GB2587621A

GB2587621A - Oral films and a methods for the manufacture and delivery thereof

Info

Publication number: GB2587621A
Application number: GB1914102.7A
Authority: GB
Inventors: Alexander Livingstone Mark; Edward Cullen John; Circhton Robert
Original assignee: Biofilm Ltd
Current assignee: Biofilm Ltd
Priority date: 2019-09-30
Filing date: 2019-09-30
Publication date: 2021-04-07
Also published as: GB201914102D0; WO2021064357A1

Abstract

An oral film comprising two or form film forming polymers, of pullulan (15-60 wt%), and preferably pectin (3-12 wt%), polyvinylpyrrolidone (20-40 wt%), cellulose (5-25 wt%), a cannabinoid composition (5-60 wt%), free from psychoactive compounds (CBD), water (3-15 %wt), with a film thickness of 50-500 µm, with the cannabinoid is present at least 0.15 mg/mm3. Also included may be preservative, emulsified, plasticizer, surfactant, sweetener, flavouring, colouring, anti-tack agent, disintegrating agent, opacifying agent. The film dissolves in contact with oral or buccal mucosa from 1 second to 5 minutes or 10 minutes to 120 minutes. A method of making the film comprises mixing the cannabinoid composition with the water, mixing in the two or more polymers, coating the liquid onto a backing to sheet to form a layer with a thickness of 100-4000 µm, drying the layer to give a film with a water content of 3-15 wt%. The film is air dried with heated air, from 10-120 minutes, by passing it through a drying tunnel. The film is cut into strips with a width of 10-30 mm, and a length of 10-85 mm.

Description

ORAL FILMS AND A METHODS FOR THE MANUFACTURE AND DELIVERY

THEREOF

FIELD OF THE INVENTION

The present invention relates to oral films for the delivery of a cannabinoid composition and more particularly to orally soluble, mucoadhesive cannabinoid films. Also provided is a method for the making the oral film and a method of administering such an oral film to deliver a cannabinoid composition.

BACKGROUND

Cannabinoids are a class of chemical compounds which act on cannabinoid receptors which alter neurotransmitter release in the human brain. Phytocannabinoids encompass over 100 cannabinoid compounds naturally produced by plants, such as those of the genus cannabis. Psychoactive cannabinoids include tetrahydrocannabinol (THC), which can be used in the treatment of neuropathic pain and other conditions. Cannabinoid compositions which are free from psychoactive cannabinoids, such as those free from THC, may be used as nutritional or dietary supplements. Although such cannabinoid compositions provide little nutritional benefit if ingested, their bioavailability can be significantly improved when absorbed into the bloodstream via the buccal cavity.

Oral delivery of cannabinoids may provide relatively low bioavailability. Other methods of delivery for cannabinoids include sub-lingual delivery, which may provide a higher bioavailability. Dosage formats delivered via this route include tinctures of oils administered via a syringe or dropper and fast dissolving films. However, these dosage formats suffer from the fact that a significant quantity of the delivered dose may be swallowed rather than be absorbed via sub-lingual delivery, resulting in a sub-optimal delivery of the cannabinoid. Additionally, in the case of an oil tincture, a variable dose of the cannabinoid oil is delivered due to the difficulty of accurately controlling the quantity added and the physical difficulties associated with administration to the sub-lingual area.

Current topical sub-lingual administration to a mucosal surface mainly involves delivery in the form of liquids, pastes, gels, patches, disks and pressed tablets. These forms often dissolve, spread easily, or get dislocated. Other oral compositions may be provided in the solid state in the form of a strip or film which adheres to mucosa! surfaces upon contact with saliva. These solid strips are simple to use and if provided in adhesive form may remain in place for sufficient time to deliver an agent by absorption. Accordingly, there is a need to provide an oral film for the delivery of cannabinoids to an oral cavity, such as under the tongue or the buccal mucosa.

Additionally, it can be difficult to incorporate an agent, such as a one or more cannabinoids for delivery into such strips or films. For instance, agents may lack the requisite solubility to form a solid solution in the oral film. Instead, the agent precipitates as solid particulates in the composition, which may be unevenly distributed throughout the solid composition.

Furthermore, the concentration of the cannabinoid in the raw form of a resin or when dissolved in an oil, can be low such that it is difficult to formulate a dosage form which has a sufficient quantity of the cannabinoid present without the film being dimensionally too large for easy application to a buccal surface. Accordingly, there is a need to provide an oral film in which one or more cannabinoids are evenly distributed and that is of a size that can be easily applied by the consumer to the mucosal surface.

Cannabinoid compositions for oral delivery are typically formulated as films with a dose of 10 to 25 mg cannabinoid oil. Cannabinoid oil may contain a mixture of non-psychoactive cannabinoids, particularly non-psychoactive phytocannabinoids. Higher doses of cannabinoid oil necessitate an increase in the thickness of the oral film. Such an increase in film thickness is difficult to achieve and may lead to a deterioration in film properties and/or may lead to a film of such thickness that it is unsuitable for administration.

A need therefore exists for oral films comprising one or more cannabinoids which can carry an increased dose of cannabinoid, whilst remaining relatively thin. Furthermore, the existing compositions generally provide only a short-term delivery. It is further desirable in certain aspects to provide an oral film that provides a longer-lasting delivery of one or more cannabinoids compared to existing products. The provision of a buccal film with an increased lifetime means that a higher delivery of cannabinoid may be achieved because the film takes longer to dissolve, thereby avoiding decreased bioavailability resulting from the disintegration of the film and the swallowing of the cannabinoids.

This invention relates to a pliable and soluble mucoadhesive oral film that is capable of providing targeted delivery of one or more cannabinoids to the buccal cavity or other oral mucosal surfaces and also to other oral surfaces such as gums.

In certain aspects, the invention relates to a mucoadhesive buccal film that is capable of providing targeted and long-lasting delivery of one or more cannabinoids to the buccal cavity. As previously discussed, the buccal delivery of cannabinoids may provide a higher bioavailability compared to oral delivery.

SUMMARY OF THE INVENTION

The present disclosure relates to oral films that are in a solid form and may be applied to inside the oral or buccal cavity. The solid film is pliable, mucoadhesive, and may be slowly soluble such that it provides sustained delivery within the oral or buccal cavity. The oral films overcome deficiencies of the prior art enabling the one or more cannabinoids to be delivered systemically via delivery to the buccal mucosa.

The oral film can be easily molded onto another surface, including substantially uneven surfaces, within the oral cavity to deliver the one or more cannabinoids thereto.

It certain aspects, it can provide good adhesion for maximum sustained delivery of one or more cannabinoid and hence, a longer duration of action.

In a first aspect, there is provided an oral film comprising: two or more film forming polymers comprising pullulan and at least one further film forming polymer, the two or more film forming polymers present in a total amount of from about 18% to about 80% by weight; a cannabinoid composition present in a total amount of from about 5% to about 60% by weight; water present in an amount of from about 3% to about 15% by weight; each of the foregoing amounts being based on the total weight of the oral film; wherein the film has a thickness of from about 50 pm to about 500 pm and wherein the cannabinoid composition is present in an amount of at least 0.15 mg per mm3 of film.

The oral film may be further defined in relation to any one or more of the 5 following embodiments, which can be combined in any order and number.

