0316] Feed rate: 20g / min

[0317] Q flow: 65mm (Syloid) / 60mm (Neusilin)

[0318] Nozzle size: 2.1mm

[0319] Drying after collection: 2 days at 30 °C under dynamic vacuum (Syloid) / 24 hours at 40 °C under vacuum (Neusilin)

[0320] In each case, the materials tested were easy to handle and no disposal issues were observed. Example 3: Evaluation of CBD / lipid-loaded mesoporous silica drug particles

[0321] According to the provided 9A to 9C The compositions of various CBD / lipid-loaded mesoporous silica drug particles prepared by the method in are provided in Table 5.

[0322] In particular, according to the description Fig. 9A The CBD / sesame oil loaded mesoporous silica drug particle preparations 1-6 in Table 5 were prepared by the process described in Fig. 9B The CBD / lipid-loaded mesoporous silica drug particle formulations were prepared using the process described in 7-10.

[0323] For the formulations provided in Table 5, all compositions showed amorphous properties, confirming adsorption of cannabinoids. Crystallinity was observed when drug loading was greater than 60%. Table 5. Composition of CBD / sesame seed oil loaded drug particles.

[0324] Sesame seed oil was replaced with pumpkin seed oil and a primary solution of 12.48% CBD (w / w), 37.40% pumpkin seed oil (w / w) and 0.1% α-tocopherol was prepared. This solution was added to the To provide drug particles with 17.5%, 15.0% and 12.5% ​​(w / w) CBD loading. This composition was found to be amorphous.

[0325] Other solid and liquid lipophilic materials were evaluated for their ability to dissolve CBD. The solid lipophilic materials evaluated are provided in Table 6A below and the solubility observations are provided in Table 6B. The liquid lipophilic materials evaluated are provided in Table 7A and the solubility observations are provided in Table 7B. Table 6A. Solid lipophilic materials Lipids HLB value Gelucire 50 / 13 11 Gelucire 48 / 16 14 Gelucire 44 / 14 11 Gelucire 43 / 01 1 Labrafil M 2130CS 9 Crodasol HS 15 Croduret 40 13 Croduret 50 14 Peceol 1 Table 7A. Liquid lipophilic materials Lipids HLB value Transcutol 14 Labrasol ALF 12 Kolliphor EL 12 Polysorbate 80 15 Polysorbate 60 15 Capryol 90 3 Polysorbate 20 15 Capryol PGMC 3 Labrafac PG 1 Lab Lipo 1349 1 Labrafil 1944 9 Labrafil 2125 9 Oleic acid 1 Corn Oil 1 Cottonseed oil 1

[0326] The solid lipophilic material was loaded with CBD at three concentrations: 300, 400 and 500 mg / g. Each mixture was then heated to 60°C for half an hour and then stirred to dissolve. 10 grams of each combination was prepared in a clear glass scintillation vial and allowed to cool before evaluating it using DSC to determine if there was any undissolved CBD. Any excipient that showed complete dissolution of CBD at 500 mg / g was further evaluated at 540, 560 and 600 mg / g. The results are shown in Table 6B. Table 6B. CBD solubility observation results

[0327] Before combining with CBD, each liquid lipophilic material was heated in an oven at 40°C for 30 minutes. 10 g of CBD was combined with 5 g of lipophilic material to produce a saturated mixture. These were stirred at 300 rpm using an oscillator plate for at least 8 hours. After stirring, the solution was centrifuged at 14800 rpm for 90 minutes to separate out any remaining undissolved CBD crystals. The resulting supernatant was sampled and the CBD content was determined to confirm the saturated solubility of the lipid. The solubility results are presented in Table 7B below. Table 7B. Solubility Observations Lipids CBD (mg / g) Transcutol 653.2 Labrasol ALF 630.8 Kolliphor EL 603.9 Polysorbate 80 598.4 Polysorbate 60 588.5 Capryol 90 582.2 Polysorbate 20 565.9 Capryol PGMC 565.3 Labrafac PG 501.8 Labrafac 1349 427.6 Labrafil 1944 424.2 Labrafil 2125 412.6 Oleic acid 347.2 Corn Oil 276.1 Cottonseed oil 255.2

[0328] The advanced lipophilic materials used for further development are shown in Table 8. Table 8. Advanced lipophilic materials

[0329] According to the description in Fig. 9C Additional CBD / lipid-loaded mesoporous silica drug particles were prepared without antioxidants using the process described in , such as formulations 1-10 in Table 8.

