UA78193C2 - Liquid vitamin emulsion composition, method for preparation thereof and use - Google Patents

Abstract

The invention provides a process for the preparation of a liquid emulsion composition having a continuous aqueous phase containing a gelling agent and a thickener and optionally a physiologically tolerable amount of at least one water soluble vitamin and/or non-vitamin drug, and a discontinuous oil phase, optionally comprising at least one lipophilic vitamin and/or non-vitamin lipophilic drug and optionally an edible triglyceride, said emulsion composition further containing at least one emulsifying agent, said process comprising: forming an aqueous composition comprising an aqueous solution of a gelling agent and a thickener and optionally at least one water soluble vitamin and/or non-vitamin drug; forming a water-immiscible liquid composition comprising at least one emulsifying agent and optionally at least one lipophilic vitamin and/or non-vitamin drug; mixing said water-immiscible composition with at least part of said aqueous composition whereby to form an oil-in-water emulsion; and if required mixing further components with said emulsion whereby to form said liquid emulsion composition.

Description

9. The method according to any of clauses 2-8, which differs 15. The method according to any of clauses 2-14, which differs in that the mentioned thickener is suitable in that the mentioned emulsifier is for consumption of a resin or mixture suitable for phospholipids or fatty acid esters. consumption of resins. 16. The method according to item 15, which differs in that 10. The method according to item 9, which differs in that the mentioned emulsifier is lecithin. this mixture of resins suitable for consumption is 17. The method according to any of items 2-16, which differs from carob gum and guar gum in that gum is added to the mentioned oil phase. a physiologically acceptable inorganic compound in the form of 11. The method according to any of items 2-10, which distinguishes the appearance of nanometer-sized particles. 18. The method according to p. 17, which is characterized by the fact that it contains triglyceride suitable for consumption - the mentioned inorganic compound is a carbide. of calcium. 12. The method according to item 11, which is characterized by the fact that 19. The method according to any of items 2-18, which is characterized by the fact that the said edible triglyceride is additionally mixed with fish oil or vegetable oil. it is a non-vitamin medicine. 13. The method according to any one of clauses 2-12, which is characterized by the fact that the oil dispersion phase of clause 1 for the preparation of medicinal products for the treatment of conditions containing vitamin E associated with vitamin deficiency. 14. The method according to p. 13, which differs in that 21. The application according to p. 20, where the conditions associated with the de-mentioned vitamin E is in the form of vitamin deficiency, selected from beriberi, nyctalopia, tocopherol, 9-tocopheryl acetate, E-tocopherol megaloblastic hematopoiesis, pernicious anemia, succinic anhydride, vitamin E ТРО5 hypoprothrombinemia, pellagra, malabsor- and/or tocotrienol syndrome. tuberculosis, scurvy, rickets.

This invention relates to emulsions and their concen- The problem of instability of vitamins in the liquid composition of trats, for example, medicinal compositions in liquid and much attention is paid in "OI! apa Umaiteg-ZoIShrie dry forms, for example, syrup, liquid concen- Miatype: Oga! ZoiIshiop" in the monograph on the foodstuff, powder or tablet and the method of their production additives OBR 24, where it is stated that the additive, which, optionally, includes atomizers, must contain not less than 9095 and not more than lin drying or freeze drying. than 25095, 15095 or 45095 indicated on the label

Many compositions, for example, pharmaceutical- quantities of certain vitamins. Therefore, vitamin components of drugs, cosmetic drugs, nutraceuticals generally contain a larger amount of certain vitamins, etc., must be produced in the form of emulsifiers than indicated on the label, taking into account their seeds in general, due to the fact that the necessary component is disintegrated under storage time and, thus, sufficiently water-insoluble, or due to the fact that they slow down the requirements of the legislation, so that the content of the vehicans prefers liquid rather than solid dosage-vitamins should be at least as high as the specified form. on the product label, throughout the term

However, the production of products in the form of an emulsion is suitable for its storage. Although it has its own problems, for example, the fact that the breakdown of the vitamin can be compensated for in this way by the stability of the emulsion itself and it can be compensated to some extent by the use of nents, and the increased volume of the emulsion relative to the acceptable excess, preferably, so that the assumed concentrated composition causes the leachable excess to be relatively small, in order to cover the costs of storage and the supine case of the dose received during transportation. the use of a relatively fresh product will

In the case, for example, of vitamin-containing compounds, the desired level should be exaggerated. This motions (for example, food additives or nutritional O5R, therefore, determines the content ranges of tic) their production in the form of a liquid composition of vitamins in a liquid composition, which are undesirably extended shelf life or extended we in relation to the legally defined content and it has a shelf life during storage, however, the required value. It is obvious that the more desirable are the problems of their own, in particular, problems, narrower ranges. So, in general, there are requirements related to the stability of vitamins. Vitamins in liquid and in the method of production of emulsions or in concentrated forms are easily destroyed in most emulsions, which have increased stability and as a result of the influence of temperature, humidity, oxygen, which have an acceptable increased stability of any light and pH. The presence of other vitamins as well as degradable components for which this will affect the disintegration pattern of each emulsifier is a filler. of my vitamin, which will further complicate the technol- Now we have determined that compositions for emul- ology of the production of a pharmaceutical composition. For oils in water with a very long shelf life, it is important to understand that it is the stability of the most repulsion that can be produced by using a combination of an unstable component determines the general life of the emulsifier, gelling agent and thickener, and the shelf life of the product. skin of water and water-immiscible liquid.

We have also determined that such stable emulsions compound, (ii) inorganic particle, and (ii) non-vitamin- can be successfully concentrated (eg, by drying) and then reconstituted. In the case of multivitamin and mineral

Therefore, from the point of view of one aspect of the emulsion invention, the main part (i.e. at least 5095) proposes a method of preparing a liquid emulsion-oil phase in the compositions of the invention preferably of a composition that has an aqueous dispersion medium containing a suitable oil for consumption (for example, containing a gelling agent and a thickener and, for example, an edible triglyceride) optionally, a physiologically acceptable amount and/or vitamin E. Vitamin E is especially preferred- at least one water-soluble vitamin. Other and/or non-vitamin drugs and oil-lipophilic vitamins may be present in the oil phase. In the case of an emulsion containing a well-dispersed phase, which preferably contains a co-medicinal agent, the vitamins can be replaced by a non-vitamin, at least one lipophilic vitamin and/or a non-vitamin lipophilic medicinal compound. min drug and, optionally, In the compositions of the invention, if suitable for consumption triglyceride, and the consumption of triglyceride is present, it is the mentioned emulsion composition additionally contains important fish oil or more preferably ros- at least one emulsifier, preferably with emulsifying oil, optionally, in whole or in part, which is selected from suitable for consumer hydrogenated, for example, coconut oil, phospholipids and complex esters of fatty acids, soybean oil, rapeseed oil, sunflower, while the mentioned method includes: oil, safflower oil, mustard oil, olive - the formation of an aqueous composition that contains vodka oil, peanut oil, etc. Especially the solution of the gelling agent and thickener and, a non-preferred oil will be an oil rich in fat necessarily, at least one water-soluble vita- acids with relatively short chains, for example and/or a non-vitamin drug, put those with a large amount Sv-Siv- or pe- the formation of a water-immiscible liquid composition, preferably Sv-C12 fatty acid residues. Oso- containing at least one emulsifier and, it is highly preferred that the average mass content necessarily, at least one lipophilic vitamin carbon in fatty acids ranged from and/or non-vitamin medicinal product, Sv to Si". Alternatively, the oil will be oil, mixing said water-immiscible compound rich in fatty acids with relatively long lances with at least part of said aqueous compounds, for example, those with a large amount of zition, thereby forming an oil-in-oil emulsion. C22- or in particular Civ-Cg2-, especially Civ-fatty acids, and acid residues. Fatty acid profiles can be adjusted as needed by mixing further components with the mentioned emulsion, thereby forming a vegetable oil or by mixing the mentioned liquid emulsion composition, cast oils from different sources. In general, there is no preference, for example, mixing in the following aqueous or highly unsaturated fatty acids. non-aqueous compositions containing a physiologically oily phase, for example, a suitable mineral compound (for example, iron, triglyceride, if it is present, and zo, zinc), sweeteners, the next gelling agent - vitamin E or a non-vitamin lipophilic agent or thickener, the following vitamins, non-vitamins of the medicinal product together mainly make up medicinal products, minerals, flavorings, color- 2095 from the weight of the entire composition, for example, up to 1095, nicks, preservatives, etc. more preferably up to 595 of the weight of the entire composition,

Preferably, at least one vitamin, preferably up to 395% by weight, and/or non-vitamin drug is present, preferably up to 195% by weight, for example, 0.05%. It is more preferable that at least 0.595 of the mass be present. I have one vitamin. Vitamin E used according to the invention

From the point of view of the next aspect of the invention, the home can be in any form in which vitamin E is offered in a liquid emulsion composition, which can be, including derivatives, analogs, has an aqueous dispersion medium containing metabolites and bioprecursors, for example, "- gelling agent , for example, agar-agar, and one or tocopherol, o-tocopheryl acetate, o-tocopherol more resins, for example, vegetable gum, and, succinic anhydride, vitamin E TROB and optionally, a physiologically acceptable amount of tocotrienols. However, it is preferable to use c- at least one water-soluble vitamin tocopheryl acetate and especially a, 1-o- and/or non-vitamin medicinal product, and butter-tocopheryl acetate. Vitamin E and suitable for well dispersed phase, which preferably contains triglycerides (if present) at least one lipophilic vitamin and/or non-vitamin are preferably present in the mass ratio of the drug and, optionally, not from 1 :100 to 1001, more preferably from 20:80 to edible triglyceride, with 98:2, even more preferably from 75:25 to 95:5, the particular emulsion composition additionally contains from 85:15 to 93: 7, or vitamin E must have at least one emulsifier, preferably an emulsifier, to provide 80-12095 of its recommended amount, which is selected from the daily acceptable amount suitable for consumption. phospholipids and esters of fatty acids. The emulsifier used in the compositions, while the aforementioned oil phase contains the main ingredient of the invention, is mainly a phospholipid. However, instead of one of the following components: (i) drops of aqueous phospholipid or, in addition to phospholipid, a possible dispersion medium that contains other emulsifiers from fatty esters that do not contain physiologically active or useful acids, for example, fatty acid esters ( for example

clade, Stivg2-fatty acids, especially Sev-fatty acids, the phase is preferably from 1:3 to 1:25, acids) and polyhydric alcohols (especially Sv- more preferably from 1:5 to 1:20, even more per-alcohols) or their polyoxyethylated derivatives, in particular important from 1:7 to 1:15, especially from 1:8 to 1:12. non-ionic surfactants such as spans Alternatively, the mass ratio of emuls- (5rap) and tween, especially polysorbate 80 (i.e. tora to the total oil phase is from 1:5

