CANNABINOID AND PSYCHEDELIC FORMULATIONS COMPRISING HYDROTROPIC AGENTS

Field of the Invention

The invention relates to the field of pharmaceutical formulations, more particularly rapidly dissolving tablet formulations of certain hydrophobic active compounds, such as cannabinoids and psychedelics.

The present invention utilizes hydrotropic agents to increase water-solubility of either cannabinoid molecules or psychedelics molecules.

Final products are in the form of tablets, buccal tablets or sublingual tablets, which are super-fast disintegrating and which are formulated to disintegrate post-administration in less than 60 seconds.

Background of the Invention

Cannabinoids and psychedelic drugs have gained prominence in recent years, with numerous therapeutic properties being claimed, researched, and developed.

Cannabinoids

Cannabinoids, as a class of compound, are well known and well characterized. The most commonly known cannabinoid is the tetrahydrocannabinol, the primary psychoactive compound in cannabis. However, this molecule is part of a large family of molecules, which include cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabinol (THC), cannabigerolic acid monomethlether (CBGAM), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabinodiol (CBND), delta-9-tetrahydrocannabivarin (THCv), cannabinol-C2 (CBN-C2), cannabinol-C4 (CBN-C4), cannabinolic acid (CBNA), cannabiorcool (CBN-C1), cannabivarin (CBV), cannaitriol (CBT), cannabitriolvarin (CBTV), cannabichromanon (CBCF), cannabifuran (CBF), cannabiglendol (OH-iso-HHCV), cannabiripsol (CBR), cannbicitran (CBT), or 6- methano-2H-l-benzoxocin-5-methanol, 10-Ehtoxy-9-hydroxy-delta-6a-tetra hydrocannabinol, cannabielsin (CBE), 8,9-dihydroxy-delta-6a-tetrahydrocannbinol, delta-8-tetrahydrocannabinol, delta-8-tetrahydrocannabinolic acid, delta-9-tetrahydrocannabinol-C4 (THC-C4), delta-9- tetrahydrocannabinoic acid A (THCA-A), delta-9-tetrahydrocannabinolic acid B (THCA-B), delta-9- tetrahydrocannabinolic acid-C4 (THCA-C4), delta-9-tetrahydrocannabiorcol (THC-C1), delta-9- tetrahydrocannabiorolic acid (THCA-C1), delta-9-tetrahydrocannabivarinic acid (THCVA), 10-Oxo- delta-6a-tetrahydrocannbinol (OTHC), dehydrocannbifuran (DCBF), delta-9-cis- tetrahydrocannabinol (cis-THC), trhydroxy-delta-9-tetrahydrocannabinol (triOH-THC), 3, 4,5,6, - tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2, cannabichromenic acid (CBCA), cannabicyclol (CBL), cannabicyclolic acid (CBLA), cannabicyclovarin (CBLV), cannabivarin (CBV), Cannabidivarin (CBDVa), cannabinodiol (CBND), cannabielsion (CBE), cannabicyclol (CBL), cannabicyloic acid (CBLA), cannabitriol (CBT), cannabidiol monomehylerther (CBDM), cannabidiolic acid (CBDA), cannabidiorcol (CBD-C1), cannabielsoic acid B (CBEA-B), cannabielsoin acid A (CBEA-A), cannabigerol (CBG), cannabigerol monomethlether (CBGM), cannabigerolic acid (CBGA), cannabigerolic acid (CBGA), cannabinodivarin (CBVD), cannabinol methlether (CBNM).

A number of cannabinoid-based pharmaceuticals are currently known, with many others being researched and in the clinic. These include nabiximols (Sativex™), dronabinol (Marinol™), and Epidiolex™. Cannabinoid pharmaceuticals include natural products (including dried plant product), isolates, extracts, and resins, as well as synthetically produced compounds.

In addition to their traditional, recreational uses, Cannabinoids have increasingly been found to have advantageous pharmaceutical properties, and are used, approved, or in clinical trials for treatment of a variety of ailments, disorders and diseases.

Psychedelics

Psychedelic drugs are also well known. Psychedelic molecules can include Psilocybin, Psilocin, or Psilocybin hydrochloride, N-methyl-3,4-methylenedioxyamphetamine (MDMA), N-methyl-3,4- methylenedioxyamphetamine hydrochloride, N-N-Dimethyltryptamine (DMT), N-N- Dimethyltryptamine hydrochloride, Lysergic Acid Diethylamide (LSD), Lysergide Tartrate, Ketamine, Ketamine hydrochloride, as well as their derivatives, salt or acid forms, or mixtures thereof.

In addition to their traditional, recreational uses, psychedelics have increasingly been found to have advantageous pharmaceutical properties, and are used, approved, or in clinical trials for treatment of a variety of ailments, disorders and diseases.

Solubility

Increasing the solubility of cannabinoids and psychedelic compounds is a current problem in industry. Solubility is one of the prime features to aid with accomplishing a desired pharmacological response. Therapeutic effectiveness of a finished product depends upon the bioavailability and ultimately is attributed to solubility of molecule moiety. Presently, numerous formulation technologies are available to enhance solubility as well as dissolution profile to enhance oral bioavailability. In addition to these technologies, Hydrotropy is one of the recognized techniques available for resolving solubility issues. Hydrotropy is suggested to be superior to the other solubilization methods, such as miscibility, micelles solubilization, cosolvency and salting in.

Hydrotropy is a molecular phenomenon whereby adding a second solute (the hydrotrope) results in an increase in the aqueous solubility of poorly soluble solutes. Solubility enhancement is one of the advantages of hydrotropes. Hydrotropes contain both hydrophobic and hydrophilic fractions in them. In comparison to surfactant, they contain a very small hydrophobic fraction. The efficiency of hydrotrope solubilization depends on the balance between hydrophobic and hydrophilic part of hydrotrope. The larger is the hydrophobic part of an additive, the better is the hydrotropic efficiency; the presence of the charge on the hydrophilic part is less significant. These are freely soluble organic compounds which enhance the aqueous solubility of organic substances by forming stack-type aggregation. Hydrophobic materials can help in processing various products.

Added substances or salts that expansion dissolvability in given dissolvable is said to "salt in" the solute and those salts that lessening solvency "salt out" the solute. A few salts with huge anions or cations that are themselves solvent in water bring about "salting in" of nonelectrolytes called "hydrotropic salts"; a wonder is known as "hydrotropism." Hydrotrophy assigns the expansion in dissolvability in water because of the nearness of enormous measure of added substances.

The mechanism by which it improves solubility is more closely related to complexation involving a weak interaction between the hydrotropic agents like sodium benzoate, sodium acetate, sodium alginate, urea, and the poorly soluble molecules.

The hydrotropic agents who are present in the synthetic and natural form which are defined as non-micelle- forming substances either liquids or solids, organic and in organic, which is capable of solubilizing insoluble compounds.