[0330] Drug release from each CBD / lipid loaded particle was determined using the dissolution test conditions described in Table A1 (Gelucire and Capryol samples) and Table A2 (Labrafil samples) and the results are summarized in Fig.10 In all cases, between about 70% and 80% of the CBD in the drug particles was released within about 6 h. Table 8. Composition of CBD / lipid loaded drug particles.

[0331] The stability of the formulations in Table 8 was evaluated after 4 weeks at 25°C and 60% RH and after 6 weeks at 40°C and 75% RH. The results are summarized in Tables 9 and 10, respectively. Each formulation was found to be amorphous and highly stable. Table 9. Stability evaluated after 4 weeks at 25°C and 60% RH. Table 10. Stability evaluated after 6 weeks at 40°C and 75% RH.

[0332] CBD / lipid loaded mesoporous silica drug particles with antioxidants were also prepared according to the method described in Fig. 9C The compositions of the drug particles are summarized in Table 11. Table 11. Composition of CBD / lipid loaded drug particles with antioxidants.

[0333] The stability of the formulations in Table 11 was evaluated after 6 weeks at 25°C and 60% RH and after 6 weeks at 40°C and 75% RH. The results are summarized in Table 12 and Table 13, respectively. Each formulation was found to be amorphous and highly stable. Table 12. Stability of antioxidants evaluated after 6 weeks at 25°C and 60% RH. Table 13. Stability of antioxidants evaluated after 6 weeks at 40°C and 75% RH.

[0334] CBE I in Labrafil 1944 composition was observed after 6 weeks at 25C / 60% RH. Croduret 40, Crodasol HS and Labrafil PG exhibited lower CBD solubility compared to corresponding lipids with similar HLB values. Based on these observations, these four lipophilic materials were not selected for commercial development.

[0335] The CBD solubility and stability of compositions containing propylene glycol monocaprylate (Capryol 90) were evaluated. CBD was dissolved in propylene glycol monocaprylate (Capryol 90) and loaded into The formulations are shown in Table 14. Other lipids were also tested and crystallization was observed. Other candidate lipids will be screened. Table 14: Composition of CBD dissolved in propylene glycol monocaprylate (Capryol 90) and loaded on Aeroperl mesoporous silica particles with antioxidants. Material %w / w Aeroperl 300 50％ CBD 30％ Capryol 90 19％ α-Tocopherol 1％

[0336] The stability of the formulations in Table 14 was evaluated after 6 weeks at 40°C and 75% RH. The results are summarized in Table 15. The formulations were all found to be amorphous and highly stable. Table 15: Stability after 6 weeks at 40°C / 75%RH

[0337] Next, a mixture of two or three lipophilic materials was used to prepare formulations. The formulations are provided in Table 16. Table 16: Composition of CBD dissolved in a single lipid or combination of lipids and loaded on Syloid XDP mesoporous silica particles with antioxidants *MTC; Medium Chain Triglycerides

[0338] The binary and ternary lipid mixtures are completely miscible and provide a medium in which CBD can be dissolved and loaded onto the mesoporous silica. The stability of the compositions described in Table 16 was evaluated after 6 weeks at 40°C and 75% RH. The results are summarized in Table 17. CBD maintained its amorphous state and was chemically stable in these compositions. Table 17: Stability of the formulations in Table 16 after 3 weeks at 40C / 75%RH Example 4: Preparation of CBD / Polymer Formulations by Solvent-Mediated Manufacturing

