Composition, method of treatment, and method of preparing thereof

Abstract

The present disclosure may broadly provide composition for applying to food comprising a cannabidiol (CBD) having a purity greater than 90% and a tetrahydrocannabinol (THC) having a purity greater than 90% at a ratio of CBD:THC of about 5:1 to about 80:1, for a combined cannabinoid concentration of up to 15 g / L, a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier system, greater than 60% w / v water, and the composition having a viscosity of 500 to 5,000 cP at 21°C, a pH of between 4-7 and being in the form of an oil-in-water nanoemulsion.

Description

COMPOSITION, METHOD OF TREATMENT, AND METHOD OF PREPARING THEREOFFIELD OF THE INVENTION

[0001] The present disclosure is directed to compositions comprising one or more cannabinoids. More particularly, the present disclosure relates to a composition for applying to food, methods of treating a subject such as companion animals using such a composition, and methods of preparing such a composition.BACKGROUND

[0002] Cannabinoids are a class of compounds derived from cannabis plants that bind to cannabinoid receptors found in animals. More than 100 cannabinoids have been isolated from cannabis plants including cannabidiol (CBD) and tetrahydrocannabinol (THC).

[0003] CBD and THC bind to cannabinoid receptors CB1 and CB2 found in the brain and other organs and have been linked to health benefits including pain management in conditions such as nerve damage, cancer, multiple sclerosis, and rheumatoid arthritis.

[0004] Preferably, the cannabinoids are administered in amounts that achieve a therapeutic effect while minimising possible side effects such as hallucination, fatigue, slow reaction times, shortterm memory loss, weight change, nausea or diarrhea.

[0005] Medical cannabinoids are typically administered orally via capsules or liquid suspension, or cannabinoid infused food products. Capsules or tablets allow more accurate dosage of the cannabinoids but may be more difficult to administer to animals such as companion animals. Cannabinoid infused food products may be easier to administer to animals but may be more difficult to dose accurately given the dose is dependent on the amount of food consumed.

[0006] The lipophilic nature of cannabinoids may negatively affect bioavailability of the cannabinoids when administered via the oral route using conventional drug delivery strategies.

[0007] Cannabinoids may be obtained from cannabis plants as crude extracts or purified isolates. Crude extracts may be full spectrum containing not only CBD and THC but also other cannabinoids and compounds such as terpenes and flavanoids. Crude extracts may not be suitable in certain applications (e.g. particularly pharmaceuticals) as they may contain unknown compounds. CBD and THC isolates are purified forms of CBD and THC separated from the other compounds founds in the plants. THC isolate is generally the purest form of THC available, typically appearing as an insoluble resinous solid.

[0008] Cannabinoids may be administered as an emulsion, such as an oil-in-water emulsion. However, due to differences in the physicochemical properties of CBD and THC isolates, stable emulsions of CBD and THC may be hard to achieve. Unstable CBD and THC emulsions may phase separate over time adversely affecting efficacy of the cannabinoids.

[0009] It is desired to address or ameliorate one or more disadvantages or limitations associated with the prior art, or to at least provide the public with a useful alternative.SUMMARY OF THE INVENTION

[0010] According to one aspect, the present disclosure may provide a composition comprising one or more cannabinoids, comprising at least THC and CBD, and a stabiliser system configured to maintain the composition in a stable oil-in-water nanoemulsion.

[0011] According to one aspect, the present disclosure may provide a composition comprising a cannabidiol (CBD) having a purity greater than 90% and a tetrahydrocannabinol (THC) having a purity greater than 90% at a ratio of CBD:THC of about 5:1 to about 80:1 , for a combined cannabinoid concentration of up to 15 g / L, up to 4% of weight of a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier system comprising a first emulsifier with an HLB 1 to 8 and a second emulsifier with an HLB of greater than 14 that in combination provides a combination HLB of between 8.5 to 16.0, and a droplet size of less than 500d.nm, a thickener, the thickener being a polysaccharide thickener, greater than 60% w / v water, and the composition having a viscosity of 500 to 5,000 cP at 21 °C, a pH of 4 to 7, and being in the form of an oil-in-water nanoemulsion.

[0012] According to one aspect, the present disclosure may provide a composition for application to food comprising a cannabidiol (CBD) having a purity greater than 90% and a tetrahydrocannabinol (THC) having a purity greater than 90% at a ratio of CBD:THC of about 5:1 to about 80:1 , for a combined cannabinoid concentration of up to 15 g / L, up to 4% of weight of a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier system comprising a first emulsifier with an HLB 1 to 8 and a second emulsifier with an HLB of greater than 14 that in combination provides a combination HLB of between 13.0 and 16.0, and a droplet size of less than 500d.nm, a microbial preservative system comprising two or more preservatives, each preservative from a different chemical class, an antioxidant, a thickener, the thickener being a polysaccharide thickener, greater than 60% w / v water, and the composition having a viscosity of 500 to 5,000 cP at 21 °C, a pH of 4 to 7, and being in the form of an oil-in-water nanoemulsion.

[0013] According to one aspect, the present disclosure may provide a veterinary composition for application to food comprisinga cannabidiol (CBD) having a purity greater than 90% and a tetrahydrocannabinol (THC) having a purity greater than 90% at a ratio of CBD:THC of about 5:1 to about 80:1 , for a combined cannabinoid concentration of up to 15 g / L, up to 4% of weight of a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier system comprising a first emulsifier with an HLB 1 to 8 and a second emulsifier with an HLB of greater than 14 that in combination provides a combination HLB of between 8.5 and 16.0, and a droplet size of less than 500d.nm, a microbial preservative system comprising two or more preservatives, each preservative from a different chemical class, an antioxidant, a thickener, the thickener being a polysaccharide thickener, greater than 60% w / v water, and the composition having a viscosity of 500 to 5,000 cP at 21 °C, a pH of 4 to 7, and being in the form of an oil-in-water nanoemulsion.

[0014] According to a further aspect, the present disclosure may provide a composition comprising one or more cannabinoids, a pharmaceutically compatible surfactant, a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier, greater than 60% w / v water, and the composition having a viscosity of 500 to 5,000 cP at 21 °C and being in the form of an oil- in-water nanoemulsion.

[0015] According to a further aspect, the present disclosure may broadly provide a composition for applying to food comprising a cannabidiol (CBD) and a tetrahydrocannabinol (THC) at a ratio of CBD:THC of about 5:1 to about 80:1 , a pharmaceutically compatible surfactant, a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier, greater than 60% w / v water, and the composition having a viscosity of 500 to 5,000 cP at 21 °C and being in the form of an oil- in-water nanoemulsion.

[0016] According to a further aspect, the present disclosure may provide a method of preparing a composition, the method comprising• mixing a pharmaceutically compatible surfactant, a pharmaceutically compatible carrier oil, and a pharmaceutically compatible emulsifier to produce a pre-emulsion mixture,• heating the pre-emulsion mixture to a first temperature to produce a heated preemulsion,• cooling the heated pre-emulsion to a second temperature to produce a cooled preemulsion,• adding one or more cannabinoids to the cooled pre-emulsion,• adding the cooled pre-emulsion to water having a temperature of the second temperature to produce an emulsion, and• stirring the emulsion for a predetermined time and at a predetermined speed to produce an oil-in-water nanoemulsion comprising one or more cannabinoids.

[0017] According to a further aspect, the present disclosure may provide a method of preparing a composition, the method comprising:• heating a pharmaceutically compatible surfactant to a first temperature,• mixing the heated pharmaceutically compatible surfactant with a pharmaceutically compatible carrier oil and a pharmaceutically compatible emulsifier to produce a pre- emulsion concentrate,• cooling the pre-emulsion concentrate to a second temperature to produce a cooled pre-emulsion concentrate,• mixing the cooled pre-emulsion concentrate with CBD and THC,• adding the cooled pre-emulsion to water having a temperature of the second temperature to produce an emulsion, and• stirring the emulsion for a predetermined time and at a predetermined speed, to produce an oil-in-water nanoemulsion comprising one or more cannabinoids.

[0018] According to a further aspect, the present disclosure may provide a method for treating or ameliorating a condition in a subject comprising• providing a composition having a viscosity of 500 to 5,000 cP at 21 °C and being in the form of an oil-in-water nanoemulsion, the composition comprising one or more cannabinoids, a pharmaceutically compatible surfactant, a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier, greater than 60% w / v water, and• administering the composition to the subject to be treated to provide 0.25 to 1 .0 mg of CBD and 0.0125 to 0.05 mg of THC per kg of subject weight.

[0019] According to an a further other aspect, the present disclosure may provide a method for treating or ameliorating symptoms of arthritis in a subject comprising• providing a composition having a viscosity of 500 to 5,000 cP at 21 °C and being in the form of an oil-in-water nanoemulsion, the composition comprisinga cannabidiol (CBD) and a tetrahydrocannabinol (THC) at a CBD:THC ratio of about 5:1 to about 80:1 , a pharmaceutically compatible surfactant, a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier, greater than 60% w / v water, and• applying the composition on to the food of the subject to be treated to provide 0.25 to 1 .0 mg of CBD and 0.0125 to 0.05 mg of THC per kg of subject weight.

[0020] The following features may apply to any of the above aspects.

[0021] The ratio of CBD:THC may be about 10:1 to about 40:1.

[0022] The ratio of CBD:THC may be about 15:1 to about 30:1.

[0023] The ratio of CBD:THC may be about 20:1 .

[0024] The composition may comprise about 0.25 to about 1 .0 % w / v of CBD and about 0.0125 to about 0.05 % w / v of THC.

[0025] The composition may comprise about 0.5 % w / v of CBD and about 0.025 % w / v of THC.

[0026] The cannabidiol and the tetrahydrocannabinol may be purified isolates.

[0027] The pharmaceutically compatible surfactant may comprise one or more nonionic surfactants.

[0028] The pharmaceutically compatible surfactant may comprise polyethylene glycol, and / or polyoxyethylene sorbitan fatty acid esters.

[0029] The pharmaceutically compatible surfactant may comprise polyethylene glycol (PEG) distearate, polyoxyethylene (40) stearate (POE40), and / or polyoxyethylene (80) sorbitan monooleate (polysorbate 80).

[0030] The pharmaceutically compatible carrier oil may comprise any suitable triglycerides.

[0031] The triglyceride may be selected from short, medium, or long chain triglyceride.

[0032] The pharmaceutically compatible carrier oil may comprise medium chain tryglycerides(MOT).

[0033] The medium chain triglycerides (MOT) may be derived from plants including but not limited to canola oil, olive oil, sunflower oil, coconut oil (including fractionated coconut oil), hemp oil, palm oils, any combinations thereof, and / or other oils suitable for consumption.

[0034] The MCT may be derived from animals including but not limited to fish oil and milk fat or combinations thereof.

[0035] The pharmaceutically compatible emulsifier may comprise soy lecithin.

[0036] The composition may have a viscosity of about 750 to about 1 ,500 cP at 21 °C .

[0037] The composition may have a viscosity of about 1 ,000 to about 4,000 cP at 21 °C .

[0038] The composition may have a viscosity of about 2,000 to about 3,000 cP at 21 °C .

[0039] The composition may have an average droplet size of about 10 nm to about 250 nm.

[0040] The composition may comprise greater than 70% w / v water.

[0041] The composition may comprise greater than 80% w / v water.

[0042] The composition may comprise greater than 90% w / v water.

