Oral solid dosage forms containing cannabinoids

Abstract

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

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 371,292, filed August 12, 2022, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] The modern use of cannabinoids in medicine requires finding more effective ways to deliver these poorly soluble compounds. In addition to poor aqueous 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, the high lipophilicity and poor water solubility of most cannabinoids can result in oral formulations that exhibit poor pharmacokinetics (e.g., low and variable bioavailability) and undesirable side effects. These suboptimal properties generally result in unpredictable and inconsistent efficacy after oral administration (e.g., variability in the onset time and / or peak of observed effects), as well as potential safety issues, such as overdosing, particularly in elderly patients.

[0004] Although there have been some recent advances using self-emulsifying drug delivery systems, oily excipients, and / or ethanol as a co-solvent, oral formulations that can reliably deliver sufficient amounts of cannabinoids in a patient-friendly formulation that provides adequate bioavailability remain a challenge.

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

[0006] In some embodiments, the present disclosure provides drug-containing particles comprising (a) one or more cannabinoids and (b) a porous solid carrier. In some embodiments, the one or more cannabinoids are adsorbed onto a porous solid carrier. As used herein, "adsorbed onto a porous solid carrier" encompasses when the cannabinoid is present on the surface of the solid carrier and / or within the pores of the porous solid carrier. The term "adsorbed onto a porous solid carrier" may be used synonymously with "adsorbed onto and / or within a porous solid carrier." In some embodiments, the present disclosure provides drug-containing particles comprising (a) one or more cannabinoids, (b) a porous solid carrier, and (c) one or more lipophilic materials. In some embodiments, the one or more cannabinoids are adsorbed onto the porous solid carrier and / or within the pores of the porous solid carrier (e.g., on and / or within the porous solid carrier). In some embodiments, the present disclosure provides drug-containing particles comprising (a) one or more cannabinoids, (b) a porous solid carrier, (c) one or more lipophilic materials, and (d) an antioxidant. In some embodiments, the one or more cannabinoids are adsorbed onto and / or within the pores of a porous solid support (e.g., onto and / or within a microporous solid support). In some embodiments, the porous solid support has one or more of the following characteristics: (i) a size of 1 to 2 cm 3 / g, (ii) an average pore volume of 250 to 375 nm, or (iii) a pore diameter of about 2 to 50 nm. In some embodiments, the porous solid support has two or more of the following characteristics: (i) a surface area of 1 to 2 cm 3 / g, (ii) an average surface area of 250 to 375 nm, or (iii) a pore diameter of about 2 to 50 nm. In some embodiments, the porous solid support has (i) a surface area of 1 to 2 cm 3The porous solid carrier may comprise (i) an average pore volume of 1000 μm / g, (ii) an average surface area of 250 to 375 μm, and (iii) a pore diameter of about 2 to 50 nm. In embodiments, the one or more cannabinoids may be part of a drug substance 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 ranging from 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 ranging from about 75% to about 99%.

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

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

[0010] In some embodiments, the mesoporous silica has an average pore size in the range of 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 magnesium silicate, magnesium aluminum silicate, or calcium magnesium silicate. In some embodiments, the silicate is an aluminosilicate, such as magnesium aluminosilicate. In some embodiments, the silicate is Neusilin®.

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

[0013] In some embodiments, the drug-containing particles comprise one or more cannabinoids, wherein the one or more cannabinoids are cannabichromene (CBC), cannabichromene acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabiditriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic 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 is nabilone. In some embodiments, the drug-containing particles comprise one or more metabolites of cannabinoids disclosed herein.

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

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

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

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

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

[0019] In some embodiments, the amount of chelating agent in the drug-containing particles ranges from about 0.05% to about 3% by weight, hi some embodiments, the amount of chelating agent in the drug-containing particles 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., α-tocopherol), carotenoids (e.g., lutein or β-carotene), tocotrienols, ascorbic acid, ascorbyl palmitate, lecithin, butylhydroxyanisole, butylhydroxytoluene (BHT), monothioglycerol, propyl gallate, curcumin, or a combination thereof. In some embodiments, the one or more antioxidants are α-tocopherol, β-carotene, ascorbic acid, ascorbyl palmitate, lecithin, butylhydroxyanisole, butylhydroxytoluene, monothioglycerol, propyl gallate, or a combination thereof.

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

[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 some embodiments, the active pharmaceutical ingredient is dissolved or suspended in the lipophilic material, and then the active pharmaceutical ingredient is adsorbed onto the porous carrier. In some embodiments, the lipophilic material comprises a polyethylene oxide-containing fatty acid ester, a polyethylene oxide glyceride, a polypropylene glycol fatty acid ester, PEG, a monoglyceride fatty acid ester, a diglyceride fatty acid ester, a triglyceride fatty acid ester, a propylene glycol diglyceride, a polyethylene oxide vegetable oil, or a combination thereof. In some embodiments, the lipophilic material comprises a polyethylene oxide-containing fatty acid ester. In some embodiments, the one or more lipophilic materials comprise a polyethylene oxide-containing fatty acid ester. In some embodiments, the one or more lipophilic materials comprise a polyethylene oxide glyceride. In some embodiments, the lipophilic material is selected from the group consisting of plant seed oils, fruit seed oils, kernel oils, mono-, di-, and triglyceride esters of palmitic acid (C16) and stearic acid (C18), and PEG-32 (MW1500) mono- and diesters of palmitic acid (C16) and stearic acid (C18); mono-, di-, and triglyceride esters of fatty acids (C8-C18); mono-, di-, and triglyceride esters of lauric acid (C12) and stearic acid (C18), and PEG-6 ( Mono- and diesters of PEG-6 (MW300); mono-, di-, and triglyceride esters of oleic acid (C18:1), and mono- and diesters of oleic acid (C18:1); 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 dicaprate / propylene glycol dicaprate; caprylic acid (C8) and capric acid (C 10PEG-8 (MW400) mono- and diesters of lauric acid (C12) and stearic acid (C18), or combinations thereof. In embodiments, the lipophilic material is mono-, di-, and triglyceride esters of fatty acids (C8-C18); mono-, di-, and triglyceride esters of lauric acid (C12) and stearic acid (C18), and PEG-6 (MW300) mono- and diesters of lauric acid (C12) and stearic acid (C18); or propylene glycol monocaprylate. In some embodiments, the lipophilic material comprises sesame seed oil, medium chain triglyceride (MCT) oil, oleic acid oil, pumpkin seed oil, or any other vegetable or fruit seed oil, and combinations thereof.

[0024] In some embodiments, the one or more lipophilic materials (e.g., two or three lipophilic materials) are present in an amount of about 10% to about 75% by weight, 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 further embodiments, the polymers are heated to a temperature of about 50° C. to about 130° C. g In some embodiments, the polymer comprises carboxymethylcellulose, polyvinylpyrrolidone (kollidon VA64), cross-linked polyvinyl N-pyrrolidone (crospovidone), hydroxypropyl methylcellulose phthalate (HPMCP50), 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% to about 50% by weight, 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 in about 1-16 hours. In some embodiments, the drug-containing particles disclosed herein release 50-90% of the one or more cannabinoids in about 3-12 hours. In some embodiments, the drug-containing particles disclosed herein release about 70% or more of the one or more cannabinoids in about 6 hours. In some embodiments, the drug-containing particles disclosed herein release about 80% or more of the one or more cannabinoids in about 12 hours.

[0028] In some embodiments, the drug-containing particles are substantially free of cannabidiol (CBD-C1), cannabidivarin (CBDV), and / or cannabidibutol (CBD-C4). In some embodiments, the drug-containing particles contain about 0.2% or less by weight of the active substance CBD-C1. In some embodiments, the drug-containing particles contain about 0.8% or less by weight of the active substance CBD-C1. In some embodiments, the drug-containing particles contain about 0.15 to about 0.8% by weight of the active substance CBDV. In some embodiments, the drug-containing particles contain about 0.5% or less by weight of the active substance CBD-C4.

[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 a tablet, capsule, or granules.

[0030] In some embodiments, the pharmaceutical composition is prepared by a process including mixing / blending (eg, high or low shear mixing / blending), spray drying, or hot melt extrusion. [Brief explanation of the drawings]

[0031] [Figure 1] 1 provides an overview of the formulation techniques used to prepare drug-containing particles of the present disclosure. [Figure 2]1 provides a schematic diagram illustrating the impregnation and release of a drug from a porous solid carrier of the present disclosure. [Figure 3] 1 is a diagram showing that a drug can be released from a porous solid carrier of the present disclosure upon contact with gastric fluid. [Figure 4] FIG. 1 shows a schematic comparing aspects of lipid-loaded and solvent-mediated methods for drug adsorption onto mesoporous silica. [Figure 5] 1 provides a flow chart illustrating the laboratory-scale preparation of drug-containing particles of the present disclosure by a solvent-mediated method. [Figure 6] 1 provides graphs of CBD release from 50 w / w% drug-loaded Syloid® and Fujisil™. [Figure 7] 1 provides a flow chart illustrating the laboratory-scale preparation of drug-containing particles of the present disclosure by a formulation method including spray drying. [Figure 8] 1 shows an exemplary spray drying apparatus that can be used to prepare drug-containing particles of the present disclosure. [Figure 9A] FIG. 1 provides a flow chart illustrating CBD / sesame oil-loaded mesoporous silica drug particle formulations 1-6 in Table 5 used to prepare drug-containing particles of the present disclosure. [Figure 9B] 1 provides a flow chart illustrating the manufacturing method of CBD / lipid-loaded mesoporous silica drug particle formulations 7-10 used to prepare drug-containing particles of the present disclosure. [Figure 9C] 1 provides a flow chart illustrating the manufacturing methods of CBD / lipid-loaded mesoporous silica drug particle formulations 1-10 in Table 8 used to prepare drug-containing particles of the present disclosure. [Figure 10] 1 provides a graph of CBD release from lipid-loaded mesoporous silica samples of the present disclosure. [Figure 11] 1 provides a flow chart illustrating the laboratory-scale preparation of drug-containing particles of the present disclosure by a solvent-mediated polymer formulation method. [Figure 12] 1 is a chart illustrating classes of polymers suitable for use in the drug-containing particles of the present disclosure. [Figure 13A]1 shows the change in CBD content in lipid-loaded formulations described in Example 3, Table 6, prepared with mesoporous silica described herein and further containing 0.2% α-tocopherol. [Figure 13B] 1 shows the change in CBD content in the same lipid-loaded formulation prepared without α-tocopherol. [Figure 14A] 1 shows the change in CBE I content in lipid-loaded formulations described herein containing 0.2% α-tocopherol. [Figure 14B] 1 shows the change in CBE I content in the same lipid-loaded formulation prepared without 0.2% α-tocopherol. [Figure 15A] 1 shows the change in CBE II content in lipid-loaded formulations described herein containing 0.2% α-tocopherol. [Figure 15B] The change in CBE II content in the same lipid-loaded formulation prepared without 0.2% α-tocopherol is shown. [Figure 16A] 1 shows the change in OH-CBD content in lipid-loaded formulations described herein containing 0.2% α-tocopherol. [Figure 16B] Figure 1 shows the change in OH-CBD content in the same lipid-loaded formulation prepared without 0.2% α-tocopherol. [Figure 17A] 1 shows the change in OH-CBD content in lipid-loaded formulations described herein containing 0.2% α-tocopherol. [Figure 17B] Figure 1 shows the change in OH-CBD content in the same lipid-loaded formulation prepared without 0.2% α-tocopherol. [Figure 18A] 1 shows CBE I content in hard fat-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 18B] 1 shows CBE II content in hard fat-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 18C]1 shows OH-CBD content in hard fat-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 18D] 1 shows the content of additional unknown degradants in hard fat-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 19A] 1 shows CBE I content in lauroyl polyoxyl-6 glyceride-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 19B] 1 shows CBE II content in lauroyl polyoxyl-6 glyceride-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 19C] 1 shows OH-CBD content in lauroyl polyoxyl-6 glyceride-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 19D] 1 shows the content of additional unknown degradants in lauroyl polyoxyl-6 glyceride-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 20A] 1 shows the CBE I content in propylene glycol monocaprylate-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 20B] 1 shows the CBE II content in propylene glycol monocaprylate-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 20C] 1 shows OH-CBD content in propylene glycol monocaprylate-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 20D] 1 shows the content of additional unknown degradants in propylene glycol monocaprylate-loaded formulations described herein containing 0.2%, 0.6%, and 1% α-tocopherol at 40° C. / 75% RH. [Figure 21A] 1 shows the relative bioavailability (Frel%) of formulations containing different ratios of CBD to lipophilic material as measured in Beagle dogs. [Figure 21B] 1 shows the relative bioavailability (Frel %) of formulations containing different ratios of CBD to lipophilic material as measured in Beagle dogs. [Figure 21C] Figure 1 shows the relative bioavailability (%Frel) of formulations containing different ratios of CBD to lipophilic material as measured in Beagle dogs. 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 formulated into capsules ("CBD OS in capsules"). [Figure 22A] 1 shows the relative bioavailability (Frel %) of formulations containing different ratios of CBD to lipophilic material in rats, as described in Example 8. [Figure 22B] 1 shows the relative bioavailability (Frel %) of formulations containing different ratios of CBD to lipophilic material in rats, as described in Example 8. [Figure 22C] 1 shows the relative bioavailability (Frel %) of formulations containing different ratios of CBD to lipophilic material in rats, as described in Example 8. [Figure 23A] 1 shows the X-ray pattern diffractogram (XRPD) of solvent-loaded drug-containing particles at time 0. [Figure 23B] 1 shows the X-ray pattern diffractogram (XRPD) of solvent-loaded drug-containing particles after one week. [Figure 24] 1 shows an X-ray pattern diffractogram (XRPD) demonstrating the amorphous nature of CBD when absorbed onto and / or within a porous carrier using the lipid-loading process described herein.

[0032] definition The term "cannabinoid" as used herein generally refers to one of a diverse class of chemical compounds that act on cannabinoid receptors in cells, inhibiting the release of neurotransmitters in the brain. Ligands for these receptor proteins include endocannabinoids (naturally produced in the body by humans and animals), phytocannabinoids (found in cannabis and some other plants), and synthetic cannabinoids (artificially produced). Thus, the term "cannabinoid" encompasses endocannabinoids and phytocannabinoids.

[0033] "Endocannabinoids" are endogenous cannabinoids that are high-affinity ligands for CB1 and CB2 receptors.

[0034] "Phytocannabinoids" are cannabinoids that are naturally occurring and can be found in the cannabis plant. Phytocannabinoids are present in extracts containing botanical drug substances that can be isolated or synthetically reproduced.

