WO2021151168A1 - Méthode de thérapie cannabinoïde - Google Patents

Méthode de thérapie cannabinoïde Download PDF

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Publication number
WO2021151168A1
WO2021151168A1 PCT/AU2021/050072 AU2021050072W WO2021151168A1 WO 2021151168 A1 WO2021151168 A1 WO 2021151168A1 AU 2021050072 W AU2021050072 W AU 2021050072W WO 2021151168 A1 WO2021151168 A1 WO 2021151168A1
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cannabinoid
administered
dose
amount
series
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PCT/AU2021/050072
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English (en)
Inventor
Musabek MAVLIANOV
Paul D.R. MACLEMAN
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AusCann Group Holdings Ltd
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Priority claimed from AU2020900271A external-priority patent/AU2020900271A0/en
Application filed by AusCann Group Holdings Ltd filed Critical AusCann Group Holdings Ltd
Publication of WO2021151168A1 publication Critical patent/WO2021151168A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/485—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present disclosure relates to methods of administering controlled doses of one or more cannabinoids throughout a course of treatment.
  • the cannabinoid is administered by means of an oral unit dosage form, wherein each unit dosage form comprises a solid pharmaceutical composition that includes the cannabinoid(s), a lipophilic solvent and a porous particulate solid, such that the use of the solid pharmaceutical composition enables consistent dosing of the cannabinoid.
  • medicinal cannabis may be administered by several means including oral capsules containing dried powdered cannabis plant material; edible ‘food’ products produced by infusing cannabis extract into a lipid phase (e.g. butter, cooking oil, edible fat) or a solvent phase (e.g.
  • lipid phase e.g. butter, cooking oil, edible fat
  • solvent phase e.g.
  • glycerol glucose, alcohol
  • hard or soft- shell gelatin capsules containing cannabinoids dissolved in medium chain triglycerides or carrier oils
  • chewing gum inhalers produced by vaporisation of dried plant material; liquid sprays or aerosols by delivery to the oral mucosa; and as nutraceuticals combined with vitamins, minerals and other nutrients within lipid nano spheres.
  • While the above means of delivery provide a useful source of medicinal cannabis, in some cases they can be associated with a significant variability in the amount of active ingredients delivered. Generally, the inconsistencies arise due to natural variability associated with the composition of plant-derived cannabinoid extracts utilised to produce the medicines, as well as poor stability and/or low bio availability of the cannabinoid actives associated with some formulations.
  • a further source of variability is associated with the physicochemical properties of cannabinoids: these compounds are lipophilic, water-insoluble and typically exist as tacky, resinous tar-like substances comprising complex mixtures of diverse chemical compounds.
  • a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject comprising administering to the subject a course of at least one cannabinoid; wherein the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 10 wt. % throughout the course; wherein the cannabinoid is administered in an oral unit dosage form comprising a solid pharmaceutical composition which comprises the cannabinoid, a lipophilic solvent and a porous particulate solid; and whereby use of the solid pharmaceutical composition enables consistent dosing of the cannabinoid.
  • the cannabinoid is administered at least once per day over a period of at least 5 days, at least once per day over a period of at least 10 days, at least once per day over a period of at least 20 days, or at least once per day over a period of at least one month.
  • the cannabinoid is administered at least twice per day over a period of at least 5 days, at least twice per day over a period of at least 10 days, at least twice per day over a period of at least 20 days, or at least twice per day over a period of at least one month.
  • the course includes at least 5 doses, at least 10 doses, at least 20 doses, at least 30 doses, at least 40 doses, or at least 50 doses.
  • the amount of the cannabinoid administered in each dose of the course is 2 mg, or the amount administered in each dose of the course is 2.5 mg, or the amount administered in each dose of the course is 3 mg, or the amount administered in each dose of the course is 4 mg, or the amount administered in each dose of the course is 5 mg, or the amount administered in each dose of the course is 6 mg, or the amount administered in each dose of the course is 8 mg, or the amount administered in each dose of the course is 10 mg, or the amount administered in each dose of the course is 15 mg, or the amount administered in each dose of the course is 20 mg, or the amount administered in each dose of the course is 25 mg, or the amount administered in each dose of the course is 30 mg, or the amount administered in each dose of the course is 40 mg, or the amount administered in each dose of the course is 50 mg, or the amount administered in each dose of the course is 100 mg, or the amount administered in each dose of the course is 150 mg, wherein the amount of the cannabinoid administered in each dose of the course is consistent
  • the amount of the cannabinoid administered in each dose of the course varies by no more than ⁇ 10 wt %, or by no more than ⁇ 5 wt %, or by no more than ⁇ 2 wt %, or by no more than ⁇ 1 wt %.
  • a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject comprising administering to the subject a course of at least one cannabinoid; wherein the course comprises i) administering a first series of doses of the cannabinoid, and subsequently ii) administering a second series of doses of the cannabinoid; wherein the amount of cannabinoid administered in each dose of the first series is consistent such that it varies by no more than ⁇ 10wt% or by no more than ⁇ 10mol% throughout the first series; wherein the amount of cannabinoid administered in each dose of the second series is consistent such that it varies by no more than ⁇ 10wt% or by no more than ⁇ 10mol% throughout the further series; wherein the amount of cannabinoid administered in each dose of the first series is different from the amount of cannabinoid administered in each dose of the second series; wherein the cannabinoid is administered
  • the first series of doses involves administration of cannabinoid at least once per day over a period of at least 5 days, at least once per day over a period of at least 10 days, at least once per day over a period of at least 20 days, or at least once per day over a period of at least one month.
  • the second series of doses involves administration of cannabinoid at least once per day over a period of at least 5 days, at least once per day over a period of at least 10 days, at least once per day over a period of at least 20 days, or at least once per day over a period of at least one month.
  • the first series of doses involves administration of cannabinoid at least twice per day over a period of at least 5 days, at least twice per day over a period of at least 10 days, at least twice per day over a period of at least 20 days, or at least twice per day over a period of at least one month.
  • the second series of doses involves administration of cannabinoid at least twice per day over a period of at least 5 days, at least twice per day over a period of at least 10 days, at least twice per day over a period of at least 20 days, or at least twice per day over a period of at least one month.
  • the first series of doses includes at least 10 doses, at least 20 doses, at least 30 doses, at least 40 doses, or at least 50 doses.
  • the second series of doses includes at least 10 doses, at least 20 doses, at least 30 doses, at least 40 doses, or at least 50 doses.
  • the amount of cannabinoid administered in each dose of the first series is 2 mg, or the amount administered in each dose of the first series is 2.5 mg, or the amount administered in each dose of the first series is 3 mg, or the amount administered in each dose of the first series is 4 mg, or the amount administered in each dose of the first series is 5 mg, or the amount administered in each dose of the first series is 10 mg, or the amount administered in each dose of the first series is 20 mg, or the amount administered in each dose of the first series is 50 mg, wherein the amount of cannabinoid administered in each dose of the first series is consistent such that it varies by no more than ⁇ 10 wt% throughout the first series.
  • the amount of cannabinoid administered in each dose of the second series is 4 mg, or the amount administered in each dose of the second series is 5 mg, or the amount administered in each dose of the second series is 6 mg, or the amount administered in each dose of the second series is 8 mg, or the amount administered in each dose of the second series is 10 mg, or the amount administered in each dose of the second series is 20 mg, or the amount administered in each dose of the second series is 40 mg, or the amount administered in each dose of the second series is 100 mg, or the amount administered in each dose of the second series is 150 mg, wherein the amount of cannabinoid administered in each dose of the second series is consistent such that it varies by no more than ⁇ 10 wt% throughout the second series.
  • the amount of cannabinoid administered in each dose of the first series varies by no more than ⁇ 5 wt % and the amount of cannabinoid administered in each dose of the second series varies by no more than ⁇ 5 wt %; b) the amount of cannabinoid administered in each dose of the first series varies by no more than ⁇ 2 wt % and the amount of cannabinoid administered in each dose of the second series varies by no more than ⁇ 2 wt %; or c) the amount of cannabinoid administered in each dose of the first series varies by no more than ⁇ 1 wt % and the amount of cannabinoid administered in each dose of the second series varies by no more than ⁇ 1 wt %.
  • the amount of cannabinoid administered in each dose of the first series is different from the amount of cannabinoid administered in each dose of the second series by at least ⁇ 10 %, preferably at least ⁇ 20 %, more preferably by at least ⁇ 30 % and still more preferably by at least ⁇ 40 % or by at least ⁇ 50 %.
  • the amount of cannabinoid administered in each dose of the second series is higher than the amount of cannabinoid administered in each dose of the first series.
  • the course comprises iii) administering a third series of doses of cannabinoid; wherein the amount of cannabinoid administered in each dose of the third series is consistent such that it varies by no more than ⁇ 10wt% or by no more than ⁇ 10mol% throughout the third series; wherein the amount of cannabinoid administered in each dose of the third series is different from the amount of cannabinoid administered in each dose of the first series and the second series.
  • the amount of cannabinoid administered in each dose of the third series is higher than the amount of cannabinoid administered in each dose of the second series.
  • the amount of cannabinoid administered in each dose of the third series is different from the amount of cannabinoid administered in each dose of the first and/or second series by at least ⁇ 10 %, preferably at least ⁇ 20 %, more preferably by at least ⁇ 30 % and still more preferably by at least ⁇ 40 % or by at least ⁇ 50 %.
  • the cannabinoid is selected from the group consisting of cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichormevarin (CBCV), cannabichromevarinic acid (CBCVA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabielsoin (CBE), cannabicyclol (CBL), cannabinodiol (CBND), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabinol (CBN), cannabinolic acid (CBNA), cannabitriol (CBT), delta-8- tetrahydrocanninol, delta-8-tetrahydrocannabinolic acid, delta-9-
  • the cannabinoid is cannabidiol (CBD). In some embodiments, the cannabinoid is delta-9-tetrahydrocannabinol (THC).
  • a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject comprising administering to the subject a course of at least two cannabinoids; wherein the course comprises i) administering a series of doses of a first cannabinoid, and ii) administering a series of doses of a second different cannabinoid; wherein the amount of first cannabinoid administered in each dose is consistent such that it varies by no more than ⁇ 10wt% or by no more than ⁇ 10mol% throughout the series of doses; wherein the amount of second cannabinoid administered in each dose is consistent such that it varies by no more than ⁇ 10wt% or by no more than ⁇ 10mol% throughout the series of dose
  • the cannabinoids are selected from the group consisting of cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichormevarin (CBCV), cannabichromevarinic acid (CBCVA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabielsoin (CBE), cannabicyclol (CBL), cannabinodiol (CBND), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabinol (CBN), cannabinolic acid (CBNA), cannabitriol (CBT), delta-8- tetrahydrocanninol, delta-8-tetrahydrocannabinolic acid, delta-9-
  • the first cannabinoid is CBD and the second cannabinoid is THC.
  • the first cannabinoid is administered once per day in the morning and the second cannabinoid is administered once per day in the evening, over a period of at least 5 days, at least 10 days, at least 20 days or at least one month.
  • the first cannabinoid is administered twice per day in the morning and in the afternoon and the second cannabinoid is administered once per day in the evening, over a period of at least 5 days, at least 10 days, at least 20 days or at least one month.
  • the method as defined herein is a method wherein: a) the amount of the first cannabinoid administered in each dose of the course varies by no more than ⁇ 5 wt % and the amount of the second cannabinoid administered in each dose of the course varies by no more than ⁇ 5 wt %; b) the amount of the first cannabinoid administered in each dose of the course varies by no more than ⁇ 2 wt % and the amount of the second cannabinoid administered in each dose of the course varies by no more than ⁇ 2 wt %; or c) the amount of the first cannabinoid administered in each dose of the course varies by no more than ⁇ 1 wt % and the amount of the second cannabinoid administered in each dose of the course varies by no more than ⁇ 1 wt %.
  • the solid pharmaceutical composition comprises an emulsifier/surfactant.
  • the solid pharmaceutical composition is self-emulsifying.
  • the emulsifier/surfactant is admixed with cannabinoid extract in the presence of lipophilic solvent, prior to incorporation to the porous particulate solid.
  • the emulsifier/surfactant is also the lipophilic solvent.
  • the lipophilic solvent may have properties that allow it to act as an emulsifier/surfactant as well as in solubilising the cannabinoid(s).
  • the emulsifier/surfactant is a polyethoxylated castor oil.
  • the solid pharmaceutical composition comprises one or more of a filler, binder and an anti-caking agent, wherein the filler, binder and/or anti caking agent is admixed with the porous particulate solid following incorporation of the cannabinoid extract by the porous particulate solid.
  • the solid pharmaceutical composition comprises one or more of a filler, binder and an anti-caking agent, wherein the filler, binder and/or anti caking agent is admixed with the porous particulate solid following incorporation of the cannabinoid extract by the porous particulate solid, and wherein microcrystalline cellulose and tricalcium phosphate are admixed with the porous particulate solid following incorporation of the cannabinoid extract.
  • the particulate porous solid is a colloidal silicon dioxide.
  • the particulate porous solid is amorphous silica.
  • the particulate porous solid is mesoporous and has a mean mesopore volume in the range of from about 1.5 to about 2.0 mL/g.
  • the particulate porous solid has a mean surface area of from about 150 to about 350 m 2 /g.
  • the particulate porous solid has a particle size dso in the range of from about 20 to about 200 pm.
  • the particulate porous solid may have a lipophilic solvent: particulate porous solid ratio of between 10:1 to 1:1, between 9:1 to 1:1, between 8:1 to 1:1, between 7:1 to 1:1, between 6:1 to 1:1, between 5:1 to 1:1, between 4:1 to 1:1, between 3:1 to 1:1, or between 2:1 to 1:1.