[0043] The composition may further comprise one or more of an antimicrobial, an antioxidant, a mineral, a vitamin, a viscosity modifier, and a preservative.

[0044] The composition may comprise:0.25 to 1.0 % w / v CBD,0.0125 to 0.05 % w / v THC,0.5 to 3.0 % w / v PEG distrearate,0.5 to 1 .5 % w / v medium chain triglycerides,0.5 to 1 .5 % w / v soy lecithin,0.01 to 0.02 % w / v vitamin E,0.0025 to 0.01 % w / v antimicrobial,0.0025 to 0.01 % w / v antioxidant, and to 97 % w / v water.

[0045] The composition may be a composition for application to food.

[0046] The pharmaceutically compatible surfactant may comprise polyethylene glycol, polyoxyethylene (40) stearate (POE40), and / or polyoxyethylene (80) sorbitan monooleate (polysorbate 80).

[0047] The pharmaceutically compatible carrier oil comprises any suitable triglycerides.

[0048] The triglyceride may be selected from short, medium, or long chain triglyceride.

[0049] The pharmaceutically compatible carrier oil may comprise medium chain triglycerides(MCT).

[0050] The pharmaceutically compatible emulsifier may comprise soy lecithin.

[0051] The first temperature may be about 45 °C to about 55 °C.

[0052] The second temperature may be about 35 °C to about 45 °C.

[0053] The pre-emulsion mixture and the aqueous phase may be prepared in separate vessels.

[0054] The method may be carried out using a high shear mixer.

[0055] The pre-emulsion concentrate may be added while stirring at the predetermined speed using a high shear mixer emulsifier workhead.

[0056] The predetermined time may be about 20 minutes to about 40 minutes.

[0057] The predetermined speed may be about 5,000 rpm to about 10,000 rpm.

[0058] The method may further comprise adding one or more of an antimicrobial, an antioxidant, a mineral, a vitamin, a viscosity modifier, and a preservative.

[0059] In one embodiment the Z-average droplet size of the composition emulsion is less than 500d.nm.

[0060] In one embodiment the Z-average droplet size of the composition emulsion is less than 500, 450, 400, 350, 300, 250, 200, 150d.nm.

[0061] The composition may be cooled and deaerated for a predetermined time, and one or more of the antimicrobial, the antioxidant, the viscosity modifier, and the preservative may be added after cooling.

[0062] The viscosity modifier may be added while mixing with a high shear mixer chopping stirrer blade at about 1 ,000 rpm.

[0063] The thickener may be selected from guar, carrageenan or xanthan gum, or a combination thereof.

[0064] The thickener is xanthan gum.

[0065] The antimicrobial, the antioxidant, and the preservative may be added while mixing at 500 rpm.

[0066] The subject may be a companion animal.

[0067] The companion animal may be a canine animal.

[0068] The food may comprise dry or wet foods.

[0069] The symptoms of arthritis may be caused by rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), fibromyalgia, or gout arthritis.

[0070] The target dose for CBD is about 0.5 mg per kg and the target does for THC is 0.025 mg per kg.

[0071] The composition is applied to food for consumption by the subject daily, twice daily, or thrice daily.

[0072] The term "comprising" as used in this specification means "consisting at least in part of. When interpreting statements in this specification which include that term, the features, prefaced by that term in each statement, all need to be present but other features can also be present. Related terms such as "comprise" and "comprised" are to be interpreted in the same manner.

[0073] It is intended that reference to a range of numbers disclosed herein (for example, 1 to 10) also incorporates reference to all rational numbers within that range (for example, 1 , 1 .1 , 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and 10) and also any range of rational numbers within that range (for example, 2 to 8, 1.5 to 5.5 and 3.1 to 4.7).

[0074] This invention may also be said broadly to consist in the parts, elements and features referred to or indicated in the specification of the application, individually or collectively, and any or all combinations of any two or more of said parts, elements or features, and where specific integers are mentioned herein which have known equivalents in the art to which this invention relates, such known equivalents are deemed to be incorporated herein as if individually set forth.BRIEF DESCRIPTION OF THE FIGURES

[0075] The invention will now be described by way of example only and with reference to the drawings in which:

[0076] Figure 1 is a flow diagram of one embodiment of the process for producing a composition according the present disclosure.

[0077] Figure 2 is a flow diagram of another embodiment of the process for producing a composition according the present disclosure.

[0078] Figure 3 is a graph showing the Clinical Sum Score (CSS) of subjects treated by a composition according to an embodiment of the present disclosure and a commercial product.DETAILED DESCRIPTION

[0079] Described is a composition comprising cannabinoids comprising high purity cannabidiol (CBD) active ingredient and isolated (high purity) tetrahydrocannabinol (THC) active ingredient within an oil in water emulsion.

[0080] In relation to the CBD active ingredient, by “high purity” this is intended to mean that the presence of the component CBD in the CBD active ingredient is greater than 90% by weight.Preferably the presence of the component CBD in the CBD active ingredient is greater than 95% by weight. Alternatively the presence of the component CBD is in the CBD active ingredient greater than 99% by weight. That is, for the high purity CBD, the presence of components that are not the CBD component (i.e. non-CBD components) in the CBD active ingredient is less than 10% by weight. Preferably the presence of non-CBD components in the CBD active ingredient are less than 5% by weight. Alternatively the presence of non-CBD components in the CBD active ingredient are less than 1% by weight.

[0081] In relation to THC active ingredient, by “high purity” this is intended to mean that the presence of the component THC in the THC active ingredient is greater than 90% by weight. Preferably the presence of the component THC in the THC active ingredient is greater than 95% by weight. Alternatively the presence of the component THC is in the THC active ingredient greater than 99% by weight. That is, for the high purity THC, the presence of components that are not the THC component (i.e. non-THC components) in the THC active ingredient is less than 10% by weight.Preferably the presence of non-THC components in the THC active ingredient are less than 5% by weight. Alternatively the presence of non-THC components in the THC active ingredient are less than 1% by weight.

[0082] The composition comprises more CBD per weight than THC. The ratio of CBD to THC in the composition may be about 5:1 to about 80:1 . The composition may comprise a combined cannabinoid concentration of up to 15 g / L.

[0083] The composition comprises a stabiliser system that maintains the composition in a stable oil-in-water nanoemulsion and thus comprises a carrier oil and water. The composition may further comprise a surfactant comprising two or more pharmaceutically compatible surfactants.

[0084] The composition may also comprise a microbial preservative system, and an antioxidant.

[0085] The composition can be accurately dosed and conveniently applied to food, for example, food for companion animals. To enable this the composition may comprise a thickener.

[0086] Without wishing to be limited by theory, the use of a stable nanoemulsions comprising CBD and THC may enhance the bioavailability and loading of the cannabinoids to enable a more consistent plasma drug profile such that the treatment may be more effective.

[0087] A shelf stable nanoemulsion, in which minimal phase separation occurs, may enable the composition or composition to be stored in a form that is ready-for-use without the need for additional mixing or handling before administration or application to food. This may improve the convenience and usability of the composition.

[0088] The application of the composition to food improves the delivery of the cannabinoids to a subject by providing a nanoemulsion having a viscosity that adheres to food such that an appropriate and repeatable dosage is delivered to the subject via consumption of the food onto which the composition is applied.

[0089] Also described is a method of preparing the composition or composition to achieve a stable nanoemulsion.

[0090] As stated above, the composition comprises (CBD) and tetrahydrocannabinol (THC) as active pharmaceutical ingredients (APIs).

[0091] Cannabinoids are a class of compounds that bind to and modulate cannabinoid receptors that are common in animals. Cannabinoids can be broadly classified into three main groups: endocannabinoids that are made endogenously within the body, phytocannabinoids that naturally occur in cannabis plants, and synthetic cannabinoids.

[0092] Phytocannabinoids are primarily isolated from plants in the genus Cannabis including Cannabis sativa. More than 100 cannabinoids have been isolated from C. sativa broadly classified into distinct types including cannabidiol (CBD), delta-8 tetrahydrocannabinol (A8THC) , delta-9 tetrahydrocannabinol (A9THC), cannabigerol (CBG), cannabichromenes (CBC), cannabicyclol (CBL), cannabielsoins (CBE), cannabinol (CBN), cannabinodiol (CBND), and cannabitriol (CBT).

[0093] The cannabinoids may comprise any cannabinoids isolated from Cannabis plant including but not limited to C. sativa, C. Indica, and C. ruderalis.

[0094] Cannabidiol (CBD) has been increasingly investigated and has shown promise as a therapeutic agent for various conditions. For example, CBD has shown therapeutic properties including anti-inflammatory, analgesic, anticonvulsant, muscle relaxant, anxiolytic, antipsychotic, antioxidant and neuroprotective properties.

[0095] CBD is highly lipophilic and poorly soluble in water with a water solubility of 12.6 mg / L. The highly lipophilic nature of CBD means that CBD is typically administered in an oil or alcohol based formulation. An issue with such formulations is that this may limit the bioavailability of CBD. Blood plasma is 90% water and thus providing active agents in an oil formulation may inhibit the distribution of the active agent in the body.

[0096] Tetrahydrocannabinol (THC) is the primary psychoactive cannabinoid compound and has been found to have antiemetic properties and used to treat chemotherapy-induced nausea andvomiting and also stimulate appetite in certain medical conditions such as anorexia. THC has also been shown to alleviate fibromyalgia and chronic neuropathic pain.

[0097] THC is highly lipid soluble and practically insoluble in water with a water solubility of 2.8 mg / L.

[0098] The one or more cannabinoids may be cannabidiol (CBD) and / or tetrahydrocannabinol (THC). The THC may be delta-8 or delta-9 THC.

[0099] It is generally recognised that cannabinoids bind to the cannabinoid receptors CB1 and CB2 to mediate effects of the cannabinoids. It is understood that CB1 receptors are expressed primarily in the central and peripheral nervous system and mediates the psychoactive properties of THC. CB2 receptors are expressed mostly in the peripheral immune system and in the central nervous system.

[0100] In embodiments comprising both CBD and THC, the combination may enhance therapeutic efficiency of the composition via synergistic interactions. For example, the CBD and THC may interact synergistically to enhance bioavailability.

[0101] Purified THC isolates are typically in solid form (crystals) and may be very difficult to emulsify. While it is possible to obtain a temporary emulsion of CBD and THC by supplying sufficient energy during the mixing process, it is difficult to obtain a stable CBD and THC emulsion in the presence of water.

[0102] As discussed above, the cannabinoids may be provided in the form as purified isolates. Purified CBD and / or isolates mainly contain CBD and / or THC without other compounds found in the crude cannabis extracts such as terpenes, flavonoids or other minor cannabinoids.

[0103] The CBD to THC ratio may be selected based on one or more factors including but not limited to disease type, disease severity, disease progression, and animal type.

[0104] For example, compositions comprising high CBD to THC ratio have been used for treatment of depression and epilepsy, high THC to CBD ratio have been used to treat nausea, while compositions comprising equal CBD to THC ratio have been used to treat pain.