In one embodiment, the pullulan may be present in an amount of from about 15% to about 60% by weight, preferably in an amount of from about 30% to about 50% by weight.

In another embodiment, the at least one further film forming polymer of the oral film is selected from the group comprising pectin, polyvinylpyrrolidone, cellulose and combinations thereof. Preferably, when the at least one further film forming polymer comprises pectin, it is present in an amount of from about 3% to about 12% by weight, more preferably it is present in an amount of from about 7% to about 11% by weight.

Alternatively, when the at least one further film forming polymer comprises polyvinylpyrrolidone, it is present in an amount of from about 20% to about 40% by weight, more preferably in an amount of from about 30% to about 38%. Typically, when the at least one further film forming polymer comprises polyvinylpyrrolidone, the pullulan is present in an amount of from about 30% to about 40% by weight.

Alternatively, when the at least one further film forming polymer comprises cellulose, it is present in an amount of from about 5% to about 25% by weight, more preferably it is present in an amount of from about 7% to about 13% by weight. Preferably, when the at least one further film forming polymer comprises cellulose, it is present in combination with one or both of pectin and polyvinylpyrrolidone. More preferably, the at least one further film forming polymer comprises pectin and cellulose.

Typically, when the at least one further film forming polymer comprises pectin and cellulose, the pullulan is present in an amount of from about 30% to about 40% by weight, the pectin is present in an amount of from about 7% to about 11% by weight and the cellulose is present in an amount of from about 7% to about 13% by weight.

In another embodiment, the cannabinoid composition may comprise one or more 30 cannabinoids. The cannabinoid composition may be free from psychoactive compounds, particularly psychoactive cannabinoids. Cannabinoid compositions free from psychoactive compounds, particularly psychoactive cannabinoids such as tetrahydrocannabinol, have utility as nutritional or dietary supplements. Thus, the cannabinoid composition may be a non-medicinal cannabinoid composition. Alternatively, the cannabinoid composition may contain one or more psychoactive compounds, particularly psychoactive cannabinoids such as tetrahydrocannabinol. Thus, the cannabinoid composition may be a medicinal cannabinoid composition. Cannabinoid compositions comprising tetrahydrocannabinol may be used in therapy, for instance in the treatment of neuropathic pain.

In another embodiment, the cannabinoid composition may be selected from the group comprising cannabinoid oil, cannabinoid resin and cannabinoid isolate. Such cannabinoid oil, cannabinoid resin and cannabinoid isolate may be free from psychoactive cannabinoids as discussed above.

In another embodiment, the oral film may further comprise one or more further components selected from the group comprising a preservative, an emulsifier, a plasticizer, a surfactant, a sweetening agent, a flavouring agent, a colouring agent, an anti-tack agent, a disintegrating agent and an opacifying agent.

In another embodiment, the buccal film can comprise a preservative. Non-limiting examples of suitable preservatives include, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), potassium sorbate, sodium sorbate, sodium benzoate, and the like. One or more preservatives can be included in the buccal film in a total amount of about 0.5% to about 5% by weight, preferably about 1.5% to about 2.5% by weight.

In another embodiment, the oral film may further comprise an emulsifier. Preferably, the emulsifier is present in an amount of from about 0.5% to about 5%, more preferably from about 1.5% to about 2.5% by weight. Preferred emulsifiers may be lecithins such as soy lecithin.

In another embodiment, the oral film may further comprise a plasticizer. Preferably the plasticizer is present in a total amount of from about 5% to about 30%, more preferably from about 18% to about 23% by weight. Preferred plasticizers include one or both of sorbitol and glycerol. More preferably, the oral film comprises both sorbitol and glycerol. Preferably, when the plasticizer comprises sorbitol, it is present in an amount of from about 5% to about 20% by weight, more preferably it is present in an amount of from about 13% to about 18% by weight. Preferably, when the plasticizer comprises glycerol, it is present in an amount of from about 2.5% to about 7% by weight, more preferably it is present in an amount of from about 4% to about 6% by weight.

In another embodiment, the oral film may further comprise a surfactant. Preferably the surfactant is present in an amount of from about 1% to about 5%, more preferably from about 2% to 3% by weight. Preferred surfactants include non-ionic surfactants, particularly polyoxyethylene sorbitan monooleates.

In another embodiment, the oral film may further comprise a sweetening agent.

Preferably the sweetening agent is present in an amount of from about 0.05% to about 1%, more preferably from about 0.1% to about 0.3% by weight. Preferred sweetening agents include sucralose.

In another embodiment, the oral film may further comprise a flavouring agent.

is Preferably the flavouring agent may be present in an amount of from about 0.03% to about 6%, preferably from about 2% to 3.5% by weight. Preferred flavouring agents include one or both of peppermint and menthol.

In another embodiment, the oral film may further comprise a colouring agent.

Preferably the colouring agent is present in an amount of from about 0.03% to about 1%, more preferably from about 0.1% to about 0.3% by weight. Preferred colouring agents include brilliant blue.

In another embodiment, the oral film may further comprise an anti-tack agent. Preferably the anti-tack agent is present in an amount of from 0.1% to about 20%, more preferably from about 1% to about 10% by weight. Preferred anti-tack agents may be one or more selected from the group comprising talc, colloidal silicon dioxide, a silicate salt, such as calcium silicate or magnesium silicate, and starch.

In another embodiment, the oral film may further comprise a disintegrating agent. Preferably the disintegrating agent is present in an amount of from 0.1% to about 20%, more preferably from about 1% to about 10% by weight. Preferred disintegrating agents 30 may be one or more selected from the group comprising carboxymethylcellulose, hydroxypropyl cellulose, croscarmellose sodium, sodium alginate, sodium starch glycolate.

In another embodiment, the oral film may further comprise an opacifying agent. Preferably the opacifying agent is present in an amount of about 0.02% to about 2% by weight. Preferred opacifying agents include titanium dioxide.

In another embodiment, the oral film may be configured to dissolve substantially completely in contact with oral or buccal mucosa in a time of about 10 minutes to about 150 minutes, typically from about 15 minutes to about 120 minutes.

In an alternative embodiment, the oral film may be configured to dissolve lo substantially completely in contact with oral or buccal mucosa in a time of 5 minutes or less, such as about 1 second to 5 minutes, typically in a time of 1 minute or less, such as about 1 second to 1 minute, more typically in a time of 30 seconds or less, such as about 1 second to 30 seconds.

In a second aspect, there is provided a method of making an oral film comprising: mixing the cannabinoid composition with water to form a premix; mixing into the premix at least the following components to form a liquid composition: two or more film forming polymers comprising pullulan and at least one further film forming polymer; coating the liquid composition onto a backing sheet to form a layer of the composition having a thickness of about 100 pm to about 4,000 pm; drying the layer to form the oral film having a total water content of from about 3% to about 15% by weight based on the total weight of the film.

The method of making the oral film may be defined in relation to any one or more of the following embodiments, together with those of the first aspect, which can be combined in any order and number.

In one embodiment of the second aspect, the oral film comprises: the two or more film forming polymers present in a total amount of from about 18% to about 80% by weight; the cannabinoid composition present in an amount of from about 5% to about 60% by weight; each of the foregoing amounts being based on the total weight of the oral film. In another embodiment, the further film forming polymer may be selected from one or both of pectin and polyvinylpyrrolidone.