  • the lipophilic solvent is selected from group consisting of a vegetable oil, a medium chain triglyceride, a long chain triglyceride, an emulsifier/surfactant, and mixtures thereof.
  • the solid pharmaceutical composition is a free flowing powder.
  • the unit dosage form is a capsule.
  • the capsule has a shell which comprises gelatin, pullulan and/or hydro xypropyl methylcellulose.
  • the capsule is enteric coated.
  • the solid pharmaceutical composition and/or unit dosage form comprises CBD, wherein following storage of the solid pharmaceutical composition and/or unit dosage form for a period of 3 months at 25°C and 60% relative humidity, the amount of CBD in the solid pharmaceutical composition and/or unit dosage form decreases by no more than 10 wt% or 10 mol%.
  • the solid pharmaceutical composition and/or unit dosage form comprises THC, wherein following storage of the solid pharmaceutical composition and/or unit dosage form for a period of 3 months at 25°C and 60% relative humidity, the amount of THC in the solid pharmaceutical composition and/or unit dosage form decreases by no more than 10 wt% or 10 mol%.
  • the solid pharmaceutical composition and/or unit dosage form comprises CBD, wherein following contacting of the solid pharmaceutical composition and/or unit dosage form with water, at least 50% by weight of the CBD is released within 1 hour.
  • the solid pharmaceutical composition and/or unit dosage form comprises THC, wherein following contacting of the solid pharmaceutical composition and/or unit dosage form with water, at least 50% by weight of the THC is released within 1 hour.
  • the aqueous environment is 0.5% aqueous hexadecyltrimethylammonium bromide comprising a phosphate buffer at pH 6.8, and the contacting is carried out at 37°C ⁇ 0.5°C with stirring at 100 rpm.
  • the disease, disorder or condition is selected from the group consisting of an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, a cardiovascular disorder, cancer, and pain.
  • a use of a cannabinoid for the manufacture of a medicament which medicament is an oral unit dosage form comprising a solid pharmaceutical composition which comprises the cannabinoid, a lipophilic solvent and a porous particulate solid, for preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, wherein the subject is administered a course of a cannabinoid; wherein the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 10 wt% or ⁇ 10 mol% throughout the course; whereby use of the solid pharmaceutical composition enables consistent dosing of the cannabinoid; and wherein the disease, disorder or condition is selected from the group consisting of an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, a cardiovascular disorder,
  • a use of a cannabinoid for the manufacture of a medicament which medicament is an oral unit dosage form comprising a solid pharmaceutical composition which comprises the cannabinoid, a lipophilic solvent and a porous particulate solid, for preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, wherein the subject is administered a course of a cannabinoid; wherein the course comprises i) administering a first series of doses of the cannabinoid, and subsequently ii) administering a further series of doses of the cannabinoid; wherein the amount of cannabinoid administered in each dose of the first series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the first series; wherein the amount of cannabinoid administered in each dose of the further series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the further series;
  • the amount of cannabinoid administered in each dose of the first series may be different from the amount of cannabinoid administered in each dose of any or all of the further series in wt% terms by at least ⁇ 10 %, preferably at least ⁇ 20 %, more preferably by at least ⁇ 30 % and still more preferably by at least ⁇ 40 % or by at least ⁇ 50 %.
  • a use of a first cannabinoid for the manufacture of a medicament which medicament is an oral unit dosage form comprising a solid pharmaceutical composition which comprises the first cannabinoid, a lipophilic solvent and a porous particulate solid
  • a second cannabinoid for the manufacture of a medicament, which medicament is an oral unit dosage form comprising a solid pharmaceutical composition which comprises the second cannabinoid, a lipophilic solvent and a porous particulate solid, for preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, wherein the course comprises i) administering a series of doses of a first cannabinoid, and ii) administering a series of doses of a second different cannabinoid; wherein the amount of first cannabinoid administered in each dose is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the series of doses; wherein the
  • a cannabinoid for use in a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, the method comprising administering to the subject a course of at least one cannabinoid; wherein the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 10 wt% or ⁇ 10 mol% throughout the course; wherein the cannabinoid is administered in an oral dosage comprising a solid pharmaceutical composition which comprises the cannabinoid, a lipophilic solvent and a porous particulate solid; and whereby use of the solid pharmaceutical composition enables consistent dosing of the cannabinoid.
  • the disease, disorder or condition is selected from the group consisting of an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, a cardiovascular disorder, cancer, and pain.
  • a cannabinoid for use in a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, the method comprising administering to the subject a course of at least one cannabinoid; wherein the course comprises i) administering a first series of doses of the cannabinoid, and subsequently ii) administering a further series of doses of the cannabinoid; wherein the amount of cannabinoid administered in each dose of the first series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the first series; wherein the amount of cannabinoid administered in each dose of the further series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the further series; wherein the amount of cannabinoid administered in each dose of the first series is different from the amount of cannabinoid administered in each dose of the further series; wherein the can
  • the amount of cannabinoid administered in each dose of the first series may be different from the amount of cannabinoid administered in each dose of any or all of the further series by at least ⁇ 10 wt%, preferably at least ⁇ 20 wt%, more preferably by at least ⁇ 30wt % and still more preferably by at least ⁇ 40 wt% or by at least ⁇ 50 wt%.
  • the disease, disorder or condition is selected from the group consisting of an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, a cardiovascular disorder, cancer, and pain.
  • a first cannabinoid and a second cannabinoid for use in a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, the method comprising administering to the subject a course of at least two cannabinoids; wherein the course comprises i) administering a series of doses of a first cannabinoid, and ii) administering a series of doses of a second different cannabinoid; wherein the amount of first cannabinoid administered in each dose is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the series of doses; wherein the amount of second cannabinoid administered in each dose is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the series of doses; wherein the first cannabinoid is administered in an oral dosage comprising a solid pharmaceutical composition which comprises the cannabinoid, a
  • the disease, disorder or condition is selected from the group consisting of an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, a cardiovascular disorder, cancer, and pain.
  • the term “about” as used herein means within 5%, and more preferably within 1%, of a given value or range. For example, “about 3.7%” means from 3.5 to 3.9%, preferably from 3.66 to 3.74%.
  • “about” is associated with a range of values, e.g., “about X% to Y%”, the term “about” is intended to modify both the lower (X) and upper (Y) values of the recited range. For example, “about 20% to 40%” is equivalent to “about 20% to about 40%”.
  • pharmaceutically acceptable with respect to a substance as used herein means that substance which is suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for the intended use when the substance is used in a pharmaceutical composition
  • terapéuticaally effective amount refers to an amount of active ingredient needed to provide a desired level of active ingredient in the bloodstream or at a target organ of to provide an anticipated physiological response.
  • a therapeutically effective amount of an active ingredient may be administered in a single dosage, or through multiple dosages of an amount that cumulatively provides a therapeutic effect.
  • the ‘therapeutic effect’ may reduce the severity of a disease, medical condition or one or more associated symptoms, and/or may be therapeutic in terms of a partial or complete cure of a disease or medical condition.
  • Therapeutic Methods The present disclosure relates to methods of administering consistent and controlled dosing of cannabinoids.
  • cannabinoids are currently available in a dried powdered form of cannabis plant material or as a resinous extract.
  • the active ingredient(s) of interest may be present in varying amounts and therefore it is difficult to administer a pre-defined therapeutically effective dosage.
  • these cannabinoid extracts are often available, for example, as edible oils or compositions for inhalers, whereby delivery of an exact and consistent dose is difficult or unattainable.
  • the resinous, highly viscous nature of many of the commercially available forms of cannabinoids makes accurate measurement and dispensing extremely difficult and therefore resists reproducible, consistent dosing.
  • cannabinoids Methods of administering cannabinoids have now been identified which provide for precise control in respect of the amount of cannabinoid that is delivered to a patient and for easier and cost-effective manufacture of the delivery forms.
  • the methods are enabled by use of solid cannabinoid-containing pharmaceutical compositions present in oral unit dosage forms.
  • the solid pharmaceutical compositions comprise known and reproducible amounts of cannabinoids, a lipophilic solvent and a porous particulate solid.
  • the solid compositions are typically obtained as free-flowing powders with known cannabinoid content, they allow to reach a target amount of desired cannabinoid in each dosage form. Further, unlike many other cannabinoid compositions, the herewith disclosed solid pharmaceutical compositions have good storage stability, and thus the amount of desired cannabinoid in dosage forms remains within the specified value.
  • the technology enables a desired dosing of cannabinoid to be administered to a patient in a controlled and consistent way throughout a course of treatment.
  • a cannabinoid of interest may be administered once a day by delivery of an oral dosage containing a dose of choice over a course of one week, wherein the same dose is delivered every day. If no adverse effects are observed, the dose may be increased in a controlled way to reach a therapeutic effect, and then maintained for long courses of treatment such as months or years. It is also possible to administer more than one cannabinoid consistently. For example, a dose of one cannabinoid agent may be administered orally in the morning, and another in the evening, and the dose of either may be increased if no side effects have developed.
  • cannabinoid-containing solid pharmaceutical compositions and oral unit dosage forms administered in accordance with the present methods may be used therapeutically and prophylactically, for example to prevent, treat and/or lessen the severity of a wide range of diseases, conditions and disorders (including, for example, treating or lessening the severity of one or more symptoms associated with such a disease, condition or disorders), e.g. those disorders for which administration of a cannabinoid may be beneficial.
  • diseases, conditions and disorders including, for example, treating or lessening the severity of one or more symptoms associated with such a disease, condition or disorders
  • disorders for which administration of a cannabinoid may be beneficial.
  • diseases, conditions and disorders include inflammatory disorders, neurological disorders, psychiatric disorders, malignancies, immune disorders, metabolic disorders, nutritional deficiencies, infectious diseases, gastrointestinal disorders, cardiovascular disorders, cancer, and pain, including chronic and neuropathic pain.
  • the methods as described herein may be applicable, although not only, to therapy and/or prophylaxis of diseases, disorders or conditions such as depression, sleeping disorders, eating disorders, cancer, multiple sclerosis, graft versus host disease (GVHD), Parkinson's, epilepsy, autism, tuberculosis, ulcerative colitis, morbus Crohn, inflammatory bowel disorder (IBD), irritable bowel syndrome (IBS), appetite stimulant, appetite depressant, obesity, diabetes, nausea, neuropathic pain, anxiety, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), gastrointestinal disorders, hypertension, incontinence, pruritus, arthritis, arthrosis, rheumatic inflammation, insomnia, mycosis, local and/or chronic pain, inflammation, attention deficit and hyperactivity disorder (ADDH), vomiting, atopic dermatitis, fibromyalgia, autoimmune deficiency syndrome (AIDS), mood disorders, erectile dysfunction,
  • diseases, disorders or conditions such as depression, sleeping disorders, eating
  • the subject to whom the cannabinoid is administered is an animal, e.g. a mammal. In some embodiments the subject is a human. In other embodiments the subject is a non-human animal, e.g. a non-human mammal.
  • the dose or frequency of administering the solid pharmaceutical composition or the oral unit dosage form as described herein may for example be dependent on factors such as the age, weight, general physical condition of the subject, or other clinical symptoms specific to the subject to be treated.
  • solid pharmaceutical compositions as defined herein.
  • the solid pharmaceutical compositions comprise a cannabinoid, a lipophilic solvent, and a porous particulate solid.
  • the substances used in the preparation of the solid pharmaceutical compositions, and of the oral unit dosage forms, are pharmaceutically acceptable.
  • the solid pharmaceutical composition comprises a cannabinoid.
  • cannabinoid refers to a class of C 21 terpenophenolic compounds that represent a group of compounds found in Cannabis sativa. The term encompasses synthetic analogues of such C 21 terpenophenolic compounds.
  • An extract comprising a mixture of cannabinoids may be used.
  • An extract which has undergone processing and/or purification to increase the proportion of one or more cannabinoids may be utilised.
  • solid pharmaceutical composition comprises one or more cannabinoids selected from the group consisting of cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichormevarin (CBCV), cannabichromevarinic acid (CBCVA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabielsoin (CBE), cannabicyclol (CBL), cannabinodiol (CBND), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabinol (CBN), cannabinolic acid (CBNA), cannabitriol (CBT), delta-8-tetrahydrocanninol, delta-8- tetrahydrocannabinolic
  • CBC
  • the solid pharmaceutical composition comprises cannabidiol (CBD).
  • CBD cannabidiol
  • cannabidiol (CBD) is the main cannabinoid present in the solid pharmaceutical composition.
  • at least 35%, at least 50%, at least 60%, at least 70%, at least 80% at least 90%, or at least 95% by weight of the cannabinoids present in the solid pharmaceutical composition is cannabidiol (CBD).
  • substantially all of the cannabinoid present in the solid pharmaceutical composition is cannabidiol (CBD).
  • the solid pharmaceutical composition comprises delta- 9-tetrahydrocannabinol (THC).
  • delta-9-tetrahydrocannabinol is the main cannabinoid present in the solid pharmaceutical composition.
  • at least 35%, at least 50%, at least 60%, at least 70%, at least 80% at least 90%, or at least 95% by weight of the cannabinoids present in the solid pharmaceutical composition is delta-9-tetrahydrocannabinol (THC).
  • substantially all of the cannabinoid present in the solid pharmaceutical composition is delta-9-tetrahydrocannabinol (THC).
  • the present disclosure encompasses provision of tailored compositions and dosage forms with different amounts and types of cannabinoid, i.e. tailored for a given indication and/or for a patient’s needs.
  • the solid pharmaceutical composition may comprise a mixture of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in a range of relative amounts.
