Composition

Abstract

The present invention relates to compositions for oral administration provided in the form of gelled oil-in-water emulsions, methods for their preparation and their use as pharmaceutical and nutraceutical products, in particular to orally administrable gelled oil-in-water emulsions that are self-supporting viscoelastic solids having a gelled aqueous phase that comprises a gelling agent that is agar, said emulsions being stabilized by a surfactant that is a plant-based protein, a plant-based polysaccharide or a derivative thereof.

Description

[Technical field]

[0001] The present invention generally relates to compositions for oral administration provided in the form of gelled oil-in-water emulsions, their preparation methods, and their use as pharmaceutical and dietary supplement products. The compositions may be provided in a soft, yet chewable, easy-to-swallow unit dosage form. More specifically, the present invention relates to oral compositions acceptable to patients and consumers who wish to abstain from consuming animal by-products, for example, those following a vegetarian or vegan diet. The present invention also relates to oral compositions acceptable to pescetarians. [Background technology]

[0002] Soft, chewable dosage forms are alternatives to traditional oral dosage forms such as tablets, capsules, elixirs, and suspensions. They are easier to swallow than tablets and capsules, and are particularly suitable for children and the elderly, as well as people suffering from swallowing disorders. Such dosage forms are a popular choice for nutritional supplements containing vitamins and / or minerals (so-called "nutraceutical products"), and are also suitable for the delivery of active pharmaceutical ingredients (Active Pharmaceutical Ingredients, APIs). The active ingredient (nutraceutical product or pharmaceutical) may be present in the form of lipids in a gelled oil-in-water emulsion, as dispersed particles, or dissolved in the oil or water phase of such an emulsion.

[0003] A range of gelling agents may be used in the preparation of soft, chewable dosage forms such as gelled oil-in-water emulsions, but gelatin is by far the most widely used due to its availability, ease of use, and its sol-gel transition temperature. Gelatin is produced by partial hydrolysis of collagen found in the skin, bones, and connective tissues of animals, and is most commonly derived from pork, beef, and fish sources. The sol-gel transition temperature of gelatin generally corresponds to the body temperature of the animal from which it is obtained. Thus, gelatin from mammalian sources has a transition temperature similar to human body temperature, resulting in a gel that is solid at room temperature but dissolves in the mouth when ingested. Thus, gelatin-based dosage forms provide a pleasant "melt in the mouth" texture or "mouthfeel". Gelatin also provides rapid and consistent dissolution kinetics of the dosage unit in the gastrointestinal tract, which may be beneficial in promoting rapid uptake of any active ingredient.

[0004] Gelatin has significant surface active properties that allow it to act as an emulsifier as well as a gelling agent. This makes it a particularly good choice for use as a gelling agent to produce chewable oil-in-water emulsions. Gelatin-based emulsions typically experience an "active filler effect" in which the oil droplets strongly interact with the surrounding gel network, and are commonly referred to as "active fillers." If the oil droplets are small enough, this interaction between the gel network and the oil droplets increases the storage modulus of the gelled emulsion compared to a gel without oil, i.e., the gel alone. In contrast, oil droplets that are distributed throughout the gel with little or no interaction with the gel network are known as "inert fillers" and result in a lower modulus of the gelled emulsion than that of the gel alone. If the oil droplets of a gelled emulsion are present as "inert fillers," the emulsion may not be stable over time. This can result in destabilization of the emulsion and "leaching out" of the oil.

[0005] Despite the many advantageous properties of gelatin for use in the manufacture of soft, chewable dosage forms, its animal origin makes it unacceptable to many patients and consumers due to religious beliefs or dietary choices. As an animal by-product, gelatin is, for example, unacceptable to vegans.

[0006] Gelling agents previously proposed for use in the manufacture of soft, chewable dosage forms, such as gelled oil-in-water emulsions, that are not of animal origin, include non-proteinaceous substances such as alginates, carrageenans, and pectins. However, the gelling properties of these materials can be difficult to control due to their need for complexation with metal ions, temperature changes, and / or pH adjustments to produce the desired "gel". This is not ideal for dosage forms manufactured on a commercial scale.

[0007] Another gelling agent that is widely used in food and other non-food applications is agar. Agar is extracted from marine red algae and contains a polysaccharide containing galactose subunits. It is a thermosetting polymer that gels at about 30-45°C. Agar melts at about 85-90°C and once dissolved, it retains its liquid state until cooled to 40°C. Due to its large hysteresis between gelling and dissolution temperatures, it has the potential for use in large-scale production of dosage units formed from gelled oil-in-water emulsions. However, unlike gelatin, which produces soft, flexible gels that can withstand a high degree of compression before breaking, agar-based gels are hard and brittle. While gelatin-based gels can withstand up to 70-90% compression before breaking, for example, agar-based gels will typically fragment under deformations on the order of 20%. This severely limits its use in the manufacture of any dosage unit that needs to be soft, chewable, and have a pleasant mouthfeel.

[0008] Unlike gelatin-based gels, agar-based gels are also prone to syneresis, i.e., the spontaneous release of water from the gel upon aging. Gels are 3D networks of polymers that crosslink with each other and trap water within their structure. If the polymer network is not disturbed, the water remains in place. However, over time, the polymers that form the gel may shrink or change their conformation, allowing the water to escape and shrinking the gel. The seepage of water from the gel is known as "syneresis", which must be minimized in any oral dosage unit due to the need for it to have a suitable shelf life, i.e., it should remain stable over an extended period of time. One of the ways in which the problem of syneresis in agar gels was originally addressed is by increasing the agar concentration. However, this can result in a harder, more solid, and more brittle gel, which is undesirable when trying to provide a soft, chewable dosage form.

[0009] Therefore, there is a continuing need for alternative soft but chewable compositions for oral delivery of pharmaceutical and / or nutraceutical products suitable for vegetarians, piscine vegetarians and vegans.In particular, there is a need for such compositions that can provide an acceptable alternative to conventional gelatin-based oil-in-water emulsions in terms of their "chew" and mouthfeel properties.Such compositions should be capable of being manufactured on a commercial scale and have suitable stability (i.e., shelf life) for use as pharmaceutical and / or nutraceutical products. Summary of the Invention [Problem to be solved by the invention]

[0010] The present invention addresses at least some of these needs. [Means for solving the problem]

[0011] The applicant proposes a gelled oil-in-water emulsion that is acceptable to vegetarian, piscineo-vegetarian or vegan patients and consumers, especially those following a vegetarian or vegan diet. The emulsion uses agar as a gelling agent and is stabilized using certain plant-based surfactants. In particular, the emulsion is stabilized by at least one surface-active protein or polysaccharide derived from a plant or its derivatives. The applicant has found that these high molecular weight (i.e. "supramolecular") plant-based surfactants are advantageous compared to low molecular weight surfactants when used to stabilize agar-based gelled oil-in-water emulsions. In particular, the inventors have found that these supramolecular surfactants provide gelled emulsions that are stable and have the desired rheological properties for oral delivery of active agents in soft but chewable dosage forms.

[0012] In one aspect, the invention provides an orally administrable gelled oil-in-water emulsion that is a self-supporting viscoelastic solid having a gelled aqueous phase that comprises a gelling agent that is agar, said emulsion being stabilized by a surfactant that is a plant-based protein, a plant-based polysaccharide, or derivatives thereof.

[0013] In another aspect, the invention provides a method for the preparation of a gelled oil-in-water emulsion as described herein, said method comprising the steps of forming an oil phase comprising one or more physiologically acceptable lipids, forming an aqueous phase comprising a gelling agent which is agar, combining said oil phase and said aqueous phase to form an oil-in-water emulsion in the presence of a surfactant which is a plant-based protein, a plant-based polysaccharide, or derivatives thereof, and gelling the emulsion.

[0014] In a further aspect, the invention provides a gelled oil-in-water emulsion as described herein for oral use as a medicament or in therapy.

[0015] In another aspect, the present invention provides a gelled oil-in-water emulsion as described herein containing at least one pharma- ceutical active ingredient, for oral use in the treatment of a condition responsive to said pharma-ceutical active ingredient.

[0016] In another aspect, the present invention provides the use of a pharma- ceutical active ingredient in the manufacture of a medicament for oral use in the treatment of a condition responsive to said pharma- ceutical active ingredient, wherein said medicament is provided in the form of a gelled oil-in-water emulsion as described herein.

[0017] In another aspect, the invention provides a method of treating a human or non-human animal subject (e.g., a patient) for a condition responsive to a pharma- ceutical active ingredient, the method comprising orally administering to the subject a pharma- ceutical effective amount of the agent in the form of a gelled oil-in-water emulsion as described herein.

[0018] In another aspect, the present invention provides the use of a gelled oil-in-water emulsion as described herein as a dietary supplement product. [Brief description of the drawings]

[0019] The invention will now be further described with reference to the following non-limiting examples and the accompanying figures. [Figure 1] Figure 1 shows the dynamic storage modulus (G'max) of agar-based gelling oil-in-water emulsions containing different surfactants. [Diagram 2] FIG. 1 shows the dynamic storage modulus (G'max) for gelled oil-in-water emulsions according to the present invention. [Diagram 3] FIG. 1 shows the hardness (force) of gelled oil-in-water emulsions according to the present invention as measured according to the Texture Profile Analysis (TPA) test. [Figure 4] FIG. 1 shows the dynamic storage modulus (G'max) for gelled oil-in-water emulsions according to the present invention. [Diagram 5]FIG. 1 shows the hardness (force) of a gelled oil-in-water emulsion according to the present invention when subjected to large scale deformation. [Figure 6] 4 shows the measured water activity of aqueous agar gels with increasing glycerol content. [Figure 7] FIG. 1 shows the hardness (force) of a gelled oil-in-water emulsion according to the present invention compared to a pure agar gel. [Figure 8] Figure 2 shows the hardness (force) of gelled oil-in-water emulsions containing gelatin as the gelling agent. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] definition The term "gel" refers to a form of matter intermediate between a solid and a liquid. The formation of a "gel" will typically involve linking or crosslinking polymer chains to form a three-dimensional network in which a solvent (e.g., water) is trapped or immobilized to form a sufficiently rigid structure that resists flow at ambient temperatures, i.e., temperatures below about 25°C, preferably below about 20°C. In rheological terms, a "gel" may be defined according to its storage modulus (or "elastic modulus") G', which describes the elasticity (energy storage) of the material, and its loss modulus (or "viscous modulus") G'', which describes the viscosity (energy loss) of the material. The ratio of the storage modulus to the loss modulus, tan δ (equal to G'' / G'), also referred to as the "loss tangent", provides a measure of how much the stress and strain are out of phase with each other.

[0021] A material that is "viscoelastic" is characterized by rheological properties that resemble in part the rheological behavior of a viscous fluid and in part the rheological behavior of an elastic solid.

[0022] The gelled oil-in-water emulsions according to the present invention are "self-supporting viscoelastic solids". This is intended to mean that they exhibit intermediate properties between solids and liquids, but have a predominantly solid behavior, i.e., they have rheological properties more similar to those of solids than to those of liquids. The "predominant behavior of solids" cannot be diluted (i.e., destroyed) by adding more solvent. In contrast, in the case of weak (or entangled) gels that lack stable (i.e., long-lived) intermolecular crosslinks, the entangled network structure of the gel can be removed by adding solvent and can be easily destroyed even at very low shear rates / shear stresses.

[0023] The gelled oil-in-water emulsions of the present invention exhibit mechanical rigidity, but in contrast to solids, they are deformable. Specifically, the gelled emulsions described herein have a storage modulus G' that is greater than their loss modulus G'' (i.e., G'>G'') over a wide frequency range, e.g., a frequency range of 0.001-10 Hz, when measured at ambient temperature (i.e., temperatures in the range of 18°C ​​to 25°C, e.g., 20°C) and 0.1% strain. The storage and loss moduli may be measured using well-known methods, e.g., using a Kinexus Ultra+Rheometer applying a C4 / 40 measurement geometry. There is no expected difference in the values ​​of the storage and loss moduli when measured using other types of rheometers within the linear viscoelastic range.

[0024] More specifically, the gelled oil-in-water emulsions described herein will have the following properties: G'>G'' over the frequency range of 0.001-10 Hz at 0.1% strain, and a storage modulus (G') at ambient temperature (i.e., a temperature in the range of 18°C ​​to 25°C, e.g., 20°C) in the range of 10-200,000 Pa, preferably 100-100,000 Pa, more preferably 500-50,000 Pa.

[0025] Weak gels will typically have a loss tangent of tan δ>0.1. For strong, or fully developed, gels, G'>>G'' and lower tan δ values ​​(<0.1) are observed. The gelled oil-in-water emulsions described herein will generally be considered "strong gels" at ambient temperatures, i.e., temperatures in the range of 18°C ​​to 25°C, e.g., 20°C.

[0026] As used herein, the term "gelation" refers to the formation of a "gel." The term is used herein in reference to both the physical properties of the aqueous phase of the emulsion and the physical properties of the oil-in-water emulsion. As will be understood, the oil droplets behave more or less like a solid when dispersed throughout the gelled aqueous phase of the oil-in-water emulsions that are the subject of the present invention. Thus, the "gelation" properties of the aqueous phase are also characteristic of the oil-in-water emulsions, i.e., they may also be considered "gelation" as described herein.