A hydrotropic molecule interacts with a less water-soluble molecule via weak van der Waals interactions such as n-n or attractive dipole-dipole interaction. The enhancement of watersolubility by hydrotrope is based on the molecular self-association of hydrotrope and on the association of hydrotrope molecules with the solute. The available proposed mechanisms can be abridged according to three designs, (i) Self-aggregation potential: Minimum hydrotropic concentration (MHC), is a critical concentration at which hydrotrope molecules start to aggregate, i.e. self-aggregation potential. Solubilization power of hydrotropes is governed by their self-aggregation potential. This potential depends upon their amphiphilic features and the nature of the solute molecule. They mainly show the volume fraction dependent solubilization potential. Hydrotropes strongly interact with the solute to generate the complexes and these complexes would then lead to higher aqueous solubility, (ii) Structure-breaker and structuremaker: An electrostatic force of the donor-acceptor molecule plays a vital role in the hydrotropic solubilization; hence, they are also termed as a structure-breaker and a structure-maker. Solutes which are capable for both hydrogen donation and acceptance help to increase solubility. Solutropic agents like urea exert their solubilizing effect by changing the nature of the solvent, specifically by altering the solvent's ability to participate in structure formation or its ability of engaging in structure formation via intermolecular hydrogen bonding. Structure-breaker hydrotropes are known as chaotropes while structure maker hydrotropes are known as kosmotrope. Kosmotrope reduces the critical micelle concentration, or CMC by increasing the hydrophobic interaction which decreases the cloud point, (iii) Ability to form micelles like structure This mechanism is based on the self-association of hydrotropes with solutes into a micellar arrangement. Basically they form stable mixed micelles with a solute molecule decreasing electrostatic repulsion between the head groups. Hydrotropes like alkylbenzene sulfonates, lower alkanoates and alkyl sulfates exhibit self-association with solutes and form micelles. Aromatic anionic hydrotrope i.e. nicotinamide, improve solubility of riboflavin via selfassociation mechanism.

There are various hydrotropic agents that have been employed to enhance aqueous solubility of various poorly water-soluble pharmaceutical molecules. This approach may confer an advantage for developing various formulations of poorly water-soluble pharmaceutical molecules combining various water-soluble excipients in safe concentration. Hydrotropic agents can be anionic, cationic or neutral, organic or inorganic and liquids or solids in nature. The aromatic hydrotropes with anionic head groups are mostly studied compounds and are large in number because of isomerism and their effective hydrotrope action may be due to the availability of interactive pi (n) orbital.

Brief Description of Figures

Figure 1 shows a photograph of a blend of CBD and hydrotropic agent, according to one aspect of the present invention.

Figure 2 shows a photograph of a blend of CBD, hydrotropic agent, and tableting excipients, according to a further aspect of the present invention.

Figure 3 shows a rapidly dissolving CBD tablet according to a further aspect of the present invention.

Summary of the Invention

According to one aspect of the present invention is provided a composition, comprising: one or more active pharmaceutical compound selected from a cannabinoid and/or a psychedelic compound; and a hydrotropic agent.

In certain embodiments, the composition further comprises at least one tableting excipient.

According to certain embodiments, the tableting excipient comprises one or more of an antiadherent, a binder, a terpene, a coating, a color, a diluent, a disintegrant, a filler, a flavor, a glidant, a lubricant, a preservative, a sorbent, and a taste enhancing agent.

According to certain embodiments, the cannabinoid is one or more compound selected from cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabinol (THC), cannabigerolic acid monomethlether (CBGAM), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabinodiol (CBND), delta-9-tetrahydrocannabivarin (THCv), cannabinol-C2 (CBN-C2), cannabinol-C4 (CBN-C4), cannabinolic acid (CBNA), cannabiorcool (CBN-C1), cannabivarin (CBV), cannaitriol (CBT), cannabitriolvarin (CBTV), cannabichromanon (CBCF), cannabifuran (CBF), cannabiglendol (OH-iso-HHCV), cannabiripsol (CBR), cannbicitran (CBT), or 6-methano-2H-l-benzoxocin-5-mehtnaol, 10-Ehtoxy-9-hydroxy-delta-6a-tetra hydrocannabinol, cannabielsin (CBE), 8,9-dihydroxy-delta-6a-tetrahydrocannbinol, delta-8-tetrahydrocannabinol, delta-8-tetrahydrocannabinolic acid, delta-9-tetrahydrocannabinol-C4 (THC-C4), delta-9- tetrahydrocannabinoic acid A (THCA-A), delta-9-tetrahydrocannabinolic acid B (THCA-B), delta- 9-tetrahydrocannabinolic acid-C4 (THCA-C4), delta-9-tetrahydrocannabiorcol (THC-C1), delta-9- tetrahydrocannabiorolic acid (THCA-C1), delta-9-tetrahydrocannabivarinic acid (THCVA), 10- Oxo-delta-6a-tetrahydrocannbinol (OTHC), dehydrocannbifuran (DCBF), delta-9-cis- tetrahydrocannabinol (cis-THC), trhydroxy-delta-9-tetrahydrocannabinol (triOH-THC), 3, 4,5,6, - tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2, cannabichromenic acid (CBCA), cannabicyclol (CBL), cannabicyclolic acid (CBLA), cannabicyclovarin (CBLV), cannabivarin (CBV), Cannabidivarin (CBDVa), cannabinodiol (CBND), cannabielsion (CBE), cannabicyclol (CBL), cannabicyloic acid (CBLA), cannabitriol (CBT), cannabidiol monomehylerther (CBDM), cannabidiolic acid (CBDA), cannabidiorcol (CBD-C1), cannabielsoic acid B (CBEA-B), cannabielsoin acid A (CBEA-A), cannabigerol (CBG), cannabigerol monomethlether (CBGM), cannabigerolic acid (CBGA), cannabigerolic acid (CBGA), cannabinodivarin (CBVD), cannabinol methlether (CBNM), or a mixture or extract thereof.

According to certain embodiments, the cannabinoid is an extract, an isolate, or a full spectrum, and is hemp-derived, cannabis plant-derived, or a synthetically produced molecule.

According to certain embodiments, the psychedelic agent is one or more compound selected from Psilocybin, Psilocin, or Psilocybin Hydrochloride, N-methyl-3,4- methylenedioxyamphetamine (MDMA), N-methyl-3,4-methylenedioxyamphetamine hydrochloride, N-N-Dimethyltryptamine (DMT), N-N-Dimethyltryptamine hydrochloride, Lysergic Acid Diethylamide (LSD), Lysergide Tartrate, Ketamine, Ketamine Hydrochloride, a pharmaceutical salt, derivative, or mixture thereof.

According to certain embodiments, the hydrotropic agent is one or more of sodium benzoate, sodium acetate, sodium alginate, urea, a chaotrope, a kosmotrope, and a micelle forming compound (alkylbenzene sulfonate, a lower alkanoate, an alkyl sulfate, nicotinamide).

According to certain embodiments, the hydrotropic agent comprises a compound with a cationic hydrophilic group, preferably a salt of aromatic amine, for example, procaine hydrochloride.

According to certain embodiments, the hydrotrophic agent comprises one or more compound with aromatic anionics.

According to certain embodiments, the compound with aromatic anionics comprises sodium benzoate, sodium salicylate, sodium p-aminosalicylate, sodium benzene sulfonate, sodium benzene di-sulfonate, sodium cinnamate, sodium 3-hydroxy-2-naphthoate, sodium para toluene sulfonate, sodium cumene sulfonate, nicotinamide, N, N - diethylnicotinamide, or N, N - dimethyl benzamide.