In another embodiment, the step of mixing the cannabinoid composition with water to form a premix may further comprise mixing one or more further liquid components. The one or more further liquid components may comprise one or more of a liquid preservative, a liquid emulsifier, a liquid plasticizer, a liquid surfactant, a liquid sweetening agent, a liquid flavouring agent, a liquid colouring agent and a liquid opacifying agent. Preferably the one or more further liquid components comprise one or io more of a liquid surfactant, such as a liquid non-ionic surfactant, a liquid plasticizer, a liquid flavouring and a liquid colouring agent.

In another embodiment, the method may further comprise, between the step of mixing the cannabinoid composition with water and the step of mixing the at least two film forming polymers into the premix, the step of mixing one or more further solid is components into the premix. The one or more further solid components may comprise one or more of a solid preservative, a solid emulsifier, a solid plasticizer, a solid surfactant, a solid sweetening agent, a solid flavouring agent, a solid colouring agent and a solid opacifying agent. Preferably, the one or more further solid components may comprise a solid flavouring agent, such as menthol and a solid sweetening agent, such as sucralose.

In another embodiment of the method, the drying comprises applying heated air to the layer of the composition on the backing sheet for a time of about 20 minutes to about 150 minutes, typically from about 20 minutes to about 120 minutes. Preferably, the heated air is applied from one or both of from above and from below the layer of the composition. In one embodiment the heated air can be applied only from above the layer of the composition. The drying may be carried out by passing the layer of the composition on the backing sheet through a drying tunnel.

In another embodiment, the drying step may provide the oral film with a water content of from about 3% to about 15%, about 5% to about 12% by weight, based on the total weight of the oral film.

In another embodiment, the method may further comprise, after the drying step, removing the oral film from the backing sheet.

In another embodiment, the method may further comprise, after the drying step, the step of cutting the oral film into individual strips having a width of from about 10 mm to about 30 mm and having a length of from about 10 mm to about 85 mm, preferably a width of from about 5 mm to about 25 mm and having a length of from about 10 mm to about 85 mm, more preferably of from about 15 to about 60 mm Most preferably the film is cut to a length of from about 30 to about 38 mm.

In a third aspect, there is provided an oral film obtainable by the method of 10 making of the second aspect and its embodiments.

In a fourth aspect, there is provided a method of delivering a cannabinoid composition to an oral or buccal cavity comprising at least the step of: -applying the oral film as described herein to a portion of an oral or buccal cavity. In further embodiments, the method of administering the active agent may be defined in relation to any one or more of the following statements, which can be combined in any order and number.

The method may be a non-medicinal method, such as for the delivery of a cannabinoid composition which is free from psychoactive compounds as a dietary or nutritional supplement.

The method may be a method of treatment, such as for the delivery of a cannabinoid composition comprising one or more psychoactive cannabinoids such as tetrahydrocannabinol. Such a method may be for the treatment of neuropathic pain.

DETAILED DESCRIPTION OF THE INVENTION

The disclosure may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Like numbers refer to like elements throughout. As used in this specification and the claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. As used in this specification, the term "comprising" may be replaced by the term "consisting essentially of' or "consisting of".

As used in this specification, the term "molecular weight" refers to weight average molecular weight. As used herein, the terms "(Yo by weight" and "wt.%" refer to the dry weight of the oral film.

As used in this specification, the term "liquid", such as a "liquid component", refers to a material in the liquid state at the relevant temperature, for instance the temperature at which the method of making the buccal film is carried out, such as ambient or room temperature. Similarly, the term "solid" such as a "solid component", refers to a material in the solid state at the relevant temperature, for instance the temperature at which the method of making the buccal film is carried out, such as ambient or room temperature.

The present invention is directed to oral films that are mucoadhesive, pliable, orally soluble, and adapted for delivery of a cannabinoid composition to the buccal cavity or an oral surface, such as the gums or buccal pouch, over a prolonged period of time. The delivery of the cannabinoid composition to the buccal cavity or an oral surface allows the absorption of cannabinoids into the bloodstream for delivery as dietary or nutritional agents or if a psychoactive cannabinoid such as THC is present, for the delivery of a medicament.

The oral film can be sized to be able to cover a suitably large area of the oral surface in order to provide the delivery of the cannabinoid composition without substantial migration of the cannabinoids to other portions of the oral cavity. Thus, the oral films provide targeted delivery of the cannabinoids to provide sustained delivery of the cannabinoids to the buccal mucosa.

The oral film is provided in substantially solid form with a substantially uniform shape. The oral film is preferably a solid or semi-solid up to a temperature of at least 40°C. Such films can each be configured to have a length and a width that is substantially greater than a thickness thereof. It is preferred that the oral film can be applied to an area of the oral cavity so that the oral film will be in the form of a substantial solid after application to the area of the oral cavity. Preferably, the oral film is provided in a substantially solid form before application to the area of the oral cavity to provide for simplified application by the user. The oral film, being in a substantially solid form after application to the area of the oral cavity, can be configured to dissolve over time to deliver the cannabinoid composition locally at the site of application in the oral or buccal cavity.

Dissolution time can may vary as described herein. It is preferred that the oral film is provided with a thickness of about 50 pm to about 500 pm, about 100 pm to about 450 pm, about 120 pm to about 4250 pm, or about 140 pm to about 400 pm. In some embodiments, the film can have a thickness of about 450 pm or less, about 425 pm or less, or about 400 pm or less. In such cases, it is understood that the film has a minimum thickness that is greater than or equal to 50 pm. The film can be provided in the form of strips having a width and length that provide for ease of application to the io area of the oral cavity, ease of handling generally, and sufficiently broad area of coverage in the oral cavity to provide sufficient local delivery of the cannabinoid composition. For example, the film can have a width of about 5 mm to about 25 mm, preferably about 20 mm to 25 mm or about 10 mm to about 20 mm. The film can have a length of about 10 mm to about 85 mm, about 15 mm to about 60 mm, preferably is about 30 mm to about 35 mm or about 20 mm to about 30 mm.

The oral film comprises the cannabinoid composition in an amount of at least 0.15 mg per mm3 of film. In order to achieve such a loading of cannabinoid composition per unit volume of film, it was found that a combination of at least two film forming polymers comprising pullulan and at least one further film forming polymer was required. It was found that in the absence of a combination of pullulan and at least one further film forming polymer, such cannabinoid composition loadings could not be achieved, either because phase separation of the components of the oral film occurred, for instance such that the cannabinoid composition was not uniformly distributed throughout the oral film or it was not possible to cast the liquid composition into an oral film or drying the liquid composition yielded a cracked oral film.

