Edible gel for healthy ingredients

Abstract

The present invention relates to a dosage form containing one or more healthful ingredients. It takes the form of a stable, shearable gel and contains at least one ingredient requiring taste masking. The taste masking is achieved by using an oil / water emulsion containing a lipid-based carrier in an amount greater than 14% by weight relative to the water content of the dosage form. When sheared, the gel releases its load, and the oil emulsion droplets provide a temporary coating on the tongue, dulling the taste of the ingredient requiring taste masking.

Description

[Technical Field]

[0001] The present invention relates to dosage forms containing one or more health ingredients, particularly but not exclusively dietary, nutritional or pharmaceutical ingredients. The dosage form is a stable, shearable gel capable of delivering multiple health ingredients in a single dosage form, including at least one ingredient requiring taste masking, particularly exemplified by the bitter ingredient bergamot. The dosage form can be used for human or animal health.

[0002] This dosage form is capable of delivering high doses of dietary, nutritional, or pharmaceutical ingredients in a single delivery vehicle, including, but not limited to, water-soluble, water-insoluble, and / or lipid-soluble ingredients that are not easily delivered via tablets or capsules. By "high," we mean at least 1 g of one or more healthful ingredients, although at least one ingredient requiring taste masking may be present in an amount from 0.1 g through 0.25 g and 0.5 g up to 1 g or more.

[0003] Taste masking is achieved by using a highly concentrated oil / water emulsion that is stabilized in a shearable gel and releases its load when sheared; the oil emulsion droplets provide a temporary coating on the tongue that dulls the taste of the ingredient requiring taste masking.

[0004] By "high concentration" oil / water emulsion is meant at least 14% by weight or more of a lipid-based carrier compared to the water content of the dosage form. [Background technology]

[0005] One of the most important factors in the successful development of a health ingredient, particularly a dietary, nutritional or pharmaceutical ingredient, is ensuring patient compliance. Currently, multiple product formats are used to deliver each of multiple, e.g., nutritional or other health, e.g., active pharmaceutical ingredients (API), products. The varying nature and number of such products leads to wide variations in compliance.

[0006] These health products, i.e., dietary, nutritional, or pharmaceutical products, may be preventative or curative in nature and include prescription drugs, over-the-counter (OTC) drugs, and nutraceuticals and dietary supplements, including products containing, alone or in combination, vitamins, minerals, elements, proteins, carbohydrates, lipids, plant-derived extracts, such as traditional Chinese medicines (TCM) or other folk remedies, and the like.

[0007] Low compliance may result from the need to take multiple tablets, capsules, or other dosage forms, such as tablets containing multiple vitamins, capsules containing omega-3, beverages containing soluble dietary fiber, etc.

[0008] Tablets and capsules can prove difficult to swallow, especially for certain patient groups such as children and the elderly. For high dose, or difficult to formulate, or combination products, compliance issues arise due to the large tablet size and administration of multiple tablets.

[0009] Other issues that cause patient compliance include the taste, smell, or organoleptic properties of the product. These organoleptic properties may relate to product taste, product robustness, product texture, product mouthfeel, taste persistence, and any other aspect of the organoleptic sensation. Ingredients with unpleasant tastes are particularly problematic, and it is products containing such ingredients that are the focus of the claimed invention.

[0010] Some products require a separate drink to facilitate swallowing or to wash residues out of the oral cavity, or require a separate solid composition to be co-administered.

[0011] Examples include sugar replacement products for hypoglycemia and whey proteins, which disperse poorly in liquids and are required in large volumes. Also, a delivery device such as a spoon, syringe, or some other metering device may be required to aid in consumption and delivery of the dose. The need for such additional devices may have a negative impact on compliance.

[0012] Other factors that influence efficacy include packaging, chemical or physical stability of the composition, bioavailability of the components, visual appeal, and convenience of delivery. Alternative dosage forms to capsules and tablets include drinks or gels containing liquids or semi-solids.

[0013] "Energy gels" are typically thick pastes containing thickeners such as xanthan gum, but because these products do not set, they leave a residue on the tongue that can be persistent and uncomfortable, and can also irritate the oropharynx, which can lead to coughing and choking.

[0014] Such highly viscous paste or gel products tend to flow slowly, but with high internal resistance and toughness, similar to honey or ketchup. Such known highly viscous pastes can be Newtonian or non-Newtonian, and can be inherently shear-thinning or shear-thickening. However, they all share the property of plastic deformation under stress, albeit with some resistance, even though such behavior is known to have a threshold, such as Bingham plastic behavior. Typically, these viscous pastes have measurable viscosities of about 5,000 to about 50,000 cP.