According to certain embodiments, the hydrotropic agent comprises one or more compound with aromatic cationics. According to certain embodiments, the compound with aromatic cationics comprises paraaminobenzoic acid hydrochloride, procaine hydrochloride, or an alkaloid (such as caffeine or nicotine).

According to certain embodiments, the hydrotropic agent comprises one or more aliphatics or linear compound.

According to certain embodiments, the aliphatic or linear compound comprises sodium alkanoate, urea, N,N-dimethyl urea, sodium citrate, sodium acetate, or metaformin hydrochloride.

According to certain embodiments, the hydrotropic agent comprises one or more of resorcinol, pyrogallol, catechol, alpha-naphthol, or beta-naphthol.

According to certain embodiments, the tableting excipient comprises an antiadherent, a binder, a terpene, a coating, a color, a diluent, a disintegrant, a filler, a flavor, a glidant, a lubricant, a preservative, a sorbent, or a taste-enhancing agent.

According to certain embodiments, the disintegrating agent comprises methyl cellulose, microcrystalline cellulose, powdered cellulose, lower alkyl substituted hydroxypropyl cellulose, crospovidone, Ac-Di-Sol™, sodium starch glycolate, various grades of Kollidon™, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, alginic acid, chitosan, polacrilin potassium, starch, pregelatinized starch, Ludiflash™, sodium alginate, or combinations thereof.

According to certain embodiments, the glidant comprises colloidal silica, silica gel, precipitated silica, silicon dioxide, colloidal silicon dioxide, LudiflashTM, calcium silicate, magnesium silicate, magnesium trisilicate, talc, starch, or combinations thereof.

According to certain embodiments, the flavoring agent comprises sucralose, tagatose, aspartame, mint, anise, raspberry, banana, grape, peach, peppermint, cherry, acesulfame potassium, saccharin, neotame, acesulfame K, or combinations thereof.

According to certain embodiments, the lubricant comprises hydrogenated vegetable oil, light mineral oil, magnesium stearate, mineral oil, polyethylene glycol, poloxamer, sodium benzoate, various grades of Avicel™, calcium stearate, glyceryl monostearate, glyceryl behenate, glyceryl palmitostearate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc, zinc stearate, or combinations thereof.

According to certain embodiments, the binder comprises saccharides and their derivatives, sucrose, lactose, starches, cellulose, methyl cellulose, polyvinlypyrrolidone, polyethylene glycol, xylitol, sorbitol, mannitol, gelatin, or combinations thereof. According to certain embodiments, the filler comprises lactose, starch, dextrose, sucrose, fructose, maltose, mannitol, sorbitol, kaolin, microcrystalline cellulose, powdered cellulose or any combination thereof.

According to certain embodiments, the terpene comprises monoterpenoids, sesquiterpenoids, sesterterpenoid, sesquarterpenoids, tetraterpenoids, triterpenoids, tetraterpenoids, Polyterpenoids, isoprenoids, steroids, or combinations thereof.

According to certain embodiments, the terpene comprises 8-dihydroionone, acetanisole, acetic acid, acetyl cedrene, anethole, anisole, benzaldehyde, bergamotene (a-cis-bergamotene, a- trans-bergamotene), bisabolol ([3-bisabolol, ot-bisabolol), borneol, bornyl acetate, butanoic/butyric acid, cadinene (ot-cadinene, y-cadinene), cafestol, caffeic acid, camphene, camphor, capsaicin, carene (A-3-carene, delta-3-carene), carotene, carvacrol, carvone, dextrocarvone, laevo-carvone, caryophyllene -caryophyllene), caryophyllene oxide, castoreum absolute, cedrene (ot-cedrene, -cedrene), cedrene epoxide (ot-cedrene epoxide), cedrol, cembrene, chlorogenic acid, cinnamaldehyde (a-amyl-cinnamaldehyde) (ot-hexyl- cinnamaldehyde), cinnamic acid, cinnamyl alcohol, citrone Ila I, citronellol, cryptone, curcumene (ot-curcumene, y-curcumene), decanal, dehydrovomifoliol, diallyl disulfide, dihydroactinidiolide, dimethyl disulfide, eicosane/icosane, elemene (8-elemene), estragole, ethyl acetate, ethyl cinnamate, ethyl maltol, eucalyptol/l,8-cineole, eudesmol (ot-eudesmol, [3-eudesmol, y- eudesmol), eugenol, euphol, farnesene, farnesol, fenchol (P-fenchol), fenchone, geraniol, geranyl acetate, germacrenes, germacrene B, guaia-l(10),ll-diene, guaiacol, guaiene (ot- guaiene), gurjunene (ot-gurjunene), herniarin, hexanaldehyde, hexanoic acid, humulene (ot- humulene, [3-humulene), ionol (3-oxo-a-ionol, 13-ionol), ionone (a-ionone, -ionone), ipsdienol, isoamyl acetate, isoamyl alcohol, isoamyl formate, isoborneol, isomyrcenol, isopulegol, isovaleric acid, isoprene, kahweol, llavandulol, limonene, y-linolenic acid, linalool, longifolene, ot-longipinene, lycopene, menthol, methyl butyrate, 3-mercapto-2-methylpentanal, mercaptan/thiols, [3-mercaptoethanol, mercaptoacetic acid, allyl mercaptan, benzyl mercaptan, butyl mercaptan, ethyl mercaptan, methyl mercaptan, furfuryl mercaptan, ethylene mercaptan, propyl mercaptan, thenyl mercaptan, methyl salicylate, methylbutenol, methyl-2- methylvalerate, methyl thiobutyrate, myrcene (p-myrcene, [3-myrcene), y-muurolene, nepetalactone, nerol, nerolidol, trans-nerolido, neryl acetate, nonanaldehyde, nonanoic acid, ocimene, octanel, octanoic acid, p-cymene, pentyl butyrate, phellandrene, phenylacetaldehyde, phenylethanethiol, phenylacetic acid, phytol, pinene (ot-pinene, -pinene), propanethiol, pristimerin, pulegone, quercetin, retinol, rutin, sabinene, sabinene hydrate, cis-sabinene hydrate, trans-sabinene hydrate, safranal, ot-selinene, ot-sinensal, [3-sinensal, [3-sitosterol, squalene, taxadiene, terpin hydrate, terpineol, terpine-4-ol, a-terpinene, y-terpinene, terpinolene, thiophenol, thujone, thymol, a-tocopherol, tonka undecanone, undecanal, valeraldehyde/pentanal, verdoxan, ot-ylangene, or umbelliferone.

According to certain embodiments, the solvent comprises one or more of water, n-hexane, ethyl acetate, diethyl ether, 2-propanol, acetone, ethanol, methanol, butane, propane, benzyl alcohol, 1,3-butylene glycol, citric acid esters of mono- and di-glycerols, glycerin, glyceryl triacetate, glyceryl tributyrate, isopropyl alcohol, monoglyceride citrate, propylene glycol, triethyl citrate, diethylene glycol and propylene glycol mono- and de-esters.

According to certain embodiments, the composition also comprises a coating.

According to certain embodiments, the coating is an immediate release coating, an enteric release coating, or a sustained release coating.