[0105] The composition may comprise a CBD to THC ratio of about 1 :1 , 2:1 , 3:1 , 4:1 , 5:1 , 6:1 , 7:1 , 8:1 , 9:1 , 10:1 12:1 , 14:1 , 16:1 , 18:1 , 20:1 , 22:1 , 24:1 , 26:1 , 28:1 , 30:1 , 32:1 , 34:1 , 36:1 , 40:1 , 42:1 , 44:1 , 46:1 , 48:1 , 50:1 , 55:1 , 60:1 , 65:1 , 70:1 , 75:1 , 80:1 , 85:1 , 90:1 , 95:1 , or 100:1 , and useful ranges may be selected between any of these ratios. For example, the composition may comprise a CBD to THC ratio of about 2:1 to about 1 :2, about 3:1 to about 1 :3, about 4:1 to about 1 ;4, about 5:1 to about 1 :5, about 6:1 to about 1 :6, about 7:1 to about 1 :7, about 8:1 to about 1 :8, about 9:1 to about 1 :9, about 10:1 to about 1 :10, about 12:1 to about 1 :12, about 14:1 to about 1 :14, about 16:1 to about 1 :16, about 18:1 to about 1 :18, about 20:1 to about 1 :20, about 22:1 to about 1 .22, about 24:1 toabout 1 :24, about 26:1 to about 26:1 , about 28:1 to about 1 :28, about 30:1 to about 1 :30, about 32:1 to about 1 :32, about 34:1 to about 1 :34, about 36:1 to about 1 :36, about 40:1 to about 1 :40, about 42:1 to about 1 :42, about 44:1 to about 1 :44, about 46:1 to about 1 :46, about 48:1 to about 1 :48, about 50:1 to about 1 :50, about 55:1 to about 1 :55, about 60:1 to about 1 :60, about 65:1 to about 1 :65, about 70:1 to about 1 :70, about 75:1 to about 1 :75, about 80:1 to about 1 :80, about 85:1 to about 1 :85, about 90:1 to about 1 :90, about 95:1 to about 1 :95, about 100:1 to about 1 :100.

[0106] The composition may comprise about 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0, 1 .1 , 1 .2, 1 .3, 1 .4, 1 .5, 1 .6, 1 .7, 1 .8, 1 .9, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, or 10.0 % by weight volume (w / v) of CBD, and useful ranges may be selected between any of these values. For example, the composition may comprise about 0.1 to about 10.0, about 0.15 to about 8.0, about 0.2 to about 6.0, about 0.25 to about 5.0, about 0.3 to about 4.0, about 0.35 to about 3.0, about 0.4 to about 2.0, about 0.45 to about 1 .5, about 0.5 to about 1 .0, about 0.55 to about 0.8, to about 0.6 to about 0.7, about 0.5 to about 2.0 % by weight volume (w / v) of CBD.

[0107] The composition may comprise about 0.01 , 0.011 , 0.012, 0.013, 0.014, 0.015, 0.016, 0.017, 0.018, 0.019, 0.02, 0.021 , 0.022, 0.023, 0.024, 0.025, 0.026, 0.027, 0.028, 0.029, 0.030, 0.035, 0.04, 0.045, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1 , 0.5, 1 .0, 1 .5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5 or 5.0 % by weight volume (w / v) of THC, and useful ranges may be selected between any of these values. For example, the composition may comprise about 0.01 to about 5.0, about 0.015 to about 4.5, about 0.02 to about 4.0, about 0.02 to about 3.0, about 0.02 to about 2.0, about 0.02 to about 1 .0 about 0.025 to about 3.5, about 0.025 to about 2.5, about 0.025 to about 1 .5, about 0.03 to about 3.0, about 0.035 to about 2.5, about 0.04 to about 2.0, about 0.045 to about 1 .5, about 0.05 to about 1 .0, about 0.05 to about 0.08, or about 0.05 to about 0.06 by weight volume (w / v) of THC.

[0108] The composition may comprise a combined cannabinoid concentration of less than 5, 6, 7, 8, 9, 10, 11 , 125, 13, 14 or 15 g / L, and useful ranges may be selected between any of these values. For example, the composition may comprise about 5 to about 15about 5 to about 12about 5 to about 10about 6 to about 15about 6 to about 14about 6 to about 11 about 7 to about 15about 7 to about 13about 7 to about 9about 8 to about 15about 8 to about 14a bout 8 to about 12 g / L combined cannabinoid concentration.

[0109] The composition may comprise other phytocannabinoids including but not limited to cannabigerol (CBG), cannabichromenes (CBC), cannabicyclol (CBL), cannabielsoins (CBE), cannabinol (CBN), cannabinodiol (CBND), and cannabitriol (CBT).

[0110] The composition may comprise about 0.01 , 0.011 , 0.012, 0.013, 0.014, 0.015, 0.016, 0.017, 0.018, 0.019, 0.02, 0.021 , 0.022, 0.023, 0.024, 0.025, 0.026, 0.027, 0.028, 0.029, 0.030, 0.035, 0.04, 0.045, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1 , 0.5, 1 .0, 1 .5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5 or 5.0 % by weight volume (w / v) of one or more of CBG, CBC, CBL, CBE, CBN, CBND, and CBT, and useful ranges may be selected between any of these values. For example, the composition may comprise about 0.01 to about 5.0, about 0.015 to about 4.5, about 0.02 to about 4.0, about 0.02 to about 3.0,about 0.02 to about 2.0, about 0.02 to about 1 .0 about 0.025 to about 3.5, about 0.025 to about 2.5, about 0.025 to about 1 .5, about 0.03 to about 3.0, about 0.035 to about 2.5, about 0.04 to about 2.0, about 0.045 to about 1 .5, about 0.05 to about 1 .0, about 0.05 to about 0.08, or about 0.05 to about 0.06 by weight volume (w / v) of one or more of CBG, CBC, CBL, CBE, CBN, CBND, and CBT.

[0111] Typically, nanoemulsions are dispersions of two or more immiscible liquids in which nanosized dispersions are stabilised by one or more surfactants and other excipients. A stable nanoemulsion will resist phase separation overtime. Conversely, a non-stable nanoemulsion may experience agglomeration and subsequent phase separation over time resulting in demulsification that adversely affects the efficacy of the composition.

[0112] Emulsions may be broadly separated into oil-in-water (o / w) or water-in-oil (w / o). In oil- in-water emulsions, water forms a continuous phase wherein the oil forms the dispersed phase. A composition according to the present disclosure may be an oil-in-water emulsion in which the cannabinoids are in the dispersed phase.

[0113] The stabiliser system may comprise one or more pharmaceutically compatible excipients including but not limited to carrier oils, emulsifiers, and water that, in combination, is configured to maintain the composition as a stable emulsion.

[0114] A stable emulsion may be broadly defined as an emulsion which resists changes in its physicochemical properties overtime.

[0115] A stable emulsion may have a high (zeta) potential. Zeta potential is the electric potential in the interfacial double layer of a dispersed particle compared to a point in the continuous phase away from the interface.

[0116] In some embodiments, the composition may have of about + / - 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, or 40 mV, and useful ranges may be selected between any of these values. For example, the composition may have a zeta potential of about + / - 20 to about 40, about 22 to about 38, about 24 to about 36, about 26 to about 34, about 26 to about 32, about 28 to about 30, about 25 to about 35.

[0117] Stable emulsions maintain the particle or droplet size under stress conditions such as temperature changes or shocks. That is, a stable emulsion may maintain the droplet size within an effective range even when subject to temperature changes over time. Put differently, a stable emulsion more effectively resist changes to the droplet size over time under stress conditions.

[0118] The emulsion may maintain a proportion of droplets within a Z-average droplet size for a predetermined time at decreased or elevated temperatures. In one embodiment the Z-average droplet size of the composition emulsion is less than 500, 450, 400, 350, 300, 250, 200, 150d.nm.

[0119] The Z-average droplet size is defined as being measure using dynamic light scattering at 25°C.

[0120] The Z-average droplet size may be less than 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490 or 500 nm, and the droplet size range may be selected between any of these values. For example, the average droplet size may be about 100 to about 500, about 100 to about 250, about 100 to about 100, about 20 to about 500, about 150 to about 450, about 150 to about 250, about 150 to about 100, about 200 to about 500, about 300 to about 100, about 400 to about 500, about 150 to about 400, about 150 to about 300, about 200 to about 400, about 200 to about 300, about 300 to about 400, about 100 to about 200, about 100 to about 300, about 100 to about 400, about 120 to about 250 nm.

[0121] The proportion of droplets may be about 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, or 99% of the droplets in the emulsion, and useful ranges may be selected between any of these values. For example, the proportion of about 70 to about 99, about 72 to about 97, about 74 to about 95, about 76 to about 93, about 78 to about 91 , about 80 to about 89, about 80 to about 99, about 80 to about 95, about 82 to about 87, about 84 to about 85% of the droplets.

[0122] The predetermined time (in which the proportion of droplets are maintained at a droplet size range or average droplet size) may be about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 30, 36, 42, 48, 54, 60 months, and useful ranges may be selected between any of these values. For example, the predetermined time may be about 1 to about 12, about 1 to about 24, about 1 to about 36, about 1 to about 48, about 1 to about 60, about 6 to about 12, about 6 to about 24, about 6 to about 36, about 6 to about 48, about 6 to about 60, about 12 to about 24, about 12 to about 36, about 12 to about 48, about 12 to about 60, about 24 to about 36, about 24 about 48, about 24 to about 60, or about 36 to 60 months.

[0123] The composition may remain as a stable emulsion for 1 or more year. For example, the composition may remain as an emulsion for 2 or more, 3 or more, 4 or more, or 5 or more years.

[0124] The elevated temperature may be about 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, or 60°C, and useful ranges may be selected between any of these values. For example, the elevated temperature may be about 30 to about 40, about 30 to about 50, about 30 to about 60, about 35 to about to 40, about 35 to about 50, about 35 to about 60, about 40 to about 45, about 40 to about 50, about 40 to about 55, about 40 to about 55, about 40 to about 60°C.

[0125] The decreased temperature may be about -20, -19, -18, -17, -16, -16, -15, -14, -13, -12, -11 , -10, -9, -8, -7, -6, -5, -4, -3, -2, -1 , 0, 1 , 2 ,3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, or 20 °C, and useful ranges may be selected between any of these values. For example, thedecreased temperature may be about -20 to about 20, about -20 to about 15, about -20 to about 10, about -20 to about 5, about -20 to about 0, about -20 to about -10, about -10 to about 20, about -10 to about 15, about -10 to about 10, about -10 to about 5, about -10 to about 0, about -10 to about -5 °C.

[0126] Emulsifiers can be included in the continuous phase, the dispersed phase, or both phases of a nanoemulsion. Emulsifier molecules typically comprise both hydrophilic and hydrophobic regions, and can thus adsorb at oil-water interfaces, reducing interfacial tension and forming a protective layer around droplets of the dispersed phase within a nanoemulsion.

[0127] The addition of one or more carrier oils may help to improve solubility of the cannabinoid compounds and / or facilitate homogeneous dispersion of the cannabinoid compound into the hydrophilic component or water-soluble matrix formed by water and at least one water-soluble agent.

[0128] The emulsifier may comprise any suitable pharmaceutically compatible surfactants. The surfactant may be nonionic, anionic, cationic, Zwitterionic (amphoteric).

[0129] The pharmaceutically compatible surfactants may comprise one or more of polyethylene glycol (PEG), polysorbate, polyvinyl alcohol (PVA), and poloxamers.

[0130] Nonionic surfactants may include but are not limited to polyoxyethylene fatty acid derivatives of the sorbitan esters, polyoxyethylene fatty alcohol ethers, sorbitan fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene polyoxypropylene block copolymers (poloxamers), polyethylene glycol 400 monostearate, lanolin alcohols, ethoxylated lanolin, monostearate ester of polyethylene glycol, and glucosides.

