Stabilized vitamin A and preparation method thereof

Abstract

Methods of making fat-soluble vitamin particles are provided. The particles exhibit extended shelf life and cooking stability, and can be prepared in the absence of inorganic acids or organic solvents. The particles are composite particles of a pH-sensitive polymer and a fat-soluble vitamin, such as vitamin A. The particles may be incorporated into food products, such as bouillon condiments, cereals, wheat flour, millet flour, tapioca flour, tapioca flour, eragrostis pilosa flour, corn flour, milk, milk powder, malt beverages, soy sauce, ready-to-eat therapeutic foods, rice or sugar. These foods can provide a stable source of vitamin A for people in need thereof.

Description

Technical Field

[0001] The present disclosure relates to the preparation of fat-soluble vitamins, and in particular to the preparation of stabilized vitamin A. Background Art

[0002] Vitamin deficiency remains a problem, particularly in low-income countries. The diets of many people in these countries do not provide adequate amounts of vitamin A, and it is difficult to fortify foods with vitamin A due to the short shelf life and cooking degradation of added vitamin A. There is a need for improved forms of vitamin A that can withstand storage at high temperatures and / or high humidity and that can maintain biologically active levels after cooking. Summary of the invention

[0003] In one aspect, composite particles of vitamin A or its derivatives are provided, the particles comprising a pH-sensitive polymer and subparticles or subdroplets of vitamin A embedded in the pH-sensitive polymer, wherein the composite particles are substantially free of organic solvents and inorganic acids, and the amount of vitamin A in the composite particles is a first concentration after preparing the particles and a second concentration after subjecting the composite particles to a 4-week shelf life test at 40°C and a 2-hour cooking test in water at 90°C, and the second concentration is greater than 60% of the first concentration, greater than 70% of the first concentration, greater than 80% of the first concentration, or greater than 90% of the first concentration. The composite particles may include vitamin A palmitate, ascorbic acid, maltodextrin, modified starch, ascorbic acid, BHT, BHA, tocopherol, or a combination thereof. It may be substantially free of surfactants. The pH-sensitive polymer may be a polymethacrylate, such as BMC. The median volume diameter D of the subparticles or subdroplets 50 The median volume diameter D of the composite microparticles may be 50 nm to 2 μm, 100 nm to 1 μm, 100 nm to 500 nm, or 200 nm to 400 nm. 50 The size may be 1 to 1000 μm, 1 to 100 μm, 1 to 10 μm, 50 to 1000 μm, 50 to 400 μm, 100 to 400 μm, 50 to 300 μm or 100 to 500 μm with a standard deviation of less than 50 μm. The composite particles may include vitamin C. The composite particles may be added to bouillon and foods including wheat flour, millet flour, cassava flour, tapioca flour, teff flour, corn flour, milk, milk powder, malt beverage, soy sauce, ready-to-eat therapeutic foods, rice or sugar.

[0004] On the other hand, a method is provided, the method comprising forming an acidified aqueous vehicle at a pH less than or equal to 6.0, combining a pH-sensitive polymer with an aqueous vehicle to form a colloidal suspension, allowing the pH of the suspension to rise to greater than 6.0, emulsifying fat-soluble vitamins or derivatives thereof, combining the colloidal suspension and the emulsified fat-soluble vitamins or derivatives thereof, limiting the pH increase after the addition of the fat-soluble vitamins or derivatives thereof to a pH of 7.0, and removing water from the suspension to produce composite microparticles comprising a matrix of the fat-soluble vitamins or derivatives thereof and a pH-sensitive polymer. Water can be removed by spray drying, fluidized bed drying, vacuum drying, rotary evaporator drying, freeze drying and / or multi-stage drying. The method may be free of surfactants and / or inorganic acids. The pH of the acidified aqueous vehicle may be reduced to 5.5 or less using an organic acid, which may be ascorbic acid, tartaric acid, or a combination of the two. The method may avoid the use of organic solvents. Fat-soluble vitamins may be emulsified in an aqueous solution comprising maltodextrin, starch, or a combination thereof. The method may include coating the composite microparticles with a polysaccharide, and the polysaccharide may be starch, modified starch and / or maltodextrin. The median volume diameter D of the resulting particles is 50 The microparticles may be larger than 1 μm and smaller than 500 μm, larger than 50 μm and smaller than 400 μm, larger than 100 μm and smaller than 200 μm. The method may include adding the composite microparticles to the food and adding the antioxidant to the fat-soluble vitamins. The antioxidant may be a synthetic antioxidant selected from at least one of BHA and BHT. The method may include adding a defoaming agent or an anti-foaming agent.

[0005] In another aspect, a food ingredient is provided, the food ingredient comprising composite microparticles, the composite microparticles comprising subparticles or subdroplets of vitamin A or its derivatives in a pH-sensitive polymer, the median volume diameter D of the composite microparticles being 50The composite microparticles are 1 to 1000 μm, 1 to 100 μm, 1 to 10 μm, 50 to 1000 μm, 50 to 400 μm, 100 to 400 μm, 50 to 300 μm or 100 to 500 μm, wherein the composite microparticles are substantially free of anionic surfactants. It may include ascorbic acid, BHT, BHA, tocopherol or a combination thereof and may be prepared without the use of inorganic acids. It may be used in broth seasoning, wheat flour, millet flour, cassava flour, manioc flour, teff flour, corn flour, milk, milk powder, malt beverage, soy sauce, instant therapeutic food, rice or sugar. It may be substantially free of inorganic acids, surfactants and organic solvents. The pH-sensitive polymer may be a polymethacrylate, such as BMC. It may include vitamin A palmitate, ascorbic acid, maltodextrin and modified starch. The subparticles or subdroplets may exhibit a median volume diameter D between 50 nm and 2 μm, between 100 nm and 1 μm, between 100 nm and 500 nm, or between 200 nm and 400 nm. 50 The composite microparticles may have a standard deviation of less than 50 μm. The food ingredient may include a soluble vitamin, such as vitamin C.

[0006] In another aspect, the food composition comprises composite microparticles comprising subparticles or subdroplets of vitamin A or a derivative thereof in a pH-sensitive polymer matrix, wherein the median volume diameter D of the composite microparticles is 50 The composite microparticles may be 1 to 1000 μm, 1 to 100 μm, 1 to 10 μm, 50 to 1000 μm, 50 to 400 μm, 100 to 400 μm, 50 to 300 μm or 100 to 500 μm, wherein the composite microparticles include a synthetic antioxidant. The synthetic antioxidant may be BHA and / or BHT. The food ingredient may include vitamin C and may be prepared without the use of an inorganic acid or an anionic surfactant. It may be substantially free of inorganic acids and organic solvents. It may be incorporated into broth seasoning, wheat flour, millet flour, cassava flour, manioc flour, teff flour, corn flour, milk, milk powder, malt beverage, soy sauce, ready-to-eat therapeutic food, rice or sugar. The pH-sensitive polymer may be a polymethacrylate, such as BMC. It may include vitamin A palmitate, ascorbic acid, maltodextrin and modified starch. The composite microparticles may have a standard deviation of less than 50 μm.

[0007] In another aspect, a method is provided, the method comprising mixing a pH-sensitive polymer with water and an organic acid to produce a suspension, adding at least one polysaccharide to the suspension, adding a fat-soluble vitamin or a derivative thereof to the suspension, adjusting the pH of the suspension to less than 6.0, emulsifying the suspension to produce a median volume diameter D 50Composite droplets less than 1 μm, limiting the pH increase to less than 8.0, and removing water from the emulsion to produce composite microparticles, which include a matrix of fat-soluble vitamins or derivatives thereof and a polymethacrylate polymer binder. The method may include allowing the pH of the suspension to rise to at least 6.0. The fat-soluble vitamins or derivatives thereof can be emulsified in an aqueous vehicle including one or more polysaccharides and an organic acid. The one or more polysaccharides can be maltodextrin and / or modified starch, and the organic acid can be ascorbic acid and / or tartaric acid. The pH-sensitive polymer can be a polymethacrylate, such as BMC.

[0008] In another aspect, a method is provided, comprising preparing an aqueous suspension of at least one polysaccharide and an organic acid, adding a fat-soluble vitamin or a derivative thereof to the suspension, mixing a solid pH-sensitive polymer into the suspension, adjusting the pH of the emulsion to less than 6.0, emulsifying the suspension to produce a median volume diameter D 50 Composite droplets of less than 1 μm, and removing water from the emulsion to produce composite microparticles, the composite microparticles comprising a matrix of fat-soluble vitamins or derivatives thereof and a polymethacrylate polymer binder. One or more polysaccharides may be maltodextrin and / or modified starch, and the organic acid may be ascorbic acid and / or tartaric acid. The pH-sensitive polymer may be a polymethacrylate, such as BMC. Any method may use water having a hardness of less than 100 ppm based on CaCO3, such as tap water having a hardness of less than 100 ppm based on CaCO3. The compositions and methods described herein may be used alone or together, and components or techniques described with respect to one system or method may be implemented with other systems or methods. In some cases, the subject matter of the present application may relate to interrelated products, alternative solutions to a particular problem, and / or multiple different uses of a single system or article. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] In the accompanying drawings,

[0010] Figure 1 is a schematic diagram and flow chart illustrating one embodiment of a system for processing and drying multivitamin granules;

[0011] Figure 2 is a schematic diagram illustrating a composite particle;

[0012] Figure 3 is a schematic diagram illustrating one embodiment of an emulsification process;

[0013] Figure 4 is a schematic diagram illustrating a second embodiment of the emulsification process;

[0014] Figure 5is a schematic diagram illustrating a third embodiment of the emulsification process;

[0015] Figure 6 Figure 1 shows data comparing the shelf life of a comparative VAP sample and a comparative commercial VAP sample;

[0016] Figure 7 Pictured Figure 6 Cooking stability of VAP samples;

[0017] Figure 8 Figure 1 shows data comparing the shelf life of experimental VAP samples and comparative commercial VAP samples;

[0018] Fig. 9 Pictured Figure 8 Cooking stability of VAP samples;

[0019] Fig.10 graphically presents data comparing the shelf life of an experimental VAP sample and a comparative commercial VAP sample; and

[0020] Fig.11 Pictured Fig.10 Cooking stability of VAP samples.