  • CBD cannabidiol
  • THC delta-9-tetrahydrocannabinol
  • the weight ratio may for example be a ratio within the range of from 1:100 to 100:1, or from 1:20 to 20:1, or from 1:10 to 10:1, or from 1:5 to 5:1, or from 1:3 to 3:1, or from 1:2 to 2:1, or about 1:1.
  • the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is at least 20:1.
  • the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 20:1. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 15:1. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 10:1.
  • CBD cannabidiol
  • THC delta-9- tetrahydrocannabinol
  • the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 8:1. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 6:1. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 5:1.
  • CBD cannabidiol
  • THC delta-9- tetrahydrocannabinol
  • the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 4:1. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 3:1. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 2:1.
  • CBD cannabidiol
  • THC delta-9- tetrahydrocannabinol
  • the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 1:1. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 1:2. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 1:3.
  • CBD cannabidiol
  • THC delta-9- tetrahydrocannabinol
  • the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 1:4. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 1:5. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 1:6.
  • CBD cannabidiol
  • THC delta-9- tetrahydrocannabinol
  • the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 1:8. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 10:1. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 1:15.
  • the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is 1:20. In some embodiments, the cannabinoid comprises a mixture of cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), and the weight ratio is at least 1:20.
  • CBD cannabidiol
  • THC delta-9- tetrahydrocannabinol
  • the concentration of one or more cannabinoids which may be present in the solid pharmaceutical composition may similarly be tailored for a given indication or patient.
  • the solid pharmaceutical composition comprises cannabidiol (CBD) and has a concentration of CBD which is a concentration within the range of from about 1 to about 150 mg CBD per 270 mg composition.
  • CBD cannabidiol
  • the solid pharmaceutical composition comprises cannabidiol (CBD) and has a concentration of CBD which is about lmg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 100 mg or 150 mg CBD per 270 mg composition.
  • CBD cannabidiol
  • the solid pharmaceutical composition comprises delta- 9-tetrahydrocannabinol (THC) and has a concentration of THC which is a concentration within the range of from about 1 to about 50 mg THC per 270 mg composition.
  • THC delta- 9-tetrahydrocannabinol
  • the solid pharmaceutical composition comprises delta- 9-tetrahydrocannabinol (THC) and has a concentration of THC which is about lmg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg, or 50 mg THC per 270 mg composition.
  • THC delta- 9-tetrahydrocannabinol
  • the solid pharmaceutical composition comprises up to 60% wt%, up to about 50 wt% cannabinoid, up to about 40 wt% cannabinoid, up to about 35 wt% cannabinoid, up to about 30 wt% cannabinoid, up to about 25 wt% cannabinoid, up to about 20 wt% cannabinoid, up to about 15 wt% cannabinoid, up to about 10 wt% cannabinoid, up to about 5 wt% cannabinoid, up to about 1 wt% cannabinoid or up to 0.5 wt% cannabinoid.
  • the amount of cannabinoid present in the solid pharmaceutical composition is in the range of from about 0.25 wt% to about 60 wt%, 0.25 wt% to about 50 wt%, 0.25 wt% to about 40 wt%, from about 0.25 wt% to about 10 wt%, from about 0.25 wt% to about 5 wt%, from about 0.25 wt% to about 4 wt%, from about 0.25 wt% to about 3 wt%, from about 0.25 wt% to about 2 wt%, from about 0.25 wt% to about 1 wt%, or about 0.25 wt%, about 0.5 wt%, about 0.75 wt%, about 1 wt%, about 1.5 wt%, about 2 wt% about 2.5 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 w
  • the solid pharmaceutical composition is produced by incorporation of a mixture comprising cannabinoid and a lipophilic solvent into and/or onto the porous particulate solid.
  • the lipophilic solvent may be a solvent having suitable properties for dissolution of and/or admixing with cannabinoid.
  • the lipophilic solvent is a vegetable oil, medium chain triglyceride, long chain triglyceride, an emulsifier/surfactant or a mixture thereof.
  • the lipophilic solvent is a vegetable oil.
  • vegetable oils include, but are not limited to, cotton seed oil, safflower oil, sunflower oil, peanut oil, linseed oil, corn oil, olive oil, coconut oil, soybean oil, sesame oil, chia ( Salvia Hispanica L.) seed oil, wheat germ oil, canola oil, castor oil, hydrogenated castor oil and any mixtures thereof.
  • the lipophilic solvent is a medium chain triglyceride.
  • MCTs medium-chain triglycerides
  • examples of medium chain triglycerides that may be suitable for use in embodiments of the present disclosure include tricaproin, tricaprylin, tricaprin, trilaurin, and mixtures thereof.
  • the medium chain triglyceride is a triglyceride of a fatty acid having from 8 to 10 carbon atoms, e.g. mixtures of tricaprylin and tricaprin may be used for example.
  • Medium chain triglycerides may, for example, be produced by processing of coconut oil or palm kernel oil.
  • the lipophilic solvent is a long chain triglyceride.
  • long-chain triglycerides refers to triglycerides whose fatty acids have an aliphatic tail of 16-20 carbon atoms.
  • long chain fatty acids that may form triglycerides that may be suitable for use in embodiments of the present disclosure include palmitic acid, oleic acid, linoleic acid, and mixtures thereof.
  • the long chain triglyceride is a triglyceride of a fatty acid having from 16 to 20 carbon atom.
  • Long chain triglycerides may, for example, be produced by processing of corn oil.
  • the lipophilic solvent is present in the solid pharmaceutical composition in an amount within the range of from about 2 wt% to about 35 wt%, or from about 5 wt% to about 35 wt%, or from about 6 wt% to about 35 wt%, or from about 8 wt% to about 35 wt%, or from about 10 wt% to about 35 wt%, or from about 12 wt% to about 35 wt%, or from about 5 wt% to about 30 wt%, or from about 6 wt% to about 30 wt%, or from about 8 wt% to about 30 wt%, or from about 10 wt% to about 30 wt%, or from about 12 wt% to about 30 wt%, or from about 5 wt% to about 25 wt%, or from about 6 wt% to about 25 wt%, or from about 8 wt% to about 25 wt%, or from about 10 wt%
  • the cannabinoid is typically present in the lipophilic solvent for loading at a dilution factor of from about 1:1 to about 1:90, and may for example depend on the concentration of cannabinoid desired in the solid pharmaceutical composition.
  • the solid pharmaceutical composition comprises a porous particulate solid.
  • a porous particulate solid Any suitable porous particulate solid which can incorporate (e.g. adsorb and/or absorb) a mixture of cannabinoid and lipophilic solvent, which is suitable for oral administration, and which can release cannabinoid following oral administration may be utilised.
  • the porous particulate solid is typically inert.
  • the porous particulate solid is a silica.
  • the silica is a colloidal silica (silicon dioxide).
  • the silica is an amorphous silica.
  • the term “amorphous” as used herein refers to a non crystalline state. Suitable examples of amorphous silica include, but are not limited to, colloidal amorphous silica sold under the trade names Aeroperl 300 Pharma grade, Syloid 244 FP Silica, Syloid XDP Silica, the Supemat range of silica, or the Aerosil range of colloidal silicon dioxide.
  • the porous particulate solid is a silica
  • the silica is present as a carrier for the cannabinoid and is not fulfilling a significant role as a glidant or other excipient, diluent or filler even though, to an extent and due to its inherent properties, it may naturally provide some benefits in one or more of these manners.
  • the porous particulate solid is a silica
  • the majority of the cannabinoid in the composition is loaded, adsorbed, absorbed, adhered or otherwise accommodated on or within this silica.
  • at least 70%, 80%, 90%, 95% or substantially all cannabinoid not free in any liquid component will loaded, adsorbed, absorbed, adhered or otherwise accommodated on or within the silica of the composition.
  • the porous particulate solid is a zinc oxide, titanium dioxide, cerium oxide or iron oxide.
  • the porous particulate solid is mesoporous.
  • mesoporous refers to pores ranging in size from about 2 nm to about 100 nm.
  • the porous particulate solid is a mesoporous silica, preferably a colloidal mesoporous silica.
  • Pores may be categorized as “open pores” that connect through and open onto a surface of a particle, or as “closed pores” that are sealed from fluid ingress from the surface of the particle.
  • the distribution of pore sizes and total pore volume of the particle may be measured using gas adsorption and pycnometry or other techniques which are known to those of skill in the art.
  • the cannabinoid(s) may be accommodated with the pores.
  • the porous particulate solid has a mean mesopore volume within the range of from about 1.5 to about 2.0 mL/g.
  • the porous particulate solid has a mean particle diameter in the range of from about 5pm to about 200pm.
  • the porous particulate solid has a mean particle diameter in the range of from about 10pm to about 175pm. In some embodiments, the porous particulate solid has a mean particle diameter in the range of from about lOpm to about 150pm.
  • the porous particulate solid has a mean particle diameter in the range of from about 10pm to about 100pm.
  • the porous particulate solid has a mean particle diameter in the range of from about 20pm to about 200pm.
  • At least 50% of the particles of the porous particulate solid have a diameter in the range of from about 20pm to about 175pm.
  • At least 90% of the particles of the porous particulate solid have a diameter in the range of from about 20pm to about 175pm.
  • the distribution of particle size may be measured using optical microscopy, laser diffraction particle size analysis, dynamic light scattering, imaging particle analysis or other techniques which are known to those of skill in the art.
  • the porous particulate solid has a surface area in the range of from about 100 to about 500 m 2 /g, or from about 200 to about 400m 2 /g, or from about 260 to about 320 m 2 /g.
  • the porous particulate solid has a mean mesopore volume within the range of from about 1.5 to about 2.0 mL/g, a mean particle diameter in the range of from about 20pm to about 200pm (preferably from about 20pm to about 150pm) , and a surface area in the range of from about 260 to about 320 m 2 /g.
  • the porous particulate solid is typically capable of incorporating (e.g. adsorbing and/or absorbing) significant quantities of cannabinoid-containing liquid.
  • the weight ratio of porous particulate composition to liquid mixture comprising lipophilic solvent and cannabinoid is in the range of from about 1:1.0 to about 1:2, from about 1:1.5 to about 1:2.
  • the particulate porous solid may have a lipophilic solvent: particulate porous solid loading ratio of between 10:1 to 1:1, between 9:1 to 1:1, between 8:1 to 1:1, between 7:1 to 1:1, between 6:1 to 1:1, between 5:1 to 1:1, between 4:1 to 1:1, between 3:1 to 1:1, or between 2:1 to 1:1.
  • the ratio of liquid self- emulsifying composition (being the lipophilic solvent plus cannabinoid plus emulsifier/surfactant and recognising the lipophilic solvent may act as emulsifier/surfactant) to the porous particulate solid may be between 1:4 to 4:1, between 1:3 to 3:1 or between 1:2 to 2:1.
  • the porous particulate solid may be present in an amount of at least 2 wt% of the solid pharmaceutical composition, or at least 3 wt%, or at least 4 wt%, or at least 5 wt%, or at least 6 wt%, or at least 8 wt%, or at least 10 wt%, or at least 12 wt%, or at least 15 wt%, or at least 18 wt%, each of which lower values may be combined with an upper value of less than 80 wt%, less than 70 wt%, less than 60 wt%, less than 50 wt%, less than 40 wt% or less than 30 wt%.
  • the porous particulate solid may be present in the solid pharmaceutical composition in an amount of between about 10 wt% to 40 wt%, about 10 wt% to 35 wt%, about 10 wt% to 30 wt%, about 15 wt% to 40 wt%, about 15 wt% to 35 wt%, about 15 wt% to 30 wt%.
  • the solid pharmaceutical composition is a free flowing powder.
  • the solid pharmaceutical composition is a solid self- emulsifying composition.
  • Such powders provide convenient, accurate and reproducible dosing of cannabinoid, since the desired amount of powder to provide a required dose of cannabinoid can readily be measured out and the loading is predictable.
  • the solid pharmaceutical composition contains an emulsifier and/or surfactant.
  • inclusion of an emulsifier in the composition is understood to facilitate formation of a liquid self-emulsifying composition.
  • the liquid self-emulsifying composition is typically prepared by dissolving at least one cannabinoid, as previously described, in the lipophilic solvent and mixing or blending the solution with the emulsifier.
  • the selected lipophilic solvent may also act as or have a role as an emulsifier/surfactant.
  • Such a liquid self-emulsifying composition can be incorporated into/onto the porous particulate solid, thereby forming a solid self-emulsifying composition.
  • solid self-emulsifying compositions have good cannabinoid release properties, in that they can assist in forming an emulsion and in releasing high levels of cannabinoid from the solid pharmaceutical composition when contacted with an aqueous environment.
  • emulsifier facilitates the dispersion and incorporation of the lipophilic mixture of cannabinoid and lipophilic solvent into/onto the porous particular solid.
  • solid self-emulsifying composition refers to a solid phase of a liquid self-emulsifying composition in the form of powders or nanoparticles suitable for use in oral solid dosage formulations.
  • the compositions typically have flowability characteristics which allow them to be accurately measured, characterised and formulated into oral solid dosage formulations.
  • the solid pharmaceutical composition comprises an emulsifier, and the emulsifier is admixed with cannabinoid extract which may or may not be in the presence of an additional lipophilic solvent (depending on whether the lipophilic solvent and emulsifier/surfactant are one and the same), prior to incorporation to the porous particulate solid.
  • the solid pharmaceutical composition may comprise a surfactant.
  • Surfactants may for example be used to increase the rate of dissolution and dispersion in an aqueous environment of the cannabinoid, by facilitating wetting thereof.
  • an emulsifier is used, in some embodiments the emulsifier is a surfactant.
  • surfactants include fatty acid and alkyl sulfonates, benzalkonium chloride, dioctyl sodium sulfo succinate, polyoxyethylene sorbitan fatty acid esters, natural surfactants such as sodium taurocho lie acid, l-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine, lecithin, and other phospholipids and mono- and diglycerides, and any combination thereof.