[0015] As used herein, the term "set" refers to a set jelly material that does not exhibit plastic behavior under stress, but rather behaves elastically under stress up to the point of failure where the jelly structure breaks down and irreversibly new interfaces are formed.

[0016] The Applicant addressed this general problem in WO 2019 / 215641 by developing a base gel comprising two different gelling agents: a primary gelling agent, which is an agarose-based polymeric gelling agent such as agar-agar; and · Multivalent ionic gelling polymers, which are alginate-based polymer gelling agents such as, but not limited to, calcium alginate.

[0017] The details disclosed therein are incorporated by reference. The agarose-based polymer provides important functional properties, namely, that it forms, in the amounts provided, a firm hydrated gel with a Bloom grade of 100-250, and does not exhibit plastic behavior under stress, but rather behaves elastically up to the point of failure where the gel structure irreversibly breaks or shears, releasing water and forming a new interface, thereby increasing its fluidity so that, upon ingestion, it becomes a drinkable gel.

[0018] This specification teaches forming emulsions incorporating up to 10% by weight of oil or lipophilic components based on the water content of the dosage form. This application addresses the specific challenge of taste masking in an agarose-based polymer gel (which can be sheared to release water) and incorporated oil, while ensuring the maintenance of gel stability and functionality, designed to deliver one or more ingredients with unpleasant tastes, which may be present in amounts of 0.1 g or more by weight. Summary of the Invention

[0019] According to a first aspect of the present invention, Ingredients that require flavor masking a first gelling agent that is an agarose-based polymeric gelling agent present at a concentration of 0.001 g (1 mg) to 0.03 g (30 mg) per gram of water, which concentration ensures hydration and formation of a firm gel having a Bloom grade of 100 to 250, wherein the gel does not exhibit plastic behavior under stress, but rather behaves elastically under stress up to a point of failure where the gel structure breaks or shears and irreversibly forms a new interface, thereby increasing the fluidity of the gel such that, upon ingestion, it becomes a drinkable gel; Oil / water emulsions, including: - at least one lipid-based carrier, - Water, and - emulsifiers, wherein the oil / water emulsion comprises at least 14% by weight of a lipid-based carrier, based on water content.

[0020] More typically, the first gelling agent, which is an agarose-based polymeric gelling agent, is present at a concentration of 0.001 g (1 mg) to 0.02 g (20 mg) per gram of water. The premise of the present invention is based on ensuring that droplets of emulsified oil are released from the gel when the gel is sheared, thereby temporarily coating the tongue and dulling the taste (to the receptors on the tongue) of any unpleasant ingredients incorporated into the gel.

[0021] Thus, the present invention requires sufficient lipid-based carrier (oil) and emulsifier to function as an effective taste masking agent while maintaining gel stability. By stable, it is meant that the oil and water components of the emulsion did not phase separate and the components did not precipitate.

[0022] It was also necessary to select an oil that also provided desirable organoleptic properties. Any suitable oil may be used, including vegetable oils, seed oils, and marine oils, as well as blends thereof.

[0023] Preferred oils were olive oil, sunflower oil, canola oil, palm oil, and oils containing medium chain triglycerides. Olive oil was particularly preferred due to its neutral and organoleptic properties.

[0024] In contrast to the invention disclosed in WO 2019 / 215641, the present invention can be used with a single agarose-based gelling agent and it is the high concentration of emulsified oil that provides effective taste masking, as it is the release of the emulsified oil upon shear that provides a "protective" (taste-blunting) coating for the tongue.

[0025] Agar has been shown to be particularly beneficial in enhancing stability. Applicant has determined that the optimum concentration of emulsified oil (by weight) is between 14% and 28% oil to water, although Applicant has determined that in some circumstances as much as 30% oil to water may be possible.

[0026] More preferably, the emulsified oil comprises at least 20% by weight of the lipid-based carrier. The incorporation of an emulsifier further improves performance. Preferred emulsifiers are one of lecithin, polyethylene glycol (PEG), and polysorbate 80.

[0027] The emulsifier should be present in an amount of 0.1% to as much as 6.0% by weight. A preferred range is 3% to 5%. Many other benefits of these shearable gels are disclosed in WO 2019 / 215641.