[0035] A "synthetic cannabinoid" is one produced by chemical synthesis. The term may include modifying an isolated phytocannabinoid, for example, by forming a pharmaceutically acceptable salt thereof.

[0036] A "substantially pure" cannabinoid is defined as a cannabinoid that is present at greater than 95% (w / w) purity. In some embodiments, "substantially pure" refers to a purity of greater than 96% (w / w), greater than 97% (w / w), greater than 98% (w / w), or greater than 99% (w / w).

[0037] "Botanical drug substance" or "BDS" is defined in the Guidance for Industry Botanical Drug Products Draft Guidance, August 2000, U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Center for Drug Discovery and Development, as "a substance derived from one or more plants, algae, or microscopic fungi. Botanical drug substances are prepared from botanical materials by one or more of the following processes: crushing, leaching, rolling, aqueous extraction, ethanol extraction, or other similar processes."

[0038] The term "pharmaceutically acceptable" means biologically or pharmacologically compatible for in vivo use in animals or humans, and can mean approved by a federal or state regulatory agency or listed in the United States Pharmacopoeia or other generally recognized pharmacopoeias (e.g., the European Pharmacopoeia, the British Pharmacopoeia, and the Japanese Pharmacopoeia) for use in animals, and particularly in humans.

[0039] Terms such as "lipophilic material(s)" may refer to materials that can dissolve in non-polar materials, such as fats, oils, and lipids. Common examples of lipophilic materials include fatty acids, fatty alcohols, oils, lipids, butters, and fats. As used herein, lipophilic materials can be either a class of lipophilic materials, such as polyethylene oxide-containing fatty acid esters, or a class of lipophilic materials, such as polyethylene oxide esters of C8 fatty acids. Additional lipophilic materials are described in U.S. Patent No. 6,294,192, which is incorporated by reference in its entirety.

[0040] For example, in embodiments, the lipophilic material of the present application may be MCT oil; oleic oil; mono-, di-, and triglyceride esters of palmitic acid (C16) and stearic acid, and PEG-32 (MW1500) mono- and diesters of palmitic acid (C16) and stearic acid (C18); mono-, di-, and triglyceride esters of fatty acids (C8-C18); mono-, di-, and triglyceride esters of lauric acid (C12) and stearic acid (C18), and PEG-32 (MW1500) mono- and diesters of palmitic acid (C16) and stearic acid (C18). EG-6 (MW300) mono- and diesters; mono-, di-, and triglyceride esters of oleic acid (C18:1), and PEG-6 (MW300) and mono- and diesters; mono- and diesters of 12-hydroxystearic acid and a mixture of polyethylene glycol glycerides, PEG-40 hydrogenated castor oil; propylene glycol monocaprylate; propylene glycol monolaurate; medium chain triglycerides; propylene glycol dicaprate / propylene glycol dicaprate; caprylic acid (C8) and capric acid (C 10 ) PEG-8 (MW400) monoesters and diesters; or combinations thereof.

[0041] The term "lipid-loaded" refers to a composition in which the cannabinoid and lipophilic material are present on a porous solid carrier. In embodiments, the cannabinoid is dissolved or suspended in the lipophilic material and the resulting solution is then combined with the porous solid carrier, whereby the cannabinoid is absorbed onto the porous solid carrier. This results in an amorphous form of the cannabinoid.

[0042] Throughout this specification, the terms "about" and / or "approximately" may be used in conjunction with numerical values and / or ranges. The term "about" is understood to mean values close to the recited value and degrees of variation recognized in the art. For example, "about 40 units" may mean within ±25% of 40 (e.g., 30-50), ±20%, ±15%, ±10%, ±9%, ±8%, ±7%, ±6%, ±5%, ±4%, ±3%, ±2%, ±1%, ±1%, less than ±1%, or any other value or range therebetween. Additionally, the phrases "less than about [value]" or "greater than about [value]" should be understood in light of the definition of the term "about" provided herein. The terms "about" and "approximately" may be used interchangeably. In some embodiments, about may mean within ±10% of a value.

[0043] Unless expressly stated otherwise, all ranges cited herein are inclusive, i.e., they include the upper and lower values of the range, and all values therebetween. DETAILED DESCRIPTION OF THE INVENTION

[0044] solid dosage form Described herein are oral solid dosage forms comprising cannabinoid-containing drug particles which, when produced according to the formulation technology outlined in Figure 1, exhibit improved solubility and oral bioavailability compared to formulations produced by other methods known in the art. Among their beneficial properties, the drug-containing particles of the present disclosure have been found to be stable, free-flowing powders which may exhibit high oil adsorption capacity and rapid drug release upon contact with gastric fluids.

[0045] In some embodiments, the present disclosure provides drug-containing particles comprising (a) one or more cannabinoids, terpenes, triglycerides, and / or sterols, and (b) a porous solid carrier. In some embodiments, the present disclosure provides drug-containing particles comprising (a) one or more cannabinoids, and one or more terpenes, triglycerides, and / or sterols, and (b) a porous solid carrier. In some embodiments, the one or more cannabinoids are present on the surface and / or within the pores of the porous solid carrier. In some embodiments, the one or more cannabinoids are present within the pores of the porous solid carrier. The association of cannabinoids on the surface of a porous solid carrier or within the pores of a solid carrier is sometimes referred to herein as "adsorption." Thus, in some embodiments, the one or more cannabinoids are adsorbed onto and / or within the porous solid carrier.

[0046] In some embodiments, the disclosure provides drug-containing particles comprising (a) one or more cannabinoids, 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 within the pores of the porous solid carrier. In some embodiments, the one or more cannabinoids are present within the pores of the porous solid carrier. In some embodiments, the disclosure provides drug-containing particles comprising (a) one or more cannabinoids, and (b) a porous solid carrier. In some embodiments, the one or more cannabinoids are present (adsorbed) on the surface and / or within the pores of the porous solid carrier. In some embodiments, the one or more cannabinoids are present within the pores of the porous solid carrier.

[0047] In some embodiments, the drug-containing particles have a composition shown in Table 11, Table 12, or Table 15.

[0048] Porous solid carrier The porous solid carrier of the present disclosure may be any porous material onto or into which one or more cannabinoids may be adsorbed, thereby providing suitable bioavailability and drug release.

[0049] In some embodiments, the porous solid carrier comprises silica (SiO), microcrystalline cellulose (MCC, e.g., Pharmacel 102), silicified microcrystalline cellulose (SMCC, e.g., Pharmacel SMCC90), chitosan, isomalt (e.g., Galen IQ721), fluorite, or a silicate. In some embodiments, the porous solid carrier comprises microcrystalline sodium carboxymethylcellulose, microcrystalline cellulose, silicified microcrystalline cellulose, chitosan, or isomalt. In some embodiments, the porous solid carrier comprises silica, microcrystalline cellulose, silicified microcrystalline cellulose, chitosan, isomalt, or a silicate. In some embodiments, the porous solid carrier comprises silica or a silicate. In some embodiments, the porous solid carrier is mesoporous silica or amorphous silica.

[0050] In some embodiments, the porous solid carriers disclosed herein are present as microparticles. In some embodiments, the porous solid support has an average particle size in the range of about 1 μm to about 1000 μm, e.g., 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 ranging from about 1 μm to about 250 μm. In some embodiments, the porous solid carrier has an average particle size ranging from about 25 μm to about 250 μm. In some embodiments, the porous solid carrier has an average particle size ranging from about 50 μm to about 150 μm. In some embodiments, the porous solid carrier has an average particle size ranging from about 40 μm to about 100 μm. In some embodiments, the porous solid carrier has an average particle size ranging from about 40 μm to about 85 μm. In some embodiments, the porous solid carrier has an average particle size ranging from about 50 μm to about 80 μm. In some embodiments, the porous solid carrier has an average particle size ranging from about 50 μm to about 70 μm. In some embodiments, the porous solid carrier has an average particle size ranging from about 10 μm to about 75 μm. In some embodiments, the porous solid carrier has an average particle size ranging from about 20 μm to about 70 μm. In some embodiments, the porous solid support has an average particle size ranging from about 25 μm to about 65 μm.

[0051] In some embodiments, the porous solid support has a porosity in the range of about 25% to about 99%, e.g., 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 support has a porosity in the range of about 50% to about 99%. In some embodiments, the porous solid support has a porosity in the range of about 75% to about 99%. In some embodiments, the porous solid support has a porosity in the range of about 25% to about 95%. In some embodiments, the porous solid support has a porosity in the range of about 50% to about 95%. In some embodiments, the porous solid support has a porosity in the range of about 75% to about 95%. In some embodiments, the porous solid support has a porosity ranging from about 85% to about 95%, hi 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%.

[0052] In some embodiments, the porous solid support is about 100 ml 2 / g~about 1000m 2 / g, for example, about 100m 2 / g, approx. 200m 2 / g, approx. 300m 2 / g, approx. 400m 2 / g, approx. 500m 2 / g, approx. 600m 2 / g, approx. 700m 2 / g, approx. 800m 2 / g, approx. 900m 2 / g, or approximately 1000m 2 / 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 m 2 / g~about 800m 2 / g, for example, about 200m 2 / g~about 800m 2 / g, approx. 200m 2 / g~about 600m 2 / g, approx. 200m2 / g~about 500m 2 / g, approx. 200m 2 / g~about 400m 2 / g, approx. 300m 2 / g~about 400m 2 / g, or approximately 250m 2 / g~about 350m 2 / g (including all ranges and values therebetween).

[0053] In some embodiments, the porous solid support has an average pore volume ranging from about 0.1 mL / g to about 5 mL / g, e.g., 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 support has an average pore volume ranging from about 1 mL / g to about 5 mL / g. In some embodiments, the porous solid support has an average pore volume in the range of about 1.5 mL to about 5 mL. In some embodiments, the porous solid support has an average pore volume in the range of about 1.5 mL to about 4 mL. In some embodiments, the porous solid support has an average pore volume in the range of about 1.5 mL to about 3 mL. In some embodiments, the porous solid support has an average pore volume in the range of about 1.5 mL to about 2.0 mL. In some embodiments, the porous solid support has an average pore volume in the range of about 1 mL to about 2 mL. In some embodiments, the porous solid support has an average pore volume in the range of about 1 mL to about 1.9 mL.

[0054] In some embodiments, the porous solid support has an average pore diameter in the range of about 1 nm to about 100 nm, for example, about 1 nm, about 2 nm, about 3 nm, about 4 nm, about 5 nm, about 10 nm, about 15 nm, about 20 nm, about 25 nm, about 30 nm, about 35 nm, about 40 nm, about 45 nm, about 50 nm, about 55 nm, about 60 nm, about 65 nm, about 70 nm, about 80 nm, about 85 nm, about 90 nm, about 95 nm, or about 100 nm (including all ranges and values therebetween). In some embodiments, the porous solid support has an average pore diameter in the range of about 2 nm to about 60 nm. In some embodiments, the porous solid support has an average pore diameter in the range of about 2 nm to about 50 nm. In some embodiments, the porous solid support has an average pore diameter in the range of about 10 nm to about 50 nm. In some embodiments, the porous solid support has an average pore diameter in the range of about 15 nm to about 30 nm. In some embodiments, the porous solid support has an average pore size in the range of about 20 nm to about 30 nm, hi some embodiments, the porous solid support has an average pore size in the range of about 15 nm to about 25 nm.

[0055] In some embodiments, the porous solid support has an oil absorption capacity of about 1 mL / g to about 10 mL / g, e.g., 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 support has an oil absorption capacity of about 1 mL / g to about 5 mL / g. In some embodiments, the porous solid support has an oil absorption capacity of about 1 mL / g to about 4 mL / g. In some embodiments, the porous solid support has an oil absorption capacity of from about 2 mL / g to about 5 mL / g.

[0056] Without being bound by any particular theory, based on the properties disclosed herein, the internal mesopores of a porous solid support (e.g., a silica material described herein) can be impregnated with a concentrated drug solution containing one or more cannabinoids (Figure 2). A stable amorphous phase can then result from the entrapment of the drug in subcritical pores and / or the strength of absorption interactions (e.g., H-bonding). Upon contact with gastric fluid, the entrapped amorphous drug can be rapidly released (Figure 3).

[0057] In some embodiments, the porous solid carrier is present in an amount ranging from about 10% to about 90% by weight, based on the total weight of the drug-containing particles, 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). In some embodiments, the porous solid carrier comprises about 20% to about 80%, about 25% to about 80%, about 30% to about 80%, about 35% to about 80%, 40% to about 80%, about 45% to about 80%, about 50% to about 80%, about 55% to about 80%, about 60% to about 80%, about 20% to about 75%, about 20% to about 70%, or In some embodiments, the porous solid carrier is present in an amount ranging from about 20% to about 65%, about 20% to about 60%, about 20% to about 55%, about 20% to about 50%, about 20% to about 45%, 25% to about 55%, about 25% to about 50%, about 30% to about 60%, about 30% to about 55%, about 30% to about 50%, or about 35% to about 50% by weight, based on the total weight of the drug-containing particles.

[0058] In some embodiments, the porous solid support is mesoporous silica. In some embodiments, the mesoporous silica is Syloid® or Fujisil™ or Aeroperol®. In some embodiments, the mesoporous silica is Syloid® XDP or Syloid® FP. In some embodiments, the mesoporous silica is Syloid® XDP. In some embodiments, the mesoporous silica is Aeroperol®.

[0059] In some embodiments, the porous solid support has one or more properties of Syloid®, Fujisil™, or Aeroperol® described herein. In some embodiments, the porous solid support has one or more properties of Syloid® XDP or Syloid® FP. In some embodiments, the porous solid support has one or more properties of Syloid® XDP. In some embodiments, the porous solid support has one or more properties of Aeroperol®. In some embodiments, the porous solid support has one, two, three, four, or five properties of Syloid® XDP or Aeroperol®. In some embodiments, the solid support has an average pore volume corresponding to the average pore volume of Syloid® XDP or Aeroperol®. In some embodiments, the solid support has an average surface area corresponding to the average surface area of Syloid® XDP or Aeroperol®. In embodiments, the solid support has a pore size corresponding to the pore size of Syloid® XDP or Aeroperol®.