[0027] Unless otherwise defined, the term "liquid" as used herein refers to a substance that is free to flow and maintains a constant volume. This includes thick and viscous liquids that flow. A "liquid" has a loss modulus (G'') greater than its storage modulus (G') and a loss tangent (tan δ) greater than 1.

[0028] As used herein, the term "surfactant" refers to a surface-active compound or composition capable of reducing the interfacial tension between two immiscible liquids (e.g., the interface between oil and water). Typically, a surfactant will be amphiphilic in nature and will contain both hydrophobic and hydrophilic components. It may consist of a single component or may be a mixture of components. When a surfactant is a mixture of components, the individual components will typically, but not necessarily, be similar in structure. To the extent that a surfactant for use in the present invention is obtained from natural products (i.e., from plants or plant parts), it will be understood that it will typically contain a mixture of different components. The surfactant may be a naturally occurring product obtained from a plant or plant part, or may be a derivative thereof as described herein (i.e., semi-synthetic).

[0029] As used herein, the term "fatty acid" refers to an unbranched or branched, preferably unbranched, hydrocarbon chain having a carboxylic acid (-COOH) group at one end, conventionally referred to as the α (alpha) end. The hydrocarbon chain may be saturated or (mono- or poly) unsaturated. By convention, the numbering of the carbon atoms begins at the α end, such that the carbon atom of the carboxylic acid group is carbon atom number 1. The other end is usually a methyl (-CH3) group, conventionally referred to as ω (omega), such that the terminal carbon atom is the ω-carbon. Any double bonds present may be in a cis or trans configuration. The nomenclature "ω-x" is used to indicate that the double bond is on the xth carbon-carbon bond, counting from the terminal carbon (i.e., the ω-carbon) toward the carbonyl carbon.

[0030] "Physiologically acceptable" means any component that is suitable for administration to the human or non-human animal body, in particular suitable for oral administration.

[0031] "Drug product" means any product intended for medical purposes, e.g., for the treatment or prevention of a disease, condition, or disorder of the human or non-human animal body, or for preventing the recurrence thereof, or for the reduction or elimination of any of the symptoms of such disease, condition, or disorder. The use and production of products as "drug products" may be heavily regulated by government agencies. Products may be prescribed by a physician, but this is not required. For example, products may be available "over the counter," i.e., without a prescription.

[0032] "Treatment" or "treating" includes any therapeutic application that can benefit a human or a non-human animal (e.g., a non-human mammal). While both human and animal treatments are within the scope of the invention, the invention is primarily directed to human treatment. Veterinary treatment includes the treatment of livestock and domestic animals (e.g., pets such as cats, dogs, rabbits, etc.). Treatment may be in respect of an existing disorder or may be prophylactic.

[0033] In contrast to pharmaceuticals, "nutraceutical products" need not be subject to regulatory approval. The term "nutraceutical product" is used herein to refer to products that are generally considered to be beneficial for maintaining or enhancing the health and / or general well-being of a human or non-human animal subject. Such substances include, in particular, nutritional supplements such as vitamins and minerals that are intended to enhance the health of a subject (e.g., a human subject).

[0034] As will be appreciated, some substances may be considered both "drugs" and "dietary supplements." The classification of a substance as either, or indeed both, may vary from country to country depending on local regulations related to drugs. It may also depend on the recommended daily dosage of a particular substance. For example, a higher daily dosage of a particular vitamin, such as vitamin D, may be regulated as a drug, while a lower daily dosage may be considered a dietary supplement.

[0035] By "pharmaceutical composition" is meant a composition in any form suitable for use for pharmaceutical purposes.

[0036] By "dietary supplement composition" is meant a composition in any form suitable for use for dietary supplement purposes.

[0037] A "pharmaceutical effective amount" refers to an amount that will produce a desired pharmacological and / or therapeutic effect, i.e., an amount of an agent effective to achieve its intended medical purpose. While the needs of individual patients may vary, determination of optimal ranges of effective amounts of any active agent is within the capabilities of one of ordinary skill in the art.

[0038] A "nutraceutical effective amount" refers to an amount that will produce a desired nutraceutical effect, i.e., an amount of an agent that is effective to achieve its intended nutraceutical purpose. While the individual needs of a subject may vary, determining the optimal range of effective amounts of any active agent is within the ability of one of ordinary skill in the art.

[0039] The term "capsule" is used herein to refer to a unitary dosage form having a casing or coating (referred to herein as a "capsule shell") that encloses a gelled oil-in-water emulsion as defined herein.

[0040] As used herein, "water activity" refers to the partial vapor pressure of water in a composition at a particular temperature divided by the standard partial vapor pressure of water at the same temperature. Thus, water activity serves as a measure of the amount of free (i.e., unbound) water in a composition. Water activity may be measured by methods well known in the art, for example, by using a Rotronic Hygrolab instrument.

[0041] As used herein, "animal by-product" is intended to refer to any product derived from, isolated from, or purified from one or more parts of an animal's body (e.g., bone, skin, tissue, meat, cartilage, hoof, horn, etc.). It is also intended to refer to any composition prepared by processing an animal by-product, such as a derivatized, functionalized, or otherwise chemically or physically modified animal by-product. As used herein, "animal by-product" is not intended to include any compound or composition derived from, isolated from, or purified from milk, eggs, or animal milk or eggs. The term "animal by-product" does not include any synthetic materials or any materials obtained from any plant, fungal, bacterial, or algal source.

[0042] As used herein, the term "vegetarian diet" generally refers to a diet that lacks any meat and also lacks any animal by-products as defined herein. A "vegetarian diet" may include animal milk and animal eggs, and any products derived, isolated, or purified therefrom. Such diets are also commonly known as "ovo-lactovegetarian" or "lacto-ovovegetarian" diets, and include milk, cheese, other dairy products, and eggs, in addition to foods from plants. A "piscine vegetarian diet" refers to a diet in which the only source of meat is fish and seafood. A "vegan diet" refers to a diet that is entirely vegetarian and includes only foods from plants (e.g., fruits, vegetables, grains, legumes, seeds, and nuts). Any reference herein to a product, substance, composition, or formulation being "suitable" for a given diet means that it is acceptable to those following that particular diet. The terms "vegetarian," "piscine vegetarian," and "vegan" are intended to refer to those who follow a vegetarian, piscine vegetarian, or vegan diet, respectively.

[0043] In a first aspect, the present invention provides an orally administrable gelled oil-in-water emulsion that is a self-supporting viscoelastic solid having a gelled aqueous phase that comprises a gelling agent that is agar, said emulsion being stabilized by a surfactant that is a plant-based protein, a plant-based polysaccharide, or derivatives thereof.

[0044] The aqueous phase of the emulsion according to the present invention comprises water and is gelled using agar as a gelling agent. The aqueous phase is also referred to herein as the "continuous phase" of the emulsion. The gelling agent may be a single type of gelling agent or may be a mixture of different types of gelling agents. When more than one gelling agent is used, at least one of the gelling agents will be agar.

[0045] Agar is well known and used in the art, for example, in food and other non-food applications. It is contemplated that any known type of agar may be used in the present invention. As used herein, the term "agar" is intended to broadly define any product containing hydrocolloid polysaccharides extracted from red algae (i.e., seaweeds of the Rhodophyta family). The hydrocolloid polysaccharides present in agar contain one or more polymers composed of galactose subunits. Sources of agar include seaweeds belonging to the following genera: Gelidium, Gracilaria, Pterocladia, and Gelidiella. Gracilaria is the major source of agar worldwide.

[0046] The nature of the agar and its properties (e.g., its gelling ability) will vary depending on the species from which the agar is extracted and the extraction method used to make it, but it is envisioned that any known agar may be used in the present invention. Agars obtained from Gracilaria species are typically more sulfated and therefore have a lower gelling ability. However, their gelling properties may be enhanced by alkaline hydrolysis of the seaweed material prior to extraction. This converts L-galactose 6-sulfate units to 3,6-anhydro-L-galactose residues, which are believed to be responsible for the gelling properties of the polymer. Alternatively, the agar before and / or after extraction may be subjected to an enzymatic treatment to remove sulfate groups.

[0047] Agar is a linear polysaccharide composed of alternating β(1,3)- and α(1,4)-linked galactopyranose residues. A substantial portion of the α-galactose residues may be present as 3,6-anhydride derivatives. The (1,3)-linked residues are D-enantiomers, while the (1,4)-linked residues are L-enantiomers. Natural chemical modifications of these structures with acidic groups (i.e., sulfate, uronic acid, and pyruvic acid) as well as non-ionic methoxy groups have been identified. Early studies suggested that agar consists of two major fractions: a neutral fraction, called "agarose," with high gelling capacity, and a charged fraction, called "agaropectin," with lower gelling capacity. More recent studies have shown that agar is essentially a complex mixture of polysaccharides ranging from neutral to charged galactan molecules. The term "agarose" refers to agarobiose, a neutral polysaccharide with high gelling ability composed of repeating disaccharide units of 4-O-(β-D-galactopyranosyl)-3,6-anhydro-α-L-galactopyranose. Polysaccharides with repeating disaccharide units of 4-O-(β-D-galactopyranosyl)-α-L-galactopyranose, in the absence of anhydride bridges, are called "agarans". Alkaline treatment of agar removes the sulfate esters on C6 of the 4-linked galactose units, forming the corresponding 3,6-anhydride forms. This treatment is widely used in industrial agar extraction from Gracilaria species to improve its gelling properties. A more detailed overview of agar can be found, for example, in Chapter 24 of the Handbook of Hydrocolloids (Sousa et al., 2021), which is incorporated herein by reference in its entirety.

[0048] Agar is approved worldwide in food products by food safety authorities including the European Food Safety Authority (EFSA) and the Food and Drug Administration (FDA) as a food additive (E-406). Agar is supplied as a powder with high solubility in water, e.g., at least 85% solubility (at 80°C). Its gel strength can vary, but is typically about 700 to about 1100 g / cm. 2(measured for a concentration of 1.5% by weight in water at 20° C.). The gelling point of agar is typically in the range of 30-45° C. (measured for a concentration of 1.5% by weight in water at 20° C.). The melting point of agar may, for example, be in the range of 80-95° C. (measured for a concentration of 1.5% by weight in water at 20° C.). Agar having a gelling point in the range of about 35 to about 45° C. (measured for a concentration of 1.5% by weight in water at 20° C.) and / or a melting point of about 80-95° C., e.g., about 85-92° C. (measured for a concentration of 1.5% by weight in water at 20° C.) is particularly preferred for use in the present invention.

[0049] Agar for use in the present invention can be obtained from a variety of commercial sources. Non-limiting examples of agar that can be used include Gelagar HDR 800 (from B. & V. srl, Italy), and Qsol™ High Solubility Agar, and Qsol Agar (from Hispanagar, Spain).

[0050] The aqueous phase of the gelled oil-in-water emulsion according to the present invention may contain agar as the only gelling agent, or may contain additional non-agar gelling agents. If other gelling agents are present, they may be selected from other gelling agents known in the art. Consistent with the intended "vegetarian" or "vegan" nature of any of the products defined herein, any additional gelling agent should not be any animal by-product. For example, there will be no mammalian gelatin. Preferably, there will be no gelatin from any source, including fish gelatin.

[0051] The gelling agent or combination of gelling agents will be present in the aqueous phase in an amount suitable to provide the desired degree of gelation as described herein. This amount will vary to some extent depending on the exact nature of the gelling agent(s) (e.g., the type of agar used) and / or other components of the aqueous phase, but a suitable amount can be readily determined by one of ordinary skill in the art. If a gelling agent other than agar is also used, the appropriate amount can be readily selected by one of ordinary skill in the art. The amount of agar may be adjusted accordingly.

[0052] In one set of embodiments, the agar may be present in the aqueous phase at a concentration of about 0.1 to about 7.5% by weight, preferably about 0.25 to about 5% by weight, in particular about 0.3 to about 3.5% by weight, for example about 0.5 to about 3% by weight (i.e. based on the weight of the aqueous phase). For example, it may be present at a concentration of 0.5, 1.0, 1.5, 2.0, 2.5, or 3.0% by weight (based on the weight of the aqueous phase). The concentration of agar based on the total weight of the composition may range from about 0.1 to about 5% by weight, preferably about 0.15 to about 4.5% by weight, more preferably about 0.2 to about 4% by weight, for example about 0.25 to about 3.5% by weight, or about 0.25 to about 3% by weight. For example, it may be present in a concentration of 0.25, 0.50, 0.75, 1.0, 1.25, 1.50, 1.75, 2.0, 2.25, 2.5, 2.75, or 3.0% by weight (based on the total weight of the composition).

[0053] The gelling emulsion described herein is stabilized by a surfactant that is a plant-based protein or polysaccharide. As used herein, the term "plant-based" is intended to refer to materials derived from (e.g., extracted from) a plant or any part of a plant, such as the fruit or seed of the plant. Such materials include derivatives of any naturally occurring components of a plant or plant part, such as derivatives obtained by chemical modification. Thus, the plant-based surfactant for use in the present invention may be natural or semi-synthetic.

[0054] Surfactants for use in the present invention are capable of stabilizing gelled oil-in-water emulsions as described herein. It will be understood that to perform this function, the surfactant should be sufficiently soluble in the aqueous phase of the emulsion under the conditions used to generate the emulsion. Due to the nature of some of the surfactants proposed for use in the present invention, particularly those containing vegetable proteins, the solubility should take into account the pH of the aqueous phase. In one embodiment, the surfactant has a solubility of at least about 5 mg / mL in an aqueous solution of pH 4.5, measured at a temperature of about 50° C. and a pressure of about 1 atm.