TmzheepF 80), ethoxylated/propoxylated block soda - up to 1:200, more preferably from 1:10 to 1:100, special polymers, for example, poloxamers, alkylpolyglycols - from 1:12 to 1:70. zides and polymers of polyacrylic acid, for example, it is believed that phospholipid or complex ester of the clades, emulsifiers of the Sagroroy and Retpshep type. of fatty acids causes the appearance of oil droplets

However, although such emulsifiers, in particular polysorbate in an emulsion with at least a partial surface 80, have found use in pharmaceutical halo- membrane, which contributes to the stability of both emulsions, with and in the field of food additives, they are not generally so and vitamin and/or non-vitamin lipophilic preferred for consumption, and drugs dispersed in drops are preferred. The use of phospholipids in the compositions of inventions of lipophilic vitamins and non-vitamin medicines. means may increase as a result of reduced

The phospholipid used in the composition of the oxygen diffusion through the oil-oil interface of the invention is mainly glycerophospholipid, liquid-water emulsion droplets, and it is desirable to concentrate phospholipid or sphingophospholipid, in addition to vitamins other than vitamin E, in the oil deposit, sphingomyidine (ZRN), cerebroside or phase would be relatively low in order to otri- ganglioside. Examples of glycerophospholipids have a low ratio between their concen- include phosphatidic acids (PA), phosphatidation in oil and the surface area of the oil-ethanolamine (PE), phosphatidylcholine (PS), phos- water. phatidyl-glycero-phosphates, M-acyl-phosphatidyl- Lipophilic or hydrophilic vitamins, or non-ethanolamines, phosphatidylserines (RB5), phosphatidamine drugs, or other substances (tob- dilinosites (RI), phosphatidylglycerols, diphosphate minerals ), present in the composition, it is possible to include glycerol and plasmalogens. Examples of lysocation in particles or droplets (for example, in a drop of phospholipids include lysophosphatidylcholine, a deoxygenated aqueous solution) within the limits of lysophosphatidylethanolamine, lysophosphatidylinole in the oil phase in an emulsion. Particles or krazytes, lysophosphatidylserines, lysophosphatidylglyps may have a small diameter, for example, 1-serines, lysophosphatidylglycerophosphates, lysodyl- 1000nm, preferably 5-800nm, especially 10-600nm. phosphatidylglycerols, lyso-ch-acyl- Particles or droplets, therefore, will be protected from phosphatidylethanolamine and lysophosphatidic acid- exposure to oxygen. So, the water-in-oil-in-water emulsion is broken. Glycerophospholipids, for example phosphates, are also considered as an emulsion according to the invention. dilcholines, are particularly preferred. Phospholipid Lipophilic vitamins suitable for use in the invention include vitamin E, vitamin A, vitetic or semi-synthetic, but phospholipid K and/or vitamin 0, especially vitamin A, vita - bird egg pods or natural phospholipids such as O and vitamin E, especially vitamin E. However, any vegetable origin, such as lecithins, is an individual or combination of these vitamins listed above, for example, soy, sunflower, them vitamins will be suitable for use in rapeseed, grain or peanut lecithins. compositions of the invention.

Semi-synthetic phospholipid refers to natural Vitamin O used in compositions for a phospholipid that has undergone chemical modification, according to the invention, can be in any active form, hydrolysis, for example, enzymatic form, including derivatives, analogues, metabolites and hydrolysis by phospholipases, such as phospholipase bioprecursors, for example cholecalciferol (vi-

Ai, Ag, B, C or O, especially by phospholipase A". tamine Oz), ergocalciferol (vitamin O2), To,25-

One phospholipid or combi-dihydroxy vitamin O, 25-hydroxy vitamin O, 1ene-nation of two or more phospholipids can be used. Lecetin hydroxy vitamin O, etc. Preferable are ergocalc, which generally contain a mixture of fociferol and, even more, cholecalciferol, of plant origin. spholipids, for example, phosphatidylcholines (PS). Vitamin Oz is usually commercially available in together with one or more PE, RI, P5, RA and 5PH. edible oil base, e.g.

One of the examples of a particularly suitable commercial product is from Kospe. Such forms may include a rationally available phospholipid suitable for consumption of triglycerides, and should be consumed, EtyPyor (from bisaz Meueg otrn, note that the total amount suitable for consumption

Hamburg, Germany), which is a defatted enzyme-consumption of triglycerides in the composition can include some derivatives of the O-vitamin mixture. lecetin enriched with lysophospholipids. Lece- Vitamin A used in the compositions for tins are also especially preferred for use- the invention, can be used in any of its as phospholipids due to the fact that they contain active forms, including analogues, derivatives, tocopherol and have their inherent antioxidant metabolites and bioprecursors, such as retino- properties. ly, retinol esters, dehydroretinol and

Emulsifiers, such as phospholipids or beta-carotene. The most preferred in the composition of fatty acid ester emulsifiers, especially according to the invention is retinol. preferred in the preparation of both aqueous and oil-Vitamin K, which is used in compositions in the liquid phase before the next emulsification. According to the invention, it can be used in any ratio of the emulsifier to the total oil - active forms, including analogues, derivatives,

metabolites and bioprecursors, such as phytothiamine 1.4mMg dione, menaquinone and menadione. riboflavin 1.6 mg

Water-soluble vitamins, suitable for use in the compositions according to the invention, niacin 18 mg, include - vitamin Be 2 mg thiamine, riboflavin, niacin, nicotinamide, group B - folic acid 200 μg of vitamin B, biotin, pantothenic acid, folic acid, vitamin B2 2 μg acid, pyridoxine, pyridoxal, pyridoxamine, biotin 0.15 mg inositol, vitamin Viig2, choline and/or ascorbic acid-pantothenic acid bmg tu. Any of these vitamins or any combination vitamin K 50mcg of the vitamins listed above can be used in the Recommended Daily Amounts of Vitamin B2 compositions of this invention. and vitamin K taken from "Mohais diideiipev5 ytog ipsiake oi

Nicotinamide (also known as vitamin B) Piyepov, 1996". can be used in any available active form, including analogues, derivatives, breakdown metabolites and precursors. However, vitamins , which are used in the composition

Thiamine (vitamin B) can be used according to the invention, is relatively stable, and therefore can be used in any available active form, including using only a small excess of vitamin analogs, derivatives, metabolites and precursors. Peniv, namely in the range of 0-2595, preferably 0-1595, revision forms include thiamine pyrophosphate, more preferably 0-1095, for example 5-1095. thiamine hydrochloride and thiamine mononitrate. The excess of vitamins A and O in 1095 guarantees

Riboflavin (vitamin Bg) can be used with a shelf life of 18 months in any available active form, including at room temperature. An excess of vitamin E (O1--o- analogues, derivatives, metabolites and precursors. Petocopheryl acetate) in 595 guarantees the same terrevazable forms include riboflavin, riboflavin suitability during storage. The following excesses of wine 5-phosphate riboflavin 5'-phosphate sodium. can be used for water-soluble vitamins:

Pantothenic acid (vitamin B group) can be used in any available active fornic acid (25905), thiamine nitrate (1095), nicotinamide (595), pyridoxine hydrochloride, including analogs, derivatives, metabolites, pop- ( 595), dexpanthenol (1095), vitamin B (2095), rednic acid, and also as salt. If she uses riboflavin (595) and folic acid (20965). is available in the form of a salt, dexpanthenol is preferred. It is desirable that the compositions according to the invention contain,

Pyridoxine (vitamin B) can be used in optional 120-4000mcg, preferably 640-96O0mcg of any available active form, including vitamin A, optionally 0.75-25mcg, preferably 4- analogues, derivatives, metabolites and precursors. (Other bmkg of vitamin O, optional 9-300mg, mainly vitamins Bie include pyridoxal and pyridoxamine, 48-72mg of vitamin C, optional 0.21-7mg, which can also be used in compositions for important 1.12- 1.68 mg of thiamine (vitamin B), optional - invention). approximately 0.24-8 mg, preferably 1.28-1.92 mg of riboflavin

Folic acid (Vitamin B) can be added (Vitamin Bg), optional 2.7-90mg, preferably 14, used in any available active form, 4-21.6mg Niacin (Vitamin Bz), optional 0.3- including analogues, derivatives, metabolites and pro- 10 mg, mostly 1.6-2.4 mg of pyridoxine (vitamin Bb), intermediates. optional 30-1000mcg, preferably 160-240mcg

Ascorbic acid (vitamin C) can be supplemented with folic acid (vitamin Be), optionally 0.6- in any available active form, bmkg, preferably 1.6-2.4 micrograms of vitamin Vig, optionally including analogues, derivatives, metabolites, preliminarily 0.225-0.75mg, preferably 0.12-0.18mg of biotin, nicks, and also as a salt, especially as sodium ascorbate, optionally 0.9-30mg, preferably 4.8 -7.2 mg pan-potassium or calcium. totenic acid (vitamin Bz) and/or 7.5-250 mcg,

Certain vitamins have a relatively low water-solubility, mainly 40-bOmkg of vitamin K. For example, riboflavin and folic acid. In addition to lipophilic vitamin/non-vitamin lilotes, and they can be included in the composition of wine products, optionally, water-soluble. in dispersed, and not in completely dissolved, form of vitamins, emulsifier (for example, phospholipid). gelling agent, thickener, and composition water

Preferably, the composition according to the invention will contain vitamins and/or minerals in the range from 15 to 50095 of the recommended daily allowance, for example, sweeteners, starches, bones ( EPA), mainly 30-20095 of the recommended daily allowance of antioxidants, isoflavones, beta-carotene, lycopene, especially 80- soluble and insoluble fiber, minerals (for example, zinc or iron, 12095 of the recommended daily allowance), dyes, modifiers bones per dose. Recommended daily acceptable pH (e.g. buffers or acidifiers, for example, as defined by the Council Directive of 24 clades, citric acid, lactic acid, malic acid of September 1990 regarding the labeling of food value acid, etc.), preservatives (e.g. benzoates for food products (90/496/EEC), there are offensive or sorbates), flavorings, etc. by him: Compositions according to the invention contain a modifier vitamin A 80Omkg of viscosity, that is, a substance that increases the viscosity vitamin O 5Mkg of the aqueous phase, which, most preferably, is vitamin E 10mg a combination of a thickener (for example, a resin) and a gel-vitamin With a bomg former, for example, a combination of agar-agar and an edible resin, such as a sweetener gum. The predominant natural sweeteners are carob fruits, guar gum (resin with chewing gum is sugar or fructose, which are usually the seeds of Suatorvs ieygadopoiora), xanthan gum is used in the form of syrups from 7095 solid copper (a polysaccharide produced by fe- substances (after drying) , and similar to this sorting of carbohydrates by gram-negative bac- bit as 7095th syrup, and fructo-oligosaccharides.