[0028] A firm gel is a "set" gel or jelly characterized by the Bloom test, which is used in industrial and scientific contexts to provide a measure of the relative firmness and strength of these gels. This test was developed by Oscar T. Bloom in 1925. The test determines the weight, in grams, required for a specified plunger (usually 0.5 inches (11 mm) in diameter) to depress the surface of the gel 4 mm at a specified temperature without irreversibly breaking the gel and forming a new interface. The result is the Bloom grade. A higher number indicates a firmer product. For example, gelatin used in food applications typically ranges from 125 Bloom to 250 Bloom.

[0029] For the purposes of this document, the terms gel and jelly are interchangeable. A set gel or jelly is somewhat elastic, meaning that it will deform under stress but will return to substantially its original shape when the stress is released. For example, gently pressing with the back of a spoon will push down on a set jelly, but when the spoon is released, the original surface will return to its original position. This is not plastic deformation, where a surface will deform under the same stress and remain deformed even after the pressure is removed. Rather than plastically deforming, a set gel or jelly will fail by irreversibly breaking down and forming new interfaces if the stress is further increased beyond its breaking point.

[0030] The oral dosage forms of the present invention may typically be provided in volumes of 5 ml to 250 ml depending on use and are delivered from a container. In the case of small containers (5 to 25 ml), this may take the form of a sachet or straw, while in the case of larger containers (25 to 250 ml), this typically takes the form of a pouch equipped with a spout or straw, whereby the suction action shears the gel, increasing its flowability with the formation of new interfaces and possibly the release of some water and emulsion.

[0031] It is the shear and formation of new interfaces and the concomitant release of the emulsion that has the advantage of promoting powerful taste masking. The agarose-based polymer gelling agent is preferably agar.

[0032] Agarose-based polymer gelling agents also advantageously behave as emulsifiers, thereby reducing the amount of additional emulsifier required. When used, the multivalent ionic gelling polymer is most preferably an alginate-based polymeric gelling agent, such as, but not limited to, calcium alginate. Alternative options include guar gum, gellan gum, xanthan gum, pectin, and kudzu.

[0033] A particularly preferred combination of gelling agents includes agar as the primary gelling agent and calcium alginate as the secondary gelling agent. This combination has proven to be particularly versatile, allowing for the formulation of two or more combinations of water-soluble, water-insoluble, and / or lipid-based ingredients together in a single dosage form.

[0034] These two fundamentally different gelling agents provide a solid gel structure through different interaction mechanisms. The advantage of this combination is its versatility as a base, as it overcomes scenarios where gelation would otherwise be inhibited by the presence of different components.

[0035] Agar consists of a mixture of two polysaccharides, agarose and agaropectin, with agarose comprising approximately 70% of this mixture. Agarose is a linear polymer composed of repeating units of agarobiose, a disaccharide composed of D-galactose and 3,6-anhydro-L-galactopyranose. Agaropectin is a heterogeneous mixture of smaller molecules present in smaller amounts, composed of alternating D-galactose and L-galactose units, many of which are modified with acidic side chains such as sulfate and pyruvate. Any known variant of agar may be used in the present invention.

[0036] Agar exhibits hysteresis, melting at 85°C and solidifying at 32-40°C. This property provides a good balance between easy melting and good gel stability at relatively high temperatures.

[0037] Gelling also helps to provide stability at room temperature (and above), which means that cold storage can be avoided. The most common alginate salt used in foods is sodium alginate. To form a gel, sodium alginate must come into contact with divalent ions, such as calcium (Ca2+). When sodium alginate is added to a solution of calcium salts, such as chloride or citrate, the sodium ions (Na+) exchange with calcium ions (Ca2+), cross-linking the polymer and forming a gel. Divalent ions, such as calcium, can form two bonds, thereby forming cross-links between alginate polymers, whereas monovalent ions, such as sodium, can only form one bond. The longer the alginate is in contact with the divalent ion solution, the more cross-links are formed, and the firmer the gel becomes. Depending on the concentration of divalent ions, the gel can be either thermoreversible (at low concentrations) or thermoirreversible (at high concentrations).

[0038] Alginate is a linear copolymer with homopolymeric blocks of (1-4)-linked β-D-mannuronic acid (M) and its C-5 epimer, α-L-guluronic acid (G), which are covalently linked together in different sequences or blocks.

[0039] Sodium alginate is the sodium salt of alginic acid. Its empirical formula is NaC6H7O6. Sodium alginate is a gum extracted from the cell walls of brown algae. Potassium alginate is a chemical compound that is the potassium salt of alginic acid. Its empirical chemical formula is KC6H7O6.