[0131] Anionic surfactants may include but are not limited to sulfates, sulfonates, and carboxylates (with counter ions such as ammonium, sodium, or potassium cations). For example, anionic surfactants may include lauryl / laureth sulfates, and alkyl sulfates, alkyl ether sulfates, alphaolefin sulfonates. Suitable anionic surfactants may include sodium alkyl sulfate, ammonium lauryl sulfate, sodium laureth sulfate, sodium lauryl sarcosinate, sodium myreth sulfate, sodium pareth sulfate, sodium stearte, sodium lauryl sulfate, a olefin sulfonate, and ammonium laureth sulfate.

[0132] Cationic surfactants may include but are not limited to quaternary ammonium compounds, cetyltrimethyllammonium bromide, and lauryldimethylbenzylammonium chloride.

[0133] Zwitterionic surfcatants may include but are not limited to cocamidopropyl betaine, cocamidopropyl hydroxysultaine, dipalmitoylphosphatidylcholine, hydroxysultaine, and sodium lauroamphoacetate.

[0134] The pharmaceutically compatible surfactant may comprise one or more of polyethylene glycol di-stearate, polyoxyethylene sorbitan monostearate (polysorbate 60), polyoxyethylene sorbitan tristearate (polysorbate 65), polyoxyethylene sorbitan monooleate (polysorbate 80), polyoxyethylenesorbitan trioleate (polysorbate 85), polyoxyethylene-(15)-stearic acid, polyoxyethylene-(20)-stearyl alcohol, polyoxyethylene-(23)-lauryl alcohol, polyoxyethylene (40) stearate, PEG-40 hydrogenated castor oil, PEG-35 castor oil, and Solutol HS-15.

[0135] The composition may comprise about 1 .0, 1 .1 , 1 .2, 1 .3, 1 .4, 1 .5, 1 .6, 1 .7, 1 .8, 1 .9, 2.0, 2.1 , 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1 , 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, or 4.0 % by weight volume (w / v) of the pharmaceutically compatible surfactant, and useful ranges may be selected between any of these values. For example, the composition may comprise about 1 .0 to about 2.0, about 1 .0 to about 3.0, about 1.0 to about 4.0, about 2.0 to about 2.25, about 2.0 to about 2.5, about 2.0 to about 2.75, about 2.0 to about 3.0, about 2.0 to about 3.25, about 2.0 to about 3.5, about 2.0 to about 4.0, about 2.25 to about 2.5, about 2.25 to about 2.75, about 2.25 to about 3.0, about 2.25 to about 3.25, about 2.25 to about 3.5, about 2.25 to about 3.75, about 2.25 to about 4.0, about 2.5 to about 2.75, about 2.5 to about 3.0, about 2.5 to about 3.25, about 2.5 to about 3.5, about 2.5 to about 3.75, about 2.5 to about 4.0, about 2.75 to about 3.0, about 2.75 to about 3.25, about 2.75 to about 3.5, about 2.75 to about 3.75, about 2.75 to about 4.0, about 3.0 to about 3.25, about 3.0 to about 3.5, about 3.0 to about 3.75, about 3.0 to about 4.0, about 3.25 to about 3.5, about 3.25 to about 3.75, about 3.25 to about 4.0, about 3.5 to about 3.75, or about 3.5 to about 4.0 % w / v of the pharmaceutically compatible surfactant.

[0136] The carrier oil for use in the composition may comprise any suitable pharmaceutically compatible carrier oil. For example, the carrier oil may be derived from natural sources including from animal, plant or petrochemical. The carrier oil may be derived from or extracted from a natural oil via a physical or chemical process.

[0137] The carrier oil may comprise triglycerides. Triglycerides are typically classified as short, medium or long chain triglycerides. In particular, the carrier oil for use in the current composition may comprise medium chain triglycerides (MOT) - that is, a triglyceride with six to 12 carbon atoms. The MOT may comprise one or more of caproic acid (C6H12O2), caprylic acid (C8H16O2), capric acid (C10H20O2), and lauric acid (C12H24O2).

[0138] There are various sources of MCTs. For example, the MOT may be, or derive from, coconut oil or palm kernel oil. The MOT may be, or derived from, dairy sources such as bovine, ovine, or caprine milk.

[0139] The carrier oil may comprise about 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, or 100% by weight MOT, and useful ranges may be selected between any of these values. For example, the carrier oil may comprise about 25 to about 35, about 25 to about 45, about 25 to about 55, about 25 to about 65, about 25 to about 75, about 25 to about 85, about 25 to about 95, about 25 to about 100, about 35 to about 45, about 35 to about 55, about 35 to about 65, about 35 to about 75, about 35 to about 85, about 35 to about 95, about 35 to about 100, about 45 to about 55, about 45 to about 65, about 45 to about 75, about 45 to about 85, about 45 to about 95, about 45 to about 100, about 55 to about 65, about 55 to about 75, about 55 to about 85, about 55 to about 95, about 55 toabout 100, about 65 to about 75, about 65 to about 85, about 65 to about 95, about 65 to about 100, about 75 to about 85, about 75 to about 95, about 75 to about 100, about 85 to about 95, about 85 to about 99, about 85 to about 100, about 90 to about 95, about 90 to about 99, about 90 to about 100, about 95 to about 99, about 95 to about 100% MCT.

[0140] The carrier oil may comprise one or more of a fatty acid ester, saturated fatty acid, omega-3 fatty acid, omega-6 fatty acid or omega 9 fatty acid, or a combination thereof.

[0141] The fatty acid ester may include but are not limited to compounds with a single fatty acid ester moiety or multiple fatty acid ester moieties. For example the fatty acid ester may comprise ethyl oleate, ethyl linoleate, or a triglyceride.

[0142] Saturated fatty acids may include but are not limited to, caproic acid, caprylic acid, capric acid, lauric acid, valeric acid, myristic acid, palmitic acid, stearic acid, arachidic acid.

[0143] Omega-3 fatty acids may include but are not limited to, hexadecatrienoic acid, alphalinolenic acid, stearidonic acid, ecosatrienoic acid, eicosapentaenoic acid, heneicosapentanoic acid, docosapentanoic acid, docosahexanoic acid, tetracosapentaenoic acid, tetracosahexanenoic acid.

[0144] Omega-6 fatty acids may include but are not limited to, linoleic acid, gamma-linolenic acid, eicosadienoic acid, dihomo-gamma-linolenic acid, arachidonic acid, docosadienoic acid, adrenic acid, docosapentaenoic acid, tetracosatetraenoic acid, tetracosapentaenoic acid.

[0145] Omega-9 fatty acids may include but are not limited to, oleic acid, eicosenoic acid, mead acid, erucic acid, nervonic acid.

[0146] Plant based oils may include but are not limited to lemon oil, sunflower oil, soybean oil, canola oil, olive oil, corn oil, peanut oil, groundnut oil, rice bran oil, coconut oil, cottonseed oil, flax seed oil, palm oil, palm kernel oil, safflower oil, soybean oil, sesame oil, amaranth oil, linseed oil, argan oil, grapeseed oil, cranberry seed oil, hazelnut oil, hemp oil, jojoba oil, macadamia oil, mustard oil, neem oil, orange oil, rapeseed oil, avocado oil, almond oil, sweet almond oil, cashew oil, castor oil, vegetable oil, walnut oil, wheatgerm oil, kukui nut oil, tamuna oil, aloe vera oil, apricot kernel oil, borage oil, camellia oil, cocoa butter oil and rosehip see oil.

[0147] Animal based oils may include but are not limited any oils derived from animal products including fish oils.

[0148] The composition may comprise about 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0, 1 .1 , 1 .2, 1 .3, 1 .4, 1 .5, 1 .6, 1 .7, 1 .8, 1 .9, 2.0, 2.1 , 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1 , 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9 or 4.0% by weight volume (w / v) of pharmaceutically compatible carrier oil, and useful ranges may be selected between any of these values. For example, the composition may comprise about 0.1 to about 0.2, about 0.1 to about 0.4, about 0.1 to about 0.6, about 0.1 to about 0.8, about 0.1 to about 1 .0, about 0.1 to about 1.1 , about 0.1 to about 1 .2, about 0.1 to about 1 .3,about 0.1 to about 1 .4, about 0.1 to about 1 .5, about 0.1 to about 1 .6, about 0.1 to about 1 .7, about 0.1 to about 1 .8, about 0.1 to about 2.0, about 0.1 to about 3.0, about 0.5 to about 1 .0, about 0.5 to about 1 .5, about 0.5 to about 2.0, about 0.5 to about 2.5, about 0.5 to about 3.0, about 0.5 to about3.5, about 0.5 to about 4.0, about 1.0 to about 1.1 , about 1 .0 to about 1 .2, about 1 .0 to about 1 .3, about 1 .0 to about 1 .4, about 1 .0 to about 1 .5, about 1 .0 to about 1 .6, about 1 .0 to about 1 .7, about1 .0 to about 1 .8, about 1 .0 to about 1 .9, about 1 .0 to about 2.0, about 1 .0 to about to 2.5, about 1 .0 to about 3.0, about 1 .0 to about 3.5, or about 1 .0 to about 4.0 % w / v of pharmaceutically compatible carrier oil.

[0149] The emulsifier for use in the formulation is used as part of an emulsifier system. The emulsifiers in the emulsifier system may be selected from any suitable pharmaceutically compatible emulsifier. The emulsifier system comprises at least two emulsifiers comprising a different Hydrophilic-lipophilic balance (HLB). The HLB is the balance of the size and strength of the hydrophilic and lipophilic moieties of a surfactant molecule. Traditionally, an emulsifier with an HLB of between 3.5 and 6 are used in water in oil emulsions, whereas an emulsifier with an HLB of between 8 to 18 are used in oil in water emulsions. The inventors have determined that the pharmaceutically compatible emulsifier system for use in the present composition comprises a first emulsifier with an HLB of about 1 to 8 and a second emulsifier with an HLB of greater than 14 such that when combined. Preferably the emulsifier system comprises a combination HLB of about 8.5, 9, 9.5, 10,10.5, 11 , 11 .5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5 or 16, and suitable ranges may be selected from any of these values (for example from about 8.5 to about 16, about 8.5 to 13, about 9 to about 16, about 9 to about 14.15, about 10 to about 16, about 10 to about 15, about 10 to about 14, about 11 to about 16, about 11 to about 15, about 11 to about 14, about 12 to about 16, about 12 to about 14 or about 13 to about 16).

[0150] The emulsifier may comprise synthetic or natural emulsifying agents.

[0151] Synthetic emulsifiers may include one or more the surfactants discussed in paragraphs

[0125] to

[0131] ,

[0152] Natural emulsifiers may be derived from plant or animals.

[0153] Plant derived emulsifiers may include but are not limited to hydrophilic colloids, alginates, acacia, tragacanth, xanthan, and pectin.

[0154] Animal derived emulsifiers may include but are not limited to gelatin, casein, egg yolk, wool fat, cholesterol, wax, and lecithin.

[0155] The emulsifier may comprise soy lecithin.

[0156] The emulsifier may comprise lecithin from sunflower, linseed, olive, rapeseed, egg, com, peanut or algae.

[0157] The emulsifier may comprise one or more of polyoxyethylene sorbitan fatty acid esters, sodium alkyl sulphates, aliphatic alcohols, esters of polyethylene glycol, ethoxylated aliphatic alcohol, and alkyl and coco glucosides.