[0021] The above and other features of the present disclosure and the manner of achieving them will become more readily apparent and better understood by referring to the embodiments of the present disclosure described below in conjunction with the accompanying drawings, in which: DETAILED DESCRIPTION

[0022] Disclosed herein are stabilized particles of vitamin A, foods fortified with vitamin A, and methods for preparing stabilized vitamin A. In a first aspect, methods for preparing vitamin A particles and various foods into which the particles can be incorporated are disclosed. The particles can be prepared in large quantities with consistent sizes so that they have predictable stability on the shelf, during cooking, and in vivo. When incorporated into foods such as broth condiments, cereals, wheat flour, millet flour, tapioca flour, cassava flour, teff flour, corn flour, milk, milk powder, malt beverages, soy sauce, instant therapeutic foods, rice, or sugar, vitamin A retains greater activity in storage and cooking than previously available vitamin A particles. The particles can also be incorporated into animal feed and non-food products such as supplements, micronutrient powders, therapeutic agents, skin care agents, and cosmetics.

[0023] The method disclosed herein relates to forming stable particles of fat-soluble vitamins in the absence of non-aqueous solvents. In addition, the pH-sensitive polymer used to encapsulate and protect vitamin A does not need to be water-soluble. The fat-soluble vitamins in the aqueous system are combined with the water-insoluble pH-sensitive polymers in the aqueous system and processed into stable, bioavailable food additives. In one aspect, vitamin A microdroplets can be produced in an emulsion and dried to form microparticles. As used herein, "microdroplets" refer to droplets of vitamin A produced during the emulsification process, while "microparticles" refer to particles produced during the drying process. Particles with a diameter of less than 1 μm are nanoparticles. "Subparticles" are particles or droplets included in larger composite particles. The particles may include a polymer that releases vitamin A after being ingested. The polymer may be natural or synthetic and may be pH-sensitive, meaning that it is stable in one pH range and unstable in another pH range. Vitamin A particles may be prepared without the use of organic solvents, mineral oils, inorganic acids, and undesirable surfactants. The absence of these materials provides a safer product that can be safely incorporated into food. The examples provided herein relate to vitamin A, but other nutrients and fat-soluble vitamins can also be processed using the methods described. Other fat-soluble vitamins include vitamins D, E, and K.

[0024] The preparation process can be a purely aqueous process. These preparation processes can use organic acids to reduce the pH value, and the process can be free of inorganic acids. The method without inorganic acids is a method that does not include the addition of inorganic acids at any node in the particle preparation method. In order to reduce the pH and promote the dissolution or dispersion of polymers and other components, organic acids can be used. In some cases, the organic acid is a vitamin. The pKa of a suitable acid can be greater than 2.5, greater than 2.9, greater than 3.5, greater than 3.75, greater than 4.0, greater than 4.25, greater than 4.5, greater than 4.75, less than 5.5, less than 5, less than 4.5, less than 4.25, less than 4.0, less than 3.75 or less than 3.5. Exemplary organic acids include ascorbic acid, tartaric acid, folic acid, stearic acid, acetylsalicylic acid, citric acid and oleic acid. A pH buffer can be included, but it can also be excluded from the method. The method described herein can also be carried out without using surfactants that may not be desired in food, and the method can be substantially free of these surfactants. These surfactants include sodium lauryl sulfate (SDS), sodium lauryl sulfate (SLS), stearyl alcohol, polysorbate, polyethylene glycol stearate, cetearyl glucoside, polyglyceryl stearate, polyglyceryl distearate, sodium stearoyl glutamate, distearyl dimethyl ammonium chloride. If the composition includes a certain compound at an undetectable level, or if the compound is detected, but the level of the compound is only due to the background level of the compound in the components used to prepare the particles, the composition is "substantially free of" the compound. In different embodiments, the water used in the method can have different purities. For example, water can be ultrapure water, reverse osmosis treated water, carbon filtered water, distilled water or tap water. In terms of CaCO3, water can have a hardness of less than 50ppm, less than 100ppm or less than 200ppm.

[0025] Vitamin A is a fat-soluble vitamin that can exist in three active forms, including retinol, retinal, and retinoic acid. As used herein, "vitamin A" includes these forms and compounds that can be converted into vitamin A in the body. These structures include, for example, carotenoids, retinyl palmitate, retinyl acetate, all-trans retinol, all-trans retinal, all-trans retinoic acid, 11-cis-retinal, 13-cis-retinoic acid, and 9-cis-retinoic acid. Carotenoids include alpha carotene, beta carotene, beta cryptoxanthin, lutein, zeaxanthin, and lycopene.

[0026] The method may include adding an antioxidant to help prolong the activity of vitamin A. The antioxidant should be selected from those that are safe for human and / or animal consumption. The antioxidant can be added at any time during the preparation process, such as in the raw material, in the emulsification stage, in the particle drying stage, in bulk packaging, or when combined with food. The antioxidant is provided in a concentration sufficient to protect vitamin A from decomposition. The mass ratio (w / w) of antioxidant to vitamin A can be, for example, greater than 1:100, greater than 1:20, greater than 1:10, greater than 1:5, less than 1:2, less than 1:4, less than 1:10 or less than 1:20. The antioxidant can be synthetic or natural. Such antioxidants can include, for example, tocopherol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butylhydroquinone (TBHQ), anoxomer, dilauryl thiodipropionate, ethoxyquinoline, nordihydroguaiaretic acid, propyl gallate, octyl gallate, 2,4,5-trihydroxybutylbenzophenone (THBP), ascorbyl palmitate, sodium ascorbate, calcium ascorbate, ascorbic acid, rosemary extract, and / or thiodipropionic acid.

[0027] The method can be completely water-based and can be free of organic solvents. As used herein, organic solvents are those hydrocarbon solvents, including aliphatic and aromatic, having a solubility of less than 10% w / w in water at room temperature. Specific organic solvents that can be excluded from those solvents include acetone, chloroform, methylene chloride, toluene, and tetrahydrofuran. In addition to being free of organic solvents, the method can also avoid the use of alcohols, aldehydes, and ketones. In some embodiments, an aqueous method is completed without the use of methylene chloride or acetone or without the use of both methylene chloride and acetone. In some embodiments, the materials used can be limited to water, organic acids, pH-sensitive polymers, antioxidants, and excipients approved for use in food.

[0028] Vitamin particles disclosed herein can be combined with polymer coatings, such as pH-sensitive polymers, which protect vitamin A from degradation, but allow vitamin A to become bioavailable in the human intestinal tract and / or animal intestinal tract. pH-sensitive polymers can be non-toxic and should be suitable for human consumption. As used herein, if the polymer is not affected at a first pH, but degrades, swells, dissolves or otherwise changes form to the extent that the material surrounded by the polymer is exposed to the environment at a second pH (pH critical point), the polymer is pH-sensitive. Typically, pH-sensitive polymers experience degradation, dispersion or dissolution at lower pH. For example, a polymer that is sensitive to pH at a pH of 6.0 will be intact when the pH is higher than 6.0, but will release material when the pH is lower than 6.0. In various embodiments, the polymer used herein can be degraded or dissolved at a pH lower than 6.0, lower than 5.5, lower than 5.0, lower than 4.5, lower than 4.0, lower than 3.5 or lower than 3.0. In this and other embodiments, the polymer can be stable and insoluble at a pH greater than 3.0, greater than 3.5, greater than 4.0, greater than 4.5, greater than 5.0, greater than 5.5, or greater than 6.0.

[0029] The pH sensitive polymers described herein may include basic groups, such as amino groups, or acidic groups, such as carboxylic acid, phosphonic acid and sulfonic acid groups. The polymer may be a natural polymer, such as a cellulose or polysaccharide polymer. The polymer may include a hydrolysis-active polycarbonate backbone. In one set of embodiments, the polymer used includes an acidic group and may be a cationic copolymer, such as a polymethacrylate. In a specific embodiment, the polymer may be an ethyl methacrylate-methacrylic acid copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate in a ratio of, for example, 2:1:1. The molecular weight of the pH sensitive polymer may be less than 50,000 g / mol, less than 100,000 g / mol, 25,000 to 75,000 g / mol, 100,000 to 200,000 g / mol, 200,000 to 300,000 g / mol, 300,000 to 400,000 g / mol, 400,000 to 500,000 g / mol, or less than 500,000 g / mol. In one embodiment, the pH sensitive polymer is an ethyl methacrylate-methacrylic acid copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate in a ratio of 2:1:1 and has an average molecular weight of 47,000. These polymers are generally referred to as basic methacrylate copolymers or BMCs. These polymers are available from Evonik under the trade name and In powder form. The polymers are available in different particle sizes, and in many embodiments, smaller particle sizes are preferred. For example, particles with a diameter of less than 1 μm or 10 μm (EUDRAGIT E PO or EUDRAGUARDProtect) have been used to provide a workable suspension of the material more quickly.

