Heat-resistant chewable oral dosage form with an agar matrix and method for the production thereof

Abstract

To provide a method for forming a chewable oral dosage form, for example, a gum having a pleasant flavor and texture.SOLUTION: A method of forming an oral dosage form is provided comprising a first step of hydrating agar and locust bean gum gelling agents; a second step of mixing the components of the agar matrix; a third step of mixing an active ingredient; a fourth step of cooking the mixture; a fifth step of flavoring; a sixth step of molding and gelling; and a seventh step of demolding, defatting and drying. An oral dosage form comprising an agar matrix combined with a gum such as locust bean gum and / or a sugar; glycerol; inulin; a flavoring agent; citric acid; a coating; and water to complete the composition, and comprising an active ingredient is provided.SELECTED DRAWING: None

Description

[Technical Field]

[0001] An object of the present invention is a method for forming chewable oral dosage forms, such as gums, that have characteristics similar to those of gelatin and a pleasant texture and taste. In particular, the present invention includes a method of forming an oral dosage form, the method comprising a first step of hydrating agar-agar and locust bean gum gelling agents; a second step of incorporating the components of the agar matrix; a third step of incorporating the active ingredient(s); a fourth step of cooking the mixture; a fifth step of flavoring; a sixth step of molding and gelling; and a seventh step of demoulding, degreasing and drying to provide a composition having an agar matrix and locust bean gum whose texture allows it to be chewed and ingested without difficulty. Similarly, oral dosage forms according to the present invention comprise an agar matrix in combination with a gum, such as locust bean gum, and / or sugar; glycerin; inulin; flavorings; citric acid; a coating; and water to complete the composition, which comprises the active ingredient. The shaped forms incorporate compositions based on active ingredients of nutraceutical or pharmaceutical nature that avoid the problem of cross-linking, thereby allowing the incorporation of active ingredients with a melting point above 40°C.

[0002] Similarly, the present invention also includes chewable oral dosage forms suitable for ingestion of the active ingredient in vegans or people who, by culture, do not consume substances of animal origin. Chewable oral dosage forms are made from an agar matrix in which the texture is modified to allow chewing and swallowing by any type of patient. Agar matrix chewable oral dosage forms provide a rubbery texture that is resistant to modification based on, for example, packaging, shipping, and ambient temperature. The oral chewable form has sufficient stability at temperatures of 40°C, important in tropical countries, to maintain its structure under these conditions while at the same time maintaining a soft texture for chewing, providing an easy-to-take alternative for the general consumer. Additionally, the oral chewable form melts at average body temperature while releasing excellent flavor. Thus, a short textured chewable oral dosage form is provided that is easy to chew and forms a stable, ingestible product.

[0003] Among others, oral dosage forms also include, but are not limited to, active nutritional ingredients such as vitamins, minerals, natural products, plants and herbs, as well as active pharmaceutical ingredients such as drugs with therapeutic properties at the level of the digestive and metabolic systems, the cardiovascular system, the genitourinary and hormonal systems, the musculoskeletal system, the nervous system, antiparasitic agents, drugs with therapeutic properties in the respiratory system, analgesics and antipyretics, without excluding all those envisaged in the index of pharmacological substances and drugs included in the Anatomical Therapeutic Chemical Classification system (ATC). The agar matrix of the chewable oral dosage form according to the present invention comprises a formulation that achieves a balance in the mixture of the above-mentioned components to provide a matrix that can be processed commercially and has stability for a shelf life of 2 years. Thus, the present invention is applicable in the nutritional or health area as it provides an oral dosage form with excellent texture, visual appearance and flavor that is capable of delivering a desired amount of active ingredient. [Background technology]

[0004] Adding nutrients to easily ingested products is a practice that dates back to the early 19th century, when French chemist Boussingault recommended adding iodine to table salt to prevent goiter in South America. In 1918, margarine was fortified with concentrated vitamin A in Denmark, and in 1931, whole milk was fortified with vitamin D in the United States. Regarding grains, the fortification of breakfast cereals began in the mid-20th century, specifically in 1941. Another first product produced under the name of fortified food was a mixture of base cereal flour and fish meal to achieve higher protein uptake, and another food fortification process was the addition of iodine to milk to prevent the problem of hypothyroidism in endemic areas.

[0005] Consumers have become increasingly aware of the need to consume foods that provide functional elements in their diets that are beneficial to their health and well-being. Therefore, what is currently needed are fortified forms of good nutrients that will help provide the necessary nutritional requirements for the human body. In Latin America in general, child malnutrition is a recurring social problem affecting a large proportion of the population, regardless of socioeconomic level. Malnutrition is mainly caused by not consuming foods that have enough nutrients (among them proteins, vitamins, minerals and antioxidants) needed by the body. In some Latin American countries, for example, Colombia, 32.2% of children between 1 and 4 years old and 37.6% of children between 5 and 12 years old suffer from anemia due to nutritional deficiencies (Instituto Colombiano de Bienestar Familiar ICBF, 2005), and it has also been found that children are generally vitamin deficient due to not consuming foods that provide a balanced diet.

