Methods for increasing bioavailability of active pharmaceutical ingredients

Abstract

Provided is a method of increasing bioavailability of at least one administered active pharmaceutical ingredient (API) in a subject in need thereof, the method comprising administering at least a first composition comprising the API and at least one nanoporous solid carrier, wherein the at least one API is contained in pores of the at least one nanoporous carrier.

Description

METHODS FOR INCREASING BIOAVAILABILITY OF ACTIVE PHARMACEUTICAL INGREDIENTSCross-Reference to Related Applications

[0001] The present application gains priority from U.S Provisional Patent Application Serial No. 63 / 624,385 filed January 24, 2024, which is incorporated by reference as if fully set-forth herein.Field of the Invention

[0002] The present invention relates to the field of pharmaceutical compositions, and more specifically to a method for increasing bioavailability of an administered oilsoluble active pharmaceutical ingredient (API), such as a cannabinoid, comprising administering the API contained in at least a first portion of pores of at least one nanoporous solid carrier.Background

[0003] The therapeutic effects of cannabis have been known for thousands of years. The main active components are named cannabinoids. So far, more than 100 cannabinoids have been discovered. Cannabis plants contain multiple cannabinoids, sometimes dozens of them. The most known cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD). Others include cannabigerol (CBG), cannabichromene (CBC) tetrahydrocannabivarin (THCV) Cannabidivarin (CBDV) and cannabinol (CBN). Cannabinoids are found in various parts of the cannabis plant. Typically, their concentration is greatest in the flower (the bud), particularly in the trichomes.

[0004] The vast majority of the patients smoke their medical cannabis, which produces a rapid pharmacological effect, generally in a matter of minutes. However, smoking is not normally a favored route of administration for certain population groups, such as children or the elderly, for whom oral administration is generally preferred.

[0005] Orally administered cannabinoids are known to have relatively low bioavailability (for example, around 4-12% for THC, around 4-20% for CBD), thereby limiting their therapeutic potential in population groups for whom the oral route is generally preferred. In particular, oral administration commonly involves consumption of large volumes of cannabis compositions in the form of emulsions in order to achieve the required dosage, which may be particularly problematic in children suffering from certain conditions, including epilepsy and autism, for whom patient compliance is known to be low.

[0006] Buccally administered cannabinoids generally reach their intended biological destination at a slow rate, such that their pharmacological effect may take place only after about 2 hours.

[0007] There is thus an unmet need for a method of administration of cannabinoids which provides increased bioavailability as compared to known methods.Summary of the invention

[0008] According to an aspect of some embodiments of the present invention, there is provided a method of increasing bioavailability of at least one administered API having a solubility in oil of at least 10 mcg / ml at 25°C in a subject in need thereof, the method comprising administering at least a first composition comprising the API and at least one nanoporous solid carrier, wherein the at least one API is contained in at least a first portion of pores of the at least one nanoporous carrier.Detailed Description of the invention

[0009] The present invention relates to a method for increasing bioavailability of an administered oil-soluble API (such as a cannabinoid) comprising administering the API contained in at least a first portion of pores of at least one nanoporous solid carrier.

[0010] The method is particularly suitable for use in oral administration, enabling a subject to consume significantly lower doses of a composition in accordance with the principles of the present invention, as compared to the doses of prior art compositions required in order to achieve the same therapeutic effect. The method therefore results in increased patient compliance.

[0011] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0012] As used herein, the term “increasing bioavailability” of an API refers to providing a bioavailability of the API that is higher than that provided by administration of the same API in compositions which are devoid of a nanoporous carrier, such as by sublingually administering cannabis oils containing the same cannabinoid at the same doses, optionally together with terpenes, in medium chain triglyceride oils.

[0013] As used herein, the term “bioavailability” refers to the rate and / or fraction of the initial dose of a drug that becomes available to its intended biological destination(s). The bioavailability of the administered API may be determined by any standard pharmaco-kinetic method as known in the art.

[0014] As used herein, the term “initial dose” refers to the dose as administered. Such as dose is selected to provide a pharmaceutically effective dose of the API. Determination of such a dose would be a matter of routine knowledge to one of ordinary skill in the art.

[0015] As used herein, the term “nanoporous” refers to a material comprising pores having a diameter in the nanometer range i.e. in the range of from about 1 nm to about 999 nm, such as about 1 nm, about 5 nm, about 10 nm, about 20 nm, about 30 nm, about 40 nm, about 50 nm, about 60 nm, about 70 nm, about 80 nm, about 90 nm, about 100 nm, about 200 nm, about 300 nm, about 400 nm, about 500 nm, about 600 nm, about 700 nm, about 800 nm, about 900 nm or up to about 999 nm. According to some such embodiments, the pores have a diameter in the range of from about 0.5 to about 200 nm. According to some embodiments, the material is mesoporous, i.e. having pores of a diameter in the range of from about 2 to about 50 nm.

[0016] As used herein, the term “discrete particles” refers to individual particles, each having a distinct shape.

[0017] As used herein, the term “emulsion” refers to a composition wherein an oil phase is dispersed in a continuous aqueous phase.

[0018] The terminology used in the description of the invention herein is for describing particular embodiments only and is not intended to be limiting of theinvention. As used in the description of the invention and the appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0019] Unless otherwise indicated, all numbers expressing quantities, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Every numerical range given throughout this specification will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.

[0020] As used herein, when a numerical value is preceded by the term "about", the term "about" is intended to indicate + / - 10% of that value.

[0021] As used herein, the terms “comprising”, “including”, "having" and grammatical variants thereof are to be taken as specifying the stated features, integers, steps or components but do not preclude the addition of one or more additional features, integers, steps, components or groups thereof. These terms encompass the terms "consisting of" and "consisting essentially of". As used herein, the terms “water content” and “moisture content” are used interchangeably.