[0060] Syloid® XDP is a commercially available silica-based product (WR Grace & Co.-Conn, Columbia, Maryland) that can be used as a porous solid carrier in the drug-containing particles described herein. In some embodiments, the Syloid® XDP of the present disclosure is used to prepare a solid dosage form (e.g., an aqueous solid formulation) from liquid components. In some embodiments, the porous solid carrier has one or more of the following properties:

[0061] [Table 1]

[0062] Fujisil™ is a commercially available silica-based product (Fuji Chemical Industries Co., Ltd.) that can be used as a porous solid carrier in the drug-containing particles described herein. In some embodiments, the Fujisil™ of the present disclosure is used to prepare a solid dosage form (e.g., an aqueous solid formulation) from liquid components. In some embodiments, the porous solid carrier has one or more of the following properties:

[0063] [Table 2]

[0064] Aeroperol® is a commercially available silica-based product (WR Grace & Co.-Conn, Columbia, Maryland) that can be used as a porous solid carrier in the drug-containing particles described herein. In some embodiments, the Aeroperol® of the present disclosure is used to prepare a solid dosage form (e.g., an aqueous solid formulation) from liquid components. In some embodiments, the porous solid carrier has one or more of the following properties:

[0065] [Table 3]

[0066] In some embodiments, the porous solid carrier is a silicate. In some embodiments, the silicate includes magnesium silicate, magnesium aluminum silicate, or calcium-magnesium silicate. In some embodiments, the silicate is an aluminosilicate, such as magnesium aluminosilicate. In some embodiments, the silicate is Neusilin®. Neusilin® is a commercially available magnesium aluminosilicate product (Fuji Chemical Industries Co., Ltd.) with the chemical formula Al2O3·MgO·1.7SiO2·×H2O that can be used as a porous solid carrier in the drug-containing particles described herein. In some embodiments, the Neusilin® of the present disclosure is used to prepare a solid dosage form (e.g., an aqueous solid formulation) from liquid ingredients. In some embodiments, the Neusilin® of the present disclosure is S1, S2, UFL2, or US2. In some embodiments, the porous solid carrier has one or more of the following properties:

[0067] [Table 4]

[0068] Cannabinoids and other active agents The term "drug substance" is used herein to refer to an active agent or mixture of active agents absorbed onto a porous solid carrier. In embodiments, the active agent is a cannabinoid. There are many known cannabinoids 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, cannabinoids suitable for use in the drug-containing particles are phytocannabinoids, endocannabinoids, synthetic cannabinoids, or combinations thereof. In some embodiments, the drug-containing particles comprise one or more metabolites or synthetically produced derivatives of one or more cannabinoids disclosed herein.

[0069] In some embodiments, the drug-containing particles comprise one or more cannabinoids, wherein the one or more cannabinoids are cannabichromene (CBC), cannabichromene acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabiditriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic 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.

[0070] In some embodiments, the drug-containing particles comprise one or more cannabinoids, wherein the one or more cannabinoids are cannabichromene (CBC), cannabichromene acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabiditriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic acid (THCVA), CBD-C4, combinations thereof, or mixtures thereof. In some embodiments, the one or more cannabinoids are cannabidiol (CBD), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV), cannabigerol (CBG), cannabidiolic acid (CBDA), combinations thereof, or mixtures thereof. In some embodiments, the one or more cannabinoids is CBD.

[0071] The drug-containing particles of the present disclosure may also include at least one cannabinoid selected from those disclosed in Handbook of Cannabis, Roger Pertwee, Chapter 1, pages 3-15.

[0072] In some embodiments, one or more cannabinoids are extracted from the cannabis plant, and the resulting extract may contain additional components extracted from the cannabis plant, including, but not limited to, terpenes and sterols.

[0073] In some embodiments, the drug-containing particles comprise one or more terpenes. In some embodiments, the terpenes comprise one or more sesquiterpenes. Non-limiting examples of terpenes and sesquiterpenes include, but are not limited to, β-farnesene, selina-3,7(11)-diene, guaia-3,9-diene, trans-caryophyllene, α-caryophyllene, trans-nerolidol, myrcene, transphytol, squalene, α-bisabolol, α-tocopherol, or combinations thereof.

[0074] In some embodiments, the drug-containing particles comprise one or more sterols, including but not limited to β-sitosterol, β-amyrin, campesterol, lupeol, or combinations thereof.

[0075] 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., α-bergumatone, α-bisbolol, β-farnesene, selina-3,7(11)-diene, guaia-3,9-diene, trans-caryophyllene, α-caryophyllene, trans-nerolidol, myrcene, transphytol, squalene, α-tocopherol, β-sitosterol, β-amyrin, campesterol, lupeol, or combinations thereof.

[0076] In some embodiments, the drug-containing particles comprise a drug substance comprising a mixture of CBD, trans-THC, CBC, CBG, CBDV, CBD-C4, cis-THC, terpenes, triglycerides, and sterols. In some embodiments, the drug substance comprises 70-100 wt% cannabinoids, 1.0-3.0 wt% terpenes, 0.8-3.0 wt% triglycerides, and / or 0.5-2.0 wt% sterols, based on the total amount of the drug substance.

[0077] In some embodiments, the mixture includes the following cannabinoids:

[0078] [Table 5]

[0079] In some embodiments, the drug-containing particles comprise a drug substance comprising the following mixture of cannabinoids, based on the total weight of the drug substance:

[0080] [Table 6]

[0081] In some embodiments, the drug-containing particles comprise nabilone, which is sold under the trade name Cesamet and consists of a racemic mixture of the following two compounds:

[0082] [ka]

[0083] In some embodiments, the drug-containing particles comprise:

[0084] [ka]

[0085] or a salt thereof. This compound and its therapeutic utility are described in WO2022 / 129908, which is incorporated herein by reference in its entirety.

[0086] The drug-containing particles of the present disclosure can include one or more cannabinoid-containing plant extracts (e.g., nabiximols) described in WO2007 / 083098, which is incorporated herein by reference in its entirety. In some embodiments, the drug-containing particles include nabiximols. Nabiximols, also known by the trade name Sativex, are available as an oral mucosal spray containing 27 mg of THC, 25 mg of CBD, and smaller amounts of other cannabinoids per milliliter. Nabiximols are used to treat spasticity, neuropathic pain, and other symptoms of multiple sclerosis.

[0087] Table A below shows the structures of certain cannabinoids, terpenes, and sterols that may be included in the drug-containing particles disclosed herein, along with their standard abbreviations. The following table is not exhaustive and merely details the cannabinoids and other potential components of the drug-containing particles identified in this application for reference purposes.

[0088] [Table 7-1] [Table 7-2] [Table 7-3] [Table 7-4] [Table 7-5]

[0089] All metabolites and prodrugs of THC, CBD, and the remaining cannabinoids are contemplated as being within the scope of this disclosure. Table B shows the structures of certain metabolites of CBD and THC.

[0090] [Table 8]

[0091] In embodiments, the drug-containing particles comprise one of the compositions of Table C or Table D:

[0092] [Table 9]

[0093] [Table 10]

[0094] When a combination or mixture of cannabinoids is present in the drug-containing particles of the present disclosure, the combination or mixture may contain any suitable ratio of cannabinoids. For example, in some embodiments, the drug-containing particles contain two cannabinoids disclosed herein in a ratio of 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.

[0095] The one or more cannabinoids may be present in any amount such that the cannabinoids become amorphous when adsorbed onto the porous solid support. 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 35%, 37.5%, about 40%, about 42.5%, about 45%, about 47.5%, about 50%, about 52.5%, about 55%, about 57.5%, about 60%, about 62.5%, about 65%, about 67.5%, about 70%, about 72.5%, or about 75% by weight. 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 amount of the drug-containing particles (including all ranges and values therebetween). In some embodiments, the one or more cannabinoids are present in an amount ranging from about 5 to about 75% by weight, about 25 to about 60% by weight, about 25 to about 50% by weight, about 30 to about 75% by weight, about 30 to about 60% by weight, about 30 to about 50% by weight, about 35 to about 75% by weight, about 35 to about 60% by weight, about 35 to about 50% by weight, about 40 to about 75% by weight, about 40 to about 60% by weight, or about 40 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 to about 75% by weight, based on the total weight of the drug-containing particle. In some embodiments, the one or more cannabinoids are present in an amount ranging from about 10 to about 60% by weight, based on the total weight of the drug-containing particle. In some embodiments, the one or more cannabinoids are present in an amount ranging from about 25 to about 50% by weight, based on the total weight of the drug-containing particle.In some embodiments, the one or more cannabinoids are present in an amount ranging from about 15 to about 40% by weight, based on the total weight of the drug-containing particle.

[0096] In some embodiments, substantially all of the one or more cannabinoids are present within the pores and / or on the surface of the porous solid support. In some embodiments, substantially all of the one or more cannabinoids are present within the pores of the porous solid support. In this context, substantially 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 on the surface of the porous solid support. In some embodiments, more than about 70%, more than about 75%, more than about 80%, more than about 85%, more than about 90%, more than about 95%, or more than about 99% of the one or more cannabinoids are present in the pores of the porous solid support.

[0097] In some embodiments, the one or more cannabinoids are present in amorphous form. In some embodiments, the adsorption of the one or more cannabinoid amorphous forms onto and / or within the porous solid carrier is determined by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and / or X-ray power diffraction (XRPD). Without being bound by any particular theory, the porous solid carriers of the present disclosure can be optimized to stabilize the amorphous form of the one or more cannabinoids with the desired pores to achieve a targeted drug release profile.

[0098] In some embodiments, drug-containing particles comprising one or more cannabinoids are substantially free of cannabidiol (CBD-C1), cannabidivarin (CBDV), and / or cannabidibutol (CBD-C4). In some embodiments, the drug-containing particles contain about 0.5% or less by weight of the active substance CBD-C1. In some embodiments, the drug-containing particles contain about 0.5% or less by weight of the active substance CBDV. In some embodiments, the drug-containing particles contain about 0.2% or less by weight of the active substance CBD-C4.

[0099] lipophilic material In some embodiments, the drug-containing particles further comprise one or more lipophilic materials. In several embodiments, the drug-containing particles comprise one lipophilic material. In several embodiments, the drug-containing particles comprise a combination of two lipophilic materials. In several embodiments, the drug-containing particles comprise a combination of three lipophilic materials.

[0100] In embodiments in which the drug-containing particle comprises two lipophilic materials, the ratio of the first lipophilic material to the second lipophilic material ranges from 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).

[0101] In embodiments in which the drug-containing particle comprises three lipophilic materials, the ratio of the first lipophilic material to the second lipophilic material to the third lipophilic material ranges from 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).

[0102] The hydrophilic-lipophilic balance ("HLB") value refers to the balance between the size and strength of the hydrophilic and lipophilic portions of a surfactant molecule. HLB values are reported on a scale ranging from 0 to 20. A lower HLB value indicates a higher oil affinity (lipophilicity). A higher HLB value indicates a higher 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 to 10 or 10 to 20. In embodiments, the lipophilic material has an HLB value in the range of 1 to 3, 4 to 6, 7 to 10, 11 to 14, or 15 to 20. In embodiments, the lipophilic material has an HLB value in the range of 11 to 15.

[0103] Non-limiting examples of lipophilic materials useful in the drug-containing particles disclosed herein include pharmaceutically acceptable fats, fatty substances, oils (including seed / kernel oils derived from plants and fruits), phospholipids, sterols, and waxes. Fats generally refer to esters of glycerol (e.g., mono-, di-, or triesters of glycerol with saturated and unsaturated fatty acids). Suitable fats and fatty substances include, but are not limited to, short-, medium-, and long-chain fatty alcohols (e.g., lauryl, myristyl, stearyl, cetyl, or cetostearyl alcohol), fatty acid esters, fatty acid glycerides (mono-, di-, and triglycerides), and fatty acids and derivatives, including hydrogenated fats. Depending on their structure and composition, fats can be either solid or liquid at normal room temperature.

[0104] Suitable oils include pharmaceutically acceptable animal oils (e.g., fatty acid esters), mineral oils (e.g., paraffin oil), vegetable oils (e.g., vegetable 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 oil, sesame oil, kernel oil, soybean oil, safflower oil, corn oil, olive oil, cottonseed oil, peanut oil, sunflower seed oil, palm oil, pumpkin seed oil, rapeseed oil, peanut oil, and animal oils and fats such as triglycerides and butter. Partially hydrogenated vegetable oils are derived from natural products and generally contain C esters such as palmitic acid and stearic acid. 14-20 Partially hydrogenated vegetable oils include mixtures of glycerides of fatty acids. 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 partially hydrogenated vegetable oils include C glycerides, which have the same properties as the naturally occurring products listed above. 14-20 Synthetically produced glycerides of fatty acids are included.

[0105] 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, including, but not limited to, phosphatidylcholine, 1,2-dierucoylphosphatidylcholine, 1,2-dimyristoylphosphatidylcholine, 1,2-dioleoylphosphatidylcholine, 1,2-dioleoylphosphatidylserine, 1,2-distearoylphosphatidylglycerol, 1,2-dipalmito ...choline, 1,2-dioleoylphosphatidylserine, 1,2-distearoylphosphatidylglycerol, 1,2-dipalmitoylphosphatidylcholine, 1,2 Choline, 1,2-distearoylphosphatidylcholine, 1,2-distearoylphosphatidylglycerol, egg yolk phosphatidylcholine, egg yolk phosphatidylglycerol, soy phosphatidylcholine, glycerophosphocholine, hydrogenated soy phosphatidylcholine, lysophosphatidylcholine, lysophosphatidylethanolamine, N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoylphosphatidylethanolamine hydrochloride, muramyl tripeptide phosphatidylethanolamine olamine, 1-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 Examples include 1-stearoyl-2-linoleoylphosphatidylglycerol, 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, and 1-pramitoyl-2-stearoyl-sn-glycero-3-phosphocholine.

[0106] 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, montan wax, ceresin wax, and microcrystalline wax.

[0107] In some embodiments, lipophilic materials suitable for use in the drug-containing particles disclosed herein include fatty acid glycerol esters, polyethylene oxide-containing fatty acid esters, and combinations thereof.

[0108] In some embodiments, the drug-containing particles of the present disclosure comprise one or more fatty acid glycerol esters. As used herein, the term "fatty acid glycerol ester" refers to an ester (i.e., a glyceride) formed between glycerol and one or more fatty acids, including mono-, di-, and triesters. Suitable fatty acids include saturated and unsaturated fatty acids having 8 to 22 carbon atoms (i.e., C8 to C22 fatty acids). In certain embodiments, suitable fatty acids include C12 to C18 fatty acids. Fatty acid glycerol esters useful in the formulation can be provided by commercially available sources. A representative source of fatty acid glycerol esters is the mixture of mono-, di-, and triesters commercially available under the trademark PECEOL® (Gattefosse, Saint-Priest-Cedex, France), commonly referred to as "glyceryl oleate" or "glyceryl monooleate." In some embodiments, when PECEOL® is used as the source of fatty acid glycerol esters in the formulation, the fatty acid glycerol esters comprise from about 32% to about 52% by weight of fatty acid monoglycerides, from about 30% to about 50% by weight of fatty acid diglycerides, and from about 5% to about 20% by weight of fatty acid triglycerides. The fatty acid glycerol esters include greater than about 60% by weight of oleic acid (C18:1) mono-, di-, and triglycerides. Other fatty acid glycerol esters include palmitic acid (C16) (less than about 12%), stearic acid (C18) (less than about 6%), linoleic acid (C18:2) (less than about 35%), linolenic acid (C18:3) (less than about 2%), arachidic acid (C20) (less than about 2%), and eicosanoic acid (C20:1) (less than about 2%). PECEOL® may also contain free glycerol (typically about 1%). In one embodiment, the fatty acid glycerol esters contain about 44% by weight fatty acid monoglycerides, about 45% by weight fatty acid diglycerides, and about 9% by weight fatty acid triglycerides, and the fatty acid glycerol esters contain about 75% by weight oleic acid (C18:1) mono-, di-, and triglycerides.Other fatty acid glycerol esters include palmitic acid (C16) (about 4%), stearic acid (C18:0) (about 2%), linoleic 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%).