[0339] CBD / polymer-loaded drug particles having the composition provided in Table 18 were prepared according to the method described in Fig.11 Prepared by the process in. Table 18. Composition of CBD-containing particles including a polymer component. Material %w / w CBD 40.0 polymer 10.0 Syloid XDP 49.8 α-Tocopherol (antioxidant) 0.2

[0340] The following polymers are each in the above composition:

[0341] HPMCP 50 (Hydroxypropyl Methylcellulose Phthalate)

[0342] Kollidon K30 (Polyvinylpyrrolidone)

[0343] Kollidon VA64 (Polyvinyl pyrrolidone / vinyl acetate)

[0344] Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer)

[0345] Kollicoat MAE (polyvinyl alcohol-polyethylene glycol copolymer)

[0346] Additional polymers suitable for inclusion in these formulations are listed in Fig.12 middle.

[0347] To determine whether drug-containing particles comprising amorphous CBD and a polymer could be produced via a continuous manufacturing process, a spray drying process was evaluated. Table 19 provides the following information on the spray drying method disclosed herein: XDP silica-containing CBD pharmaceutical particle composition. Table 19. Compositions of CBD and polymer-containing particles subjected to spray drying.

[0348] The spray drying process was carried out on a Buchi B-290 apparatus using the following parameters:

[0349] Inlet temperature: 80℃

[0350] Cooling machine temperature: -20℃

[0351] Air Extractor: 100%

[0352] Feed rate: 20g / min

[0353] Q flow: 60mm

[0354] Nozzle size: 2.1mm

[0355] Drying after collection: 24h, at 40°C, under vacuum

[0356] Kollidon K30 was evaluated in formulations, however, drug-containing particles incorporating this polymer did not process well and require further optimization. Example 5: Stability study of lipid-loaded mesoporous silica drug particles containing antioxidants

[0357] The presence of antioxidants was evaluated in two stages to study their effect on stability

[0358] Phase 1: The formulation containing 100 mg CBD per capsule was evaluated at two levels (0% and 0.2%) of alpha-tocopherol and stability was measured for 6 weeks at ambient and accelerated conditions of 40°C / 75%RH and 25°C / 60%RH. The formulation tested is described in Table 6 of Example 3. To evaluate the effect of alpha-tocopherol, 0.2% alpha-tocopherol was added to the formulation described in Table 6. The changes in API (CBD) content and impurities were measured over 6 weeks and are shown in Figures 13 to 17. An overview of the formulation tested is shown in Table 20. Table 21 shows the specification settings for feasible product candidates.

[0359] Fig.13A 0.2% α-tocopherol was shown to protect CBD from degradation at 25°C / 60% RH for 6 weeks, while Fig. 13B The results show that the CBD content measured by similar formulations prepared without α-tocopherol decreased. A similar trend was observed when the degradants were measured under accelerated conditions. Specifically, the presence of α-tocopherol reduced the amount of CBE I ( Fig.14A and Fig. 14B )、CBE II( Fig.15A and Fig. 15B ) and other unknown degradants ( Fig.16A and Fig. 16B Under the same accelerated storage conditions, except for OH-CBD, formulations containing α-tocopherol demonstrated better stability performance when compared to formulations without α-tocopherol ( Fig.17A and Fig. 17B ) Table 20. Compositions with antioxidants Table 21. Stability criteria *NMT=Not more than

[0360] Phase 2: The stability of formulations containing 100 mg CBD and 0.2%, 0.6% or 1.0% α-tocopherol per capsule was evaluated at 25°C / 60% RH, 30°C / 65% RH and 40°C / 75% RH for 12 weeks. The compositions of the tested formulations are summarized in Table 22. Table 22. Composition

[0361] The XRPD diffraction patterns of the tested formulations at the 12-week time point are shown in Fig.24 No change in the amorphous state of the formulation was observed after storage at 40°C / 75%RH for 12 weeks.