[0040] Calcium alginate is made from sodium alginate by removing the sodium ions and replacing them with calcium, and has the chemical formula C 12 H 14 CaO 12 It has. The gel formulations of the present invention can be used to deliver unpleasant tasting ingredients, including: i) water soluble; ii) water-insoluble, or iii) lipids, It contains a component that is

[0041] Typically, but not necessarily, a dose containing greater than 0.1 g of at least one ingredient requiring taste masking, and optionally 1 g to 40 g of additional ingredients, which may include other nutraceutical or health ingredients, is delivered in a gel volume of 5 to 45 ml.

[0042] Although the base gel formulation can be used to package a single ingredient requiring taste masking, the format allows it to hold ingredients that are typically difficult to formulate into a single dosage form due to their different properties, and is particularly effective for delivering multiple health ingredients, including ingredients requiring taste masking, in an easy-to-take, easy-to-use dosage form that can be orally administered by squeezing or sucking the gel from a container.

[0043] A single ingredient requiring flavor masking will most likely be delivered in a smaller volume format (5 ml to 25 ml), whereas larger formats (25 ml to 250 ml) are preferred when multiple health ingredients, especially ingredients required in large doses, are required along with ingredients requiring flavor masking.

[0044] Such multiple healthy components may include, for example, proteins, carbohydrates, dietary fats, vitamins, and minerals. Proteins optionally include milk protein concentrate, whey protein concentrate, soy protein isolate, and sodium caseinate, which may additionally include amino acids such as one or more of L-glutamine, L-glycine, L-leucine, L-isoleucine, L-valine, beta-alanine, L-arginine, and taurine.

[0045] Carbohydrates, as desired, include, for example, maltodextrin, inulin, fructose, and glucose syrup. Dietary fats optionally include vegetable oils, fish oils, coconut oil, mono-, di-, and triglycerides of fatty acids, and lecithin.

[0046] Vitamins include, as desired, vitamin C (ascorbic acid), vitamin K (menaquinone-7), vitamin E (dl-α-tocopheryl acetate), niacin (niacinamide), vitamin A (retinyl acetate), pantothenic acid (D-calcium pantothenate), D-biotin, folic acid, vitamin D (cholecalciferol), vitamin B6 (pyridoxine hydrochloride), riboflavin (riboflavin 5-sodium phosphate), thiamine (thiamine hydrochloride), vitamin B12 (cyanocobalamin), creatine monohydrate, beta-carotene, lutein, lycopene oleoresin, choline chloride, L-carnitine, nicotinamide, D-calcium pantothenate, riboflavin, pyridoxine hydrochloride, pteroylmonoglutamic acid, phytomenadione, resveratrol, α-ketoglutaric acid, calcium hydroxymethylbutyrate (HMB), tricreatine malate.

[0047] Minerals optionally include essential trace mineral sources and salts such as one or more of tripotassium citrate, sodium chloride, trisodium citrate, magnesium oxide, zinc gluconate, ferrous fumarate, manganese gluconate, copper gluconate, potassium iodide, sodium molybdate, chromium picolinate, sodium selenite, chromium chloride, potassium iodide, sodium fluoride, sodium chloride, potassium chloride, calcium hydroxide, sodium ascorbate, magnesium hydroxide, potassium hydroxide, ferrous lactate, zinc sulfate, manganese sulfate, and phosphates such as one or more of sodium triphosphate, tricalcium phosphate, potassium phosphate.

[0048] Any or all of these may be incorporated into the emulsion. Other components may include: Antioxidants, such as one or more of ascorbyl palmitate, vitamin C (ascorbic acid), and vitamin E (d-alpha tocopherol).

[0049] pH adjusters, such as one or more of citric acid and ascorbic acid, are used in an amount to obtain a pH of 4-7. Preservatives, such as sorbic acid or its salts, for example potassium sorbate.

[0050] In one embodiment, the gels of the present invention are used to deliver ingredients in the form of encapsulated stable emulsions. The lipid component, e.g., sunflower oil or olive oil, is emulsified with water, usually with stirring, and then gelled with agar. Additional emulsifiers may be added to facilitate emulsification before gelling.

[0051] Typical food grade or pharmaceutical grade emulsifiers are added, such as lecithin, esters of monoglycerides of fatty acids, and mono-, di-, and triglycerides of fatty acids. It is also possible to provide multiphase combinations. For example, ingredients may be more stable in an oil-in-water emulsion. The solidified gel formed can trap and immobilize the multiple phases, enhancing stability and, for example, taste masking. The solidified gel is easily sheared during delivery to form a new wet interface, thereby facilitating delivery and taste masking upon emulsion release.

[0052] In storage, the formulation has a firm jelly form and is stable at room temperature, but when subjected to suction or other gentle force, it shears to form a new wet interface that facilitates swallowing because the gel interface formed is slippery due to its inherent wetness caused by the moisture in its structure.