[0109] In other embodiments, the formulation may include a mixture of fatty acid glycerol esters, such as any of those disclosed herein. In still other embodiments, one or more fatty acid glycerol esters may be used in combination with other lipophilic materials described herein, such as one or more polyethylene oxide-containing fatty acid esters described herein.

[0110] In some embodiments, the drug-containing particles described herein comprise at least one polyethylene oxide-containing lipophilic material, such as a polyethylene oxide-containing fatty acid ester. As used herein, the term "polyethylene oxide-containing fatty acid ester" refers to a fatty acid ester comprising a polyethylene oxide group (i.e., also known as a polyethylene glycol group) covalently attached to a fatty acid via an ester bond. Polyethylene oxide-containing fatty acid esters include polyethylene glycol (PEG) mono- and di-fatty acid esters. Suitable polyethylene oxide-containing fatty acid esters are derived from fatty acids containing saturated and unsaturated fatty acids having 8 to 22 carbon atoms (i.e., polyethylene oxide esters of C8 to C22 fatty acids). In certain embodiments, suitable polyethylene oxide-containing fatty acid esters are derived from fatty acids containing saturated and unsaturated fatty acids having 12 to 18 carbon atoms (i.e., polyethylene oxide esters of C12 to C18 fatty acids). Exemplary polyethylene oxide-containing fatty acid esters include saturated C8 to C22 fatty acid esters. In certain embodiments, suitable polyethylene oxide-containing fatty acid esters include saturated C12 to C18 fatty acids.

[0111] 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 particle. Typical average molecular weights of the polyethylene oxide group can be about 350 to about 6000. In one embodiment, the average molecular weight for the polyethylene oxide group is about 1500, about 2000, about 4000, about 6000, and any value or range therebetween. In one embodiment, the average molecular weight for the polyethylene oxide group is about 1500.

[0112] In some embodiments, when the drug-containing particle contains a polyethylene oxide-containing fatty acid in the lipophilic material, the lipophilic material may contain only one type of polyethylene oxide-containing fatty acid. In other embodiments, the polyethylene oxide-containing fatty acid in the lipophilic material may contain a mixture of polyethylene oxide-containing fatty acid esters (PEG mono- and di-fatty acid esters). In several embodiments, the polyethylene oxide-containing fatty acid ester 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), linoleic acid (C18:2), linolenic acid (C18:3), arachidic acid (C20), eicosenoic acid (C20:1), or behenic acid (C22). In embodiments, the polyethylene oxide-containing fatty acid ester is a laurate, palmitate, or stearate (i.e., mono- and di-laurates of polyethylene glycol, mono- and di-palmitates of PEG, mono- and distearates of PEG). Mixtures of these esters can also be used.

[0113] The polyethylene oxide-containing fatty acid esters useful in the formulations of the present disclosure can be provided by commercially available sources. An exemplary polyethylene oxide-containing fatty acid ester (a mixture of mono- and diesters) is commercially available under the name GELUCIRE® (Gattefosse, Saint-Priest-Cedex, France).

[0114] In embodiments, the lipophilic material of the present disclosure comprises polyethylene oxide-containing fatty acid esters, polyethylene oxide glycerides, polypropylene glycol fatty acid esters, PEG, monoglyceride fatty acid esters, diglyceride fatty acid esters, triglyceride fatty acid esters, propylene glycol diglycerides, polyethylene oxide vegetable oils, or combinations thereof.

[0115] In some embodiments, the lipophilic material comprises 1) saturated or unsaturated C8-C22 fatty acid monoglycerides, 2) saturated or unsaturated C8-C22 fatty acid diglycerides, 3) saturated or unsaturated C8-C22 fatty acid triglycerides, 4) polyethylene glycol (PEG), 5) PEG-fatty acid (C8-C22) monoesters, 6) PEG-fatty acid (C8-C22) diesters, or any combination thereof. In some embodiments, the lipophilic material comprises C6-C18 fatty acid monoglycerides, diglycerides, and / or triglyceride esters. 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 polyethylene glycol-containing C8-C22 fatty acids. In some embodiments, the lipophilic material comprises a polyethylene glycol-containing C8-C22 fatty acid monoester. In some embodiments, the lipophilic material comprises a polyethylene oxide-containing C8-C22 fatty acid diester. In some embodiments, the lipophilic material comprises a mono-, di-, or triglyceride and polyethylene glycol described herein. In some embodiments, the lipophilic material comprises a mono-, di-, and triglyceride and a polyethylene glycol-containing fatty acid monoester described herein. In some embodiments, the lipophilic material comprises a mono-, di-, and triglyceride and a polyethylene glycol-containing fatty acid diester described herein. In several embodiments, the lipophilic material comprises any combination of the components described in this paragraph.

[0116] In some embodiments, the one or more lipophilic materials in the drug-containing particle comprise one or more polyethylene oxide-containing fatty acid esters. In some embodiments, the one or more lipophilic materials in the drug-containing particle comprise one or more glyceride fatty acid esters. In some embodiments, the polyethylene oxide-containing fatty acid esters or glyceride fatty acid esters comprise one or more fatty acid residues. In several embodiments, the fatty acid residues comprise C6-C22 fatty acids, e.g., 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 several embodiments, the fatty acid residues comprise residues of C8-C20 fatty acids. In some embodiments, the C6-C20 fatty acids include residues 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 acids include residues 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 include a polyethylene glycol derivative of a vegetable oil. In some embodiments, one or more lipophilic materials in the drug-containing particle comprise a C8-C20 monoglyceride. In some embodiments, one or more lipophilic materials in the drug-containing particle comprise a C8-C20 diglyceride. In some embodiments, one or more lipophilic materials in the drug-containing particle comprise a C8-C20 triglyceride.

[0117] In some embodiments, the lipophilic material comprises stearoyl polyoxylglyceride, stearoyl polyethylene oxide, lauroyl polyoxylglyceride, oleoyl polyoxylglyceride, monoesters / diesters of hydroxystearic acid and polyethylene glycol, PEG-hydrogenated castor oil, propylene glycol monocaprylate, propylene glycol monolaurate, medium chain triglycerides, propylene glycol dicaproate / dicaprate, caprylocaproyl polyoxylglyceride, or combinations thereof.

[0118] In some embodiments, the lipophilic material is selected from the group consisting of mono-, di-, and triglyceride acids of fatty acids and PEG-32 (MW 1500) mono- and diesters of palmitic acid (C16) and stearic acid (C18); mono-, di-, and triglyceride esters of fatty acids (C8-C18); mono-, di-, and triglyceride esters of lauric acid (C12) and stearic acid (C18) and PEG-6 (MW 300) mono- and diesters; oleic acid (C18:1) Mono-, di-, and triglyceride esters of PEG-6 (MW 300) and mono- and diesters; mono- and diesters of 12-hydroxystearic acid and a mixture of polyethylene glycol glycerides; PEG-40 hydrogenated castor oil; propylene glycol monocaprylate; propylene glycol monolaurate; medium chain triglycerides; propylene glycol dicaprate / propylene glycol dicaprate; caprylic acid (C8) and capric acid (C 10 ) PEG-8 (MW400) monoesters and diesters; or combinations thereof.

[0119] In some embodiments, the lipophilic material is selected from mono-, di-, and triglyceride esters of palmitic acid (C16) and stearic acid (C18), and PEG-32 (MW1500) mono- and diesters of palmitic acid (C16) and stearic acid (C18) (e.g., stearoyl polyoxyl-32 glyceride: GELUCIRE® 50 / 13); mono-, di-, and triglyceride esters of fatty acids (C8-C18) (e.g., hard fat: GELUCIRE® 43 / 01); mono-, di-, and triglyceride esters of lauric acid (C12) and stearic acid (C18), and PEG-6 (MW300) mono- and diesters of lauric acid (C12) and stearic acid (C18) (e.g., lauroyl polyoxyl-6-glyceride). mono-, di-, and triglyceride esters of oleic acid (C18:1) and PEG-6 (MW300) mono- and diesters of oleic acid (C18:1) (e.g., oleoyl polyoxyl-6-glyceride: LABRAFIL® 1944); polyethylene glycol mono- and diesters of 12-hydroxystearic acid (e.g., CRODASOL® HS); PEG-40 hydrogenated castor oil (e.g., CRODURET® 40), propylene glycol monocaprylate (e.g., CAPRYOL® 90); propylene glycol monolaurate (e.g., LAUROGLYCOL® 90); medium-chain triglycerides (e.g., LABRAFAC® lipophile WL1349, MIGLYOL® 810N); propylene glycol / propylene glycol dicaprate (e.g., LABRAFAC® PG); caprylic acid (C8) and capric acid (C 10 ), PEG-8 (MW400) mono- and diesters (e.g., caprylocaproyl polyoxy-8-glyceride: LABRASOL® ALF), or combinations thereof.

[0120] In some embodiments, the one or more lipophilic materials of the present disclosure include polyethylene oxide-containing fatty acid esters, GELUCIRE® (e.g., GELUCIRE® 44 / 14, GELUCIRE® 50 / 13, GELUCIRE® 53 / 10, GELUCIRE® 43 / 01, and GELUCIRE® 48 / 16). The numbers in these names refer to the melting points and hydrophilic / lipophilic balance (HLB) of these materials, respectively. GELUCIRE® 44 / 14, GELUCIRE® 50 / 13, GELUCIRE® 53 / 10, and GELUCIRE® 43 / 01 are mixtures of (a) mono-, di-, and triesters of glycerol (glycerides), and (b) mono- and diesters of polyethylene glycol (macrogols). In some embodiments, the lipophilic material comprising a polyethylene oxide-containing fatty acid ester further comprises free polyethylene glycol (e.g., PEG 1500). In several embodiments, one or more lipophilic materials of the present disclosure comprise polyglycolized glycerides prepared by the alcoholysis reaction of natural oils with polyethylene glycol (PEG).

[0121] GELUCIRE® 44 / 14 is a lauroyl polyoxyl / macrogol 32 glyceride NF / EP, containing mono-, di-, and triglyceride fractions and PEG-32 (MW 1500) mono- and diesters of predominantly lauric acid (C12). GELUCIRE® 50 / 13 is a stearoyl polyoxyl / macrogol 32 glyceride according to the National Formulary (NF) / European Pharmacopoeia (EP), containing mono-, di-, and triglycerides of palmitic acid (C16) and stearic acid (C18) and PEG-32 (MW 1500) mono- and diesters.

[0122] GELUCIRE® 43 / 01 is a hard fat composed of mono-, di-, and triglyceride esters of fatty acids (C8 to C18) according to the European Pharmacopoeia (EP) and (C16) and the National Formulary (NF).

[0123] GELUCIRE® 48 / 16 is a pure PEG ester. In some embodiments, the lipophilic material of the present disclosure includes palmitic acid (C16) and stearic acid (C18) mono-, di-, and triglycerides and PEG-32 (MW1500) mono- and diesters (GELUCIRE® 50 / 13). In some embodiments, the lipophilic material includes mono-, di-, and triglyceride esters of fatty acids (C8-C18) (GELUCIRE® 43 / 01).

[0124] Lauric acid (C12) is the primary fatty acid component of the glycerides and polyethylene glycol esters in GELUCIRE® 44 / 14. GELUCIRE® 44 / 14 is described as a mixture of glyceryl dilaurate (a lauric acid diester with glycerol) and PEG dilaurate (a lauric acid diester with polyethylene glycol), commonly known as PEG-32 glyceryl laurate (Gattefosse), lauroyl macrogol-32 glycerides EP, or lauroyl polyoxyglycerides USP / NF. GELUCIRE® 44 / 14 contains lauric acid (C12) esters (30%-50%), myristic acid (C14) esters (5-25%), palmitic acid (C16) esters (4-25%), stearic acid (C18) esters (5-35%), caprylic acid (C8) esters (less than 15%), and capric acid (C10) esters (less than 12%). GELUCIRE® 44 / 14 may also contain free glycerol (typically less than about 1%). In a representative formulation, GELUCIRE® 44 / 14 contains approximately 47% lauric acid (C12) ester, approximately 18% myristic acid (C14) ester, approximately 10% palmitic acid (C16) ester, approximately 11% stearic acid (C18) ester, approximately 8% caprylic acid (C8) ester, and approximately 12% capric acid (C10) ester. GELUCIRE® 44 / 14 is produced by the reaction of hydrogenated palm kernel oil with polyethylene glycol (average molecular weight 1500). GELUCIRE® 44 / 14 contains approximately 20% mono-, di-, and triglycerides, approximately 72% mono- and di-fatty acid esters of polyethylene glycol 1500, and approximately 8% polyethylene glycol 1500.

[0125] Palmitic acid (C16) (40-50%) and stearic acid (C18) (48-58%) are the major fatty acid components of the glycerides and polyethylene glycol esters in GELUCIRE® 50 / 13, also known as PEG-32 glyceryl palmitate (Gattefosse), stearoyl macrogolglycerides EP, or stearoyl polyoxylglycerides USP / NF. GELUCIRE® 50 / 13 contains palmitic acid (C16) esters (40%-50%), stearic acid (C18) esters (48-58%) (more than about 90% stearic and palmitic acid esters), lauric acid (C12) esters (less than 5%), myristic acid (C14) esters (less than 5%), caprylic acid (C8) esters (less than 3%), and capric acid (C10) esters (less than 3%). GELUCIRE® 50 / 13 may also contain free glycerol (typically less than about 1%). In a representative formulation, GELUCIRE® 50 / 13 contains palmitic acid (C16) ester (approximately 43%), stearic acid (CIS) ester (approximately 54%) (stearic acid and palmitic acid esters approximately 97%), lauric acid (C12) ester (less than 1%), myristic acid (C14) ester (approximately 1%), caprylic acid (C8) ester (less than 1%), and capric acid (C10) ester (less than 1%). GELUCIRE® 50 / 13 is also known as PEG-32 glyceryl stearate (Gattefosse).