[0022] Unless indicated otherwise, percent is weight percent and ratio is weight / weight ratio.

[0023] The particulars shown herein are by way of example and for purposes of illustrative discussion of the various embodiments of the present invention only and are presented in the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.

[0024] The present invention will now be described by reference to more detailed embodiments. This invention may, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

[0025] Additional advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.

[0026] According to an aspect of some embodiments of the present invention, there is provided a method of increasing bioavailability of at least one administered API having a solubility in oil of at least 10 mcg / ml at 25°C in a subject in need thereof, the method comprising administering at least a first composition comprising the API and at least one nanoporous solid carrier, wherein the at least one API is contained in at least a first portion of pores of the at least one nanoporous carrier.

[0027] According to some embodiments, the API has a solubility of up to about 10 mg / ml, such as about 10 mcg / ml, about 20 mcg / ml, about 50 mcg / ml, about 100 mcg / ml, about 200 mcg / ml, about 300 mcg / ml, about 400 mcg / ml, about 500 mcg / ml, about 600 mcg / ml, about 700 mcg / ml, about 800 mcg / ml, about 900 mcg / ml, about 1 mg / ml, about 2 mg / ml, about 5 mg / ml or about 10 mg / ml.

[0028] According to some embodiments, the API comprises a cannabinoid.

[0029] According to some embodiments, the API is selected from the group consisting of an omega-3 oil, vitamin E, vitamin K and combinations thereof.

[0030] According to some embodiments, administering comprises orally administering.

[0031] According to some embodiments, administering comprises sublingual, buccal or dermal administration.

[0032] According to some embodiments, the at least one administered cannabinoid is one cannabinoid, two cannabinoids, three cannabinoids, four cannabinoids, five cannabinoids or more than five cannabinoids.

[0033] According to some embodiments, administering comprises providing an emulsion.

[0034] According to some embodiments, the emulsion is formed in situ within the body of the subject upon administering the composition.

[0035] According to some embodiments, the least one carrier comprises at least one selected from the group consisting of silica, zeolite, granular active carbon and combinations thereof.

[0036] According to some embodiments, the at least one carrier has a surface area between about 50 m2 / gr and 1000 m2 / gr, such as about 50 m2 / gr, about 55 m2 / gr, about 60 m2 / gr, about 65 m2 / gr, about 70 m2 / gr, about 75 m2 / gr, about 80 m2 / gr, about 85 m2 / gr, about 90 m2 / gr, about m2 / gr, or about 100 m2 / gr.

[0037] According to some embodiments, an internal surface of the at least one carrier is lipophilic.

[0038] According to some embodiments, an internal surface of the at least one carrier is hydrophilic.

[0039] According to some embodiments, the nanoporous carrier comprises discrete particles.

[0040] According to some embodiments, a concentration of the at least one nanoporous carrier is between about 30wt% and 99wt% (such as about 30wt%, about 35wt%, about 40wt%, about 45wt%, about 50wt%, about 55 wt%, about 60wt%, about 65wt%, about 70wt%, about 75wt%, about 80wt%, about 85wt%, about 90wt%, about 95wt% or about 99wt%) of the total composition.

[0041] According to some embodiments, a concentration of the at least one cannabinoid is between about lwt% and 70wt% (such as about lwt%, about 5wt%, about 10wt%, about 15wt%, about 20wt%, about 25wt%, about 30wt%, about 35wt%,about 40wt%, about 45wt%, about 50wt%, about 55wt%, about 60wt%, about 65wt% or about 70wt%) of the total composition.

[0042] According to some embodiments, a combined concentration of the at least one cannabinoid and the at least one carrier is about 80wt%, about 85wt%, about 86wt%, about 87wt%, about 88wt%, about 89wt%, 90wt%, about 91wt%, about 92wt%, about 93wt%, about 94wt%, about 95wt%, about 96wt%, about 97wt%, about 98wt%, about 99wt%, or about 100wt% of the total composition.

[0043] According to some embodiments, the at least one cannabinoid is selected from the group consisting of tetrahydrocannabinolic acid (THCA), tetrahydrocannabinol (THC), cannabidiolic acid (CBDA), cannabidiol (CBD), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabichromenic acid (CBCA), cannabichromene (CBC), tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabivarin (THCV), cannabidivarinic acid (CBDVA), cannabidivarin (CBDV) and combinations thereof.

[0044] According to some embodiments, administering provides a dose of from about 0.2mg to about 100 mg (such as about 0.2 mg, about 0.5 mg, about 1 mg, about 5 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg or about 100 mg) cannabinoid.

[0045] According to some embodiments, the at least one cannabinoid comprises at least two cannabinoids, wherein a first of the at least two cannabinoids is present in acid form and a second of the at least two cannabinoids is present in decarboxylated form.

[0046] According to some embodiments, a weight / weight ratio between a total amount of cannabinoids in acid form and a total amount of cannabinoids in decarboxylated form is greater than 2:1. According to some embodiments, a weight / weight ratio between a total amount of cannabinoids in decarboxylated form and a total amount of cannabinoids in acid form is greater than 2:1.

[0047] According to some embodiments, the weight / weight ratio between the total amount of cannabinoids in acid form and the total amount of cannabinoids in decarboxylated form is up to about 1000:1. According to some embodiments, the weight / weight ratio between the total amount of cannabinoids in acid form and the total amount of cannabinoids in decarboxylated form is about 3:1, about 5:1, about10:1, about 50:1, about 100:1, about 200:1, about 300:1, about 400:1, about 500:1, about 600:1, about 700:1, about 800:1, about 900:1 or about 1000:1.