[0006] Although several oral dosage forms with different sensory properties are known, most of these are rejected by consumers due to their appearance, taste and texture. The state of the art has advanced, for example, as disclosed in European Patent EP 1074183 by Aoki, Miwa et al. This patent exemplifies edible gelatin containing 0.3-1.2% by weight of agar, 0.01-0.6% by weight of xanthan gum, and 0.01-0.6% by weight of locust bean gum as gelling agents. This edible gelatin is characterized by having pulp-like granules and texture obtained by a method in which the gelling agents are mixed in an amount of agar exceeding the total amount of the xanthan gum and locust bean gum, in a ratio of xanthan gum to locust bean gum of 1:4 to 4:1, the mixture is heated to obtain a solution, the solution is then cooled to obtain a gel, the resulting gel is frozen, and thawed to obtain a gum. While this development is feasible in terms of gum structure and shaping, it is based on gelatin of animal origin and is not suitable for all types of consumers due to its origin, appearance, taste, and texture.

[0007] Another technological development is defined in US Pat. No. 7,067,150 to Farber, Michael et al., which discloses an oral delivery system for functional materials such as drugs, dietary supplements, botanicals and vitamins. The delivery system comprises an ingestible matrix in which the functional material is substantially uniformly and completely dispersed and degradation of the functional material is minimized, the matrix comprising one or more carbohydrates; one or more sugars, sugar syrups and / or sugar alcohols; one or more hydrocolloids including gelatin; one or more polyhydric alcohols; one or more sources of monovalent or divalent cations; and water. The combination of carbohydrate and hydrocolloid in the matrix ensures that the delivery system readily retains the solvent component, thus preventing separation of the solvent from the other components of the matrix. The invention also provides methods for preparing and using the delivery system. This development is also based on the matrix of an oral dosage form in gelatin of animal origin, and therefore is not suitable for all types of consumers. As shown in the prior art, among the oral dosage forms that are more accepted by consumers are gums made from gelatin, which, due to their gelling properties, are a preferred alternative in the formulation of pharmaceutical or dietary supplement forms. Suitable gelatin substitutes with gelling properties are starch, carrageenum, and agar.

[0008] Agar is an effective gelling agent of plant origin that can produce non-sticky gels with a crispy texture. Agar is made from red algae, including Gelidium, Euchema, and Gracilaria, and has special properties that make it applicable to a variety of uses, unlike other gelling agents. Gums made from agar-agar are targeted at a very dynamic market that is at the forefront of new consumer requirements, where current consumer trends feature verifiable products (non-GMO, organic, halal, kosher), and therefore plant-based materials have more potential to be verified compared to any product of animal origin. Other types of evaluation factors include religious groups, ethnic minority groups, consumers based on vegetarian / vegan diets, and health reasons related to patient and / or consumer needs. Furthermore, agar has established itself as a preferred alternative due to its physical and chemical properties that promote consumer preference and acceptance of the production process, including, among others, its stability and performance, low sensitivity to heat or moisture, its ability to avoid cross-linking, low sensitivity to pH and advantages in reducing external water migration, as well as high mechanical strength, organoleptic advantages, e.g., tasteless, odorless, bright / glossy, and easy chewing and administration. On the other hand, in modern times, i.e., in an era when stress, fatigue and difficulty in falling asleep are among the biggest problems of people and when minerals and vitamins are natural alternatives to meet this need, the need to provide vitamins, minerals, plant-based dietary supplement compositions or simply active pharmaceutical ingredients that are easy to take is extremely important.

[0009] Furthermore, several clinical trials and meta-analyses have been conducted showing significant effects on reducing migraines, lowering the risk of colorectal cancer, calcium absorption in bones, and improving constipation. Due to changes in dietary habits and reduced magnesium content in foods, people's daily intake of magnesium is insufficient, for which supplementation would be beneficial. Chewable forms are one solution for the administration of plant-based vitamins, minerals, dietary supplement compositions or actual active ingredients of pharmaceutical nature that are easy to take. Chewable forms such as gums are a pleasant, available, and convenient alternative to dietary supplements because they can be taken at any time, do not require water, and are easy to swallow. However, for active ingredients with melting points above 40°C, commercially available chewable gel forms are not a viable alternative. Therefore, another important problem to be solved is to create a chewable oral gel form of vegetable origin that, in addition to forming a chewable oral dosage form based on a gel of vegetable origin, also comprises a matrix that overcomes the cross-linking problem that is very common in gelatin-based preparations and can integrally incorporate active ingredients with a melting point higher than 40°C, which is not an option available in commercially available chewable gel forms. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] US Patent Application Publication No. 2002 / 0128460 [Patent Document 2] Special Publication No. 2001-510341 [Patent Document 3] International Publication No. 2009 / 047859 [Patent Document 4] International Publication No. 2005 / 025622 [Patent Document 5] Japanese Patent Application Laid-Open No. 2001-045989 [Patent Document 6] Special Publication No. 2013-529928 Summary of the Invention