[0126] In some embodiments, the one or more lipophilic materials of the present disclosure comprise a fatty acid diester glyceride (e.g., lauroyl macrogol-6 glyceride, also known as lauroyl polyoxyl-6 glyceride, or LABRAFIL® M 2130). Exemplary fatty acid diester glycerides include oleoyl macrogol-6 glyceride or oleoyl polyoxyl-6 glyceride (e.g., LABRAFIL® M 2130, LABRAFIL® M 1944), and linoleyl macrogol-6 glyceride (also known as LABRAFIL® M 2125, corn oil PEG-6 esters, or linoleyl polyoxyl-6 glyceride). LABRAFIL® M2130 contains mono-, di-, and triglycerides of lauric acid (C12) and stearic acid (C18) and PEG-6 (MW300) and mono- and diesters; LABRAFIL® M1944 contains mono-, di-, and triglycerides of oleic acid (C18:1) and PEG-6 (MW300) and mono- and diesters; and LABRAFIL® M2125 contains mono-, di-, and triglycerides of linoleic acid (C18:2) and PEG-6 (MW300) and mono- and diesters. In some embodiments, the lipophilic material of the present disclosure includes lauroyl polyoxyl-6 glyceride (LABRAFIL® M2130). In some embodiments, the lipophilic material includes oleoyl polyethylene glycol-6 glyceride (LABRAFIL® M1944).

[0127] In some embodiments, the one or more lipophilic materials of the present disclosure include a mixture of mono- and diesters of 12-hydroxystearic acid and polyethylene glycol (CRODASOL™ HS HP), a compatible mixture of caprylocaproyl polyethylene glycol glycerides (CRODASOL™ CCMG400), polysorbate 20 (and) PEG-25 hydrogenated castor oil and propylene glycol (CRODASOL™ PHC), PEG-6 caprylic / capric glycerides and PEG-60 almond glycerides (CRODASOL™ AC), or a combination thereof. In some embodiments, the one or more lipophilic materials are a mixture of mono- and diesters of 12-hydroxystearic acid and polyethylene glycol (CRODASOL™ HS HP).

[0128] In some embodiments, the one or more lipophilic materials of the present disclosure comprise a plant-derived ethoxylated nonionic surfactant (e.g., PEG-40 hydrogenated castor oil, also known as CRODURET™). In embodiments, the one or more lipophilic materials comprise PEG-40 hydrogenated castor oil (CRODURET™ 40), PEG-50 hydrogenated castor oil (CRODURET™ 50), PEG-60 hydrogenated castor oil (CRODURET™ 60), PEG-7 hydrogenated castor oil (CRODURET™ 7), or mixtures thereof. In embodiments, the one or more lipophilic materials comprise PEG-40 hydrogenated castor oil (CRODURET™ 40).

[0129] In some embodiments, the one or more lipophilic materials of the present disclosure include propylene glycol monocaprylate (eg, CAPRYOL® 90, a propylene glycol ester of caprylic acid (C8)).

[0130] In some embodiments, the one or more lipophilic materials of the present disclosure include propylene glycol laurate (e.g., LAUROGLYCOL® 90 or LAUROGLYCOL FCC, also known as propylene glycol monolaurate). In embodiments, the propylene glycol laurate is a mixture of mono- and diesters of lauric acid. In embodiments, the propylene glycol laurate comprises a monoester to ester ratio of about 90:10. In embodiments, lipophilic materials including propylene glycol laurate may also contain esters of caprylic acid, capric myristic acid, and / or palmitic acid.

[0131] In some embodiments, the one or more lipophilic materials of the present disclosure include caprylocaproyl polyoxyl-8 glycerides (e.g., LABRASOL® ALF). In embodiments, such glycerides are caprylic (C8) and capric (C 10 In some embodiments, the glycerides include PEG-8 (MW400) mono- and diesters of caprylic acid (C8) and capric acid (C 10 ) mono-, di- and triglycerides.

[0132] In some embodiments, the drug-containing particles comprise one or more triglycerides. The triglycerides may include any combination of short-, medium-, long-, or very-long-chain triglycerides, or any combination thereof, or any combination of short-, medium-, long-, or very-long-chain triglycerides. In some embodiments, the short-chain triglycerides include fatty acids having a triglyceride chain containing 1 to 5 carbon atoms. In some embodiments, the short-chain triglycerides include fatty acids having a triglyceride chain containing 6 to 12 carbon atoms. In some embodiments, the short-chain triglycerides include fatty acids having a triglyceride chain containing 13 to 21 carbon atoms. In some embodiments, the short-chain triglycerides include fatty acids having a triglyceride chain containing 22 or more carbon atoms. The hydrocarbon chains in the triglycerides may be saturated or unsaturated. If the hydrocarbon chain is unsaturated, it can have any number of double or triple bonds, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0133] In some embodiments, the one or more lipophilic materials of the present disclosure comprise a medium-chain triglyceride (e.g., LABRAFAC™ lipophile WT1349). In some embodiments, the one or more lipophilic materials comprise a medium-chain triglyceride of caprylic (C8) and capric (C10) acids (LABRAFAC™ lipophile WT1349), or a glycerol triester of caprylic and capric acids (MIGLYOL® 810, MIGLYOL® 812, MIGLYOL® 829, or MIGLYOL® 840). In several embodiments, the one or more lipophilic materials comprise a propylene glycol ester of caprylic (C8) and capric (C10) acids (LABRAFAC™ PG). In embodiments, the one or more lipophilic materials include glycerol monocaprylocapriate (Type I) (LABRAFAC™ MC60), which contains caprylic acid (C8) and capric acid (C10).

[0134] In some embodiments, the lipophilic material comprises one or more vegetable 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 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 oil, pumpkin seed oil, or a mixture thereof. In several embodiments, the lipophilic material comprises one or more vegetable oils. In embodiments, the vegetable oil comprises one or more plant seed oils, fruit seed oils, kernel oils, sesame seed oil, medium chain triglyceride (MCT) oil, oleic acid oil, pumpkin seed oil, interesterified vegetable oil, polyoxyethylene hydrogenated vegetable oil, PEG hydrogenated castor oil, or combinations thereof.

[0135] In some embodiments, the one or more lipophilic materials are present in an amount sufficient to provide the 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% 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 particle. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 5 to about 75% by weight based on the total weight of the drug-containing particle. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 10 to about 75% by weight based on the total weight of the drug-containing particle. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 15 to about 75% by weight based on the total weight of the drug-containing particle. In some embodiments, the one or more lipophilic materials are present in an amount ranging from about 20 to about 75% by weight based on the total weight of the drug-containing particle. In some embodiments, one or more lipophilic materials are present in an amount ranging from about 15 to about 75% by weight based on the total weight of the drug-containing particle. The lipophilic materials are present in an amount ranging from about 5 to about 50% by weight, based on the total weight of the drug-containing particles. In some embodiments, the lipophilic materials are present in an amount ranging from about 10 to about 50% by weight, based on the total weight of the drug-containing particles. In some embodiments, the lipophilic materials are present in an amount ranging from about 15 to about 50% by weight, based on the total weight of the drug-containing particles. In some embodiments, the lipophilic materials are present in an amount ranging from about 20 to about 50% by weight, based on the total weight of the drug-containing particles. In some embodiments, the lipophilic materials are present in an amount ranging from about 5 to about 75% by weight, based on the total weight of the drug-containing particles. In some embodiments, the lipophilic materials are present in an amount ranging from about 10 to about 75% by weight, based on the total weight of the drug-containing particles. In some embodiments, the lipophilic materials are present in an amount ranging from about 15 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 particle at about 5 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, or about 75 wt%, based on the total weight of the drug-containing particle.

[0136] polymer In some embodiments, the drug-containing particles further comprise one or more polymers. In some embodiments, the polymers have a glass transition temperature (T) in the range of about 50° C. to about 130° C. g In some embodiments, the polymer comprises polyvinylpyrrolidone (Kollidon VA64), cross-linked polyvinyl N-pyrrolidone (crospovidone), hydroxypropyl methylcellulose phthalate (HPMCP50), polyvinyl alcohol-polyethylene glycol copolymer (kollicoat), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (soluplus), polyvinyl alcohol, or a combination thereof. In some embodiments, the one or more polymers are present in an amount ranging from about 10% 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 particle. In some embodiments, the polymer is provided as a coating on the drug-containing particle.

[0137] Chelating Agents (CA) and Antioxidants (AO) The drug-containing particles disclosed herein optionally include a chelating agent. In some embodiments, the chelating agent is EDTA, citric acid, or curcumin.

[0138] In some embodiments, the amount of chelating agent in the drug-containing particles is in the range of about 0.05% to about 3% by weight, e.g., 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% by weight. , 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% by weight (including all ranges and values therebetween). In some embodiments, the amount of chelating agent in the drug-containing particles is in the range of about 0.05% to about 0.5% by weight. In some embodiments, the amount of chelating agent in the drug-containing particles ranges from about 0.05% to about 0.4% by weight, about 0.05% to about 0.35% by weight, about 0.05% to about 0.3% by weight, about 0.05% to about 0.25% by weight, or about 0.05% to about 0.2% by weight.

[0139] The drug-containing particles disclosed herein optionally contain one or more antioxidants. In some embodiments, 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, butylhydroxyanisole, butylhydroxytoluene (BHT), monothioglycerol, propyl gallate, curcumin, or a combination thereof. In some embodiments, the one or more antioxidants are α-tocopherol, β-carotene, ascorbic acid, ascorbyl palmitate, lecithin, butylhydroxyanisole, butylhydroxytoluene, monothioglycerol, propyl gallate, or a combination thereof. In some embodiments, the one or more antioxidants are α-tocopherol.

[0140] In some embodiments, the amount of one or more antioxidants in the drug-containing particles ranges from about 0.05% to about 3% by weight, e.g., 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%, and the like. In some embodiments, the amount of one or more antioxidants in the drug-containing particles is in the range of about 0.05% to about 2.5% by weight, about 0.05% to about 2.0% by weight, about 0.05% to about 1.5% by weight, about 0.05% to about 1.0% by weight, or about 0.05% to about 0.5% by weight. In some embodiments, the amount of one or more antioxidants in the drug-containing particles ranges from about 0.05% to about 2.0% by weight. In some embodiments, the amount of one or more antioxidants in the drug-containing particles ranges from about 0.1% 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%.

[0141] In some embodiments, the drug-containing particles comprise any combination of a chelating agent and one or more antioxidants disclosed herein. In some embodiments, the chelating agent is EDTA, citric acid, or a polyphenol component (e.g., curcumin), and the one or more antioxidants are a tocopherol derivative (e.g., α-tocopherol), a carotenoid (e.g., lutein or β-carotene), a tocotrienol, ascorbic acid, ascorbyl palmitate, lecithin, butylhydroxyanisole, butylhydroxytoluene (BHT), monothiolglycerol, propyl gallate, curcumin, or a combination thereof. In some embodiments, the drug-containing particles comprise one of the following combinations of antioxidant(s) and chelating agent (CA):

[0142] [Table 11]

[0143] Drug release profile The release of one or more cannabinoids from the drug-containing particles can be immediate or modified, depending on the application. In some embodiments, the drug-containing particles are formulated for immediate release. In some embodiments, the drug-containing particles are formulated for modified release, e.g., delayed or sustained release. In some embodiments, the drug-containing particles disclosed herein release 50-90% of the one or more cannabinoids in about 1-16 hours. In some embodiments, the drug-containing particles disclosed herein release 50-90% of the one or more cannabinoids in about 2-12 hours. In some embodiments, the drug-containing particles disclosed herein release 50-90% of the one or more cannabinoids in about 3-12 hours. In some embodiments, the drug-containing particles disclosed herein release at least about 50% of the one or more cannabinoids in about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, or about 12 hours. In some embodiments, the drug-containing particles disclosed herein release at least about 60% of the one or more cannabinoids in about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, or about 12 hours. In some embodiments, the drug-containing particles disclosed herein release at least about 70% of the one or more cannabinoids in about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, or about 12 hours. In some embodiments, the drug-containing particles disclosed herein release at least about 80% of the one or more cannabinoids in about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, or about 12 hours. In some embodiments, the drug-containing particles disclosed herein release at least about 90% of the one or more cannabinoids in about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, or about 12 hours.

[0144] In embodiments, the drug-containing particles disclosed herein release at least 20% in 10 minutes. In embodiments, the drug-containing particles disclosed herein release 20% to 50% in 10 minutes. In embodiments, the drug-containing particles disclosed herein release at least 30% in 15 minutes. In embodiments, the drug-containing particles disclosed herein release 30% to 70% in 15 minutes. In embodiments, the drug-containing particles disclosed herein release at least 40% in 20 minutes. In embodiments, the drug-containing particles disclosed herein release 40 to 80% in 20 minutes. In embodiments, the drug-containing particles disclosed herein release at least 45% in 30 minutes. In embodiments, the drug-containing particles disclosed herein release 45 to 85% in 30 minutes. In embodiments, the drug-containing particles disclosed herein release at least 50% in 45 minutes. In embodiments, the drug-containing particles disclosed herein release 50-85% in 50 minutes.

[0145] In embodiments, drug release (dissolution) is measured under the United States Pharmacopoeia (USP) Dissolution Test (711). In some embodiments, drug release (dissolution) is measured using Apparatus I or Apparatus II. In some embodiments, dissolution (release) rates are tested using USP Apparatus II (75 rpm paddle) in 900 mL of an appropriate buffer at 37±0.5°C. In some embodiments, the buffer has a pH ranging from about 1 to about 7, e.g., about 1, about 1.5, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5, about 5, 5.5, about 6, about 6.5, about 6.8, and about 7 (including all values and subranges therebetween). The pH of the buffer can be selected based on the approximate pH of the gastrointestinal tract where release will be measured. For example, a pH of 1 can be used to measure gastric dissolution, while a higher pH up to 7.4 (e.g., 4.5, 5, 5.5, etc.) can be used to measure intestinal dissolution. Test conditions (eg, run time, medium, run time, speed, volume, etc.) may be varied.

[0146] In embodiments, drug release (dissolution) is measured under the dissolution test conditions set forth in Table A1.

[0147] [Table 12]

[0148] In some embodiments, drug release (dissolution) is measured under the dissolution test conditions set forth in Table AB.

[0149] [Table 13]

[0150] In some embodiments, dissolution testing is performed for 30 minutes for immediate release. In some embodiments, dissolution testing is performed for at least 3 hours (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) for delayed release. In some embodiments, the buffer is 0.1 M HCl at pH 1, 0.01 M HCl at pH 2, or acetate buffer at pH 4.5.