[0030] The concentration of vitamin A in the dry granules may be greater than 1 mass%, greater than 10 mass%, greater than or equal to 12 mass%, greater than or equal to 14 mass%, greater than or equal to 15 mass%, greater than or equal to 16 mass%, greater than or equal to 18 mass%, greater than or equal to 20 mass%, greater than or equal to 22 mass%, or greater than or equal to 24 mass%. In addition, the amount of fat-soluble vitamin (vitamin A) relative to the pH-sensitive polymer may be greater than or equal to 0.1:1, 1:1, 1.2:1, 1.5:1, 2:1, or 10:1 by weight. In addition to vitamin A and the pH-sensitive polymer, the balance of the granules (about 10-90%) may include, for example, starch, modified starch, maltodextrin, sugar, gum arabic, antioxidants, water-soluble vitamins such as vitamin C, fat-soluble vitamins such as vitamins D and K, and colorants.

[0031] Other materials that can be used in the granules include excipients, such as colorants, mixing aids, emulsifiers, antifoaming agents, defoaming agents, and textural enhancers, such as starches, modified starches, and maltodextrins. In some embodiments, the excipients can improve the method and / or product. For example, modified starch can improve the suspension of vitamin A in an aqueous system, and when combined with vitamin A (liquid), it can produce an entity that interacts with the pH-sensitive polymer to a greater extent than when the modified starch is not present. Modified starches include materials made from corn, waxy corn, cassava / tapioca, potato, or wheat, and can exhibit a pH of 3.5 to 4.5 in a 9% aqueous slurry. One of these modified starches can be present in an aqueous slurry of 1% to 4.5. 100 is commercially available. In other embodiments, excipients can improve the method. In some cases, the incorporation of pH-sensitive polymers in aqueous systems can result in the formation of foam within the mixture, which can reduce the quality of the emulsion, hinder subsequent ingredient additions, reduce product yields, and / or produce dry particles of lower quality and / or greater variability. The addition of antifoaming agents and / or defoaming agents can prevent the formation of foam within the mixture and / or destroy the formation of foam by reducing the surface tension of droplets at the surface. Antifoaming agents / defoaming agents can be oil-based, water-based, or silicone-based, and can involve ingredients such as vegetable oils, monoglycerides, diglycerides, polydimethylsiloxanes, and silicon dioxide. One of these defoaming agents can be MD-3000 is commercially available.

[0032] exist Figure 1A set of implementation modes is shown in the figure. Figure 1The equipment and techniques shown in provide examples of how these methods can be employed. As shown, the process is divided into a liquid preparation process 101 and a drying process 102. All components can be fed into an emulsion tank 112 and passed through a high-pressure homogenizer 116. Both the vitamin and polymer components can be in liquid form at room temperature and can be mixed together. The liquid preparation process 101 uses a container 110, in which vitamin A (e.g., retinyl palmitate) 150 and an antioxidant 152 are weighed. The polymer can be dispersed in a mixer 114, and the organic acid can be added before or after the polymer is added to the mixer 114. Any excipients, such as modified starch, can be added via stream 140. In the mixer 114, the polymer 160 (e.g., EUDRAGUARD Protect) is mixed in its original powder form with a fixed amount of organic acid 162 in water. The amount of water used should be sufficient to form a usable suspension of the polymer, and can be, for example, 2-20 times the amount of the polymer by weight. The temperature of the water can be between 10-50°C, 20-40°C, 30-40°C, or 30-35°C. The initial pH of the mixture just after the acid and polymer are mixed can be, for example, less than 7.5, less than 7.0, less than 6.5, less than 6.0, less than 5.5, less than 5.0, less than 4.5, or less than 4.0. The specific range of initial pH can be 3.0 to 5.0, 3.5 to 5.0, 4.0 to 5.5, 4.0 to 5.0, 4.5 to 5.0, 5.0 to 6.0, and 6.0 to 7.0. The amount of organic acid mixed with the polymer can be provided in terms of the molar amount of the organic acid to the kilograms of the polymer. In various embodiments, the ratio can be in the range of 1:10 to 2:1, 1:5 to 5:1, 1:3 to 2:1, 1:2 to 5:1, 1:1 to 1:1.2, or 1.05:1 to 1.20:1. For example, per kg EudraGuardProtect, per 5L water corresponding to 1.2mol of ascorbic acid to achieve an initial pH of 4.5 to 5.0. When the solid polymer particles dissociate and the polymer molecules become suspended, the pH of the mixture increases. In order to improve the droplet and particle morphology, the pH is allowed to increase to greater than 5.5, greater than 6.0, greater than 6.5 or greater than 7.0. In some embodiments, the pH increase is not operated by adding any alkali or buffer after the initial mixing, but is only regulated by the fixed amount of acid added at the beginning of the mixing process and the pH increase due to the polymer. The mixture is stirred until the solution is partially or completely clarified. Clarity can be determined by measuring turbidity, showing a threshold value of less than 100, less than 50, less than 40, less than 30, less than 20, less than 10, less than 5 or less than 2 nephelometric turbidity units (NTU) in various embodiments. The process can take less than 24 hours, less than 12 hours, less than 3 hours or less than 1 hour. In some embodiments, the suspension is clarified in about 30 minutes.The suspension may be used immediately or may be stored stably for days, weeks or months before forming into dry granules. A suspension is considered stable if it does not separate into different phases.

[0033] Suspended polymers from mixer 114, vitamin A and antioxidants from 110, and any excipients can be mixed in emulsification tank 112. All three feeds from pipeline 140, container 110, and mixer 114 can be free of organic solvents. They can be added to emulsification tank 112 in any order and can be added continuously or in batches. The emulsification tank can be pre-loaded with an aqueous solution of one, two, three or more polysaccharides, such as starch, maltodextrin, or both. In one set of embodiments, the method is performed on a batch basis, wherein vitamin A palmitate (VAP) and antioxidants are transferred to emulsification tank 112 and emulsified before adding the polymer suspension. A suspension of acidified polymer can be added to the VAP emulsion, wherein the colloidal polymer suspension can self-assemble around the VAP droplets. Emulsification tank 112 includes a mixer capable of emulsifying vitamin A and suspended polymers. Mixing can occur at a temperature range of, for example, 10-60°C, 20-50°C, 30-40°C, or 30-35°C. The mixer can be, for example, an agitator, a vortex mixer, a rotary mixer, or an in-line mixer. In one set of embodiments, the mixer is a high shear dispersing blade mixer. The mixture in the emulsification tank 112 can pass through a high pressure homogenizer 116 to further emulsify the components. In one embodiment, the high pressure emulsifier is a BOS model MG2-350S. As shown, the mixture can pass through the high pressure homogenizer 116 and then be recycled back to the emulsification tank 112. The stability of the emulsion or suspension depends on many factors, including the size of the vitamin A droplets. Use Droplet size is measured by volume using laser diffraction at 3000 x 10 in standard analysis mode. In general, the smaller the droplet size, the more stable the emulsion. In various embodiments, the median volume D of the droplet size is 50 It can be less than 1.0 μm, less than 800 nm, less than 600 nm, less than 500 nm, less than 400 nm, or less than 350 nm. Size consistency has been shown to be important, and it is believed that a unimodal size distribution around the average size can produce a better performing product. The standard deviation of the vitamin A droplet size can be less than 200 nm, less than 100 nm, or less than 50 nm. The emulsification tank 112 can be monitored to assess the quality of the emulsion by measuring various parameters including, for example, droplet size, color, pH, temperature, and turbidity. When the emulsion reaches the desired droplet size, for example, less than 5 μm, less than 1 μm, less than 500 nm, less than 400 nm, or less than 350 nm, it can be transferred to the drying process 102. In some embodiments, the batch is emulsified for more than 30 min, more than 1 hr, or more than 6 hr.

[0034] In other embodiments, a single-pass online homogenization method can be used. In this case, an overhead high shear dispersing mixer in a main tank can be used to produce an initial emulsion. This high shear dispersing mixture can obtain a volume median droplet size of, for example, less than 50 μm, less than 30 μm, or less than 10 μm. In order to reduce the droplet size, the emulsion is then fed to an online high shear pump and a homogenizer. This reduces the VAP droplet size to, for example, less than 5 μm, less than 1 μm, less than 500 nm, less than 400 nm, or less than 350 nm. The emulsion can then be transferred to a spray dryer (or other dryer) to form composite particles.

[0035] In the drying process 102, the suspension from the emulsifying cylinder 112 is flowed to a dryer, such as a spray dryer 120. The spray dryer 120 includes an air inlet 170 that can supply a heated air stream. The spray dryer 120 atomizes the liquid fed by one or more spray devices or nozzles 118, and forms solid particles because water is removed. The spray device can be selected from a variety of types, such as pressure, air atomization, spin or rotating disk, ultrasonic, piezoelectric and electrostatic. As shown, the spray dryer 120 is supplied by an air stream 170 and includes an internal fluidized bed dryer 124 with an additional fluidizing air stream 172. In some embodiments, the dryer may not include an internal bed or may have an external bed 128 supplied by an air stream 182, or may have both an internal bed and an external bed. The fine powder formed during the drying process is transported to a cyclone separator 126 and / or is transported from the top of an external fluidized bed dryer 128 by a conduit 174 via an extractor on the top of the dryer. Cyclone separator 126 also includes an exhaust port for moisture and air. The captured fine powder is recycled to spray dryer 120 via conduit 176. Depending on the desired degree of agglomeration, these fine powders are directed to conduits 178 or 180. In some embodiments, when fine powder is directed to the upper half or upper third of spray dryer 120 through conduit 178, better yield and particle size are obtained. This is considered to be due to the reduction of larger particle formation and agglomeration on the side of the dryer. Fine powder can be coated with partially dried droplets and make less adhesion to the dryer wall. Fluidized bed dryer 128 separates the desired product, dried vitamin A powder, from the dryer fine powder by gravity. Optionally, cyclone separator 130 and / or bag filter can be used to collect product. The collected particles pass through screen 132, and screen 132 can remove particles that are considered too large, such as particles of 2 times, 5 times or 10 times, 50 times or 100 times the volume median particle size. After sieving, the granules are dry and can be stored or incorporated into food. Optional post-production processes may include packaging, grinding, sizing and adding components such as colorants, antioxidants, dehydrating agents, lubricants and other micronutrients.