Rzeidotopadaceae), gum arabic or ca-acesulfame K, for example, in the mass ratio of tragacanth. Other examples of thickeners include 2:1-1:2, especially in the mass ratio of cellulose derivatives, for example, methylcellulose-0.9:1-1:0.9. zu, carboxymethyl cellulose. A particularly preferred combination of hydroxypropyl cellulose, methyl hydroxypropyl aspartame, acesulfame and inulin and/or fruc- lulose and hydroxypropyl methyl cellulose and moto-oligosaccharides is used, because this combination has synedified corn-based starches, corn-based flavor effect, relatively effective of waxy ripeness, potatoes, wheat, rice and tapering the sweetening effect of sugar and sugar. The combination of gelling agent and thickener, while hiding the unpleasant taste of artificial sweeteners, will be used in general sweetener concentrates. Fructooligosaccharides can be obtained in fractions of 0.01-5 mass 95 from the total liquid by partial hydrolysis of inulin, and they are of an emulsion composition, more preferably 0.05-3 exist under the trade name Caiose, and they can be mass 95, especially 0.1- 1.5 mass 95. Combine - get from Ogaii 5A, Tiepep, Belgium. This gelling and thickening firm also supplies inulin under the trade name to increase the physical stability of the emulsion. Kapiiyipe. Fructooligosaccharides also have

A gelling agent is defined as a substance capable of forming a gel after dissolving in water. Annex- Veopip-Mei)i Ipaiviev, MeciiShu-zyg-5eipe, France. di gelling agents include alginates, more In general, inulin or fructooligosaccharides will be specifically Ma-alginate, K-alginate, MNa-alginate, used in concentrations of 100-5000 mass-

Ma-alginate or Ca-alginate, propylene glycol parts to 2 mass parts of aspartame and aceginate, carrageenans, more specifically capasulfame. carrageenan, iota-carrageenan, or lambda-carrageenan. The sweetener content in gellan gum, more specifically, high-acylated gellan gum compositions will depend on the specific sweeteners, gellan gum or low-acylated gellan, that are used, and whether a renewal is necessary. gum, pectins, more specifically high-conduct the composition before consumption. Therefore, the methoxylated pectin or sweetener content will be chosen with the aim of low methoxylated pectin and gelatin, more providing a pleasant sweet taste when consumed, specifically gelatin of animal origin or from the bath. Naturally, the content of the sweetener will be constant. The gelling agent is preferably used in the form of 0.05-1 mass 95 where concentrations of 0.02-1 mass 90 of the total com- strong artificial sweeteners, for example, approx. 0.03-0.4 mass 905, are used, especially 0.1-0.3 mass 9o. Where 0.04-0.3 mass percent is used. One of the special ones is natural sweeteners (for example, the invert in the preferred gelling agents is agar-agar, and it is sugar or fructose), they can usually consist of - especially preferably used together with the addition of up to 20-50 mass 95, more preferably 30-50 one or several suitable for mass consumption 95 of the total composition based on resins, for example with locust bean gum and dry substances. tree and guar gum (from Suatorz seeds) For compositions intended for teenagers and

Ieigadopioba). The thickener is mainly used by children who do not need to use low-calorie products in a concentration of 0.05-1.5 mass 905 of the total product, unlike artificial sweeteners in the composition. natural sweeteners can be preferred

Compositions according to the invention are intended for drinking (for example, sugar alcohols) and non-carcinogenic oral consumption. For oral consumption - sweeteners. However, for products intended for composition preferably contain sweetened them for adults, which should be followed low- and flavorings, so that the consumer can better their low-calorie diet, may be preferred. Sweetened, applied, artificial sweeteners. can be natural sweeteners, for example, mono-, di- and polysaccharides, for example, use in the compositions of the invention, including sucrose, fructose, fructooligosaccharides, fruit (for example, pineapple or citrus) (oligofructose ), glucose, glucose syrup-concentrates and concentrated aqueous and non-aqueous pom, invert sugar, maltodextrins or flavorings such as aromatic oils, for example- sugar alcohols such as sorbitol, sorbitol clad, citrus oils, for example, orange oil syrup, maltitol, maltitol syrup, lactitol, mannitol, (V.R.) after cold pressing. Orange xylitol, isomalt, etc., or artificial sweeteners - concentrate, for example, orange concentrate in the eyes. Examples of strong artificial sweeteners - 65" Brix, is particularly acceptable. Flavoring agents include aspartame, acesulfame K, neo- will be used in a concentration sufficient to give the composition, optionally, after salts of saccharin (i.e., sodium saccharin) and cyclamate dilutions with a pleasant taste. For example, malic and cyclamic acid. You can use one son concentrate at 65" Brix, you can use a sweetener or a combination of two or more doubles in a concentration of 1-20 mass 95 relative to the whole emulsion, preferably in a concentration of 2-15 ma- Suitable preservatives for use in owls 95. Alternatively, orange oil BP, the compositions of the invention include permitted for consumption obtained as a result of cold pressing, preservatives, for example, potassium and used in a concentration of 0.04 -0.03 mass 9bo, sodium salts of sorbic, benzoic and parahydro- mainly 0.06-0.2 mass 95 relative to all emu- sybenzoino and acids. Potassium sorbate is particularly beneficial. respectable The preservative will generally be applied

It should be understood that the use of aromatizers in a concentration of 0.05-1.5 mass 9o relative to rivulets or acidifiers that are soluble in the water of the entire emulsion, preferably 0.1-0.3 mass 95. phase (for example, fruit concentrates or (for example, monic acid can be used as a dye), can affect the solubility of beta-carotene. Beta-carotene gives emulsions orange-vitamins in this phase, and that in such cases it may be necessary to dilute the aqueous phase for the purpose of taste, when orange flavoring is used, to prevent precipitation. So, teasers are preferred. It is possible to use beta-carotene in an acidulant such as lactic acid and a water-based oily suspension (3090 saturated (E5) soluble flavorings such as citrus oils or beta-carotene from Cospe) or in the form of soluble water-soluble flavorings such as as flavoring of beta-carotene in cold water (7950 solution of beta-carotene with the taste of strawberry, raspberry, passion fruit, carotene in cold water from Kospe). exotic fruits, peach and apricot, and other Acidulants, for example, milk or apple- non-citrus flavorings, such as concentrated acid, can be included in the composition of pineapple. do It is preferable to use lactic acid,

Where aromatic oil is used, it is available in the 8096th solution called Rigas and can be dispersed in the oil phase together with li-80, from Rigas Biospet ru. The pH of the emulsion should be lipophilized to less than 6 with more regu-pophilic vitamins or non-vitamins, with more predominant drugs, or with their combination less than 5, for example, so that it constitutes a dia, or as an alternative and preferred method - grade 3-5. Where flavoring and lipophilic vitamins and/or fructo-oligosaccharides are not used in the compositions of the invention, it is preferred that the medicinal agents are dispersed separately to maintain a pH above 4 to prevent hydrolysis. of the entire emulsion - with this method, it is possible to minimize - in the preferred embodiment of the invention, any influence of the aromatic oil on the stability of the physiologically acceptable inorganic compound in vitamins. In these circumstances, a phospholipid or another form of nanometer-sized particles (for example, an emulsifier is preferably dissolved in an aromatic clade, 1-1000nm, preferably 5-800nm, especially 10-oils, and two oil phases, one of which contains arobOOnm) is added to the dispersed phase of the emulsion with mematic oil, and the other - lipophilic vitamins and/or that of further stabilization of the oil-in-water emulsion. non-vitamin lipophilic drugs, intensively The inorganic compound used must be mixed with the aqueous phase. This can be done with a higher density than the oil phase and separately (wherein the two emulsions are then mixed also preferably higher density than the aqueous together) or sequentially (wherein one oil phase. Suitable inorganic compounds include phase, usually a vitamin phase, intensively mix calcium salts, i.e. calcium carbonate, lactate with some or all of the aqueous phase, calcium gluconate, calcium citrate, malate, and the second oil phase then intensively mix calcium, calcium hydroxide and calcium phosphate, mixed with the resulting emulsion (not necessarily preferably calcium carbonate. Others are suitable after diluting the emulsion)). include sodium salts, magnesium salts, and zinc salts

In general, the low density of oils in the dispersed phase. Predominantly an inorganic compound is the carbonate phase of the emulsion is one of the main causes of physical calcium, which is commercially available in the form of instability, resulting in the destruction of powder with nanometer-sized particles. emulsion formation. The density of orange oil BP becomes The inorganic compound thus increases the range of 0.85-0.88g/ml, and thus the oil phase, and it can, if desired, be much less than the density of all water should be applied in quantities sufficient to form a phase, which in this case is the range of an oil-in-water emulsion of uniform density. 1.16-1.23g/ml, for example, 1.16-1.19g/ml. Therefore, from the point of view of the next aspect, the invention of a suitable gelling system and a liquid emulsion composition is proposed as a thickener, which has an aqueous dispersion medium that is the interface between the two phases. In this regard, the system includes a gelling agent and a thickener and, optionally, a gelling agent and a thickener that is used in a physiologically acceptable amount of at least one for the pharmaceutical compositions of this invention, is a water-soluble vitamin and/or non-vitamin unique. This system exhibits the properties of a drug, and a dispersed oil phase, gel-solution-gel, when subjected to shear stress. which contains at least one lipophilic vitamin-