According to certain embodiments, the coating is a sugar coating, a film coating, a compression coating, or a microencapsulation coating.

According to certain embodiments, the coating comprises a pharmaceutical polymer such as a cellulosics, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), ethyl cellulose (EC) vinyls, such as polyvinyl alcohol, acrylics, such as methacrylic acid / ethylacrylate copolymers natural derivatives, such as shellac or alginates.

According to certain embodiments, the coating comprises a plasticizing agent such as polyhydric alcohols, propylene glycol, polyethylene glycol (PEG), glycerol, Acetate esters, triacetin (glycerol triacetate), triethyl citrate (TEC), glycerides, acetylated monoglycerides oils, mineral oil or a vegetable oils.

According to certain embodiments, the coating comprises colorants or pigments such as indigo carmine, tartrazine, allura red, and quinoline yellow, titanium dioxide, iron oxides, pearlescent pigments (containing mica), vegetable juice, carotenoids, and turmeric.

According to certain embodiments, the coating comprises glidants such as talc, waxes, carnauba wax, stearates; flavors such as sweeteners, which may be natural or high intensity artificial (such as sucralose), natural or artificial flavors, such as mint, vanilla, or berry; viscosity modifiers, such as carbohydrates, such as lactose, polydextrose, or starch gums, such as acacia or xanthan gum.

In certain embodiments, the composition comprises: between 10 wt% and 90 wt%, preferably between 20 wt% and 60 wt%, more preferably about 40 wt% hydrotropic agent (as a function of total of hydrotropic agent and pharmaceutical compound), and between 10wt% and 90 wt%, preferably between 40 wt% and 80 wt%, more preferably about 60 wt% pharmaceutical compound (as a function of total of hydrotrophic agent to pharmaceutical compound).

In certain embodiments, the composition further comprises one or more of lactose, povidone, calcium stearate, croscarmellose sodium, Ac-Di-Sol, and optionally flavoring agent.

In certain embodiments, the composition further comprises lactose, povidone, calcium stearate, croscarmellose sodium, Ac-Di-Sol, and flavoring agent. In certain embodiments, the composition comprises about 10 wt% hydrotropic agent, about 22.2 wt% pharmaceutical compound, about 2.8 wt% lactose, about 3.0% povidone, about 3.0% calcium stearate, about 25.0 wt% croscarmellose sodium, about 30.0% Ac-Di-Sol, and about 4.0% flavoring agent.

In certain embodiments, the hydrotropic agent comprises a 1:2 wt ratio of sodium citrate and urea.

In certain embodiments, the pharmaceutical compound is a CBD.

In certain embodiments, the composition has disintegration properties such that, when tableted, it fully disintegrates in a normal sublingual environment in less than 30 seconds.

In certain embodiments, the composition comprises: 50 wt% to 65 wt%, preferably about 60wt% hydrotropic agent and 35 to 50 wt%, preferably about 40wt% pharmaceutical compound (as a function of total of hydrotrophic agent to pharmaceutical compound).

In certain embodiments the composition further comprises mannitol, croscarmellose sodium, methyl cellulose, talc, and kollidon.

In certain embodiments, the composition comprises about 12.5 wt% hydrotropic agent, about 8.1wt% pharmaceutical compound, about 1.4wt% mannitol, about 2.2wt% methyl cellulose, about 2.2wt% talc, about 44.1 wt% croscarmellose sodium, and about 29.4 wt% kollidon.

In certain embodiments, the hydrotropic agent comprises urea and sodium citrate.

In certain embodiments, the hydrotropic agent is a 10:41 wt ratio of urea and sodium citrate.

In certain embodiments, the pharmaceutical compound is a CBD and a THC.

In certain embodiments, the composition further comprises sucrose, killicoat, magnesium stearate, mint powder, and collidon CL.

In certain embodiments, the composition comprises about 18 wt% pharmaceutical compound, about 10.0 wt% hydrotropic agent, about 3.2wt% sucrose, about 2.7wt% killicoat, about 4.0% magnesium stearate, about 2.0wt% mint powder, about 30.0wt% collidon CL, and about 30.0 wt% Ac-Di-Sol.

In certain embodiments, the hydrotropic agent comprises sodium citrate and sodium acetate.

In certain embodiments, the hydrotropic agent is a 1:1 wt ratio of sodium citrate and sodium acetate.

In certain embodiments, the pharmaceutical compound is a CBD and a CBN. In certain embodiments, the composition further comprises sucrose, killicoat, magnesium stearate, mint powder, croscarmellose sodium, and collidon CL.

In certain embodiments, the composition comprises about 18.2 wt% pharmaceutical compound, about 13.3 wt% hydrotropic agent, about 4.2% sucrose, about 2.7wt% killicoat, about 3.3% magnesium stearate, about 1.7% mint powder, about 30.0 wt% croscarmellose sodium, and about 26.7 wt% kollidon CL.

In certain embodiments, the hydrotropic agent comprises sodium citrate, urea, and sodium acetate.

In certain embodiments, the hydrotropic agent is a 3:1:2 wt ratio of sodium citrate, urea, and sodium acetate.

In certain embodiments, the pharmaceutical compound is a combination of CBD and THC.

In certain embodiments, the composition is a 150:666 wt ratio of THC:CBD.

In certain embodiments, the composition comprises about 0.88 wt% pharmaceutical compound, about 16.1 wt% hydrotropic agent, about 5.1% sucrose, about 3.2wt% killicoat, about 4.0% magnesium stearate, about 2.0% mint powder, about 36.3 wt% croscarmellose sodium, and about 32.3 wt% kollidon CL.

In certain embodiments, the hydrotropic agent comprises sodium citrate, urea, and sodium acetate.

In certain embodiments, the hydrotropic agent is a 3:1:2 wt ratio of sodium citrate, urea, and sodium acetate.

In certain embodiments, the pharmaceutical compound is LSD.

In certain embodiments, the composition comprises about 1.8 wt% pharmaceutical compound, about 16.2 wt% hydrotropic agent, about 1.0% lactose, about 3.2 wt% povidone, about 4.0 wt% calcium stearate, about 2.0 wt% peppermint powder, about 24.2% croscarmellose sodium, and about 28.3% Ac-Di-Sol.

In certain embodiments, the hydrotropic agent comprises urea and sodium acetate.

In certain embodiments, the hydrotropic agent is a 1:2 wt ratio of urea and sodium acetate.

In certain embodiments, the pharmaceutical compound is psilocybin. According to a further aspect of the present invention is provided a method of manufacturing a composition as hereindescribed, comprising: dissolving or suspending one or a mixture of said hydrotropic agent in an aqueous or nonaqueous solvent or mixture of solvents to form a solution or suspension; adding the one or more pharmaceutical compound to the solution or suspension; drying to evaporate the solvent and form a blend powder.

In certain embodiments, the blend powder is a water soluble blend powder.

According to a further aspect of the present invention is provided a method of manufacturing a tablet composition, comprising: blending the blend powder as hereindescribed with at least one tableting excipient to form an excipient blend; compressing the resultant excipient blend into a tablet.

According to a further aspect of the present invention is provided a method of manufacturing a coated tablet composition, comprising: coating a tablet as hereindescribed with one or more coating compound.