[0158] The emulsifier may be selected from any of the emulsifiers shown below. That is, the high HLB emulsifier may be a polysorbate, POE40, Span60:Tween60, lecithin,, sorbitan monooleate.

[0159] The low HLB emulsifier may be selected from lecithin or any other emulsifier with an HLB of 1 to 8.

[0160]

[0161] The composition may comprise about 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0, 1 .1 , 1 .2, 1 .3, 1 .4, 1 .5, 1 .6, 1 .7, 1 .8, 1 .9, 2.0, 2.1 , 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1 , 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9 or 4.0% by weight volume (w / v) of the pharmaceutically compatible emulsifier, and useful ranges may be selected between any of these values. For example, the composition may comprise about 0.1 to about 0.2, about 0.1 to about 0.4, about 0.1 to about 0.6, about 0.1 to about 0.8, about 0.1 to about 1 .0, about 0.1 to about 1.1 , about 0.1 to about 1 .2, about 0.1 to about 1 .3, about 0.1 to about 1 .4, about 0.1 to about 1 .5, about 0.1 to about 1 .6, about 0.1 to about 1 .7, about 0.1 to about 1 .8, about 0.1 to about 2.0, about 0.5 to about 1 .0, about 0.5 to about 1 .5, about 0.5 to about 2.0, about 0.5 to about 2.5, about 0.5 to about 3.0, about 0.5 to about 3.5, about 0.5 to about 4.0, about 1 .0 to about 1.1 , about 1 .0 to about 1 .2, about 1 .0 to about 1 .3, about 1 .0 to about 1 .4, about 1 .0 to about 1 .5, about 1 .0 to about 1 .6, about 1 .0 to about 1 .7, about 1 .0 to about 1 .8, about 1 .0 to about 1 .9, about 1 .0 to about 2.0, about 1 .0 to about to 2.5, about 1 .0 to about 3.0, about 1 .0 to about 3.5, or about 1 .0 to about 4.0 % w / v of pharmaceutically compatible emulsifier.

[0162] The composition may comprise greater than 60 %w / v water.

[0163] The composition may comprise about 60, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98 %w / v water, and useful ranges may be selected between any of these values. For example, the composition may comprise about 60 to about 70, about 60 to about 80, about 60 to about 90, about 60 to about 95, about 60 to about 98, about 70 to about 75, about 70 to about 80, about 70 to about 85, about 70 to about 90, about 70 to about 95, about 70 to about 98, about 70 to about, about 80 to about 85, about 80 to about 90, about 80 to about 95, about 80 to about 98% w / v water.

[0164] The composition may comprise one or more additional excipients including but not limited to an antioxidant, an antimicrobial, a mineral, a vitamin, a viscosity modifier, a buffering agent, a flavour or palatability enhancer, a chelating agent, and a preservative. It will be understood that certain excipients may perform more than one functional role.

[0165] An antioxidant may be added to pharmaceutical formulations to prevent the oxidation of active ingredients over time. Typically a pharmaceutical product requires a shelf life to account for the time taken between manufacture and use. During this time an active agent may be exposed to oxygen whether in the formulation or from the atmosphere leading to its oxidation. THC is highly unstable in the presence of oxygen, readily degrading and oxidizing into cannabinol (CBN) when exposed to air, meaning its potency significantly decreases overtime due to oxygen exposure. As such, preferably the composition includes an antioxidant. It will be appreciated that if the pharmaceutical composition is for immediate use, then an antioxidant may not be required owing to the limited degradation that will occur in a short period of time. However, where the composition is contemplated to have some degree of shelf time such as greater than 1 week, 1 , 2, 3, 4, 5, or 6 months then the addition of an antioxidant is preferred to reduce the degree of degradation of the active agents such as THC. The antioxidant may comprise one or more of ascorbic acid, tocopherols (for example, a-tocopherol), lutein, zeaxanthin, gallic acid, hydroxycinnamic acids, or resveratrol. In some embodiments, the antioxidant may comprise butylated hydroxyanisole (BHA).

[0166] A microbial preservative may be added to a composition to reduce the growth of organisms in the composition, such as bacterial and fungi. Microbial growth can degrade the active agents in a medication, so using antimicrobials helps ensure the actives remain effective throughout the composition’s shelf life. It will be appreciated that if the pharmaceutical composition is for immediate use, then a microbial preservative may not be required owing to the limited degradation that will occur in a short period of time. However, where the composition is contemplated to have some degree of shelf time such as greater than 1 week, 1 , 2, 3, 4, 5, or 6 months then the addition of a microbial preservative is preferred to reduce the degree of degradation of the active agents such as CBD and THC. Where a microbial preservative is used in the composition it comprises two or more preservatives, the preservatives being from a different chemical class. The microbial preservatives may be selected from parabens such as methyl, ethyl, propyl, butyl, or heptyl paraben, potassium sorbate, phenoxyethanol, germall, citric acid, benzoic acid, sorbic acid, ethylenediaminetetraacetic acid (EDTA) or sodium benzonate. A stated the preservative system comprises a combination of preservatives from different chemical classes.

[0167] The preservative system may comprise for example:• A paraben and EDTAA paraben and potassium sorbate Potassium sorbate and Phenoxyethanol Phenoxyethanol, a paraben and EDTA• Potassium sorbate, a paraben and germall

[0168] In some embodiments, the preservative may comprise a salt of the preservative. For example, sodium methyl paraben, and sodium propyl paraben, tetrasodium EDTA.

[0169] In one embodiment at least one of the microbial preservatives is selected from a chelating class of preservatives such as tetrasodium EDTA, citric acid, dimercaprol or diethylenetriaminepentaacetic acid (DTPA). Preferably one of the preservatives is EDTA.

[0170] A pH buffering agent may be required to maintain the stability and efficacy of the active agents by preventing significant pH changes, which can affect the solubility, chemical structure, and ultimately, the therapeutic effectiveness of the composition throughout storage and administration. Additionally, without wishing to be bound by theory, a pH of about 4 to 7 has been found to be optional for the antimicrobial system of the composition. Thus the presence of a buffering agent may be used to maintain the pH between 4 and 7. Various buffering agents are known in the art of pharmaceutical formulations. Preferably a pharmaceutically compatible buffer would be selected for use.

[0171] One or more buffering agent may be added to adjust the aqueous phase to obtain a predetermined pH level to prevent acid breakdown of CBD and to ensure optimal pH for the other excipients such as the preservative. For example, the buffering agent may be added to obtain a pH of about 4 to about 6.

[0172] The buffering agent may be selected from one or more of citric acid, sodium hydroxide and trisodium citrate.

[0173] The mineral may comprise one or more of copper, sodium, calcium, potassium, chromium, magnesium, molybdenum, iron, or zinc.

[0174] The vitamin may comprise one or more of vitamins A, Bi, B2, B3, Bs, Be, B7, B9, B12, C, D, E, K, and choline.

[0175] The composition as described may comprise one or more cannabinoids comprising at least THC, a emulsifier system comprising a first emulsifier with an HLB 1 to 8 and a second emulsifier with an HLB of greater than 14 that in combination provides a combination HLB of between 8.5 and 16.0, and a droplet size of less than 500d.nm,0.1 to 3% of weight of a pharmaceutically compatible carrier oil, greater than 60% w / v water.

[0176] The composition may comprise a cannabidiol (CBD) and a tetrahydrocannabinol (THC) at a ratio of CBD:THC of about 5:1 to about 80:1 ,a emulsifier system comprising a first emulsifier with an HLB 1 to 8 and a second emulsifier with an HLB of greater than 14 that in combination provides a combination HLB of between 8.5 and 16.0, and a droplet size of less than 500d.nm,0.1 to 3% of weight of a pharmaceutically compatible carrier oil, greater than 60% w / v water, and

[0177] Administration of the active pharmaceutical agents may be carried out by applying the composition to food. The composition’s application to food as an emulsion may effectively deliver the cannabinoids to non-human animals such as companion animals.

[0178] Veterinary medicines in solid form, such as tablets or capsules, may be harder to administer to companion animals. For example, the animals often identify the tablet or capsule and avoid consuming it reducing the efficacy of the treatment.

[0179] Conversely, veterinary medicines in granular or powder form may adversely affect the palatability of the food to which the medicine is applied to.

[0180] By providing a composition in the form of an emulsion, the composition may be more easily and effectively applied to food without adversely affecting palatability while ensuring the appropriate dose is administered to the animal. As discussed elsewhere in the specification, providing the composition as a nanoemulsion may also improve bioavailability and efficacy of the composition. Additionally, the volume of composition (selected to obtain the required plasma provide of APIs) can be applied to an amount of food that the subject intends to, or would reliably, eat. In comparison, providing a food dosed with a set concentration of active pharmaceutical ingredient (API) requires the subject to consume the entire amount of food to obtain the desired amount of API.

[0181] The composition could be sprayed on the food, or applied to the food using a metered device, or a syringe.

[0182] The composition may be applied to food for consumption by the subject once daily, twice daily, or thrice daily.

[0183] Once applied to the food it is desired that the formulation remain on the food so that the subject consumes the composition as they eat the food. A composition with a low viscosity may run off the food. However, a composition with too high a viscosity will be difficult to apply to the food.

[0184] Viscosity is a measure of a fluid’s internal flow resistance. Viscosity may be measured and defined using a rotational viscometer. A rotational viscometer measures the rotational force (i.e. torque) required to revolve an object within the liquid to be tested. Visocsity is commonly defined centiPoise (cP) or millipascal-second (mPa-S). For example, castor oil has a viscosity of 1 ,000 to 2,000 cP (or mPa-S), honey as a viscosity of 2,000 to 3,000 cP (or mPa-S), and molasses has a viscosity of 5,000 to 10,000 cP (or mPa-S). Unless otherwise specified, viscosity is defined in thisspecification in centiPoise (cP) at 21°C at 100rpm using standard rotational viscometer spindles or in millipascal-second (mPa-S).

[0185] To facilitate adhesion or retention of the composition on the food, the composition may have a viscosity of 500, 1 ,000, 1 ,500, 2,000, 2,500, 3,000, 3,500, 4,000, 4,500, 5,000, 5,500, 6,000, 6,500, 7,000, 7,500 or 8,000 cP at 21 °C and useful ranges may be selected between any of these values. For example, the composition may comprise a viscosity of about 500 to about 800, about 500 to about 1 ,000, about 500 to about 1200, about 500 to about 1400, about 500 to about 1600, about 500 to about 1800, about 500 to about 2,000, about 500 to about 3,000, about 500 to about 4,000, about 500 to about 5,000, about 500 to about 6,000, about 500 to about 7,000, about 500 to about 8,000, about 700 to about 1 ,000, about 700 to about 1 ,500, about 700 to about 2,000, about 700 to about 2,500, about 700 to about 3,000, about 700 to about 4,000, about 700 to about 5,000, about 700 to about 6,000, about 700 to about 7,000, about 700 to about 8,000, about 1 ,000 to about 1 ,500, about 1 ,000 to about 2,000, about 1 ,000 to about 3,000, about 1 ,000 to about 4,000, about 1 ,000 to about 5,000, about 1 ,000 to about 6,000, about 1 ,000 to about 7,000, about 1 ,000 to about 8,000 cP at 21 °C.

[0186] The composition may be configured to comprise a viscosity that enables the composition to adhere to the food to which it is applied to avoid wastage and to ensure that an appropriate amount of the composition is administered to an animal subject, such as a companion animal, that consumes the food to which the composition is applied.