[0151] For enteric coating ingredients, testing may be performed using USP Apparatus II (paddle at 75 rpm) in 900 mL of a first buffer at pH 4.5 for 3 hours at 37±0.5° C., followed by 900 mL of a second buffer at pH 6.8.

[0152] In some embodiments, the drug-containing particles disclosed herein are formulated to be bioequivalent, for example, compared to conventional formulations that do not include a porous solid carrier. In some embodiments, conventional formulations include one or more cannabinoids (e.g., CBD) dissolved in sesame oil. That is, in some embodiments, the drug-containing particles have a mean C of 100 or less than that of conventional oil-based cannabinoid pharmaceutical products when administered to humans or animals, such as mice, rats, beagle dogs, or minipigs. max , average AUC, and average Tmax The mean maximum plasma concentration (C max ), mean AUC, and / or mean T max As used herein, Cmax , AUC, and T maxは , refers to the mean or median value measured for a population of subjects.

[0153] In some embodiments, the drug-containing particles disclosed herein are formulated to have improved pharmacokinetic properties, for example, compared to conventional formulations that do not include a porous solid carrier. That is, in some embodiments, the drug-containing particles have an average C of conventional oil-based cannabinoid pharmaceutical products when administered to humans or animals, such as mice, rats, beagle dogs, or minipig models. max or a mean maximum plasma concentration (C ) that is about 5%, about 10%, about 15%, about 20%, about 25%, 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% higher than the mean AUC max ) or mean AUC. max Alternatively, AUC refers to the mean or median value measured for a population of subjects.

[0154] In some embodiments, administration of drug-containing particles at a dose equivalent to 10 mg / kg provides an AUC ranging from about 80% to about 125% of about 722 ng*hr / mL. In such embodiments, the AUC ranges from about 550 ng*hr / mL to about 950 ng*hr / mL, e.g., 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, and the like. hr / mL, about 750ng*hr / mL, about 770ng*hr / mL, about 790ng*hr / mL, about 810ng*hr / mL, about 830ng*hr / mL, about 850ng*hr / mL, about 870ng*hr / mL, about 890ng*hr / mL, about 910ng*hr / mL, about 930ng*hr / mL, or about 950ng*hr / mL (including all values and ranges).

[0155] In some embodiments, administration of drug-containing particles at a dose equivalent to 10 mg / kg results in a C of about 80% to about 125% of that of about 150 ng / mL. max In such embodiments, the subject has a C of about 50 ng / mL to about 190 ng / mL, e.g., 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, up to about 190 ng / mL (including all values and ranges). max It has.

[0156] In some embodiments, administration of the drug-containing particles results in an increase in CBD levels in a subject of 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 340%, about 360%, about 380%, about 400%, about 420%, about 440%, about 460%, about 480%, about 500%, about 520%, 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 820%, about 830%, about 840%, about 850%, about 860%, about 870%, about 880%, about 890%, about 900%, about 910%, about 920%, about 930%, about 940%, about 950%, about 960%, about 970%, about 980%, about 990%, about 1000%, about 1010%, about 1020%, In some embodiments, administration of drug-containing particles in a formulation of the present disclosure provides 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, administration of drug-containing particles in a formulation of the present disclosure provides a relative bioavailability (Frel%) of about 30% to about 100% compared to CBD dissolved in sesame oil containing the same dose of CBD.

[0157] drug-containing particles In some embodiments, the pharmaceutical composition comprises about 10-60% of a drug substance described herein and about 20%-80% of a porous solid carrier, hi some embodiments, the pharmaceutical composition comprises about 15-40% of a drug substance described herein and about 40%-60% of a porous solid carrier.

[0158] In some embodiments, the pharmaceutical composition comprises about 10-60% of a drug substance described herein, about 20-80% of a porous solid carrier, and about 10-50% of one or more lipophilic materials. In some embodiments, the pharmaceutical composition comprises 15-40% of a drug substance described herein, about 40-60% of a porous solid carrier, and about 15-35% of one or more lipophilic materials.

[0159] In some embodiments, the pharmaceutical composition comprises 10-60% of a drug substance described herein, about 20%-80% of a porous solid carrier, about 10-50% of one or more lipophilic materials, and about 0.1-2% of an antioxidant. In some embodiments, the pharmaceutical composition comprises 15-40% of a drug substance described herein, about 40%-60% of a porous solid carrier, about 15-35% of one or more lipophilic materials, and about 0.2-1% of an antioxidant.

[0160] Method for producing drug-containing particles In some embodiments, the drug-containing particles of the present disclosure are made according to a solvent-mediated method, in which one or more cannabinoids are loaded onto a porous solid support (e.g., mesoporous silica) from a solution (see FIG. 4). In some embodiments, the solvent-mediated method is carried out according to the steps provided in FIG. 5. In some embodiments, the drug-containing particles made according to the solvent-mediated method disclosed herein are free-flowing powders. In some embodiments, the free-flowing powders are stable at elevated temperatures (e.g., 25° C. or 40° C.) for a period of more than 1 week, more than 2 weeks, more than 3 weeks, more than 4 weeks, more than 5 weeks, more than 6 weeks, more than 7 weeks, more than 8 weeks, more than 9 weeks, more than 10 weeks, more than 11 weeks, or more than 12 weeks.

[0161] In some embodiments, the drug-containing particles of the present disclosure are produced according to a solvent-mediated method, in which one or more cannabinoids, one or more polymers disclosed herein, and one or more optional antioxidants disclosed herein are loaded onto a porous solid support (e.g., mesoporous silica) from solution. In some embodiments, the solvent-mediated method is carried out according to the steps provided in Figure 8.

[0162] In some embodiments, the solvent-mediated process disclosed herein comprises spray drying or freeze drying a solution of one or more cannabinoids or derivatives disclosed herein, one or more polymers disclosed herein, and one or more optional antioxidants disclosed herein onto a porous solid support. In some embodiments, the solvent-mediated process comprising spray drying is carried out according to the steps provided in Figures 9A-C or 10.

[0163] In some embodiments, the method of preparing a drug-containing particle of the present disclosure comprises:

[0164] (a) combining a porous solid support, one or more cannabinoids, an optional polymer, one or more optional antioxidants, and an optional chelating agent to form a mixture;

[0165] (b) adding a solvent to the mixture, optionally with heating, to form a slurry;

[0166] (c) sonicating and / or stirring the slurry for a period of time; and

[0167] (d) evaporating the solvent to obtain a dry powder.

[0168] In some embodiments, the agitation in step (c) comprises low shear or high shear powder mixing techniques, such as manual mixing or the use of a mechanically driven paddle, blade mixer, or twin-screw mixer.

[0169] The evaporation in step (d) can be carried out according to any suitable method known in the art. In some embodiments, the evaporation in step (d) is carried out under reduced pressure. In some embodiments, the evaporation in step (d) is carried out under reduced pressure and / or at elevated temperature. In certain embodiments, the evaporation can be carried out by removing the solvent at an appropriate temperature, by spray drying, by freeze drying, or a combination thereof. In some embodiments, the evaporation includes secondary drying, which can be carried out, for example, in a vacuum oven until the residual solvent is within the ICH limits.

[0170] In some embodiments, the drug-containing particles of the present disclosure are produced according to a lipid-loading method, in which one or more cannabinoids are combined with a lipophilic material disclosed herein and mixed with a porous solid support to facilitate loading (see FIG. 4). In some embodiments, the lipid-loading method is carried out according to one or more of the processes provided in FIG. 12. In some embodiments, the drug-containing particles produced according to the lipid-loading method disclosed herein are free-flowing powders. In some embodiments, the free-flowing powders are stable at elevated temperatures (e.g., 25°C or 40°C) for more than 1 week, more than 2 weeks, more than 3 weeks, more than 4 weeks, more than 5 weeks, more than 6 weeks, more than 7 weeks, more than 8 weeks, more than 9 weeks, more than 10 weeks, more than 11 weeks, or more than 12 weeks.

[0171] In some embodiments, the method of preparing a drug-containing particle of the present disclosure comprises:

[0172] (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;

[0173] (b) stirring the mixture of step (a) for a period of time until homogeneous;

[0174] (c) adding the homogeneous mixture of step (b) to a porous solid support; and

[0175] (d) stirring the mixture of step (c) for a period of time until homogeneous.

[0176] Pharmaceutical Composition 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 a tablet, capsule, or granules. In some embodiments, the drug-coated particles can be filled into a capsule and, optionally, combined with various excipients described herein and compressed into a tablet. The pharmaceutical compositions disclosed herein can be prepared by any suitable method known in the art. In some embodiments, the method comprises blending the drug-containing particles with one or more pharmaceutically acceptable excipients and / or carriers. In some embodiments, the method comprises a dry granulation (roller compaction) process.

[0177] Pharmaceutically acceptable excipients include fillers, diluents, flow agents, disintegrants, binders, and lubricants. Other pharmaceutically acceptable excipients include acidifying agents, alkalizing agents, preservatives, antioxidants, buffers, chelating agents, coloring agents, complexing agents, emulsifying and / or solubilizing agents, flavoring agents, perfumes, wetting agents, sweetening agents, and humectants.

[0178] Flavoring agents and flavor enhancers make the dosage form more palatable to the patient. Common pharmaceutical flavoring agents and flavor enhancers that may be included in the compositions and / or combinations of the present invention include fruit flavors, sucrose, maltol, vanillin, ethyl vanillin, menthol, citric acid, fumaric acid, ethyl maltol, and tartaric acid.

[0179] In some embodiments, the drug-containing particles disclosed herein are prepared in a formulation having one of the following non-limiting compositions:

[0180] [Table 14-1] [Table 14-2]

[0181] Embodiment 1. Drug-containing particles, comprising:

[0182] (a) one or more cannabinoids, and

[0183] (b) a porous solid support;

[0184] The drug-containing particles, wherein the one or more cannabinoids are adsorbed onto and / or within the porous solid carrier.

[0185] 2. The drug-containing particle of embodiment 1, wherein the porous solid carrier is a microparticle.

[0186] 3. The drug-containing particles according to embodiment 1 or 2, wherein the porous solid carrier has an average particle size in the range of about 1 μm to about 250 μm.

[0187] 4. The drug-containing particles according to any one of embodiments 1 to 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.

[0188] 5. The drug-containing particle according to any one of embodiments 1 to 4, wherein the porous solid carrier has a porosity in the range of about 75% to about 99%.

[0189] 6. The porous solid carrier is about 100 m 2 / g~about 1000m 2 The drug-containing particles according to any one of embodiments 1 to 5, having an average surface area ranging from 1000 to 10000 / g.

[0190] 7. The drug-containing particle according to any one of embodiments 1 to 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.

[0191] 8. The drug-containing particle according to any one of embodiments 1 to 7, wherein the porous solid carrier has an average pore volume ranging from about 1 mL / g to about 2 mL / g.

[0192] 9. The drug-containing particle according to any one of embodiments 1 to 7, wherein the porous solid carrier has an average pore size ranging from about 1 nm to about 100 nm.

[0193] 10. The drug-containing particle according to any one of embodiments 1 to 9, wherein the porous solid carrier has an average pore size ranging from about 2 nm to about 60 nm.

[0194] 11. The drug-containing particle according to any one of embodiments 1 to 9, wherein the porous solid carrier has an average pore size ranging from about 10 nm to about 50 nm.

[0195] 12. The drug-containing particle according to any one of embodiments 1 to 11, wherein the porous solid carrier has an average pore size ranging from about 15 nm to about 30 nm.

[0196] 13. The drug-containing particle of any one of embodiments 1-12, wherein the porous solid carrier has one or more of the following characteristics: (i) 1 to 2 cm 3 / g, (ii) an average surface area in the range of 250 to 375; or (iii) pore diameters in the range of about 2–50 nm;

[0197] 14. The drug-containing particle of any one of embodiments 1-13, wherein the porous solid carrier has two or more of the following characteristics: (i) 1 to 2 cm 3 / g, (ii) an average surface area in the range of 250 to 375; or (iii) pore diameters in the range of about 2–50 nm;

[0198] 15. The porous solid support is (i) 1 to 2 cm 3 / g, (ii) an average surface area in the range of 250 to 375; and (iii) The drug-containing particle according to any one of embodiments 1 to 14, having a pore size in the range of about 2 to 50 nm.

[0199] 16. The drug-containing particle of any one of embodiments 1 to 14, wherein the porous solid carrier comprises silica (SiO2), microcrystalline cellulose, silicified microcrystalline cellulose, chitosan, isomalt, or a silicate.

[0200] 17. The drug-containing particle of any one of embodiments 1 to 16, wherein the porous solid carrier comprises silica or a silicate.

[0201] 18. The drug-containing particle of any one of embodiments 1 to 17, wherein the porous solid carrier comprises silica.

[0202] 19. The drug-containing particle of any one of embodiments 16 to 18, wherein the silica comprises mesoporous silica or amorphous silica.

[0203] 20. The drug-containing particle of any one of embodiments 16 to 19, wherein the silica comprises mesoporous silica.

[0204] 21. The drug-containing particle of any one of embodiments 1 to 11, wherein the porous solid carrier comprises a silicate.

[0205] 22. The drug-containing particle of embodiment 21, wherein the silicate comprises an aluminosilicate.

[0206] 23. The drug-containing particle of embodiment 22, wherein the silicate comprises magnesium aluminosilicate.

[0207] 24. The drug-containing particle of any one of embodiments 1 to 23, wherein the porous solid carrier is present in an amount ranging from about 20% by weight to about 80% by weight, based on the total weight of the drug-containing particle.

[0208] 25. The drug-containing particle of any one of embodiments 1 to 24, wherein the 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 particle.

[0209] 26. The drug-containing particle of any one of embodiments 1-25, wherein the one or more cannabinoids comprise cannabichromene (CBC), cannabichromene acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabiditriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic acid (THCVA), CBD-C4, OH-CBD, CBD-C4, 6-OH-CBD, 7-OH-CBD, 7-COOH-CBD, 11-COOH-THC, or 11-OH-THC.

[0210] 27. A drug-containing particle described in any one of embodiments 1 to 26, wherein the one or more cannabinoids comprise CBD.

[0211] 28. A drug-containing particle described in any one of embodiments 1 to 27, wherein 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 particle.

[0212] 29. A drug-containing particle described in any one of embodiments 1 to 28, wherein 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 particle.

[0213] 30. A drug-containing particle described in any one of embodiments 1 to 29, wherein the one or more cannabinoids are present in an amount ranging from about 15% by weight to about 40% by weight, based on the total weight of the drug-containing particle.