[0362] 18A to 18D showed that 0.2%, 0.6% and 1% α-tocopherol generally protected CBD from 43 / 10 decomposed in the loaded formulation as determined by the amount of degraders CBE I, CBEII, OH-CBD and total degraders. 43 / 01 showed anomalous data with 0.6% alpha-tocopherol content producing the worst results and 0.2% and 1% performing better.

[0363] FIG. 19A to FIG. 19D showed that 0.2%, 0.6% and 1% α-tocopherol generally protected CBD from M2130 decomposed in the loaded formulations as determined by the amount of degraders CBE I, CBE II, OH-CBD and total degraders. The best performance was demonstrated with 1% (w / w) alpha tocopherol content.

[0364] FIG. 20A to FIG. 20D showed that 0.2%, 0.6% and 1% α-tocopherol generally protected CBD from 90% decomposition in the loaded formulation as determined by the amount of degraders CBE I, CBEII, OH-CBD and total degraders. The best performance was demonstrated with 0.6% (w / w) alpha tocopherol content. Example 6: Capsule Preparation

[0365] Drug-containing granules were prepared and added to capsules as described in Example 3. Capsules containing 100 mg cannabinoid drug substance and 150 mg cannabinoid drug substance were prepared as described in Table 23 and Table 24. Table 23. 100 mg capsules. Table 24. 150 mg capsules. Example 7. Dog Studies

[0366] The compositions described in Table 25 were administered to beagle dogs. Plasma levels and gastrointestinal tolerability were evaluated compared to an oral solution of CBD in sesame oil prepared in capsules ("CBD oral solution in capsules"). The results are also presented in Table 25.

[0367] Target Overview

[0368] Bioavailability is similar or better than that of CBD oral solution in capsules

[0369] No vomiting

[0370] Liquid / soft stools <2

[0371] Total obs < 3.25

[0372] No loss of appetite

[0373] The CBD oral solution in the capsule sets the baseline of the target profile. The candidate product has characteristics that are equivalent or superior to the CBD oral solution. Compositions that do not meet the target profile are not advanced. As shown in Table 25, compositions containing CBD dissolved in lipids and loaded on porous solid carriers ("lipid-loaded carriers") exhibit superior pharmacokinetics compared to compositions containing CBD dissolved in the same lipids (see also Table 26) and spray-dried compositions prepared with the same lipids. In addition, the lipid-loaded carrier composition exhibits superior gastrointestinal tolerance than all compositions (including CBD oral solutions). FIG. 21A to FIG. 21C The weight ratio of CBD to lipophilic material was shown not to significantly affect bioavailability.

[0374] Using porous carriers and 40 / 01, 90 and The composition prepared by M2130 has a favorable profile and was chosen because it is advanced. Table 27. Overview • Lipid loaded formulations provided a favorable profile and produced encouraging physical and chemical data. CBD remains in an amorphous form even without the use of antioxidants Syloid retains free-flowing powder properties and has a drug loading of 24% Neuselin retains free-flowing powder properties and has a drug loading of 21% Like sesame seed oil, pumpkin seed oil was evaluated using MPS and Neusilin and exhibited desirable properties. • It was found that the introduction of a chelating agent and / or AO combination can provide improved stability to the formulation. Example 8. Rat studies

[0375] The compositions described in Table 25 were administered to rats. The bioavailability of the compositions was evaluated compared to an oral solution of CBD in sesame oil or a suspension in water-methylcellulose ( FIG. 22A to FIG. 22C ). No adverse events were observed in the rat model study.

Claims

1. A drug-containing particle, comprising: (a) a drug substance containing one or more cannabinoids; and (b) a porous solid support, wherein the one or more cannabinoids are adsorbed onto the porous solid carrier, and wherein the porous solid carrier has one or more of the following properties: (i) an average pore volume of about 1 mL / g to about 2 mL / g; (ii) About 250m 2 / g to about 375m 2 Average surface area per gram; or (iii) A pore size of about 2 nm to about 50 nm.