[0053] This novel formulation provides a chemically and physically stable matrix that can be used to encapsulate water-soluble components, water-insoluble lipids, and fat-soluble components alike, and provide effective taste masking.

[0054] The encapsulation results in reduced surface contact with the taste buds, but upon shearing, the emulsion is released to coat the tongue, thereby dulling the taste. Unlike viscous, paste-like gels, the gels of the present invention leave minimal residue other than displaced water and are significantly easier to swallow because the set jelly shears upon inhalation, as opposed to alternative solid / semi-solid formats that are plastic (not elastic).

[0055] Advantageously, they are sheared so that they release their components quickly, even at high doses, and the released emulsion provides additional taste masking. Unlike tablets or capsules, this platform has the flexibility to provide a combination of different health ingredients in a single dosage form, which is advantageous compared to currently available alternatives.

[0056] The additional use of alginate means that some beneficial calcium salts can be incorporated as part of the gelling process. Thus, in formulations aimed at bone health, calcium and / or magnesium salts (e.g., calcium citrate or carbonate) can aid in gelling by complexing. Calcium citrate can also enhance flavor.

[0057] The solid suspension may contain nano-ground materials such as curcumin or glucosamine in a manner that may enhance their bioavailability. Agar produces clear gels without colored spots, but both agar and alginate gels are visually very clear, but more importantly, alginate crosslinking produces more structured gels with a different gelling mechanism than carbohydrate nonionic gelling polymers, improving versatility and performance.

[0058] However, the addition of Ca, Mg, and Zn salts, such as chloride or citrate, prevents agar and some other gum polymers from setting. Therefore, to achieve good setting results, agar and alginate must be used in a specific weight / weight ratio. A preferred ratio is an excess of agar relative to alginate, such as an agar-to-alginate ratio of greater than 8:1 to 1:1, more preferably greater than 5:1 to 1:1, and most preferably greater than about 3:1. Agar acts as an emulsifier and gelling agent, while alginate forms a structured gel with metal 2+ ions (Ca2+, Mg2+, Zn2+) to counteract the effect of these ions when agar alone is present.

[0059] Both agar and alginate are suitable for vegans, vegetarians, and most religious diets, whereas gelatin is not, as it is an animal protein, usually obtained from pigs.

[0060] An advantage of agar-alginate combination gels is that they are less sensitive to temperature than other gelling agents. They are also less affected by components that can inhibit gelation, such as oils, pH changes, and high concentrations of complex carbohydrates such as maltodextrin. Agar-alginate gels also tend to set faster, which is an advantage in manufacturing, facilitating faster and stronger production.

[0061] The lipids used in the practice of the present invention include any suitable food-grade oil of animal or vegetable origin. Non-limiting examples include corn oil, olive oil, sunflower oil, and coconut oil. The lipid material may advantageously include a lipid vitamin, such as either vitamin D or vitamin E.

[0062] Other preferred features include: A dosage form comprising one or more health ingredients, which are water-soluble and fat-soluble ingredients. A dosage form, wherein the one or more water-soluble health ingredients include or are selected from the group consisting of water-soluble vitamins, carbohydrates, sugars, and amino acids.

[0063] A dosage form wherein the one or more fat-soluble ingredients comprise or are selected from the group consisting of oils, particularly fish oils and algal oils, DHA, EPA, and fat-soluble vitamins D and E. A dosage form comprising one or more of proteins, vitamins, minerals, trace elements, and plant extracts or marine organism extracts.

[0064] A dosage form in which one or more health ingredients are present in an amount of at least 1 g. The dosage form further comprising a second gelling agent which is a multivalent ion-gelling polymeric gelling agent which is an alginate-based polymeric gelling agent.

[0065] Preferably, the first gelling agent is present in an amount greater than the second gelling agent, and even more preferably, the agarose-based polymeric gelling agent and the alginate-based polymeric gelling agent are present in a ratio of greater than 1:1 to 3:1.

[0066] Additionally, the dosage form is packaged in either: a pouch with an opening to facilitate drinking of the gel by squeezing and / or sucking; sachets or straws; syringe; or Any other packaging that facilitates delivery by sucking, squeezing, or pushing the gel out of the package.

[0067] Additionally, compliance with veterinary products in animal species such as pets, livestock, or other domesticated animals is also a challenge, as it can be very difficult for animal keepers to ensure that their animals ingest oral delivery forms such as tablets or capsules or powders.