[0036] During the preparation process, droplets of vitamin A palmitate (VAP) and suspended polymer droplets fuse to form composite microdroplets of vitamin A and pH-sensitive polymer. It is believed that the pH-sensitive polymer surrounds the vitamin A droplets because the hydrophobic portion of the polymer is attracted to the fat-soluble vitamin. Once they are emulsified together, the polymer and vitamin A palmitate can form emulsified co-droplets of vitamin A palmitate and related polymers, whose volume median diameter can be 50nm to 2μm, 100nm to 1μm, 100nm to 500nm, or 200nm to 400nm. In some cases, the resulting dry particles may include a continuous mass of vitamin A embedded in a pH-sensitive polymer, and the volume median diameter (D 50 ) between, for example, 50 and 2000 μm. However, in other cases, upon drying, it is believed that these co-droplets of vitamin A and polymer coalesce into composite droplets, such as Figure 2 . Note that this figure is an approximation for illustration purposes and that actual particles may not be spherical and may not contain any particular number of discrete vitamin A subparticles. Composite particle 200 includes a plurality of individual submicron particles 210 of vitamin A, which may have a volume median diameter similar to the emulsion droplets of vitamin A formed during the liquid phase. In the liquid state, pH-sensitive polymer 216 may preferentially align around the subdroplets of vitamin A. Once dried, these submicron particles of vitamin A have a volume median diameter D 50 It can be, for example, 100-500 nm, 200-400 nm, or 300-450 nm. A plurality of submicron vitamin A particles can be held together by a polymer and an excipient to form a composite particle 200 comprising vitamin A, a polymer, an antioxidant, and an excipient 212. In various embodiments, the volume median diameter D of these composite particles is 50 It may be 1 to 1000 μm, 1 to 100 μm, 1 to 10 μm, 50 to 1000 μm, 50 to 400 μm, 100 to 400 μm or 50 to 300 μm. The composite particles may also be coated with a starch coating 214, which may help prevent the composite particles from clumping and agglomerating.

[0037] The vitamin A particles described herein can be incorporated into foods such as broth seasoning, rice, pasta, flour, sugar, cornmeal and other foods that are usually cooked before consumption, and / or milk, milk powder, soy sauce, malt beverages, instant therapeutic foods and other foods or seasonings that are usually not cooked before consumption. The vitamin A composite particles can retain more than 50%, more than 60%, more than 70%, more than 80% or more than 90% of the vitamin A activity after cooking at 90°C for 120 minutes. It has been previously found that the vitamin A particles of the prior art can exhibit good short-term stability in hot water, but the same particles exhibit poor shelf life under typical storage conditions. In contrast, the composite particles described herein can maintain more than 70%, more than 80% or more than 90% of the vitamin A activity at 40°C and 75% relative humidity over a storage period of 28, 60, 90 or 120 days. The particles can retain more than 40%, more than 50%, more than 60%, more than 70% or more than 80% of the original potency after i) storage at 40°C and 75% relative humidity for 6 months and ii) cooking at 90°C for 120 minutes. The particles also show improved stability when other nutritional additives are included. For example, iron has been shown to hinder the shelf life of vitamin A, but the reduction in shelf life is minimized in the current formulation under storage or cooking conditions. The vitamin A particles can be mixed into food at a concentration that provides sufficient nutrition to the person consuming the food. For example, the particles can be mixed into food, such as broth seasoning, with a vitamin A (RE) concentration (wt / wt) of 0-1300 mg RE / kg fortified food, 13-510 mg RE / kg fortified food, 19-320 mg RE / kg fortified food or 19-200 mg RE / kg fortified food. The amount in wheat flour can be, for example, 0-46mgRE / kg, 0.46-18mgRE / kg, 0.69-11mgRE / kg or 0.69-7.0mgRE / kg. The amount in sugar can be, for example, 0-120mgRE / kg, 1.2-49mgRE / kg, 1.8-31mgRE / kg or 1.8-19mgRE / kg. After the particles are mixed with the food, the resulting fortifying material can be packaged and stored. Packaging can be selected to protect the fortifying material from moisture and oxygen. The material added to the fat-soluble vitamins to prepare the vitamin particles of this paper can be limited to the material recorded in the Codex General Standard for Food Additives.

[0038] Example

[0039] In one set of experiments, the manufacturing conditions and components were varied to determine the best combination for making stable vitamin A granules. Granules were prepared essentially as provided above, with the changes provided below.

[0040] Emulsification process

[0041] Before the granules can be dried, the liquid vitamin A is emulsified and mixed with a pH-sensitive polymer. In order to reduce preparation time, reduce preparation costs and improve the product, several different vitamin emulsification processes have been designed and tested. All processes described can be purely aqueous, without the presence of solvents, inorganic acids and surfactants.

[0042] Emulsification process #1 Figure 3 , and 3 mixing containers are used. The first container is loaded with vitamin A palmitate (VAP) stabilized by an antioxidant, such as butylated hydroxyanisole (BHA) and / or butylated hydroxytoluene (BHT) or tocopherol (TOC). The first container can be heated to form a liquid of a vitamin A / antioxidant mixture. Vitamin A can be provided together with an antioxidant, however, the same or different antioxidants can be added before or during the heating process. The second container contains i) a pH-sensitive polymer, in this case a basic methacrylate copolymer (BMC), ii) one or more organic acids, in this case ascorbic acid (ASA), and water. The second container is mixed for at least 3.5 hours or at least 12 hours to form a colloidal suspension. The third container is first used to mix other emulsion components, such as one or more polysaccharides (maltodextrin (MD), modified starch (MS)), an organic acid, such as ASA, and water. After the initial liquid preparation is completed, the stabilized VAP from the first container is combined and homogenized with the ingredients in container 3 using a high pressure homogenizer (HPH) to produce an initial VAP emulsion. The BMC colloidal suspension in container 2 is then mixed into the VAP emulsion (without HPH) to form the final emulsion to be spray dried. The preparation of the first container and the second container can be completed before all ingredients are combined. For example, the first container and the second container can be prepared on the first day, mixed overnight, and then combined on the second day. This method is called a "3-container" scheme.

[0043] Emulsification process #2 also used a 3-vessel approach and was identical to process #1, but as follows:

[0044] The second container (BMC) is mixed for a shorter period of time, such as less than 3.5 hours, less than 3 hours, less than 2 hours, or less than 1 hour. This allows the polymer emulsion to be prepared on the same day as the final emulsion, but it does not provide overnight mixing.

[0045] Emulsification process #3 use Figure 4 The 2-container protocol shown was followed:

[0046] The first container is loaded with vitamin A palmitate (VAP) stabilized by an antioxidant, such as butylated hydroxyanisole (BHA) and / or butylated hydroxytoluene (BHT) or tocopherol (TOC). The first container can be heated to form a liquid of a vitamin A / antioxidant mixture. Vitamin A can be provided together with an antioxidant, however, the same or different antioxidants can be added before or during the heating process. The second container contains i) a pH sensitive polymer, in this case a basic methacrylate copolymer (BMC), ii) one or more organic acids, in this case ascorbic acid (ASA), and water. The second container is mixed for at least 0.5 to 3 hours to form a colloidal suspension. Additional emulsion components, such as one or more polysaccharides (maltodextrin (MD), modified starch (MS)), an organic acid, such as ASA, and water are added to the second container. After the initial liquid preparation was completed, the stabilized VAP from the first container was combined and homogenized in container 2 using a high pressure homogenizer (HPH) in the presence of BMC, modified starch and maltodextrin to produce a VAP emulsion ready for drying.

[0047] Emulsification process #4 Figure 5 As shown, a 2-container approach was used and proceeded as follows:

[0048] The first container is charged with vitamin A palmitate (VAP) stabilized by an antioxidant, such as butylated hydroxyanisole (BHA) and / or butylated hydroxytoluene (BHT) or tocopherol (TOC). The first container can be heated to form a liquid of the vitamin A / antioxidant mixture. The vitamin A can be provided with the antioxidant, however, the same or different antioxidant can be added before or during the heating process. The second container is first used to mix additional emulsion components, such as one or more polysaccharides (maltodextrin (MD), modified starch (MS)), an organic acid, such as ASA, and water. After the initial liquid preparation is completed, the stabilized VAP from the first container is combined and homogenized with the ingredients in container 2 using a high pressure homogenizer (HPH) to produce an initial VAP emulsion. Dry BMC (untreated) is added to the initial VAP emulsion. The resulting suspension in container 2 is mixed for more than 0.5, 1, 3 or 6 hours to provide a VAP / BMC emulsion ready for drying.

[0049] Drying process

[0050] After forming an emulsion of the VAP and polymer, the mixture is dried to produce a powdered product. Several different spray drying processes have been tested in order to reduce costs, improve the product, and evaluate different scales of preparation. Drying can include coating the particles with an agent to improve flowability and prevent caking. Materials such as starch have been found to be useful as coatings. After drying, the powdered product is collected and optionally passed through a 10 mm, 5 mm, 2 mm, or 1 mm sieve to remove large aggregates or foreign matter. The material can then be packaged into bags, cartons, barrels, or other containers, or it can be incorporated into food. One packaging process uses aluminum bags that are heat-sealed under vacuum. These packages have been shown to minimize the loss of vitamin activity.