The oral film according to the present disclosure can comprise two or more forming polymers comprising pullulan and at least one further film forming polymer. Consequently, pullulan is always present as one of the at least two film forming polymers. Pullulan is a polysaccharide polymer consisting of maltotriose units. In preferred embodiments, it has been found that particularly suitable films can be prepared when the further film forming polymer is selected from one or more of the group comprising pectin, polyvinylpyrrolidone and cellulose. In some embodiments, a combination of pullulan and pectin may be utilized as the two or more film forming polymers. In other embodiments, a combination of pullulan and polyvinyl pyrrolidone may be utilized as the two or more film forming polymers. In other embodiments, a combination of pullulan and cellulose may be utilized as the two or more film forming polymers. In other embodiments, a combination of pullulan, pectin and cellulose may be utilized as the two or more film forming polymers. In other embodiments, a combination of pullulan, polyvinyl pyrrolidone and cellulose may be utilized as the two or more film forming polymers. In other embodiments, a combination of pullulan, pectin lo and polyvinyl pyrrolidone may be utilized as the two or more film forming polymers. In further embodiments, a combination of pullulan, pectin, polyvinyl pyrrolidone and cellulase may be utilized as the two or more film forming polymers.

Preferably, the at least two film forming polymers comprise pullulan and pectin, optionally in combination with cellulose.

The two or more film forming polymers are present in a total amount of from about 18% to about 80% by weight. Preferably, the pullulan may be present in an amount of from about 15% to about 60% by weight, more preferably in an amount of from about 30% to about 50% by weight.

In addition to pullulan, at least one further film forming polymer is present in the oral film. The at least one further film forming polymer may comprise pectin, polyvinylpyrrolidone and combinations thereof. The use of such further film forming polymers decreases the dissolution rate of the oral film, increasing its residence time in the oral or buccal cavity to allow prolonged delivery of the cannabinoid composition. Preferably, when the at least one further film forming polymer comprises pectin, it is present in an amount of from about 3% to about 12% by weight, more preferably it is present in an amount of from about 7% to about 11% by weight.

Alternatively, when the at least one further film forming polymer comprises a polyvinylpyrrolidone, it is present in an amount of from about 20% to about 40% by weight, more preferably in an amount of from about 30% to about 38%. Typically, when the at least one further film forming polymer comprises polyvinylpyrrolidone, the pullulan is present in an amount of from about 30% to about 40% by weight.

If it is desirable to increase the dissolution rate of the film, the at least one further film forming polymer may comprise cellulose, such as microcrystalline cellulose. Preferably the cellulose may have a molecular weight in the range of from about 20 000 Da to about 50 000 Da, more preferably about 30 000 Da to about 40 000 Da. In addition to its film forming properties, cellulose acts as a disintegrating agent to increase the dissolution rate of the film, and as an anti-tack agent allowing stacks of film to be stored without sticking together. When the at least one further film forming polymer comprises cellulose, it is present in an amount of from about 5% to about 25% by weight, more preferably it is present in an amount of from about 7% to about 13% by lo weight. Preferably, when the at least one further film forming polymer comprises cellulose, it is present in combination with one or both of pectin and polyvinylpyrrolidone. More preferably, the at least one further film forming polymer comprises pectin and cellulose. Typically, when the at least one further film forming polymer comprises pectin and cellulose, the pullulan is present in an amount of from about 30% to about 40% by weight, the pectin is present in an amount of from about 7% to about 11% by weight and the cellulose is present in an amount of from about 7% to about 13% by weight.

In some embodiments, at least two film forming polymers may be utilized in a defined ratio. For example, pullulan and a polyvinylpyrrolidone may be combined in a ratio of 3:1 to 1:3, 2:1 to 1:2, or preferably about 1:1. Pullulan and pectin may be combined in a ratio of 7:1 to 3:1, preferably about 5:1. Such ranges were found to provide high loading of the cannabinoid composition in the oral film, whilst also providing a delivery duration of at least 15 minutes.

A cannabinoid composition is included in the oral film. The cannabinoid composition may comprise one or more cannabinoids, particularly one or more phytocannabinoids. The one or more phytocannabinoids may be a botanical extract of cannabinoids such as a cannabidiol extract or resin from a plant of the genus cannabis, such as one or more compounds extracted and isolated from a plant of the genus cannabis. The botanical extract may include one or more compounds selected from the group comprising terpenes, tetrahydrocannabinols (THCs), cannabidiol (CBD), and/or can In one embodiment, the cannabinoid composition may contain one or more psychoactive compounds, particularly psychoactive cannabinoids such as tetrahydrocannabinol. The one or more psychoactive compounds may be present in a therapeutically effective amount. Thus, the cannabinoid composition may be a medicinal cannabinoid composition. Cannabinoid compositions comprising tetrahydrocannabinol may be used in therapy, for instance in the treatment of neuropathic pain.

In an alternative embodiment, the cannabinoid composition may be free from psychoactive compounds, particularly psychoactive cannabinoids. Cannabinoid lo compositions free from psychoactive compounds, particularly psychoactive cannabinoids such as tetrahydrocannabinol, have utility as nutritional or dietary supplements. Thus, the cannabinoid composition may be a non-medicinal cannabinoid composition. As used herein, there term "free from psychoactive compounds" means that the cannabinoid composition does not comprise any psychoactive compounds at psychotropic levels. For instance, the cannabinoid composition may comprise less than mg/g, preferably less than 2 mg/g psychoactive compounds such as THC.

In another embodiment, the cannabinoid composition may be selected from the group comprising cannabinoid oil, cannabinoid resin and cannabinoid isolate. Such cannabinoid oil, cannabinoid resin and cannabinoid isolate may be free from psychoactive compounds, such as psychoactive cannabinoids as discussed above. Alternatively, such cannabinoid oil, cannabinoid resin and cannabinoid isolate may be medicinal compositions comprising psychoactive cannabinoids as discussed above. For instance, cannabinoid oil resin may comprise or consist essentially of or consist of cannabidiol (CBD), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV) and cannabigerol (CBG). Alternatively, cannabinoid oil may consist essentially of or consist of cannabidiol (CBD), cannabidivarin (CBDV) and cannabigerol (CBG). Typically, cannabinoid oil resin may comprise from about 60% to about 70% cannabidiol, from about 5% to about 15% cannabidivarin, from about 0% to about 5% tetrahydrocannabivarin and from about 0.5% to about 4% cannabigerol by weight.

For instance, cannabinoid oil may comprise or consist essentially of or consist of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabigerol (CBG), cannabigerolic acid (CBGA), tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA). Alternatively, cannabinoid oil may consist essentially of or consist of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabigerol (CBG), cannabigerolic acid (CBGA), and tetrahydrocannabinolic acid (THCA). Further alternatively, cannabinoid oil may consist essentially of or consist of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabigerol (CBG) and cannabigerolic acid (CBGA). Typically, cannabinoid oil may comprise from about 6% to about 10% cannabidiol, from about 1% to about 3% cannabidiolic acid, from about 0.05% to about 0.15% cannabigerol, from about 0.02% to about 0.06% cannabigerolic acid, from about 0% to about 0.15% tetrahydrocannabinol and from lo about 0.01% to about 0.5% tetrahydrocannabinolic acid by weight.

It is apparent that whilst the cannabinoid resin comprises approximately from about 60% to about 70% cannabidiol, the corresponding oil comprises about 6% to about 10% cannabidiol. Consequently, the cannabinoid resin constitutes a more concentrated source of cannabidiol, and can therefore be used in smaller amounts compared to cannabinoid oil for a similar delivery of cannabidiol.

Furthermore, cannabinoid isolate may comprise or consist essentially of or consist of cannabidiol. Typically, cannabinoid isolate comprises at least 90%, preferably at least 95% and more preferably at least 99% cannabidiol by weight.