[0068] It may also offer the advantage of improving compliance with veterinary products. Advantages of the present invention include: Flavor masking: The gel of the present invention can mask any mixture of nutrients and most unpleasant, strong, and unpleasant flavorings, such as bitter, sweet, fish oil, curcumin (spice / pungent), etc. Additionally, large volumes of nutrients can be formulated into one easy-to-take dosage form: multiple ingredients and large doses can be combined into a single dosage form. Overcomes the risk of choking caused by large tablets: Gels are much easier to swallow than pills. This format aids all swallowing problems, whether they are young children or the elderly, or simply those with a predisposition to swallowing disorders. Stable at room temperature. Because it is a gel, it is stable without the need for storage in a cool place. Contains water as an ingredient. The presence of "trapped" yet "releasable" water ensures that hydration is achieved even when released as an emulsion, and no additional fluid is required to make the product swallowable. This also aids digestion and improves mouthfeel.

[0069] Hereinafter, embodiments of the present invention will be further described with reference to the accompanying drawings. [Brief explanation of the drawings]

[0070] [Figure 1] FIG. 1 is a diagram of a dosage form of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0071] A general process for manufacturing the gel formulation is shown in Example 1 below. [Example]

[0072] Example 1 Manufacturing method First, all water-soluble ingredients are dissolved in water. These may include nutrients such as glucose, as well as preservatives and dilute acids (for pH adjustment). An exemplary preservative is potassium sorbate, and exemplary pH adjusters, if needed, are weak acids such as citric acid, ascorbic acid, acetic acid, or dilute HCl.

[0073] To facilitate efficient addition of the gelling agent, it is preferable to stir and heat the solution to near boiling point. The agar and, if desired, sodium alginate are slowly added and gradually hydrated with steady, constant stirring to ensure adequate dispersion or dissolution. The dispersion or solution is held at or near boiling point for 4-5 minutes, a sufficient time to ensure adequate hydration, particularly for the agar.

[0074] A separate emulsion is formed by mixing oil, water, and any other ingredients to be incorporated into the emulsion. The two components are then mixed and the finished product is filled, for example into sachets, and allowed to cool to form a firm gel.

[0075] The sachet may be a simple sachet or tube for small volumes (5-25 ml), or a pouch as shown in Figure 1 for larger volumes (25-250 ml). The pouch (1) is formed, for example, from plastic or foil layers and is sealed together around its periphery at edges (3) incorporating a filling and dispensing opening with a stopper (4), a spout (5), and a cap (6). The pouch is filled through a mouthpiece (5) and secured with a cap (6), which may be equipped with a frangible seal. In use, the subject removes the cap and drinks the gel by squeezing and / or sucking the gel from the pouch (1) through the spout (5).

[0076] Alternative packaging for delivery may include a sachet or straw, a syringe, or any other packaging that facilitates delivery by sucking, squeezing, or pushing the gel out of the packaging.

[0077] When making gels, it is desirable to limit the heating time to minimize water loss due to evaporation, as excessive evaporation can lead to product variability. Preferably, agar is used at a concentration of 0.001g (1mg) to 0.02g (20mg) per 1g of water, more preferably 0.005g (5mg) to 0.01mg (10mg) per 1g of water, and most preferably 0.006g (6mg) to 0.009g (9mg) per 1g of water (corresponding to 1ml).

[0078] When used, the alginate is used at a concentration of 0.0005g (0.05mg) to 0.01g (10mg) per 1g of water, more preferably 0.001g (1mg) to 0.008g (8mg) per 1g of water, and most preferably 0.001g (1mg) to 0.005g (5mg) per 1g of water.

[0079] To promote the gel formation of the alginate, a divalent ion source is added together with the alginate. Suitable ingredients include calcium salts, zinc salts, and / or magnesium salts. For example, calcium citrate, magnesium citrate, or zinc citrate are good forms of soluble salts and can also provide mineral supplementation. However, other salts may also be used.

[0080] Preferred lipids for forming emulsions are neutral oils such as olive oil and sunflower oil. Typically, lipid levels are added at 14-28% w / w of total water, although concentrations up to 30% are sometimes used. The water component may be "split" and the gel and emulsion may be mixed.

[0081] Advantageously, a mechanical homogenizer, such as a Silverson homogenizer, is used to facilitate emulsion formation. Any known food-grade emulsifier, such as lecithin, may be added to improve the quality and physical stability of the emulsion. Preferably, the emulsifier is of non-animal origin, such as soy lecithin, rather than egg lecithin.