The aqueous phase has the structure of a gel at rest, which is a non-vitamin and/or non-vitamin drug and does not block the emulsion droplets in the three-dimensional gel-forming grid, necessarily, suitable for consumption of a triglyceride and thickener. The emulsion, however, will flow easily, wherein said emulsion composition flows when subjected to only slight stress additionally contains at least one emulsifier, shear, such as turning the bottle neck down preferably emulsifier selected from the attachment or shaking the bottle. The emulsion will gradually lose its viscosity in the mouth and, thus, the consumer of fatty acid esters, while the said oil will not feel its slipperiness. phase contains at least one of the following components

nents: (i) drops of an aqueous dispersion medium of fat-soluble vitamins (especially vitamin A, which contains dissolved in it physiologically and vitamin O), it is preferable to prepare two oily active useful compounds, (ii) an inorganic particle of the composition, while the first contains vitamins and and (ii) non-vitamin lipophilic medicinal compound. emulsifier (for example, phospholipid), and the second mis-

Compositions according to the invention are emulsions of oil in an emulsifier (for example, the same phospholipid, preferably with a narrow size distribution) and the following oil component. drops of oil (triglyceride) with an average weight, In the method of the invention, the gelling agent, the size of the drops (i.e. the diameter) (which can be measured, for example, agar-agar, must be heated in a water well, for example, by light microscopy and medium to a temperature that exceeds its comparison with the scale of 1-10μm), which is the temperature of gelation, for example, up to 95- the range of 1-5μm, more preferably 1-4μm, the most - 100"C for agar-agar, in order for it to dissolve - more preferably 2 -4μm. Emulsification is preferred. However, vitamins should not be affected, but it is carried out in such a way as to have only a temperature of more than 40"C, preferably more than a large excess of the size of the droplet fraction, i.e. 30"C. Cooling of the liquid gelling solution to have droplets whose diameter exceeds 5 μm.cha (for example, agar-agar) can be carried out

This can be achieved by mixing the aqueous by adding an additional solution, such as phase and oil phase, using a mixing solution of sorbitol and/or a thickener solution (dissolving device of high intensity, high speed guar gum and/or locust bean gum colloidal mill (Koghita , migop, bimegzop or trees.) During the cooling of the gelling agent

Attention!) or a high-pressure homogenizer (micro- (e.g., agar-agar), thickeners and main fluidizer), for example, a high-shear rotor- the mass of the sweetener solution should be taken care of, but a stator mixer that can, for example, not to form gel. Get the gelling solution from U5iga! ztrN, UNIPDEP, OEBE. One of (e.g., agar-agar) should be cooled from 32 to Examples of suitable mixers are Oiah 600 with 2870 by gentle mixing. Mix with a 200 or 20P rod. Preferably, the application should be such that the viscosity is not over-built dispersion chamber (for example, Oiah exceeds 300OmpPa:-:s (centipoise (cp5)), preferably 600, type 22/2), because this can guarantee that that but 2500 mPaies, especially 1500 mPaies after only a small amount of air can get into the cooling to 252C. emulsion or not at all. The total volume of water used is

The formation of emulsification may be more effective. It should be minimal, however, when using only a part of the aqueous phase with the fluid, so that the vitamins (if they are present) retain their stability in the solution. The number of the phase or its subsequent parts. water, which is used for cooking various

On a small scale, the method according to the invention of aqueous compositions will usually be chosen to preferably include the preparation of at least two, so that it constitutes at least a minimum, and more preferably at least three aqueous compositions to obtain compositions that can be rinsed and at least one, preferably two seines and mix together, the total desired content of their compositions. The first aqueous composition contains water can be achieved by adding water or a solution of a thickener (for example, vegetable gum aqueous solutions of the following components. This or a mixture of vegetable gums, for example, galac- method can compensate for losses that are nastomannans) and a preservative, and part of this possible evaporation. to be used for the preparation of the previous It is not necessary to produce and process the emulsion, while the rest will be combined with the new in an inert atmosphere (for example, a second aqueous composition, which is an aqueous solution of nitrogen or inert (for example, a noble nom of the gelling agent ( (e.g., agar-agar). Su- gas)), partial vacuum or with the introduction of nitrogen, a mixture of vitamin powder and/or non-vitamin medica- so as to minimize the contact of oxygen with the vitamir agent can be dissolved or dispersed with nom 0, vitamin A and vitamin E. Alternatively, either in the first or in the second aqueous solution, the contact with oxygen can be reduced by preparing or in the combined aqueous composition, preferably, by preparing a lipophilic vitamin composition and emulsifying the mixture of vitamin powder and/or non-wetting it with a thickener solution under inert conditions, the drug was dispersed in the third atmosphere. aqueous composition, optionally, together with the following - To prepare emulsions according to the invention with foaming components, such as sweeteners, and it is advisable to use a high-shear rotary - this third aqueous composition is mixed with a combined stator mixer or built-in high-speed aqueous composition before or preferably after an oblique dispersive rotor-stator mixer. admixture of the previous emulsion. Preliminary One preferred option for preparing an emulsion of fat-soluble vitamins or non-vitamins on a small scale according to the invention of lipophilic drugs, or their combi- includes the following steps. nation with arbitrary aromatic oils and hydrogen 1. Heating the first portion of water to 60"C. vitamin dispersion is preferably added to 2. Adding agar-agar together with calcium sorbitol at a temperature of 24-267C. - minimizes possible losses of vitamins and/or non-vitamin drugs during the method 3. Heating to 952 to dissolve the agar

Where an oil component is used, add agar and obtain a liquid (A). as an aromatic oil, which can reduce the

4. Maintaining the temperature of the liquid (A) of bottles, sachets, test tubes, etc., however, preferably at the temperature of gelation (28-35"7С), for example, use containers containing several classes of temperature maintenance in 5076. doses, for example, bottles with a volume of 50-1000ml, re- 5. Heating the second portion of water to 7070. it is important to bottle with a volume of 500ml. If the containers 6. Adding a mixture of locust bean gum transmits light, preferably so that they are trees and guar gum (resins from seeds brown in color, for example, with brown-

Suatorzviv eigadopoiora) in a ratio of 65:35 and discolored polyethylene terephthalate (PET). Mixing with a high-speed mixer, rather than sealing the containers, resulting in a liquid (B). It is desirable to fill the hole in the neck of the bottle above the emulsion with a gas that does not contain oxygen, for example, with nitrogen. class of maintaining the temperature at 5070. As mentioned above, deaeration or introduction of 8. Separation of part of the liquid (B), for example, 5- nitrogen, is optional, used during taking 1095, cooling it to about 30"C and diluting preparation of an emulsion product to exclude the day with water to reduce the viscosity to a level suitable for emulsification, oxygen. is the liquid (C). You in the traditional way in relation to 1 part 9. Combining the rest of the liquid (B) with the liquid (A) to 5 parts of the volume of the diluent, for example, and maintaining the temperature of the liquid (0) above the lead water or mineral water, mol- the temperature of gelation, such as support milk, fruit juice or any other 5076. non-alcoholic drink. Where used 10. Addition of sorbitol solution and gradual water, ode Rye diluted composition can be a temperature decrease to 30-3570. transparent liquid or an opaque liquid with a 11. Dexpanthenol is slightly heated in water with a distinct aroma. bath so that it can be easily transferred and In a further aspect of the invention, the emulsion can be added to the main liquid (0). to dry, for example, using traditional 12. Addition of lecetin to O-o- methods of spray drying or drying of tocopheryl acetate and heating to 50"C, in order to dissolve the lecetin by freezing, in order to obtain a concentrate, and cooling to approximately an emulsion. 306. Therefore, with from the point of view of the next aspect of the invention, 13. Addition of lipophilic vitamins (for example, an emulsion concentrate is proposed, which contains vitamin A, vitamin 0, beta-carotene and welcomes drops of edible oil, mine K), resulting in liquid (E). dispersed in a gelling agent, thickener and 14. Mixing citrus oil (e.g. emulsifier, while the mentioned emul- orange oil concentrate) with lecetin and slight heating contains at least one lipophilic vitamin. heating, for example to 30"C , to dissolve lece- From the point of view of an even further aspect of inventions. The resulting liquid is liquid (P). 15. Slow addition of liquid (E) to the liquid of the emulsion according to the invention, while mentioning (C) with the use of a mixing device, the method includes drying, preferably of juicy intensity to obtain preliminary spray drying or drying frost-emulsions. Then admixture to the liquid (PE) is also with mixing, while the liquid emulsion has an aqueous dis- by using a mixing device of high persian medium, which contains gelling intensity (i.e. dispersing device Oiah and a thickener, and an oil dispersed phase with an attachment 600 with a rod 200) . A preliminary emu-nogy for oil consumption is obtained, while the mentioned lsia is a liquid (5). the emulsion additionally contains at least one emu- 16. Mixing in powder form! a mixture of vitamin-emulsifier, preferably an emulsifier selected from the following (i.e., nicotinamide, thiamine mononitrate, fish-suitable for consumption phospholipids and components of flavin, pyridoxine, hydrochloride, folic acid esters of fatty acids. acid, vitamin Vig, and sorbitol) together with ascorby - In one embodiment of the invention, the method with a new acid and citric acid monohydrate - includes drying a liquid emulsion, where the mentioned liquid in a bath with water using a mixing emulsion contains in its oily dispersed phase a high intensity device with a dispersive non-vitamin lipophilic medicinal compound. rod, as a result of which a liquid (H) is obtained. In the next embodiment of the invention 17. Cooling the main liquid (0) to about

Homogenization of mixtures for 2 minutes with a non-vitamin medicinal compound in the application medium. by moving a high-intensity mixing device with a dispersive rod. At the same time, the method includes drying the liquid emulsion, where it is mentioned to worry that air does not get into the liquid emulsion contains in its oily dispersed mixture. phase a non-vitamin lipophilic medicinal compound and 18. Filling the bottles with the obtained mixture additionally contains in its aqueous dispersion and their hermetic closure in a nitrogen atmosphere. a non-vitamin medicinal compound in the environment.