[0048] According to some embodiments, the composition further comprises at least one terpene, such as one terpene, two terpenes, three terpenes, four terpenes, five terpenes or more than five terpenes. According to some such embodiments, the at least one terpene is contained in at least a second portion of pores of the at least one solid nanoporous carrier. According to some embodiments, the first portion of pores in which the at least one cannabinoid is contained and the second portion of pores in which the at least one terpene is contained are the same portion of pores. According to some embodiments, the first portion of pores in which the at least one cannabinoid is contained and the second portion of pores in which the at least one terpene is contained are different portions of pores. According to some embodiments, there is an overlap between the first portion of pores in which the at least one cannabinoid is contained and the second portion of pores in which the at least one terpene is contained, such that some of the pores of the first and second portions are the same and carry both the at least one cannabinoid and the at least one terpene, while other pores are different and carry only one of the at least one cannabinoid or the at least one terpene.

[0049] According to some embodiments, a weight / weight ratio of the total amount of terpenes / total amount of cannabinoids in the composition is from about 0.05 to about 1.0, such as about 0.05, about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9 or about 1.0.

[0050] According to some embodiments, about 90wt%, about 91wt%, about 92wt%, about 93wt%, about 94wt%, about 95wt%, about 96wt%, about 97wt%, about 98wt%, about 99wt%, or about 100wt% of the at least one cannabinoid is contained in at least a first portion of the pores of the carrier.

[0051] According to some embodiments, the at least one terpene is selected from the group consisting of pinene, limonene, linalool, myrcene, borneol terpineol, geraniol, eucalyptol, terpinolene, sabinene, ocimene, terpinene, caryophyllene, humulene, nerolidol, guaiol, bisabolol and combinations thereof.

[0052] According to some embodiments, the composition further comprises at least one substance that increases the concentration of the API in the body of the subject byinhibiting breakdown of the API. Non-limiting examples of such substances include terpenes, sesamin, piperine and bergamottin and inhibitors of the cytochrome P450 family of enzymes, such as CYP3A4 and CYP2C9.

[0053] According to some embodiments, the composition further comprising an emulsifier. According to some such embodiments, the emulsifier is contained in at least a third portion of pores of the at least one solid nanoporous carrier.

[0054] According to some embodiments, the third portion of pores in which the at least one emulsifier is contained, the second portion of pores in which the at least one terpene is contained, and the first portion of pores in which the at least one cannabinoid is contained are the same portion of pores. According to some embodiments, at least one of the first portion of pores in which the at least one cannabinoid is contained, the second portion of pores in which the at least one terpene is contained, and the third portion of pores in which the at least one emulsifier are contained are different portions of pores. According to some embodiments, there is an overlap between the first portion of pores in which the at least one cannabinoid is contained, the second portion of pores in which the at least one terpene is contained, and the third portion of pores in which the at least one emulsifier is contained, such that some of the pores of the first, second and third portions are the same and carry each of the at least one cannabinoid, the at least one terpene and the at least one emulsifier, while other pores are different and carry only one or two of the at least one cannabinoid, the at least one terpene and the at least one emulsifier.

[0055] According to some embodiments, the emulsifier comprises any pharmaceutically acceptable emulsifier.

[0056] According to some embodiments, the nanoporous carrier is the sole carrier present in the composition and comprises discrete particles.

[0057] According to some such embodiments, each particle of the carrier comprises the same one or more cannabinoids and each particle optionally further comprises a same at least one additional component selected from the group consisting of one or more terpenes and one or more surfactants.

[0058] According to some embodiments, a first portion of the particles of the sole carrier comprise a first cannabinoid and a second portion of the particles comprise a second cannabinoid.

[0059] According to some embodiments, a first portion of the particles of the sole carrier comprise at least a first cannabinoid and a second portion of the particles comprise at least a first terpene. According to some such embodiments, the first portion of the particles is devoid of a terpene and the second portion of the particles is devoid of a cannabinoid. Alternatively, according to some embodiments, one of the first portion and the second portion of the particles comprises a cannabinoid and a terpene.

[0060] According to some embodiments, a first portion of the particles of the sole carrier comprise at least a first cannabinoid and a second portion of the particles comprise at least a first surfactant. According to some such embodiments, the first portion of the particles is devoid of a surfactant and the second portion of the particles is devoid of a cannabinoid. Alternatively, according to some embodiments, one of the first portion and the second portion of the particles comprises a cannabinoid and a surfactant.

[0061] According to some embodiments, a first portion of the particles of the sole carrier comprise at least a first surfactant and a second portion of the particles comprise at least a first terpene. According to some such embodiments, the first portion of the particles is devoid of a terpene and the second portion of the particles is devoid of a surfactant.

[0062] According to some embodiments, the composition comprises at least two carriers, wherein a first carrier is different from a second carrier, and wherein at least a portion of each of the carriers comprises the same or different cannabinoids and optionally at least one same or different additional components selected from the group consisting of a terpene and a surfactant, according to options disclosed herein for single carriers.

[0063] According to some embodiments, the composition further comprising a liquid carrier. According to some such embodiments, the liquid carrier is contained in at least a fourth portion of pores of the at least one solid nanoporous carrier. According to some embodiments, the liquid carrier is any pharmaceutically acceptable liquid carrier. According to some embodiments, the liquid carrier is selected from the group consisting of vegetable oils (soy, olive-oil, sesame, grape-seed), medium chaintriglycerides (MCT), alcohol, other pharmaceutically acceptable liquid carriers and combinations thereof.

[0064] According to some embodiments, the first portion of pores in which the at least one cannabinoid is contained, the second portion of pores in which the at least one terpene is contained, the third portion of pores in which the at least one emulsifier is contained and the fourth portion of pores in which the at least one liquid carrier is contained are the same portion of pores. According to some embodiments, at least one of the first portion of pores in which the at least one cannabinoid is contained, the second portion of pores in which the at least one terpene is contained, the third portion of pores in which the at least one emulsifier is contained and the fourth portion of pores in which that at least one liquid carrier is contained are different portions of pores. According to some embodiments, there is an overlap between the first portion of pores in which the at least one cannabinoid is contained, the second portion of pores in which the at least one terpene is contained, the third portion of pores in which the at least one emulsifier is contained and the fourth portion of pores in which the at least one emulsifier is contained, such that some of the pores of the first, second, third and fourth portions are the same and carry each of the at least one cannabinoid, the at least one terpene, the at least one emulsifier and the at least one liquid carrier, while other pores are different and carry only one, two or three of the at least one cannabinoid, the at least one terpene, the at least one emulsifier and the at least one liquid carrier.