[0082] In a preferred process, the emulsion is prepared as a separate cold water-mixed precursor, as described above, and combined with a separate hot water-agar precursor (the water being divided appropriately) to speed cooling and gel formation.

[0083] Additional components may be dissolved or dispersed in the gel or emulsion. If the nutritional component is neither water-soluble nor fat-soluble, it may be prepared as a suspension in either lipid or water. It is advantageous if the component is ground to a fine particle size, as this may improve suspension stability and may also increase bioavailability. Advantageously, insoluble components may be ground under wet or dry conditions, and may be ground by ball milling, media milling, or nano-milling, or by high-shear homogenizer. Grinding may be carried out in the presence of grinding aids such as leucine, sodium lauryl sulfate, and metal stearates.

[0084] After heating, the liquid formulation can be metered hot into the desired container and allowed to set as a gel. More specifically, for example, in the case of a hypoglycemic product, the following is carried out during the manufacturing process:

[0085] The gel manufacturing process includes: Weigh out suitable amounts of non-gelling agents (e.g., glucose, potassium sorbate, water) and add them to a suitable mixing vessel in the following order: glucose (or other carbohydrate) if desired, potassium sorbate or other preservative if desired, and water.

[0086] Provide steady stirring, e.g., at laboratory scale, this is a magnetic stir bar. Cover to minimize evaporation and water loss. The specified nutrients required for the composition are pre-weighed. These non-gelling ingredients are mixed while the contents of the container are heated. Nutrients are added to the container one at a time, and after they are completely dispersed and dissolved, the next nutrient is added. Once all nutrients have been added, the mixture is mixed for an additional 2-3 minutes.

[0087] The gelling agent (agar) is pre-weighed. Stir for 2-3 minutes to ensure all drug is incorporated and no longer visible. If using insoluble components, incorporate using a homogenizer.

[0088] Using a homogenizer, an emulsion is mechanically formed from the lipid, a portion of the water, and at least the ingredient to be taste-masked, with appropriate heating. This emulsion is added to the gel portion and the formulation is cooled to gel.

[0089] The Bloom test is used to assess the resulting grade of the set gel, and it is preferred that Bloom grades of at least 100, up to 110, 120, 130 and 140 are obtained.

[0090] Preferably, a bloom grade of less than 250, less than 220, less than 200 to less than 180 is obtained. An optimum bloom grade of 140-180 is desired.

[0091] Example 2 Development and Testing A preferred base gel to which multiple ingredients, particularly nutritional ingredients, that promote health or well-being (not shown) are added includes agar due to its water releasing capabilities.

[0092] Example 1 of WO 2019 / 215641 teaches that lipids may be added to the formulations described therein in amounts up to 10% w / w of the water (i.e., up to 2.5 g in 25 ml of water), Example 2 therein teaches a formulation containing 0.5 g omega-3 in 24 g of water (about 2%), and Examples 4-5 have omega-3 levels of 1 g in 24 g of water (about 4%).

[0093] Applicant found that for bitter test ingredients such as bergamot, the oils and emulsifiers also present did not adequately mask the product at such concentrations. Therefore, a series of experiments were conducted to investigate how the taste of ingredients in water-releasing gels could be better addressed. Key test data are provided in the following examples.

[0094] [Table 1]

[0095] In taste tests, the product was very bitter. Therefore, the applicant decided to incorporate into the emulsion, according to Example 2b, an ingredient with an unpleasant taste profile (exemplified by bergamot).

[0096] [Table 2]

[0097] This product, with an oil-in-water emulsion concentration of 0.3% w / w to water (0.08 / 25 x 100), did not improve the taste profile. In Examples 2c to 2f, the oil level was increased in steps from 1.5%, 4.5%, 7.5% to a maximum of 10.5%.

[0098] [Table 3]

[0099] [Table 4]

[0100] [Table 5]

[0101] [Table 6]

[0102] At the highest concentration, although there was a significant improvement in taste, the product was still considered unpalatable. Example 2g explored the incorporation of bergamot into a variant of a ketogenic product (high in lipid content) under development.

[0103] [Table 7]

[0104] This product, with a 14% concentration of oil-in-water emulsion (3 / 21.5 x 100), significantly improved the taste profile. The bitterness was reduced but still noticeable. Importantly, the initial bitterness disappeared very quickly. Thus, increasing the lipid concentration reduced the bitterness.

[0105] Based on the above findings, the applicant further increased the oil content to identify the effect on both taste and stability, the results of which are shown in Examples 2h-2j.

[0106] [Table 8]

[0107] Further improvements in taste were noted and olive oil was considered to be a better tasting oil with better organoleptic properties than sunflower oil.