[0187] The composition may comprise one or more pharmaceutically compatible viscosity or rheology modifiers. The viscosity or rheology modifier is selected from a polysaccharide thickener such as xanthan gum.

[0188] Without wishing to be bound by theory the thickened composition may inhibit the ability of antimicrobial preservatives from effectively accessing all of the composition thus necessitating the antimicrobial system as described, being two or more antimicrobial compounds of differing chemical classes.

[0189] The composition may comprise one or more beneficial microorganisms such as probiotics including but not limited to Limosilactobacillus, Bacillus, Weissella, Lactobacillus and Bifidobacterium strains

[0190] The composition may also be delivered by oral, sublingual, buccal, and / or rectal administration.

[0191] It will be understood that excipients disclosed in the specification may have multiple functional roles.

[0192] The composition may be prepared by preparing a pre-emulsion mixture. The preemulsion mixture may be prepared by mixing a pharmaceutically compatible surfactant, apharmaceutically compatible carrier oil, and a pharmaceutically compatible emulsifier. The preemulsion is then heated to a first temperature. After being held at the first temperature the premixture is then stirred and cooled to a second temperature. One or more cannabinoids may then be added to the cooled pre-mixture. An aqueous phase is also prepared by heating water to the second temperature, to which the pre-emulsion mixture is slowly added, preferably with mixing. The result composition is then stirred for a predetermined time and at a predetermined speed.

[0193] In some embodiments, the pre-emulsion mixture is maintained at the first temperature while excipients and APIs are added.

[0194] The CBD and THC may then be added to the cooled pre-mixture.

[0195] The pre-emulsion mixture may comprise excipients of a stabiliser system (stabiliser excipients) and one or more cannabinoids.

[0196] The composition may be prepared as shown in Figure 1 by preparing a pre-emulsion mixture and an aqueous phase. The pre-emulsion mixture may be prepared by adding a first stabiliser excipient which is heated to and maintained at a first temperature. Second, third, or further stabiliser excipients (not shown) are added. One or more optional excipients, for example, an antioxidant may be added. The mixture is allowed to cool and maintained at a second temperature. The APIs, such as CBD and THC, are then added. The aqueous phase may be prepared by heating water to the second temperature in a separate vessel. The pre-emulsion mixture is added to the heated water while stirring. Stirring is maintained at a predetermined speed for a predetermined time. Stirring is stopped and allowed to cool. Additional optional excipients may be added while stirring or mixing.

[0197] The composition may also be prepared as shown in Figure 2. The pre-emulsion mixture is prepared as shown in Figure 1 . Water heated is heated to the second temperature and added directly to the pre-emulsion mixture while stirring. Stirring is maintained at a predetermined speed for a predetermined time. Stirring is then stopped and the mixture allowed to cool. Optional excipients may be added while stirring.

[0198] The pre-emulsion mixture may be prepared as a concentrate such that one batch of the pre-emulsion concentrate may be used to prepare multiple batches of the composition (i.e. the final product) to improve the efficiency of the method.

[0199] The pre-emulsion concentrate may be prepared as a batch of about 1 , 2, 3, 4, 5, 6 , 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, or 20 L, and useful ranges may be selected between any of these values. For example, about 1 to about 5, about 1 to about 10, about 1 to about 15, about 1 to about 20, about 5 to about 10, about 5 to about 15, about 5 to about 20, about 10 to about 15, about 10 to about 20 L.

[0200] At least one stabiliser excipient may be added to a first vessel and heated to and maintained at a first temperature.

[0201] The stabiliser excipients may include but are not limited to a pharmaceutically compatible surfactant, a pharmaceutically compatible carrier oil, and a pharmaceutically compatible emulsifier.

[0202] The first temperature may be about 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, or 60 °C, and useful ranges may be selected between any of these values. For example, the first temperature may be about 40 to about 45, about 40 to about 50, about 40 to about 55, about 40 to about 60, about 45 to about 50, about 45 to about 55, about 45 to about 60, about 50 to about 60 °C.

[0203] At the first temperature, any stabiliser excipients not yet added may be added to the heated mixture and stirred until clear and allowed to cool to a second temperature.

[0204] In some embodiments, the second temperature may be about 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, or 50 °C, and useful ranges may be selected between any of these values. For example, the second temperature may be about 30 to about 35, about 30 to about 40, about 30 to about 45, about 30 to about 50, about 40 to about 45, or about 40 to about 50 °C.

[0205] Other excipients may optionally be added following addition of the stabiliser excipients.

[0206] Another stage of the method may broadly comprise preparing an aqueous phase.

[0207] Water may be added to a second vessel and heated to the second temperature.

[0208] At the second temperature, the pre-emulsion mixture or concentrate may be added to the heated water whilst stirring for a predetermined time and at a predetermined speed.

[0209] The predetermined time may be about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 minutes, and useful ranges may be selected between any of these values. For example, the predetermined time may be about 10 to about 15, about 10 to about 20, about 10 to about 25, about 10 to about 30, about 10 to about 35, about 10 to about 40, about 10 to about 45, about 10 to about 50, about 10 to about 55, about 10 to about 60,

[0210] Water may be added directly to the pre-emulsion mixture and stirred for a predetermined time and at a predetermined speed.

[0211] The method may be carried out using any suitable mixer, agitator, stirrer, or homogeniser.

[0212] The method may be carried out using a high shear mixer.

[0213] The predetermined speed may be about 5,000, 5,250, 5,500, 5,750, 6,000, 6,250, 6,500, 6„750, 7,000, 7250, 7,500, 7,750, 8,000, 8,250, 8,500, 8,750, 9,000, 9,250, 9,500, 9,750, 10,000, 10,250, 10,500, 10,750, 11 ,000, 11 ,250, 11 ,500, 11 ,750, or 12,000 revolutions per minute (RPM), and useful ranges may be selected between any of these values. For example, the predetermined speed may beabout 5,000 to about 6,000, about 5,000 to about 7,000, about 5,000 to about 8,000, about 5,000 to about 9,000, about 5,000 to about 10,000, about 5,000 to about 11 ,000, about 5,000 to about 12,000,

[0214] Stirring may be maintained at a rate of about 0.1 , 0.11 , 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21 , 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.30, 0.31 , 0.32, 0.33, 0.34, 0.35, 0.36, 0.37, 0.38, 0.39, or 0.40 kW / h per litre (1 ,5A), and useful ranges may be selected between any of these values. For example, stirring may be maintained at a rate of about 0.1 to about 0.15, about 0.1 to about 0.20, about 0.1 to about 0.25, about 0.1 to about 0.30, about 0.1 to about 0.35, about 0.1 to about 0.4, about 0.15 to about 0.20, about 0.15 to about 0.25, about 0.15 to about 0.30, about 0.15 to about 0.35, about 0.15 to about 0.40, about 0.2 to about 0.25, about 0.2 to about 0.30, about 0.2 to about 0.35, or about 0.2 to about 0.4 kW / h per litre (1 ,5A).

[0215] The step of stirring for a predetermined time and at a predetermined speed obtains nanosized droplets. This step may also be referred to as a homogenisation step when a homogeniser is used.

[0216] Homogenisation may be performed at rate of about 0.3, 0.6, 0.9, 1.2, 1.5, 1.8, 2.1 , 2.4, 2.7, 3.0, 3.3, 3.6, 3.9, 4.2, 4.5, 4.8, 5.1 , 5.4, 5.7, or 6.0 Amps per hour per litre of product (A / h / L), and useful ranges may be selected between any of these values. For example, about 0.3 to about 6.0, about 0.6 to about 5.7, about 0.9 to about 5.4, about 1 .2 to about 5.1 , about 1 .5 to about 4.8, about 1 .8 to about 4.5, about 2.1 to about 4.2, about 2.4 to about 3.9, about 2.7 to about 3.6, about 3.0 to about 3.3, about 0.9 to about 1 .4, about 1 .5 to about 3.6, or about 3.6 to about 6.0 Amps per hour per litre of product (A / h / L).

[0217] The nano-sized droplets has a DOO droplet size of about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 1230, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 600, 700, 800, 900, 1 ,000 nm, and useful ranges may be selected between any of these values. For example, the nano-sized droplets may be about 10 to about 50, about 10 to about 100, about 10 to about 150, about 10 to about 200, about 10 to about 250, about 10 to about 300, about 10 to about 350, about 10 to about 400, about 10 to about 450, about 10 to about 500, about 10 to about 600, about 10 to about 700, about 10 to about 800, about 10 to about 900, about 10 to about 1 ,000, about 50 to about 100, about 50 to about 150, about 50 to about 200, about 50 to about 250, about 50 to about 300, about 50 to about 350, about 50 to about 400, about 50 to about 450, about 50 to about 500, about 100 to about 250, about 100 to about 300, about 100 to about 350, about 100 to about 400, about 100 to about 450, about 100 to about 500, about 200 to about 300, about 200 to about 400, about 200 to about 500, about 200 to about 600, about 200 to about 700, about 200 to about 800, about 200 to about 900, about 200 to about 1 ,000, about 300 to about 400, about 300 to about 500, about 300 to about 600, about 300 to about 700, about 300 to about 800, about 300 to about 900, about 300 to about 1 ,000 nm.

[0218] An emulsification head of a high shear rotor or stator laboratory mixer is used for stirring.

[0219] After the predetermined time, stirring is ceased and the mixture is allowed to cool and deaerate.

[0220] Optionally, a viscosity modifier may be added whilst mixing with a chopping stirrer blade at a speed of about 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1 ,000, 1 ,050, 1 ,100, 1 ,150, 1 ,200, 1 ,250, 1 ,300, 1 ,350, 1 ,400, 1 ,450, or 1 ,500 RPM, and useful ranges may be selected between any of these values. For example, the viscosity modifier may be added whilst mixing with a chopping stirrer blade at a speed of about 500 to about 600, about 500 to about 800, about 500 to about 1 ,000, about 500 to about 1200,

[0221] Optionally, one or more of an antimicrobial, antioxidant, and preservative may be added whilst stirring at a speed of about 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1 ,000 RPM, and useful ranges may be selected between any of these values.

[0222] Cannabinoids may be helpful in treating or ameliorating the symptoms of a number of health conditions including but not limited to inflammatory disorders, pain, anxiety, epilepsy, multiple sclerosis and spasticity, gastrointestinal disorders (for example, nausea and vomiting, motility disorders), Parkinson’s disease, Huntington’s disease, diabetes and diabetic complications, cerebrovascular disorders and glaucoma, skin conditions (such as atopic dermatitis), appetite loss, and sleep disorders.

[0223] Pain disorders may include but are not limited to intractable cancer pain, neuropathic pain, chronic pain or postoperative pain.

[0224] Inflammatory disorders may include but are not limited to rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), fibromyalgia, or gout arthritis.

[0225] Described is a method for treating or ameliorating symptoms of arthritis in a subject. A composition is provided that has a viscosity of 500 to 5,000 cP at 21 °C and is in the form of an oil-in- water nanoemulsion. The composition comprises a cannabidiol (CBD) and a tetrahydrocannabinol (THC) at a CBD:THC ratio of about 5:1 to about 80:1 , a pharmaceutically compatible surfactant, a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier, and greater than 60% w / v water. The composition is then applied to the food of the subject to be treated to provide 0.25 to 1 .0 mg of CBD and 0.0125 to 0.05 mg of THC per kg of the subject weight.