[0051] Drying process #1 used a multi-stage spray dryer and was performed as follows:

[0052] The emulsion is fed into the spray dryer by pump or pressure while the emulsion is slightly stirred. The drying system can be combined with Figure 1 The spray dryer 120 is the same or similar to the system described above. The emulsion is atomized using a nozzle 118 and dried with a heated air stream 170, forming solid particles as the water evaporates. The spray dryer 120 includes an internal fluidized bed dryer 124 and an optional external fluidized bed 128. The fine powder formed during the drying process is transported to a cyclone separator 126 via an extractor 174 on the top of the dryer, and the captured fine powder is recycled via a conduit 176, recycled to the spray dryer near the nozzle via a conduit 178, or recycled to the internal fluidized bed chamber via a conduit 180, depending on the desired degree of agglomeration. The external fluidized bed dryer 128 separates the fine powder 184 from the desired product, the dried vitamin A powder. After drying, the powdered product 186 is collected directly or collected by an optional cyclone separator 130 or a bag filter, and can be passed through a screen 132. The product 188 can then be packaged 134 or incorporated into food.

[0053] Drying process #2 used a recirculating starch cloud on a multi-stage spray dryer and was performed as follows:

[0054] The emulsion is fed into the spray dryer by pump or pressure while the emulsion is slightly stirred. The drying system can be combined with Figure 1The spray dryer is shown in Figure 1 and is identical or similar to the system described above. The emulsion is atomized using a nozzle 118 and dried with a heated air stream 170, because water evaporates and forms solid particles. In the drying process, the native starch 154 is fed into the drying chamber 120 via a pipeline 190 using a feeder 122 to gather and coat the particles. The spray dryer includes an internal fluidized bed dryer 124 and an optional external fluidized bed 128. The fine powder formed in the drying process, and the unused native starch particles are transported to a cyclone separator 126 via an extractor 174 on the top of the dryer, and the captured fine powder is recycled via a conduit 176, recycled to the spray dryer near the nozzle via a conduit 178, or recycled to the internal fluidized bed chamber via a conduit 180, depending on the required degree of agglomeration. The fluidized bed dryer 128 separates the fine powder from the desired product, the dried vitamin A powder. After drying, the powdered product 186 is collected directly or passed through an optional cyclone 130 or bag filter and may be passed through a screen 132. The product 188 may then be packaged 134 or incorporated into a food product.

[0055] Drying process #3 used a single stage spray dryer and was performed as follows:

[0056] The emulsion is fed to a spray dryer. The emulsion is atomized using a nozzle and dried with a heated air stream, forming solid particles as the water evaporates. A cyclone separator separates the exhaust gas from the desired product, dry Vitamin A powder. After drying, the powder product is collected and can be passed through a sieve. The material can then be packaged or incorporated into food products.

[0057] Drying process #4 used a fluid bed dryer and was performed as follows:

[0058] The emulsion is fed to a fluidized bed dryer. The emulsion is atomized using a nozzle and dried with a heated air stream, forming solid particles as the water evaporates. Native starch is loaded into the fluidized bed, which agglomerates with the particles as they dry. After drying, the powder product is collected and can be passed through a sieve. The material can then be packaged or incorporated into food products.

[0059] After drying, the composite particles may have a moisture content of less than 10 wt%, less than 5 wt%, or less than 3 wt%.

[0060] Particle Formation Example

[0061] Example 1

[0062] 104.0 g BMC was added to a solution of 395.0 g ultrapure water and 20.5 g L-ascorbic acid (pH 7.2) and then mixed overnight at 20° C. The next day, in a separate container, 10.4 g BHA was added to 104.0 g BHT stabilized VAP oil preheated to 50° C. The VAP mixture was added to a 50° C. solution containing 14.8 g maltodextrin DE19, 133.3 g HI-CAP 100 modified starch and 20.5 g L-ascorbic acid in 197.6 g ultrapure water and emulsified using an APV Model 2000 high pressure homogenizer. The BMC dispersion (pH 7.2) was added to the container and stirred by an IKA Ultra-Turrax T25 high shear mixer. The emulsion (pH 6.3) was dried for 43 minutes on a Diosna Minilab RC fluidized bed dryer with 100.0 g of native starch powder and an inlet air temperature of 75° C. The volume median droplet diameter and span of the final emulsion (0.4 μm and 1.5, respectively) and the volume median particle size and span of the product (502 μm and 1.2, respectively) were determined using a Malvern Mastersizer 3000. The residual moisture content was 4.5%.

[0063] Example 2

[0064] 104.0 g BMC was added to a solution of 395.1 g ultrapure water and 20.5 g L-ascorbic acid and then mixed overnight at 20°C. The next day, in a separate container, 10.4 g BHT was added to 104.0 g BHT-stabilized VAP oil preheated to 50°C. The VAP mixture was added to a 50°C solution containing 14.8 g maltodextrin DE19, 133.3 g HI-CAP 100 modified starch and 20.5 g L-ascorbic acid in 197.5 g ultrapure water and emulsified using an APV Model 2000 high pressure homogenizer. The BMC dispersion was added to the container and stirred by an IKA Ultra-Turrax T25 high shear mixer. The emulsion was dried in a Buchi mini spray dryer B-290 with an inlet air temperature of 100°C and an outlet temperature of 63°C for 29 minutes. The volume median droplet diameter and span of the final emulsion (0.5 μm and 1.9 respectively) and the volume median particle size of the product (10 μm) were determined using a Malvern Mastersizer 3000. The residual moisture content was 3.2%.

[0065] Example 3

[0066] 15.1 kg of unstabilized VAP oil was heated in a 60°C water bath for at least 12 hours and 1.5 kg of BHT was added. 15.1 kg of BMC was added to a solution of 203.0 kg of reverse osmosis water (RO) and 3.0 kg of L-ascorbic acid and stirred at 40°C for 2.5 hours. 29.6 kg of maltodextrin DE19, 32.7 kg of HI-CAP 100 modified starch and 3.0 kg of L-ascorbic acid were added to the container, followed by the VAP mixture. Emulsification was performed using a BOS MG2-350S high pressure homogenizer. The emulsion was dried in an Entropie Serit SME 180AB1 pilot multistage spray dryer with an internal fluidized bed for 150 minutes. The inlet / outlet air temperatures of the spray drying tower were 140°C / 68°C, respectively, and the inlet air temperature of the internal fluidized bed dryer was 55°C. The fine powder was recycled to the internal fluidized bed. The volume median droplet diameter and span of the final emulsion (0.4 μm and 1.6 respectively) and the volume median particle size and span of the product (95 μm and 1.4 respectively) were determined using a Malvern Mastersizer 3000. The residual moisture content was 2.2%.

[0067] Example 4

[0068] 20.4 kg of unstabilized VAP oil was heated on a heating belt set at 70 ° C for at least 12 hours and 2.0 kg of BHT was added. The VAP mixture was added to a 50 ° C solution containing 2.9 kg of maltodextrin DE19, 26.2 kg of HI-CAP100 modified starch and 4.0 kg of L-ascorbic acid in 140.0 kg of RO water and emulsified using a BOS MG2-350S high pressure homogenizer. 20.4 kg of BMC was added to a solution of 60.0 kg of RO water and 4.0 kg of L-ascorbic acid and then mixed at ambient temperature for 3 hours. The BMC dispersion was added to a container with the VAP mixture and stirred. The emulsion was dried on an Entropie Serit SME 180AB1 pilot multi-stage spray dryer with a recirculating starch cloud and an internal fluidized bed. During the 300-minute drying process, 68.9 kg of native starch was added to the drying tower. The inlet / outlet air temperature of the tower was 230°C / 90°C, respectively, and the inlet air temperature of the internal fluidized bed dryer was 90°C. The fine powder was recycled to the internal fluidized bed. The volume median droplet diameter and span of the final emulsion (0.4 μm and 1.2, respectively) and the volume median particle size and span of the product (297 μm and 1.5, respectively) were determined using a Malvern Mastersizer 3000. The residual moisture content was 4.2%.

[0069] Example 5

[0070] 11.3 kg of TOC-stabilized VAP oil was heated with a heating belt set at 70°C for at least 12 hours and then added to a separate solution containing 33.4 kg of maltodextrin DE19, 14.5 kg of CAPSUL TA modified starch and 2.2 kg of L-ascorbic acid in 138.0 kg of RO water and emulsified using a BOS MG2-350S high pressure homogenizer. 11.3 kg of BMC was added to 45.0 kg of RO water and 2.3 kg of L-ascorbic acid in a separate container and then stirred at ambient temperature for 3 hours. The BMC dispersion was added to the VAP mixture and stirred. The emulsion was dried on an Entropie Serit SME 180AB1 pilot multistage spray dryer with an internal fluidized bed for 465 minutes. The inlet / outlet air temperatures of the spray drying tower were 155°C / 68°C, respectively, and the inlet air temperature of the internal fluidized bed dryer was 60°C. The fine powder was recycled to the internal fluidized bed. The volume median droplet diameter and span of the final emulsion (0.4 μm and 1.6 respectively) and the volume median particle size and span of the product (86 μm and 1.5 respectively) were determined using a Malvern Mastersizer 3000. The residual moisture content was 2.7%.