[0214] 31. The drug-containing particle of any one of embodiments 1 to 30, wherein the ratio of the porous solid carrier to the active pharmaceutical ingredient is 10:1 to 1:5.

[0215] 32. The drug-containing particle of any one of embodiments 1 to 30, wherein the ratio of the porous solid carrier to the active pharmaceutical ingredient is 2:1 to 1:2.

[0216] 33. The drug-containing particle of any one of embodiments 1-32, wherein the one or more cannabinoids are present in amorphous form.

[0217] 34. The drug-containing particles of any one of embodiments 1-33, wherein the adsorption is measured by SEM, DSC, and / or XRPD.

[0218] 35. The drug-containing particle of any one of embodiments 1-34, wherein substantially all of the one or more cannabinoids are adsorbed within the pores of the porous solid carrier.

[0219] 36. The drug-containing particle of any one of embodiments 1 to 35, wherein the one or more cannabinoids are adsorbed within the pores of the porous solid carrier.

[0220] 37. The drug-containing particle of any one of embodiments 1-36, comprising a lipophilic material.

[0221] 38. The drug-containing particle of embodiment 39, wherein the lipophilic material comprises a stabilizer, viscosity modifier, and / or processability enhancer.

[0222] 39. The drug-containing particle of embodiment 37 or 38, wherein the lipophilic material comprises one or more non-ionic surfactants.

[0223] 40. The drug-containing particles of embodiment 39, wherein the one or more nonionic surfactants comprise polyoxyethylene sorbitan fatty acid esters (polysorbates, Tween®), polyoxyethylene 15 hydroxystearic acid (macrogol 15 hydroxystearate, solutol HS15®), polyoxyethylene castor oil derivatives (cremophor® EL, ELP, RH40), polyoxyethylene stearic acid (myrj®), sorbitan fatty acid esters (span®), polyoxyethylene alkyl ethers (brij®), polyoxyethylene nonylphenol ethers (Nonoxynol®), or combinations thereof.

[0224] 41. The drug-containing particle of embodiment 39 or 40, wherein the lipophilic material comprises one or more polyoxyglycerides.

[0225] 42. A drug-containing particle according to any one of embodiments 39 to 41, wherein the lipophilic material is one or more polyethylene oxide-containing fatty acid esters, one or more fatty acid glycerol esters, one or more.

[0226] 43. The drug-containing particle of embodiment 33 or 34, wherein the lipophilic material comprises one or more of stearoyl polyoxyl-32 glycerides (gelucire 50 / 13, gelucire 43 / 01), lauroyl polyoxyl-6-glycerides (labrafil M2130), oleoyl polyoxyl-6-glycerides (labrafil 1944), monoesters / diesters of 12-hydroxystearic acid and macrogol (crodasol HS), PEG-40 hydrogenated castor oil (croduret 40), propylene glycol monocaprylate (capryol 90), medium-chain triglycerides (labrafac 1349), propylene glycol dicaproate / dicaprate (labrafac PG), caprylocaproyl polyoxyl-8-glycerides (labrasol ALF), or combinations thereof.

[0227] 39. The drug-containing particle of any one of embodiments 32 to 38, wherein the lipophilic material is present in an amount of about 1% by weight to about 75% by weight, based on the total weight of the drug-containing particle.

[0228] 40. A drug-containing particle described in any one of embodiments 32 to 38, wherein the lipophilic material is present in an amount ranging from about 25% by weight to about 35% by weight, based on the total weight of the drug-containing particle.

[0229] 41. The drug-containing particle of any one of embodiments 1 to 23, wherein the weight ratio of the solid carrier to the total weight of the drug substance and the lipophilic material is in the range of 3:1 to 1:1.

[0230] 42. The drug-containing particle of embodiment 33 or 34, wherein the lipophilic material is sesame seed oil or pumpkin seed oil.

[0231] 43. The drug-containing particle of embodiment 42, wherein the lipophilic material is present in an amount ranging from about 25% by weight to about 75% by weight, based on the total weight of the drug-containing particle.

[0232] 44. The drug-containing particle of embodiment 42, wherein the sesame seed oil is present in an amount ranging from about 45% to about 60% by weight, based on the total weight of the drug-containing particle.

[0233] 45. A drug-containing particle according to any one of embodiments 1 to 44, comprising a polymer.

[0234] 46. The polymer has a T of about 50°C to about 130°C. g 46. The drug-containing particle of embodiment 45, having

[0235] 47. The drug-containing particle of embodiment 45 or 46, wherein the polymer comprises polyvinylpyrrolidone (kollidon VA64), cross-linked polyvinyl N-pyrrolidone (crospovidone), hydroxypropyl methylcellulose phthalate (HPMCP50), polyvinyl alcohol-polyethylene glycol copolymer (kollicoat), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (soluplus), polyvinyl alcohol, or a combination thereof.

[0236] 48. The drug-containing particle of any one of embodiments 45-47, wherein the polymer is present in an amount of about 1% by weight to about 75% by weight, based on the total weight of the drug-containing particle.

[0237] 49. The drug-containing particle of any one of embodiments 45-47, wherein the polymer is present in an amount of about 10% by weight to about 50% by weight, based on the total weight of the drug-containing particle.

[0238] 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.

[0239] 51. The drug-containing particle of any one of embodiments 1-50, further comprising a chelating agent.

[0240] 52. The drug-containing particles of embodiment 51, wherein the chelating agent comprises EDTA, citric acid, or curcumin.

[0241] 53. The drug-containing particles of embodiment 51, wherein the chelating agent comprises citric acid or curcumin.

[0242] 54. A drug-containing particle described in any one of embodiments 51 to 53, wherein the amount of the chelating agent is in the range of about 0.05% by weight to about 3% by weight, based on the total weight of the drug-containing particle.

[0243] 55. A drug-containing particle described in any one of embodiments 51 to 53, wherein the amount of the chelating agent is in the range of about 0.05% by weight to about 0.1% by weight, based on the total weight of the drug-containing particle.

[0244] 56. A drug-containing particle according to any one of embodiments 1 to 55, comprising one or more antioxidants.

[0245] 57. The drug-containing particles of embodiment 56, wherein the one or more antioxidants comprise α-tocopherol, β-carotene, ascorbic acid, ascorbyl palmitate, lecithin, butylated hydroxyanisole, butylated hydroxytoluene, monothiolglycerol, propyl gallate, or a combination thereof.

[0246] 58. The drug-containing particle of embodiment 56 or 57, wherein the antioxidant comprises α-tocopherol.

[0247] 59. A drug-containing particle described in any one of embodiments 56 to 58, wherein the one or more cannabinoids are present in an amount ranging from about 0.05% by weight to about 3% by weight, based on the total weight of the drug-containing particle.

[0248] 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% by weight to 1% by weight, based on the total weight of the drug-containing particle.

[0249] 61. A drug-containing particle described in any one of claims 1 to 60, wherein about 30 to 90% of the one or more cannabinoids is released in about 3 to 12 hours.

[0250] 62. A drug-containing particle described in any one of claims 1 to 60, wherein approximately 50 to 90% of the one or more cannabinoids is released in approximately 3 to 12 hours.

[0251] 63. A drug-containing particle described in any one of claims 1 to 60, wherein greater than about 80% of the one or more cannabinoids is released in about 3 to 12 hours.

[0252] 64. A drug-containing particle described in any one of claims 1 to 61, comprising about 0.2% by weight or less of cannabidiol chol (CBD-C1).

[0253] 65. The drug-containing particle of any one of claims 1 to 64, comprising about 0.8% by weight or less of cannabidivarin (CBDV).

[0254] 66. The drug-containing particle of any one of claims 1 to 65, comprising less than about 0.5% by weight of cannabidibutol (CBD-C4).

[0255] 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.

[0256] 68. The pharmaceutical composition of claim 67, wherein the pharmaceutical composition is a tablet, capsule, or granule.

[0257] 69. The pharmaceutical composition of any one of claims 1-68, wherein the drug-containing particles are prepared by a process including spray drying or hot melt extrusion.

[0258] 70. A method for preparing drug-containing particles according to any one of claims 1 to 32 and 45 to 66, comprising: (a) combining the porous solid support, the one or more cannabinoids, and optionally the polymer to form a mixture; (b) adding a solvent to the mixture to form a slurry; (c) sonicating and / or stirring the slurry; and (d) evaporating the solvent to obtain a dry powder.

[0259] 71. A method for preparing drug-containing particles according to any one of claims 1 to 44 and 51 to 66, comprising: (a) combining said one or more cannabinoids with said one or more lipophilic materials to form a mixture; (b) stirring the mixture of step (a) until homogeneous; (c) adding the homogeneous mixture of step (b) to the porous solid support; and (d) stirring the mixture of step (c) until homogeneous. [Example]

[0260] Example 1: Evaluation of solvent-mediated drug loading on mesoporous silica

[0261] Drug-containing particles having the compositions presented in Table 1 were prepared according to the solvent-mediated manufacturing method described in FIG.

[0262] [Table 15]

[0263] Stability Testing: The stability of the CBD-containing drug particles in Table 1 was evaluated after 7 days at an accelerated temperature of 60°C. Stability achievement criteria are shown in Table 2A. The amounts of CBD degradants CBE I, CBE II, and OH-CBD, as well as THC, are shown in Table 2A as percent of active ingredients.

[0264] [Table 16]

[0265] [Table 17]

[0266] The formulations were stored at 60°C and evaluated for amorphousness by XRPD at 0 and 7 days. XRPD diffractograms for the initial and 1-week time points are shown in Figures 23A and 23B, respectively. The diffractograms show that all of the 25 wt% and 50 wt% batches were amorphous by XRPD. The 75 wt% Fujisil batch was not amorphous and showed peaks indicative of crystalline CBD. There was no change in the crystalline state of any of the batches after 7 days of storage at 60°C.

[0267] Table 2: Drug release profiles. Drug release from 50 wt% CBD-loaded Syloid particles and 50 wt% CBD-loaded Fujisil particles was evaluated. As shown in Figure 6, CBD was effectively released from Syloid silica, reaching 80% release at 60 minutes. In addition, Syloid exhibited superior flow properties after loading with the active pharmaceutical ingredient compared to Fukisil. Therefore, Syloid was selected for further development.

[0268] Example 2: Evaluation of CBD-loaded mesoporous silica drug particles prepared by spray drying

[0269] The spray-dried drug-containing particles were characterized as shown in Tables 3 and 4. The particles were prepared according to the method described in Figure 7. An exemplary spray-drying apparatus is depicted in Figure 8.

[0270] [Table 18]

[0271] [Table 19]

[0272] The spray drying process was carried out in a Buchi B-290 apparatus using the following parameters:

[0273] Inlet temperature: 60℃ (Syloid) / 80℃ (Neusilin)

[0274] Chiller temperature: -20℃

[0275] Aspirator: 100%

[0276] Feeding rate: 20g / min

[0277] Q-flow: 65mm (Syloid) / 60mm (Neusilin)

[0278] Nozzle size: 2.1mm

[0279] Drying after collection: 2 days at 30°C under dynamic vacuum (Syloid) / 24 hours at 40°C under vacuum (Neusilin)

[0280] In all cases, the materials tested were easily processed and no handling problems were observed.

[0281] Example 3: Evaluation of CBD / lipid-loaded mesoporous silica drug particles The compositions of various CBD / lipid-loaded mesoporous silica drug particles prepared according to the method provided in Figures 9A-C are shown in Table 5.

[0282] In particular, CBD / sesame oil-loaded mesoporous silica drug particle formulations 1-6 in Table 5 were prepared according to the process described in Figure 9A. CBD / lipid-loaded mesoporous silica drug particle formulations 7-10 were prepared according to the process described in Figure 9B.

[0283] For the formulations shown in Table 5, all compositions exhibited amorphous properties, confirming cannabinoid adsorption. Crystallinity was observed when the drug loading exceeded 60%.

[0284] [Table 20-1] [Table 20-2]

[0285] A primary solution of 12.48% (w / w) CBD, 37.40% (w / w) pumpkin seed oil, and 0.1% α-tocopherol was prepared by substituting sesame seed oil with pumpkin seed oil. This solution was added to Neusilin® in ratios of 1:1, 1.5:1, and 2.3:1 to provide drug particles loaded with 17.5%, 15.0%, and 12.5% (w / w) CBD. This composition was found to be amorphous.

[0286] Other solid and liquid lipophilic materials were evaluated for their ability to dissolve CBD. The solid lipophilic materials evaluated are listed below in Table 6A, with solubility observations shown in Table 6B. The liquid lipophilic materials evaluated are listed in Table 7A, with solubility observations shown in Table 7B.

[0287] [Table 21]

[0288] [Table 22]

[0289] 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 30 minutes and then stirred to dissolve. Ten grams of each combination was prepared in a clear glass scintillation vial, cooled, and then evaluated using DSC to determine whether any undissolved CBD was present. Any excipients that demonstrated complete CBD solubility at 500 mg / g were further evaluated at 540, 560, and 600 mg / g. The results are shown in Table 6B.

[0290] [Table 23]

[0291] Each liquid lipophilic material was heated in an oven at 40°C for 30 minutes before being combined with CBD. 10g of CBD was combined with 5g of lipophilic material to create a saturated mixture. These were agitated at 300 rpm using a shaker plate for at least 8 hours. After agitation, the solution was centrifuged at 14800 rpm for 90 minutes to separate any remaining undissolved CBD crystals. The resulting supernatant was sampled and assayed for CBD content to confirm saturated lipid solubility. The dissolution results are presented in Table 7B below.

[0292] [Table 24]

[0293] Lipophilic materials that are being taken forward for further development are listed in Table 8.

[0294] [Table 25]

[0295] Additional CBD / lipid-loaded mesoporous silica drug particles, for example, formulations 1-10 in Table 8, were prepared according to the process described in Figure 9C without antioxidants.

[0296] Using the dissolution test conditions listed in Tables A1 (Gelucire and Capryol samples) and A2 (Labrafil samples), drug release from each of the CBD / lipid-loaded particles was measured, and the results are summarized in the dissolution graph in Figure 10. In all cases, approximately 70%-80% of the CBD in the drug particles was released within approximately 6 hours.

[0297] [Table 26]

[0298] 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 very stable.

[0299] [Table 27]

[0300] [Table 28]

[0301] CBD / lipid-loaded mesoporous silica drug particles containing antioxidants were also prepared according to the process described in Figure 9C to evaluate the stability of these materials. The composition of these drug particles is summarized in Table 11.

[0302] [Table 29-1] [Table 29-2]

[0303] 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 Tables 12 and 13, respectively. Each formulation was found to be amorphous and very stable.