Preferably the cannabinoid composition may be present in the oral film in an amount of from about 15% to about 25% by weight, more preferably in an amount of from about 18% to about 22% by weight.

Water is present in the oral film. The water may be substantially pure water; however, salts, buffers, or the like also may be included in the water. In some embodiments, the water can comprise about 0.5% to about 15% by weight, typically about 3% to about 15%, or about 1% to about 14%, about 2% to about 13%, about 5% to about 12%, or about 7% to about 11% by weight of the overall oral film. The water content of the oral film may affect the film's properties. For example, it can be particularly useful for the film to be dried to a final moisture content or final water content, and such moisture content or water content can be within a range as defined above. The moisture level affects the properties of the film and its manufacture. When the moisture content of the composition is above 15% by weight, the film may have insufficient tensile strength and be too pliable. When the moisture content is below 0.5% by weight, the film may be too brittle.

In various embodiments, the oral film can further comprise one or more further components. The one or more optional further components may be selected from one or more of the group comprising a preservative, an emulsifier, a plasticizer, a surfactant, a sweetening agent, a flavouring agent, a colouring agent, an anti-tack agent, a disintegrating agent and an opacifying agent.

In further embodiments, the oral film can comprise one or more preservatives. Non-limiting examples of suitable preservatives include, butylated hydroxytoluene lo (BHT), butylated hydroxyanisole (BHA), potassium sorbate, sodium sorbate, sodium benzoate, and the like. One or more preservatives can be included in the oral film in a total amount of about 0.5% to about 5% by weight, preferably about 1.5% to about 2.5% by weight.

The buccal film may further comprise one or more emulsifiers. Preferably, the emulsifier is present in an amount of from about 0.5% to about 5%, more preferably from about 1.5% to about 2.5% by weight. Preferred emulsifiers may be lecithins such as soy lecithin.

The oral film can comprise one or more plasticizers, such as one or more physiologically acceptable plasticizers. In one embodiment, the plasticizer is a hydrophilic plasticizer, such as one or more of the group comprising a polyol such as glycerol, and monosaccharides, oligosaccharides, lipids, sorbitol and sorbitan. Preferred plasticizers are one or both of glycerol and sorbitol, more preferably both glycerol and sorbitol. Preferably, when the plasticizer comprises sorbitol, it is present in an amount of from about 5% to about 20% by weight, more preferably it is present in an amount of from about 13% to about 18% by weight. Preferably, when the plasticizer comprises glycerol, it is present in an amount of from about 2.5% to about 7% by weight, more preferably it is present in an amount of from about 4% to about 6% by weight.

The oral film may comprise one or more surfactants. The surfactant may be an ionic surfactant or a non-ionic surfactant. Preferably the non-ionic surfactant comprises one or more fatty acids, which may be saturated or unsaturated. More preferably the non-ionic surfactant comprises at least one unsaturated fatty acid such as oleic acid and/or linoleic acid and optionally at least one saturated fatty acid such as palmitic acid and/or stearic acid. Still more preferably, the surfactant comprises a polyoxyethylene sorbitan monooleate. Preferably the surfactant is present in the oral film in an amount of from about 1% to about 5%, more preferably from about 2% to 3% by weight.

The oral film may comprise one or more sweetening agents. The sweetening agent may be a sugar substitute, such as an artificial sugar substitute or a natural sugar substitute. The artificial sugar substitute may be selected from the group comprising sucralose, aspartame, advantame, saccharin, acesulfame potassium and cyclamate, 10 with sucralose being preferred. The natural sugar substitute may be selected from the group comprising erythritol, mannitol, stevia, sorbitol and xylitol. Preferably the sweetening agent is sucralose. In some embodiments, a sweetening agent can be present in an amount in the range of from about 0.05% to about 1%, more preferably from about 0.1% to about 0.3% by weight.

The oral film may comprise one or more flavoring agents. The flavouring agent may be an artificial flavouring or a natural flavouring. The flavouring agent may be one or more selected from the group comprising herb flavouring, such as mint, for instance spearmint or peppermint, a spice flavouring such as ginger, cinnamon or vanilla, a fruit flavouring such as apple, grape, orange, pear or strawberry and menthol. Preferably the flavouring agent is one or both of peppermint and menthol. More preferably the flavouring agent is peppermint and menthol. Preferably the flavouring agent may be present in an amount of from about 0.03% to about 6%, preferably from about 2% to 3.5% by weight. Preferably, when the flavouring agent comprises peppermint, it is present in an amount of from about 0.5% to about 5% by weight, more preferably it is present in an amount of from about 2% to about 3% by weight. Preferably, when the flavouring agent comprises glycerol, it is present in an amount of from about 0.03% to about 1% by weight, more preferably it is present in an amount of from about 0.2% to about 0.5% by weight.

The oral film may comprise one or more colouring agents. The colouring agents may be natural or artificial coloring agents as desired. Preferably, the colouring agent may be brilliant blue also known as FD & C blue no. 1 and lakes thereof. Preferably the colouring agent is present in an amount of from 0.03% to about 1%, more preferably from about 0.1% to about 0.3% by weight.

The oral film may comprise one or more anti-tack agents. An anti-tack agent is an anti-adherent which prevents films in their final form from adhering to each other or other surfaces such as the product pack. Preferably the anti-tack agent is present in an amount of from 0.1% to about 20%, more preferably from about 1% to about 10% by weight. Preferred anti-tack agents may be one or more selected from the group comprising talc, colloidal silicon dioxide, a silicate salt, such as calcium silicate or magnesium silicate, and starch.

The oral film may comprise one or more disintegrating agents. A disintegrating agent is a material that enables more rapid disintegration of the film either by swelling or water wicking and thus increases the rate of water uptake and thus dissolution of the film. Preferably the disintegrating agent is present in an amount of from 0.1% to about 20%, more preferably from about 1% to about 10% by weight. Preferred disintegrating is agents may be one or more selected from the group comprising carboxymethylcellulose, hydroxypropyl cellulose, croscarmellose sodium, sodium alginate, sodium starch glycolate.

The oral film can comprise one or more opacifying agents. Suitable opacifying agents can include any material suitable for causing a solid form of the oral film to be substantially opaque. For example, metal oxides may be utilized as opacifying agents, and specific, non-limiting examples of suitable metal oxides include titanium dioxide, zinc oxide, and iron oxide. Examples of other materials suitable for use as an opacifying agent include magnesium carbonate, talc, and the like. One or more opacifying agents, and particularly one or more metal oxides, may be included in the oral film in a total amount of about 0.02% to about 2% by weight, about 0.05% to about 1.5% by weight, or about 0.08% to about 1% by weight.

The present oral films can be particularly beneficial to deliver cannabinoid compositions to areas of the oral or buccal cavity. In such embodiments, the present oral films, particularly when on a surface of the oral cavity, are effective to deliver the cannabinoid compositions for an extended duration of time. While it is desirable for the oral film to be dissolvable within the oral or buccal cavity, the oral film must persist in the oral or buccal cavity for a sufficient time to deliver the cannabinoids. Preferably, the present oral film dissolves within the oral or buccal cavity after application to a surface thereof and provides the desired absorption into the bloodstream for a time of at least 10 minutes, at least 30 minutes, or at least 45 minutes (e.g., up to a time of about 150 minutes or up to a time of about 120 minutes). In some embodiments, the present oral film dissolves within the mouth and provides delivery of the cannabinoid composition for a time of about 10 minutes to about 150 minutes, or about 15 to about 120 minutes or about 45 minutes to about 120 minutes.