[0071] Example 6

[0072] 11.4kg of unstabilized VAP oil was heated on a heating belt set at 70°C for at least 12 hours, and 0.7kg of BHT was added. 11.3kg of BMC was added to a solution of 44.0kg of RO water and 1.8kg of L-tartaric acid, and then mixed at ambient temperature for 3 hours (final pH was 6.8). The VAP mixture was added to a 50°C solution containing 35.3kg of maltodextrin DE19, 14.5kg of CAPSUL TA modified starch in 140.0kg of RO water, and emulsified using a BOS MG2-350S high pressure homogenizer. The BMC dispersion was added to the container and stirred (final pH was 6.17). The emulsion was dried for 465 minutes on an EntropieSerit SME 180AB1 pilot multistage spray dryer with an internal fluidized bed. The inlet / outlet air temperatures of the spray drying tower were 146°C / 63°C, respectively, and the inlet air temperature of the internal fluidized bed dryer was 60°C. The fines were recycled to the internal fluidized bed. The volume median droplet diameter and span of the final emulsion (0.4 μm and 1.5 respectively) and the volume median particle size and span of the product (71 μm and 1.5 respectively) were determined using a Malvern Mastersizer 3000. The residual moisture content was 3.1%.

[0073] Example 7

[0074] 17.5kg unstabilized VAP oil was heated on a heating belt set at 70°C for at least 12 hours, and 1.0kg of BHA and 1.0kg of BHT were added. 17.5kg of BMC was added to 60.0kg of RO water and 3.5kg of L-ascorbic acid, and stirred at ambient temperature for 3 hours (final pH was 7.08). The VAP mixture was added to a 50°C solution containing 33.7kg of maltodextrin DE19, 22.5kg of CAPSUL TA modified starch and 3.5kg of L-ascorbic acid in 143.0kg of RO water, and emulsified using a BOSMG2-350S high pressure homogenizer. The BMC dispersion was added to the container and stirred (final pH was 5.95). The emulsion was dried 585 minutes on an Entropie Serit SME 180AB1 pilot multistage spray dryer with an internal fluidized bed. The inlet / outlet air temperature of the spray drying tower was 145°C / 65°C, respectively, and the inlet air temperature of the internal fluidized bed dryer was 60°C. The fine powder was recycled to the internal fluidized bed. The volume median droplet diameter and span of the final emulsion (0.4 μm and 1.9, respectively) and the volume median particle size and span of the product (102 μm and 1.6, respectively) were determined using a Malvern Mastersizer 3000. The residual moisture content was 2.3%.

[0075] Example 8

[0076] 16.2 kg of unstabilized VAP oil was heated on a heating belt set at 70°C for at least 12 hours and 0.5 kg of BHA and 0.5 kg of BHT were added. The VAP mixture was added to a 50°C solution containing 16.2 kg of CAPSUL TA modified starch and 3.2 kg of L-ascorbic acid in 140.0 kg of RO water and emulsified using a BOS MG2-350S high pressure homogenizer. 3.2 kg of L-ascorbic acid and 16.2 kg of BMC powder were added and stirred. The emulsion was dried for 300 minutes on an EntropieSerit SME 180AB1 pilot multistage spray dryer with recirculating starch cloud and internal fluidized bed. During the drying process, 36.6 kg of native starch was added to the drying tower. The inlet / outlet air temperatures of the tower were 220°C / 97°C, respectively, and the inlet air temperature of the internal fluidized bed dryer was 90°C. The fine powder was recycled to the internal fluidized bed. The volume median droplet diameter and span of the final emulsion (0.4 μm and 2.3 respectively) and the volume median particle size and span of the product (262 μm and 1.1 respectively) were determined using a Malvern Mastersizer 3000. The residual moisture content was 3.1%.

[0077] Comparative Example 9

[0078] 18.5g 5M sulfuric acid is added to 413.3g ultrapure water containing 5.3g sodium lauryl sulfate and 104.0g BMC, and mixed overnight at 20 ℃.On the second day, 14.8g maltodextrin DE19 and 133.3g HI-CAP 100 modified starch are added to 206.7g ultrapure water, heated to 50 ℃ and stirred for 30 minutes.104.0g BHT stabilized VAP oil is added, and the mixture is emulsified for 10 minutes using IKA Ultra-Turrax T25 high shear mixer.The mixture is added to the container containing BMC dispersion, and IKA Ultra-Turrax T25 high shear mixer is emulsified for 5 minutes (final pH is 6.8).The emulsion is dried 77 minutes on a Diosna Minilab RC fluidized bed dryer equipped with 100.0g native starch powder and an inlet air temperature of 75 ℃. The volume median droplet diameter and span of the final emulsion (0.6 μm and 1.3, respectively) were determined using a Malvern Mastersizer 3000. The residual moisture content was 2.5%.

[0079] Comparative Example 10

[0080] 49.0g 6M sulfuric acid was added to 393.7g ultrapure water, followed by 5.4g sodium lauryl sulfate and 104.0g BMC, and mixed overnight at 20°C. The next day, 14.8g maltodextrin DE19 and 133.2g HI-CAP 100 modified starch were added to 197.0g ultrapure water, heated to 50°C and stirred for 30 minutes. 104.0g BHT stabilized VAP oil was added, and the mixture was emulsified for 5 minutes using an IKA Ultra-Turrax T25 high shear mixer. The emulsion was added to the BMC dispersion and stirred (final pH was 2.0). The emulsion was dried for 135 minutes on a Diosna Minilab RC fluidized bed dryer equipped with 150.0g native starch powder and an inlet air temperature of 65°C. The volume median droplet diameter (0.96 μm) of the final emulsion was determined using a Malvern Mastersizer 3000. The residual moisture content was 2.5%.

[0081] Embodiment 11

[0082] 15.2g BHA / BHT stabilized VAP oil is added to a 50°C solution containing 27.8g maltodextrin DE19, 18.5g PE-100 modified starch and 2.9g L-ascorbic acid in 56.7g ultrapure water, and an IKA Eurostar 20 digital overhead stirrer is used, followed by an IKA Ultra-Turrax T25 high shear mixer emulsification. 2.9g L-ascorbic acid and 14.4g BMC powder are added to the container and stirred (final pH is 5.5). The emulsion is dried 23 minutes on a Buchi small spray dryer B-290 at an inlet air temperature of 100°C and an outlet temperature of 62°C. The volume median droplet diameter and span (0.9 μm and 3.9, respectively) of the final emulsion are measured using a MalvernMastersizer 3000. The residual moisture content is 4.9%.

[0083] Example 12

[0084] 202.2 g of BMC was added to 970.0 g of ultrapure water containing 40.2 g of L-ascorbic acid and then mixed at 40° C. for 3.5 hours. The dispersion (pH 6.2) was stored at 2-8° C. without stirring and protected from light for 10 weeks (pH 6.6 after storage). In addition, 32.1 g of BHA / BHT stabilized VAP oil was added to a 50° C. solution containing 55.5 g of maltodextrin DE19, 37.0 g of PE-100 modified starch and 5.7 g of L-ascorbic acid in 197.0 g of ultrapure water and emulsified using an APV Model 2000 high pressure homogenizer. 173.0 g of the stored BMC dispersion was added to the container and stirred using an IKA Ultra-Turrax T25 high shear mixer (pH 5.17). The emulsion was dried for 22 minutes on a Buchi mini spray dryer B-290 at an inlet air temperature of 100°C and an outlet temperature of 62°C. The volume median droplet size and span of the emulsion (0.4 μm and 1.2, respectively) were determined using a Malvern Mastersizer 3000. The residual moisture content was 4.3%.

[0085] Comparative Example 13

[0086] 68.4g BMC and 7.6g unstabilized VAP oil were added to 1062g methylene chloride to form a solution. The feed was atomized using a 30' rotating disk suspended in the air. Excess native starch was dispersed on the receiving bed below. Partially dried BMC / VAP particles fell on the bed and were coated with starch. The coated particles were collected and sieved to remove excess starch. The volume median particle size and span (125 μm and 1.4 respectively) of the product were measured using a Malvern Mastersizer 3000.

[0087] Embodiment 14

[0088] 17.5kg unstabilized VAP oil was heated at least 12 hours on a heating belt set at 60°C, and 1.0kg of BHA and 1.0kg of BHT were added. 17.5kg of BMC was added to 57.0kg of RO water and 3.5kg of L-ascorbic acid, and stirred at ambient temperature for 3 hours (final pH was 7.05). The VAP mixture was added to a 50°C solution containing 33.7kg of maltodextrin DE19, 22.5kg of PE 100 modified starch and 3.5kg of L-ascorbic acid in 137.0kg of RO water, and emulsified using a BOS MG2-350S high pressure homogenizer. The BMC dispersion was added to the container and stirred (final pH was 5.9). The emulsion was dried 240 minutes on an Entropie Serit SME 180AB1 pilot multistage spray dryer with an internal fluidized bed. The inlet / outlet air temperature of the spray drying tower was 160°C / 71-78°C, respectively, and the inlet air temperature of the internal fluidized bed dryer was 60°C. The fine powder was recycled to the vicinity of the nozzle in the spray drying tower. The volume median droplet diameter and span of the final emulsion (0.3 μm and 1.3, respectively) and the volume median particle size and span of the product (178 μm and 1.2, respectively) were determined using a Malvern Mastersizer 3000. The residual moisture content was 3.5%.

[0089] VAP content test

[0090] The actual amount of VAP in the composite particles was measured to compare it with the theoretical amount of VAP based on the addition to the process. The powder samples were added to a solution including 1:9 water:THF containing 0.1% BHT, vortexed, and centrifuged at 8,000RCF for 5 minutes. The supernatant was diluted 10 times in ACN containing 0.1% BHT, vortexed, filtered through a 0.2μm filter, and analyzed by HPLC. HPLC was used for all vitamin A measurements in this article. The samples were flowed through a C18 reverse phase column with a mobile phase of 97:3 methanol:water and analyzed at 325nm using a UV-visible detector. The VAP content was calculated based on a linear calibration curve. The results are provided in Table 1 and show that all samples contained VAP concentrations within the expected range.