  • the surfactant is a non-ionic surfactant.
  • non ionic surfactant refers to an organic compound having covalently bonded heteroatom-containing (e.g. oxygen-containing) hydrophilic groups which are bonded to hydrophobic parent structures, and which are capable of lowering the surface tension between two non-miscible liquids, in particular a hydrophilic liquid and a hydrophobic liquid.
  • non-ionic surfactants include ethoxylated linear alcohols, ethoxylated alkyl-phenols, acid ethoxylated fatty acids, glycerol esters, esters of hexitols and cyclic anhydrohexitols.
  • the surfactant is a polyethoxylated non- ionic surfactant.
  • the surfactant is a polyethoxylated castor oil (also known as polyoxyl castor oil), such as that sold under the trade name Kolliphor ® EL.
  • the lipophilic solvent is medium chain triglycerides and the solid pharmaceutical composition comprises an emulsifier/surfactant which is a polyethoxylated castor oil.
  • the emulsifier/surfactant is present in the solid pharmaceutical composition in an amount of from about 1 wt% to about 30 wt%, or from about 1 wt% to about 25 wt%, or from about 1 wt% to about 20 wt%, or from about 1 wt% to about 15 wt%, or from about 1 wt% to about 10 wt %, or from about 2 wt% to about 15 wt%, or from about 2 wt% to about 10 wt%, or from about 2 wt% to about 8 wt%, or from about 2 wt% to about 6 wt%, or about 2 wt%, or about 3 wt%, or about 4 wt%, or about 5 wt%, or about 6 wt%.
  • the solid pharmaceutical composition may comprise one or more further pharmaceutical excipients.
  • additional excipients may be blended with the resulting solid cannabinoid-containing composition.
  • excipients include fillers, binders, anti-caking agents, disintegrants, lubricants, glidants, preservatives, antioxidants, surfactants, effervescent excipients, colouring agents, coating agents, and sweetening agents.
  • excipients are typically used for their customary purposes and in typical amounts without adversely affecting the properties of the compositions. They are not used as a carrier for a cannabinoid to any significant extent.
  • the solid pharmaceutical composition comprises a filler and/or a binder.
  • suitable examples of fillers and binders include, but are not limited to, lactose, mannitol, xylitol, microcrystalline cellulose, methyl cellulose, dibasic calcium phosphate (anhydrous and dihydrate), starch, and any combinations thereof.
  • the solid pharmaceutical composition comprises microcrystalline cellulose.
  • An anti-caking agent may be included to prevent the formation of lumps (caking) and to assist flowability properties of the solid pharmaceutical composition.
  • the solid pharmaceutical composition comprises an anti-caking agent.
  • anti-caking agents include, but are not limited to, silicon dioxide, lactose, tricalcium phosphate, and any combination thereof.
  • the solid pharmaceutical composition comprises tricalcium phosphate.
  • the solid pharmaceutical composition comprises one or more of a filler, binder and an anti-caking agent.
  • the filler, binder and/or anti-caking agent is admixed with the porous particulate solid following incorporation of the cannabinoid extract.
  • the solid pharmaceutical composition comprises microcrystalline cellulose and/or tricalcium phosphate. In some embodiments that microcrystalline cellulose and/or tricalcium phosphate are admixed with the porous particulate solid following incorporation of the cannabinoid extract.
  • the filler/binder such as microcrystalline cellulose, may be present in the solid pharmaceutical composition at between about 15 wt% to 60 wt%, about 20 wt% to 50 wt%, about 25 wt% to 40 wt%.
  • the anti-caking agent such as tricalcium phosphate, may be present in the solid pharmaceutical composition at between about 5 wt% to 30 wt%, about 8 wt% to 25 wt%, about 10 wt% to 20 wt%.
  • the solid pharmaceutical composition comprises an emulsifier/surfactant, a filler and/or binder, and an anti-caking agent.
  • the solid pharmaceutical composition comprises polyethoxylated castor oil, microcrystalline cellulose and tricalcium phosphate.
  • the lipophilic solvent is medium chain triglycerides
  • the solid pharmaceutical composition comprises polyethoxylated castor oil, microcrystalline cellulose and tricalcium phosphate.
  • Disintegrants may be added to oral solid pharmaceutical formulations to aid in their de-aggregation and to cause rapid break-up of the solids when they come into contact with moisture.
  • the solid pharmaceutical composition comprises a disintegrant. Suitable examples of disintegrants include, but are not limited to, corn starch, potato starch, sodium starch glycolate, sodium alginate, sodium carboxy methyl cellulose, methyl cellulose, and croscarmellose sodium, crospovidone, and crosslinked forms of polyvinyl pyrrolidone, and any combinations thereof.
  • Lubricants and glidants may be added to solid pharmaceutical formulations to enhance powder flow by reducing inter-particle friction.
  • the solid pharmaceutical composition comprises a lubricant and/or glidant.
  • lubricants include, but are not limited to, magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, and any combination thereof.
  • glidants include, but are not limited to, metal silicates, silicon dioxides such as colloidal anhydrous silica, higher fatty acid metal salts, metal oxides, alkaline earth metal salts, metal hydroxides, and any combination thereof.
  • a lubricant such as magnesium stearate or sodium stearyl fumarate, may be present in the solid pharmaceutical composition at between about 0.3 wt% to 2 wt%, about 0.4 wt% to 1.5 wt%, about 0.5 wt% to 1.0 wt%.
  • Preservatives may be added to solid pharmaceutical compositions to prolong the storage life of the composition, for example by reducing degradation and alteration of the active ingredient over time.
  • the solid pharmaceutical composition comprises a preservative.
  • Suitable examples of preservatives include, but are not limited to, sulphites, benzalkonium chloride, methyl paraben, propyl paraben, benzyl alcohol, sodium benzoate, and any combination thereof.
  • Antioxidants are a class of preservatives which inhibit or reduce oxidation of other molecules when added to compositions, such as active ingredient.
  • the solid pharmaceutical composition comprises one or more antioxidants.
  • Suitable examples of antioxidants include, but are not limited to, phenolic-based antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butyl-hydroquinone (TBHQ), 4-hydroxymethyl-2,6-di-tert- butylphenol (HMBP), 2,4,5-trihydroxy-butyrophenone (THBP), propyl gallate (PG), triamyl gallate, gallic acid (GA), vitamin E (alpha-tocopherol), tocopherol acetate, reducing agents such as L-ascorbic acid (vitamin C), L-ascorbyl palmitate, L-ascorbyl stearate, thioglycolic acid (TGA) ascorbyl palmitate (ASP), sulph
  • Effervescent excipients may be used in powders and tablets in combination with acidic agents to cause a reaction that produces carbon dioxide.
  • the solid pharmaceutical composition comprises an effervescent excipient. Suitable examples of effervescent excipients include sodium bicarbonate, potassium bicarbonate, magnesium bicarbonate, ammonium bicarbonate.
  • the effervescent excipients may be combined with acidic agents, typically weak organic acids such as citric acid and/or ascorbic acid.
  • the solid pharmaceutical composition comprises an acidic agent.
  • the solid pharmaceutical composition comprises and effervescent excipient and an acidic agent.
  • the solid pharmaceutical composition may additionally include inorganic salts such as sodium chloride, potassium chloride, calcium chloride, sodium phosphate, potassium phosphate, sodium bicarbonate and organic salts such as sodium citrate, potassium citrate, sodium acetate and so forth.
  • inorganic salts such as sodium chloride, potassium chloride, calcium chloride, sodium phosphate, potassium phosphate, sodium bicarbonate and organic salts such as sodium citrate, potassium citrate, sodium acetate and so forth.
  • the solid pharmaceutical compositions may for example be produced by incorporating a mixture containing the cannabinoid and lipophilic solvent into/onto a porous particulate solid.
  • Cannabinoids are typically obtained by extraction from cannabis plants.
  • the extracts may be subjected to purification and/or other processing techniques for example to increase the purity of a desired cannabinoid or cannabinoids in the mixture.
  • Cannabinoid extracts may be present in the form of resins, which can be highly viscous. They can also be present in the form of mixtures of cannabinoid with lipophilic solvent. If obtained in the form of a resin, the extract will typically be combined with a quantity of lipophilic solvent. Such an approach is advantageous since the mixtures containing lipophilic solvent and cannabinoid extract are typically less viscous than, for example, cannabinoid resins, and facilitate accurate provision of the composition having the desired cannabinoid profile.
  • density measurements for cannabinoid in medium chain triglycerides have been found to be approximately 0.95g per mL, for concentrations of cannabinoid at about 20 mg/mL and at about 260 mg/mL.
  • the cannabinoid extract and/or the mixture of cannabinoid and lipophilic solvent may be analysed to understand the cannabinoid profile, e.g. whether one or more cannabinoids are present and/or how much of a cannabinoid is present and/or the weight ratio of or more cannabinoids.
  • Any suitable analysis technique may be utilised.
  • One such example of a suitable technique is high pressure liquid chromatography (HPLC).
  • HPLC high pressure liquid chromatography
  • Other analytical techniques include gas chromatography (GC), gas chromatography-mass spectrometry, high pressure liquid chromatography-mass spectrometry, liquid chromatography-NMR spectroscopy and so forth.
  • the extract or mixture can be diluted with lipophilic solvent as required to reach the desired concentration. Separate cannabinoid mixtures could also be blended to provide the precise profile desired.
  • the resulting mixture containing cannabinoid and lipophilic solvent can then be incorporated into/onto the porous particulate solid.
  • the mixture containing cannabinoid and lipophilic solvent is typically a liquid, e.g. a solution containing cannabinoid and lipophilic solvent.
  • the mixture comprises cannabinoid and lipophilic solvent in a weight ratio in the range of from about 1:1 to about 1:90, or from about 1:1 to about 1:50, or from about 1:3 to about 1:30. Any suitable means of contacting the mixture containing cannabinoid and lipophilic solvent with the porous particulate solid may be used which enables cannabinoid to be incorporated into and/or onto the porous particulate solid in a controlled manner.
  • a mixer equipped with a suitable stirrer or impellor may be used.
  • a high shear mixer blender or high shear mixer granulator may be used, for example.
  • a high shear mixer granulator is used, such as a high shear mixer granulator produced by GMA and sold under the PMATM brand name.
  • the rate of addition of the mixture containing cannabinoid and lipophilic solvent to porous particulate solid may be controlled.
  • the incorporation step comprises adding the mixture containing cannabinoid and lipophilic solvent dropwise to the porous particulate solid, e.g. with continuous gentle mixing, followed by blending of the resulting mixture for a period sufficient to obtain the solid pharmaceutical composition.
  • the mixture containing cannabinoid and lipophilic solvent may for example be added dropwise with a dripper, e.g.
  • an orifice size of between 0.1 mm to 10 mm for example in the range of from 0.3 mm to 2 mm, or from 2 mm to 6 mm, or from 3 mm to 5 mm, or about 3.0mm, about 3.1 mm, about 3.2 mm, about 3.3 mm, about 3.4 mm, about 3.5 mm, about 3.6 mm, about 3.7 mm, about 3.8 mm, about 3.9 mm, about 4.0 mm, about 4.1 mm, about 4.2 mm, about 4.3 mm, about 4.4 mm, about 4.5 mm, about 4.6 mm, about 4.7 mm, about 4.8 mm, about 4.9 mm, or about 5.0 mm.
  • a pump which provides for controlled addition may be used, for example a peristaltic pump, such as those produced by Watson Marlow.
  • a peristaltic pump is used on conjunction with a nozzle having a small orifice size, e.g. in the range of from 3mm to 5 mm.
  • a nozzle having a small orifice size e.g. in the range of from 3mm to 5 mm.
  • the rate of addition of the mixture containing cannabinoid and lipophilic solvent to the porous particulate solid may for example be in the range of from 50 to 2000 drops per minute, e.g. in the range of from 1000 to 2000 drops per minutes, or 500 to 1000 drops per minute, or 60 to 600 drops per minute, or 60 to 360 drops per minute, or 1250 to 1750 drops per minute, or about 1500 drops per minute.
  • the mixture containing particulate porous solid, cannabinoid and lipophilic solvent may be gently mixed, e.g. at an impeller speed in the range of from 50 to 400 rpm.
  • the components may in some embodiments be mixed, and then held without further active mixing for a further period. Such an approach may facilitate contacting of the surfaces of the porous particulate solid with the mixture containing cannabinoid and lipophilic solvent, and also allow time for droplets of the mixture containing cannabinoid and lipophilic solvent to settle within pores of the porous particulate solid.
  • the mixture containing cannabinoid and lipophilic solvent is mixed with the porous particulate solid for a period in the range of from 2 minutes to 2 hours, or from 5 minutes to 60 minutes.
  • the mixture may for example be blended following addition of the mixture containing cannabinoid and lipophilic solvent at a speed in the range of from 100 to 1000 rpm.
  • the mixture containing porous particulate solid, lipophilic solvent and cannabinoid is held for a period in the range of from 10 minutes to 24 hours, or from 30 minutes to 12 hours, prior to carrying out further processing.
  • the step of incorporating the mixture containing cannabinoid and lipophilic solvent into/onto the porous particulate solid comprises spraying the mixture containing cannabinoid and lipophilic solvent onto the porous particulate solid.
  • the porous particulate solid is continuously stirred whilst the mixture containing cannabinoid and lipophilic solvent is sprayed.
  • the resulting mixture is blended for a period following addition of the mixture containing cannabinoid and lipophilic solvent (e.g. for a period in the range of from 5 minutes to 60 minutes).