The ability to deliver the cannabinoid composition can depend upon the ability of the oral film to persist within the oral or buccal cavity, particularly being substantially adhered to a specific area of a surface of the oral or buccal cavity, for a sufficiently long period of time. It is generally understood that the oral film, when adhered to a surface of the oral or buccal cavity in a substantially solid form, will be expected to dissolve over time due to contact with saliva and/or other mucosal secretions within the oral or buccal cavity.

Preferably, a solid form of the oral film when substantially adhered to a surface of the oral or buccal cavity can remain in a semi-solid or solid state for a time of about 15 minutes or greater, about 20 minutes or greater, about 30 minutes or greater, or about 45 minutes or greater. It is understood that the solid form of the oral film will be expected to substantially completely dissolve within the oral or buccal cavity within a maximum time, such as a maximum time of about 150 minutes, or about 120 minutes. In certain embodiments, the oral film can remain in a semi-solid or solid state when in the oral or buccal cavity for a time of about 10 minutes to about 180 minutes, about 15 minutes to about 120 minutes, about 20 minutes to about 100 minutes, or about 30 minutes to about 90 minutes. As such, the oral film, when present in the oral or buccal cavity in a substantially solid form, can be configured to dissolve substantially completely when in contact with mucosa in a time of about 10 minutes to about 120 minutes.

Alternatively, when substantially adhered to a surface of the oral or buccal cavity can dissolve in less than 5 minutes, preferably less than 1 minute and more preferably less than 30 seconds. Typically, such forms of the oral film comprise cellulose as one of the at least one further film formers. The cellulose may function as a disintegrating agent to increase the dissolution rate.

In one or more embodiments, there is provided methods of making oral films as described herein. Preferably, the methods comprise first formulating a premix that includes the cannabinoid composition and water. Specifically, this can include dispersing the cannabinoid composition in water while mixing. This can be achieved, for example, using a homogenizer. The mixing can be carried out in a high shear mixer, for instance an Ultra-Turrax T-50 at speed 3. Any liquid components can also be added at this stage, such as one or more of the group comprising a liquid preservative, a liquid emulsifier, a liquid plasticizer, a liquid surfactant, a liquid sweetening agent, a liquid flavouring agent, a liquid colouring agent and a liquid opacifying agent.

Preferably the one or more further liquid components added at this stage may comprise one or more of a liquid surfactant, such as a liquid non-ionic surfactant, a liquid plasticizer, a liquid flavouring and a liquid colouring agent.

After the premix has been formed (i.e., the cannabinoid composition has been substantially dispersed in water), the remaining components of the oral film can be mixed into the premix to form the main mixture. At a minimum, the method of preparation can comprise mixing into the premix at least the two or more film forming polymers to form the liquid composition. The liquid composition will be a viscous liquid, and mixing thus may be carried out using, for example, a high shear vacuum mixer to achieve mixing and degassing of the solution to form a liquid composition. Mixing is preferably carried out until a substantially homogeneous mixture is achieved and all of the components of the oral film have been incorporated into the solution.

When one or more solid further solid components are present, the method may further comprise, between the step of mixing the cannabinoid composition with water and mixing the at least two film forming polymers into the premix, the step of mixing a one or more further solid components into the premix.

In another embodiment, the method may further comprise, between the step of mixing the cannabinoid composition with water and the step of mixing the at least two film forming polymers into the premix, the step of mixing one or more further solid components into the premix. The one or more further solid components may comprise one or more of the group comprising a solid preservative, a solid emulsifier, a solid plasticizer, a solid surfactant, a solid sweetening agent, a solid flavouring agent, a solid colouring agent and a solid opacifying agent. Preferably, a solid flavouring agent, such as menthol and a solid sweetening agent, such as sucralose may be added at this stage Optional further solid components can be added to the liquid composition after the addition of the two or more film forming polymers.

The so-formed liquid composition can then be cast as a film. To facilitate the forming of a film, the liquid composition can be coated onto a backing sheet to form a layer of the liquid composition having the desired thickness as otherwise described herein. The backing sheet preferably is coated with a release layer, such as a wax or similar coating that will all of the formed film to be readily released therefrom. A knife or other blade may be used to coat the liquid composition to the desired thickness. Preferably, the film has a sufficient viscosity such that, after coating onto the backing sheet, the liquid composition will not substantially spread and will thus remain substantially consistent in thickness across the total surface of the coated liquid composition.

The liquid composition may be cast as a film with a wet thickness in the range of from 0.1 to 4 mm, preferably of from 0.25 to 3 mm, more preferably from 0.5 to 1.5 11101, still more preferably about 1 mm.

The liquid composition finally can be dried to the desired total water content as otherwise described herein to achieve the end product in a substantially solid form. Drying can comprise applying heated air to the layer of the liquid composition on the backing sheet. Such heated air may be provided at a temperature that is above ambient and up to a temperature that is below the melting point of the film forming polymer(s). For example, the air can be a temperature of about 30°C to about 60°C. If desired, ambient temperature air or even cooled air may be applied to facilitate drying of the film. The drying air may be applied for a time of about 5 minutes to about 150 minutes, typically about 20 minutes to about 120 minutes. The oral film can be configured such that drying takes a minimum amount of time regardless of the application of drying air. Thus, while the application of the drying air can expedite drying, the film will typically take a time of at least 10 minutes, at least 20 minutes, at least 30 minutes, or at least 40 minutes to achieve the desired water content and thus be a self-supporting, solid composition that is no longer tacky and may be further processed for packaging of the product. In particular, drying may require a time of about 15 minutes to about 240 minutes, about 30 minutes to about 220 minutes, about minutes to about 200 minutes, or about 60 minutes to about 150 minutes. In some embodiments, the drying air may be applied from all sides, such as both above and below the layer of the liquid composition or only from below the layer of the composition or only from above the layer of the composition (and, as such, application of air from below the layer of the composition (i.e., application of air to the backing layer) may be excluded). As a non-limiting example, drying of the film may be carried out by passing the layer of the liquid composition on the backing sheet through a drying tunnel. In such tunnel, drying air may be applied along the entire length of the drying tunnel or only at a portion of the tunnel. Drying air may be forced air (e.g., provided via fans or blowers).

In some embodiments, convection heating may be used for drying. As such, heating elements above the film layer may generate convective currents that facilitate drying of the film.

After the film has dried, the film may be cut to desired dimensions. For example, this may comprise cutting the film into individual strips having a width of about 10 mm to about 30 mm and having a length of about 10 mm to about 85 mm. Cutting to other dimensions as otherwise described herein is also encompassed. The individual film strips may be packaged as desired into containers with a defined number of strips per package.

The oral film obtainable by the method of making disclosed herein may be used in a method of delivering a cannabinoid composition to an oral or buccal cavity. The method comprises at least the step of: applying the oral film obtained as described herein to a portion of an oral or buccal cavity.