Containers used can be In one embodiment of the invention, the method containers containing a single dose, for example, includes drying, preferably spray su-

drying or freeze-drying of a liquid emul- When freeze-drying is carried out, where lipophilic or hydrophilic vitamins or other aqueous phase of the emulsion may include concentrating agents (e.g., minerals and/or non-vitamin or excipients that promote lyophilization, drugs) are present in particles or, for example, sucrose, sorbitol, lactose, malto- droplets (for example, drops of deoxygenated dextrin, maltose or mannitol aqueous solution) within the droplets of the oil phase When spray drying is carried out, in an emulsion. Particles or droplets may have neve- the emulsion may not contain vitamins (or may not contain a face diameter, for example 1-1000nm, preferably 5- vitamins, except vitamin E), while vitamins 80Onm, especially 10-600nm. Particles or droplets introduced into the spray zone of the sprayer will thus be protected from exposure to oxygen. drying device.

Therefore, dried emulsions of water-in-oil-in-water and Alternatively, when the drying is carried out emulsion-in-emulsion are also compositions that by spray drying, the emulsion can be according to the present invention. do not contain vitamins (or do not contain water-soluble

In a preferred embodiment, the method for vitamins), while the vitamins are introduced into the zone of the invention includes drying, preferably spray-spraying of a spray device for bulk drying or freeze drying, drying. The aqueous phase of the emulsion may include a solid-liquid emulsion that has a physiologically acceptable carrier, for example, sucrose, sorbitol, lactose, an inorganic compound in the form of nanometh- or maltodextrin particles, to provide a concentrate of a uniform size (for example, 1-1000 nm, preferably 5- emulsion about volume and mass.8b0Onm, especially 10-600nm), for example particles The emulsion concentrate can be reconstituted in calcium carbonate water. These particles are intended for the formation of an oil-in-water emulsion for consumption and stabilization of the emulsion. An inorganic compound that is diluted or diluted before use preferably has a higher density. Emulsion concentrate can be packed in than the oil phase, and preferably a higher density or capsules, pressed into tablets or powder than the water phase. Suitable inorganic compounds in the form of any suitable solid include calcium salts, i.e. carbonate in calcium form. tion, calcium lactate, calcium gluconate, citrate Freeze-drying can be carried out calcium, calcium malate, calcium hydroxide and pho- using traditional equipment for calcium sphate, preferably calcium carbonate. Other freeze-drying, such as 51egi5, Germany- suitable compounds include sodium salts, magnesium salts, or Ov5i-Egoia, France. The method of drying ammonia and zinc salt. Predominantly, the inorganic compound used for emulsifying vitamin, mineral, and/or non-vitamin drugs is calcium carbonate, which is commercially available in the form of a fine powder with nanometer-scale particles. An example of such a compound is SaiyutopF y, a freeze-drying emulsion with a dry content that can be obtained from Zresiaiu Mipeg!5. substance (i.e. without water) up to 60 mass 95, re-

Saiyutoge O is a precipitated calcium carbonate that weighs about 20% by mass. The emulsion consists of very small calcite crystals is heated to minus 80°C and kept at this temperature for 1-12 hours. Primary drying

Calcium carbonate has a density of 2.7 g/cm3, and this is done by keeping the emulsion for a while, it is very suitable for increasing the density for 12-144 hours at a pressure of 0.01-0.04 hPa, with a dark oil phase for the formation of an emulsion of oil in a temperature of holding from minus 45 to minus 6570 water with a uniform density. An inorganic compound, and at a condensation temperature from minus 80 to minus 80, therefore, increases the density of the oil phase, and it can be 90"C. Secondary drying is carried out by applying in quantities sufficient to increase the pressure to 0.1 hPa and increase the temperature to form oil-in-water emulsions with a uniform density. Therefore, it is also considered that the concentrate The duration of secondary drying is 6-24 emulsions, which contains an inorganic compound in ventilation of the drying chamber with a dry composition corresponding to the present invention, with nitrogen.

Edible oil using spray drying, however, is preferred in this regard, for example, can be either technology, as this technology is less expensive, may contain edible triglyceride and is more suitable for large-scale reed and/ or vitamin E. production. Equipment for spraying

The emulsion that is dried, preferably contains drying can be obtained from Appudgo ARM or CEA gelling agent (for example, agar-agar), thickener Migo A/5, both companies are located in Denmark. The method (for example, guar gum and/or the gum of spray-dried fruits for vitamin and/or carob tree) and emulsifier (predominantly select- mineral emulsion will usually include cut from edible phospholipids spray-dried emulsion containing dry re- and complex fatty acid esters, for example, pho- urea (i.e. without water) up to 60 mass 95, a transphospholipid such as lecetin). approximately 50 mass 95, and with temperature

When freeze drying is carried out, the liquid is in the range of 30-507"C, preferably 40-507C, the aqueous phase of the emulsion preferably contains at least more preferably 30-40"C. The inlet temperature is one water-soluble vitamin, and the oil phase of air is 100-1807"C (for example, 160- preferably contains at least one lipophilic vi- 180"C) in small-scale production and 180- tamine. 2507" in large-scale production, while in both cases the outlet or outlet temperature of the composition of the invention is 60-1007С (for example, multiminerals such as zinc are included in the process, 60-807С), the liquid emulsion is sprayed, for example , iron, calcium, iodine, magnesium, and phosphorus. Predominantly, either through the use of dental sprays, minerals are present in the form of inorganic crystals at a rotation speed of 20,000-35,000 rpm, and/or organic salts in the aqueous phase of the composition, tive per minute, or through the use of nozzle - for example, as calcium lactate, zinc sulfate, yoke atomizers at a pressure of 160-180 bar and with potassium dioxide, iron sulfate and/or magnesium carbonate. by introducing dusty components of the product, according to Suitable compounds are well known in the industry. vitamins and small crystals Predominantly minerals form a complex from a solid carrier into the spray zone. mainly crystalline, more polycarboxylic acids (for example, EOTA (essentially small crystals of sucrose, sorbitol, lactose, lentiaminetetraacetic acid) and OTRA (diet- or maltodextrin are also added to the area of lentriaminepentaacetic acid)) to prevent spraying. Emulsion is usually produced by oxidation of vitamins in the aqueous phase. Suitable mineral- by means of a high-pressure homogenizer or ral salts can be used in equimolar high-intensity mixing device, concentrations with pyrophosphate in order to result in oil droplets that are to get pyrophosphate complexes. diameter in the submicron range and up to 1- Minerals are optionally present as 15- 2μm. Water-soluble vitamins and/or minerals can be added as dry ingredients in the form of advance, preferably 80-12095 of the recommended daily mix and together with dusty components of the permissible amount, which is established by the Direct product or crystals solid media, like the Council (see above). clade, sucrose, sorbitol, lactose or maltodext- calcium in 0Omg rin, in the spray zone from above or below phosphorus in 0Omg of the spray drying device. It is possible iron 14mg to use a drying device with a flow in magnesium Z0Omg in one direction, with opposite flows or with zinc 15mg mixed flows. In the system of the atomizing iodine 150μg drying device, a pseudo-fluid 2mg layer at the base of the drying chamber can be included, where water-manganese 1mg, soluble vitamins and/or minerals can be added, chromium 5OmμKg as dry ingredients in the form of a pre-mix and selenium 4Omkg together with the dust-like components of the product or molybdenum 150 μg crystals of a solid carrier, for example, sucrose, The next aspect of the present invention is proponu- sorbitol, lactose or maltodextrin. In both of them, a kit for restoring the emulsion compo- both get a loosened agglomerate, which according to the invention. From the point of view of this aspect, the wine demonstrates good properties of instant solubility, a set containing the first and fluidity is proposed, i.e., the agglomerate will disperse - a container that contains a physiologically acceptable diluting - aqueous liquid, for example, water or an aqueous solution , than and the second container, which contains the concentrate according to

Doses of the composition according to the invention can be consumed with the invention, for example, an emulsion concentrate. you between meals and during meals, and Kits according to the invention can also include they are suitable for consumption by elderly people - a measuring container and/or a container for mixtures with reduced gastric acid secretion. bathing

Compositions according to the invention can be used. The first container may essentially not contain vitamin, and/or mineral, and/or non-vitamin in therapeutic or prophylactic treatment. This forms the next aspect of the invention. From the point of view of the medicinal product. Alternatively, it may view this aspect of the invention provides a method of containing soluble or dispersible vitamins for the treatment of humans or mammalian animals, intended and/or minerals. Preferably, the first container for the treatment of conditions associated with vitamin deficiency contains sterile water, optionally , from solutions (for example, beriberi, nyctalopia, megalobla- containing vitamins, minerals, aromatase hematopoiesis, pernicious anemia, hypoprorama, sweeteners, etc. thrombinemia, pellagra, malabsorption syndrome, In the next preferred option, performed - scurvy, rickets), while the mentioned method includes the non-vitamin lipophilic medicinal agent of the invention - oral administration to the mentioned subject of the compound can be included in the oil phase of the emulsion, zition or supplement according to the invention, optional and/or hydrophilic non-vitamin the medicinal product, after its dilution in a physiologically acceptable amount, can be included in the aqueous phase of the emulsion together with the aqueous liquid. or in the absence those lipophilic and/or hydrophilic

It will be obvious to a specialist in the field that vitamins. positions, processes and methods according to the invention can From the point of view of this aspect, the invention can be extended to the manufacture of other food additive pharmaceutical compositions in the form of emulsifiers. For example, the composition according to the invention can be a solution that contains an oily dispersed phase, which can be used for the production of a multi-mineral oil suitable for consumption from non-odorous compositions, combined multi-vitamin and necessarily dissolved or dispersed in it mineral compositions. Therefore, in a preferred non-vitamin medicinal compound, preferably a lipophilic non-vitamin medicinal compound, preparations (for example, loratadine and pseudo- or a mixture of non-vitamin compounds, and aqueous dysephedrine, acrivastine and pseudoephedrine), an expectorant medium that contains a gelling/mucolytic preparations (for example, bromide and thickener (for example, guar gum (from xin seeds), ammonium chloride, acetyl cysteine,