2. The drug-containing particle according to claim 1, wherein the porous solid carrier is a microparticle.

3. The drug-containing particle of claim 1 or 2, wherein the porous solid carrier has an average particle size of about 1 μm to about 250 μm.

4. The drug-containing particle of any one of claims 1 to 3, wherein the porous solid carrier has an average particle size of about 50 μm to about 150 μm, or about 40 μm to 100 μm.

5. The drug-containing particle of any one of claims 1-4, wherein the porous solid carrier has a porosity of about 75% to about 99%.

6. The drug-containing particle of any one of claims 1-5, wherein the porous solid carrier has an average pore size of about 10 nm to about 50 nm.

7. The drug-containing particle of any one of claims 1-6, wherein the porous solid carrier has an average pore size of about 15 nm to about 30 nm.

8. The drug-containing particle according to any one of claims 1 to 7, wherein the porous solid carrier has two or more of the following characteristics: (a) an average pore volume of about 1 mL / g to about 2 mL / g; (b) About 250m 2 / g to about 375m 2 Average surface area per gram; or (c) A pore size of about 2 nm to about 50 nm.

9. The drug-containing particle according to any one of claims 1 to 8, wherein the porous solid carrier has: (a) an average pore volume of about 1 mL / g to about 2 mL / g; (b) About 250m 2 / g to about 375m 2 Average surface area per gram; and (c) A pore size of about 2 nm to about 50 nm.

10. The drug-containing particle according to any one of claims 1 to 9, wherein the porous solid carrier comprises silicon dioxide (SiO2), microcrystalline cellulose, silicified microcrystalline cellulose, chitosan, isomalt or a silicate.

11. The drug-containing particle according to any one of claims 1 to 10, wherein the porous solid carrier comprises silicon dioxide or a silicate.

12. The drug-containing particle of any one of claims 1-11, wherein the porous solid carrier comprises silicon dioxide.

13. The drug-containing particle according to any one of claims 10 to 12, wherein the silicon dioxide comprises mesoporous silicon dioxide or amorphous silicon dioxide.

14. The drug-containing particle of any one of claims 10-12, wherein the silicon dioxide comprises mesoporous silicon dioxide.

15. The drug-containing particle of any one of claims 1-14, wherein the porous solid carrier comprises a silicate.

16. The drug-containing particle of claim 15, wherein the silicate comprises an aluminosilicate.

17. The drug-containing particle of claim 15, wherein the silicate comprises magnesium aluminum silicate.

18. The drug-containing particle of any one of claims 1-17, wherein the porous solid carrier is present in an amount of about 20 wt% to about 80 wt% based on the total weight of the drug-containing particle.

19. The drug-containing particle of any one of claims 1 to 18, wherein the solid carrier is present in an amount of about 30 wt% to about 50 wt% based on the total weight of the drug-containing particle.

20. The drug-containing particle of any one of claims 1-19, wherein the one or more cannabinoids comprise cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabichromene (CBL), cannabinol (CBN), cannabigerol propyl variant (CBNV), dihydroxycannabinol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabinol (THCV), tetrahydrocannabinolic acid (THCVA), CBD-C4, OH-CBD, CBD-C4, 6-OH-CBD, 7-OH-CBD, 7-COOH-CBD, 11-COOH-THC or 11-OH-THC.

21. The drug-containing particle of any one of claims 1-20, wherein the one or more cannabinoids comprises CBD.

22. The drug-containing particle of any one of claims 1-21, wherein the one or more cannabinoids are present in an amount of about 5 wt% to about 75 wt% based on the total weight of the drug-containing particle.

23. The drug-containing particle of any one of claims 1-22, wherein the one or more cannabinoids are present in an amount of about 10 wt% to about 60 wt% based on the total weight of the drug-containing particle.

24. The drug-containing particle of any one of claims 1-23, wherein the one or more cannabinoids are present in an amount of about 15 wt% to about 40 wt% based on the total weight of the drug-containing particle.