[0065] According to some embodiments, the composition further comprises at least one oil-soluble, non-cannabinoid compound having a solubility in medium-chain triglycerides (MCT) of at least 10 mcg / ml at 25°C. According to some embodiments, the oil-soluble, non-cannabinoid compound is any pharmaceutically acceptable drug formulated as a lipid-based delivery system, such as those disclosed by Savla et al. (Drug Development and Industrial Pharmacy, vol. 43(11): pp. 1743-1758 (2017)), which is incorporated by reference as if fully set out herein.

[0066] According to some embodiments, the additional compound is contained in at least a fifth portion of pores of the at least one solid nanoporous carrier. According to some such embodiments, the first portion of pores in which the at least one cannabinoid is contained, the second portion of pores in which the at least one terpene is contained, the third portion of pores in which the at least one emulsifier is contained, the fourth portion of pores in which the at least one liquid carrier is contained, and thefifth portion of pores in which the at least one additional compound is contained are the same portion of pores. According to some embodiments, at least one of the first portion of pores in which the at least one cannabinoid is contained, the second portion of pores in which the at least one terpene is contained, the third portion of pores in which the at least one emulsifier is contained, the fourth portion of pores in which that at least one liquid carrier is contained, and the fifth portion of pores in which the at least one additional compound is contained are different portions of pores. According to some embodiments, there is an overlap between the first portion of pores in which the at least one cannabinoid is contained, the second portion of pores in which the at least one terpene is contained, the third portion of pores in which the at least one emulsifier is contained, the fourth portion of pores in which the at least one emulsifier is contained, and the fifth portion of pores in which the at least one additional compound is contained, such that some of the pores of the first, second, third, fourth and fifth portions are the same and carry each of the at least one cannabinoid, the at least one terpene, the at least one emulsifier, the at least one liquid carrier, and the at least one additional compound, while other pores are different and carry only one, two, three, or four of the at least one cannabinoid, the at least one terpene, the at least one emulsifier, the at least one liquid carrier and the at least one additional compound.

[0067] According to some embodiments, the composition is provided in the form of a product selected from the group consisting of tablets, gel capsules, foods and beverages.

[0068] According to some embodiments, the product further comprises a water- soluble non-cannabinoid compound having a solubility in water of at least 1 mg / ml at 25°C.

[0069] According to some embodiments, the non-cannabinoid compound is selected from the group consisting of anti-oxidants, anti-inflammatory agents, nutraceuticals, pharmaceutical drugs, compounds that increase blood flow and combinations thereof.

[0070] According to some embodiments, the oil-soluble non-cannabinoid compound is selected from the group consisting of poly-unsaturated fatty acids (PUFA), vitamins, co-enzyme Q, carotenes, terpenes and combinations thereof.

[0071] According to some embodiments, the PUFA is selected from the group consisting of omega-3 PUFA, omega-6 PUFA and combinations thereof.

[0072] According to some embodiments, the water-soluble, non-cannabinoid compound is selected from the group consisting of anti-oxidants, anti-inflammatory agents, nutraceuticals, pharmaceutical drugs and combinations thereof.

[0073] According to some embodiments, the water-soluble, non-cannabinoid compound selected from the group consisting of flavonoids, sulforaphane, folinic acid, a vitamin from the B vitamins group, vitamin C, probiotics, digestive enzymes, camel milk and combinations thereof.

[0074] According to some embodiments, the compound for increasing blood flow is selected from the group consisting of a B -vitamin, Vitamin K, Vitamin C, Vitamin E, Omega-3, Omega-7, iron, L-arginine, coenzyme Q, nattokinase, ginger, garlic, curcumin, turmeric, black pepper, piperine, capsaicin, thyme and combinations thereof.

[0075] According to some embodiments, each of the particles of the nanoporous carrier comprises a cannabinoid.

[0076] According to some embodiments, the method further comprises administering a second composition comprising at least one cannabinoid and at least one nanoporous solid carrier, wherein the at least one cannabinoid of the second composition is contained in pores of the at least one nanoporous carrier of the second composition, wherein the second composition is provided in the form of a product selected from the group consisting of tablets, gel capsules, foods and beverages, and wherein the second composition is different from the first composition. According to some such embodiments, the at least one cannabinoid of the second composition is selected from the group consisting of tetrahydrocannabinolic acid (THCA), tetrahydrocannabinol (THC), cannabidiolic acid (CBDA), cannabidiol (CBD), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabichromenic acid (CBCA), cannabichromene (CBC), tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabivarin (THCV), cannabidivarinic acid (CBDVA), cannabidivarin (CBDV) and combinations thereof.

[0077] According to some embodiments, the method further comprises administering a third composition comprising a third nanoporous carrier and at least one terpene. According to some such embodiments, the at least one terpene of the third composition is selected from the group consisting of pinene, limonene, linalool,myrcene, borneol terpineol, geraniol, eucalyptol, terpinolene, sabinene, ocimene, terpinene, caryophyllene, humulene, nerolidol, guaiol, bisabolol and combinations thereof.

[0078] According to some embodiments, the subject is a child. According to some such embodiments, the child has been diagnosed as suffering from a condition related to the central nervous system, such as a condition selected from the group consisting of epilepsy, autism spectrum disorder, attention deficiency disorder (ADD), attention deficiency hyperactive disorder (ADHD) and Tourette syndrome.