[0055] The surfactant for use in the present invention is suitable for use in oral pharmaceuticals or food products. It may be, for example, any surfactant that is acceptable for use in food products, i.e., food-grade proteins, polysaccharides, or any derivatives thereof that are suitable for human consumption. Typically, it is a surfactant that is approved for use as a food additive by a food-related government agency (e.g., the European Food Safety Authority or the United States Food and Drug Administration). Surfactants that have an E number and are therefore approved for use as a food additive in the European Union are particularly suitable for use in the present invention.

[0056] The vegetable surfactants for use in the present invention include vegetable proteins, vegetable polysaccharides, or any derivatives or combinations thereof. Derivatives include products obtained by chemical and / or physical modification of vegetable proteins, vegetable polysaccharides, and mixtures thereof. Chemical modification may include, for example, functionalization to introduce one or more functional groups, or hydrolysis to reduce the molecular weight of the material. Functionalization is particularly suitable since it can be used to adjust the hydrophobic / hydrophilic properties of the product. Suitable functional groups and methods for their introduction are well known in the art. Non-limiting examples of functional groups include, for example, aliphatic groups, carboxyl groups, amine groups, and amide groups. Functionalization may also include reaction with another compound to form a complex, for example, reaction with a glycol such as propylene glycol ("Propylene Glycol, PG"). Physical methods may include, but are not limited to, ultra-purification to adjust the molecular weight distribution of the material.

[0057] Suitable vegetable protein derivatives for use in the present invention include, for example, hydrolyzed proteins. Derivatives of vegetable polysaccharides for use in the present invention include, for example, polysaccharides that have been hydrophobically modified to impart desired surfactant properties and / or water solubility.

[0058] The vegetable protein and vegetable polysaccharide surfactants for use in the present invention have a high molecular weight and are generally considered to be "supermolecular". In one embodiment, the vegetable surfactant has a weight average molecular weight Mw of about 10 kDa or more, such as about 15 kDa or more, 20 kDa or more, or 25 kDa or more. Typically, the vegetable surfactants for use in the present invention have a weight average molecular weight in the range of about 10 to about 500 kDa, such as about 20 to about 450 kDa, or about 25 to about 450 kDa, or about 30 to about 450 kDa, about 40 to about 450 kDa, about 50 to about 450 kDa, about 60 to about 450 kDa, or 70 to about 450 kDa, or 80 to about 450 kDa. In another set of embodiments, the surfactant for use in the present invention may have a weight average molecular weight in the range of about 10 to about 80 kDa, preferably about 20 to about 70 kDa, for example about 30 to about 70 kDa. Methods for measuring molecular weight are well known in the art. A method typically used to measure the molecular weight of any protein is, for example, SEC-MALLS (Size Exclusion Chromatography-Multiple Angle Laser Light Scattering).

[0059] Vegetable proteins and their derivatives having surfactant properties and suitable for use in the present invention are well known in the art. Vegetable proteins are typically provided in two major forms: isolate and concentrate. Unless otherwise stated, any reference to "protein" herein includes protein in the form of isolate and concentrate. Concentrate may contain, for example, fat, carbohydrates and bioactive compounds. Isolate is processed to remove fat and carbohydrates and may, in some cases, have lower levels of any bioactive compounds.

[0060] Plants of the legume family (Fabaceae or Leguminosae) are important sources of proteins known for use in food products and may be used in the present invention. Typically, such proteins are obtained from the fruit or seeds of the plant. Legumes include, for example, Glycine max (soybean), Phaseolus sp. (kidney bean), Pisum sativum (pea), Cicer arietinum (chickpea), and Arachis hypogaea (peanut). Examples of legume plants from which protein materials for use in the present invention may be derived include, but are not limited to, pea, kidney bean, chickpea, lentil, soybean (also known as soybean), and peanut. Other plant-based proteins that may be used in the present invention include, for example, proteins obtained from rice, sunflower, potato, and chia.

[0061] Proteins in legumes include water-soluble albumins, and salt-soluble globulin storage proteins (7S vicilin and / or 11S legumin splits) (see, e.g., Boye et al., "Pulse proteins: Processing, characterization, functional properties and applications in food and feed" - Food Research International 43(2):414-431, 2010, the entire contents of which are incorporated herein by reference). These globular proteins consist mainly of polymorphic subunits bound together by non-specific hydrophobic interactions. Vicilins are trimers, while legumins are hexamers (see, e.g., Schwenke, "Reflection about the functional potential of legume proteins A Review" - Food / Nahrung 45(6):377-381, 2001, the entire contents of which are incorporated herein by reference). Pulse proteins are relatively rich in beta-sheet structure compared to cereal or animal proteins, conferring high structural flexibility.This helps stabilize the emulsions as the proteins undergo significant conformational changes as they adsorb to the emulsion droplets, exposing their hydrophobic residues to the oil phase and forming a highly stable interfacial layer (see, e.g., Tang et al., "A comparative study of physicochemical and conformational properties in three vicilins from Phaseolus legumes: Implications for the structure-function relationship" - Food Hydrocolloids 25(3):315-324, 2011, and Sharif et al., "Current progress in the utilization of native and modified legume proteins as emulsifiers and encapsulants - A review" - Food Hydrocolloids 76:2-16, 2018, the contents of which are incorporated herein by reference in their entireties).

[0062] Particularly suitable for use in the present invention are proteins obtained from pea or kidney beans, including isolates and concentrates of such proteins. Those derived from soybeans and fava beans are particularly suitable.

[0063] Pea protein isolates and kidney bean protein isolates are highly refined or purified forms of pea protein or kidney bean protein. Pea protein isolates typically have a minimum protein content of about 80% (dry basis), while kidney bean protein isolates may have a minimum protein content of about 65%, and sometimes as much as 90% (dry basis). Pea protein can be obtained from various species of pea. Bean protein can be obtained from various species of beans, including, but not limited to, broad beans and soybeans. Soy protein isolates are highly refined or purified forms of soy protein with a minimum protein content of about 90% (dry basis). Soy protein isolates are made from defatted soy flour, from which most of the non-protein components, such as fat and carbohydrates, have been removed. Pea protein and kidney bean protein, including isolates and concentrates, are suitable for vegetarian and vegan diets. Commercial sources of pea protein include Nutralys and Hill Pharma. Commercial sources of bean proteins, such as fava bean protein, include Vestkorn and Hill Pharma. Commercial sources of soy protein include PHH (Supro590).

[0064] Plant polysaccharides and their derivatives that have surface active properties and are suitable for use as surfactants in the present invention are well known in the art. These include, for example, cellulose, starch, alginates, and their derivatives. Often, these materials are chemically modified to impart the required surface active properties and / or to provide the desired degree of water solubility.

[0065] In one embodiment, the polysaccharide for use in the present invention is a hydrophobically modified polysaccharide. By "hydrophobically modified polysaccharide" is meant a polysaccharide incorporating one or more hydrophobic groups. Typically, such materials are produced by reacting a portion of the side chains along the polymer backbone with at least one hydrophobic group. Such hydrophobic groups include, for example, alkyl, alkenyl, cycloalkyl, aryl, and arylalkyl groups. The alkyl and alkenyl groups may be linear or branched. The hydrophobic groups may contain up to about 22 carbon atoms. In some cases, such groups may be short chain alkyl groups, e.g., C1-6 or C1-3 alkyl groups. Methyl, ethyl, and propyl groups are particularly suitable.

[0066] Natural cellulose materials are typically not water-soluble. They contain many hydroxyl groups, which form strong intermolecular hydrogen bonds that prevent the approach of water molecules. Chemical modification of cellulose to replace some of the hydrogen atoms of the hydroxyl groups with substituents such as methyl (-CH3), hydroxypropyl (-CH2CHOHCH3), or hydroxyethyl (-CH2CH2OH) groups interrupts the intermolecular hydrogen bonds and makes cellulose water-soluble. Examples of modified cellulose materials suitable for use in the present invention include methyl cellulose (MC), hydroxypropyl methyl cellulose (HPMC), and carboxy methyl cellulose (CMC).

[0067] Modified starches which may be used as surfactants in the present invention include acetylated starch, hydroxypropyl starch, hydroxypropyl distarch phosphate, sodium starch octenyl succinate, and acetylated oxidized starch. Specific examples of suitable starches include the following food grade starches: E1401 modified starch, E1402 alkali modified starch, E1403 bleached starch, E1404 oxidized starch, E1410 monostarch phosphate, E1412 distarch phosphate, E1413 phosphorylated distarch phosphate, E1414 acetylated distarch phosphate, E1420 acetylated starch, monostarch acetate, E1422 acetylated distarch adipate, E1430 glycerin distarch, E1440 hydroxypropyl starch, E1441 hydroxypropyl starch, E1442 hydroxypropyl distarch phosphate, E1450 sodium starch octenyl succinate, and E1451 acetylated oxidized starch. Preferred for use in the present invention are starches having the following E numbers: E1414, E1420, E1422, E1440, E1441, E1442, E1450, and E1451.

[0068] Alginates suitable for use as surfactants in the present invention are those that are hydrophobically modified. A chemically modified alginate that can be used in the present invention is propylene glycol alginate (PGA). PGA is an ester of alginic acid in which some of the carboxyl groups are esterified with propylene glycol, some are neutralized with a suitable alkali, and some remain free. PGA is available under the E number E405.

[0069] In certain embodiments, the plant surfactant for use in the present invention may comprise a combination of protein and polysaccharide, for example a polysaccharide-protein complex or conjugate, or it may comprise a mixture of protein and polysaccharide.

[0070] Vegetable gum exudates are also suitable for use as surfactants in the present invention, such as gum arabic and gum ghatti. Gum arabic is a material obtained from two sub-Saharan species, Acacia senegal and Acacia seyal. It is widely used in the food industry with E number E-414. It is a complex mixture of glycoproteins and polysaccharides, mainly composed of arabinose and galactose. Gum ghatti is the dried exudate of the Anogeissus latifolia tree, a member of the family Combriaceae, and is a complex water-soluble polysaccharide.

[0071] Any of the plant-based surfactants described herein may be used in combination.In one embodiment of the present invention, for example, the plant-based protein or its derivative described herein may be used in combination with gum arabic.A preferred combination is pea protein or kidney bean protein, protein isolate or protein concentrate, and a plant gum exudate (e.g., gum arabic), for example, broad bean protein in combination with gum arabic.

[0072] The surfactant (or combination of surfactants) is present in an amount effective to provide the emulsion with the desired stability. The amount will vary depending on factors such as the exact nature of the surfactant(s), the relative ratio of the oil and water phases, and the presence (and amount) of any other components of the emulsion that may act as emulsifiers. Taking these factors into account, the appropriate amount of vegetable surfactant(s) may be readily determined by one of skill in the art. A suitable amount may, for example, be in the range of 0.1 to 5.0% by weight, preferably 0.25 to 4.0% by weight, in particular 0.5 to 3.0% by weight, e.g., 1.0 to 2.5% by weight (based on the total weight of the entire composition). For example, the amount of surfactant(s) may be 1.0, 1.25, 1.5, 1.75, 2.0, 2.25, or 2.5% by weight, based on the total weight of the composition. When a combination of surfactants is used, their relative amounts may be readily selected by one of skill in the art.

[0073] When using a surfactant comprising a combination of a plant-based protein or derivative thereof, such as pea or kidney protein, a protein isolate, or a protein concentrate (e.g., broad bean protein), and a vegetable gum exudate (e.g., gum arabic), each component may be present in an amount ranging from 0.5 to 2.0% by weight (based on the total weight of the composition), preferably 1.0 to 1.5% by weight. For example, a surfactant comprising 1.0 to 2.0% by weight of broad bean protein and 0.5 to 1.5% by weight of gum arabic may be particularly suitable.

[0074] In one set of embodiments, glycerol may be present in the aqueous phase of the emulsion. Advantageously, glycerol may be present in an amount effective to reduce the water activity of the composition and thus reduce microbial growth. The water activity may be reduced, for example, to less than about 0.8, for example, in the range of 0.5-0.8, or in the range of 0.6-0.75, or in the range of 0.65-0.75. The proportion of water in the aqueous phase of the emulsion may be replaced, for example, by glycerol. For example, up to 90% by weight of the water may be replaced with glycerol. In other embodiments, 10-90% by weight, preferably 50-85% by weight, for example 55-75% by weight of the water may be replaced with glycerol. When glycerol is present, this may reduce the amount of any preservative that may be required to provide a product with a suitable shelf life. In some cases, the need for a preservative to be present may be avoided. As described herein, the presence of a sugar alcohol in the aqueous phase also contributes to a reduction in water activity. The amount of glycerol may be adjusted to take into account the amount of any sugar alcohol that may be present, in some embodiments glycerol may be substituted for the sugar alcohol, or the presence of glycerol may reduce the amount of the sugar alcohol.

[0075] When present, glycerol may be provided in an amount of up to 60% by weight, preferably 20 to 60% by weight, for example 30 to 60% by weight, based on the total weight of the composition.