25. The drug-containing particle according to any one of claims 1 to 24, wherein the ratio of the porous solid carrier to the drug substance is 10:1 to 1:

5.

26. The drug-containing particle according to any one of claims 1 to 24, wherein the ratio of the porous solid carrier to the drug substance is 2:1 to 1:

2.

27. The drug-containing particle of any one of claims 1-26, wherein the one or more cannabinoids are present in an amorphous form.

28. The drug-containing particle of any one of claims 1 to 27, wherein adsorption is determined by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and / or X-ray powder diffraction (XRPD).

29. The drug-containing particle of any one of claims 1 to 28, wherein substantially all of the one or more cannabinoids are adsorbed into the pores of the porous solid carrier.

30. The drug-containing particle of any one of claims 1-29, wherein the one or more cannabinoids are adsorbed into the pores of the porous solid carrier.

31. The drug-containing particle of any one of claims 1-30, comprising a lipophilic material.

32. The drug-containing particle of claim 31, wherein the lipophilic material comprises a stabilizer, a viscosity modifier and / or a processability enhancer.

33. The drug-containing particle of claim 31 or 32, wherein the lipophilic material comprises one or more non-ionic surfactants.

34. The drug-containing particles of claim 33, wherein the one or more nonionic surfactants comprise polyoxyethylene sorbitan fatty acid esters (polysorbates, ), polyoxyethylene 15 hydroxystearate (polyethylene glycol 15 hydroxystearate, )、Polyoxyethylene castor oil derivatives ( EL, ELP, RH 40), polyoxyethylene stearate Sorbitan fatty acid esters Polyoxyethylene alkyl ether Polyoxyethylene nonylphenol ether or a combination thereof.

35. The drug-containing particle of any one of claims 31-34, wherein the lipophilic material comprises polyethylene oxide-containing fatty acid esters, polyethylene oxide glycerides, polypropylene glycol fatty acid esters, PEG, monoglycerol fatty acid esters, diglycerol fatty acid esters, triglycerol fatty acid esters, propylene glycol diglycerides, polyethylene oxide vegetable oils, or a combination thereof.

36. The drug-containing particle of claim 35, wherein the lipophilic material comprises polyoxyethylene glyceride.

37. The drug-containing particles of claim 35 or 36, wherein the lipophilic material comprises mono-, di- and tri-glycerides of palmitic (C16) and stearic (C18) acids and PEG-32 (MW 1500) mono- and di-glycerides of palmitic (C16) and stearic (C18) acids; mono-, di- and tri-glycerides of fatty acids (C8 to C18); mono-, di- and tri-glycerides of lauric (C12) and stearic (C18) acids and PEG-6 (MW 300) mono- and di-glycerides of lauric (C12) and stearic (C18) acids; mono-, di- and tri-glycerides of oleic (C18:1) acids and PEG-6 (MW 300) mono- and di-glycerides of oleic (C18:1) acids. 300) and mono- and diesters; mixtures of mono- and diesters of 12-hydroxystearic acid with macrogol glycerides; PEG-40 hydrogenated castor oil; propylene glycol monocaprylate; propylene glycol monolaurate; medium chain triglycerides; propylene glycol dicaprylate / dicaprate; caprylic (C8) and capric (C 10 ) acid PEG-8 (MW 400) monoesters and diesters; or combinations thereof.

38. The drug-containing particles of claim 35 or 36, wherein the lipophilic material is mono-, di- and tri-glycerides of fatty acids (C8 to C18); mono-, di- and tri-glycerides of lauric (C12) and stearic (C18) acids and PEG-6 (MW 300) mono- and di-esters of lauric (C12) and stearic (C18) acids; or propylene glycol monocaprylate.