[0079] According to some embodiments, the method further comprises adding the composition to a liquid prior to administering the composition, wherein an emulsion is formed. According to some embodiments, the liquid is selected from the group consisting of water, juice, milk, a milk analogue, a soup and combinations thereof.

[0080] According to some embodiments, adding the composition to the liquid comprises immersing in the liquid a porous receptacle (such as a teabag or tea infuser) comprising the composition.

[0081] According to some embodiments, the liquid is administered in the form of a beverage (such as tea, milk shake, a carbonated drink, etc.). According to some such embodiments, the beverage may further comprise additional components such as a flavorant (such as chocolate, fruit extract and the like), a sweetener, a colorant and the like. According to some embodiments, the beverage is administered at a temperature in the range between about 30°C and 60°C, such as about 30°C, about 35°C, about 40°C, about 45°C, about 50°C, about 55°C or about 60°C.

[0082] According to some embodiments, the liquid is administered incorporated into a food product, such as oatmeal, mashed potatoes, fruit puree, a milk or fruit pudding and the like.

[0083] According to some embodiments, the liquid is administered by consuming together with a breakfast cereal.

[0084] According to some embodiments, administering comprises administering in buccal form. According to some embodiments, administering comprises administering in the form of a candy.

[0085] According to some embodiments, administering comprises administering in the form of a sublingual tablet, wherein an emulsion is formed upon contact of the tablet with the saliva of the subject.

[0086] According to some embodiments, adding the composition to water is performed no more than 60 minutes prior to administering the composition to the subject.

[0087] According to some embodiments, the composition is prepared by a method comprising(i) providing a solid carrier comprising a nanoporous material;(ii) providing a source comprising at least one cannabinoid, which source is selected from the group consisting of cannabis plant materials, fermentation products, synthetic products, and bio-reactor products;(iii) extracting the source to form an extract comprising the at least one cannabinoid;(iv) optionally, purifying the extract to form a purified extract;(v) optionally diluting the extract or purified extract in a liquid carrier to form a diluted extract; and(vi) adsorbing at least one selected from the group consisting of the extract, the purified extract and the diluted extract on the carrier, whereby the composition is formed.

[0088] According to some embodiments, the method further comprises adsorbing at least one additional cannabinoid and / or at least one terpene on the carrier.

[0089] According to some embodiments, the composition is prepared by a method comprising(i) providing a composition comprising the cannabinoid and at least one nanoporous solid carrier, wherein the at least one cannabinoid is contained in at least a portion of pores of the at least one nanoporous solid carrier(ii) providing at least one composition selected from(a) a composition comprising at least one terpene and at least one nanoporous solid carrier, wherein the at least one terpene is contained in at least a portion of pores of the at least one nanoporous solid carrier;(b) a composition comprising at least one emulsifier and at least one nanoporous solid carrier, wherein the at least one emulsifier is contained in at least a portion of pores of the at least one nanoporous solid carrier;(c) a composition comprising at least one liquid carrier and at least one nanoporous solid carrier, wherein the at least one liquid carrier is contained in at least a portion of pores of the at least one nanoporous solid carrier;(d) a composition comprising at least one at least one oil-soluble, non-cannabinoid compound and at least one nanoporous solid carrier, wherein the at least one oil-soluble, non-cannabinoid compound is contained in at least a portion of pores of the at least one nanoporous solid carrier; and(iii) blending the composition (i) with at least one of the compositions (ii).

[0090] According to a further aspect of some embodiments of the present invention, there is provided an emulsion comprising a cannabinoid, wherein the emulsion is formed in situ upon administering the cannabinoid absorbed in pores of a nanoporous silica carrier to a subject.

[0091] According to a further aspect of some embodiments of the present invention, there is provided a method for providing an emulsion comprising a cannabinoid to a subject in need thereof, the method comprising administering the cannabinoid absorbed in pores of a nanoporous silica carrier to the subject, wherein the emulsion is formed in situ.

[0092] According to a further aspect of some embodiments of the present invention, there is provided a method of treatment comprising administering to a subject in need thereof a composition comprising a nanoporous carrier and at least one cannabinoid adsorbed in pores of said nanoporous carrier, wherein said composition is administered at a dosage in the range of from about 0.2 mg to about 100 mg (such as about 0.2 mg, about 0.5 mg, about 1 mg, about 5 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg or about 100 mg) cannabinoid.

[0093] According to a further aspect of some embodiments of the present invention, there is provide a composition comprising(a) a cannabinoid and at least one nanoporous solid carrier, wherein the at least one cannabinoid is contained in at least a first portion of pores of the at least one nanoporous carrier, the composition further comprising at least two, at least three or all four selected from the group consisting of:(b) a terpene contained in at least a second portion of pores of the at least one solid nanoporous carrier;(c) an emulsifier contained in at least a third portion of pores of the at least one solid nanoporous carrier;(d) a liquid carrier contained in at least a fourth portion of pores of the at least one solid nanoporous carrier; and(e) at least one oil-soluble, non-cannabinoid compound selected from the group consisting of anti-oxidants, anti-inflammatory agents, nutraceuticals, pharmaceutical drugs and combinations thereof, wherein the oil-soluble non-cannabinoid compound has a solubility in medium-chain triglycerides (MCT) of at least 10 mcg / ml at 25 °C, which non-cannabinoid compound is contained in at least a fifth portion of pores of the at least one solid nanoporous carrier.