[0011] Therefore, a first object of the present invention is to avoid the drawbacks of the prior art. More particularly, the primary objective of the present invention is to produce a chewable oral dosage form using a matrix of plant origin, such as agar, and to incorporate within said matrix natural or synthetic compounds having nutritional or pharmaceutical properties whose organoleptic properties provide a positive consumer experience. In particular, oral dosage forms with a matrix of plant origin, with characteristics similar to gelatin of animal origin, which overcomes the cross-linking problem so common in gelatin preparations and thus allows the incorporation of active ingredients with a melting point above 40°C. An equally important objective is to create a chewable oral dosage form suitable for ingestion of the active ingredient in vegans or people who by culture do not consume substances of animal origin, the texture of which is modified to allow it to be chewed and taken by any type of patient. Another important object includes an agar matrix chewable oral dosage form that provides a stable, strong rubbery texture important in tropical countries, for example, through packaging, shipping, and modification based on ambient temperature, so that the chewable oral dosage form retains its shape and at the same time retains a soft texture when chewed for ingestion, melts at body temperature, and releases excellent flavor. In particular, an object of the present invention is a method for forming chewable oral dosage forms comprising a first step of hydrating agar and locust bean gum gelling agents; a second step of incorporating the components of the agar matrix; a third step of incorporating the active ingredient; a fourth step of cooking the mixture; a fifth step of flavoring; a sixth step of molding and gelling; and a seventh step of demoulding, degreasing and drying.

[0012] It is also an important objective to form a chewable oral dosage form comprising an agar matrix in combination with gums such as locust bean gum and / or sugars; glycerin; inulin; flavorings; citric acid; coating, and water to complete the composition, which may include, but is not limited to, all those contemplated in the Index of Pharmacological Substances and Drugs contained in the Anatomical Therapeutic Chemical Classification (ATC) system, including vitamins, minerals, active ingredients from natural plants and herbal products; and pharmaceutically active ingredients, such as drugs with therapeutic properties at the level of the digestive and metabolic systems, the circulatory system, the genitourinary and hormonal systems, the musculoskeletal system, the nervous system, antiparasitic agents, drugs with therapeutic properties in the respiratory system, analgesics, and antipyretics. The novel features believed to be fundamental to the present invention are set forth with particularity in the appended claims, and additional advantages thereof will be better understood from the following detailed description of preferred embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0013] The object of the present invention is a chewable oral dosage form having an agar matrix in combination with gums such as locust bean gum and / or sugars; glycerin; inulin; flavorings; citric acid; a coating, and water to complete the composition, which composition contains vitamins, minerals, active ingredients derived from natural plant and herbal products, and pharmaceutically active ingredients. In particular, the present invention comprises oral dosage forms with a matrix of plant origin for providing active ingredient-based compositions of dietary supplement or pharmaceutical nature, which can incorporate active ingredients with a melting point above 40°. The agar matrix chewable oral dosage form provides a strong rubbery texture that is stable at temperatures of 40°C, which is important in tropical countries, due to modifications based on, for example, packaging, shipping, and ambient temperature, so that the chewable oral dosage form retains its shape and at the same time retains a smooth texture when chewed for ingestion, melts at body temperature, and releases excellent flavor.

[0014] Thus, a short textured chewable oral dosage form is formed which creates a product that is easy to chew and swallow.Agar is an unbranched polysaccharide obtained from the cell walls of several species of Gelidium, Eucheuma and Gracilaria algae, which gives it species-dependent properties and color. Chemically, agar is a polymer of galactose subunits, resulting from the mixing of two polysaccharides: agaropectin and agarose. The polysaccharides in agar are part of the cell wall structure of algae. In the presence of water, agar has gelatinous properties and is widely used as a culture medium in bacteriology.

[0015] However, the present invention aims to use agar to develop a matrix that can bring the characteristics of gelatin to a composition that can contain a dietary supplement or a pharmaceutically active ingredient. Gums are resinous substances, water-soluble polysaccharides with adhesive properties, high molecular weights, and complex structures. Their consistency is solid, but can vary depending on their origin and processing conditions. They are particularly characterized by elasticity. Gums have the ability to form gels and increase viscosity, and are therefore widely used in the food and pharmaceutical industries due to their emulsifying, stabilizing, and thickening properties. Some examples of gums for food and pharmaceutical use include, but are not limited to, gums extracted from marine plants (e.g., agar and alginates), gums extracted from the seeds of terrestrial plants, gums obtained as exudates from terrestrial plants (e.g., gum arabic, gum tragacanth, carob gum), and gums obtained from microbiological processes, such as xanthan gum, among other types of gums available and applicable in both industries within these categories. The locust bean gum of interest to the present invention acts as a co-adjuvant agent, but does not increase the gel strength of the mixture with agar, but in the process modifies the structure of the agar to resemble gelatin, resulting in shorter structures when chewed.

[0016] For the present invention, the manufacture of an oral chewable form has been developed from a combination of a gelling agent such as agar and a gum such as locust bean gum. Carob gum is soluble in water from 80°C, while agar is soluble in water at 75°C, and both have a melting point of 92°C (at 2,600 m) and their gelation begins at 75°C. The combination of agar and locust bean gum is offered under the trademark AGARO ID 300®. As the solids increase in mixtures containing these gelling agents, the gelling temperature also increases. The importance of the point at which gelling begins is that if the process involves movement of the mixture, the gel that begins to form at higher temperatures will be sheared and the final product will have a softer texture, lower gel strength and a higher probability of syneresis. Various types of natural or artificial sweeteners have been used in oral chewable forms, including natural sweeteners such as sucrose, tapioca syrup, and inulin-based sugars, as well as sweetener additives such as stevia, provided that these sweeteners achieve stabilization of the agar-based gelling agent matrix. Sugar-based sweeteners, such as sucrose, tapioca syrup, and inulin, can produce a firm gel structure with optimal handling and sensory properties. The balance between the matrix components and their interaction with the active ingredient is essential to obtain a stable gel matrix. Other types of sweeteners are suitable for people with dietary restrictions, such as diabetics.