[0076] The oil phase of the emulsion comprises a physiologically acceptable lipid or a mixture of different physiologically acceptable lipids. Depending on the nature of the lipid (or lipids), the oil phase itself may have nutraceutical and / or pharmaceutical properties. Thus, in some embodiments, the lipid constituting the oil phase of the emulsion may be a nutraceutical product or a pharmaceutical product. Examples of such lipids include, for example, the essential fatty acids described herein. Alternatively, the oil phase may act as a carrier for lipophilic pharmaceuticals or a carrier for lipophilic nutraceuticals. In this case, the active agent may be dissolved or dispersed in the oil phase.

[0077] A wide variety of different lipids are known for oral use in pharmaceutical and / or nutraceutical products, and any of these may be used in the oil phase of the emulsion described herein.Lipid sources include, but are not limited to, vegetable oils such as rapeseed oil, sunflower oil, corn oil, olive oil, sesame oil, palm kernel oil, coconut oil, nut oil (e.g., almond oil or peanut oil), algae oil and hemp oil.Fish oil and lipids derived from fish oil are also suitable for use in certain compositions according to the present invention.Compositions containing these products are acceptable, for example, to fish vegetarians.

[0078] Lipids derived from natural sources typically contain a mixture of different lipid components. Thus, in one embodiment, the oil phase will contain a mixture of different lipids. For example, the oil phase may contain a mixture of lipids with different chain lengths and / or different degrees of saturation.

[0079] Lipids for use in the present invention may be liquid, solid, or semi-solid at ambient temperature (i.e., at a temperature of about 18°C ​​to about 25°C). Those that are liquid at such temperatures are generally preferred. Any combination of liquid, solid, and semi-solid lipids may also be used. Solid lipids having a melting point below about 100°C, preferably below about 70°C, for example below about 50°C, may be used in the present invention. Solid lipids that may be used include butter, solid coconut splits, cocoa butter or cocoa fat, etc. If desired, the overall melting point of the lipids constituting the oil phase may be adjusted by mixing different lipids, for example by mixing a solid lipid (e.g., butter) with a liquid oil. An overall melting point in the range of 45-50°C may be desirable.

[0080] Lipids for use in the present invention include, in particular, fatty acids and their derivatives. These include both naturally occurring fatty acids and their derivatives, as well as synthetic analogues. In one embodiment, the oil phase may comprise a mixture of different fatty acids, or fatty acid derivatives.

[0081] The hydrocarbon chain of the fatty acid or fatty acid derivative may be saturated or unsaturated, and it may be unbranched or branched. Preferably, it will be unbranched. Typically, the hydrocarbon chain will contain 4-28 carbon atoms, and generally have an even number of carbons. Fatty acids vary in their chain length and may be classified as "short", "medium", "long", or "very long" chain fatty acids. Those with a hydrocarbon chain of 5 carbons or less are referred to as "short chain fatty acids", those with a hydrocarbon chain of 6-12 carbons are referred to as "medium chain fatty acids", those with a hydrocarbon chain of 13-21 carbons are referred to as "long chain fatty acids", and those with a hydrocarbon chain of 22 carbons or more are referred to as "very long chain fatty acids". Any of these may be used in the present invention.

[0082] In one embodiment, the oil phase will comprise a saturated fatty acid or a derivative of a saturated fatty acid, including but not limited to any of the derivatives described herein. Medium chain saturated fatty acids and their derivatives find particular use in the present invention. Particularly preferred are those having 8 to 12, e.g., 8, 10 or 12 carbon atoms in the hydrocarbon chain, i.e., caprylic acid (C8), capric acid (C10), or lauric acid (C12), and any derivatives thereof. Typically, the saturated fatty acid or its derivative may be used as a carrier for one or more active ingredients in the oil phase, e.g., as a carrier for a pharmaceutical or nutritional supplement.

[0083] The saturated fatty acids and their derivatives for use in the present invention may be naturally occurring or they may be synthetically produced. Most typically, they will be naturally occurring and therefore may be used in the form of a mixture of different fatty acids and / or different fatty acid derivatives. Sources of saturated fatty acids and their derivatives include, for example, coconut oil and palm kernel oil.

[0084] In another embodiment, the oil phase may comprise unsaturated fatty acids or derivatives thereof whose carbon chain contains one or more carbon-carbon double bonds. The double bonds may be in the cis or trans configuration, or any combination thereof in which one or more double bonds are present. Those in which the double bonds are in the trans configuration are generally less preferred due to the need to reduce the consumption of so-called "trans fats" as part of a healthy diet. Thus, fatty acids and their derivatives having cis-configured double bonds are preferred. Mono- and polyunsaturated fatty acids and their derivatives are well known in the art. Such fatty acids typically contain 12 to 26 carbons, more commonly 16 to 22 carbons, and have mono- or polyunsaturated hydrocarbon chains. They include, in particular, polyunsaturated fatty acids (Poly Unsaturated Fatty Acids, PUFAs), such as essential fatty acids.

[0085] Oils containing long-chain unsaturated fatty acids and their derivatives find particular use in the present invention, for example in any composition intended for use as a dietary supplement.Particularly important essential fatty acids that can be used include omega-3 fatty acids, omega-6 fatty acids, and omega-9 fatty acids.Examples of omega-3 fatty acids include alpha-linolenic acid (ALA), stearidonic acid (SDA), eicosatrienoic acid (ETE), eicosatetraenoic acid (ETA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), tetracosapentaenoic acid, and tetracosahexaenoic acid. Examples of omega-6 fatty acids include linoleic acid, gamma-linolenic acid, eicosadienoic acid, dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), docosatetraenoic acid, adrenic acid, docosapentaenoic acid, and calendic acid. Examples of omega-9 fatty acids include oleic acid, eicosenoic acid, mead acid, erucic acid, and nervonic acid.

[0086] Sources of unsaturated fatty acids and their derivatives include oils obtained from various fish, plants, algae and microbial sources.Particularly suitable sources are algae oils and vegetable oils, but fish oils may also be suitable for those who follow a piscine vegetarian diet.All of these oils are rich in omega-3, omega-6 and omega-9 fatty acids.Fish oils may be obtained, for example, from anchovies, sardines and mackerel.

[0087] Any known derivative of fatty acid may be used in the present invention. These include, in particular, carboxylic acid esters, carboxylic acid anhydrides, glycerides (i.e., mono-, di-, or triglycerides) and phospholipids. As used herein, the term "derivative" in the context of fatty acids also encompasses any pharma- ceutically acceptable salt of fatty acid. Suitable salts are well known to those skilled in the art and include, but are not limited to, lithium, sodium, potassium, ammonium, meglumine, and diethylamine salts.

[0088] Examples of carboxylic acid esters of fatty acids include those in which R is a straight chain or branched chain alkyl group, typically a short chain alkyl group, preferably selected from, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, and n-hexyl. 1-6 Included are compounds having a terminal -CO2R group that is an alkyl group.

[0089] When the fatty acid derivative is a carboxylic acid anhydride, it is preferably a C 15 alkyl group, wherein R is a straight or branched alkyl group, typically a short chain alkyl group, preferably selected from, for example, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl and n-hexyl. 1-6 It may contain a terminal -CO2COR group which is an alkyl group.

[0090] Glycerides are esters derived from glycerol and up to three fatty acids. The fatty acids present may be any of those described herein, and therefore may be, for example, saturated or unsaturated. In the case of diglycerides and triglycerides, the fatty acid components may be the same or different. For example, they may be of different chain length.

[0091] In one embodiment, the lipid carrier for use in the present invention may comprise a medium chain triglyceride (MCT). MCTs are triglycerides that contain two or three medium chain fatty acids, which may be the same or different. Sources of MCTs include, for example, coconut oil and palm kernel oil. The fatty acids present in MCTs are typically saturated medium chain fatty acids. For example, MCTs in coconut oil include C 6-12 Fatty acids, mainly C8 and C 10 A typical fatty acid composition of MCT oil obtained from coconut oil may include, for example, 0.1% by weight caproic acid (C6:0), 55% by weight caprylic acid (C8:0), 44.8% by weight capric acid (C10:0), and 0.1% by weight lauric acid (C12:0).

[0092] Phospholipids generally consist of a glycerol molecule attached to a hydrophilic "head" group consisting of two fatty acids (the "tail" group) and a phosphate group. The phosphate group may be modified by linkage to choline, ethanolamine, or serine. In one embodiment, the oil phase may be composed in whole or in part of a phospholipid, such as vegetable lecithin.

[0093] The amount of oil present in the compositions of the invention will depend on factors such as the nature of the oil, the nature of any pharmaceutical or dietary supplements that may be present, and the desired loading, and may vary as required. The oil phase may, for example, constitute 5-50% by weight, preferably 10-45% by weight, e.g., 15-40% by weight, 15-30% by weight, or 20-25% by weight of a gelled oil-in-water emulsion.

[0094] As will be appreciated, in the compositions of the present invention, the oil provides a discontinuous phase within the continuous aqueous phase that is gelled. Thus, the oil is dispersed throughout the gelled aqueous phase in the form of oil droplets (also referred to herein as oil "particles"). The gelling of the aqueous phase provides a stable emulsion that prevents the oil droplets from aggregating, for example, to prevent physical collisions between the droplets. When preparing a gelled emulsion, the vegetable surfactant is initially dissolved in the aqueous phase, but migrates to the oil-water interface, where it helps to stabilize the oil phase. Without being bound by theory, it is believed that the non-uniform distribution of the large molecules of surfactant around the oil droplets acts to provide a friction layer that provides a "semi-active filler" effect.

[0095] The size of the oil particles in the gelled oil-in-water emulsion is not particularly limited. For example, oil particles having a volumetric size within the range of about 100 nm to about 100 μm, preferably about 500 nm to about 75 μm, particularly about 750 nm to about 50 μm, for example, about 1000 nm to about 40 μm may be provided. The volumetric average particle size may be in the range of about 5 nm to 50 μm, preferably about 5 to 30 μm, for example, about 5 to 25 μm. As used herein, "volume average" refers to the volume moment average or De Brouckere Mean Diameter (also known as the "D[4,3]" value). This reflects the size of the particles that make up the majority of the sample volume and is most sensitive to the presence of large particles in the size distribution.

[0096] An essentially uniform size distribution of the oil particles may be desirable. 90 The value indicates the size that 90% of the oil particles in all oil droplets meet. D 90 The value may be in the range of 15 to 80 μm, preferably 25 to 65 μm, and in particular 30 to 50 μm. 50 Value and D 10 The values ​​indicate the size values ​​that 50% and 10% of the oil droplets meet among the total of all oil droplets. D 50 The value may be in the range of 10 to 45 μm, in particular 15 to 35 μm, for example 18 to 25 μm. 10The value may be in the range of 0.5 to 20 μm, in particular 3 to 15 μm, for example 5 to 10 μm.

[0097] The size and size distribution of lipid droplets can be determined using methods and equipment conventional in the art, for example, using a Malvern Mastersizer 3000 (Worcestershire, UK) connected to a Hydro MV, wet dispersion unit (Malvern, Worcestershire, UK). Analysis of the data can be performed using the manufacturer's software (Mastersizer 3000, v1.0.1). The test can be performed by dissolving and diluting the gelled emulsion in a suitable solvent (1:100) at 50°C. Suitable solvents include Milli-Q water and 10% (v / v) HCl solution (the latter may minimize aggregation during the test). The refractive index of water and corn oil are set to 1.33 (solvent) and 1.47 (dispersed phase), respectively, and the absorptivity of the dispersed droplets is set to 0.01. To avoid multiple scattering or low intensity of scattered light, the dissolved emulsion is added to a dispersion unit (containing about 125 mL of water) until about 10% obscuration is obtained.

[0098] The size and size distribution of the oil particles may vary. If desired, size reduction of the oil particles can be achieved by a variety of different means, for example, by mechanical processes, or by chemical processes including the selection of smaller lipid molecules, or indeed by a combination of these approaches. Suitable chemical methods for achieving size reduction of oil particles may include the selection of a particular type of lipid (or combination of lipids) that can form smaller oil droplets. For example, certain oils, such as MCT, tend to generate a finer dispersion of oil droplets. Mechanical reduction involves the use of shear forces to break up large oil droplets into small nanoscale particles. Thus, smaller particles may be generated by suitable adjustments to the method used to generate the emulsion, for example, by varying the shear forces and / or duration of mixing of the oil and water phases. Using higher shear forces and / or longer mixing times will generate smaller oil particles. Appropriate shear may be achieved, for example, using a conventional homogenizer such as a rotor stator mixer, for example, an Ultra-turrax® homogenizer. A problem often encountered in mechanical processes for the production of oil-in-water emulsions is particle reagglomeration (i.e., coalescence), which is addressed in the present invention by the use of a gelled aqueous phase which helps to stabilize the emulsion, and by the use of surfactants which reduce the energy required for emulsification (by reducing interfacial tension) and protect the droplets from reagglomeration.

[0099] The aqueous phase (ie, the continuous phase) of the gelled oil-in-water emulsion may constitute 50-95% by weight of the composition, preferably 55-90% by weight, for example 60-85% by weight, 70-85% by weight, or 75-80% by weight.

[0100] In addition to water, gelling agent(s), and surfactant(s), other physiologically acceptable substances may also be present in the aqueous phase, such as pH adjusting agents (e.g., buffering agents), viscosity adjusting agents (e.g., thickeners, plasticizers), sweeteners, bulking agents (i.e., fillers), antioxidants, fragrances, flavorings, and coloring agents. The nature and concentrations of such materials may be readily determined by one of ordinary skill in the art.