Suatorziz ieigadopoiora) and/or the gum of the fruits of carbocysteine, coquilana, creosote, domidol, carob tree), and an emulsifier (mainly that, zin, senega root, terpinhydrate), antitussives selected from fo- preparations suitable for consumption (for example, codeine, dextromethorphan, spholipids and esters of fatty acids), and, noscapine, ethylmorphine, acetyldihydrocodeine, ben- optionally, hydrophilic non-vitamin medicated zonate, chlophedianol, clobutinol, dimemorphan, compound or mixture of compounds. drotebanol, levopropoxyphene, morclofon, te-

The use or introduction into the composition of libacon, ziperprol), antihistamines (napophilic non-vitamin medicinal compounds in this example, acrivastine, cetirizine, ebastine, dec- the method of making an emulsion can contribute to the increase of bioavailability, in particular oral pizotifen, trimethobenzamide), anti-infective bioavailability, non-vitamin drugs, drugs that include antibiotics, such as pe- especially drugs with poor water-dissolving nicillins, cephalosporins, beta-lactam antibiotics, because the compound is used in aminoglycosides, tetracyclines, chloramphenim, which is readily absorbed, such as soluble col, macrolides, clindamycin, spectinomycin, and/or a solubilized form. From the stomach, polymexin B, colistin, vancomycin, bacitracin, the intestinal tract, lipophilic non-vitamin drugs isoniazid, rifampin, ethambutol, streptomycin, the agents can be easily absorbed by ordinary chypyrazinamide, ethionamide, cycloserine, and aminosalin into the portal blood or by lymphatic absorption. acid, non-opioid analgesics (eg. Lymphatic absorption is possible because clade, paracetamol, acetylsalicylic acid, fatty acids and bile salts are present during ibuprofen). Absorption of a number of other biologically active digestion. The substance of lipophilic, non-vitamin, lipophilic and/or sparingly soluble substances of drugs can be absorbed in connection with the micellar phase. Examples of such substances are: cortione can participate in the creation of chylomicrons, costeroid hormones (for example, hydrocortisone, which are transferred into the lymphatic circulation. Thanks to ab-prednisone, prednisone), androgenic hormones (absorbed in the form of fat balls into the lymphatic system example, testosterone, nandrolone), progestogens, lipophilic, non-vitamin drugs, non-hormones (eg, progesterone, norethisterone, pass through any intermediate stage of dissolution), estrogens (eg, megastol, ethynination, which often becomes the rate-limiting stage of - lestradiol, mestranol), drugs for the treatment of poorly soluble and lipophilic Parkinson's disease absorption (for example, levodopa, carbidofa), tamine drugs. anticonvulsant drugs (for example, carbamazepine

The bioavailability of drugs that undergo the first foam, phenytoin), antifungal drugs (for example, at the stage of metabolism in the gastrointestinal tract, griseofulvin, clotrimazole), antibacterial or in the liver, can be increased due to the absorption of drugs (for example, nitrofurantoin, through the lymphatic system . The next advantage, sulfapyridine, tetracycline, ceftrioxane) against which is a consequence of promoting absorption, can be viral drugs (eg, zidovudine), tricyc- increasing the rate of absorption, as a result of which personal antidepressants (eg, imipramine, amit- a clinical effect occurs quickly . riptilin), immunosuppressants (for example,

In addition, the inclusion of non-vitamin medicinal cyclosporin A, dihydrocyclosporin 0), an antitumor agent in the lipid phase of the emulsion can protect linoleic drugs (for example, 5-fluorouracil, chloro- molecule of drugs from acid sererambucil, mercaptopurine, fenretinide), anti-inflammatory drugs in the stomach and thereby protect medicinal lariat drugs (for example, halofantrine), agents from disintegration in the gastric fluid, which, in its vasodilators (for example, cyclandelate), tran- turn, will increase bioavailability. vilizators (for example, gepiron), antihistamines

The term "medicinal compound" used drugs (for example, repirinast, cinnarizine, here does not include essential nutrients or their fexofenadine), substances that regulate lipid bioprecursors, that is, vitamins, triglyceride metabolism (for example, probucol), anticoagulants ( for example, dicoumarol), beta-blockers (for example

Examples of possible lipophilic non-vitamins - clade, propranolol), therapeutic vitamins (e.g. drugs for the dispersed phase and clade, menatetrenone), hypotensive drugs hydrophilic non-vitamin drugs for (e.g. felodipine, nifedipine, penclomedin), the aqueous phase, which are especially appropriate for pero- antiparasitic drugs (e.g., atovacral administration, are analgesics, such as synthetivone), diuretics (e.g., spironolactone), opioid opioids (e.g., fentanyl, allentanil, phenytoin agonists (e.g., oxycodone ), antidepressants, ntanil) and nonsteroidal anti-inflammatory drugs (eg, vanoxerin), antidiabetic drugs (eg, naproxen, phenylbutazone, ace- drugs (eg, glibenclamide). tilsalicylic acid). Liquid formulations are also useful, especially in the treatment of children and adults. We include probucol, diazepam, danazol, halofantrine, and anticonvulsants such as carbamazepine, cyclosporine A, phenytoin, and benzodiazepines (eg, diazepam, acid-regulating agents stomach - clonazepam, midazolam and nitrazepam), adrenergic and stomach ulcer treatment, such as cimetidine,

ranitidine, famotidine, omeprazole and lansoprazole are also suitable for use with reference to the following non-limiting examples. positions of the invention. Example 1

Combination products can be easily prepared Preparation of liquid syrup where lipophilic non-vitamin drugs Ingredients: contained in the dispersed phase while hydro- vitamin oil mixture (6b,5g total): philic non-vitamin drug dissolved 0 -o-tocopheryl acetate Atom in dispersion water environment. Antitussives- vitamin A palmitate 539mMg lion and anti-cold pharmaceuticals are cholecalciferol concentrate 165mg common combination products where anti- lecithin 500mg cough medicine is combined with one or medium-chain triglycerides two analgesics. Preferable possible (Cv-Ci2) 596mg anti-cough and anti-cold drug-vitamin powder mixture (10g - all means are dextomethorphan, bromhexine, etc.): nicotinamide b, Zmg acetyl cysteine. thiamine nitrate 612 mg

High doses of drugs can be taken due to the precision of the dose volume, when pyridoxine hydrochloride 765 mg can be taken as a single dose up to 10 ml. The possible dose for lipophilic non-folic acid 45mMg vitamin drugs will depend on the sorbitol powder 1728mMg solubility in the dispersed phase, but it can dexpanthenol 2g reach 500mg in the case when the drug itself ascorbic acid 28g is a liquid lipid. More commonly, lipophilic potassium sorbate 3.5g or drugs will range from sorbitol 7095 (which does not form crystals) /3.55Kg of submicron amounts to 100mg. The content of hydrophilic agar-agar Ag non-vitamin drugs contained in sorbitol powder 54g dispersion medium will depend in the same way on water solubility, however, the available volume for citric acid monohydrate 20g dissolution is greater, as a result of which There is orange oil 3.4 g, the possibility of including a large amount of active lecithin 0.0 g of substance per dose. purified water 2190 g

You can also prepare special emulsions, such as multi-emulsions. ry 60"C emulsion, to which agar-agar is added and water-in-oil-in-water is dispersed, as discussed earlier, with a high-speed mixing device. Su- may be appropriate where ephemeris is expected to be heated to 95"C, to dissolve the agar-agar and active protection of the active ingredient. Stomach to get liquid (A). The temperature of the fluid (A) is controlled by hormones, such as insulin, which is an example of this, maintained above the gelation temperature (28°C, where the hormones must be protected from heat), for example, they maintain the temperature of teolytic enzymes in the stomach intestinal 50"C. The second portion of water is heated to room temperature during the absorption process. ry 70"С. A mixture of carob fruit gum

From the point of view of the next aspect of the invention, the vahmola from the seeds of the Suatorbviv plant is proposed in the co-proposed pharmaceutical emulsion according to the ratio of 65:35 is added and dispersed with the invention, while the said emulsion contains at least one lipophilic and/or hydrophilic device using a high-speed mixing device and obtains a liquid (B ). The temperature of a non-vitamin drug, where the dispersed phase of the liquid (B) is maintained above the temperature of the gel-emulsion contains a physiologically acceptable disorganization of the liquid (A), for example, maintains a compound in the form of nanometer-sized particles at a temperature of 5070. Part of the liquid (B), for example (for example, 1-1000nm, preferably 5-800nm, clade 5-1095, separate and cool to tempe- especially 10-600nm) for the purpose of further stabilization approximately 30"C and dilute with water from the oil-in-water emulsion or water-in-emulsions in order to reduce the viscosity to a level suitable for oil-in-water. Inorganic compound used- emulsion formation. The resulting liquid is a liquid preferably having a higher density than the mass (C) . The rest of the liquid (B) is combined with liquid (A) and the liquid phase, and preferably a higher density than the resulting liquid, liquid (0), sub-aqueous phase. Suitable inorganic compounds are included at a temperature that above the temperature, calcium salts dissolve, i.e calcium carbonate, gel-forming, for example, at 50"C. Add calcium tat, calcium gluconate, calcium citrate, liquid sorbitol, and gradually lower the temperature to 30-35°C. Dexpanthenol is carefully heated to a tion, preferably calcium carbonate. it was possible to easily re- compounds include sodium salts, magnesium salts and salts carry and then added to the main liquid (0). which is commercially available at temperatures up to 50°C to dissolve lecithin, and powder with nanometer-sized particles. cool to 30"C. Lipophilic vitamins (eg

The inorganic compound, therefore, increases the density of masks, vitamin A, vitamin O, beta-carotene and vitamin ly phase, and it can be applied if desired- K) is added and liquid (E) is obtained. Citrus oil in quantities sufficient to form an oil emulsion (for example, orange oil) is mixed with butter in water of uniform thickness. lecetin and slightly heated, for example, to