  • the mixture may for example be blended following addition of the mixture containing cannabinoid and lipophilic solvent, at a speed in the range of from 100 to 1000 rpm.
  • the resulting mixture is held for a period (e.g. in the range of from 30 minutes to 12 hours) before carrying out further processing.
  • the resulting composition may for example then be sieved through a classifying sieve, typically from 200 micron to 1000 micron, in particular 425 micron.
  • the solid pharmaceutical composition may contain additional excipients, such as an emulsifier/surfactant (e.g. polyethoxylated castor oil), a filler/binder (e.g. microcrystalline cellulose) and/or an anti-caking agent (e.g. tricalcium phosphate).
  • emulsifier/surfactant e.g. polyethoxylated castor oil
  • filler/binder e.g. microcrystalline cellulose
  • an anti-caking agent e.g. tricalcium phosphate
  • the method comprises steps of blending a first cannabinoid extract having a first cannabinoid profile, and a second cannabinoid extract having a second different cannabinoid profile, and an emulsifier/surfactant, in the presence of a lipophilic solvent, to produce a modified cannabinoid extract; and incorporating (e.g.
  • such solid self-emulsifying compositions have good cannabinoid release properties, in that they can assist in forming an emulsion and in releasing high levels of cannabinoid from the solid pharmaceutical composition when contacted with an aqueous environment, and that addition of emulsifier/surfactant facilitates the dispersion and adsorption/absorption of the lipophilic mixture of cannabinoid and lipophilic solvent to the porous particular solid.
  • an antioxidant e.g. a lipophilic antioxidant such as vitamin E (a- tocopherol)
  • the antioxidant is typically also added to the mixture containing cannabinoid and lipophilic solvent prior to incorporation.
  • those excipients may for example be blended with the cannabinoid-containing porous particulate solid following the incorporation step. Accordingly, in some embodiments, one or more excipients selected from a filler, binding agent and anti-caking agent is blended with the cannabinoid-containing porous particulate solid following the incorporation step. In some embodiments, microcrystalline cellulose and/or tricalcium phosphate is blended with the cannabinoid- containing porous particulate solid following the incorporation step.
  • excipients may if desired be incorporated in a blending step following incorporation of the modified cannabinoid extract to the porous particulate solid.
  • a lubricant and/or glidants may be added in such a blending step.
  • a lubricant is added following the incorporation step.
  • the lubricant is magnesium stearate or sodium stearyl fumarate.
  • Solid excipients added during the blending step may, for example, be sieved prior to mixing with other components of the solid pharmaceutical formulation.
  • any solid excipients may be sieved through a classifying sieve, typically from 200 micron to 1000 micron, in particular 425 micron.
  • the blending step may be carried out using any suitable equipment, for example in some embodiments a blender may be used, e.g. operated at a chopper speed in the range of from 100 rpm to 500 rpm.
  • the blending step is carried out for a sufficient period of time to ensure that the components are well mixed.
  • the components are blended for a period of time in the range of up to 1 hour, up to 30 minutes, up to 15 minutes, from 5 minutes up to 1 hour, from 5 minutes up to 30 minutes or from 5 minutes up to 15 minutes.
  • the desired cannabinoid profile has not been achieved during contacting of the lipophilic solvent/cannabinoid blend with the porous particulate solid it is possible to mix the solid pharmaceutical composition, formed as described above, with a ‘placebo’ or ‘blank’ composition.
  • This placebo or blank composition may have all of the components of the solid pharmaceutical composition apart from the cannabinoid. This effectively allows for a dilution of the solid pharmaceutical composition to provide for the desired cannabinoid profile in the end unit dosage form. Again, this can be easily and accurately achieved using the flowable powders of the present invention providing for an advantage over the manufacture of dosage forms directly from viscous cannabinoid oils or resins.
  • Dosage Forms The methods of the present disclosure involve the use of oral unit dosage forms comprising the solid pharmaceutical composition.
  • the oral dosage form may be a capsule, such as a hard gelatine capsule or a soft gelatine capsule, or a hydroxypropyl methylcellulose capsule, or a pullulan capsule.
  • the dosage form is a capsule having a shell which comprises gelatin.
  • the dosage form is a capsule which comprises hydroxypropyl methyl cellulose.
  • the oral dosage form is a tablet, such as an effervescent tablet.
  • the oral dosage form is a powder, present in a sachet. It may be an effervescent powder for example, or a powder for suspension.
  • the oral dosage form is a sub-lingual or buccal delivered form for local absorption.
  • the oral dosage form is an immediate release dosage form, such as an immediate release capsule.
  • Immediate release capsules include those containing capsule shells formed of excipients such as gelatin or hydroxypropyl methyl cellulose (HPMC).
  • the oral dosage form is a modified release dosage form, such as a modified release capsule.
  • dosage forms contain excipients that may facilitate sustained/extended release of active from the dosage form over a period of time following oral administration, and/or which may facilitate delayed release of the active from the dosage form.
  • an enteric-coated capsule may be utilised, i.e. a capsule (such as a gelatin or HPMC capsule) which is treated/coated with a material to prevent or reduce degradation in the stomach but permits release of the active further on in the gastrointestinal tract, e.g. in the small intestine.
  • the dosage form may incorporate or comprise a coating that prevents or reduces degradation of the dosage form in an acidic environment.
  • the dosage form is a unit dosage form, e.g. such as a capsule, tablet, caplet, or sachet containing a predetermined dose of cannabinoid- containing solid pharmaceutical composition.
  • the unit dosage form e.g.
  • the capsule contains lmg of CBD, or 2.5 mg of CBD, or 5 mg of CBD, or 10 mg of CBD, or 20 mg of CBD, 40 mg of CBD, 50 mg of CBD, 100 mg of CBD, or 150 mg of CBD.
  • the unit dosage form contains lmg of THC, or 2.5 mg of THC, or 5 mg of THC, or 10 mg of THC, or 20 mg of THC, or 40 mg of THC.
  • the unit dosage form contains CBD and THC, for example in a weight ratio of at least 20:1, at least 1:20, in a weight ratio in the range of from 20:1 to 1:20, about 20:1, about 19:1, about 18:1, about 17:1, about 16:1, about 15:1, about 14:1, about 13:1, about 12:1, about 11:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, about 1:11, about 1:12, about 1:13, about 1:14, about 1:15, about 1:16, about 1:17, about 1:18, about 1:19, or about 1:20.
  • the dosage form is a unit dosage form (e.g. capsule), at least 70% by weight of all cannabinoids present in the unit dosage form is CBD, and no other cannabinoid is present in the unit dosage form at more than 5% by weight.
  • the dosage form is a unit dosage form (e.g. capsule), at least 70% by weight of all cannabinoids present in the unit dosage form is THC, and no other cannabinoid is present in the unit dosage form at more than 5% by weight.
  • any suitable method for producing the oral dosage forms from the solid pharmaceutical composition may be used.
  • the solid pharmaceutical composition may be filled into capsules, e.g. using an encapsulation machine.
  • the filled capsules may then be packaged in a suitable container (e.g. in blister packs, and further in a carton).
  • a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject comprising administering to the subject a course of at least one cannabinoid; wherein the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 10 wt% throughout the course; wherein the cannabinoid is administered in an oral unit dosage form comprising a solid pharmaceutical composition which comprises the cannabinoid, a lipophilic solvent and a porous particulate solid; and whereby use of the solid pharmaceutical composition enables consistent dosing of the cannabinoid.
  • a cannabinoid for use in a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, the method comprising administering to the subject a course of at least one cannabinoid; wherein the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 10 wt% or ⁇ 10 mol% throughout the course; wherein the cannabinoid is administered in an oral dosage comprising a solid pharmaceutical composition which comprises the cannabinoid, a lipophilic solvent and a porous particulate solid; and whereby use of the solid pharmaceutical composition enables consistent dosing of the cannabinoid.
  • the disease, disorder or condition may for example be selected from the group consisting of an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, a cardiovascular disorder, cancer, and pain.
  • a cannabinoid for the manufacture of a medicament, which medicament is an oral unit dosage form comprising a solid pharmaceutical composition which comprises the cannabinoid, a lipophilic solvent and a porous particulate solid, for preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, wherein the subject is administered a course of a cannabinoid; wherein the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 10 wt% or ⁇ 10 mol% throughout the course; whereby use of the solid pharmaceutical composition enables consistent dosing of the cannabinoid; and wherein the disease, disorder or condition is selected from the group consisting of an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, a cardiovascular disorder, cancer, and pain.
  • the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 10 wt% throughout the course, and the consistent dosing is enabled by use of the solid pharmaceutical composition and oral unit dosage form described above.
  • the solid pharmaceutical composition can be produced to contain a specific concentration of the cannabinoid or cannabinoids of interest.
  • the solid pharmaceutical composition is also typically a free-flowing powder, which enables accurate amounts of the composition (and thus the cannabinoid) to be measured/formed into an oral unit dosage form. Further, as discussed above it has been found that the solid pharmaceutical composition has good stability properties such that, on storage over time, there are low levels of degradation of the cannabinoid. This means that where capsules from a single batch are administered to a subject over a prolonged period of time, the amount of cannabinoid administered in each dose is again consistent.
  • the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 10 wt% throughout the course.
  • every dose of cannabinoid administered would be within 10 weight % of 10 mg, i.e. between 9 and 11 mg. This is facilitated by the use of the solid pharmaceutical composition and its manufacture, which provides for unit dosage forms having a consistent amount of cannabinoid.
  • the amount of the cannabinoid administered in each dose of the course varies by no more than ⁇ 5 wt %, or by no more than ⁇ 2 wt%, or by no more than ⁇ 1 wt%, or by no more than ⁇ 0.5 wt%, or by ⁇ 0.25 wt%.
  • the method involves administration of a course of cannabinoid.
  • a course of therapy involves administration of at least one series of doses of one or more cannabinoids over an extended time period.
  • the course involves administration of cannabinoid at time points during a period of at least 5 days, at least 10 days, at least 15 days, at least 20 days, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, or at least 1 year.
  • the course involves administration of cannabinoid at time points during a period in the range of from 5 days to 1 year, 5 days to 6 months, 5 days to 3 months, 5 days to 2 months, 5 days to 1 month, 5 days to 20 days, 5 days to 10 days, 10 days to 1 year, 10 days to 6 months, 10 days to 3 months, 10 days to 2 months, 10 days to 1 month, 10 days to 20 days, 20 days to 1 year, 20 days to 6 months, 20 days to 3 months, 20 days to 2 months, 20 days to 1 month, 1 month to 1 year, 1 month to 6 months, 1 month to 3 months, 1 month to 2 months, 2 months to 1 year, 2 months to 6 months, 2 months to 3 months, 3 months to 1 year, 3 months to 6 months, 6 months to 1 year, about 5 days, about 10 days, about 20 days, about 1 month, about 2 months, about 3 months, about 6 months, or about 1 year.
  • the administration of the cannabinoid(s) will occur at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20,
  • the course involves administration of cannabinoid at least once per day, at least twice per day, at least 3 times per day, or at least 4 times per day, or once per day, or twice per day, or three times per day, or 4 times per day.
  • the cannabinoid is administered at least once per day over a period of at least 5 days, over a period of at least 10 days, over a period of at least 20 days, over a period of at least 1 month, over a period of at least 2 months, over a period of at least 3 months, over a period of at least 6 months, or over a period of at least 12 months.
  • the cannabinoid is administered once per day over a period in the range of from 5 days to 1 year, 5 days to 6 months, 5 days to 3 months, 5 days to 2 months, 5 days to 1 month, 5 days to 20 days, 5 days to 10 days, 10 days to 1 year, 10 days to 6 months, 10 days to 3 months, 10 days to 2 months, 10 days to 1 month, 10 days to 20 days, 20 days to 1 year, 20 days to 6 months, 20 days to 3 months, 20 days to 2 months, 20 days to 1 month, 1 month to 1 year, 1 month to 6 months, 1 month to 3 months, 1 month to 2 months, 2 months to 1 year, 2 months to 6 months, 2 months to 3 months, 3 months to 1 year, 3 months to 6 months, 6 months to 1 year, about 5 days, about 10 days, about 20 days, about 1 month, about 2 months, about 3 months, about 6 months, or about 1 year.
  • the cannabinoid is administered at least twice per day over a period of at least 5 days, over a period of at least 10 days, over a period of at least 20 days, over a period of at least 1 month, over a period of at least 2 months, over a period of at least 3 months, over a period of at least 6 months, or over a period of at least 12 months.
  • the cannabinoid is administered twice per day over a period in the range of from 5 days to 1 year, 5 days to 6 months, 5 days to 3 months, 5 days to 2 months, 5 days to 1 month, 5 days to 20 days, 5 days to 10 days, 10 days to 1 year, 10 days to 6 months, 10 days to 3 months, 10 days to 2 months, 10 days to 1 month, 10 days to 20 days, 20 days to 1 year, 20 days to 6 months, 20 days to 3 months, 20 days to 2 months, 20 days to 1 month, 1 month to 1 year, 1 month to 6 months, 1 month to 3 months, 1 month to 2 months, 2 months to 1 year, 2 months to 6 months, 2 months to 3 months, 3 months to 1 year, 3 months to 6 months, 6 months to 1 year, about 5 days, about 10 days, about 20 days, about 1 month, about 2 months, about 3 months, about 6 months, or about 1 year.
  • the cannabinoid is administered at least three times per day over a period of at least 5 days, over a period of at least 10 days, over a period of at least 20 days, over a period of at least 1 month, over a period of at least 2 months, over a period of at least 3 months, over a period of at least 6 months, or over a period of at least 12 months.