[0017] In general, the active ingredients may be selected from vitamins, minerals, natural plants and herbal products; and active pharmaceutical ingredients, such as drugs with therapeutic properties at the level of the digestive and metabolic systems, the cardiovascular system, the genitourinary and hormonal systems, the musculoskeletal system, the nervous system, antiparasitic agents, drugs with therapeutic properties in the respiratory system, analgesics and antipyretics, without excluding all those envisaged in the index of pharmacological substances and drugs included in the Anatomical Therapeutic Chemical Classification system (ATC). Among any active ingredients particularly suitable for forming the oral chewable form of the present invention are vitamins, such as vitamin D2, vitamin A, vitamin C, vitamin D and its derivatives and / or analogues, vitamin E, vitamin B complex, such as vitamins B1, B3, B5, B9 and B12, and vitamin K2. The oral chewable forms of the present invention may also contain, among others, probiotics, fruit extracts, plant extracts, minerals such as zinc, calcium, magnesium, iron, selenium, chromium, phosphorus, potassium, copper; omega-3 fatty acids such as EPA and DHA, folic acid, iodine, biotin, choline, ginger, lutein, blueberry, and acerola.

[0018] The oral chewable forms of the present invention may also include a combination of saffron extract and vitamin D3, e.g., cholecalciferol; a combination of pyridoxine HCl, cyanocobalamin, and ginseng extract; a combination of magnesium citrate, melatonin, and passionflower (Passiflora incarnata L.); a combination of lemon balm (melissa officinalis) and L-theanine; a combination of saffron (Crocus sativus L.) and cholecalciferol; and ascorbic acid, zinc citrate, and elderberry (sambucus nigra).

[0019] The method of the present invention therefore comprises: (i) a first step of hydrating agar and locust bean gum gelling agents, which comprises mixing agar combined with locust bean gum (AGAROID 300®) in an amount between 0.1% and 4.0%, in particular between 0.2% and 2.0%, more particularly between 0.3% and 1.8% of the total mass of the composition with a sweetener in an amount ranging between 6% and 10%, until a homogeneous mixture is obtained, followed by adding a certain amount of water and stirring until the mixture is completely dissolved; (ii) a second step incorporating the components of the agar matrix, in which glycerin is added to the mixture of the first step (i) in an amount between 1% and 3% of the total composition together with liquid inulin in an amount between 7% and 12% of the total composition and powdered inulin in an amount between 5% and 10% of the total composition, optionally mixed with a sweetener in an amount between 20% and 28% of the total composition, and then stirred until completely dissolved; (iii) a third step of incorporating the active ingredient, in which a certain amount of the active ingredient and, optionally, a sweetener in an amount between 7% and 10% of the total composition are premixed until a homogeneous mixture is obtained, and then added to the mixture of the second step (ii) and stirred until it is completely incorporated; (iv) a fourth step of cooking the mixture obtained in the third step (iii) at a temperature between 80°C and 100°C for 30±5 minutes, wherein the solids must have a Brix between 72° and 74°; and (v) A fifth flavoring step, which comprises transferring the cooked paste from the fourth step (iv) to a flavoring tank and adding black carrot in an amount between 0.1% and 1%, particularly between 0.2% and 0.4%, together with flavoring agent in an amount between 0.1% and 1%, particularly between 0.4% and 0.8%, and citric acid in an amount between 0.23% and 0.29%.

[0020] For the second stage of incorporating the ingredients, glycerin can be replaced with sorbitol or invert syrup. Similarly, potato starch can be used as an alternative to inulin for the same function. Similarly, the addition of citric acid can balance the flavor of the product; in this case, the acid is added last in the fifth stage, after all the other added ingredients have been fully incorporated into the mixture. Once the mixture is prepared, molding of the final oral dosage form can begin. The final oral dosage form can include shapes and colors based on the type or purpose of marketing. This requires a highly stable wax-based coating that provides gloss, moisture resistance, and excellent lubrication to control the adhesion of the pieces to each other. The coating can include coatings based on natural oils and waxes and / or blends of sweeteners, mannitol, or powdered flavors, and can be formulated with additional flavors in combination. Therefore, the method then further comprises the following steps: (vi) a sixth step of molding and gelling, in which the mixture of the fifth step is deposited in a mold at a temperature between 75°C and 89°C, and the temperature for gelling is reduced to a temperature between 2°C and 8°C; and (vii) A seventh step of demoulding, degreasing and drying, which comprises demoulding, followed by degreasing and then drying the chewable oral dosage form by dispersing it in a drying rack or basket at a temperature of 30±3°C and a relative humidity of 25±5%.