30"С to dissolve lecithin. The resulting liquid was weighed, raised from 0.06 to 40Pa and reduced to liquid (P). Liquid (E) is slowly added to the rival in the opposite order. dynes (C) in the mixing device The results of the first test showed that the pre-emulsion is obtained. The reproducibility of the clockwise and counterclockwise rotation (P) was also mixed with the mixing hand of the clock was good. Only a slight high-intensity device (i.e. dispersion hysteresis was observed when increasing and the reduced Oiah 600 device with a rod 200). The stress-reducing except for the smallest readings, the preliminary emulsion is a liquid (5). Stress mixtures. Thus, a sample of demonstrative vitamin powder (i.e., nicotinamide, thiamine) destroys the thixotropic behavior only at low mononitrate, riboflavin, pyridoxine hydrochloride stress levels. At higher levels of naride, folic acid, and sorbitol) mix together spring (Z0Pa) struc within the limits of the liquid, it breaks down with ascorbic acid and lemon juice monohydrate. For the sample, it was obvious that the acid was diluted in a portion of water in the mixing device with a characteristic shift. high-intensity structure with a dispersive rod. The results of the second test showed that the liquid (H) The main thing is that for the stress that was applied and which sta- liquid (0) is cooled to about 25"C and the final is less than 0.8Pa (or for speeds less give liquid (C) and liquid (H). Mixtures of homogenization- than 1c7), the rotation speed fluctuated irregularly for 2 minutes in the mixing device nominally, which indicated structural changes within the range of high intensity with the dispersion rod, the sample, when the sample was sheared. taking care that air did not get into the Rheological characteristic showed the presence - mixture. The resulting mixture is poured into bottles and, thixotropy or time-dependent reduced - optional, hermetically sealed in atmospheric viscosity at low shear stress, which is ferric nitrogen. reversible. In other words, the emulsion demonstrates

The vitamin emulsion is homogeneous and smoothly gel-solid-gel properties. The second liquid yellow or orange syrup with osvi- test demonstrated the presence of structural biting citrus taste. Syrup has pH, 0-3.6, permutation at low stress levels and viscosity of 300-1000mPa.s and density of 1.16-1.23g/ml, possibility of fluidity. at 20"C. The diameter of all oil droplets in the emulsion is 2-5 μm. These results explain the excellent physical properties of the emulsion. stability of the emulsion and the presence of thixotropy

Study of the nature of the viscosity of the vitamin at very low shear stress (for example, emulsions were carried out using a device from the emulsion can be poured after a slight uphea- adjustable stress, which is called a bottle).

OK 200, from Kpeoteiigis Zsiepiyysie. The first test, Example 2 that was applied was the thixotropy loop test, Chemical stability where after setting the sample was left for 10 Stability studies were carried out with the aim of minutes. Then rotation along the arrow was carried out to determine the chemical resistance of the liquid multivitamin watch of the upper suspension, and at the same time, the high-volume product. The product was produced by applying stress from 0 to 40Pa for 10 minutes as described in Example 1. Two ports were prepared, then reducing it to OPa in the next 10 minutes of the product, which underwent a stability study. Lin After a period of immobility, which was 40 The following time was used to obtain minutes, the same sequence of actions, trials: however, they were carried out in the direction against the arrow of 20"C/relative humidity 0, W, 6, 12 and 19 months.

The second test that was used was the environmental stress test (ES): sponge stress, in which the sequence The following results for the vitamin content of the stress was programmed, firstly, after 18 months, for two portions, an increase and then a decrease were obtained tension, respectively, at 20"С/relative humidity of the insect. Each tension was constant throughout the medium: for a certain period of time. The tension that stagnated

O-o-stocopherol (moloml) | 60 | 55 | 630 | 6 | 99235 | vlb?2 | 2

Pamin (m//Omlu | 09 | 1095 | 099 | 096,097 | 97595 | 088089 | 895

Folic acid spot (mcg//Omlu | 75 | 2095 | 900 | 921922 | la | 714725 | giv

The initial value according to the analysis for retinol The products were analyzed for all vitamins is slightly too high due to the initial high level of knowledge, aroma, appearance, pH, setting at 10695 of the nominal value in the raw material. total number of viable microorganisms,

test for E. Soyya, antimicrobial effectiveness test. No delamination was observed in the stony preservation, potassium sorbate, viscosity, density, and even the average size of oil droplets or the microscopic picture (droplet size, dispers- the number of drops in the product samples taken from phase). hu, inside and at the bottom of any bottle that is

Thanks to the initial analysis, two portions were left to dry. meant that the vitamin content was very close to The average oil droplet size for the quarter-nominal amount, indicating that during several servings was in the range of 3.1-6.2 µm. There was no significant loss of activity during stack processing, but the average size of the oil droplets did not affect the vitamins. they claimed no difference between the freshly prepared ones

A lower limit for the vitamin content of servings and stored servings. for this product, it is 90905 from the specified number. The destruction of the emulsion and dispersion were not observed. It can be seen that within this limit the phase transitions in any of the samples tested and the vitamins are all right, demonstrating that there was no difference between the just excesses for vitamins are sufficient for their prepared portions and portions, that the shelf-life when stored for 18 years was checked in order to determine the stability at 2570 months at 20"C and relative humidity of the environment and relative humidity of 60905. environment. This confirms that the product is homogeneous

After the analysis after 18 months, it was determined that the dosage of lipophilic vitamins that miss all other physical, microbiological and sensorial requirements are in the dispersed phase of the product. met the list of specified requirements. Example 4

Example C Preparation of 5000 ml of liquid multivitamin

Physical stability of sugar syrup and mineral syrup.

Stability studies were carried out with the aim of determining the physical stability of a liquid multi-vitamin oil mixture of 17.5 g of a multi-vitamin composition. Two servings of the Pry-I-c-tocopheryl acetate 9600mg clade 2 product were compared with two freshly prepared servings of vitamin A palmitate 950mg. We analyzed four cholecalciferol concentrate 540mg products that were stored in their original packaging - in beta-carotene 20905 1500mg black polyethylene terephthalate bottles with a volume of beta-carotene 3090 3125mMg 50Oml. lecetin t52mg

Previously prepared portions were stored at vitamin powder mixture 34, 84g 257C and relative humidity 60965. nicotinamide 19.2g

The average size of oil droplets and homothiamine nitrate 1.60g emulsion geneticity was studied using a seed microscope (AchiozKor) with a 40-fold magnification. folic acid Z0Zmg

Photographs of the emulsions were taken with the help of an OiIutry5 OR 10 digital camera, and biotin 109mg, the droplet size was determined using the OIutriz OR software. ascorbic acid 14g

In order to study the homogeneity of the sodium ascorbate At, OZg emulsion, the following procedure was performed. iron sulfate 52.34 g

The liquid content of each bottle was poured into 50 doses of zinc sulfate of 36.88 g, 1 Oml. Bottles were not shaken before pouring potassium iodide 123mg individual doses of 10ml to form the most critical disodium pyrophosphate 74.06g tical situation for determining any non-homo-agar-agar 4.13g emulsion genity. The results are shown below. a mixture of galactomannans 17.34 g

Results: potassium sorbate 7.50g

The samples were examined under a microscope in order to determine the homogeneity of the contents on top, inside fructose 55g and at the bottom of each bottle. Purified water 2214 two separate measurements were performed on each microscopic invert sugar 3350g preparation on a glass slide, and it was determined that the diameter of oil droplets was 0.5μm and above. described in Example 1, except that

Samples of 10 ml from each bottle were examined for minerals included in this composition. Disodium pyrophosphate is visually determined in order to determine the presence of butyrate sulfate dissolved in a portion of water and added to the base film on the surface of the emulsion in each chemical solution at a temperature of 40-457"C. Sulphate glass. No presence of oleic iron, zinc sulfate and potassium iodide is added to the films in any chemical beaker being examined- the same basic solution when the temperature of li.falls below 4070.

All samples had a homogeneous appearance. The purpose of disodium pyrophosphate is to act as

A liquid emulsion of all four portions is easy and a complexing agent with respect to minerals. It is a mini-smoothly poured without the presence of any metallic aftertaste of minerals and prevents lumps. possible catalytic effect regarding the breakdown of unstable vitamins in solution.

Vitamin and mineral syrup has a pleasant taste of apricot, its viscosity is 400 - after 18 months, for two portions of the product, 1200 mPaes at 202C, density 1.19-1.23g/cm3 and ktu were obtained, respectively, at 20"C/relative humidity at the root 3iZ,o-3.5. of the excess medium:

Two portions of the emulsion were tested for stability as described in Example 2. Its results are shown in the table below.

Peche vo.) ol | hg | pam hek | vase | dead

Pyridoxine (m/eml) | 08 | 1095 | 088 | 0885087 | 99495 | 089,088 | here

Yodome/vmlu 0010101013100900, 55 1.946070

Zincim/emlui 777178 555 | 84 | 8 gva | lo25 | 8482 | about

The average indicators in this example were for the delodizer, 2) at 25"С and relative humidity as high as possible when compared with the composition of 6095 and 3) at 30"С and relative humidity of 60905.

Examples 1. This was due to the fact that the test tubes were examined for the presence of any lower limit for the vitamin content for the destruction or coalescence of the dispersed phase of this product was up to 10095 of the given number after 30 days. Samples were also examined for bone. You can see that with all the vitamins in this definition, did any syneresis occur. the border is all right, which demonstrates that selected Syneresis is a phenomenon that can occur in liquid excesses for vitamins are sufficient for the term formulations containing a gelling agent. It is believed that the shelf life during storage for 18 months is a consequence of changes that occur in the polymer 20"С and relative humidity of the surrounding sereti and which cause the shrinkage of the gel, leading to the release of a transparent aqueous phase, devoid of sta-

In fact, excesses for all vitamins can be gelling agents and thickeners. Samples, reduced to exactly the same levels that were selected in which demonstrate syneresis, change to nor-

Examples 1. Vitamin C is an exception, and its ultra-small homogeneous appearance, when the samples slightly excess should be 6095 with the fact that it is shaken or when the bottles are turned upside down, the amount was 10095 of the given amount downwards. the end of the shelf-life when stored, if the observa- Observations were recorded by digitizing at 20"C and the relative humidity of the ambient photographing the tubes in the cabinet from the regulatory environment. The excess in 2090 is sufficient light conditions. for vitamin Vig to provide a given amount In 5 test tubes different types of emulsifiers were introduced. This is at the end of the shelf life (18 were I shgokU Eb8 or RoIochateg 188 from VABEF, months). Roiuzograie 80 from Og. MU. Kor AS, Retshep, which is

All other physical, microbiological and sensorial polyacrylic acid polymer from ВЕсСооагисп requirements met the list of specified requirements when Zresiaiu Spetis!5, Tego5e 1500, which is a steara- were analyzed after 18 months. volume PEG-6 by Satset5zze and RishgoYi! Zieagidne UM.