According to a further aspect of the present invention is provided a method of manufacturing a composition as hereindescribed, comprising: making a solid dispersion of one or a mixture of said hydrotropic agent and the pharmaceutical compound; adding at least one excipient and mixing; compressing the resultant excipient blend into a tablet.

Description

The present disclosure provides hydrotropic agents application in developing tablet, buccal tablets, or sublingual tablets containing either cannabinoid molecules or psychedelics molecules. Tablets or sublingual tablets contain other acceptable excipients or mixtures of excipients and methods of preparing fast disintegrating oral composition.

Hydrotropic agents may include compounds with a cationic hydrophilic group. For example, they may include, but not limited to, salts of aromatic amines, such as procaine hydrochloride.

Hydrotropic agents may include aromatic anionics and examples include, but not limited to, sodium benzoate, sodium salicylate, Sodium p-Aminosalicylate, sodium benzene sulfonate, sodium benzene di-sulfonate, sodium cinnamate, sodium 3-hydroxy-2-naphthoate, sodium para toluene sulfonate, sodium cumene sulfonate, nicotinamide, N , N -diethylnicotinamide and N , N -dimethyl benzamide.

Hydrotropic agents may contain aromatic cationics and examples include, but not limited to, Paraaminobenzoic acid hydrochloride, Procaine hydrochloride and alkaloids like caffeine and nicotine. In other embodiments, hydrotropic agents contain aliphatics and linear compounds and examples include, but not limited to, Sodium alkanoate, urea and N,N-dimethyl urea, sodium citrate, sodium acetate, metaformin hydrochloride.

Some other examples of hydrotropic agents may include, but not limited to, Resorcinol, pyrogallol, catechol, a and [3-naphthols.

In some other embodiments, it is also possible to increase solubility of poorly water soluble cannabis and psychedelics by using different ratio of one or more of the aforementioned agents in a blend of hydrotropic agents. The main advantage of this technique is that it reduces the concentration of individual hydrotropic agents which directly reduces the side effects of individual hydrotropic agent.

The invention includes dissolving one or mixture of hydrotropic agents in aqueous or nonaqueous solvents or mixture of solvents. Suitable solvents for this purpose include, but are not limited to, water, n-hexane, ethyl acetate, diethyl ether, 2-propanol, acetone, methanol, ethanol, butane, propane, benzyl alcohol, 1,3-butylene glycol, citric acid esters of mono- and di-glycerols, glycerin, glyceryl triacetate, glyceryl tributyrate, isopropyl alcohol, monoglyceride citrate, propylene glycol, triethyl citrate, diethylene glycol and propylene glycol mono- and de-esters or a mixture of two or more solvents. Once dissolved, one or mixture of cannabinoid molecules or psychedelic molecule(s) will be added to the solution. The final mixture is then dried to evaporate the solvent, leaving the water-soluble blend powder. The resulting blend powder can be compounded into various formulations to produce tablet, buccal tablets, or sublingual tablets.

Other embodiments of this invention include suspending one or mixture of hydrotropic agents in aqueous or nonaqueous solvents or mixture of solvents. Once suspension is prepared, one or mixture of cannabinoid molecules or psychedelic molecule(s) will be added to the suspension. The final suspension blend is then dried to evaporate the solvent(s), leaving the water-soluble blend powder. The resulting blend powder can be compounded into various formulations to produce tablet, buccal tablets, or sublingual tablets.

Solid dispersions (SD) are one of the most popular approaches to improving molecule release of poorly soluble molecules. It can be developed as a molecular mixture of one or more cannabinoids or psychedelics molecules with hydrotropic agents wherein the molecule release profile is driven by the hydrotropic properties. It helps to increase solubility, dissolution profile of poor water-soluble molecules. A single hydrotrope or blend of hydrotropes has been effectively used to formulate the solid dispersion. In case of solid dispersion, hydrotropes enhance solubility as well as dissolution kinetics due to complete amorphization and intermolecular interactions with desired molecule or mixture of molecules. In some other embodiments of this invention, SD can be employed to blend one or mixture of hydrotropic agents with one or mixture of cannabinoid molecules or psychedelic molecule(s). The resulting blend powder can be compounded into various formulations to produce tablet, buccal tablets, or sublingual tablets. In some embodiments, Psychedelic molecules can include Psilocybin, Psilocin, or Psilocybin Hydrochloride, their derivatives, or a mixture of thereof.

In some other embodiments, Psychedelic molecules can include N-methyl-3,4- methylenedioxyamphetamine (MDMA), N-methyl-3,4-methylenedioxyamphetamine hydrochloride, N-N-Dimethyltryptamine (DMT), N-N-Dimethyltryptamine hydrochloride, Lysergic Acid Diethylamide (LSD), Lysergide Tartrate, their derivatives, or a mixture of thereof.

In some embodiments, Psychedelic molecules can include Ketamine and/or Ketamine Hydrochloride, their derivatives, or a mixture of thereof.

In some embodiments, Psychedelic molecules can include any of aforementioned molecules or mixture of thereof.

In some embodiments, cannabinoid molecules can include one or mixture of, cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabinol (THC), cannabigerolic acid monomethlether (CBGAM), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabinodiol (CBND), delta-9-tetrahydrocannabivarin (THCv), cannabinol-C2 (CBN-C2), cannabinol-C4 (CBN-C4), cannabinolic acid (CBNA), cannabiorcool (CBN-C1), cannabivarin (CBV), cannaitriol (CBT), cannabitriolvarin (CBTV), cannabichromanon (CBCF), cannabifuran (CBF), cannabiglendol (OH-iso-HHCV), cannabiripsol (CBR), cannbicitran (CBT), or 6-methano-2H-l- benzoxocin-5-mehtnaol, 10-Ehtoxy-9-hydroxy-delta-6a-tetra hydrocannabinol, cannabielsin (CBE), 8,9-dihydroxy-delta-6a-tetrahydrocannbinol, delta-8-tetrahydrocannabinol, delta-8 tetrahydrocannabinolic acid, delta-9-tetrahydrocannabinol-C4 (THC-C4), delta-9 tetrahydrocannabinoic acid A (THCA-A), delta-9-tetrahydrocannabinolic acid B (THCA-B), delta-9 tetrahydrocannabinolic acid-C4 (THCA-C4), delta-9-tetrahydrocannabiorcol (THC-C1), delta-9 tetrahydrocannabiorolic acid (THCA-C1), delta-9-tetrahydrocannabivarinic acid (THCVA), 10-Oxo delta-6a-tetrahydrocannbinol (OTHC), dehydrocannbifuran (DCBF), delta-9-cis tetrahydrocannabinol (cis-THC), trhydroxy-delta-9-tetrahydrocannabinol (triOH-THC), 3, 4, 5, 6, tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2, cannabichromenic acid (CBCA), cannabicyclol (CBL), cannabicyclolic acid (CBLA), cannabicyclovarin (CBLV), cannabivarin (CBV), Cannabidivarin (CBDVa), cannabinodiol (CBND), cannabielsion (CBE), cannabicyclol (CBL), cannabicyloic acid (CBLA), cannabitriol (CBT), cannabidiol monomehylerther (CBDM), cannabidiolic acid (CBDA), cannabidiorcol (CBD-C1), cannabielsoic acid B (CBEA-B), cannabielsoin acid A (CBEA-A), cannabigerol (CBG), cannabigerol monomethlether (CBGM), cannabigerolic acid (CBGA), cannabigerolic acid (CBGA), cannabinodivarin (CBVD), cannabinol methlether (CBNM).