[0094] According to some embodiments, the composition comprises:(a) a cannabinoid and at least two nanoporous solid carriers, wherein the at least one cannabinoid is contained in at least a first portion of pores of at least one of the at least two nanoporous carriers and at least two, at least three or all four selected from the group consisting of:(b) a terpene contained in at least a second portion of pores of at least one of the at least two solid nanoporous carriers;(c) an emulsifier contained in at least a third portion of pores of at least one of the at least two solid nanoporous carriers;(d) a liquid carrier contained in at least a fourth portion of pores of at least one of the at least two solid nanoporous carriers;(e) at least one oil-soluble, non-cannabinoid compound selected from the group consisting of anti-oxidants, anti-inflammatory agents, nutraceuticals, pharmaceutical drugs and combinations thereof, wherein the oil-soluble non-cannabinoid compound has a solubility in medium-chain triglycerides (MCT) of at least 10 mcg / ml at 25 °C,which non-cannabinoid compound is contained in at least a fifth portion of pores of the at least two solid nanoporous carriers.

[0095] According to some embodiments, there is provided a product comprising a composition as disclosed herein, selected from the group consisting of tablets, gel capsules, foods, beverages and a porous receptacle comprising said composition.

[0096] According to some embodiments, the product further comprises at least one water-soluble, non-cannabinoid compound selected from the group consisting of antioxidants, anti-inflammatory agents, nutraceuticals, pharmaceutical drugs and combinations thereof, wherein said water-soluble non-cannabinoid compound has a solubility in water of at least 1 mg / ml at 25°C.

[0097] According to some embodiments, there is provided a method of increasing bioavailability of at least one administered cannabinoid in a subject in need thereof, the method comprising administering to the subject a composition as disclosed herein.

[0098] According to some embodiments, administering comprises orally administering.

[0099] According to some embodiments, administering comprises providing an emulsion.

[0100] According to some embodiments, the emulsion is formed in situ.ExamplesMaterials

[0101] Cannabinoids: CBD isolate, THC isolate and extracts were sourced from Bazelet Medical Cannabis, Or-Akiva, Israel.

[0102] The extracts were Bazelet’ s commercial products, Special T (24% THC, 7% CBD) and Special C (32% CBD), both of which are enriched with terpenes and diluted in medium chain triglycerides oil (MCT).

[0103] Silica: Pharmaceutical-grade SYLOID® XDP 3050 and XDP 3150 were sourced from GRACE GmbH, Worms, Germany.Example 1: Production of a CBD-carrying composition

[0104] 8 gr of Special C oil (a commercial product of Bazelet (Or-Akiva,Israel) containing 32% CBD, enriched with alpha pinene, linalool, limonene and terpinolene, and diluted in medium chain triglyceride (MCT)) were gradually added to lOgr of granular nanoporous silica while vigorously stirring, to produce a free-flowing powder containing 55wt% silica (solid carrier), 14% CBD (cannabinoid), 31% MCT (liquid carrier) and 1.4% terpenes.Example 2: Production of a THC+CBD-carrying composition

[0105] 9 gr of Special T oil (a commercial product of Bazelet (Or-Akiva, Israel) containing 24% THC and 7%CBD, enriched with the same terpenes as for Example 1, and diluted in MCT) were gradually added to lOgr of granular nanoporous silica while vigorously stirring, to produce a free-flowing powder containing 53wt% silica (solid carrier), 11% THC and 3% CBD (cannabinoids), 33% MCT (liquid carrier) and 1.5% terpenes.Example 3: Production of a CBD + terpene emulsion

[0106] 145mg of a powder produced according to the method of Example 1, carrying 20mg CBD and 2.2mg terpenes, were added to 100ml water in a cup, while gently stirring for 2 minutes. The water turned opaque, indicating the formation of an emulsion. The cup was kept without stirring for 2 hours. The water remained opaque.Example 4: Production of a CBD +THC + terpene emulsion

[0107] 91 mg of a powder produced according to Example 2, carrying lOmg THC, 2.7mg CBD and 1.4mg terpenes, were added to 100ml water in a cup, while gently stirring for 2 minutes. The water turned opaque, indicating the formation of an emulsion. The cup was kept without stirring for 2 hours. The water remained opaque.Comparative Example A:[ooio8] lOOmg of granular nanoporous silica, as used in Example 1, were added to 100ml water in a cup, while gently stirring for 2 minutes. A dispersion of the silica granules was observed. The cup was kept without stirring. Within less than 10 minutes, the granules settled at the bottom of the cup. The water layer clarified.Comparative Example B:

[0109] lOOmg of Special C oil, as used in Example 1, were added to 100ml water in a cup, while gently stirring for 2 minutes. A dispersion of the oil was observed. The cup was kept without stirring. Within less than 3 minutes, oil separated out and formed oil droplets on top of the water. The water layer clarified.Comparative Example C:

[0110] lOOmg of Special T oil, as used in Example 2, were added to 100ml water in a cup, while gently stirring for 2 minutes. A dispersion of the oil was observed. The cup was kept without stirring. Within less than 3 minutes, oil separated out and formed oil droplets on top of the water. The water layer clarified.Example 5: Stability of a CBD-carrying composition

[0111] Silica-containing Special C oil, produced according to Example 1, was tested for stability of cannabinoids and terpenes over a period of eight months at a temperature of 22°C and humidity of about 50%, by addition of Igr of loaded silica granules to an appropriate amount of ethanol and analyzed using gas chromatography for terpenes and HPLC for cannabinoids. No change was seen in the amounts of either CBD or terpenes present in the oil at the end of the 8-month test period.Example 6: Dissolution kinetics of a TEIC+ CBD-carrying composition

[0112] Special T oil, produced according to Example 2, was subjected to a dissolution test by determination of release of cannabinoids from granules, stimulating release in humans after ingestion.

[0113] Loaded silica granules were tested for release of THC, CBD and terpenes using 1 liter of a dissolution medium containing 2% sodium lauryl sulfate (SLS) in water at a rotation speed of 100 rpm at 37°C.

[0114] Samples of the medium were taken at various time points and analyzed at Bazelet analytical unit, using gas chromatography for terpenes and HPLC for THC and CBD. The release yields were calculated against the content of the granules after absorption.