[0101] The presence of a bulking agent (i.e., a filler) in the aqueous phase helps to reduce microbial growth by lowering the water activity. The water activity may be reduced, for example, to less than about 0.8, for example, in the range of 0.5-0.8, or in the range of 0.6-0.75, or in the range of 0.65-0.75. The amount and type of bulking agent may be readily selected by one of skill in the art. Suitable examples include, but are not limited to, sugar alcohols, sugars, and mixtures thereof. Suitable sugar alcohols include sorbitol, and xylitol, and mixtures thereof. Sugars that may be used include trehalose, sucrose, glycerol, and mixtures thereof. The bulking agent may constitute 45-70% by weight, preferably 50-65% by weight, for example 55-60% by weight, based on the aqueous phase. In some cases, the bulking agent(s) selected may also function as a sweetener depending on their concentration. For example, the composition of the present invention may contain xylitol in an amount of, for example, 0.5 to 50% by weight, preferably 1 to 40% by weight, for example, 15 to 40% by weight, in order to improve the taste.

[0102] If the aqueous phase contains a sweetener, it is typically selected from natural sweeteners such as sucrose, fructose, glucose, reduced glucose, maltose, xylitol, maltitol, sorbitol, mannitol, lactitol, isomalt, erythritol, polyglycitol, polyglucitol, glycerol, and stevia, and artificial sweeteners such as aspartame, acesulfame-kappa, neotame, saccharin, and sucralose. The use of non-cariogenic sweeteners is preferred.

[0103] In one embodiment, a viscosity modifier may also be provided in the aqueous phase. Suitable viscosity modifiers include other hydrocolloids such as starch, modified starches (e.g., hydroxyethyl starch, hydroxypropyl starch), xanthan, galactomannans (e.g., guar gum and locust bean gum), karaya gum, tragacanth gum, and any combination thereof. As will be appreciated, the viscosity modifier may have some surfactant properties and may also aid in stabilizing the emulsion. The thickening effect of the viscosity modifier depends on the type of material (e.g., hydrocolloid) used and its concentration, other components, and the pH of the formulation, etc., but suitable amounts may be readily determined by one of ordinary skill in the art. Typical amounts of any viscosity modifier that may be present may range from 0.1 to 5% by weight, preferably 0.2 to 2.5% by weight, e.g., 0.5 to 2.0% by weight, of the total composition.

[0104] Flavoring agents may be present in the composition and may aid in taste-masking certain lipids, such as those containing omega-3 fatty acids. Suitable flavoring agents include, but are not limited to, citrus flavoring agents, such as orange oil, lemon oil, or lime oil.

[0105] The pH adjusting agent may be readily selected by one skilled in the art and includes food grade acids such as citric acid. Buffering agents may also be used to adjust the pH and include organic acid / base buffer systems. Suitable buffering agents are well known in the art and include, for example, sodium citrate and malic acid. The pH of the aqueous phase of the emulsion may be adjusted to a range of 2 to 8, particularly 3 to 7, preferably 3.5 to 6, for example 4 to 5.

[0106] When antioxidants are present in the aqueous phase, they are water-soluble and include, for example, ascorbic acid, citric acid, and their salts, such as sodium ascorbate. Depending on the choice of oil, these may be provided in a form that contains an antioxidant, such as, for example, vitamin E. When present, the amount of any antioxidant(s) may be up to 3% by weight, such as up to 1% by weight, of the total formulation.

[0107] In addition to the lipid(s), the oil phase of the emulsion may also contain physiologically acceptable lipid-soluble materials, if desired, such as pharma- ceutically acceptable drugs, antioxidants (e.g., vitamin E), flavoring agents, and coloring agents.

[0108] In some embodiments, additional physiologically active agents may also be present in the gelled emulsions described herein. These may be provided in the aqueous and / or oily phases, and may be dissolved and / or dispersed in one or both of these phases. Other active agents that may be present in the oily phase include lipophilic active agents.

[0109] In one embodiment, a gelled oil-in-water emulsion according to the present invention may comprise, consist essentially of, or consist of the following components: (a) water, (b) at least one vegetable surfactant; (c) one or more physiologically acceptable lipids; (d) agar; (e) one or more bulking agents; (f) optionally, one or more pH adjusters; (g) optionally, one or more viscosity modifiers (e.g., thickeners or plasticizers); and (h) optionally, one or more additional physiologically active agents.

[0110] By "consisting essentially of" it is intended that the emulsions will be substantially free (e.g., free of) other components that would materially affect their properties. By "consists of" it is intended that the emulsions will be substantially free (e.g., free of) components other than those listed.

[0111] In one set of embodiments, the composition of the invention may be provided in the form of a dosage unit. By "dose unit" it is intended that the composition is to be taken orally by the subject (e.g., administered to a patient) "as received", i.e., will not be destroyed or dissolved prior to oral delivery. The weight of the dosage unit will therefore be such that it is suitable for delivering the composition in the present method. For example, it may have a total weight in the range of 50 to 3,000 mg, e.g., 250 to 3,000 mg or 500 to 2,500 mg, in particular, 100 to 2,000 mg, e.g., 750 to 2,000 mg, in particular, 100 to 1,500 mg, more particularly, 400 to 1,500 mg, more particularly, 400 to 1,000 mg.

[0112] In one set of embodiments, the dosage units will generally be quite large, for example having a mass of 400-3,000 mg, for example 600-1,500 mg. The total dosage unit weight may be selected as needed. For example, it may be scaled up or down depending on the nature of the selected active ingredients and their intended doses.

[0113] Each dosage unit typically consists of a self-supporting gelled oil-in-water emulsion as described herein. As will be understood, in this case the dosage unit will contain only the defined oil and water phases, i.e., no other components. Individual dosage units may be prepared from larger pieces of the gelled emulsion, for example, divided by cutting. More typically, however, each dosage unit will be formed by extrusion or molding from a liquid emulsion, or an incompletely gelled emulsion, prior to gelling (i.e., at a temperature above the gelling temperature of the gelling agent).

[0114] Alternatively, the gelled oil-in-water emulsion core may be provided with a suitable coating of a physiologically acceptable coating material. Such coatings may be conventional in the pharmaceutical and nutraceutical industries and may be applied by any conventional means, for example by dipping or spraying. In one set of embodiments, the gelled oil-in-water emulsions described herein may thus be provided with a coating. For example, they may be provided within a capsule shell that dissolves in the mouth. Viewed from another aspect, therefore, the invention provides an orally administrable capsule comprising a capsule shell encapsulating a gelled oil-in-water emulsion as described herein.

[0115] In the capsules of the present invention, the shell may be any physiologically acceptable material, but will typically be a sugar, a biopolymer, or a synthetic or semi-synthetic polymer that is soluble or degradable in saliva or fluids in the gastrointestinal tract. The shell may be soft, but is preferably substantially rigid. Particularly desirably, the capsule will have a "jelly bean" consistency. The shell will preferably be of a material and thickness to prevent oxidation of the contents. The shell may comprise a sugar or cellulose, e.g., sorbitol. The use of sugar and cellulose as capsule shell materials is well known in the pharmaceutical and nutraceutical fields.

[0116] Thus, the capsule shell material may typically be a sugar, e.g., sucrose, fructose, maltose, xylitol, maltitol, or sorbitol, but may also include hydrocolloid materials, e.g., carrageenan, alginates, pectin, cellulose, modified cellulose, starch, modified starch, gum arabic, etc. The capsule shell may also contain other ingredients, e.g., artificial sweeteners, colors, fillers, flavoring agents, antioxidants, etc.

[0117] The capsule shell may be preformed so that the oil-in-water emulsion can be filled into the shell as a liquid or once solidified. Alternatively, a shell precursor (e.g., a solution) may be coated onto the hardened emulsion, for example, using standard coating techniques. If desired, the capsule may be further coated, for example, with a wax.

[0118] The preparation of the gelled oil-in-water emulsions described herein may be carried out by emulsification of the aqueous phase components and the oil phase components. It will be understood that the emulsification is carried out under conditions where the aqueous phase is liquid (e.g., viscous liquid), i.e., prior to the formation of a gel. Thus, the emulsification is carried out at a temperature above the sol-gel transition temperature of the agar gelling agent. Subsequent cooling of the emulsion below the sol-gel temperature results in the desired gelled emulsion.

[0119] Prior to emulsification, any selected active agent may be added to the oil phase and / or water phase of the composition. This may be carried out, for example, by dissolving the active agent in the selected oil or water phase prior to forming the emulsion. Alternatively, prior to emulsification, the selected active agent(s) may be added to the mixture of water phase components and oil phase components. During the emulsification process, active agents typically migrate to the oil phase or water phase depending on their hydrophilic / lipophilic properties.

[0120] The formation of the emulsion may be achieved by conventional techniques and by using well-known equipment, for example homogenizers based on the rotor-stator principle. The speed and duration of stirring may be adjusted as needed, for example varied to achieve the desired shear forces and provide the desired droplet size.

[0121] Emulsification will generally be carried out under controlled atmosphere to avoid oxidative degradation of lipids and / or any active agents.For example, emulsification may be carried out in the presence of a non-oxidizing gas such as nitrogen.Degassing to remove air bubbles may also be carried out during the manufacturing process, for example, before mixing the components of the emulsion, after the liquid emulsion is formed, before packaging the hardened emulsion, etc.Degassing may be carried out using conventional means such as applying vacuum or sparging with a non-oxidizing gas (e.g., nitrogen).

[0122] After emulsification and gelation, the emulsion may be dried to reduce the water content, however, when dried it will still retain the continuous gelled water phase described herein and a water content within the ranges defined herein.

[0123] The gelled oil-in-water emulsion will typically be provided in the form of a dosage unit as described herein. The individual dosage units may be formed by methods such as molding, extrusion or cutting. Typically, however, the dosage units will be formed by filling the liquid emulsion into individual molds, such as a blister pack, which are then sealed. The dosage units will typically be in the form of a tablet or lozenge.

[0124] The method for preparing a gelled oil-in-water emulsion as described herein forms a further aspect of the present invention. Viewed from a further aspect, the present invention therefore provides a method for preparing an orally administrable gelled oil-in-water emulsion, said method comprising forming an oil phase comprising one or more physiologically acceptable lipids, forming an aqueous phase comprising a gelling agent which is agar, combining said oil phase and said aqueous phase to form an oil-in-water emulsion in the presence of a vegetable surfactant as described herein, and gelling said emulsion. If necessary, the emulsion may be divided into individual dosage units before or after gelling.

[0125] The dosage unit is preferably individually packaged in an airtight container, for example, a sealed wrapper, or more preferably, a blister of a blister pack.Accordingly, in another aspect, the present invention provides a package that includes an airtight compartment and a lighttight compartment that contains a dosage unit of the composition according to the present invention.By excluding both air (i.e. oxygen) and light from the packaged dosage unit, the long-term stability of the active ingredient is enhanced.

[0126] The package according to the invention is preferably provided in the form of a blister pack containing at least 2 dosage units, for example 2 to 100, preferably 6 to 30 dosage units. A blister pack generally comprises a metal, metal / plastic laminate, or plastic sheet substrate with molded recesses into which the dosage forms are placed. The pack is usually sealed with a foil, generally a metal or metal / plastic laminate foil, for example by applying heat and / or pressure to the area between the recesses. The use of metal or metal / plastic laminate to form the blister pack helps to prevent air (i.e. oxygen), light, and moisture from penetrating the contents of the blister pack, thus enhancing the stability of the active ingredient(s). The package according to the invention is preferably filled under a non-oxidizing gas atmosphere (e.g. nitrogen) or flushed with such a gas before sealing.

[0127] The use of agar as a gelling agent in the composition according to the invention provides further advantages with regard to the packaging of individual dosage units in blister packs and their removal by the end user. When the emulsion in liquid form is used to fill the cavities of the blister pack (i.e. before gelling), the emulsion is in intimate contact with the inner surface of the cavities. After the dosage units are set and the blister pack is sealed, it is important that the dosage units can be easily removed from the blister pack. The presence of gelatin, which was initially developed as an adhesive, in known gelatin-based compositions can make them difficult to remove from certain surfaces, such as surfaces made from plastic materials, especially when liquid emulsions containing gelatin are brought into contact with the surface and allowed to harden. In such cases, once hardened, the dosage units tend to adhere to the surface and must be peeled off, often resulting in fragmentation of the dosage units during the process, which is unacceptable. When packaging any conventional gelatin-based dosage units, the inner surface of the blister pack needs to be coated with a suitable release agent, such as a neutral oil or a neutral fat. Specially developed blister pack materials are available that incorporate release agents on the inside surface, but add cost to the packaging process. The use of a release agent also results in a surface coating of the release agent on the dosage unit once removed from the blister pack, which can result in an unpleasant feel or taste of the product.

[0128] In contrast to the use of gelatin, agar-based dosage units do not adhere to conventional blister pack materials. This means that standard materials can be used, including metal / plastic laminates, or plastic films to which plastic / metal foil laminates are heat sealed. Suitable blister trays with preformed cavities may be formed from laminated materials, such as, for example, Tekniflex® Aclar® VA10600 (TekniPlex), Perlalux® (Perlen Packaging), Formpack® (Amcor), and Regula® (Constantia Flexible). Such materials do not have any surface coatings that contain release agents.

[0129] Thus, in one embodiment, the dosage units of the invention may be packaged in a blister pack having an inner surface that is not coated with a release agent. Such blister packs containing the dosage units described herein form a further aspect of the invention.