In some embodiments, the cannabinoid is a mixture of one or more cannabinoid compounds (e.g., a mixture of THC and CBD or CBD and CBN).

In other embodiments of the disclosure, the cannabinoid is a cannabidiol or tetrahydrocannabinol isolate. In yet other embodiments of the disclosure, the cannabinoid is a hemp-derived or cannabis-derived cannabinoid molecules as purified, non-purified or fullspectrum isolates or extracts. Yet, in some other embodiments they are synthesized.

In some embodiments, cannabinoid molecules are extracts, isolates, full spectrum, of hemp or cannabis plant or synthesized molecules.

In some embodiments, the cannabinoid is a cannabinoid isolate. The term "cannabinoid isolate" as used herein refers to cannabinoids that have been isolated or extracted from a Cannabis plant by extraction methods known in the art. Once isolated, the cannabinoid can be refined so that the final crystalized powder is 99% pure of the cannabinoid of interest. For example, a CBD isolate can be a concentrated form of the active cannabidiol in a crystalized powder form. Cannabinoid isolates can have a purity of up to 99% (e.g., 99% or more CBD and no THC or 99% or more THC and no CBD) and can be odorless and tasteless.

In some embodiments, the cannabinoid is a hemp-derived cannabidiol. The term "hemp" as used herein refers to a Cannabis plant that contains less than 0.3% THC.

Yet another aspect of the disclosure provides a method for preparing a rapidly dissolving oral composition comprising: (i) preparing a mixture of powder comprising a cannabinoid or a psychedelic; (ii) blending the ingredients prepared in step (i) with at least one tableting excipient; and (iii) compressing the blend of step (ii) into a tablet.

In some embodiments, the composition is formulated to be relatively stable in relatively dry, room temperature environments, but to disintegrate in less than 60 seconds when administered.

In some embodiments, an excipient is a substance formulated alongside the active ingredient of a composition that can confer a therapeutic enhancement of the active ingredient (e.g., improving disintegration of the composition). Excipients can include a variety of different types of ingredients, including but not limited to, antiadherents, binders, terpenes, coatings, colors, diluents, disintegrants, fillers, flavors, glidants, lubricants, preservatives, sorbents, and taste enhancing agents. As used herein, non-active ingredients may be referred to generally as an excipient or identified as a type of excipient (e.g., a disintegrant or glidant). It will be appreciated that certain excipients can be categorized as more than one type of excipient (e.g., magnesium stearate is an excipient that can be used as a lubricant or antiadherent).

In some embodiments, the composition further comprises a disintegrating agents or mixture of disintegrating agents. Disintegrants expand and dissolve when wet (e.g., contacted by saliva) causing an oral dosage form (e.g., a tablet) to break apart and release the active ingredients. Disintegrants can help the oral dosage form to rapidly dissolve. Acceptable disintegrants include, but are not limit to, methyl cellulose, microcrystalline cellulose, powdered cellulose, lower alkyl substituted hydroxypropyl cellulose, crospovidone, Ac-Di-Sol™, sodium starch glycolate, various grades of Kollidon™, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, alginic acid, chitosan, polacrilin potassium, starch, pregelatinized starch, Lud if lash™, sodium alginate, or combinations thereof. In some embodiments, the composition further comprises a glidant or mixture of glidants. Glidants are used to promote powder flow by reducing interparticle friction and cohesion. Glidants can be used in combination with lubricants. Acceptable glidants include, but are not limited to, colloidal silica, silica gel, precipitated silica, silicon dioxide, colloidal silicon dioxide, LudiflashTM, calcium silicate, magnesium silicate, magnesium trisilicate, talc, starch, or combinations thereof.

In some embodiments, the composition further comprises a flavoring agent or mixture of flavoring agents. A flavor or taste enhancing agent, as used in the pharmaceutical industry for inactive ingredients, refers to natural or artificial tastes, which may include fragrances and colors of the flavoring. They are also referred to as sweetners, can make an oral dosage form become more palatable and can mask unpleasant organoleptic properties (e.g., taste and smell). Acceptable taste enhancing agents include, but are not limited to, sucralose, tagatose, aspartame, mint, anise, raspberry, banana, grape, peach, peppermint, cherry, acesulfame potassium, saccharin, neotame, acesulfame K, and the like, or combinations thereof.

In some embodiments, the composition further comprises a lubricant or mixture of lubricants. Lubricants can prevent ingredients from clumping together and from sticking to tableting machines. Acceptable lubricants include, but are not limited to, hydrogenated vegetable oil, light mineral oil, magnesium stearate, mineral oil, polyethylene glycol, poloxamer, sodium benzoate, various grades of Avicel™, calcium stearate, glyceryl monostearate, glyceryl behenate, glyceryl palmitostearate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc, zinc stearate, and mixtures thereof.

In some embodiments, the composition further comprises a binder or mixture of binders. Acceptable binders include, but are not limited to, saccharides and their derivatives, sucrose, lactose, starches, cellulose, methyl cellulose, polyvinlypyrrolidone, polyethylene glycol, xylitol, sorbitol, mannitol, or gelatin. Dry binders are added to a powder blend, either following a wet granulation step or as part of a direct powder compression formula.

In some embodiments, the composition further comprises a filler or mixture of fillers. A filler can be any pharmaceutically acceptable filler or diluent, including, but not limited to lactose, starch, dextrose, sucrose, fructose, maltose, mannitol, sorbitol, kaolin, microcrystalline cellulose, powdered cellulose or any combination thereof. The filler can consist of a mixture of water soluble fillers to reduce the chance of unpleasant grittiness when the tablet dissolves in the oral cavity of the patient. The filler can also be a direct compression sugar such as confectioners sugar, dextrin, dextrose, fructose, lactose or sucrose, maltose, mannitol or sorbitol, dextrates, polydextrose, sorbitol, or other sugars and sugar derivatives.

In some embodiments, the composition further comprises coating. Tablets may be coated for immediate release, enteric release, or sustained release. Coating may happen via sugar coating, film coating, compression coating, or microencapsulation coating techniques or any other applicable techniques. A typical coating may contain: a pharmaceutical polymer such as Cellulosics, such as hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), and ethyl cellulose (EC) vinyls, such as polyvinyl alcohol, acrylics, such as methacrylic acid / ethylacrylate copolymers natural derivatives, such as shellac or alginates. Coating may or may not contain a plasticizing agent such as polyhydric alcohols, propylene glycol, polyethylene glycol (PEG), glycerol, Acetate esters, triacetin (glycerol triacetate), triethyl citrate (TEC), glycerides, acetylated monoglycerides oils, mineral oil or vegetable oils. Coating may also contain colorants and pigments such as indigo carmine, tartrazine, allura red, and quinoline yellow, titanium dioxide, iron oxides, pearlescent pigments (containing mica), vegetable juice, carotenoids, and turmeric. It also may contain glidants such as talc, waxes, carnauba wax, stearates. It may also contain flavors such as sweeteners, which may be natural or high intensity artificial (such as sucralose), natural or artificial flavors, such as mint, vanilla, or berry. It also may contain viscosity modifiers, such as carbohydrates, such as lactose, polydextrose, or starch gums, such as acacia or xanthan gum.