[0226] The subject for treatment may be a human subject. The subject for treatment may be a non-human subject such as a non-human mammal, an avian, an amphibian, or a reptile.

[0227] The non-human mammal may be selected from a canine, feline, equine, avian, bovine, porcine, simian, murine, lapine, or ovine.

[0228] The animal subject may comprise working, zoo, livestock or companion animals. For example, the animal subject may be a dog, cat, bird, rabbit, mouse, guinea pig, hamster, ferret, pig, chinchilla, rat, horse, donkey, cattle, buffalo, yak, reindeer, sheep, goat, camel, llama, alpaca, deer, parrot, passerine, fowl, chicken, duck, turkey, turtle, lizard, snake, iguana, tiger, lion, bear, elephant, giraffe, rhino, monkey, or ape.

[0229] The CBD to THC ratio may be selected based on one or more factors including but not limited to disease type, disease severity, disease progression, and animal type.

[0230] The CBD target dose may comprise about 0.1 , 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1 .0, 1 .1 , 1 .15, 1 .2, 1 .25, 1 .3, 1 .35, 1 .4, 1 .45, or 1 .5 mg of CBD per kg of subject weight, and useful ranges may be selected between any of these values.

[0231] The THC target dose may comprise about 0.01 , 0.015, 0.02, 0.025, 0.03, 0.35, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095, or 0.1 mg of THC per kg of subject weight, and useful ranges may be selected between any of these values.

[0232] The composition may be applied to food for consumption by the subject once daily, twice daily, or thrice daily.

[0233] In some embodiments, the composition is applied to food for consumption by the subject, weekly, fortnightly, or monthly.EXAMPLESExample 1 - Emulsification

[0234] A range of experiments were conducted to investigate emulsification of the formulation across emulsifiers with a range of final combination HLB from 8.7 to 13.9.

[0235] The Tables below show the formulation and emulsifiers that were tested.Table 1 . Test of single emulsifier - POE40Table 2. Test of emulsifiers with a final HLB of 8.7Table 3. Test of emulsifiers with a final HLB of 11 .0Table 4. Test of emulsifiers with a final HLB of 11 .8Table 5. Test of emulsifiers with a final HLB of 13.9Table 6. Test of emulsifiers with a final HLB of 14Table 7. Test of emulsifiers with a final HLB of 15.7Table 8. Test of emulsifiers with a final HLB of 16.7

[0236] As shown in Table 1 as single emulsifier was tested - POE40. Using the same formulation as in Table 1 , additional single emulsifier formulation were also tested with the single emulsifier being:• Polysorbate 80 (HLB 15),• Polysorbate 20 (HLB 16), or• Lecithin (HLB 4).

[0237] None of the single emulsifier systems emulsified the formulation.

[0238] Each of the other combination emulsifier systems were successful at emulsifying the formulations.Example 2 - Emulsifier particle size

[0239] Following on from Example 1 that demonstrated that combination emulsification systems were successful at emulsifying the formulation, the particle size of the combination emulsification systems was also tested as follows.• The MCT was set at 0.5%• 4.1% of POE and LCT was added at changing ratios to achieve a range of HLB• The formulations were emulsified into water• Appearance, 1 week physical stability at RT and particle size was evaluated / testedTable 9. Experimental setup of formulations to test particle size

[0240] A further experiment was run to assess the impact of changing the ingredients whilst maintaining the HLB the formulationThe MCT was set at 0.5% as per final formulation2.9%w / v of POE and 1 ,2%w / v Span80 (HLB 4.3) added at ratio shown to achieve HLB of the test formulationEmulsified into waterAppearance, 1 week physical stability at RT and particle size was evaluated / tested

[0241] The droplet particle size was measured using a Malvern Zetasizer Nano-ZS with the following settings (taking into account the presence of a thickening agent):Table 10. Set up of droplet particle size measurement apparatus

[0242] Droplet size range: The Z-average droplet size test results for all batches which were made with the HLBs ranging from 8.7 - 16.7 came in under l OOd.nm.Example 3 - Preservative

[0243] A range of preservatives were tested as shown in Table 11 below.

[0244] A result of “growth” indicates the grown of organisms. A result of “reduction” indicates a significant reduction in growth of organisms.

[0245] The preservatives were tested on the full formulation as shown in Table 14 F1 , varying only the preservatives.Table 11. Preservative systems testedExample 4 - Thickener

[0246] A range of thickeners were tested as shown below. A visual inspection was conducted of the formulations as per Table 14 F1 with the thickener varied.Table 12. Thickeners tested

[0247] As shown above in Table 12, polysaccharide thickeners such as xanthan gum, carrageenan and guar gum were successful in thickening and stabilising the formulation.Example 5 - Stability

[0248] A number of other key stability affectors of Table 13 F1 formulation were also tested as shown below with the results of those studies.Medium chain 1.08 1.02 triglyceridesSoy lecithin 1 .05 1 .0Vitamin E 0.016 0.015Antimicrobial 0.005Antioxidant 0.005Potassium sorbate - 0.005Citric Acid - 0.005Trisodium Citrate - 0.005BHA - 0.100Water 94.5 94.8TOTAL 100 100Example 7 - Method of manufacture

[0250] This example demonstrates a method of manufacturing an embodiment of the composition according to the present disclosure to produce a stable nanoemulsion measuring between 10 nm and 250 nm.

[0251] Preparation of pre-emulsion mixture: a) Add polyethylene glycol (PEG) distearate to vessel and heat to 50°C and maintain. b) Add medium chain triglyceride (coconut fatty acid) and stir until clear. c) Add soy lecithin and stir until clear. d) Add Vitamin E, stir and allow to cool to 40°C. e) Add CBD and stir until clear and maintain at 40°C. f) Add THC and stir until clear maintain at 40°C.

[0252] Preparation of aqueous phase: g) Add water to emulsification vessel fitted with Silverson emulsification head. h) Heat to 40°C. i) Slowly add pre-emulsion mixture into emulsification vessel while stirring using the emulsification head set to 80% speed (9250 rpm). j) Maintain stirring speed for 30 minutes (1 ,5A - 0.24kW / h per litre). k) Stop stirring and whilst cooling and allow deaeration (observe that resultant liquid should be opaque and not separate). l) Add viscosity modifier whilst mixing at 1 ,000 rpm with chopping stirrer blade. m) Add potassium sorbate whilst stirring at 500 rpm. n) Add citric acid whilst stirring at 500 rpm.o) Add trisodium citrate whilst stirring at 500 rpm.

[0253] Mixing and stirring was performed using a Silverson® high shear mixer (L5M-A Laboratory Mixer) at 9200 rpm for 30 min at 1 litre of formulation.Example 8 - Stability

[0254] This example demonstrates the stability of the nanoemulsion comprising both CBD and THC according to an embodiment of the invention.

[0255] Two nanoemulsions were prepared based on formulations F031 and F032 shown in Table 15 below. The nanoemulsions were prepared in batches and tested for stability by subjecting the nanoemulsions to stress conditions of elevated temperature.Table 15. Formulation F031 and F032CBD 0.5 0.5THC 0.025 0.025Polyethylene glycol di-stearate 1 .32 2.65Medium chain triglycerides 0.51 1.02Soy lecithin 0.5 1 .0Vitamin E 0.007 0.015Water 97.14 94.79TOTAL 100 100

[0256] Two nanoemulsions, batch 922-2a and 922-3a, were subjected to temperatures of 25 °C for 72 hours as a room temperature control. Two nanoemulsions, batch 922-2b and 922-3b, were subjected to an elevated temperature of 40 °C for 72 hours.

[0257] Table 16 below shows droplet size of the nanoemulsions in the presence of heat stress.Table 16. Comparison of emulsion droplet size (mean particle diameter) under stress conditionsFormulation Batch Stability Condition MPD (nm)F031 922-2a 72 h at 25 °C 105F031 922-2b 72 h at 40°C 116F032 922-3a 72 h at 25 °C 127F032 922-3b 72 h at 40 °C 124

[0258] The results indicate that droplet size of the nanoemulsions subjected to stress conditions of elevated temperatures of 40°C remained relatively stable when compared to the nanoemulsions kept at 25 °C.Example 9 - Efficacy

[0259] This study demonstrates the efficacy of a composition according to an embodiment of the invention to ameliorate symptoms associated with osteoarthritis (OA) in dogs.

[0260] The composition (Composition 1) used this study comprised APIs of 4.76 g / L cannabidiol (CBD) and 0.24 g / L delta-9-tetrahydrocannibinol (THC).

[0261] The composition was evaluated against Metacam®, an anti-inflammatory oral suspension for dogs, a non-steroidal anti-inflammatory drug (NSAID). The API in Metacam® is Meloxicam, commonly prescribed as a conventional treatment for OA in dogs.

[0262] Twenty dogs with clinical signs of OA as evidenced by a Clinical Sum Score (CSS) >4, and basal Canine Brief Pain Index (CBPI) Pain Severity Score (PSS) and Pain Interference Score (PIS) >2 for each between Day -10 and Day -1 , and on Day 0 were used for this study. The dogs had a minimum weight of 5 kg.

[0263] All dogs included in the study are otherwise in good general health based on a complete general physical examination, and routine blood (haematology and biochemistry) examination results were within normal limits.

[0264] Fifteen dogs were treated with composition 1 and five dogs were treated with the positive control as shown in Table 17 below. All dogs displayed mild to moderate pain at the start of the treatment.

[0265] Nine dogs and eleven bitches were enrolled, with two dogs and three bitches allocated to the positive control group, while the remaining seven dogs and eight bitches were allocated to the IVP group. One bitch dropped out early, leaving seven of each sex in the group treated with Composition 1 . One dog was entire while the other animals were neutered / spayed. The average age of animals was 10.7 years for both groups.

[0266] The dogs were treated twice daily with composition 1 , or once daily for Metacam® for 42 days. The treatments were added to the dogs’ food at normal feeding times for all dogs except for one dog in the Composition 1 treatment group, who was orally dosed (due to feeding habits and fussiness).Table 17. Treatment detailsTreatment group Concentration Treatment dose Treatment frequencyComposition 1 4.76 g / L CBD o.5 mg / kg Twice daily0.24 g / L THCMetacam® 1.5 g / L Day 1 0.2 mg / kg; Once dailyDay 2+ 0.1 mg / kg

[0267] A veterinarian supporting the study completed a physical and locomotion examination including a Clinical Sum Score (CSS) between 10 and 1 day prior to enrolment.

[0268] The CSS is the total of each individual score for posture (Table 18), lameness at a walk (Table 19), lameness at a trot (Table 20) and pain response on palpation / manipulation (Table 21).Table 18: Posture (dog standing)Score Description0 Normal stance1 Slightly abnormal stance; partially weight bearing, but paw remains firmly in contact with floor2 Markedly abnormal stance: partially weight bearing with minimal contact between paw and floor3 Severely abnormal stance: non-weight bearingTable 19: Lameness at a walkScore Description0 No lameness; normal weight bearing on all limbs2 Mild lameness; partially weight bearing on one or more limbs4 Obvious lameness; partially weight bearing on one or more limbs6 Marked lameness; non-weight bearing on one or more limbsTable 20: Lameness at a trotScore Description0 No lameness; normal weight bearing on all limbs2 Mild lameness; partially weight bearing on one or more limbs4 Obvious lameness; partially weight bearing on one or more limbs6 Marked lameness; non-weight bearing on one or more limbsTable 21 : Pain on palpation / manipulationScore Description0 No pain on palpation / manipulation of affected joint(s)1 Milk pain (e.g. turns head in recognition)2 Moderate pain (e.g. pulls limb away)3 Severe pain (e.g. vocalises or becomes aggressive or will not allow vet to palpate / manipulate the joint due to pain)

[0269] A CSS was completed on Days 0, 21 and 42.