[0115] It was found that the dissolution rates of THC, CBD and terpene were similar, with over 85% of each released within 30 minutes.

Claims

CLAIMS1. A method of increasing bioavailability of at least one administered active pharmaceutical ingredient (API) having a solubility in oil of at least 10 mcg / ml at 25°C in a subject in need thereof, the method comprising administering at least a first composition comprising the API and at least one nanoporous solid carrier, wherein said at least one API is contained in at least a first portion of pores of said at least one nanoporous carrier.

2. The method of claim 1, wherein the API comprises a cannabinoid.

3. The method of claim 1, wherein said increasing said bioavailability comprises increasing a rate at which an initial dose of said API becomes available to an intended biological destination.

4. The method of claim 1, wherein said increasing said bioavailability comprises increasing a fraction of an initial dose of said API which becomes available to an intended biological destination.

5. The method of claim 1, wherein said administering comprises orally administering.

6. The method of claim 1, wherein said administering comprises providing an emulsion.

7. The method of claim 6, wherein said emulsion is formed in situ.

8. The method of claim 1, wherein said at least one carrier comprises at least one selected from the group consisting of silica, zeolite, granular active carbon and combinations thereof.

9. The method of claim 1 , wherein said at least one carrier has a surface area between 50 m2 / gr and 1000 m2 / gr.

10. The method of claim 1, wherein an internal surface of said at least one carrier is lipophilic.

11. The method of claim 1, wherein an internal surface of said at least one carrier is hydrophilic.

12. The method of claim 1, wherein said at least one nanoporous carrier comprises discrete particles.

13. The method of claim 1, wherein a concentration of said at least one nanoporous carrier is between 30wt% and 99wt% of the total composition.

14. The method of claim 2, wherein a concentration of said at least one cannabinoid is between lwt% and 70wt% of the total composition.

15. The method of claim 2, wherein said at least one cannabinoid is selected from the group consisting of tetrahydrocannabinolic acid (THCA), tetrahydrocannabinol (THC), cannabidiolic acid (CBDA), cannabidiol (CBD), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabichromenic acid (CBCA), cannabichromene (CBC), tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabivarin (THCV), cannabidivarinic acid (CBDVA), cannabidivarin (CBDV) and combinations thereof.

16. The method of claim 2, wherein said administering provides a dose of from 0.2- 100 mg cannabinoid.

17. The method of claim 2, wherein, wherein said at least one cannabinoid comprises at least two cannabinoids, wherein a first of said at least two cannabinoids is present in acid form and a second of said at least two cannabinoids is present in decarboxylated form.

18. The method of claim 17, wherein the weight / weight ratio between a total amount of cannabinoids in acid form and a total amount of cannabinoids in decarboxylated form is greater than 2:1.

19. The method of claim 17, wherein a weight / weight ratio between the total amount of cannabinoids in decarboxylated form and the total amount of cannabinoids in acid form is greater than 2:

120. The method of claim 2, wherein said composition further comprises at least one terpene.

21. The method of claim 20, wherein said at least one terpene is contained in at least a second portion of pores of said at least one solid nanoporous carrier.

22. The method of claim 20, wherein a weight / weight ratio of the total amount of terpenes / total amount of cannabinoids in the composition is from 0.05 to 1.0.

23. The method of claim 20, wherein said at least one terpene is selected from the group consisting of pinene, limonene, linalool, myrcene, borneol terpineol, geraniol,eucalyptol, terpinolene, sabinene, ocimene, terpinene, caryophyllene, humulene, nerolidol, guaiol, bisabolol and combinations thereof.

24. The method of claim 2, wherein said composition further comprises an emulsifier.

25. The method of claim 24, wherein said emulsifier is contained in at least a third portion of pores of said at least one solid nanoporous carrier.

26. The method of claim 2, wherein said composition further comprises a liquid carrier.

27. The method of claim 26, wherein said liquid carrier is contained in at least a fourth portion of pores of said at least one solid nanoporous carrier.

28. The method of claim 2, wherein said composition further comprises at least one oil-soluble non-cannabinoid compound having a solubility in medium-chain triglycerides (MCT) of at least 10 mcg / ml at 25 °C,29. The method of claim 28, wherein said at least one non-cannabinoid compound is contained in at least a fifth portion of pores of said at least one solid nanoporous carrier.

30. The method of claim 2, wherein the composition is provided in the form of a product selected from the group consisting of tablets, gel capsules, foods and beverages.

31. The method of claim 30, wherein said product further comprises at least one water-soluble, non-cannabinoid compound having a water solubility of at least Img / ml at 25°C.

32. The method of claim 28 or 31, wherein said non-cannabinoid compound is selected from the group consisting of anti-oxidants, anti-inflammatory agents, nutraceuticals, pharmaceutical drugs, compounds that increases blood flow and combinations thereof,33. The method of claim 32, wherein said non-cannabinoid compound is selected from the group consisting of poly-unsaturated fatty acids (PUFA), vitamins, co-enzyme Q, carotenes, terpenes and combinations thereof.

34. The method of claim 33, wherein said PUFA is selected from the group consisting of omega-3 PUFA, omega-6 PUFA and combinations thereof.

35. The method of claim 32, wherein said non-cannabinoid compound is selected from the group consisting of flavonoids, sulforaphane, folinic acid, a vitamin from theB vitamins group, vitamin C, probiotics, digestive enzymes, camel milk and combinations thereof.

36. The method of claim 32, wherein said compound that increases blood flow is selected from the group consisting of a B-vitamin, Vitamin K, Vitamin C, Vitamin E, Omega-3, Omega-7, iron, L-arginine, coenzyme Q, nattokinase, ginger, garlic, curcumin, turmeric, black pepper, piperine, capsaicin, thyme and combinations thereof.

37. The method of claim 1, wherein said subject is a child.

38. The method of claim 37, wherein said child has been diagnosed as suffering from a condition related to the central nervous system.