In some embodiments, the composition further comprises a terpene. The term "terpene" as used herein refers to an organic compound that is derived biosynthetically from units of isopentenyl pyrophosphate. Terpene molecules found in plants can be the primary constituents of essential oils and can produce fragrances and smells. Terpenes can be monoterpenoids, sesquiterpenoids, sesterterpenoid, sesquarterpenoids, tetraterpenoids, triterpenoids, tetraterpenoids, Polyterpenoids, isoprenoids, and steroids. Terpenes can be: a-, [3-, y-, oxo-, isomers, or combinations thereof. Examples of terpenes include, but are not limited to, 8-dihydroionone, acetanisole, acetic acid, acetyl cedrene, anethole, anisole, benzaldehyde, bergamotene (ot-cis- bergamotene, a-trans-bergamotene), bisabolol (P-bisa bolol, ct-bisa bolol), borneol, bornyl acetate, butanoic/butyric acid, cadinene (ot-cadinene, y-cadinene), cafestol, caffeic acid, camphene, camphor, capsaicin, carene (A-3-carene, delta-3-carene), carotene, carvacrol, carvone, dextro-carvone, laevo-carvone, caryophyllene [3-caryophyllene), caryophyllene oxide, castoreum absolute, cedrene (ot-cedrene, [3-cedrene), cedrene epoxide (ot-cedrene epoxide), cedrol, cembrene, chlorogenic acid, cinnamaldehyde (a-amyl-cinnamaldehyde) (ot-hexyl- cinnamaldehyde), cinnamic acid, cinnamyl alcohol, citronellal, citronellol, cryptone, curcumene (ot-curcumene, y-curcumene), decanal, dehydrovomifoliol, diallyl disulfide, dihydroactinidiolide, dimethyl disulfide, eicosane/icosane, elemene (8-elemene), estragole, ethyl acetate, ethyl cinnamate, ethyl maltol, eucalyptol/l,8-cineole, eudesmol (ot-eudesmol, [3-eudesmol, y- eudesmol), eugenol, euphol, farnesene, farnesol, fenchol ( -fe ncho I), fenchone, geraniol, geranyl acetate, germacrenes, germacrene B, guaia-l(10),ll-diene, guaiacol, guaiene (ot-guaiene), gurjunene (ot-gurjunene), herniarin, hexanaldehyde, hexanoic acid, humulene (ot-humulene, [3- humulene), ionol (3-oxo-ot-ionol, 13-ionol), ionone (ot-ionone, [3-ionone), ipsdienol, isoamyl acetate, isoamyl alcohol, isoamyl formate, isoborneol, isomyrcenol, isopulegol, isovaleric acid, isoprene, kahweol, llavandulol, limonene, y-linolenic acid, linalool, longifolene, ot-longipinene, lycopene, menthol, methyl butyrate, 3-mercapto-2-methylpentanal, mercaptan/thiols, [3- mercaptoethanol, mercaptoacetic acid, allyl mercaptan, benzyl mercaptan, butyl mercaptan, ethyl mercaptan, methyl mercaptan, furfuryl mercaptan, ethylene mercaptan, propyl mercaptan, thenyl mercaptan, methyl salicylate, methylbutenol, methyl-2-methylvalerate, methyl thiobutyrate, myrcene (p-myrcene, [3-myrcene), y-muurolene, nepetalactone, nerol, nerolidol, trans-nerolido, neryl acetate, nonanaldehyde, nonanoic acid, ocimene, octanel, octanoic acid, p- cymene, pentyl butyrate, phellandrene, phenylacetaldehyde, phenylethanethiol, phenylacetic acid, phytol, pinene (ot-pinene, [3-pinene), propanethiol, pristimerin, pulegone, quercetin, retinol, rutin, sabinene, sabinene hydrate, cis-sabinene hydrate, trans-sabinene hydrate, safranal, a- selinene, ot-sinensal, [3-sinensal, [3-sitosterol, squalene, taxadiene, terpin hydrate, terpineol, terpine-4-ol, a-terpinene, y-terpinene, terpinolene, thiophenol, thujone, thymol, a-tocopherol, tonka undecanone, undecanal, valeraldehyde/pentanal, verdoxan, ot-ylangene, or umbelliferone.

A general method of preparing a tablet of the present invention is as follows. A hydrotropic agent or a cocktail of hydrotropic agents, in fine powdered form, is dissolved or suspended in a suitable solvent. A pharmaceutical compound is added. The resultant solution or suspension is dried using known methodology, such as a solvent vaporization chamber, or by spray drying, yielding a powder containing the pharmaceutical compound and the hydrotropic agent or cocktail. The resultant power has a fairly even distribution of hydrotropic agent and pharmaceutical compound. This powder can be utilized for tableting, by adding suitable excipients.

The hydrotropic agent or cocktail of hydrotropic agents is selected, for example, from the agents hereindescribed. The hydrotropic agent or cocktail is selected bearing in mind the properties of the pharmaceutical compound. Hydrotropic agent or cocktail is selected or optimized based on physiochemical properties and structure of target cannabinoid or psychedelic molecule(s) and solubility is optimized based on systematic design of experiments.

The solvent is selected as suitable for dissolving or suspending the hydrotropic agent. Class 1, 2, or 3 solvents can be used for this purpose. Class 1 solvents are the most toxic, such that their use should be avoided in the production of pharmaceutical products. These solvents are, but not limited to, benzene, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethene, 1,1,1- trichloroethane. Class 2 solvents have non-genotoxic animal carcinogens or possible causative agents of other irreversible toxicity such as neurotoxicity or teratogenicity. Class 2 solvents include, but not limited to, acetonitrile, chlorobenzene, chloroform, cyclohexane, hexane, methanol and formamide. Class 3 solvents have low toxic potential to man and no health-based exposure limit is needed. Class 3 solvents include, but not limited to, acetic acid, acetone, anisole, 1-butanol, 2-butanol, butyl acetate, ethanol, ethyl acetate, and formic acid. It is preferred to use class 3 solvents as they are regarded as less toxic and of lower risk to human health. It is the most preferred to use water as solvent. In all production methodologies, the solvent is evaporated to make a blend of hydrotropic agent(s) and desired molecule of cannabinoid(s) or psychedelic.

Typically, both the hydrotropic agent and the cannabinoid or psychedelic compound are in powdered / solid form such as, but not limited to CBD and CBN. In some cases, the molecule may be in liquid form such as THC (in ethanol) or THC (in oil).