[0021] In the sixth step, the additional function of the citric acid flavoring is to increase the solubility of the active ingredient added in the third step. Cooling the molds for gelation in the sixth step involves providing various means, such as a cooling room, an air tunnel, etc., in which the molds are induced to gently and slowly lower their temperature. For defatting in the seventh step, the product is placed in a rotating drum, and the product in the basket is rotated to homogenize the fat on the surface of the chewable form. For the seventh stage drying, the tunnel dryer was set at a relative humidity of 25±5°C, a temperature between 30±3°C, and a laminar air velocity of 0.15 m / s. 3 / sec. Optionally, the oral chewable form can also be sweetened. To this end, the method also includes: (viii) An eighth step of sweetening and packaging, wherein the dry chewable oral dosage forms are introduced into a sweetening machine and sweeteners are added until coating is complete, for which the steam pressure is adjusted between 275 Pa and 413 Pa, the speed is between 1 and 5 Kg units / min and the amount of sweetener is between 6% and 10%, and once sweetened, they are inspected and packaged.

[0022] Based on the above method, a chewable oral dosage form is obtained comprising an agar matrix combined with locust bean gum and / or sugar; glycerin; liquid and powdered inulin; active ingredients, such as vitamins or minerals; flavorings; citric acid; coating, and water to complete the composition. The key point to obtain chewable oral dosage forms according to the present invention with firmness characteristics is that they do not undergo syneresis over time and thus behave well throughout the process: - Correct hydration of gelling agents. -Achieve established cooking times and temperatures. -Maintain the recommended temperature in the system to avoid gelation and subsequent shear due to the gelation process. The drying process must be gentle and at the same time efficient so that excess water is removed to an established level.

[0023] Following the procedure and paying attention to these precautions at each step will result in a hard and stable product over time, forming a chewable oral dosage form and providing a magnesium-based composition with an agar matrix that has a chewable texture and can be effectively taken. One of the parameters that characterize the agar matrix chewable oral dosage form is the gel strength, which indicates its hardness.Generally, gel strength is proportional to the concentration of agar in the solution.Therefore, it has been experimentally proven that when agar with high gel strength is used, a chewable form with desired hardness can be obtained with a small amount of agar. Thus, the oral chewable form may comprise a composition comprising agar gelling agent in the range of 0.1% to 4.0% combined with locust bean gum; sweetener in the range of between 6% to 30%; glycerin in the range of between 1% to 3%; liquid inulin in the range of between 7% to 12%; inulin powder in the range of between 5% to 10%; flavoring agent in the range of between 0.1% to 1%; citric acid in the range of between 0.1% to 0.5%; wax-based coating in the range of between 0.5% to 3%; and black carrot in the range of 0.1% to 1% combined with between 0.1% to 85%, preferably between 10% to 60%, and more preferably between 25% to 35% of the active ingredient, as well as water to complete the composition.

[0024] Among other flavorings for the chewable forms of the present invention may include: Among the flavorings available for human consumption are strawberry, watermelon, mango, lemon, peppermint, orange, passion fruit, banana, coconut, acerola, blueberry, currant, mandarin, papaya, grapefruit, acai, chamomile, and ginger. Similarly, fruit extracts may include various sweet fruits, citrus fruits, berries, fruit combinations, and all fruit and plant extracts having suitable flavor characteristics. The active ingredients may be selected from vitamins, minerals, natural plants and herbal products, as well as active pharmaceutical ingredients, such as drugs with therapeutic properties at the level of the digestive and metabolic systems, the cardiovascular system, the genitourinary and hormonal systems, the musculoskeletal system, the nervous system, antiparasitic agents, drugs with therapeutic properties in the respiratory system, analgesics and antipyretics, but do not exclude all those envisaged in the index of pharmacological substances and drugs included in the Anatomical Therapeutic Chemical Classification system (ATC). Active ingredients may include vitamins, among others, such as vitamin D2, vitamin A, vitamin C, vitamin D and its derivatives and / or analogues, vitamin E, B-complex vitamins, such as vitamins B1, B3, B5, B9 and B12, and vitamin K2. Active ingredients may also include probiotics, fruit extracts, plant extracts, minerals such as zinc, calcium, magnesium, iron, selenium, chromium, phosphorus, potassium, copper; omega-3 fatty acids such as EPA and DHA, folic acid, iodine, biotin, choline, ginger, lutein, blueberry, and acerola, among others.