The oral or buccal cavity may be that of a human.

In one embodiment, the method may be a non-medicinal method, such as for the delivery of a cannabinoid composition which is free from psychoactive compounds.

Such a cannabinoid composition which is free from psychoactive compounds may be used as a dietary or nutritional supplement.

In another embodiment, the method of delivering may be a method of treatment, such as for the administration of a cannabinoid composition comprising one or more psychoactive cannabinoids such as tetrahydrocannabinol. Such a method may be for the treatment of neuropathic pain.

In such methods, the oral film may first be released from its sterile packaging. Subsequently, any backing sheet is removed, for instance by peeling the oral film from the backing sheet. Once the oral film is free from any other layers, it may be applied to a portion of an oral or buccal cavity.

The present oral film is comfortable to use in the oral cavity. In addition, the oral films provide a soft, comfortable barrier. The present oral films remain substantially in place once adhered to a localized site within the oral cavity. The oral film can be easily molded and applied over the area of the oral cavity where administration is desired.

The film easily adheres to the gum or other oral mucosal surface and thereby provides delivery of the cannabinoid composition to the desired site. To this end, the film is preferably configured to be repositionable for a minimum period of time to allow for ease of application. Once the film has adhered to the oral surface, the film is substantially unable to be moved or removed and reapplied without tearing or otherwise destroying the film. Preferably, once the oral film has been applied and adhered to the surface of the oral cavity, the film remains in place for the duration of delivery of the cannabinoid composition (i.e., until complete dissolution of the oral film), and the film is not dislodged from its location by activities such as talking or drinking.

EXAMPLES

Table 1 below provides ingredients included in an embodiment of the oral film of the present invention. The components are listed by order of addition. Table 1 also includes the weight percentage of each ingredient, based on the total weight of the oral film. The primary function of each ingredient is also included.

Table 1: Oral Film Composition Ranges Batch Ingredient Function Weight Percentage Premix Water Polymeric solvent 3-15 wt. % Premix Cannabinoid composition Cannabinoid 5-60 wt. % Premix Peppermint Flavouring 0.5-5 wt. % Premix Glycerol Plasticizer 2.5-7 wt. % Premix Polysorbate 80 Non-ionic 1-5 wt. % surfactant Premix Brilliant Blue Colorant 0.03-1 wt. % Main Menthol Flavouring 0.03-1 wt. % Main Sucralose Sweetening agent 0.1-1 wt. % Main Sorbitol (Neosorb P60) Plasticizer 5-20 wt. % Main Soy lecithin Emulsifier 0.5-5 wt. % Main Polyvinylpyrrolidone or pectin Film forming 20-40 wt. % or 3-polymer 12 wt. % Main Pullulan Film forming 15-60 wt. % Main Cellulose polymer 5-25 wt.% Film forming polymer

Example 1

An oral film was prepared as follows according to the proportions shown in Table 2 below. Cannabinoid resin was added to a stainless steel pot. To this pot, water and the other liquid components such as the liquid non-ionic surfactant (Polysorbate 80), liquid plasticizer (glycerol), liquid flavouring (peppermint oil) and liquid colouring (Brilliant Blue) were added and the components mixed using an IKA Ultra Turrax T50 homogeniser at speed 3 for a duration of three minutes to form a premix. The solid flavourings, namely menthol and sucralose, solid plasticizer (sorbitol) and solid emulsifier (soy lecithin) were then added to the premix with the at least two film formers (pullulan and pectin) in portions while the components were mixed at speed 3 for six minutes to provide a liquid composition. Upon completion of the addition of the at least two film formers, the liquid composition was mixed at speed 4 for one minute.

The liquid composition was degassed under vacuum for fifteen minutes.

Table 2: Film content (DEV04704) Component Supplier % w/w Dry Cannabinoid resin C BD Oil 20.0 Europe Pullulan Nagase 44.0 Pectin Azelis 9.0 Glycerol Brenntag 5.0 Neosorb P60 (sorbitol) Roquette 14.6 Polysorbate 80 (non- Azelis 2.5 ionic surfactant) Soy lecithin Special Ingredients 1.9 Brilliant blue Claremant 0.2 Menthol Tastetech 0.3 Peppermint Givaudan 2.4 Sucralose Merck 0.2 The degassed liquid composition was cast at thickness of 1 mm using a Sheen 1133N Film Coater with stainless steel knife onto PE coated paper. The film was dried under an air drying hood for 25-40 mins to provide an oral film with a thickness of 0.205 MM.

The liquid composition produced was deemed to be of a good quality and the film produced was visually assessed and deemed to be of a high quality, i.e. an evenly dried, single-phase film with sufficient tensile strength to be further processed.

The oral film of Example 1 had a cannabinoid resin loading of 0.16 mg/mm3.

Example 2

An oral film was prepared in a similar manner to Example 1 but with the proportions shown in Table 3 below. In contrast to Example 1, no glycerol was added to the premix. Instead, an additional at least one further film forming agent of microcrystalline cellulose (Avicel supplied by DuPont) was added in addition to pectin. The microcrystalline cellulose was added at the same time as the other film forming polymers pullulan and pectin.

The liquid composition was degassed under vacuum for fifteen minutes.

Table 3: Film content (DEV04709) Component Supplier % w/w Dry Cannabinoid resin CBD Oil 25.0 Europe Pullulan Nagase 36.7 Pectin Azelis 9.0 Avicel (microcrystalline cellulose) DuPont 10.0 Neosorb P60 (sorbitol) Roquette 12.2 Polysorbate 80 (non- Azelis 2.5 ionic surfactant) Soy lecithin Special Ingredients 1.5 Brilliant blue Claremant 0.2 Menthol Tastetech 0.3 Peppermint Givaudan 2.4 Sucralose Merck 0.2 The degassed liquid composition was cast at three thicknesses, namely 0.35 mm 10 0.40 mm and 0.90 mm using a Sheen 1133N Film Coater with stainless steel knife onto PE coated paper. The film was dried under an air drying hood for 25-40 mins to provide final film thicknesses of 0.076 mm, 0.086 mm and 0.182 mm respectively.

The liquid composition produced were deemed to be of a good quality and the film produced was visually assessed and deemed to be of a high quality, i.e. an evenly dried, single-phase film with sufficient tensile strength to be further processed.

The oral films of Example 2 had a cannabinoid resin loading of 0.17 mg/me (for a film thickness of 0.076 mm); 0.19 mg/me (for a film thickness of 0.086 mm); and 0.18 mg/mm3 (for a film thickness of 0.182 mm).

This formulation allows for the oral films to be cast at a lower thickness whilst still providing a relatively high dose of cannabinoid per strip. As these strips are coated at less than 1 mm thickness they dissolve more quickly than the strip of Example 1.

Comparative Examples A-C An a prepared as follows according to the proportions shown in Table 4 below. Cannabinoid resin was added to a stainless steel pot. To this pot, water and the other liquid components were added as in Example 1 and the components mixed using an IKA Ultra Turrax T50 homogeniser at speed 3 for a duration of three minutes to form a premix. The colouring and flavourings, namely brilliant blue, peppermint and menthol were then added simultaneously and the premix mixed at speed 3 for a further three minutes. The at least two film formers (pullulan and pectin) were then added to the premix in portions while the components were mixed at speed 3 for six minutes to provide a liquid composition. Upon completion of the addition of the at least two film formers, the liquid composition was mixed at speed 4 for one minute.