39. The method of claim 38, wherein said condition is selected from the group consisting of epilepsy, autism spectrum disorder, attention deficiency disorder (ADD), attention deficiency hyperactive disorder (ADHD) and Tourette syndrome.

40. The method of claim 1, further comprising adding said composition to a liquid prior to said administering, wherein an emulsion is formed.

41. The method of claim 40, wherein said liquid is selected from the group consisting of water, juice, milk, milk analogue, soup and combinations thereof.

42. The method of claim 41, wherein said liquid is administered in the form of a beverage.

43. The method of claim 42, wherein said beverage is selected from the group consisting of a tea, and a shake.

44. The method of claim 42, wherein said beverage is administered at a temperature in the range between 30°C and 60°C.

45. The method of claim 40, wherein said adding to said liquid comprises immersing in the liquid a porous receptacle comprising said composition.

46. The method of claim 40, wherein the composition is provided in the form a sublingual tablet and wherein said emulsion is formed upon contact of said tablet with saliva of the subject.

47. The method of claim 40, wherein said adding said composition to a liquid is performed no more than 60 minutes prior to said administering.

48. The method of claim 2, wherein said composition is prepared by a method comprising(i) providing a solid carrier comprising a nanoporous material;(ii) providing a source comprising at least one cannabinoid, which source is selected from the group consisting of cannabis plant materials, fermentation products, synthetic products, and bio-reactor products;(iii) extracting said source to form an extract comprising said at least one cannabinoid;(iv) optionally, purifying said extract to form a purified extract;(v) optionally diluting said extract or purified extract in a liquid carrier to form a diluted extract;(vi) adsorbing at least one selected from the group consisting of said extract, said purified extract and said diluted extract on said carrier, whereby said composition is formed.

49. The method of claim 48, further comprising, adsorbing at least one additional cannabinoid and / or at least one terpene on said carrier.

50. The method of claim 2, wherein said composition is prepared by a method comprising(i) providing a composition comprising said cannabinoid and at least one nanoporous solid carrier, wherein said at least one cannabinoid is contained in at least a portion of pores of said at least one nanoporous solid carrier(ii) providing at least one composition selected from(a) a composition comprising at least one terpene and at least one nanoporous solid carrier, wherein said at least one terpene is contained in at least a portion of pores of said at least one nanoporous solid carrier;(b) a composition comprising at least one emulsifier and at least one nanoporous solid carrier, wherein said at least one emulsifier is contained in at least a portion of pores of said at least one nanoporous solid carrier;(c) a composition comprising at least one liquid carrier and at least one nanoporous solid carrier, wherein said at least one liquid carrier is contained in at least a portion of pores of said at least one nanoporous solid carrier;(d) a composition comprising at least one at least one oil-soluble, non-cannabinoid compound and at least one nanoporous solid carrier, wherein said at least one at leastone oil-soluble, non-cannabinoid compound is contained in at least a portion of pores of said at least one nanoporous solid carrier; and(iii) blending said composition (i) with at least one of the compositions (ii).

51. A composition comprising(a) a cannabinoid and at least one nanoporous solid carrier, wherein said at least one cannabinoid is contained in at least a first portion of pores of said at least one nanoporous carrier, the composition further comprising at least two, at least three or all four selected from the group consisting of:(b) a terpene contained in at least a second portion of pores of said at least one solid nanoporous carrier;(c) an emulsifier contained in at least a third portion of pores of said at least one solid nanoporous carrier;(d) a liquid carrier contained in at least a fourth portion of pores of said at least one solid nanoporous carrier;(e) at least one oil-soluble, non-cannabinoid compound selected from the group consisting of anti-oxidants, anti-inflammatory agents, nutraceuticals, pharmaceutical drugs and combinations thereof, wherein said oil-soluble non-cannabinoid compound has a solubility in medium-chain triglycerides (MCT) of at least 10 mcg / ml at 25°C, which non-cannabinoid compound is contained in at least a fifth portion of pores of said at least one solid nanoporous carrier.

52. The composition of Claim 51, comprising(a) a cannabinoid and at least two nanoporous solid carriers, wherein said at least one cannabinoid is contained in at least a first portion of pores of at least one of said at least two nanoporous carriers and at least two, at least three or all four selected from the group consisting of:(b) a terpene contained in at least a second portion of pores of at least one of said at least two solid nanoporous carriers;(c) an emulsifier contained in at least a third portion of pores of at least one of said at least two solid nanoporous carriers;(d) a liquid carrier contained in at least a fourth portion of pores of at least one of said at least two solid nanoporous carriers;(e) at least one oil-soluble, non-cannabinoid compound selected from the group consisting of anti-oxidants, anti-inflammatory agents, nutraceuticals, pharmaceutical 1drugs and combinations thereof, wherein said oil-soluble non-cannabinoid compound has a solubility in medium-chain triglycerides (MCT) of at least 10 mcg / ml at 25 °C, which non-cannabinoid compound is contained in at least a fifth portion of pores of said at least two solid nanoporous carrier.

53. A product comprising the composition of claim 52, selected from the group consisting of tablets, gel capsules, foods, beverages and a porous vessel comprising said composition.

54. The product of claim 53, further comprising at least one water-soluble, non- cannabinoid compound selected from the group consisting of anti-oxidants, antiinflammatory agents, nutraceuticals, pharmaceutical drugs and combinations thereof, wherein said water-soluble non-cannabinoid compound has a solubility in water of at least 1 mg / ml at 25 °C.

55. A method of increasing bioavailability of at least one administered cannabinoid in a subject in need thereof, the method comprising administering said product of Claim 53.

56. The method of claim 55, wherein said administering comprises orally administering.

57. The method of claim 55, wherein said administering comprises providing an emulsion.

58. The method of claim 57, wherein said emulsion is formed in situ.