[0025] Example 1 In the illustrative examples, chewable oral dosage forms according to the present invention may comprise agar gelling agent in the range of 0.1% to 4.0% combined with locust bean gum; sweetener in the range of between 6% and 30%; glycerin in the range of between 1% and 3%; liquid inulin in the range of between 7% and 12%; inulin powder in the range of between 5% and 10%; flavoring agent in the range of between 0.1% and 1%; citric acid in the range of between 0.1% and 0.5%; wax-based coating in the range of between 0.5% and 3%; and black carrot in the range of 0.1% to 1% together with the active ingredients in Table 1, and water to complete the composition. [Table 1]

[0026] Example 2 The oral chewable composition of Example 1 contains the active ingredients in Table 2. [Table 2]

[0027] Example 3 Another example of the oral chewable form of the composition of Example 1 containing the active ingredients of Table 3. [Table 3]

[0028] Example 4 The oral chewable form of the composition of Example 1 containing the fatty acid-based active ingredient of Table 4. [Table 4]

[0029] Example 5 A composition in oral chewable form comprising an active ingredient based on magnesium and vitamins according to Table 5. [Table 5]

[0030] Example 6 The oral chewable form of the composition of Example 1 containing the active ingredients according to Table 6. [Table 6]

[0031] Example 7 Another example of the oral chewable form of the composition of Example 1 containing the active ingredients of Table 7. [Table 7]

[0032] Example 8 The oral chewable form of the composition of Example 1 containing the active ingredient combination of Table 8. [Table 8]

[0033] Example 9 The oral chewable form of Example 1 containing the active ingredients of Table 9, among many other options. [Table 9]

[0034] Example 10 This example discloses a chewable oral agar gum composition comprising the composition in the form of Example 1 and containing the active ingredients of Table 10. [Table 10]

[0035] Example 11 Another example of the composition of Example 1 in oral chewable form, containing the active ingredients of Table 11. [Table 11]

[0036] Example 12 An example of a chewable oral composition of Example 1 containing the active ingredients of Table 12. [Table 12]

[0037] Example 13 An example of a chewable oral composition of Example 1 containing the active ingredients of Table 13. [Table 13]

[0038] Example 14 Another example of the chewable oral composition of Example 1, comprising the active ingredients of Table 14. [Table 14]

[0039] Example 15 A final example of the chewable oral composition of Example 1, containing the active ingredients of Table 15. [Table 15] This Example 15, among others, combines agar gelling agent in the range of 0.1% to 4.0% combined with locust bean gum; sweetener in the range of between 6% to 30%; glycerin in the range of between 1% to 3%; liquid inulin in the range of between 7% to 12%; inulin powder in the range of between 5% to 10%; flavoring agent in the range of between 0.1% to 1%; citric acid in the range of between 0.1% to 0.5%; wax-based coating in the range of between 0.5% to 3%; black carrot in the range of 0.1% to 1%; and water to complete the composition, combined with magnesium citrate. This Example 15 specifically defines a composition containing magnesium. Magnesium is a mineral required for over 300 biochemical functions in the human body, and currently there is a deficiency of this mineral in the daily diet.

[0040] For the present invention, more than 20% magnesium must be exceeded, which typically results in a very unstable matrix in state of the art gums due to the volume and low solubility of magnesium citrate, but the matrix according to the present invention has been achieved by forming an agar matrix chewable oral dosage form that effectively contains between 28% and 32% magnesium citrate. The agar matrix chewable oral dosage form according to the present invention comprises a formulation that achieves a balance in the mixture of the above-mentioned components to provide a matrix that can be processed commercially and has stability for a shelf life of 2 years.

[0041] Thus, the present invention is applicable in the nutritional or health area as it provides an oral dosage form with excellent texture, visual appearance and flavor that is capable of delivering a desired amount of active ingredient. Only some of the preferred embodiments of the present invention have been illustrated by way of example, and in this regard, it should be recognized that the method for producing an agar matrix chewable oral dosage form having gelatin-like characteristics, as well as a pleasant texture and taste and shape configuration, can be selected from multiple options in accordance with the claims without departing from the general spirit of the present invention.

Claims

1. 1. A method of forming a chewable oral dosage form, comprising: (i) a first stage of hydrating the gelling agents agar and locust bean gum, comprising mixing agar combined with locust bean gum in an amount ranging from 0.1% to 4.0%, in particular between 0.2% and 2.0%, more particularly between 0.3% and 1.8% of the total mass of the composition, with a sweetener in an amount ranging from 6% to 10%, until a homogeneous mixture is obtained, then adding a certain amount of water and stirring until dissolution of the mixture is complete; (ii) a second step incorporating the components of the agar matrix, in which glycerin is added to the mixture of the first step (i) in an amount between 1% and 3% of the total composition together with inulin liquid in an amount between 7% and 12% of the total composition and inulin powder in an amount between 5% and 10% of the total composition, optionally mixed with a sweetener in an amount between 20% and 28% of the total composition, and then stirred until completely dissolved; (iii) a third step of incorporating the active ingredient, in which a certain amount of the active ingredient and optionally a sweetener in an amount between 7% and 10% of the total composition are premixed until a homogeneous mixture is obtained, and then added to the mixture of the second step (ii) and stirred until it is completely incorporated; (iv) a fourth step of cooking the mixture from the third step (iii) at a temperature between 80°C and 100°C for 30±5 minutes, wherein the solids must have a Brix of between 72° and 74°; and (v) a fifth flavoring step, comprising transferring the cooked paste from the fourth step (iv) to a flavoring tank and adding black carrot in an amount between 0.1% and 1%, in particular between 0.2% and 0.4%, together with flavoring agent in an amount between 0.1% and 1%, in particular between 0.4% and 0.8%, and citric acid in an amount between 0.23% and 0.29%. A method comprising:

2. (vi) a sixth step of molding and gelling, in which the mixture of the fifth step (v) is deposited into a mold at a temperature between 75°C and 89°C, and the temperature for gelling is reduced to a temperature between 2°C and 8°C; and (vii) a seventh step of demoulding, degreasing and drying, which comprises demoulding, followed by degreasing and then drying the chewable oral dosage form by dispersing it in a stool or drying basket at a temperature of 30±3° C. and a relative humidity of 25±5%.