The liquid composition was degassed under vacuum for fifteen minutes.

Table 4: Film content Component Supplier % w/w Dry Comparative Example A (DEV04685) Comparative Example B (DEV04690) Comparative

Example C

(DEV04693) Cannabinoid resin CBD oil 20.0 10.0 10 Europe Pullulan Nagase 63.5 - - Sodium alginate IMCD 71.7 -Polyvinylpyrrolidone BTC - 71.9 Glycerol Brenntag 8.7 9.8 9.8 Polysorbate 80 (non-ionic surfactant) Sigma Aldrich 3.2 3.6 3.6 Menthol Tastetech 0.9 0.9 0.9 Peppermint Givaudan 2.4 2.4 2.4 Titanium dioxide Azelis 1.4 1.4 1.4 The degassed liquid composition was cast at thickness of 1 mm using a Sheen 1133N Film Coater with stainless steel knife onto PE coated paper. The film was dried under an air drying hood for 25-40 mins.

The oral film of Comparative Example A contained only pullulan as the film forming polymer and was cast at a thickness of 0.55 mm to provide a cannabinoid resin loading of 0.12 mg/mm3. Any increase of the amount of cannabinoid resin beyond the level of 20% by weight in this formulation was found to result in a distinct phase separation between the cannabinoid resin and casting liquid composition.

The oral film of Comparative Example B contained only sodium alginate as the lo film forming polymer and was cast at a thickness of 0.55 mm to provide a cannabinoid resin loading of 0.09 mg/mm3. It was not possible to increase the coating thickness to 1 mm to increase the amount of cannabinoid resin delivered per film strip of a given surface area e.g. 32 x 22 mm.

The oral film of Comparative Example C contained only polyvinylpyrrolidone as the film forming polymer and was cast at a thickness of 1 mm to provide an cannabinoid resin loading of 0.06 mg/mm3. Although it was possible to cast this film at a coating thickness of 1 mm, it was relatively rigid and unsuitable to use as an oral film.

Many modifications and other embodiments of the disclosure will come to mind to one skilled in the art to which this disclosure pertains having the benefit of the teachings presented in the foregoing description; and it will be apparent to those skilled in the art that variations and modifications of the present disclosure can be made without departing from the scope or spirit of the disclosure. Therefore, it is to be understood that the disclosure is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

Claims

Claims 1. An oral film comprising: two or more film forming polymers comprising pullulan and at least one further film forming polymer, the two or more film forming polymers present in a total amount of from about 18% to about 80% by weight; a cannabinoid composition present in a total amount of from about 5% to about 60% by weight; water present in an amount of from about 3% to about 15% by weight; lo each of the foregoing amounts being based on the total weight of the oral film; wherein the film has a thickness of from about 50 pm to about 500 pm and wherein the cannabinoid composition is present in an amount of at least 0.15 mg per mm3 of film.
2. The oral film of claim 1 wherein the pullulan is present in an amount of from about 15% to about 60% by weight.
3. The oral film of claim 1 or claim 2 wherein the at least one further film forming polymer comprises pectin, polyvinylpyrrolidone and combinations thereof.
4. The oral film of any of the preceding claims wherein the at least one further film forming polymer comprises pectin in an amount of from about 3% to about 12% by weight.
5. The oral film of any of the preceding claims wherein the at least one further film forming polymer comprises polyvinylpyrrolidone in an amount of from about 20% to about 40% by weight.
6. The oral film of claim 5 wherein the pullulan is present in an amount of from about 20% to about 40% by weight.
7. The oral film of any of the preceding claims wherein the at least one further film forming polymer comprises cellulose in an amount of from about 5% to about 25% by weight.
8. The oral film of any of the preceding claims, wherein the cannabinoid composition is free from psychoactive cannabinoids and is selected from the group comprising cannabinoid oil, cannabinoid resin and cannabinoid isolate.
9. The oral film of any of the preceding claims, wherein the cannabinoid 10 composition is present in an amount of from about 15% to about 25% by weight.
10. The oral film of any of the preceding claims, further comprising one or more of: - a preservative in an amount of from about 0.5% to about 5% by weight; -an emulsifier in an amount of from about 0.5% to about 5% by weight; - a plasticizer in an amount of from about 5% to about 30% by weight; - a surfactant in an amount of from about 1% to about 5% by weight; - a sweetening agent in an amount of from about 0.05% to about 1% by weight; - a flavouring agent in an amount of from about 0.03% to about 6% by weight; 20 -a colouring agent in an amount of from 0.03% to about 1% by weight; - an anti-tack agent in an amount of from 0.1% to about 20% by weight; - a disintegrating agent in an amount of from 0.1% to about 20% by weight; and - an opacifying agent in an amount of about 0.02% to about 2% by weight.
11. The oral film of any of the preceding claims, wherein the film is configured to dissolve substantially completely in contact with oral or buccal mucosa in a time of about 10 minutes to about 120 minutes.
12. The oral film of any of claims Ito 10, wherein the film is configured to dissolve substantially completely in contact with oral or buccal mucosa in a time of about 1 second to about 5 minutes.
13. A method of making an oral film comprising: mixing the cannabinoid composition with water to form a premix; mixing into the premix at least the following components to form a liquid composition: two or more film forming polymers comprising pullulan and at least one further film forming polymer; coating the liquid composition onto a backing sheet to form a layer of the composition having a thickness of about 100 pm to about 4,000 pm; drying the layer to form the oral film having a total water content of from about 3% to about 15% by weight based on the total weight of the film.
14. The method of claim 13, wherein the oral film comprises: the two or more film forming polymers present in a total amount of from about 15 18% to about 80% by weight; the cannabinoid composition present in an amount of from about 5% to about 60% by weight; each of the foregoing amounts being based on the total weight of the oral film
15. The method of claim 13 or claim 14, wherein, the step of mixing the cannabinoid composition with water to form a premix further comprises mixing one or more further liquid components selected from one or more of a liquid preservative, a liquid emulsifier, a liquid plasticizer, a liquid surfactant, a liquid sweetening agent, a liquid flavouring agent, a liquid colouring agent and a liquid opacifying agent.
16. The method of any one of claims 13 to 15, further comprising, between the step of mixing the cannabinoid composition with water and the step of mixing the at least two film forming polymers into the premix, the step of mixing one or more further solid components selected from one or more of a solid preservative, a solid emulsifier, a solid plasticizer, a solid surfactant, a solid sweetening agent, a solid flavouring agent, a solid colouring agent and a solid opacifying agent.
17. The method of any of claims 13 to 16, wherein the drying comprises applying heated air to the layer of the composition on the backing sheet for a time of about 10 minutes to about 120 minutes.
18. The method of claim 17, wherein the heated air is applied from one or both of from above and from below the layer of the composition.
19. The method of claim 17 or claim 18, wherein the drying is carried out by passing the layer of the composition on the backing sheet through a drying tunnel.
20. The method of any of claims 13 to 19, further comprising cutting the oral film into individual strips having a width of about 10 mm to about 30 mm and having a length of about 10 mm to about 85 mm.