[0130] The gelled oil-in-water emulsions according to the invention find use both as medicines, i.e. for therapeutic purposes, and as dietary supplement products to maintain or enhance the health and / or general well-being of human or animal subjects. For this purpose, they are intended to be taken orally, chewed lightly in the mouth and then swallowed. It is not intended that they should remain in the mouth or need to be chewed for extended periods. Due to their soft texture, a light chew is sufficient to fragment the dosage form into smaller pieces that are easily swallowed. What the applicant has surprisingly found is that the gelled oil-in-water emulsions according to the invention have a much better mouthfeel than pure aqueous agar gels. While aqueous agar gels are brittle and "fracture" in the mouth when chewed, the emulsions described herein are more resistant to deformation and less likely to fracture when chewed. This provides a much more acceptable chewing experience for the patient or consumer.

[0131] For example, when used as a dietary supplement, the compositions described herein may be used as a supplement (e.g., a dietary supplement) to maintain the general health and / or well-being of a subject. Any agent known for its dietary supplemental effect may be provided in the composition, and suitable agents are well known in the art. Suitable dietary supplements include, but are not limited to, any of the following: essential fatty acids (e.g., monounsaturated and polyunsaturated fatty acids), essential amino acids (e.g., taurine, tryptophan, tyrosine, cysteine, and homocysteine), vitamins (e.g., vitamins A, B1-B12, C, D, E, K, and folic acid), minerals (e.g., iodine, selenium, iron, zinc, calcium, and magnesium), flavonoids, carotenoids (e.g., β-carotene, α-carotene, lutein, zeoxantaine, xanthophylls, and lycopene), phytosterols, saponins, probiotics, dietary fiber (e.g., insoluble fiber and β-glucan), and botanical extracts (e.g., aloe vera, evening primrose oil, garlic, ginger, ginseng, green tea, caffeine, and cannabinoids). When magnesium or calcium is present, they will generally be used in the form of a phosphate salt.

[0132] In particular, the gelled oil-in-water emulsions described herein may be used as a source of one or more essential fatty acids, such as PUFAs (Poly Unsaturated Fatty Acids) or their esters, such as omega-3 fatty acids, omega-6 fatty acids, and / or omega-9 fatty acids, and their ester derivatives. Examples of omega-3 acids include alpha-linolenic acid (ALA), stearidonic acid (SDA), eicosatrienoic acid (ETE), eicosatetraenoic acid (ETA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), tetracosapentaenoic acid, and tetracosahexaenoic acid. Examples of omega-6 acids include linoleic acid, gamma-linolenic acid, eicosadienoic acid, dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), docosatetraenoic acid, adrenic acid, docosapentaenoic acid, and calendic acid. Examples of omega-9 acids include oleic acid, eicosenoic acid, mead acid, erucic acid, and nervonic acid. Omega-3 acids, particularly EPA and DHA, are highly preferred.

[0133] The health benefits of essential fatty acids, especially omega-3 fatty acids, are well known. For example, they can lower the amount of triglycerides and / or lower the amount of cholesterol. Omega-3 fatty acids are essential for daily life and health. The beneficial effects of EPA and DHA on lowering serum triglycerides are well known. They are also well known for other health benefits, such as the cardioprotective effects in preventing cardiac arrhythmias, stabilizing atherosclerotic plaques, reducing platelet aggregation, and lowering blood pressure. Therefore, they are used to treat and / or prevent vascular diseases. Other benefits of omega-3 fatty acids include the prevention and / or treatment of inflammation and neurodegenerative diseases, and the improvement of cognitive development and cognitive function.

[0134] The essential fatty acids may form part or all of the oil phase in the gelling emulsion, preferably at least 10% by weight, more particularly at least 50% by weight, especially at least 80% by weight of that phase. They may be used as single compounds or as a mixture of compounds, for example vegetable or fish oils. Free fatty acids, monoacylglycerides and diacylglycerides may be prepared by complete or partial hydrolysis of triacylglycerides, for example acid, base or enzyme-catalyzed hydrolysis, for example using lipases such as pancreatic lipase and / or lipases that may be produced from bacteria as fermentation products. Alkyl esters of essential fatty acids may be prepared by transesterification using a suitable alkanol or by esterifying the free fatty acid with the alkanol. When free fatty acids are used, they may be in acid form or salt form (for example completely or partially in salt form) and preferably constitute 5-75% by weight, especially 10-35% by weight, of the essential fatty acids in the oil phase. The salt form may be preferred.

[0135] The gelled oil-in-water emulsions described herein can also be used as pharmaceuticals in the treatment or prevention of a range of medical conditions responsive to the selected active agent(s). As will be appreciated, the nature of such conditions will depend on the active agent(s) selected, but can be readily determined by one of skill in the art.

[0136] Any drug substance having the desired therapeutic and / or prophylactic effect may be used, including lipophilic or hydrophilic drug substances.

[0137] Suitable drug substance classes include, but are not limited to, any of the following: analgesics, anti-inflammatory agents, anti-cancer agents, cardiovascular agents, biological agents, anti-allergy agents (e.g., antihistamines), decongestants, antiemetics, agents affecting gastrointestinal function, agents acting on blood and blood-forming organs, agents affecting renal and cardiovascular function, antifungals, urological agents, hormones, antibacterial agents, antiepileptic agents, tranquilizers, antipsychotics, psychostimulants, anticholinesterase agents, and carotenoids.

[0138] Examples of specific drug substances that may be used in the compositions of the present invention include temazepam, diphenhydramine, zolpidem, triazolam, nitrazepam, testosterone, estradiol, progesterone, benzodiazepines, barbiturates, cyclosporine, insulin, calcitonin, dextromethorphan, pseudoephedrine, phenylpropanolamine, bromocriptine, apomorphine, selegiline, amitriptyline, dextroamphetamine, phentermine, mazindol, compazine, chlorpromazine, perphenazine, fluoxetine, and fluoxetine. Xetine, buspirone, clemastine, chlorpheniramine, dexochlorpheniramine, astemizole, loratadine, paracetamol, ketoprofen, naproxen, ibuprofen, sodium acetazolamide, acetylsalicylic acid, aminophylline, amiodarone hydrochloride, ascorbic acid, atenolol, bendroflumethiazide, calcium folinate, captopril, cetirizine hydrochloride, chloramphenicol sodium succinate, chlorpheniramine maleate, chlorpromazine hydrochloride cimetidine hydrochloride, ciproxacin hydrochloride, clindamycin hydrochloride, clonidine hydrochloride, codeine phosphate, cyclizine hydrochloride, cyclophosphamide, dexamethasone sodium phosphate, dicloxacillin sodium, dicyclomine hydrochloride, diltiazem hydrochloride, diphenhydramine hydrochloride, disopyramide phosphate, doxepin hydrochloride, enalapril maleate, erythromycin ethylsuccinate, flecainide acetate, fluphenazine hydrochloride, folic acid, granisterone hydrochloride, guaifenesin, haloperidol lactate, hydralazine hydrochloride, hydroxychloroquine morphine sulfate, hydromorphone hydrochloride, hydroxyzine hydrochloride, indomethacin sodium, isoniazid, isoprenaline hydrochloride, ketorolac trometamol, labetalol hydrochloride, lisinopril, lithium sulfate, mesoridazine benzilate, methadone hydrochloride, methylphenidate hydrochloride, methylprednisolone sodium succinate, metoprolol tartrate, metronidazole sulfate, methyldopa, mexiletine hydrochloride, molydone hydrochloride, morphine sulfate, naltrexone hydrochloride, neomycin sulfate, ondansetron hydrochloride, orciprenaline sulfate, oxacillin sodium,Oxybutynin chloride, oxycodone hydrochloride, paracetamol, penicillamine, pentoxifylline, pethidine hydrochloride, phenobarbital sodium, phenoxymethylpenicillin potassium, phenylephrine hydrochloride, phenytoin sodium, potassium iodide, primaquine phosphate, procainamide hydrochloride, procarbazine hydrochloride, prochlorperazine maleate, promazine hydrochloride, promethazine hydrochloride, propranolol hydrochloride, pseudoephedrine hydrochloride, pyridostigmine bromide, hydrochloride Pyridoxine, ranitidine hydrochloride, salbutamol sulfate, sodium ethacrynate, sotalol hydrochloride, sumatriptan succinate, terbinafine hydrochloride, terbutaline sulfate, tetracycline hydrochloride, thioridazine hydrochloride, thiothixene hydrochloride, trifluoperazine hydrochloride, triprolidine hydrochloride, sodium valproate, vancomycin hydrochloride, vancomycin hydrochloride, verapamil hydrochloride, warfarin sodium, astaxanthin, lutein, CoQ10, and fenofibrate.

[0139] The amount of drug substance per unit dose of the composition of the invention will conveniently be in the range of 10-100% of the recommended daily dose for an adult or child.

[0140] Viewed from another aspect, the present invention therefore provides a gelled oil-in-water emulsion as described herein for use in therapy.

[0141] Viewed from yet another aspect, the present invention provides a gelled oil-in-water emulsion as described herein containing at least one pharma- ceutical active ingredient, for oral use in the treatment of a condition responsive to said pharma-ceutical active ingredient.

[0142] In another aspect, the present invention provides the use of a pharma- ceutical active ingredient in the manufacture of a medicament for oral use in the treatment of a condition responsive to said pharma- ceutical active ingredient, wherein said medicament is provided in the form of a gelled oil-in-water emulsion as described herein.

[0143] Corresponding medical methods of treatment form a further aspect of the invention. Viewed from yet another aspect, the present invention therefore provides a method of treating a human or non-human animal subject (e.g. a patient) for dealing with a condition responsive to a pharma- ceutical active ingredient, said method comprising orally administering to said subject a pharma- ceutical effective amount of said agent in the form of a gelled oil-in-water emulsion as described herein.

[0144] In another aspect, the present invention provides the use of a gelled oil-in-water emulsion as described herein as a dietary supplement. Corresponding methods of administering the gelled oil-in-water emulsion to achieve a dietary supplement effect also form part of the present invention.

[0145] Viewed from another aspect, the invention therefore provides a method of administering an active agent to a human or non-human animal subject to enhance and / or maintain the health or well-being of said subject, said method comprising orally administering to said subject a nutraceutical effective amount of an active agent in the form of a gelled oil-in-water emulsion as described herein.

[0146] In another aspect, the present invention provides the use of a gelled oil-in-water emulsion as described herein as a dietary supplement product.

[0147] When used in any of the above treatments or methods, or as a dietary supplement or pharmaceutical formulation, the effective amount of the active agent can be readily determined.

[0148] The amount of an effective dose for any particular subject will depend on a variety of factors, including the disorder and its severity, the identity and activity of the particular composition, the subject's (e.g., patient's) age, weight, general health, timing of administration, duration of treatment, other drugs used in combination with the treatment, etc. It is well within the skill of one of ordinary skill in the art to select the desired dose to achieve the desired therapeutic effect.

[0149] The invention will now be further described with reference to the following non-limiting examples and the accompanying figures. [Figure 1] Dynamic storage modulus (G'max) of agar-based gelling oil-in-water emulsions containing different surfactants. FIG. 2 shows the dynamic storage modulus (G′max) for a gelled oil-in-water emulsion according to the present invention. [Figure 3] Figure 3 shows the hardness (force) of a gelled oil-in-water emulsion according to the present invention, measured according to the Texture Profile Analysis (TPA) test. FIG. 4 shows the dynamic storage modulus (G′max) for a gelled oil-in-water emulsion according to the present invention.

[0023] FIG. 5 shows the hardness (force) of a gelled oil-in-water emulsion according to the present invention when subjected to large scale deformation. [Figure 6] Measured water activity of aqueous agar gels with increasing glycerol content. [Figure 7] Hardness (force) of a gelled oil-in-water emulsion according to the present invention compared to a pure agar gel. [Figure 8] Hardness (force) of gelled oil-in-water emulsions containing gelatin as the gelling agent.

[0150] [Example] Test Method: 1. Rheological characterization of agar and agar emulsion gels 1a- Small scale deformation Rheological analysis of the gels was carried out using a rheometer (Malvern Kinexus ultra+, Westborough, USA). The lower plate was a KNX0127, curved sandblasted lower plate with a diameter of 50 mm. The upper geometry was a CP4 / 40, 4° angle cone with a diameter of 40 mm for gelatin emulsion gels, and a sawtooth PP40X SW1648SS for agar gels and agar emulsion gels. Instrument calibration (0 gap) was performed before the analysis. After gel preparation, approximately 2 grams of gel was placed on the lower plate, which was heated to 60 °C. The rheometer was operated in a shear strain control mode of 0.1% and the frequency was set to 1 Hz. The selected strain was confirmed to be within the linear viscoelastic region for all samples. To avoid evaporation, the gelatin emulsion gel samples were covered with silicone oil (10 cS fluid, Dow Corning, UK) prior to the measurements. Viscoelastic properties of the samples were obtained using a temperature gradient of 2°C / min with starting and ending temperatures of 60°C and a holding time of 15 min at 20°C for gelatin emulsion gels. For agar emulsion gels, the final temperature was 90°C and oscillations continued for 10 min at 90°C. Results were analyzed using rSpace from Kinexus software. The gelling and melting temperatures of the samples were estimated as the temperatures corresponding to a phase angle of 45° in the cooling and heating processes, respectively. The maximum storage modulus (G') (Pa) was determined as the highest measured point during hardening at 20°C.