[0304] [Table 30]

[0305] [Table 31]

[0306] CBE I was observed for the Labrafil 1944 composition after 6 weeks at 25°C / 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.

[0307] Compositions containing propylene glycol monocaprylate (Capryol 90) were evaluated for CBD solubility and stability. CBD was dissolved in propylene glycol monocaprylate (Capryol 90) and loaded into Aeroperl®. The formulations are shown in Table 14. Other lipids were also tested and crystallization was observed. Additional lipid candidates will be screened.

[0308] [Table 32]

[0309] 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 found to be amorphous and very stable.

[0310] [Table 33]

[0311] Formulations were then prepared using mixtures of two or three lipophilic materials and are shown in Table 16.

[0312] [Table 34-1] [Table 34-2]

[0313] The binary and ternary lipid mixtures were completely miscible and provided a medium in which CBD could be dissolved and loaded onto the mesoporous silica. The stability of the compositions listed in Table 16 was evaluated after 6 weeks at 40°C and 75% RH. The results are summarized in Table 17. CBD remained amorphous and chemically stable in these compositions.

[0314] [Table 35]

[0315] Example 4: Preparation of CBD / polymer formulations by solvent-mediated manufacturing CBD / polymer-loaded drug particles having the compositions presented in Table 18 were prepared according to the process described in Figure 11.

[0316] [Table 36] The following polymers were each present in the above composition: HPMC50 (hydroxypropyl methylcellulose phthalate) Kollidon K30 (Polyvinylpyrrolidone) Kollidon VA64 (Polyvinylpyrrolidone / Vinyl Acetate) Soluplus (Polyvinylcaprolactam-Polyvinylacetate-Polyethyleneglycol Graft Copolymer) Kollicoat MAE (Polyvinyl alcohol-Polyethylene glycol copolymer)

[0317] Additional polymers suitable for inclusion in these formulations are listed in FIG.

[0318] 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.

[0319] Table 19 shows CBD-containing drug particle compositions comprising Syloid® XDP silica prepared according to the spray drying method disclosed herein.

[0320] [Table 37]

[0321] The spray drying process was carried out in a Buchi B-290 apparatus using the following parameters:

[0322] Inlet temperature: 80℃

[0323] Chiller temperature: -20℃

[0324] Aspirator: 100%

[0325] Feeding rate: 20g / min

[0326] Q flow rate: 60mm

[0327] Nozzle size: 2.1mm

[0328] Drying after collection: Under vacuum at 40℃ for 24 hours

[0329] Kollidon K30 was evaluated in the formulation, but drug-containing particles incorporating this polymer did not process well and require further optimization.

[0330] Example 5: Stability study of lipid-loaded mesoporous silica drug particles containing antioxidants The presence of antioxidants was evaluated in two stages to investigate its effect on stability.

[0331] Stage 1: Formulations containing 100 mg of CBD per capsule were evaluated at two levels of α-tocopherol (0% and 0.2%), and stability was measured over 6 weeks at ambient and accelerated conditions, 40°C / 75% RH and 25°C / 60% RH. The formulations tested are described in Example 3, Table 6. To evaluate the effect of α-tocopherol, 0.2% α-tocopherol was added to the formulations described in Table 6. Changes in API (CBD) content and impurities were measured over 6 weeks and are shown in Figures 13-17. A summary of the formulations tested is provided in Table 20. Table 21 shows the specifications established for viable product candidates. Figure 13A shows that 0.2% α-tocopherol protects CBD from degradation over 6 weeks at 25°C / 60% RH, while Figure 13B shows the decrease in CBD content measured in a similar formulation prepared without α-tocopherol. A similar trend was observed when measuring degradants under accelerated conditions. Specifically, the presence of α-tocopherol reduced the amount of CBE I (Figure 14A vs. 14B), CBE II (Figure 15A vs. 15B), and other unknown degradants (Figure 16A vs. 16B). Formulations containing α-tocopherol exhibit better stability performance when compared to formulations without α-tocopherol under the same accelerated storage conditions, excluding OH-CBD (Figure 17A vs. 17B).

[0332] [Table 38]

[0333] [Table 39]

[0334] Stage 2: Formulations containing 100 mg of CBD per capsule and 0.2%, 0.6%, or 1.0% α-tocopherol were evaluated for stability over 12 weeks at 25°C / 60% RH, 30°C / 65% RH, and 40°C / 75% RH.

[0335] The compositions of the formulations tested are summarized in Table 22.

[0336] [Table 40]

[0337] The XRPD diffractogram of the test formulation at 12 weeks is shown in Figure 24. No change in the amorphous state of the formulation was observed upon storage at 40°C / 75% RH for 12 weeks. Figures 18A-D show that 0.2%, 0.6%, and 1% α-tocopherol generally prevented CBD degradation in Gelucire® 43 / 10-loaded formulations over 12 weeks at 40°C / 75°C, reducing the amount of degradants CBE I, CBE II, OH-CBD, and total degradants. However, Gelucire® 43 / 01 showed anomalous data with 0.6% α-tocopherol content producing the poorest results, with 0.2% and 1% showing better results. Figures 19A-D show that 0.2%, 0.6%, and 1% α-tocopherol generally prevent CBD degradation in Labrafil® M2130-loaded formulations over 12 weeks at 40°C / 75°C, with the best performance demonstrated by 1% (w / w) α-tocopherol content. Figures 20A-D show that 0.2%, 0.6%, and 1% α-tocopherol generally prevent CBD degradation in Capryol® 90-loaded formulations over 12 weeks at 40°C / 75°C, with the best performance shown by an α-tocopherol content of 0.6% (w / w).

[0338] Example 6: Capsule preparation Drug-containing particles were prepared and added to capsules as described in Example 3. Capsules containing 100 mg of cannabinoid drug substance and 150 mg of cannabinoid drug substance were prepared as described in Tables 23 and 24.

[0339] [Table 41]

[0340] [Table 42]

[0341] Example 7. Dog Study

[0342] [Table 43-1] [Table 43-2] [Table 43-3] [Table 43-4] [Table 43-5]

[0343] Goal Profile

[0344] Similar or better bioavailability in capsules compared to CBD oral solution

[0345] No vomiting

[0346] Liquid / loose stools <2

[0347] Total ob<3.25

[0348] No loss of appetite

[0349] The CBD oral solution in capsules established a baseline target profile. Product candidates had properties comparable to or superior to the CBD oral solution. Compositions that did not meet the target profile were not advanced. As shown in Table 25, compositions containing CBD dissolved in lipids and loaded onto porous solid carriers ("lipid carriers") exhibited superior pharmacokinetics compared to compositions prepared with the same lipids and spray-dried CBD-containing compositions (see also Table 26). Furthermore, the lipid-loaded carrier compositions exhibited superior gastrointestinal tolerability compared to all compositions, including the CBD oral solution. Figures 21A-C demonstrate that the weight ratio of CBD to lipophilic material does not significantly affect bioavailability.

[0350] [Table 44-1] [Table 44-2]

[0351] Compositions prepared using a porous carrier and GELUCIRE® 40 / 01, CAPRYOL® 90, and LABRAFIL® M2130 had favorable profiles and were selected for forward movement.

[0352] [Table 45] overview Lipid-loaded formulations offer a favorable profile from which positive physical and chemical data are generated. CBD remains in amorphous form without the use of antioxidants Syloid maintained flowable powder properties at 24% drug loading Neuselin maintained flowable powder properties at 21% drug loading Similar to sesame seed oil, pumpkin seed oil was evaluated with MPS and Neusilin and showed desirable properties. · The introduction of a combination of chelating agents and / or AOs was found to improve the stability of the formulation.

[0353] Example 8. Rat studies The compositions listed in Table 25 were administered to rats. The bioavailability of the compositions was evaluated in comparison to an oral solution of CBD in sesame oil or a suspension in water methylcellulose (Figures 22A-C). No adverse events were observed in the rat model study.

Claims

1. A drug-containing particle, comprising: (a) a drug substance comprising one or more cannabinoids; and (b) a porous solid support; The one or more cannabinoids are adsorbed onto the porous solid support, the porous solid support comprising: (i) an average pore volume of about 1 mL / g to about 2 mL / g; (ii) Approximately 250m ２ / g ~ approx. 375m ２ / g average surface area, 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. 3. The drug-containing particle according to claim 1, wherein the porous solid carrier has an average particle size of about 1 μm to about 250 μm.

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

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

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

8. The porous solid support is (a) an average pore volume of about 1 mL / g to about 2 mL / g; (d) Approximately 250m ２ / g ~ approx. 375m ２ / g average surface area, or The drug-containing particle according to any one of claims 1 to 7, having two or more of the following characteristics: (c) a pore diameter of about 2 nm to about 50 nm.

9. The porous solid support is (a) an average pore volume of about 1 mL / g to about 2 mL / g; (d) Approximately 250m ２ / g ~ approx. 375m ２ / g of average surface area, and (c) the drug-containing particle according to any one of claims 1 to 8, having a pore size of about 2 nm to about 50 nm.

10. The porous solid support is silica (SiO ２ 10. The drug-containing particle of claim 1, comprising: 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 silica or a silicate.

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

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

14. The drug-containing particle according to any one of claims 10 to 12, wherein the silica comprises mesoporous silica.

15. The drug-containing particle according to any one of claims 1 to 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 aluminate.

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

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

20. 20. The drug-containing particle of any one of claims 1 to 19, wherein the one or more cannabinoids comprise cannabichromene (CBC), cannabichromene acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabidiol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic 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 to 20, wherein the one or more cannabinoids include CBD.

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

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

24. 24. The drug-containing particle of any one of claims 1 to 23, wherein the one or more cannabinoids are present in an amount of about 15% to about 40% by weight, 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 active pharmaceutical ingredient 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 active pharmaceutical ingredient is 2:1 to 1:

2.

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

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

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

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

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

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

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

34. 34. The drug-containing particle of claim 33, wherein the one or more non-ionic surfactants comprise polyoxyethylene sorbitan fatty acid esters (polysorbates, Tween®), polyoxyethylene 15 hydroxystearic acid (macrogol 15 hydroxystearate, solutol HS15®), polyoxyethylene castor oil derivatives (cremophor® EL, ELP, RH40), polyoxyethylene stearic acid (myrj®), sorbitan fatty acid esters (span®), polyoxyethylene alkyl ethers (brij®), polyoxyethylene nonylphenol ethers (Nonoxynol®), or combinations thereof.

35. The drug-containing particle of any one of claims 31 to 34, wherein the lipophilic material comprises polyethylene oxide-containing fatty acid esters, polyethylene oxide glycerides, polypropylene glycol fatty acid esters, PEG, monoglyceride fatty acid esters, diglyceride fatty acid esters, triglyceride fatty acid esters, propylene glycol diglycerides, polyethylene oxide vegetable oils, or combinations thereof.

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

37. The lipophilic material may be selected from the group consisting of mono-, di-, and triglyceride esters of palmitic acid (C16) and stearic acid (C18), and PEG-32 (MW 1500) mono- and diesters of palmitic acid (C16) and stearic acid (C18); mono-, di-, and triglyceride esters of fatty acids (C8-C18); mono-, di-, and triglyceride esters of lauric acid (C12) and stearic acid (C18), and PEG-6 (MW 300) mono- and diglyceride esters of lauric acid (C12) and stearic acid (C18). and diesters; mono-, di-, and triglyceride esters of oleic acid (C18:1), and PEG-6 (MW 300) and mono- and diesters of oleic acid (C18:1); 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 dicaprate / propylene glycol dicaprate; caprylic acid (C ８ ) and capric acid (C １０ 37. The drug-containing particle of claim 35 or 36, comprising PEG-8 (MW 400) mono- and diesters of PEG-8 (MW 400); or a combination thereof.

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

39. The drug-containing particle of claim 35, wherein the vegetable oil comprises one or more of plant seed oils, fruit seed oils, kernel oils, sesame seed oil, medium-chain triglyceride (MCT) oil, oleic acid oil, pumpkin seed oil, interesterified vegetable oil, polyoxyethylene hydrogenated vegetable oil, PEG-40 hydrogenated castor oil, or a combination thereof.

40. 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 to 38, wherein the lipophilic material is present in an amount of about 1% to about 75% by weight, based on the total weight of the drug-containing particle.

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

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

1.

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

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

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

47. The polymer has a T ｇ The drug-containing particle of claim 44, having:

48. The drug-containing particle of claim 46 or 47, wherein the polymer comprises polyvinylpyrrolidone (kollidon VA64), cross-linked polyvinyl N-pyrrolidone (crospovidone), hydroxypropyl methylcellulose phthalate (HPMCP50), 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 to 48, wherein the polymer is present in an amount of about 1% to about 75% by weight, based on the total weight of the drug-containing particle.

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

51. The drug-containing particle of any one of claims 46 to 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 to 51, further comprising a chelating agent.

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

54. 53. 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 to 54, wherein the amount of the chelating agent is in the range of about 0.05% by weight to about 3% by weight, based on the total weight of the drug-containing particle.

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

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

58. 58. The drug-containing particle of claim 57, wherein the one or more antioxidants comprise α-tocopherol, β-carotene, ascorbic acid, ascorbyl palmitate, lecithin, butylhydroxyanisole, butylhydroxytoluene, monothiolglycerol, propyl gallate, or a combination thereof.

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

60. 60. The drug-containing particle of any one of claims 57 to 59, wherein the amount of the one or more antioxidants is in the range of about 0.05% by weight to about 3% by weight, 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 is in the range of about 0.2% by weight to about 1% by weight, based on the total weight of the drug-containing particle.

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

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

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

65. 65. The drug-containing particle of any one of claims 1 to 64, comprising about 0.2% by weight or less of cannabidiol (CBD-C1).

66. 66. The drug-containing particle of any one of claims 1 to 65, comprising about 0.8% by weight or less of cannabidivarin (CBDV).

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

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

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

71. 10. A method for preparing a drug-containing particle according to any one of the preceding claims, comprising: (a) combining the porous solid support, the one or more cannabinoids, and optionally the polymer to form a mixture; (b) adding a solvent to the mixture to form a slurry; (c) sonicating and / or stirring 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 a drug-containing particle according to any one of claims 1 to 45 and 52 to 69, comprising: (a) combining said one or more cannabinoids with said one or more lipophilic materials to form a mixture; (b) stirring the mixture of step (a) until homogeneous; (c) adding the homogeneous mixture of step (b) to the porous solid support; and (d) stirring the mixture of step (c) until homogeneous, thereby absorbing the one or more cannabinoids onto the porous solid support.

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

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

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

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

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

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

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

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

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

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

83. 10. The drug-containing particle of any one of the preceding claims, wherein the drug release is measured using the United States Pharmacopoeia (USP) dissolution test (711).

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

85. 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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