[0108] [Table 9]

[0109] [Table 10]

[0110] Both Examples 2i and 2j were able to mask the bitterness of bergamot well. They were also stable, meaning that the oil and water components of the emulsion did not phase separate and the components did not precipitate.

[0111] conclusion From the tests conducted, the applicant has come to the following broad conclusions: Lipid-based carriers at 0.3% to 10.5% gave stable gels with a soft texture, but the emulsions did not adequately mask the bitter / bergamot flavor. Lipid-based carriers at 10.5% to 14% gave a more stable gel with a firmer texture and emulsions with reduced bitterness. As the concentration increased, a significant improvement was observed compared to the prior art oils. Concentrations of 14% to 28.0% oil (and up to 30%, not shown) gave the firmest textured, stable gels, and greatly eliminated bitterness, and any perceived unpleasant taste was only temporary.

[0112] It will be appreciated that a skilled nutritionist will be able to formulate the above variations using their general skill and knowledge.

Claims

1. Oral dosage form, • Ingredients that require flavoring, - A first gelling agent, which is an agarose-based polymer gelling agent present at a concentration of 0.001 g (1 mg) to 0.03 g (30 mg) per gram of water, wherein the concentration ensures the hydration and formation of a firm gel having a bloom grade of 100 to 250, and the gel does not exhibit plastic behavior under stress, but rather elastic behavior under stress until the structure of the gel breaks or is sheared, irreversibly forming a new interface, thereby increasing the fluidity so that the gel becomes a drinkable gel when ingested. Oil / water emulsions containing the following: - At least one lipid-based carrier, - Water, and - Emulsifier, An oral dosage form comprising the oil / water emulsion, wherein the oil / water emulsion comprises at least 14% by weight of the lipid-based carrier based on its water content.

2. The dosage form according to claim 1, wherein the oil / water emulsion comprises at least 20% by weight of the lipid-based carrier based on the water content.

3. The dosage form according to claim 1 or 2, wherein the oil / water emulsion contains up to 30% by weight of the lipid-based carrier, based on the water content.

4. The dosage form according to claim 1 or 2, wherein the agarose-based polymer gelling agent is agar.

5. The dosage form according to claim 1 or 2, wherein the lipid-based carrier is selected from olive oil, sunflower oil, coconut oil, and medium-chain triglyceride (MCT) oil, or a blend containing these oils.

6. The dosage form according to claim 1 or 2, wherein the emulsifier is lecithin, polyethylene glycol (PEG), or polysorbate 80.

7. The dosage form according to claim 1 or 2, further comprising one or more preservatives.

8. The dosage form according to claim 7, wherein the preservative is sorbic acid.

9. The dosage form according to claim 1 or 2, further comprising a pH adjuster.

10. The dosage form according to claim 9, wherein the pH adjusting agent is used in an amount that maintains the pH in the range of 4 to 7.

11. The dosage form according to claim 1 or 2, further comprising one or more health-promoting ingredients in addition to the aforementioned flavoring ingredients.

12. The dosage form according to claim 11, wherein the further one or more health-promoting ingredients are selected from water-soluble ingredients and lipid-soluble ingredients.

13. The dosage form according to claim 12, wherein the further one or more water-soluble health components are selected from the group comprising or consisting of water-soluble vitamins, carbohydrates, sugars, and amino acids.

14. The dosage form according to claim 12, wherein the one or more lipid-soluble components are selected from the group comprising or consisting of oils, particularly fish oil and algae oil, DHA, EPA, and lipid-soluble vitamins D and E.

15. The dosage form according to claim 12, further comprising one or more of the following: proteins, vitamins, minerals, trace elements, and plant extracts or marine biological extracts.

16. The dosage form according to claim 12, wherein the one or more health-promoting ingredients are present in an amount of at least 1 g.

17. The dosage form according to claim 1 or 2, further comprising a second gelling agent which is a polyvalent ion-gelling polymer gelling agent that is an alginate-based polymer gelling agent.

18. The dosage form according to claim 17, wherein the first gelling agent is present in a larger amount than the second gelling agent.

19. The dosage form according to claim 18, wherein the agarose-based polymer gelling agent and the alginate-based polymer gelling agent are present in a ratio greater than 1:1 to 3:

1.

20. A pouch (1) having an opening (5) for facilitating the drinking of the gel by squeezing and / or sucking; Small pouch or straw; Syringe; or Any other packaging that facilitates delivery by sucking, squeezing, or squeezing the gel from the packaging, The dosage form according to claim 1 or 2, which is packaged in one of the following:

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