[0270] On Day 0 CSS, there no statistical treatment group differences for sex (p=0.7484), age (p=0.3063) or liveweight (p=0.1083), meaning the groups were balanced for all these variables.There was also no age x treatment or liveweight x treatment differences (p>0.76) at enrolment.

[0271] Day 0 CSS was similar between the two groups: 9.0 in the Composition 1 treatment group and 8.20 in the positive control group (p=0.0.4306; Table 22). Mean CSS at Day 21 was 3.50 and 4.15 for the positive control and Composition 1 groups, respectively, an average improvement of 4.43 and 4.85. Both the absolute value and the change from baseline (Day 0) were statistically similar (p=0.7475 and p=0.7955, respectively; Table 22). Mean CSS at Day 42 was similar between the treatment groups (p=0.8031) as was the change from Day 0 (p=0.9422).Table 22: Clinical sum score (CSS; least squares mean) at enrolment (Day -1 / Day 0), Day 21 and 42 (excludes dog that dropped out early)Treatment Group Clinical Sum Score Change in Clinical SumScoreEnrolment (D -1 / 0) D21 D42 DO-21 DO-42Composition 1 9.00 4.15 2.93 4.29 5.65Metacam® 7.93 3.50 2.80 4.50 5.70P value 0.4306 0.7475 0.8031 0.7955 0.9422

[0272] On Day 21 and 42, heavier dogs had a higher CSS which demonstrates the same pattern seen on Day 0 (prior to treatment) with a tendency for heavier dogs to respond less to treatment. Age also had a significant effect on CSS and change from Day 0 where older dogs had a higher CSS and smaller changes between Day 0 and 21 , and Day 0 and 42.

[0273] Figure 3 is a graph showing reduction of the CSS for each dog after 42 days of treatment. Dogs 1 to 5 were treated with the positive control, while Dogs 6 to 19 were treated with Composition 1 . Generally, a CSS reduction of 2 is deemed to be efficacious. The positive control treatment group showed a CSS reduction of between 4 and 7. Comparatively, the Composition 1 treatment group showed a CSS reduction of between 3 and 9. One dog did not appear to respond to the treatment.

[0274] The results demonstrate that Composition 1 is efficacious in ameliorating symptoms of OA in dogs.

[0275] Although embodiments have been described with reference to a number of illustrative embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the preferred embodiments should be considered in a descriptive sense only and not for purposes of limitation, and also the technical scope of the invention is not limited to the embodiments. Furthermore, the present invention is defined not by the detailed description of the invention but by the appended claims, and all differences within the scope will be construed as being comprised in the present disclosure.

[0276] Many modifications will be apparent to those skilled in the art without departing from the scope of the present invention as herein described with reference to the accompanying drawings.

Claims

WE CLAIM1 . A composition comprising a cannabidiol (CBD) having a purity greater than 90% and a tetrahydrocannabinol (THC) having a purity greater than 90% at a ratio of CBD:THC of about 5:1 to about 80:1 , for a combined cannabinoid concentration of up to 15 g / L, up to 4% of weight of a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier system comprising a first emulsifier with an HLB 1 to 8 and a second emulsifier with an HLB of greater than 14 that in combination provides a combination HLB of between 8.5 to 16.0, and a droplet size of less than 500d.nm, a thickener, the thickener being a polysaccharide thickener, greater than 60% w / v water, and the composition having a viscosity of 500 to 5,000 cP at 21 °C, a pH of 4 to 7, and being in the form of an oil-in-water nanoemulsion.

2. The composition of claim 1 , wherein the CBD:THC ratio is 20:1 .

3. The composition of claim 1 or claim 2, comprising about 0.25 to about 1 .0 % w / v of CBD and about 0.0125 to about 0.05 % w / v of THC.

4. The composition of any one of claims 1 to 3, comprising about 0.5 % w / v of CBD and about 0.025 % w / v of THC.

5. The composition of any one of claims 1 to 4, wherein the cannabidiol (CBD) and the tetrahydrocannabinol (THC) are purified isolates.

6. The composition of any one of claims 1 to 4, wherein the cannabidiol (CBD) and the tetrahydrocannabinol (THC) have a purity of greater than 90% by weight.

7. The composition of any one of claims 1 to 4, wherein the cannabidiol (CBD) and the tetrahydrocannabinol (THC) have a purity of greater than 95% by weight.

8. The composition of any one of claims 1 to 4, wherein the cannabidiol (CBD) and the tetrahydrocannabinol (THC) have a purity of greater than 99% by weight.

9. The composition of any one of claims 1 to 8 comprising a microbial preservative system comprising two or more preservatives, each preservative being from a different chemical class.

10. The composition of claim 9 wherein at least one of the microbial preservatives is from the chelating class of microbial preservatives.

11. The composition of any one of claims 1 to 10 comprising an antioxidant.

12. The composition of any one of claims 1 to 11 , wherein the pharmaceutically compatible surfactant comprises polyethylene glycol, and / or polyoxyethylene sorbitan fatty acid esters.

13. The composition of any one of claims 1 to 12, wherein the pharmaceutically compatible surfactant comprises polyethylene glycol (PEG) distearate, polyoxyethylene (40) stearate, and / or polyoxyethylene (80) sorbitan monooleate (polysorbate 80).

14. The composition of any one of claims 1 to 13, wherein the pharmaceutically compatible carrier oil comprises a medium chain triglyceride (MOT).

15. The composition of claim 14, wherein the MOT is derived from plants selected from one or more of canola oil, olive oil, sunflower oil, coconut oil, hemp oil, palm oils, or fractions thereof.

16. The composition of any one of claims 1 to 15, wherein the pharmaceutically compatible emulsifier comprises soy lecithin.

17. The composition of any one of claims 1 to 16, wherein the composition has a viscosity of about 1 ,000 to about 4,000 cP at 21 °C .

18. The composition of any one of claims 1 to 17, wherein the composition has an Z-average droplet size of less than about 10Od.nm to about 500d.nm.

19. The composition of any one of claims 1 to 18, comprising greater than 70% w / v water.

20. The composition of any one of claims 1 to 18, comprising greater than 80% w / v water.21 . The composition of any one of claims 1 to 18, comprising greater than 90% w / v water.

22. The composition of any one of claims 1 to 21 , further comprising one or more of an antimicrobial, an antioxidant, a mineral, a vitamin, a viscosity modifier, and a preservative.

23. The composition of any one of claims 1 to 22, comprising:0.25 to 1 .0 % w / v CBD,0.0125 to 0.05 % w / v THC,2.0 to 3.0 % w / v PEG distrearate,0.5 to 1 .5 % w / v medium chain triglycerides,0.5 to 1 .5 % w / v soy lecithin,0.01 to 0.02 % w / v vitamin E,0.0025 to 0.01 % w / v antimicrobial,0.0025 to 0.01 % w / v antioxidant, and93 to 97 % w / v water.

24. A method of preparing a composition, the method comprising:• heating a pharmaceutically compatible surfactant to a first temperature,• mixing the heated pharmaceutically compatible surfactant with a pharmaceutically compatible carrier oil and a pharmaceutically compatible emulsifier to produce a pre-emulsion concentrate,• cooling the pre-emulsion concentrate to a second temperature to produce a cooled preemulsion concentrate,• mixing the cooled pre-emulsion concentrate with CBD and THC,• adding the cooled pre-emulsion to water having a temperature of the second temperature to produce an emulsion, and• stirring the emulsion for a predetermined time and at a predetermined speed,• to produce an oil-in-water nanoemulsion comprising one or more cannabinoids.

25. The method of preparing an composition of claim 24, wherein the pharmaceutically compatible surfactant comprises polyethylene glycol, and / or polyoxyethylene sorbitan fatty acid esters.

26. The method of preparing an composition of claim 24 or claim 25, wherein the pharmaceutically compatible carrier oil comprises a medium chain triglyceride (MCT).

27. The method of preparing a composition of claim 26, wherein the MCT is derived from plants selected from one or more of canola oil, olive oil, sunflower oil, coconut oil, hemp oil, palm oils, or fractions thereof.

28. The method of preparing a composition of any one of claims 24 to 27, wherein the pharmaceutically compatible emulsifier comprises soy lecithin.

29. The method of preparing an composition of any one of claims 24 to 28, wherein the first temperature is about 45 to about 55 °C.

30. The method of preparing an composition of any one of claims 24 to 29, wherein the second temperature is about 35 to about 45 °C.31 . The method of preparing an composition of any one of claims 24 to 30, wherein the method is carried out using a high shear mixer.

32. The method of preparing an composition of claim 31 , wherein the pre-emulsion mixture is added while stirring at the predetermined speed using a high shear mixer emulsifier workhead.

33. The method of preparing an composition of any one of claims 24 to 32, wherein the predetermined time is about 20 to about 40 minutes.

34. The method of preparing an composition of any one of claims 24 to 33, wherein the predetermined speed is about 5,000 to about 10,000 rpm.

35. The method of preparing an composition of any one of claims 24 to 34, wherein the stirring for a predetermined time and at a predetermined speed is maintained at a rate of about 0.2 to about 0.3 kW / h per litre at 1 ,5A.

36. The method of preparing an composition of any one of claims 24 to 35, further comprising adding one or more of an antimicrobial, an antioxidant, a mineral, a vitamin, a viscosity modifier, and a preservative.

37. The method of preparing an composition of claim 36, wherein the composition is cooled and deaerated for a predetermined time, and one or more of the antimicrobial, the antioxidant, the viscosity modifier, and the preservative is added after cooling.

38. The method of preparing an composition of claim 36 or 37, wherein the viscosity modifier is added while mixing with a high shear mixer chopping stirrer blade at about 1 ,000 rpm.

39. The method of preparing an composition of any one of claims 36 to 38, wherein the antimicrobial, the antioxidant, and the preservative are added while mixing at 500 rpm.

40. A method for treating or ameliorating symptoms of arthritis in a subject comprising• providing a composition having a viscosity of 500 to 5,000 cP at 21 °C and being in the form of an oil-in-water nanoemulsion, the composition comprising a cannabidiol (CBD) and a tetrahydrocannabinol (THC) at a CBD:THC ratio of about 5:1 to about 80:1 , a pharmaceutically compatible surfactant, a pharmaceutically compatible carrier oil, a pharmaceutically compatible emulsifier, greater than 60% w / v water, and• applying the composition on to the food of the subject to be treated to provide 0.25 to 1 .0 mg of CBD and 0.0125 to 0.05 mg of THC per kg of subject weight.41 . The method of claim 40, wherein the subject is a companion animal.

42. The method of claim 40 or claim 41 , wherein the companion animal is a canine animal.

43. The method of any one of claims 40 to 42, wherein the food comprises dry or wet food.

44. The method of any one of claims 40 to 43, wherein the symptoms of arthritis is caused by rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), fibromyalgia, or gout arthritis.

45. The method of any one of claims 40 to 44, wherein the target dose for CBD is about 0.5 mg per kg and the target does for THC is 0.025 mg per kg.

46. The method of any one of claims 40 to 45, wherein the composition is applied to food for consumption by the subject daily, twice daily, or thrice daily.

Images