[0151] 1b-Large-scale deformation The texture properties of the gels were analyzed with a TA.XT plusC Texture Analyser (Stable Micro Systems Ltd., UK). Upon preparation, the gels were cast using a cylindrical mould of standard dimensions (height 19.6 mm, diameter 8 mm). The gels were allowed to cure for 18 hours at ambient temperature before analysis. Single compression analysis and standard texture profile analysis (TPA) were performed using a 5 kg load cell. A 35 mm diameter cylinder aluminium probe P / 35, supplied by Stable Micro Systems Ltd., was used. For the 75% large strain single compression, the pre- and post-test speeds were 2 mm / s, while the test speed was 0.5 mm / s and the trigger force was 5 grams. The strain height was measured automatically during compression. Maximum stress (g) and strain (%) data at break were obtained from the splitting moment of the gels. The slope (N / m) was calculated by the ratio of the forces at 2% and 3% strain. Young's modulus (N / m 2 ) was calculated from the slope by the following formula:

[0152]

number

[0153] The gel area is the contact area between the gel and the probe.

[0154] 2. Texture Profile Analysis (TPA Test) Standard TPA was performed at room temperature with 20% strain double compression applying a TA.XT plusC Texture Analyser (Stable Micro Systems Ltd., UK) using a 5 kg load cell and a P / 35 aluminium probe. A cylindrical mould of standard dimensions (height 19.6 mm, diameter 8 mm) was used. The gels were allowed to cure for 18 hours at ambient temperature before analysis. The pre-test, test and post-test speeds were 1 mm / s and the trigger force was 5 grams. The strain height was measured automatically during compression. Hardness, adhesiveness, elasticity, cohesiveness, springiness, tackiness and chewiness parameters were measured. Data were analysed with Exponent connect software.

[0155] 3. Syneresis Measurement Syneresis measurements were based on the weight loss of the gel. The gels were weighed and sealed in airtight, moisture-proof aluminum foil. After freezing at -20°C, thawing at ambient temperature and removing excess liquid, the gels were weighed again and the difference in gel weight was normalized to the percent loss.

[0156] 4. Water Activity Measurement Water activity was measured at ambient temperature using a HygroPalm HC2-AW (Rotronic, Switzerland). Samples were placed in the measurement chamber and the water activity was recorded after 45 min.

[0157] Example 1 - Gelled oil-in-water compositions and methods of preparation Composition: Exemplary gelled oil-in-water compositions according to the present invention are listed in the table below: It will be understood that any component that may be present in an amount of 0% by weight is optional.

[0158] [Table 1]

[0159] Preparation method: In the following methods, the pH adjuster is an organic acid / base buffer system consisting of trisodium citrate and malic acid, and the plasticizer, if present, is glycerol. 1. Mix agar, sugar alcohol, and optional sweetener(s) into a homogenous powder mixture. 2. Weigh out sterile water into a bottle and add the powder mixture to the water. 3. Place the bottle in a 90°C water bath and mix with magnetic stirring at 100 rpm for 30 minutes. If glycerol is used, heat it separately at 60°C for 30 minutes. 4. Reduce the temperature to 60° C. and mix the aqueous phase with magnetic stirring for an additional 30 minutes (approximately 60 minutes total). If glycerol is used, add the heated glycerol to the mixture via syringe. 5. Mix the oil along with any flavor and / or colorant(s) in a beaker and preheat to 50° C. for 30 minutes (40 minutes out of a total of 60 minutes). 6. When the ingredients are completely dissolved, slowly add the surfactant and trisodium citrate to the water phase. If the surfactant contains any vegetable protein, it is added at a temperature below the denaturation temperature of the vegetable protein. Mix for 10 minutes and slowly (carefully and gradually) add the malic acid. Mix the mass for an additional 10 minutes. 7. If using an antifoaming agent, add half of this agent and leave without stirring for 1 minute. 8. Weigh the bottle containing the water phase and vacuum the mass. Add the (heated) water loss and mix for 1 minute. 9. Add the oil phase to the agar mass (water phase) and homogenize the two phases for approximately 10 minutes using a high speed blender such as an Ultra-Turrax. 10. If appropriate, add the second half of the (heated) antifoam agent and leave without stirring for 1 minute. 11. Weigh the bottle and vacuum the mass. Add the (heated) water loss and mix for 1 minute. 12. If desired, fill the resulting emulsion into blisters of a blister pack and seal.

[0160] Example 2 - Gelled Oil-in-Water Emulsion - Typical Formulation

[0161] [Table 2] The emulsion may be prepared according to the general method of Example 1.

[0162] Example 3 - Gelled oil-in-water emulsion containing algae oil

[0163] [Table 3]

[0164] The emulsion is prepared according to the general method of Example 1.

[0165] Example 4 - Gelled Oil-in-Water Emulsion Containing Sunflower Oil

[0166] [Table 4] The emulsion is prepared according to the general method of Example 1.

[0167] Example 5 - Gelled oil-in-water emulsion containing algae oil

[0168] [Table 5]

[0169] The emulsion is prepared according to the general method of Example 1.

[0170] Example 6 - Gelled oil-in-water emulsion containing algae oil

[0171] [Table 6]

[0172] The emulsion is prepared according to the general method of Example 1 using trehalose and sucrose as sugar alcohols. After homogenization of the two phases, 50% by weight of citric acid is added until a pH of 4.5 is reached.

[0173] Example 7 - Multivitamin supplement

[0174] [Table 7]

[0175] The emulsion is prepared according to the general method of Example 1. Vitamin D and Vitamin K are added to the oil in step 5 and Vitamin B12 is added to the water phase in step 6.

[0176] Example 8 - Multimineral Supplement

[0177] [Table 8]

[0178] The emulsion is prepared according to the general method of Example 1. Minerals are added to the water phase in step 6.

[0179] Example 9 - Calcium Supplements

[0180] [Table 9]

[0181] The emulsion is prepared according to the general method of Example 1. Calcium phosphate is added to the aqueous phase along with broad bean protein and sodium tricitrate.

[0182] Example 10 - Multivitamin supplement

[0183] [Table 10]

[0184] Emulsions are prepared according to the general method of Example 1. Fat soluble vitamins (E, A, D3) are mixed into the oil as in Example 7, and water soluble vitamins (C, B3, B6, B12, folic acid, D-biotin) as well as iodine are mixed as in Example 8 with CaHPO4.

[0185] Example 11 - Gelled Oil-in-Water Emulsion Containing Corn Oil

[0186] [Table 11]

[0187] The emulsion is prepared according to the general method of Example 1.

[0188] Example 12 - Gelled oil-in-water emulsion containing corn oil

[0189] [Table 12]

[0190] The emulsion is prepared according to the general method of Example 1.

[0191] Example 13 - Packaging Blister Pack: Prior to curing, the emulsions produced in any of Examples 1-12 may be filled into blister trays made from metal / plastic laminates or plastic films to which the plastic / metal foil laminate is heat sealed. Blister trays with preformed cavities may be made from laminate materials such as Tekniflex® Aclar® VA10600 (TekniPlex), Perlalux® (Perlen Packaging), Formpack® (Amcor), and Regula® (Constantia Flexible).

[0192] The liquid emulsion produced in any of Examples 1-12 is filled into the blister tray using a syringe, ensuring that the cavity is filled evenly and completely. The blister tray is then flushed with nitrogen for 5-10 seconds and sealed with metal / plastic or metal / heat seal lacquer coated foil by applying a flat iron set at 160°C for 2-4 seconds. The samples are left to cure at room temperature for 24 hours and subjected to a controlled holding chamber at 40°C, 65% RH for 30 days. Samples were removed from the controlled chamber on days 5, 10, 15, 20, 25, and 30. After 24 hours at room temperature, the blister pack is opened. The amount of residue adhering to the tray and the force required to remove the unit dose from the pack are recorded on a scale of 1-9, where 1 indicates no adhesion and very little force required to remove the unit dose ("pop out") and 9 indicates complete adhesion to the foil and the unit dose must be peeled from the foil. Each of the laminate materials listed above received a score of 1, 2, or 3 (predominantly 1 or 2) in each test.

[0193] Small piece: Prior to curing, the emulsions produced in any of Examples 1-12 may be extruded into individual pieces and then, once cured, sealed into individual plastic / metal foil laminate pouches. Alternatively, the single extruded piece, once cured, may be cut into individual pieces as needed prior to packaging.

[0194] Example 14 - Coated Gelled Emulsion The hardened emulsion produced in any of Examples 1-12 may be coated with a sorbitol solution containing sorbitol (80% by weight), lemon flavoring agent (0.15% by weight), yellow colorant (0.5% by weight), and water (an additional 100% by weight). The coating solution may be cured at 99-95°C for 4-5 hours before application. Coating is carried out by dipping or panning at 20-45°C. Several layers of coating material may be added with drying between each layer until the final composite layer is hard.

[0195] Alternatively, the liquid emulsion prepared in any of Examples 1-12 may be filled into a soft capsule shell prior to hardening. The capsule shell material may typically be a sugar, such as sucrose, fructose, maltose, xylitol, maltitol, or sorbitol, but may also contain hydrocolloid materials such as carrageenan, alginates, pectins, cellulose, modified cellulose, starch, modified starch, or gum arabic. The capsule shell may contain additional ingredients such as artificial sweeteners, colors, flavors, and antioxidants.

[0196] Example 15 - Effect of different surfactants on dynamic storage modulus (G'max) Gelling oil-in-water emulsions containing 2.5 wt% agar were prepared using soy protein, pea protein (Nutralys F85M), propylene glycol alginate (degree of esterification: 84%) (PG alginate), Tween 80, and LACTEM as surfactants. Gelling oil-in-water emulsions with agar concentrations ranging from 0.75 to 3 wt% were also produced using soy protein. All formulations were tested for their rheological properties.

[0197] The following formulation, containing 2.5% by weight agar as the gelling agent, was prepared according to the general protocol of Example 1.

[0198] [Table 13]

[0199] Formulations with agar concentrations ranging from 0.75 to 3.0% by weight were also prepared using soy protein as a surfactant. Any changes in agar concentration were compensated for by an equivalent change in sorbitol content.

[0200] Soy protein, pea protein, and PG alginate are high molecular weight surfactants (i.e., "supermolecular"), whereas Tween 80 and LACTEM are low molecular weight surfactants. Tween 80 is a polysorbate surfactant derived from polyethoxylated sorbitan and oleic acid. LACTEM consists of lactic acid esters of mono- and diglycerides.

[0201] No stable emulsions could be prepared with Tween 80 or LACTEM. For all other formulations, the dynamic storage modulus (G'max) was measured according to the small-scale deformation test described herein. The results are shown in Figure 1. When using supramolecular surfactants (soy protein / pea protein, and PG alginate), it could be observed that the small-scale deformation modulus of the solid emulsions increases with increasing agar concentration. Without being bound by theory, this is believed to be due to a friction layer around the droplets generated by the non-uniform distribution of large molecules ("hairy"), which provides a "semi-active filler" effect. This effect increases with increasing agar concentration. All supramolecular surfactants gave stable emulsions.

[0202] Example 16 - Compression Test The following formulation, containing 2.5% by weight agar as the gelling agent, was prepared according to the general protocol of Example 1.

[0203] [Table 14]

[0204] Formulations with agar concentrations ranging from 0.25 to 3.0% by weight were also prepared, with changes in agar concentration being compensated for by an equivalent change in sorbitol content.

[0205] While still liquid, the emulsion (1 ml) was poured into a standard non-stick blister foil pack and sealed with a flat iron at 150°C. After 24 hours at room temperature, the agar emulsion solidified and a compression test was performed to evaluate the minimum agar concentration that could be squeezed out of the blister form without destroying the gelling tablet. The lowest agar concentration that could be tolerated without fracturing was 0.75 wt%. This corresponds to a G'max of approximately 15 kPa. The highest acceptable agar concentration was found to be 2.5 wt% based on visual observation that the solution became very thick before solidification. This corresponded to a viscosity measured at 55°C of 60 Pa.s at a shear rate of 1 / s and 23 Pa.s at a shear rate of 10 / s.

[0206] Example 17 - Effect of different surfactants Tests were carried out to evaluate the effect of surfactant molecular weight. As reported in Example 15, high molecular weight surfactants - soybean protein and pea protein, and propylene glycol alginate (PG alginate) - provided stable emulsions with high dynamic storage modulus (G'max). This was attributed to the formation of "hairy" droplet surface formation, which acts as a semi-active filler through increased friction. In the following series of experiments, hydroxypropyl methylcellulose (HPMC) materials with the same degree of substitution but with various weight average molecular weights were tested. HPMC materials with the following properties were obtained from Shin-Etsu Tylose GmbH.

[0207] [Table 15]

[0208] The basic formulation used in this series of experiments was as follows:

[0209] [Table 16]

[0210] Preparation of oil-in-water emulsion: 1. Agar and sugar alcohol were mixed as dry powders and added to a bottle with the correct amount of water. The bottle was placed in a 90°C water bath and magnetically stirred for 30 minutes. 2. The bottle was transferred to a 50°C water bath and equilibrated for 15 minutes. This is the stage where the HPMC surfactant was added and the mixture was left for 30 minutes to allow the HPMC to dissolve. 3. Pre-heated (50°C) corn oil was added and homogenization was carried out using an Ultra-Turrax for 5 minutes. 4. The resulting emulsion was reconstituted at 55°C for 10 minutes before rheological testing. Rheological experiments were carried out applying a Kinexus Ultra+Rheometer with 5.C 4 / 40 measurement geometry. G' values ​​for different systems were recorded after applying a strain of 0.1%, a frequency of 1 Hz, a temperature gradient from 50 to 20°C, and a holding time of 20 min at 20°C.