  • the cannabinoid is administered three times per day over a period in the range of from 5 days to 1 year, 5 days to 6 months, 5 days to 3 months, 5 days to 2 months, 5 days to 1 month, 5 days to 20 days, 5 days to 10 days, 10 days to 1 year, 10 days to 6 months, 10 days to 3 months, 10 days to 2 months, 10 days to 1 month, 10 days to 20 days, 20 days to 1 year, 20 days to 6 months, 20 days to 3 months, 20 days to 2 months, 20 days to 1 month, 1 month to 1 year, 1 month to 6 months, 1 month to 3 months, 1 month to 2 months, 2 months to 1 year, 2 months to 6 months, 2 months to 3 months, 3 months to 1 year, 3 months to 6 months, 6 months to 1 year, about 5 days, about 10 days, about 20 days, about 1 month, about 2 months, about 3 months, about 6 months, or about 1 year.
  • the cannabinoid is administered at least four times per day over a period of at least 5 days, over a period of at least 10 days, over a period of at least 20 days, over a period of at least 1 month, over a period of at least 2 months, over a period of at least 3 months, over a period of at least 6 months, or over a period of at least 12 months.
  • the cannabinoid is administered four times per day over a period in the range of from 5 days to 1 year, 5 days to 6 months, 5 days to 3 months, 5 days to 2 months, 5 days to 1 month, 5 days to 20 days, 5 days to 10 days, 10 days to 1 year, 10 days to 6 months, 10 days to 3 months, 10 days to 2 months, 10 days to 1 month, 10 days to 20 days, 20 days to 1 year, 20 days to 6 months, 20 days to 3 months, 20 days to 2 months, 20 days to 1 month, 1 month to 1 year, 1 month to 6 months, 1 month to 3 months, 1 month to 2 months, 2 months to 1 year, 2 months to 6 months, 2 months to 3 months, 3 months to 1 year, 3 months to 6 months, 6 months to 1 year, about 5 days, about 10 days, about 20 days, about 1 month, about 2 months, about 3 months, about 6 months, or about 1 year.
  • the course includes at least 10 doses, at least 20 doses, at least 30 doses, at least 40 doses, at least 50 doses, at least 60 doses, at least 70 doses, at least 80 doses, at least 90 doses, at least 100 doses, at least 150 doses, at least 200 doses, at least 250 doses, or at least 300 doses.
  • the course includes a number of doses in the range of from 10 to 300 doses, from 20 to 300 doses, from 30 to 300 doses, from 40 to 300 doses, from 50 to 300 doses, from 60 to 300 doses, from 70 to 300 doses, from 80 to 300 doses, from 90 to 300 doses, from 100 to 300 doses, from 150 to 300 doses, from 200 to 300 doses, from 250 to 300 doses, from 10 to 250 doses, from 20 to 250 doses, from 30 to 250 doses, from 40 to 250 doses, from 50 to 250 doses, from 60 to 250 doses, from 70 to 250 doses, from 80 to 250 doses, from 90 to 250 doses, from 100 to 250 doses, from 150 to 250 doses, from 200 to 250 doses, from 10 to 200 doses, from 20 to 200 doses, from 30 to 200 doses, from 40 to 200 doses, from 50 to 200 doses, from 60 to 200 doses, from 70 to 200 doses, from 80 to 200 doses, from 90 to 200 doses, from 100 to
  • the amount of the cannabinoid administered in each dose of the course is 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg or 100 mg, wherein the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 10 wt% throughout the course.
  • the amount of the cannabinoid administered in each dose of the course is 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg or 100 mg, wherein the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 5 wt% throughout the course.
  • the amount of the cannabinoid administered in each dose of the course is 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg or 100 mg, wherein the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 2 wt% throughout the course.
  • the amount of the cannabinoid administered in each dose of the course is 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg or 100 mg, wherein the amount of the cannabinoid administered in each dose of the course is consistent such that it varies by no more than ⁇ 1 wt% throughout the course.
  • the cannabinoid is selected from the group consisting of cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichormevarin (CBCV), cannabichromevarinic acid (CBCVA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabielsoin (CBE), cannabicyclol (CBL), cannabinodiol (CBND), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabinol (CBN), cannabinolic acid (CBNA), cannabitriol (CBT), delta-8-tetrahydrocanninol, delta-8- te
  • the cannabinoid is cannabidiol (CBD). In some embodiments, the cannabinoid is delta-9-tetrahydrocannabidiol (THC). In some embodiments, a mixture of cannabinoids is administered. In some embodiments, a mixture of cannabidiol (CBD) and delta-9-tetrahydrocannabidiol (THC) is administered.
  • the weight ratio may for example be a ratio within the range of from 1:100 to 100:1, or from 1:20 to 20:1, or from 1:10 to 10:1, or from 1:5 to 5:1, or from 1:3 to 3:1, or from 1:2 to 2:1, or about 1:1.
  • a mixture of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) is administered, and the weight ratio of CBD to THC is at least 20:1, or 20:1 or 15:1 , or 10:1, or 8:1, or 6:1, or 5:1, or 4:1, or 3:1, or 2:1, or 1:1, or 1:2, or 1:3, or 1:4, or 1:5, or 1:6, or 1:8, or 1:10, or 1:15, or 1:20 or at least 1:20.
  • the present disclosure also provides for the administration of a course of therapy where the dosage of cannabinoid is altered during the course of therapy (e.g. raised or lowered), but that within each series of doses, the amount of cannabinoid administered is consistent.
  • Some patients can experience side effects when initially administered cannabinoid therapies, but after a period of time can develop tolerance to the cannabinoid, such that the dose can be increased to provide more therapeutically effective levels.
  • the initial amount of cannabinoid dosed is too high for an individual and they experience side effects, there may be a need to step down the dosage for a period of time to reduce or eliminate the side effects, and then potentially increasing the dosage again if/once the patient develops tolerance.
  • a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject comprising administering to the subject a course of at least one cannabinoid; wherein the course comprises i) administering a first series of doses of the cannabinoid, and subsequently ii) administering a second series of doses of the cannabinoid; wherein the amount of cannabinoid administered in each dose of the first series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the first series; wherein the amount of cannabinoid administered in each dose of the second series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the further series; wherein the amount of cannabinoid administered in each dose of the first series is different from the amount of cannabinoid administered in each dose of the second series; wherein the cannabinoid is administered in an oral dosage form
  • a cannabinoid for use in a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, the method comprising administering to the subject a course of at least one cannabinoid; wherein the course comprises i) administering a first series of doses of the cannabinoid, and subsequently ii) administering a further series of doses of the cannabinoid; wherein the amount of cannabinoid administered in each dose of the first series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the first series; wherein the amount of cannabinoid administered in each dose of the further series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the further series; wherein the amount of cannabinoid administered in each dose of the first series is different from the amount of cannabinoid administered in each dose of the further series; wherein the cannabinoid is
  • the disease, disorder or condition is selected from the group consisting of an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, a cardiovascular disorder, cancer, and pain.
  • a cannabinoid for the manufacture of a medicament, which medicament is an oral unit dosage form comprising a solid pharmaceutical composition which comprises the cannabinoid, a lipophilic solvent and a porous particulate solid, for preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, wherein the subject is administered a course of a cannabinoid; wherein the course comprises i) administering a first series of doses of the cannabinoid, and subsequently ii) administering a further series of doses of the cannabinoid; wherein the amount of cannabinoid administered in each dose of the first series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the first series; wherein the amount of cannabinoid administered in each dose of the further series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the further series; wherein the amount of cann
  • the amount of cannabinoid administered in each dose of the first series is different from the amount of cannabinoid administered in each dose of the second series in wt% terms by at least ⁇ 10 %, preferably at least ⁇ 20 %, more preferably by at least ⁇ 30 % and still more preferably by at least ⁇ 40 % or by at least ⁇ 50 %.
  • Further series of doses may, within each said further series, differ from the first and second and any additional further series of doses by the same relative % amounts.
  • the amount of the cannabinoid administered in each dose of the first series of the course is consistent such that it varies by no more than ⁇ 10 wt% throughout the series.
  • the amount of the cannabinoid administered in each dose of the second series of the course is consistent such that it varies by no more than ⁇ 10 wt% throughout the series.
  • every dose of cannabinoid administered would be within 10 weight % of 5 mg, i.e. between 4.5 and 5.5 mg, and over the second 3 month period every dose of cannabinoid administered would be within 10 weight % of 10 mg, i.e. between 9 and 11 mg.
  • a) the amount of cannabinoid administered in each dose of the first series varies by no more than ⁇ 5 wt % and the amount of cannabinoid administered in each dose of the second series varies by no more than ⁇ 5 wt %; b) the amount of cannabinoid administered in each dose of the first series varies by no more than ⁇ 2 wt % and the amount of cannabinoid administered in each dose of the second series varies by no more than ⁇ 2 wt %; or c) the amount of cannabinoid administered in each dose of the first series varies by no more than ⁇ 1 wt % and the amount of cannabinoid administered in each dose of the second series varies by no more than ⁇ 1 wt %.
  • the first series of doses involves administration of cannabinoid at time points during a period of at least 2 days, at least 3 days, at least 5 days, at least 10 days, at least 15 days, at least 20 days, or at least 1 month. In some embodiments, the first series of doses involves administration of cannabinoid at time points during a period in the range of from 2 days to 1 month, 2 days to 20 days, 2 days to 10 days, 2 days to 5 days, 5 days to 1 month, 5 days to 20 days, or 5 days to 10 days.
  • the second series of doses involves administration of cannabinoid at time points during a period of at least at least 5 days, at least 10 days, at least 15 days, at least 20 days, at least 1 month, at least 2 months, at least 3 months, at least 6 months, or at least 1 year.
  • the second series of doses involves administration of cannabinoid at time points during a period in the range of from 5 days to 1 year, 5 days to 6 months, 5 days to 3 months, 5 days to 2 months, 5 days to 1 month, 5 days to 20 days, 5 days to 10 days, 10 days to 1 year, 10 days to 6 months, 10 days to 3 months, 10 days to 2 months, 10 days to 1 month, 10 days to 20 days, 20 days to 1 year, 20 days to 6 months, 20 days to 3 months, 20 days to 2 months, 20 days to 1 month, 1 month to 1 year, 1 month to 6 months, 1 month to 3 months, 1 month to 2 months, 2 months to 1 year, 2 months to 6 months, 2 months to 3 months, 3 months to 1 year, 3 months to 6 months, 6 months to 1 year, about 5 days, about 10 days, about 20 days, about 1 month, about 2 months, about 3 months, about 6 months, or about 1 year.
  • the first series of doses involves administration of cannabinoid at least once per day, at least twice per day, at least 3 times per day, or at least 4 times per day, or once per day, or twice per day, or three times per day, or 4 times per day.
  • the second series of doses involves administration of cannabinoid at least once per day, at least twice per day, at least 3 times per day, or at least 4 times per day, or once per day, or twice per day, or three times per day, or 4 times per day.
  • the first series of doses involves administration of cannabinoid at least once per day over a period of at least 5 days, at least once per day over a period of at least 10 days, at least once per day over a period of at least 20 days, or at least once per day over a period of at least one month.
  • the second series of doses involves administration of cannabinoid at least once per day over a period of at least 5 days, at least once per day over a period of at least 10 days, at least once per day over a period of at least 20 days, or at least once per day over a period of at least one month.
  • the first series of doses involves administration of cannabinoid at least twice per day over a period of at least 5 days, at least once per day over a period of at least 10 days, at least once per day over a period of at least 20 days, or at least once per day over a period of at least one month.
  • the second series of doses involves administration of cannabinoid at least twice per day over a period of at least 5 days, at least once per day over a period of at least 10 days, at least once per day over a period of at least 20 days, or at least once per day over a period of at least one month.
  • the first series of doses includes at least 10 doses, at least 20 doses, at least 30 doses, at least 40 doses, at least 50 doses, at least 60 doses, at least 70 doses, at least 80 doses, at least 90 doses, at least 100 doses, at least 150 doses, at least 200 doses, at least 250 doses, or at least 300 doses.
  • the first series of doses includes a number of doses in the range of from 10 to 300 doses, from 20 to 300 doses, from 30 to 300 doses, from 40 to 300 doses, from 50 to 300 doses, from 60 to 300 doses, from 70 to 300 doses, from 80 to 300 doses, from 90 to 300 doses, from 100 to 300 doses, from 150 to 300 doses, from 200 to 300 doses, from 250 to 300 doses.
  • the second series of doses includes at least 10 doses, at least 20 doses, at least 30 doses, at least 40 doses, at least 50 doses, at least 60 doses, at least 70 doses, at least 80 doses, at least 90 doses, at least 100 doses, at least 150 doses, at least 200 doses, at least 250 doses, or at least 300 doses.
  • the second series of doses includes a number of doses in the range of from 10 to 300 doses, from 20 to 300 doses, from 30 to 300 doses, from 40 to 300 doses, from 50 to 300 doses, from 60 to 300 doses, from 70 to 300 doses, from 80 to 300 doses, from 90 to 300 doses, from 100 to 300 doses, from 150 to 300 doses, from 200 to 300 doses, from 250 to 300 doses.
  • the amount of cannabinoid administered in each dose of the first series is 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, or 50 mg, wherein the amount of cannabinoid administered in each dose of the first series is consistent such that it varies by no more than ⁇ 10 wt% throughout the first series.
  • the amount of cannabinoid administered in each dose of the second series is 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, or 150 mg, wherein the amount of cannabinoid administered in each dose of the second series is consistent such that it varies by no more than ⁇ 10 wt% throughout the second series.
  • the amount of cannabinoid administered in each dose of the second series is higher than the amount of cannabinoid administered in each dose of the first series. This may be the case for example where a patient has been issued an initial low dose and, after a period of time where no significant side effects have been observed, the dosage is then increased.