[0091] Table 1

[0092] Example VAP content (% theory ± standard deviation) 1 104.9±0.4 2 98.3±1.0 3 89.5±0.4 4 84.4±0.4 5 90.5±1.0 6 85.0±0.4 7 106.0±0.4 8 94.0±0.7 9 <![CDATA[118.4 1 ]]> 10 <![CDATA[101.3 1 ]]> 11 94.1±1.2 12 89.5±0.7 13 <![CDATA[79.7 1,2 ]]> 14 93.3±0.3

[0093] 1 Single measurement only.

[0094] 2 Since the amount of starch used to coat the granules in the spray tower process is unknown, the theoretical content is not precise.

[0095] Cooking stability test

[0096] The composite particles of Examples 1-14 and commercial comparative VAP powders available from BASF were tested for their resistance to degradation under cooking conditions. 20 mg of powder was added to 2.0 mL of water and vortexed. The suspension was heated at 90° C. for 2 hours while mixing at 500 rpm using an Eppendorf ThermoMixer C. The mixture was cooled to room temperature, frozen and lyophilized for at least 24 hours. The content of vitamin A in the resulting powder was analyzed as described above and reported in Table 2, expressed as a percentage of the amount measured before cooking. The data show that the composite particles (except comparative examples 10 and 13) lose much less active vitamin A than the powders. The commercial comparative powders lost 30% to 60% of the initial vitamin A, while the test examples showed a loss of 0-16%, or less than about half of the amount lost by the commercial comparative powders.

[0097] Table 2

[0098]

[0099]

[0100] 1 The measurements were performed in multiple replicates and reported as mean ± standard deviation. All other samples were measured in single replicates only.

[0101] Storage stability test

[0102] To test the storage stability under exposure to the environment, 10 samples were exposed to 40°C for 28 to 36 days. One gram of each sample in samples 1-10, 13 and 14 was evenly distributed in an open petri dish with a diameter of 4.5 cm and stored in a Memmert UF75 universal oven at 40°C and ambient relative humidity for at least 4 weeks. The vitamin A content of the powder was analyzed as described above. The results shown in Table 3 show that the retention rate of the initial vitamin A concentration is between 44% and 91%.

[0103] Table 3

[0104]

[0105] Shelf stability

[0106] Six examples were tested for long term storage when stored in packaging suitable for vitamin A and foods containing vitamin A. 20-30 g of powder samples were placed in vacuum sealed aluminum bags and stored under ambient conditions for 6 months. The powders were analyzed for vitamin A content as described above. The results provided in Table 4 indicate that the retention of the experimental samples tested was at least 95%.

[0107] Table 4

[0108]

[0109] Study on the stability of broth seasoning 1

[0110] The VAP composite particles from comparative examples 9 and 13, as well as commercial controls (BASF-VAP250-FG and BASF-VAP250-MS-CWD), were combined with Nestlé Maggi Star bouillon powder (0.67 mg VAP per g bouillon seasoning) and mixed until uniformly dispersed. 4 g fortified bouillon seasoning tablets were formed on a manual tablet press using a punch and die. The tablets were stored at 40°C / 75% RH according to the ICH guideline for accelerated stability testing for all world zones. Tablets were sampled regularly for VAP content and cooking stability. The bouillon seasoning tablets were dissolved in water at a concentration of 91 mg / mL, 4-10 mL samples were frozen, freeze-dried for at least 24 hours, and then the powder was analyzed for vitamin A content as described above. Cooking stability analysis was performed by dissolving the bouillon seasoning tablets in water at a concentration of 91 mg / mL, diluting 4-5 times in water, and heating to 90°C for 2 hours. The total sample mass remained constant during cooking. 10 mL samples were frozen and lyophilized for at least 72 hours. The powders were analyzed for vitamin A content as described above. 24 month stability results are shown in Table 1. Figure 6 The error bars represent standard deviations. The results show that the retention of the comparative examples was 40% or more, while the commercial control powder degraded to a level of less than 10% of its original vitamin A activity. The 24-month stability results after storage plus cooking at 90°C for 2 hours are shown in Figure 7 The error bars represent standard deviations. The results showed that the retention of the comparative examples was 30% or more, while the commercial control powder was degraded to a level below the quantitation limit of the analytical method.

[0111] Study on the stability of broth seasoning 2

[0112] The VAP composite particles from Examples 1 and 2, as well as a commercial control (BASF-VAP250-FG), were combined with Nestlé Maggi Star bouillon powder (0.67 mg VAP per g bouillon seasoning) and mixed until uniformly dispersed. 4 g fortified bouillon seasoning tablets were formed on a manual tablet press using a punch and die. The tablets were stored at 40°C / 75% RH according to the ICH guidelines for accelerated stability testing for all world regions. The tablets were sampled regularly for VAP content and cooking stability according to the test methods described in Bouillon Seasoning Stability Study 1. 18 month stability results are shown in Table 1. Figure 8The error bars represent standard deviations. The results show that the retention of the experimental examples was 60% or more, while the commercial control powder degraded to a level of about 10% of its original vitamin A activity. The 18-month stability results after storage plus cooking at 90°C for 2 hours are shown in Fig. 9 The error bars represent standard deviations as shown. The results show that the retention rates of Examples 1 and 2 were 40% or more, while the commercial control powder was degraded to a level of less than 10% of its original vitamin A activity.

[0113] Study on the stability of broth seasoning 3

[0114] The VAP composite particles from Examples 4-8, as well as a commercial control (BASF-VAP250-FG), were combined with Nestlé Maggi Star bouillon powder (0.35 mg VAP per g bouillon seasoning) and mixed until uniformly dispersed. 11 g fortified bouillon seasoning tablets were formed using a Bonals Technologies P40 rotary press and packaged using a Theegarten BCW3 packaging machine. The tablets were stored at 40°C / 75% RH in accordance with the ICH guidelines for accelerated stability testing for all world regions. The tablets were sampled regularly for VAP content and cooking stability following the test methods described in Bouillon Seasoning Stability Study 1. The 6-month stability results are as follows Fig.10 The error bars represent standard deviations. The results show that the retention of the experimental examples was 70% or more, while the commercial control powder degraded to a level of about 25% of its original vitamin A activity. The 6-month stability results after storage plus cooking at 90°C for 2 hours are shown in Fig.11 The error bars represent standard deviations as shown. The results show that the retention rates of Examples 4-8 were 40% or more, while the commercial control powders were degraded to a level of less than 20% of their original vitamin A activity.

[0115] The results of the above bouillon seasoning stability studies are provided in Tables 5 and 6 below. Table 5 provides the amount of VAP recovered after the storage times provided in the table. Table 6 provides the amount of VAP recovered after the samples were cooked at 90°C for 2 hours after the storage times provided in the table. The results of Examples 1 and 2 show the same or better stability as Comparative Example 9 (inorganic acid and SDS surfactant) and Comparative Example 13 (organic solvent). The experimental examples show that the method provides stable vitamin A composite particles without the use of inorganic acids, surfactants or organic solvents. All materials used to prepare these experimental examples can be found in the Codex General Standard for Food Additives.

[0116] Table 5

[0117]

[0118] *N / R indicates that the result was not reported because the measured vitamin A content was below the quantification limit of the analytical method

[0119] Table 6

[0120]

[0121] *N / R indicates that the result was not reported because the measured vitamin A content was below the quantitation limit of the analytical method. Sub-particle size measurement

[0122] The powder was dispersed in hot water to determine the subparticle size. 1 g of powder was added to 20 g of water preheated to 50°C and stirred. The volume median subparticle size and span were measured using a Malvern Mastersizer 3000. The volume median subparticle size of the powder from Example 12 was 0.4 μm and the span was 1.3, and the volume median subparticle size of the powder from Example 14 was 0.4 μm and the span was 1.2.

[0123] Although several embodiments of the present invention have been described and illustrated herein, a person of ordinary skill in the art will readily conceive of various other devices and / or structures for performing the functions described herein and / or obtaining the results and / or one or more advantages described herein, and each of these changes and / or modifications is considered to be within the scope of the present invention. More generally, it will be readily understood by those skilled in the art that all parameters, dimensions, materials, and configurations described herein are intended to be exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on one or more specific applications for which the teachings of the present invention are used. Those skilled in the art will recognize or be able to determine many equivalents of the specific embodiments of the present invention described herein using only routine experiments. Therefore, it should be understood that the foregoing embodiments are presented only by way of example, and within the scope of the appended claims and their equivalents, the present invention may be practiced in a manner different from that specifically described and protected by the claims. The present invention relates to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods, if such features, systems, articles, materials, kits, and / or methods are not mutually contradictory, is included within the scope of the present invention.

[0124] All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0125] Unless expressly indicated to the contrary, the indefinite articles "a" and "an" as used herein in the specification and claims should be understood to mean "at least one".

[0126] As used herein in the specification and claims, the phrase "and / or" should be understood to mean "either or both" of the elements so conjoined, i.e., in some cases the elements are conjunctive and in other cases disjunctive. Other elements other than those specifically defined by the "and / or" phrase may optionally be present, whether related or unrelated to those elements specifically defined, unless explicitly stated to the contrary.

[0127] All references, patents and patent applications, and publications cited or referred to in this application are hereby incorporated by reference in their entirety.

[0128] The claimed content is as attached.