[0211] The results are presented in Table 1.

[0212] [Table 17]

[0213] An increase in weight average molecular weight from 24 to 94 kDa resulted in a doubling of the G'max value when HPMC was used as the supramolecular surfactant. No further increase in molecular weight was observed. It was observed by visual inspection that the lowest Mw HPMC surfactants gave higher syneresis (release of the aqueous phase) than the higher Mw ones. All HPMC formulations were able to retain oil when exposed to mechanical stress. Thus, the higher Mw surfactants give an additional benefit other than increased gel strength, namely less syneresis and better retention of oil.

[0214] Example 18 - Study demonstrating the effect of increasing agar concentration on gelling oil-in-water compositions containing agar and gum arabic Using a method similar to Example 1, a 50 g formulation was prepared containing the following ingredients:

[0215] [Table 18]

[0216] Droplet size and size distribution were measured using a Malvern Mastersizer 3000 (Worcestershire, UK) connected to a Hydro MV, wet dispersion unit (Malvern, Worcestershire, UK). Analysis of the data was performed using the manufacturer's software (Mastersizer 3000, v1.0.1). Tests were performed by dissolving and diluting the gelled emulsions in a 10% (v / v) HCl solution (1:100) at 50°C. The refractive indexes of water and corn oil were set to 1.33 (solvent) and 1.47 (dispersed phase), respectively, and the absorptivity of the dispersed droplets was set to 0.01. To avoid multiple scattering or low intensity of the scattered light, each dissolved emulsion was added to the dispersion unit (containing about 125 mL of water) until about 10% obscuration was obtained. The droplet size distributions of the different emulsions are shown in Table 2.

[0217] [Table 19]

[0218] The dynamic storage modulus (G'max) was measured according to the small-scale deformation test described herein. The results in Figure 2 show the shear modulus (elastic component) of the resulting emulsion as a function of temperature and time. The formulation containing 1.13 wt% agar (Example 18A) had a G'max of 15,650 Pa, while the formulation containing 1.50 wt% agar (Example 18B) had a G'max of 21,220 Pa. This confirms the increase in gel strength with increasing agar concentration. Both formulations exhibited "solid-like" properties over a wide temperature range.

[0219] Example 19 - Testing of gelling oil-in-water compositions containing agar with and without gum arabic. Using a method similar to Example 1, a 50 g formulation was prepared containing the following ingredients:

[0220] [Table 20]

[0221] The droplet size and size distribution were measured as described in Example 18. The results are shown in Table 3.

[0222] [Table 21]

[0223] Texture analysis was performed using the standard TPA test described herein, and the results are shown in Table 4 and Figure 3.

[0224] [Table 22]

[0225] In general, it was found that the presence of gum arabic resulted in a slightly softer gelled emulsion with smaller droplet size.

[0226] Example 20 - Droplet size and size distribution Using a method similar to Example 1, a 50 g formulation was prepared containing the following ingredients:

[0227] [Table 23]

[0228] Droplet size and size distribution were measured as described in Example 18. Rheological analysis was performed according to the small-scale deformation test described herein. According to standard rheological measurement methods, Tg and Tm were determined when the phase angle was below or above 45° under a given temperature gradient, strain, and frequency. The results are provided in Table 5 and Figure 4.

[0229] [Table 24]

[0230] Example 21 - Droplet size and size distribution Using a method similar to Example 1, a 50 g formulation was prepared containing the following ingredients:

[0231] [Table 25]

[0232] Droplet size and size distribution were measured as described in Example 18. The results are provided in Table 6.

[0233] [Table 26]

[0234] Example 22 - Large scale modification of gelled oil-in-water emulsions Large scale deformation of agar-based emulsions prepared according to Examples 19A and 19B was compared with that of purely aqueous agar gels. Purely aqueous agar gels were prepared by mixing agar (2 wt%) and Milli-Q-water (MQH2O) at 90° C. The mixture was cooled to ambient temperature for further characterization of the gels.

[0235] Testing was performed according to the large scale deformation method described herein, and the results are shown in Figure 5 and Table 7.

[0236] [Table 27]

[0237] The Young's modulus (or relatedly the initial slope of the force / deformation curve) is somewhat higher for the agar-based gelling emulsions according to the invention, which means that they offer higher resistance at very low deformations. However, these compositions preserved much more structure after fracture (at about 25% strain) compared to pure aqueous agar gels. This means that the agar-based gelling emulsions according to the invention do not shatter in the mouth and therefore offer a more appealing chewing experience.

[0238] Example 23 - Syneresis Test An experiment was carried out to compare the syneresis of agar-based emulsions according to Examples 20 and 21B (containing 1.5% and 2.0% agar by weight, respectively) with that of a pure aqueous agar gel. The pure aqueous agar gel was made according to the same method as in Example 22. Each gel was subjected to freeze-thaw cycles and the average weight loss was measured as described in the syneresis test described herein. The results are shown in Table 8.

[0239] [Table 28]

[0240] Pure agar gel loses more than 50% of its original water content after freeze-thaw cycling, indicating significant syneresis. The water loss of the gelled oil-in-water emulsion according to the invention is about 20 times lower. The agar content does not significantly affect the degree of syneresis, and both gelled emulsions according to the invention showed acceptable syneresis properties.

[0241] Example 24 - Effect of glycerol Aqueous solvents for use in producing formulations according to the invention may be modified by incorporating glycerol. Aqueous agar gels were produced in which water was successively exchanged with glycerol to measure relative changes in the properties of the aqueous gel. The glycerol concentration was varied from 0 to 90% by weight and the water activity was measured as described herein. The results are shown in FIG. 6. A water activity of less than 0.8 was achieved with a 50:50 mixture of water:glycerol. At this water activity, microbial growth is prevented. By using glycerol instead of water, it is possible to lower the water activity and reduce the need for sugar alcohols to obtain a product stable to microbial degradation.

[0242] G'max and gelation temperature were also measured for different gels according to the small-scale deformation method described herein. With increasing glycerol content, an increase in dynamic storage modulus was observed up to 50% inclusion of glycerol. The gelation temperature began to decrease significantly around the same glycerol concentration. Large-scale deformation and penetration showed an increase in resistance as the glycerol content increased up to 50%. This is almost consistent with the small-scale deformation results (G'). At the same time, an increase of up to about 30% in the compression distance before breakage was recorded at low and medium glycerol contents. This was also confirmed in the chewing test, where the glycerol-containing gels were perceived as more "gelatin-like" than those without glycerol.

[0243] Example 25 - Testing of gelled oil-in-water compositions with higher oil content and comparison with gelatin-based oil-in-water compositions. A gelling oil-in-water composition containing agar and broad bean protein and 40 wt% oil was prepared according to Example 21B, but without paprika, lemon, or stevia. Oil was gradually added, first to 25 wt%, then to 30 wt%, then to 35 wt%. At each step, the oil was first mixed with a magnet or spatula before homogenizing using an ultra turrax machine. The final 5 wt% oil (up to 40 wt%) was incorporated by pure shaking due to the very high viscosity that the ultra turrax could not mix properly. A pure agar gel (no oil) was made as a comparison. For comparison, an aqueous gelatin gel was also made using 6.67 wt% 260 Bloom type B bovine gelatin in water. This was gelled overnight at 4°C in a cylinder and fully equilibrated to room temperature before texture measurement.

[0244] Large scale deformation measurements were performed as described herein. The results for the agar-based compositions (without oil and with 40 wt.% oil) are provided in Figure 7, and the results for the gelatin gels are shown in Figure 8. These are also provided in Table 9.

[0245] [Table 29]

[0246] The Young's modulus becomes more comparable to that of gelatin gels in agar gels containing 40% oil by weight compared to agar gels without oil. The overall maximum gel strength decreases with the presence of oil, but shows the same large-scale preservation of structure (relatively greater than in the absence of oil, but sugar alcohols alone contribute very significantly to the preserved structure at high strains).

[0247] Gelatin gels typically break at much higher strains and show high resistance at high deformations compared to the deformations of chewing.What makes the agar gel formulations containing oil and supramolecular surfactants according to the present invention more comparable to gelatin is, for example, the particular preservation of structure at strains of more than 40%.

[0248] Droplet size measurements were also performed on agar-based emulsions with different oil contents. The emulsions were slightly flocculated after dilution with water and peptized by adding SDS before droplet size measurements. Successful peptization was confirmed by optical microscopy before measurements. The droplet sizes of the emulsions are given in Table 10.

[0249] [Table 30]

Claims

1. 1. An orally administrable gelled oil-in-water emulsion that is a self-supporting viscoelastic solid having a gelled aqueous phase that comprises a gelling agent that is agar, An emulsion, wherein the emulsion is stabilized by a surfactant which is a plant-based protein, a plant-based polysaccharide, or a derivative thereof.

2. 2. The orally administrable gelled oil-in-water emulsion of claim 1, wherein the surfactant is a plant protein or a derivative thereof.

3. 3. An orally administrable gelled oil-in-water emulsion according to claim 2, wherein said protein is obtained from a legume, preferably from pea or kidney bean.

4. 4. The orally administrable gelled oil-in-water emulsion of claim 3, wherein said protein is fava bean protein or soy protein.

5. 2. The orally administrable gelled oil-in-water emulsion of claim 1, wherein the surfactant is a plant-based polysaccharide or a derivative thereof.

6. 6. The orally administrable gelled oil-in-water emulsion of claim 5, wherein said surfactant is a hydrophobically modified polysaccharide.

7. 6. The orally administrable gelled oil-in-water emulsion of claim 5, wherein the surfactant is cellulose or a cellulose derivative, starch or a starch derivative, or propylene glycol alginate.

8. 2. The orally administrable gelled oil-in-water emulsion of claim 1, comprising agar at a concentration of about 0.1 to about 5% by weight, based on the total weight of the emulsion.

9. 10. The orally administrable gelled oil-in-water emulsion of claim 1, further comprising glycerol.

10. 2. The orally administrable gelled oil-in-water emulsion of claim 1, wherein the aqueous phase constitutes 50-95% by weight of the emulsion, preferably 55-90% by weight, such as 60-85% by weight, 70-85% by weight, or 75-80% by weight.

11. 2. The orally administrable gelled oil-in-water emulsion of claim 1, wherein the aqueous phase further comprises one or more bulking agents, such as a sugar alcohol or a sugar.

12. 12. An orally administrable gelled oil-in-water emulsion according to claim 11, wherein the bulking agent is present in a concentration of 45 to 70% by weight, preferably 50 to 65% by weight, for example 55 to 60% by weight, based on the aqueous phase.

13. 2. The orally administrable gelled oil-in-water emulsion of claim 1 having an oil phase comprising one or more physiologically acceptable lipids derived from rapeseed oil, sunflower oil, corn oil, olive oil, sesame oil, palm kernel oil, coconut oil, nut oil, algae oil or hemp oil.

14. 2. The orally administrable gelled oil-in-water emulsion of claim 1, having an oil phase that constitutes 5-50% by weight of the emulsion, preferably 10-45%, for example 15-40%, 15-30%, or 20-25%.

15. 10. The orally administrable gelled oil-in-water emulsion of claim 1 further comprising at least one pharma- ceutical active agent.

16. 10. The orally administrable gelled oil-in-water emulsion of claim 1 further comprising at least one nutraceutical active.

17. 17. The orally administrable gelled oil-in-water emulsion of claim 16, wherein said nutraceutical active is a vitamin or mineral.

18. 10. The orally administrable gelled oil-in-water emulsion of claim 1 provided in a unit dosage form.

19. 20. The orally administrable gelled oil-in-water emulsion of claim 18, wherein said unit dosage form is uncoated.

20. 20. A package comprising an airtight compartment and a lighttight compartment containing a dosage unit of a gelled oil-in-water emulsion according to claim 18 or claim 19.

21. 21. The package of claim 20, which is a blister pack formed from a material that is not coated with a release agent.

22. A process for the preparation of an orally administrable gelled oil-in-water emulsion according to any one of claims 1 to 19, comprising the steps of: The method further comprising: forming an oil phase comprising one or more physiologically acceptable lipids; forming an aqueous phase containing a gelling agent that is agar; combining the oil phase with the aqueous phase to form an oil-in-water emulsion in the presence of a surfactant that is a plant protein, a plant polysaccharide, or a derivative thereof; gelling the emulsion; A method comprising:

23. 20. A gelled oil-in-water emulsion according to any one of claims 1 to 19 for oral use as a medicament or in therapy.

24. 20. A gelled oil-in-water emulsion according to any one of claims 1 to 14, 18 and 19 further comprising at least one pharma- ceutical active ingredient for oral use in the treatment of a condition responsive to said pharma- ceutical active ingredient.

25. 20. Use of a gelled oil-in-water emulsion according to any one of claims 1 to 14 and 16 to 19 as a nutritional supplement product.

26. A gelled oil-in-water emulsion according to any one of claims 1 to 14 and 16 to 19 for use as a dietary supplement.

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