Example 1: Formulation A - CBD rapidly dissolving tablets

A rapidly dissolving tablet according to the disclosure and referred to herein as Formulation A was produced as follows. 300 g of hydrotropic agent was suspended in 100 ml of water. The hydrotropic agent used was a 1:2 weight ratio of sodium citrate and urea. 666 g of pure CBD extract powder either from plant or synthesized was added to the suspension and mixed for 20 min using either mechanical stirrer or a magnetic stirrer at 200 rpm. The water was dried out of the suspension using a Rotavap™, or another suitable solvent vaporization method, at about 60 C, to form a powder containing the hydrotropic agent and the CBD. This resultant powder blend was then grinded and passed through a 500 microns sift.

Powdered excipients (83 g lactose, 90 g povidone, 120 g flavoring agent such as peppermint powder, 90 g calcium stearate, 750 g croscarmellose sodium and 900 g Ac-Di-Sol ^TM ) were added to the hydrotropic agent/CBD powder and the resultant blend was mixed for 20 min until visually uniform. The resultant powder blend was compressed into 30000 sublingual tablets each containing 20 mg CBD and weighting 100 mg total.

The tablets were tested for solubility and were found to disintegrate in less than 30 seconds in a typical oral environment (containing saliva at body temperature).

Example 2: Formulation B - CBD/THC rapidly dissolving tablets or sublingual tablets

A rapidly dissolving tablet according to the disclosure and referred to herein as Formulation B is produced as follows. Hydrotropic agent (100 g urea and 410 g sodium citrate) are dissolved in a 10:90 (vokvol) ratio of isopropanokwater. 165 g CBD and 165 g THC is added and the resultant formulation is mixed using a mechanical mixer at 300 rpm for about 20 minutes. The mixture is dried to a solid dispersion powder using a Rotavap™ or another suitable solvent vaporization method, at about 60 C, to form a powder containing the hydrotropic agent. The resultant powder is blended into a fine powder using a mortar and pestle and sieved with a 500 micron sift.

Powdered excipients (56 g mannitol, 90 g methyl cellulose, 90 g talc, 1800 g croscarmellose sodium and 1200 g Kollidon™) are added to the hydrotopic agent/CBD/THC powder and the resultant blend is mixed for 30 min until visually uniform. The resultant powder blend is compressed into the desired number of tablets or sublingual tablets. This blend results in 30000 tablets, each 150 mg, containing 10 mg CBD and 10 mg THC.

Complete disintegration of the tablets is expected to be faster than 60 seconds, in a mouth environment.

Example 3: Formulation C - CBD / CBN rapidly disintegrating tablets or sublingual tablets

A rapid disintegrating sublingual tablet according to the disclosure and referred to herein as formulation C was produced as follows. A solid dispersion was made by dispersion of 660 g CBD and 150 g CBN into 225 g of sodium benzoate and 225 g of sodium acetate hydrotropic agents, all in solid powder form. This solid dispersion can also be made by various other methods such as addition of solvent (most preferably water) and vaporization to obtain solids, and well mixed for 30 minutes. The resultant fine powder was sieved using a 500 micron sift, and were visually uniform (shown in Figure 1).

Then other excipients were added to this blend, specifically, 143 g sucrose, 120 g Killicoat™, 180 g magnesium stearate, 90 g mint powder and 2700 g disintegrating agents (a 1:1 wt mixture of Ac-Di-Sol™ and Kollidon CL™). The blend was mixed using a mechanical mixer or a v-blender for 20 min. The blend was visually uniform (shown in Figure 2). The blend was then compressed into sublingual tablets or tablets of desired size and dose. This blend resulted in 30000 tablets, each weighing 150 mg and containing 20 mg CBD and 5 mg CBN (tablets shown in Figure 3).

These tablets were found to disintegrate within 15 seconds in FDA approved equipment for the simulation of an oral environment.

Example 4: Formulation D - rapidly disintegrating sublingual tablet of CBD and THC

A rapid disintegrating sublingual tablet according to the disclosure and referred to herein as formulation D can be produced as follows. A solid dispersion is made by mixing 100 g urea, 200 g sodium acetate and 300 g sodium citrate for 20 min. Then, 666 g CBD and 150 g THC are added to the mixture and well mixed for 30 minutes. The mixture is dried to a solid dispersion powder using a Rotavap™ or another suitable solvent vaporization method, at about 65 C, to form a powder containing the hydrotropic agent. Blend is made into fine powder using a mortar and pestle and sieved with a 500 micron sift.

Excipients are added to this blend: 188 g sucrose, 120 g Killicoat™, 150 g magnesium stearate, 75 g mint powder, 1350 g croscarmellose sodium and 1200 g Kollidon CL™. The blend is mixed using a mechanical mixer or a v-blender for 30 min and compressed into sublingual tablets or tablets of desired size and dose. This blend results in 30000 tablets, each weighing 150 mg and containing 20 mg CBD and 5 mg THC.

Example 5: Other Cannabinoid Formulations

The products of Examples 1-4 can be made with other cannabinoids instead of CBD or THC. For example, the Examples can be repeated, utilizing similar amounts of CBN, or other cannabinoids, either as single ingredients or (as shown in Example 4) in a desired ratio.

Example 6: LSD rapidly dissolving tablets

A rapidly dissolving tablet according to the disclosure and referred to herein as Formulation E can be produced as follows. 100 g of urea, 200 g sodium citrate and 300 g of sodium acetate are suspended in 100 ml of water. 33 g of LSD powder is added to the suspension and mixed for 30 min using either mechanical stirrer or a magnetic stirrer at 300 rpm. The water is dried out of the suspension using a Rotavap™, or another suitable solvent vaporization method, at about 50 C, to form a powder containing the hydrotropic agent and LSD. Powder blend is then grinded and passed through a 500 microns sift.

Powdered excipients (72 g sucrose, 120 g Kollicoat IR, 75 g flavoring agent such as peppermint powder, 150 g magnesium stearate, 900 g croscarmellose sodium and 1050 g Kollidon CL™) are added to the hydrotropic agent/LSD powder and the resultant blend is mixed for 20 min and/or until visually uniform. The resultant powder blend is compressed into 30000 sublingual tablets each containing 1 mg LSD and weighting 100 mg total. The tablets exhibit excellent solubility in a sublingual environment, completely disintegrating in less than 30 seconds.

Example 7: Psilocybin rapidly dissolving tablets

A rapidly dissolving tablet according to the disclosure can be produced as follows. 200 g of urea and 400 g of sodium acetate are suspended in 100 ml of water. 67 g of Psilocybin powder either extracted from mushroom or synthesized is added to the suspension and mixed for 20 min using either mechanical stirrer or a magnetic stirrer at 300 rpm . The water is dried out of the suspension using a Rotavap™, or another suitable solvent vaporization method, at about 50 C, to form a powder containing the hydrotropic agent and Psilocybin. Powder blend iss then grinded and passed through a 500 micron sift; the resultant powder blend is visually uniform.

Powdered excipients (38 g lactose, 120 g povidone, 75 g flavoring agent such as peppermint powder, 150 g calcium stearate, 900 g croscarmellose sodium and 1050 g Ac-Di-Sol™) are added to the hydrotropic agent/ Psilocybin powder and the resultant blend is mixed for 20 min until visually uniform. The resultant powder blend is compressed into 30000 sublingual tablets each containing 2 mg Psilocybin and weighting 100 mg total. The tablets exhibit excellent solubility in a sublingual environment, completely disintegrating in less than 30 seconds.