39. The drug-containing particle of claim 35, wherein the vegetable oil comprises one or more vegetable seed oils, fruit seed oils, kernel oils, sesame seed oils, medium chain triglyceride (MCT) oils, oleic acid oils, pumpkin seed oils, interesterified vegetable oils, polyoxyethylene hydrogenated vegetable oils, PEG40-hydrogenated castor oils, or combinations thereof.

40. The drug-containing particle of claim 39, wherein the lipophilic material is sesame seed oil or pumpkin seed oil.

41. The drug-containing particle of any one of claims 31-38, wherein the lipophilic material is present in an amount of about 1 wt% to about 75 wt% based on the total weight of the drug-containing particle.

42. The drug-containing particle of any one of claims 31-39, wherein the lipophilic material is present in an amount of about 25 wt% to about 35 wt% based on the total weight of the drug-containing particle.

43. The drug-containing particle of any one of claims 1-42, wherein the weight ratio of the solid carrier to the combined weight of the drug substance and the lipophilic material is in the range of 3:1 to 1:

1.

44. The drug-containing particle of claim 43, wherein the lipophilic material is present in an amount of about 25 weight % to about 75 weight % based on the total weight of the drug-containing particle.

45. The drug-containing particle of claim 40, wherein the sesame oil is present in an amount of about 45 wt% to about 60 wt% based on the total weight of the drug-containing particle.

46. ​​The drug-containing particle of any one of claims 1-45, comprising a polymer.

47. The drug-containing particle of claim 44, wherein the polymer has a T of about 50°C to about 130°C. g .

48. The drug-containing particles of claim 46 or 47, wherein the polymer comprises polyvinyl pyrrolidone (kollidon VA64), cross-linked polyvinyl N-pyrrolidone (crospovidone), hydroxypropyl methylcellulose phthalate (HPMCP 50), polyvinyl alcohol-polyethylene glycol copolymer (kollicoat), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (soluplus), polyvinyl alcohol, or a combination thereof.

49. The drug-containing particle of any one of claims 46-48, wherein the polymer is present in an amount of about 1 wt% to about 75 wt% based on the total weight of the drug-containing particle.

50. The drug-containing particle of any one of claims 46-49, wherein the polymer is present in an amount of about 10 wt% to about 50 wt% based on the total weight of the drug-containing particle.

51. The drug-containing particle of any one of claims 46-50, wherein the polymer is provided as a coating on the drug-containing particle.

52. The drug-containing particle of any one of claims 1-51, further comprising a chelating agent.

53. The drug-containing particle of claim 52, wherein the chelating agent comprises EDTA, citric acid, or curcumin.

54. The drug-containing particle of claim 52, wherein the chelating agent comprises citric acid or curcumin.

55. The drug-containing particle of any one of claims 52-54, wherein the amount of the chelating agent ranges from about 0.05 wt% to about 3 wt% based on the total weight of the drug-containing particle.

56. The drug-containing particle of any one of claims 52-54, wherein the amount of the chelating agent ranges from about 0.05 wt% to about 0.1 wt% based on the total weight of the drug-containing particle.

57. The drug-containing particle of any one of claims 1-56, comprising one or more antioxidants.

58. The drug-containing particle of claim 57, wherein the one or more antioxidants comprise alpha-tocopherol, beta-carotene, ascorbic acid, ascorbyl palmitate, lecithin, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, propyl gallate, or a combination thereof.

59. The drug-containing particle of claim 57 or 58, wherein the antioxidant comprises alpha-tocopherol.

60. The drug-containing particle of any one of claims 57-59, wherein the amount of the one or more antioxidants ranges from about 0.05 wt% to about 3 wt% based on the total weight of the drug-containing particle.

61. The drug-containing particle of claim 60, wherein the amount of the one or more antioxidants ranges from about 0.2 weight % to about 1 weight % based on the total weight of the drug-containing particle.

62. The drug-containing particle of any one of claims 1-61, wherein about 30% to about 90% of the one or more cannabinoids are released in about 3 hours to about 12 hours.