  • the amount of cannabinoid administered in each dose of the second series is lower than the amount of cannabinoid administered in each dose of the first series. This may be the case for example where a subject experiences side effects following administration of the initial dose, which then needs to be lowered.
  • the methods also encompass administration of further series of doses of cannabinoid, e.g. third series, fourth series and so on.
  • a patient’s dosage may be increased stepwise over time, e.g. from 2mg, up to 4mg, up to lOmg and so forth.
  • the course comprises iii) administering a third series of doses of cannabinoid; wherein the amount of cannabinoid administered in each dose of the third series is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the third series; wherein the amount of cannabinoid administered in each dose of the third series is different from the amount of cannabinoid administered in each dose of the first series and the second series.
  • the amount of cannabinoid administered in each dose of the third series is higher than the amount of cannabinoid administered in each dose of the second series.
  • the present disclosure also provides for the administration of a course of therapy where different cannabinoids are administered (e.g. at different times of the day), but within each series of doses (e.g. within a first series of doses of a first cannabinoid, and within a second series of doses of a second cannabinoid), the amount of cannabinoid administered is consistent.
  • a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject comprising administering to the subject a course of at least two cannabinoids; wherein the course comprises i) administering a series of doses of a first cannabinoid, and ii) administering a series of doses of a second different cannabinoid; wherein the amount of the first cannabinoid administered in each dose is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the series of doses; wherein the amount of the second cannabinoid administered in each dose is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the series of doses; wherein the first cannabinoid is administered in an oral dosage comprising a solid pharmaceutical composition which comprises the cannabinoid, a lipophilic solvent and a porous particulate solid; wherein the second cannabinoid
  • first cannabinoid and a second cannabinoid for use in a method of preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, the method comprising administering to the subject a course of at least two cannabinoids; wherein the course comprises i) administering a series of doses of a first cannabinoid, and ii) administering a series of doses of a second different cannabinoid; wherein the amount of first cannabinoid administered in each dose is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the series of doses; wherein the amount of second cannabinoid administered in each dose is consistent such that it varies by no more than ⁇ 10wt% or ⁇ 10 mol% throughout the series of doses; wherein the first cannabinoid is administered in an oral dosage comprising a solid pharmaceutical composition which comprises the cannabinoid, a lipophilic solvent and
  • the disease, disorder or condition is selected from the group consisting of an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, a cardiovascular disorder, cancer, and pain.
  • a first cannabinoid for the manufacture of a medicament, which medicament is an oral unit dosage form comprising a solid pharmaceutical composition which comprises the first cannabinoid, a lipophilic solvent and a porous particulate solid
  • a second cannabinoid for the manufacture of a medicament, which medicament is an oral unit dosage form comprising a solid pharmaceutical composition which comprises the second cannabinoid, a lipophilic solvent and a porous particulate solid, for preventing, treating and/or lessening the severity of a disease, disorder or condition in a subject, wherein the subject is administered a course of the first and second cannabinoids; wherein the course comprises i) administering a series of doses of a first cannabinoid, and ii) administering a series of doses of a second different cannabinoid; wherein the amount of the first cannabinoid administered in each dose is consistent such that it varies by no more than ⁇ 10wt% or ⁇
  • the amount of the cannabinoid administered in each dose of the first series of the course is consistent such that it varies by no more than ⁇ 10 wt% throughout the series.
  • the amount of the cannabinoid administered in each dose of the second series of the course is consistent such that it varies by no more than ⁇ 10 wt% throughout the series.
  • every dose of CBD administered would be within 10 weight % of 5 mg CBD, i.e. between 4.5 and 5.5 mg
  • over the second series of THC doses every dose of THC administered would be within 10 weight % of 5 mg THC, i.e. between 4.5 and 5.5 mg.
  • a) the amount of cannabinoid administered in each dose of the first series varies by no more than ⁇ 5 wt % and the amount of cannabinoid administered in each dose of the second series varies by no more than ⁇ 5 wt %; b) the amount of cannabinoid administered in each dose of the first series varies by no more than ⁇ 2 wt % and the amount of cannabinoid administered in each dose of the second series varies by no more than ⁇ 2 wt %; or c) the amount of cannabinoid administered in each dose of the first series varies by no more than ⁇ 1 wt % and the amount of cannabinoid administered in each dose of the second series varies by no more than ⁇ 1 wt %.
  • the cannabinoids are selected from the group consisting of cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichormevarin (CBCV), cannabichromevarinic acid (CBCVA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabielsoin (CBE), cannabicyclol (CBL), cannabinodiol (CBND), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabinol (CBN), cannabinolic acid (CBNA), cannabitriol (CBT), delta-8- tetrahydrocanninol, delta-8-tetrahydrocannabinolic acid, delta-9-
  • cannabinoid therapies at different points in time, e.g. dosing of CBD during the daytime (e.g. in the morning and/or in the afternoon) and dosing of THC in the evening, prior to sleep.
  • the first cannabinoid is CBD and the second cannabinoid is THC.
  • the first series of doses involves administration of cannabinoid at time points during a period of at least at least 5 days, at least 10 days, at least 15 days, at least 20 days, at least 1 month, at least 2 months, at least 3 months, at least 6 months, or at least 1 year.
  • the second series of doses involves administration of cannabinoid at time points during a period in the range of from 5 days to 1 year, 5 days to 6 months, 5 days to 3 months, 5 days to 2 months, 5 days to 1 month, 5 days to 20 days, 5 days to 10 days, 10 days to 1 year, 10 days to 6 months, 10 days to 3 months, 10 days to 2 months, 10 days to 1 month, 10 days to 20 days, 20 days to 1 year, 20 days to 6 months, 20 days to 3 months, 20 days to 2 months, 20 days to 1 month, 1 month to 1 year, 1 month to 6 months, 1 month to 3 months, 1 month to 2 months, 2 months to 1 year, 2 months to 6 months, 2 months to 3 months, 3 months to 1 year, 3 months to 6 months, 6 months to 1 year, about 5 days, about 10 days, about 20 days, about 1 month, about 2 months, about 3 months, about 6 months, or about 1 year.
  • the second series of doses involves administration of cannabinoid at time points during a period of at least at least 5 days, at least 10 days, at least 15 days, at least 20 days, at least 1 month, at least 2 months, at least 3 months, at least 6 months, or at least 1 year.
  • the second series of doses involves administration of cannabinoid at time points during a period in the range of from 5 days to 1 year, 5 days to 6 months, 5 days to 3 months, 5 days to 2 months, 5 days to 1 month, 5 days to 20 days, 5 days to 10 days, 10 days to 1 year, 10 days to 6 months, 10 days to 3 months, 10 days to 2 months, 10 days to 1 month, 10 days to 20 days, 20 days to 1 year, 20 days to 6 months, 20 days to 3 months, 20 days to 2 months, 20 days to 1 month, 1 month to 1 year, 1 month to 6 months, 1 month to 3 months, 1 month to 2 months, 2 months to 1 year, 2 months to 6 months, 2 months to 3 months, 3 months to 1 year, 3 months to 6 months, 6 months to 1 year, about 5 days, about 10 days, about 20 days, about 1 month, about 2 months, about 3 months, about 6 months, or about 1 year.
  • the first series of doses involves administration of cannabinoid at least once per day, at least twice per day, at least 3 times per day, or at least 4 times per day, or once per day, or twice per day, or three times per day, or 4 times per day.
  • the second series of doses involves administration of cannabinoid at least once per day, at least twice per day, at least 3 times per day, or at least 4 times per day, or once per day, or twice per day, or three times per day, or 4 times per day.
  • the first series of doses involves administration of the first cannabinoid once per day in the morning, and administration of the second cannabinoid once per day in the evening. In some embodiments, the first series of doses involves administration of the first cannabinoid twice per day in the morning, and administration of the second cannabinoid once per day in the evening.
  • the first cannabinoid is administered once per day in the morning and the second cannabinoid is administered once per day in the evening, over a period of at least 5 days, at least 10 days, at least 20 days or at least one month.
  • the first cannabinoid is administered twice per day in the morning and in the afternoon and the second cannabinoid is administered once per day in the evening, over a period of at least 5 days, at least 10 days, at least 20 days or at least one month.
  • the first series of doses includes at least 10 doses, at least 20 doses, at least 30 doses, at least 40 doses, at least 50 doses, at least 60 doses, at least 70 doses, at least 80 doses, at least 90 doses, at least 100 doses, at least 150 doses, at least 200 doses, at least 250 doses, or at least 300 doses.
  • the first series of doses includes a number of doses in the range of from 10 to 300 doses, from 20 to 300 doses, from 30 to 300 doses, from 40 to 300 doses, from 50 to 300 doses, from 60 to 300 doses, from 70 to 300 doses, from 80 to 300 doses, from 90 to 300 doses, from 100 to 300 doses, from 150 to 300 doses, from 200 to 300 doses, from 250 to 300 doses.
  • the second series of doses includes at least 10 doses, at least 20 doses, at least 30 doses, at least 40 doses, at least 50 doses, at least 60 doses, at least 70 doses, at least 80 doses, at least 90 doses, at least 100 doses, at least 150 doses, at least 200 doses, at least 250 doses, or at least 300 doses.
  • the second series of doses includes a number of doses in the range of from 10 to 300 doses, from 20 to 300 doses, from 30 to 300 doses, from 40 to 300 doses, from 50 to 300 doses, from 60 to 300 doses, from 70 to 300 doses, from 80 to 300 doses, from 90 to 300 doses, from 100 to 300 doses, from 150 to 300 doses, from 200 to 300 doses, from 250 to 300 doses.
  • the amount of cannabinoid administered in each dose of the first series is 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, or 50 mg, wherein the amount of cannabinoid administered in each dose of the first series is consistent such that it varies by no more than ⁇ 10 wt% throughout the first series.
  • the amount of cannabinoid administered in each dose of the second series is 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, or 150 mg, wherein the amount of cannabinoid administered in each dose of the second series is consistent such that it varies by no more than ⁇ 10 wt% throughout the second series.
  • capsules containing solid pharmaceutical compositions comprising a cannabinoid, lipophilic solvent and porous particulate solid exhibit good storage stability properties, with low levels of degradation of cannabinoid.
  • the solid pharmaceutical composition or oral unit dosage form comprises a cannabinoid
  • the amount of the cannabinoid in the solid pharmaceutical formulation, unit dosage form or kit decreases by no more than 10 wt% or 10 mol%.
  • the cannabinoid is CBD. In some embodiments, the cannabinoid is THC. In some embodiments, the cannabinoid is a mixture of CBD and THC.
  • the amount of cannabinoid in the solid pharmaceutical formulation, unit dosage form or kit decreases by no more than 7.5 wt% or 7.5 mol% following storage for a period of 3 months at 25°C.
  • the amount of cannabinoid in the solid pharmaceutical formulation, unit dosage form or kit decreases by no more than 5 wt% or 5 mol% following storage for a period of 3 months at 25°C. In some embodiments, the amount of cannabinoid in the solid pharmaceutical formulation, unit dosage form or kit decreases by no more than 3 wt% or 3 mol% following storage for a period of 3 months at 25°C.
  • Adherence is an issue which can be associated with some cannabinoid- containing formulations.
  • Cannabinoids can adhere to some materials, e.g. some plastics. When in solution, through fluid dynamics, some active molecules will come into contact with the container.
  • the present solid compositions which contain the cannabinoid incorporated into/onto the porous particulate solid, are understood to protect and/or house the cannabinoid active, providing limited opportunity for contacting of cannabinoid to materials and/or adherence to those materials.
  • dosage forms comprising solid pharmaceutical compositions which contain cannabinoid, lipophilic solvent and porous particulate solid release cannabinoid effectively under aqueous conditions.
  • composition or dosage form as defined herein, wherein following contacting of the composition or unit dosage form with an aqueous environment, at least 50% by weight of cannabinoid is released within 1 hour.
  • At least 60%, at least 70%, at least 80%, at least 90%, or at least 95% by weight of cannabinoid is released within 1 hour.
  • released refers to cannabinoid being present in the aqueous environment, rather than in and/or on or in some manner physically and intimately associated with the porous particulate solid.
  • the amount of cannabinoid released at a given time may, for example, be measured by determining the concentration of cannabinoid in the aqueous environment.
  • the solid pharmaceutical composition or oral unit dosage form comprises CBD, and wherein following contacting of the solid pharmaceutical composition or oral unit dosage form with an aqueous environment, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 95% by weight of the CBD is released within 1 hour. In some embodiments, at least 50% by weight of the CBD is released within 45 minutes, within 30 minutes, within 20 minutes or within 15 minutes.
  • At least 70% by weight of all cannabinoids present in the solid pharmaceutical composition or dosage form is CBD, and no other cannabinoid is present in the solid pharmaceutical composition or dosage form at more than 5% by weight, and wherein following contacting of the solid pharmaceutical composition or dosage form with an aqueous environment, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 95% by weight of the CBD is released within 1 hour. In some embodiments, at least 50% by weight of the CBD is released within 45 minutes, within 30 minutes, within 20 minutes or within 15 minutes.
  • the solid pharmaceutical composition or oral unit dosage form comprises THC, and wherein following contacting of the solid pharmaceutical composition or oral unit dosage form with an aqueous environment, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 95% be weight of the THC is released within 1 hour. In some embodiments, at least 50% by weight of the THC is released within 45 minutes, within 30 minutes, within 20 minutes or within 15 minutes.
  • At least 70% by weight of all cannabinoids present in the solid pharmaceutical composition or dosage form is THC, and no other cannabinoid is present in the solid pharmaceutical composition or dosage form at more than 5% by weight, and wherein following contacting of the solid pharmaceutical composition or dosage form with an aqueous environment, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 95% by weight of the THC is released within 1 hour. In some embodiments, at least 50% by weight of the THC is released within 45 minutes, within 30 minutes, within 20 minutes or within 15 minutes.