10. The method of claim 1 further comprising:

3. (viii) an eighth step of sweetening and packaging, in which the dry chewable oral dosage forms are introduced into a sweetening machine and sweeteners are added until coating is complete, for which the steam pressure is adjusted between 275 Pa and 413 Pa, the speed is 1-5 Kg units / min and the amount of sweetener is between 6% and 10%, and once sweetened, they are inspected and packed; 3. A method for forming the chewable oral dosage form of claims 1 and 2, further comprising:

4. 4. A method for forming chewable oral dosage forms according to claims 1, 2 and 3, characterized in that the flavor is divided into a combination of flavors and fragrances and a wax-based coating.

5. 5. The method of forming a chewable oral dosage form of claim 4, wherein the flavoring is selected from strawberry, watermelon, mango, lemon, peppermint, orange, passion fruit, banana, coconut, acerola, blueberry, currant, tangerine, papaya, grapefruit, acai, chamomile, and ginger, or combinations thereof.

6. 6. The method of claim 5, wherein the active ingredients can be selected from vitamins, minerals, natural plants and herbal products; and active pharmaceutical ingredients, such as drugs with therapeutic properties at the level of the digestive and metabolic systems, the circulatory system, the genitourinary and hormonal systems, the musculoskeletal system, the nervous system, antiparasitic agents, drugs with therapeutic properties in the respiratory system, analgesics and antipyretics, and combinations thereof.

7. 4. A method for forming a chewable oral dosage form according to claims 1, 2 and 3, characterized in that the active ingredient is selected from vitamins such as vitamin D2, vitamin A, vitamin C, vitamin D and its derivatives and / or analogues, vitamin E, B complex vitamins such as vitamins B1, B3, B5, B9 and B12, and vitamin K2; probiotics; fruit extracts; plant extracts; minerals selected from zinc, calcium, magnesium, iron, selenium, chromium, phosphorus, potassium, copper; omega-3 fatty acids selected from EPA and DHA; folic acid, iodine, biotin, choline, ginger, lutein, cranberry and acerola, or combinations thereof.

8. 4. A method for forming a chewable oral dosage form according to claims 1, 2 and 3, characterized in that the sweetening agents include organic sugars, sucrose, tapioca syrup and inulin-based sugars.

9. 4. A method for forming a chewable oral dosage form according to claims 1, 2 and 3, characterized in that the sweetener comprises a sweetening additive.

10. In the seventh step (vii) of drying, the chewable oral dosage form units are dried in a tunnel dryer at a temperature of between 30±3°C and a laminar air velocity of 0.15 m / s, under conditions of 25±5% relative humidity. 3 4. A method for forming the chewable oral dosage form of claims 1, 2 and 3, characterized in that the particles are dispersed into a single layer at 1 / second.

11. 1. A chewable oral dosage form comprising a composition comprising: an agar gelling agent in combination with locust bean gum in the range of 0.1% to 4.0% of the total weight of the composition; a sweetener in the range of between 6% to 30% of the total weight of the composition; glycerin in the range of between 1% to 3% of the total weight of the composition; liquid inulin in the range of between 7% to 12% of the total weight of the composition; powdered inulin in the range of between 5% to 10% of the total weight of the composition; a flavoring agent in the range of between 0.1% to 1% of the total weight of the composition; citric acid in the range of between 0.1% to 0.5% of the total weight of the composition; a wax-based coating in the range of between 0.5% to 3% of the total weight of the composition; and black carrot in the range of 0.1% to 1% of the total weight of the composition, combined with an active ingredient and water to complete the composition.

12. 12. Oral chewable form according to claim 11, characterized in that the flavor is divided into a combination of flavors and fragrances and a wax-based coating.

13. 13. The chewable oral dosage form of claim 12, wherein the flavoring is selected from strawberry, watermelon, mango, lemon, peppermint, orange, passion fruit, banana, coconut, acerola, blueberry, currant, mandarin, papaya, grapefruit, acai, chamomile, and ginger, or a combination thereof.

14. 12. The chewable oral dosage form of claim 11, wherein the sweetening agents include organic sugars, sucrose, tapioca syrup and inulin-based sugars.

15. 12. The chewable oral dosage form of claim 11, wherein the sweetener comprises a sweetening additive.

16. 12. The chewable oral dosage form of claim 11, characterized in that the active ingredients are selected from vitamins, minerals, natural plants and herbal products; and active pharmaceutical ingredients, such as drugs with therapeutic properties at the level of the digestive and metabolic system, the circulatory system, the genitourinary and hormonal system, the musculoskeletal system, the nervous system, antiparasitic agents, drugs with therapeutic properties in the respiratory system, analgesics and antipyretics, or combinations thereof.