63. The drug-containing particle of any one of claims 1-61, wherein about 50% to about 90% of the one or more cannabinoids are released within about 3 hours to about 12 hours.

64. The drug-containing particle of any one of claims 1-61, wherein greater than about 80% of the one or more cannabinoids are released by about 12 hours.

65. The drug-containing particle of any one of claims 1-64, comprising no greater than about 0.2% by weight cannabidiolic acid (CBD-C1).

66. The drug-containing particle of any one of claims 1-65, comprising no greater than about 0.8% cannabidiol (CBDV) by weight.

67. The drug-containing particle of any one of claims 1-66, comprising less than about 0.5% by weight butyl-cannabidiol (CBD-C4).

68. A pharmaceutical composition comprising a plurality of drug-containing particles according to any one of claims 1 to 67 or a combination thereof, and at least one pharmaceutically acceptable excipient.

69. The pharmaceutical composition of claim 68, wherein the pharmaceutical composition is a tablet, a capsule or a granule.

70. The pharmaceutical composition of any one of claims 1-69, wherein the drug-containing particles are prepared by a process comprising spray drying or hot melt extrusion.

71. A method of preparing the drug-containing particles of any preceding claim, the method comprising: (a) combining a porous solid carrier, one or more cannabinoids, and optionally a polymer to form a mixture; (b) adding a solvent to the mixture to form a slurry; (c) sonicating and / or agitating the slurry; and (d) evaporating the solvent to obtain a dry powder, thereby absorbing the one or more cannabinoids onto the porous solid carrier.

72. A method for preparing the drug-containing particles of any one of claims 1-45 and 52-69, the method comprising: (a) combining one or more cannabinoids and one or more lipophilic materials to form a mixture; (b) stirring the mixture of step (a) until homogeneous; (c) adding the homogenous mixture of step (b) to the porous solid support; and (d) stirring the mixture of step (c) until homogenous, thereby absorbing the one or more cannabinoids onto the porous solid carrier.

73. The drug-containing particle of any one of claims 1-61, wherein at least 20% of the one or more cannabinoids are released from the drug-containing particle within 10 minutes.

74. The drug-containing particle of any one of claims 1-61 and 73, wherein 20-50% of the one or more cannabinoids are released from the drug-containing particle within 10 minutes.

75. The drug-containing particle of any one of claims 1-61 and 74, wherein at least 30% of the one or more cannabinoids are released from the drug-containing particle within 15 minutes.

76. The drug-containing particle of any one of claims 1-61 and 73-75, wherein at least 30-70% of the one or more cannabinoids are released from the drug-containing particle within 15 minutes.

77. The drug-containing particle of any one of claims 1-61 and 73-76, wherein at least 40% of the one or more cannabinoids are released from the drug-containing particle within 20 minutes.

78. The drug-containing particle of any one of claims 1-61 and 73-77, wherein 40-80% of the one or more cannabinoids are released from the drug-containing particle within 20 minutes.

79. The drug-containing particle of any one of claims 1-61 and 73-78, wherein at least 45% of the one or more cannabinoids are released from the drug-containing particle within 30 minutes.

80. The drug-containing particle of any one of claims 1-61 and 73-79, wherein 45-85% of the one or more cannabinoids are released from the drug-containing particle within 30 minutes.

81. The drug-containing particle of any one of claims 1-61 and 73-80, wherein at least 50% of the one or more cannabinoids are released from the drug-containing particle within 45 minutes.

82. The drug-containing particle of any one of claims 1-61 and 73-81, disclosing the drug-containing particle wherein 50-85% of the one or more cannabinoids are released from the drug-containing particle within 50 minutes.

83. The drug-containing particle of any preceding claim, wherein drug release is measured using the United States Pharmacopeia (USP) Dissolution Test (711).

84. The drug-containing particle of claim 83, wherein drug release is measured using Apparatus II.

85. The drug-containing particle of claim 83 or 84, wherein drug release is measured using 0.1 M HCl buffer at pH 1.

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