  • Tests for determining release profiles of active ingredient from pharmaceutical compositions and dosage forms (e.g. capsules) in an aqueous environment are known in the art. For example, dissolution tests for tablets and capsules is described in the British Pharmacopeia (see Appendix XII B. Dissolution). In some embodiments, dissolution testing is carried out in accordance with the British Pharmacopeia Dissolution Test for Tablets and Capsules. In some embodiments, dissolution testing is carried out in accordance with the British Pharmacopeia Dissolution Test for Tablets and Capsules, using Apparatus 2 (Paddle apparatus).
  • the aqueous environment is 0.5% aqueous hexadecyltrimethylammonium bromide comprising a phosphate buffer at pH 6.8, and wherein the contacting is carried out at 37°C ⁇ 0.5°C with stirring at 100 rpm.
  • compositions and dosage forms of the present disclosure provide predictable and high oral bio availability of cannabinoid following oral administration, and provide a good pharmacokinetic profile of the active.
  • the compositions and dosage forms may achieve one or more of the following compared with administration of a comparable dose of cannabinoid by a conventional oral dosage formulation such as an oil: a) higher plasma C max of cannabinoid; b) increased AUC; and c) improved Tmax. This may in turn enable dosing of lower amounts of cannabinoid compared with existing conventional oral formulations.
  • compositions and dosage forms are also expected to provide reduced variability in pharmacokinetic parameters of the active over a course of therapy involving repeated administrations, given that the compositions and dosage forms have precisely controlled amounts of cannabinoid active, and have good storage stability properties.
  • Example 1 Analysis of Cannabinoid Content in Cannabinoid Extracts
  • cannabinoid extracts containing certain amounts of cannabinoid agent(s).
  • Cannabinoid content in cannabinoid extracts was analysed by validated methodology that included HPLC analysis.
  • the assays showed that batch A predominantly contained THC, and batch B predominantly contained CBD.
  • Solid pharmaceutical compositions including the amounts of active ingredients and excipients as described in the tables below were prepared according to the following procedures.
  • MCT medium chain triglyceride
  • cannabinoid may be present in a resin at about 80% by weight of the resin, with the remainder being MCT.
  • MCT MCT-coefficient of a solid pharmaceutical composition containing e.g. 10 mg cannabinoid
  • 12.25 mg of an 80% strength resin was used, and an additional amount of 47.75 mg MCT was also used to make up the combined total of 60 mg. This is reported in the table below as 10 mg API and 50mg MCT.
  • emulsifier/surfactant polyoxyl castor oil: Kolliphor ® EL
  • the required amount of colloidal anhydrous silica was transferred to the blender and the pre-defined amount of lipophilic solution of the cannabinoid(s) was added dropwise at a rate of approximately 60-360 drops per minute to the silica which was under continuous stirring at an impeller speed of between 150 to 400 rpm.
  • the mixture was blended for about 10 minutes at an impeller speed of 200-1000 rpm. Any lumps were removed by passing the solid self-emulsifying composition through a 425 micron aperture sieve.
  • each of the dry powder excipients was sieved through a 425 micron aperture sieve.
  • the pre-sieved microcrystalline cellulose and tricalcium phosphate were transferred to the blender and spread over the solid self- emulsifying composition bed.
  • the impeller speed was then set to between 200 and 500 rpm and the mixture was blended for approximately 15-30 minutes until a homogeneous blend was achieved.
  • the final master blend was then discharged into a suitable intermediate bulk container for transport and/or storage.
  • the final master blend may be processed in an encapsulation machine to fill hard shell gelatin capsules (i.e. oral unit dosage forms).
  • hard shell gelatin capsules i.e. oral unit dosage forms.
  • the filled hard shell gelatin capsules may then be packaged in blister packs and further packaged in approved size “shelf-ready” cartons.
  • Cannabinoid content was analysed in the solid pharmaceutical compositions contained in capsules (oral unit dosage forms) as prepared in Example 2.
  • Solid pharmaceutical compositions were analysed for cannabinoid content by validated HPLC assays.
  • a capsule content i.e. solid pharmaceutical composition comprising oral unit dosage forms
  • HPLC grade methanol was added.
  • the resulting mixture was submitted to ultrasonication for at least 30 minutes, before being centrifuged at 16400 rpm for 5 minutes.
  • the supernatant was transferred into a HPLC vial.
  • the resulting soluble components were analysed for their cannabinoid content by validated HPLC-UV analysis.
  • Results of assays for a representative batch of solid oral dosage forms comprising the solid pharmaceutical composition 4 of Example 2 (containing lOmg THC and lOmg CBD) are shown in Table 3.
  • Solid pharmaceutical compositions were also analysed for common pathogens using validated microbiological assays. Results of assays for a representative batch of solid oral dosage forms comprising the solid pharmaceutical composition 4 of Example 2 (containing lOmg THC and lOmg CBD) are shown in Table 4.
  • Solid pharmaceutical compositions were also analysed for homogeneity in loading between two different loading levels and different batches (4 of potency level 1 for solid pharmaceutical composition 7 described above and 3 of potency level 2 for solid pharmaceutical composition 9 as described above).
  • the relative standard deviation (RSD) is extremely low for all batches indicating a very low degree of variation between batches, as is shown in Table 5.
  • capsule weights capsule (with their inherent variability) plus powder) for 2230 capsules in a batch were tested and provided a minimum weight of 323 mg, a maximum of 374.1, a mean of 356.2, a standard deviation of 8.3 and an RSD of 2.3% again indicating a high degree of homogeneity and consistency between capsules within a batch.
  • Dissolution media was prepared by dissolving 34g potassium dihydrogen phosphate and 4.5g of sodium hydroxide in 5L of water. pH was adjusted to pH 6.8 ⁇ 0.05 with phosphoric acid or sodium hydroxide solution. 25g of CTAB was added and the solution mixed thoroughly. The media was filtered under vacuum through a Millipore 0.45 pm HVLP filter prior to use.
  • Test parameters were as follows:
  • Dissolution test parameters 10 mL sample was withdrawn from each vessel at the timepoints indicated in the table below, filtered through a 0.45 pm nylon filter, analysed by HPLC. The volume withdrawn was replaced with 10 mL dissolution media from the further vessel. The test was repeated with a further batch of 6 capsules (12 capsules in total). Results are shown in Table 8 and indicate the % cannabinoid released.
  • Table 8 In vitro dissolution profile of cannabinoid agents from oral dosage forms containing lOmg THC and lOmg CBD The results show that the cannabinoid agents are released from capsule oral unit dosage forms at a high rate, with approximately 50% dissolved after 15 minutes.
  • the objective of this study is to deliver a desired dose of a cannabinoid consistently to human patients throughout a course of treatment.
  • the absence/presence of adverse effects may be evaluated by clinical observations.
  • the results can be analysed on an ongoing basis to determine whether the dose needs to be adjusted and whether an alternative cannabinoid agent should be administered.
  • the main potential side effects include dry mouth; drowsiness, dizziness, headache; reduced attention span, reactivity, judgment, and/or problem-solving ability; psycho motor impairment; feeling high (relaxed, euphoric, distorted perception).
  • Example 6.1 Oral delivery of a consistent amount of a cannabinoid agent over a course of treatment.
  • Consistent unchanged dosage of a cannabinoid agent is administered to human subjects via oral unit dosage forms as described in Example 2 over a course of treatment.
  • Human subjects presenting with a condition for which cannabinoid therapy is indicated are administered capsules containing solid pharmaceutical composition 1 of Example 2 above, so as to provide a dose of 2.5 mg of cannabidiol (CBD) per capsule.
  • CBD cannabidiol
  • the subjects are administered a single capsule once per day for 3 days. If no adverse reactions are observed, the dose is maintained for a period of one month. Due to the properties of the solid pharmaceutical composition and its preparation, a consistent dose of 2.5 mg of CBD will be administered each day with a dosage variation of less than 5% each day throughout the course.
  • Example 6.2 Oral delivery of a controlled increasing amount of a cannabinoid agent over a course of treatment.
  • a stepwise increasing controlled dosage regimen of cannabinoid therapy is administered to human subjects via oral unit dosage forms as described in Example 2 over a course of treatment.
  • the aim is to gradually increase the dosage administered up to therapeutically effective levels whilst minimising the incidence and severity of adverse reactions/side effects, by administration of controlled dosages of cannabinoid.
  • Human subjects presenting with a condition for which cannabinoid therapy is indicated are administered capsules containing solid pharmaceutical composition 1 of Example 2 above, so as to provide a dose of 2.5 mg of (cannabidiol) CBD per capsule (“first dose”).
  • first dose 2.5 mg of (cannabidiol) CBD per capsule
  • second dose 5 mg of CBD per day
  • a second series of doses is administered. The delivery of the second dose is achieved by administering two of the same capsules containing 2.5 mg of CBD, so as to provide a dose of 5 mg of CBD.
  • the subject is administered CBD according to this 5mg per day regimen for a period of 3 days.
  • a third series of doses is administered, with the dose is doubled again to lOmg of CBD per day, achieved by administering four 2.5mg CBD-containing capsules once per day.
  • the subject is maintained on the lOmg CBD per day dosage regimen for a period of one month.
  • the dosage of cannabinoid is halved and therapy continued for a period of 6 days. If a further adverse reaction is experienced or if the previous adverse reaction continues, the course of therapy is discontinued. If no further adverse reaction is observed and the previous adverse reaction is discontinued during that period, the dosage of cannabinoid is doubled whilst continuing to monitor the subject. Due to the properties of the solid pharmaceutical composition and its preparation, consistent dosages of 2.5mg of CBD, 5 mg of CBD and lOmg CBD will be administered with a dosage variation of less than 5% each day throughout each series of doses of the course.
  • Example 6.3 Oral delivery of a controlled dose of two different cannabinoid agents
  • a dosage regimen which constitutes administration of a controlled amount of CBD during the daytime and administration of a controlled amount of THC in the evening (e.g. prior to sleep) is beneficial.
  • Human subjects are administered a first series of doses, of capsules containing a solid pharmaceutical composition 1 as per Example 2 above, so as to provide a dose of 2.5 mg of cannabidiol (CBD) per capsule.
  • the subjects are administered a single capsule twice per day, in the morning, and in the early afternoon.
  • the subjects are also administered a second series of doses, of capsules containing a solid pharmaceutical composition 1 as per Example 2 above, so as to provide a dose of 2.5 mg of THC per capsule.
  • the subjects are administered a single capsule once per day, in the evening prior to sleep.
  • Example 6.4 Oral delivery of controlled micro-dose amounts of a cannabinoid agents over a course of treatment. For some patients and conditions, a dosage regimen which constitutes administration of a micro-dose amount of a cannabinoid is beneficial.
  • Human subjects are administered capsules containing a solid pharmaceutical composition which is analogous to solid pharmaceutical composition no. 1 as per Example 2 above, with the exception that the dose per capsule is 0.25mg CBD.
  • the subjects are administered a single capsule once per day over a period of 3 days. If no adverse reactions are observed, the dosage is maintained for a period of one month.

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Abstract

La présente invention concerne des méthodes d'administration de formes posologiques orales solides comprenant des cannabinoïdes, et comprenant en outre des solvants lipophiles et des solides particulaires poreux, les formes posologiques comprenant une dose consistante d'un ou de plusieurs cannabinoïdes.
PCT/AU2021/050072 2020-01-31 2021-02-01 Méthode de thérapie cannabinoïde WO2021151168A1 (fr)

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WO2015065179A1 (fr) * 2013-10-29 2015-05-07 Echo Pharmaceuticals B.V. Pastille comprimée comprenant du cannabidiol, son procédé de fabrication, et utilisation d'une telle pastille pour le traitement oral de troubles de psychose ou d'anxiété
WO2015065180A1 (fr) * 2013-10-29 2015-05-07 Echo Pharmaceuticals B.V. Comprimé contenant du delta 9-tétrahydrocannabinol, procédé de fabrication associé et utilisation de ce comprimé pour un traitement oral
WO2016014454A1 (fr) * 2014-07-21 2016-01-28 Pharmaceutical Productions, Inc. Composition de forme galénique solide pour une administration par voie buccale ou sublinguale de cannabinoïdes
WO2018058235A1 (fr) * 2016-09-27 2018-04-05 CannTab Therapeutics Limited Formulations de cannabinoïdes à libération prolongée
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WO2011063164A2 (fr) * 2009-11-18 2011-05-26 Steady Sleep Rx Co., Inc. Médicaments de cannabinoïde à libération prolongée
WO2015065179A1 (fr) * 2013-10-29 2015-05-07 Echo Pharmaceuticals B.V. Pastille comprimée comprenant du cannabidiol, son procédé de fabrication, et utilisation d'une telle pastille pour le traitement oral de troubles de psychose ou d'anxiété
WO2015065180A1 (fr) * 2013-10-29 2015-05-07 Echo Pharmaceuticals B.V. Comprimé contenant du delta 9-tétrahydrocannabinol, procédé de fabrication associé et utilisation de ce comprimé pour un traitement oral
WO2016014454A1 (fr) * 2014-07-21 2016-01-28 Pharmaceutical Productions, Inc. Composition de forme galénique solide pour une administration par voie buccale ou sublinguale de cannabinoïdes
WO2018058235A1 (fr) * 2016-09-27 2018-04-05 CannTab Therapeutics Limited Formulations de cannabinoïdes à libération prolongée
WO2019135225A1 (fr) * 2018-01-03 2019-07-11 Icdpharma Ltd. Compositions de cannabinoïdes auto-emulsifiantes solides
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