17. 12. The chewable oral dosage form of claim 11, wherein the active ingredient is selected from vitamins, such as vitamin D2, vitamin A, vitamin C, vitamin D and its derivatives and / or analogues, vitamin E, B-complex vitamins, such as vitamins B1, B3, B5, B9 and B12, and vitamin K2; probiotics; fruit extracts; plant extracts; minerals selected from zinc, calcium, magnesium, iron, selenium, chromium, phosphorus, potassium, copper; omega-3 fatty acids selected from EPA and DHA; folic acid, iodine, biotin, choline, ginger, lutein, cranberry and acerola, or combinations thereof.

18. 12. The chewable oral dosage form of claim 11, comprising 1% to 1.5% agar gelling agent combined with locust bean gum; sugar in the range of 6% to 30%; glycerin in the range of 1% to 3%; liquid inulin in the range between 7% and 10%; inulin powder in the range of 6% to 8%; flavoring in the range of 1%; citric acid in the range of 0.5%; coating in the range of 1.5%; black carrot in the range of 0.3%, together with magnesium citrate, and optionally calcium and vitamin D, and water to complete the composition.

19. 12. The chewable oral dosage form of claim 11, comprising 1% to 1.5% agar gelling agent combined with locust bean gum; sugar in the range of 6% to 30%; glycerin in the range of 1% to 3%; liquid inulin in the range between 7% and 10%; powdered inulin in the range of 6% to 8%; flavoring in the range of 1%; citric acid in the range of 0.5%; coating in the range of 1.5%; black carrot in the range of 0.3%, together with magnesium citrate, melatonin and passionflower, and water to complete the composition.

20. 12. The chewable oral dosage form of claim 11, characterized in that it comprises 1% to 1.5% agar gelling agent combined with locust bean gum; sugar in the range of 6% to 30%; glycerin in the range of 1% to 3%; liquid inulin in the range between 7% to 10%; inulin powder in the range of 6% to 8%; flavoring in the range of 1%; citric acid in the range of 0.5%; coating in the range of 1.5%; black carrot in the range of 0.3% together with a mixture of pyridoxine HCl, vitamin B6, vitamin B12 and ginseng extract, and water to complete the composition.

21. 12. The chewable oral dosage form of claim 11, comprising 1% to 1.5% agar gelling agent combined with locust bean gum; sugar in the range of 6% to 30%; glycerin in the range of 1% to 3%; liquid inulin in the range between 7% and 10%; inulin powder in the range of 6% to 8%; flavoring in the range of 1%; citric acid in the range of 0.5%; coating in the range of 1.5%; black carrot in the range of 0.3%, together with a mixture of magnesium citrate, melatonin and passionflower, and water to complete the composition.

22. 12. The chewable oral dosage form of claim 11, comprising 1% to 1.5% agar gelling agent combined with locust bean gum; sugar in the range of 6% to 30%; glycerin in the range of 1% to 3%; liquid inulin in the range between 7% and 10%; inulin powder in the range of 6% to 8%; flavoring in the range of 1%; citric acid in the range of 0.5%; coating in the range of 1.5%; black carrot in the range of 0.3% together with a mixture of lemon balm and L-theanine, and water to complete the composition.

23. 12. The chewable oral dosage form of claim 11, comprising 1% to 1.5% agar gelling agent combined with locust bean gum; sugar in the range of 6% to 30%; glycerin in the range of 1% to 3%; liquid inulin in the range between 7% and 10%; inulin powder in the range of 6% to 8%; flavoring in the range of 1%; citric acid in the range of 0.5%; coating in the range of 1.5%; black carrot in the range of 0.3%, together with a mixture of saffron and vitamin D3, and water to complete the composition.

24. 12. The chewable oral dosage form of claim 11, comprising 1% to 1.5% agar gelling agent combined with locust bean gum; sugar in the range of 6% to 30%; glycerin in the range of 1% to 3%; liquid inulin in the range between 7% and 10%; inulin powder in the range of 6% to 8%; flavoring in the range of 1%; citric acid in the range of 0.5%; coating in the range of 1.5%; black carrot in the range of 0.3% together with ascorbic acid, zinc citrate and optionally a mixture of elderberry, vitamins, minerals, folic acid or combinations thereof, and water to complete the composition.

25. 12. The chewable oral dosage form of claim 11, comprising 1% to 1.5% agar gelling agent combined with locust bean gum; sugar in the range of 6% to 30%; glycerin in the range of 1% to 3%; liquid inulin in the range between 7% and 10%; inulin powder in the range of 6% to 8%; flavoring in the range of 1%; citric acid in the range of 0.5%; coating in the range of 1.5%; black carrot in the range of 0.3% together with probiotics, such as Bacillus coagulans and fruit and plant extracts, and optionally a mixture of vitamins, minerals, biotin, choline, iodine, lutein, acerola and combinations thereof, and water to complete the composition.

26. 12. The chewable oral dosage form of claim 11, comprising 1% to 1.5% agar gelling agent combined with locust bean gum; sugar in the range of 6% to 30%; glycerin in the range of 1% to 3%; liquid inulin in the range between 7% and 10%; inulin powder in the range of 6% to 8%; flavorings in the range of 1%; citric acid in the range of 0.5%; coating in the range of 1.5%; and black carrot in the range of 0.3% in combination with omega-3 fatty acids.

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