Claims

1. A composite particle of vitamin A or a derivative thereof, the particle comprising: pH sensitive polymers; and Subparticles or subdroplets of vitamin A embedded in the pH-sensitive polymer, wherein the composite particles are substantially free of organic solvents and inorganic acids, and the amount of vitamin A in the composite particles is a first concentration after preparing the particles and a second concentration after subjecting the composite particles to both a 4-week shelf life test at 40°C and a 2-hour cooking test in water at 90°C, and the second concentration is greater than 60% of the first concentration, greater than 70% of the first concentration, greater than 80% of the first concentration, or greater than 90% of the first concentration.

2. The composite particle according to claim 1, comprising vitamin A palmitate, ascorbic acid, maltodextrin and modified starch.

3. The composite particle according to claim 1, further comprising ascorbic acid, BHT, BHA, tocopherol or a combination thereof.

4. The composite particles according to claim 1, wherein The composite particles are substantially free of surfactant.

5. The composite particles according to claim 1, wherein The pH sensitive polymer includes polymethacrylate.

6. The composite particles according to claim 5, wherein The pH sensitive polymer includes BMC.

7. A composite particle according to any one of the preceding claims, wherein The median volume diameter D of the subparticle or subdroplet 50 Between 50nm and 2μm, between 100nm and 1μm, between 100nm and 500nm, or between 200nm and 400nm.

8. The composite particle according to any one of claims 1 to 6, wherein The median volume diameter D of the composite particles 50 Between 1 to 1000 μm, 1 to 100 μm, 1 to 10 μm, 50 to 1000 μm, 50 to 400 μm, 100 to 400 μm, 50 to 300 μm or 100 to 500 μm.

9. The composite particles according to claim 7, wherein The standard deviation of the volume diameters of the composite particles is less than 50 μm.

10. The composite particles according to claim 1, wherein The composite particles include vitamin C.

11. A broth seasoning comprising the composite particles according to claim 1.

12. Wheat flour, millet flour, tapioca flour, cassava flour, teff flour, corn flour, milk, milk powder, malt beverage, soy sauce, ready-to-eat therapeutic food, rice or sugar comprising the composite particle of claim 1.

13. A method comprising: forming an acidified aqueous vehicle at a pH of less than or equal to 6.0; combining a pH-sensitive polymer with the aqueous vehicle to form a colloidal suspension; allowing the pH of the suspension to rise to greater than 6.0; Emulsified fat-soluble vitamins or their derivatives; combining the colloidal suspension and the emulsified fat-soluble vitamin or derivative thereof to form a dispersion; limiting the pH increase after adding the fat-soluble vitamin or derivative thereof to pH 7.0; and Water is removed from the dispersion to produce composite microparticles comprising a matrix of a fat-soluble vitamin or a derivative thereof and a pH-sensitive polymer.

14. The method according to claim 13, wherein: The water is removed by spray drying, fluidized bed drying, vacuum drying, rotary evaporator drying, freeze drying and / or multi-stage drying.

15. The method according to claim 13, wherein: The method is free of at least one of a surfactant and an inorganic acid.

16. The method according to claim 13, wherein: The pH of the acidified aqueous vehicle is lowered to 5.5 or less using an organic acid.

17. The method according to claim 16, wherein: The organic acid is ascorbic acid, tartaric acid or both.

18. The method according to claim 13, wherein: The method does not contain organic solvents.

19. The method according to claim 13, wherein: The fat-soluble vitamins are emulsified in an aqueous solution including maltodextrin, starch, or a combination thereof.

20. The method of claim 13, comprising coating the composite microparticles with a polysaccharide.

21. The method according to claim 20, wherein: The polysaccharide is selected from at least one of starch, modified starch and maltodextrin.

22. The method according to claim 13, wherein: The median volume diameter D of the composite microparticles 50 Greater than 1 μm and less than 500 μm, greater than 50 μm and less than 400 μm, greater than 100 μm and less than 200 μm.

23. The method of claim 13, further comprising adding the composite microparticles to food.

24. The method of claim 13, comprising adding an antioxidant to the fat-soluble vitamins.

25. The method of claim 13, wherein: The antioxidant comprises a synthetic antioxidant, and the synthetic antioxidant is selected from at least one of BHA and BHT.

26. A method according to any one of claims 13 to 25, comprising adding a defoaming or anti-foaming agent.

27. A food ingredient comprising: Composite microparticles, comprising subparticles or subdroplets of vitamin A or its derivatives in a pH-sensitive polymer, wherein the median volume diameter D of the composite microparticles is 50 Between 1 to 1000 μm, 1 to 100 μm, 1 to 10 μm, 50 to 1000 μm, 50 to 400 μm, 100 to 400 μm, 50 to 300 μm or 100 to 500 μm, wherein the composite microparticles are substantially free of anionic surfactants.

28. The food ingredient of claim 27, further comprising ascorbic acid, BHT, BHA, tocopherol, or a combination thereof.

29. The food ingredient of claim 27, prepared without the use of mineral acids.

30. A bouillon seasoning comprising the food ingredient of claim 27.

31. The food ingredient of claim 27, wherein The food composition is substantially free of inorganic acids, surfactants and organic solvents.

32. Wheat flour, millet flour, tapioca flour, cassava flour, teff flour, corn flour, milk, milk powder, malt beverage, soy sauce, ready-to-eat therapeutic food, rice or sugar comprising the food ingredient of claim 27.

33. The food ingredient of claim 27, wherein The pH sensitive polymer includes polymethacrylate.

34. The food ingredient according to claim 33, wherein The pH sensitive polymer includes BMC.

35. The food ingredient of claim 27, comprising vitamin A palmitate, ascorbic acid, maltodextrin and modified starch.

36. The food ingredient according to any one of claims 27-29 or 31 or 33-35, wherein The median volume diameter D of the subparticle or subdroplet 50 Between 50nm and 2μm, between 100nm and 1μm, between 100nm and 500nm, or between 200nm and 400nm.

37. The food ingredient according to any one of claims 27-29 or 31 or 33-35, wherein The standard deviation of the composite microparticles is less than 50 μm.

38. The food ingredient of claim 36, wherein The food ingredient includes vitamin C.

39. A food ingredient comprising: Composite microparticles, comprising subparticles or subdroplets of vitamin A or its derivatives in a pH-sensitive polymer matrix, wherein the median volume diameter D of the composite microparticles is 50 Between 1 to 1000 μm, 1 to 100 μm, 1 to 10 μm, 50 to 1000 μm, 50 to 400 μm, 100 to 400 μm, 50 to 300 μm or 100 to 500 μm, wherein the composite microparticles include a synthetic antioxidant.

40. The food ingredient according to claim 39, wherein The synthetic antioxidant is selected from BHA and BHT.

41. The food ingredient of claim 39 comprising vitamin C.

42. The food ingredient of claim 39, prepared without the use of inorganic acids or anionic surfactants.

43. The food ingredient of claim 39, wherein The food composition is substantially free of inorganic acids and organic solvents.

44. Wheat flour, millet flour, tapioca flour, cassava flour, teff flour, corn flour, milk, milk powder, malt beverage, soy sauce, ready-to-eat therapeutic food, rice or sugar comprising the food ingredient of any one of claims 39-43.

45. The food ingredient according to any one of claims 39 to 43, wherein The pH sensitive polymer includes polymethacrylate.

46. ​​The food ingredient according to claim 45, wherein The pH sensitive polymer includes BMC.

47. The food ingredient of claim 44, comprising vitamin A palmitate, ascorbic acid, maltodextrin and modified starch.

48. The food ingredient of claim 39, wherein The standard deviation of the composite microparticles is less than 50 μm.

49. A bouillon seasoning comprising the food ingredient of any one of claims 39-43.

50. A method comprising: mixing a pH-sensitive polymer with water and an organic acid to produce a suspension; adding at least one polysaccharide to the suspension; adding a fat-soluble vitamin or a derivative thereof to the suspension; adjusting the pH of the suspension to less than 6.0; The suspension is emulsified to produce a median volume diameter D 50 Composite droplets smaller than 1 μm; Limiting pH increases to less than 8.0; and Water is removed from the emulsion to produce composite microparticles comprising a matrix of a fat-soluble vitamin or a derivative thereof and a polymethacrylate polymer binder.

51. The method of claim 50, comprising allowing the pH of the suspension to rise to at least 6.

0.

52. The method of claim 50, comprising emulsifying the fat-soluble vitamin or derivative thereof in an aqueous vehicle comprising one or more polysaccharides and an organic acid.

53. The method of claim 50, wherein: The one or more polysaccharides are selected from maltodextrin and modified starch, and the organic acid is selected from ascorbic acid and tartaric acid.

54. The method of claim 50, wherein: The pH sensitive polymer is polymethacrylate.

55. The method of claim 54, wherein: The polymethacrylate is BMC.

56. A method comprising: preparing an aqueous suspension of at least one polysaccharide and an organic acid; adding a fat-soluble vitamin or a derivative thereof to the suspension; mixing a solid pH-sensitive polymer into the suspension; adjusting the pH of the emulsion to less than 6.0; The suspension is emulsified to produce a median volume diameter D 50 Composite droplets smaller than 1 μm; as well as Water is removed from the emulsion to produce composite microparticles comprising a matrix of a fat-soluble vitamin or a derivative thereof and a polymethacrylate polymer binder.

57. The method of claim 56, wherein: The one or more polysaccharides are selected from maltodextrin and modified starch, and the organic acid is selected from ascorbic acid and tartaric acid.

58. The method of claim 56, wherein: The pH sensitive polymer includes polymethacrylate.

59. The method of claim 58, wherein: The polymethacrylate includes BMC.

60. The method of claim 13, 50 or 56, wherein: The aqueous vehicle, aqueous suspension or water includes water having a hardness of less than 100 ppm as CaCO3.

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