Examples 5, 6, 7, 8 and 9: Variations of emulsifier 1009, which is a distearate of poly-glyceryl-b from

The cooking method described by Saketsuze was used. in Example 1. The initial viscosity was recorded, the emulsifier was distributed between the oil phase, the average size of the oil droplets and the outer and water phase in order to promote the process of dis- appearance. persia and emulsification. 100 mg emulsifier disper

The compositions were poured into amber glass bottles in the aqueous phase in the case of examples 5, 6, 8 of the same color with a volume of 200 ml and in tubes of transparent and 9, and 500 mg were added to the aqueous phase in the case of the glass, which were closed with lids. The bottles and test tubes of Example 7 were placed under the following conditions: 1) at 7"C and the composition and results of the analysis are given below. relative humidity of the surrounding environment in the

determining whether any syneresis occurred.

Iinrdedient- /| . | 5 | 6 | 7 | 8 | 9 | Syneresis is a phenomenon that can occur in liquids - it is a consequence of changes that occur in polymer bio 2.82 | 2.82 g 2, in 2g | 2.82 g 2.82 g those; tocopheryl acetate, , , , , mesh and which cause the gel to shrink, leading to the release of a transparent aqueous phase devoid of sta-; which demonstrate syneresis, change to nor-

Triglycerides from serie zmo | goodbye | zvomg | goodbye | 360 mg by the bottom chain of a small homogeneous appearance when the samples are slightly shaken or when the bottles are turned upside down

Popisorbate 80 zam --2Ш2Ш231--52З-ЛН8-- Observations were recorded by digital

Roiochateg 188 Ho Tzom 3 З831ИЗШШЗ31353531 of photographing test tubes in a cabinet with regulation

Retiivp TV-2 chinchilla stitched light conditions.

Rishgo! likely | GG zom | In four test tubes, different types of gel-inducing 1500 shin shi shi Ш Ш Ш EE ruminators were introduced in combination with a mixture of galactomannans, such as Seisaipp ОО 3252, which is iota-carrageenan

Pyridoxine about avome | 4vomg | 45 ohm | 45 ohm | 459 mg | from EMS Vioroiuteg, Rgoiapai! GE 120M, which is sodium alpnate also from HMS Bureauuteg ve iamine nitrate MG MG MG MG MG pectin IIM-5 C5, which is a low-esterified pectin! ' and tinom from SR Keiso and Keisodeya! I-T 100, which is highly acylated gellan gum from Te 1.23vg | 1.236g | 1.236g | 1.236g | 1.236g Myshgabzheyi Keiso Sotrapu. 100 mg of emulsifier 16.89) 16.89) 16.89) 16.89g ) 16.89g was dispersed in the aqueous phase in all samples.

The following modifications of the method were carried out with bit 7095 in order to dissolve the gelling agent and to promote controlled gelation. Small - 10.44 | 10.44 g 10.44 | 10, | 104g of the amount of calcium ions (0.5-1.2MM Ca") was added to

Sorbitol powder 1 3361 3361 3361 3361 336 but This is mandatory for the purpose of promoting oleugenesis

Lemon monohydrate. t 12.18 g | 12.18g | 12.18g | 12, and 18g | 12.18 g of yum in the composition of gellan gum.

Purified water: |3000ml|3000Oml | 3000 ml | 3000 ml | 3000 ml of Seisahip OS 3252 was heated in a portion of water until

Viscosity (mpe-o) 1050 ) 1050 702 where it dissolved. Prepared the second portion of the average size

The average size of sorbitol, potassium sorbate and calcium chloride particles and salt droplets (µm) 3.8 ze 4 30 3.7 two solutions were mixed together at a temperature that exceeded 702C after 30 days. Regulated gel formation

I and I occurred when liquid sorbitol was added and when

It can be seen from the results that all portions contained di- the temperature dropped below the temperature of the gel-disperse phase with a satisfactorily low formation value (60-702С) for iota-carrageenan. medium-sized drops (in the range of 1-5 μm). Rhoiapai! GE 120M was dissolved in a portion of water at

Examples 5-9 all demonstrated satisfactory room temperature and mixed solution stability at all temperatures after 30 nm of thickener as described above. Regulated he- days. The average diameter of their oil droplets leuformation occurred when the two solutions were mixed and we also obtained no evidence of emulsion breakdown or syneresis due to the subsequent addition of liquid sorbitol. in any test tube with samples. Sepi-pectin GM-5 C5 is low-esterified

Examples 10, 11, 12 and 13: Variants of fast-acting geleutopectin with high calcium reactant | And that ability. The gelling agent was heated in portions

We used the method of preparation described in water together with calcium chloride to the temperature in Example 1. The initial 902C values were recorded. The thickener solution was added as described in : their : viscosities, average oil droplet size, etc., and gelation started when the tempera- appearance. | ture decreased due to the addition of liquid sorb-

The compositions were poured into amber glass bottles. of the same color with a volume of 200 ml and in test tubes with transparent KeisodeI GT 100 detects the gel-forming glass, which were closed with lids. Bottles and test tubes effect at very low quantities in the presence of . oh . placed under the following conditions: 1) at 77C and mono- or divalent ions. The gelling agent was added to the relative humidity of the environment in the heater in a portion of water up to 902С, and the thickener was added, where and to the refrigerator, 2) at 25 (o: and relative humidity, as in Example 10. The obvious gelling agent- 6090 and 3) at 30 "C and a relative humidity of 6095. this effect was observed when the temperature / The test tubes were examined for the presence of any decreased due to the addition of liquid sorbitol. destruction or coalescence of the dispersed phase. The compositions and results of the analyzes are given below - after 30 days. The samples were also examined in order to che.

refrigerator, 2) at 252C and relative humidity

Vitamin oil di I I PO PI 6095 and 3) at 302C and relative humidity 6095.

PI sato-tocopheryl acetate Y The test tubes were examined for the presence of any destruction or coalescence of the dispersed phase

Hopecalcium concentrate! earth | earth | earth | wemg | after 30 days. The samples were also examined for ferrol and to determine if any syneresis had occurred.

Glycerides With an average zvome | will call | zvomg | zvomg | Syneresis is a phenomenon that can occur in liquid formulations containing a gelling agent. They believe that

Beta-carotene suspension is the result of changes that occur in the polymer

zoo meshes and which cause the gel to shrink, leading to the release of a transparent aqueous phase devoid of 10000100 bilising gelling agents and thickeners. Samples showing syneresis change to a normal homogenous appearance when the samples are shaken slightly or when the bottles are turned upside down. !

Observations were recorded by digital 1.23bg | 123bg | 1236 | 1.236g of taking photos of test tubes in a cabinet with adjustable 16.89 | 16.89 | 16.89 g | 16.89 g under the given light conditions.

Three tubes were used for research

Non-crystalline sorbitol! . Y. another 7095 2.1Zkg | 2.1 Zkg | 2.1 Zkg | 2.13 kg of different types of thickener in combination with agar-agar.

Seisagip OO 3252 pet shi SHY PO The three thickeners used were Keigoi!

Rgoiapaig120M | | from | | | RO, which is a hapipap polysaccharide from KeiYiso OK Tsa,.,

Oelispectin has c5 MZ-A - 5,900 tvo Madapii from Adgisaiez (4. and a combination of acacia tree gum and hapitap polysaccharide. 1 bOmg of the emulsifier was dispersed in the aqueous phase in all samples.

Compositions and results of analyzes are given below 12 hours 12vg zoboml | Zoboml | 30 boml | zoboml brsmnna oil the amount of GH drops (μm) through 30 2.7 3.4 ze Triglycerides 3 medium chain

In all examples for 10-13, which included various Beta-Carotene Suspension 3096! 1740 mg | i40mg | 140 mg of gelling agents and galactomannan thickener obtained excellent emulsions with a viscosity in the range of 300-1000 mPas and an average particle size of the dispersed phase in the range of 2 µm.

All of Examples 10-13 demonstrated excellent stability with respect to the average size or breakdown of the emulsion in the two formulations containing carrageenan and pectin, respectively. Composition that weighs 16.89g 16.89g 16.89g tive gelan gum, began to demonstrate at 30"C. The formulation containing sodium alginate demonstrated signs of emulsion breakdown and syneresis in Kos in 1544. Igadapium gum both at 25"C and at 30"C. This can to be a consequence of unsatisfactory gelation, resulting in an inhomogeneous granular gel.

Examples 14, 15 and 16: Variants of thickeners Y Zbbbmy 1 Zbbbmp 1 Zbbbmy

The method of preparation described was used (Viscosity 00000000 tomPas vvomPa-s | 111omPa-s in Example 1. The indicators of the initial viscosity, the average size of oil droplets and the appearance of droplets (μm: Average size of oil!) were recorded. drops (µm) after 30 days 21 3.7 2.6

The compositions were poured into amber-colored glass bottles with a volume of 200 ml and into tubes made of transparent glass, which were closed with lids. Bottles and test tubes results regarding viscosity and average dis- . relative humidity of the environment in the zone of 600-1100mPas and 2-5μm, respectively.

Stability results after 30 days for three temperature readings. Some syneresis

Examples 14-16 demonstrated an excellent sta- occurred for the composition containing 2095 oil phase pain in relation to the average droplet size, and in all three samples. Syneresis, which we observed no evidence of destruction, disappeared when the bottles were slightly shaken. emulsion or syneresis at any temperature - Examples 19, 20 and 21: Spray drying. of liquid emulsions

Examples 17 and 18 Liquid emulsion (A)

The method of preparation described in Example 1 was used. Initial viscosity, average oil droplet size, and appearance were recorded. vitamin A palmitate, 1.7 mln. IU/g 1.20 mg

The compositions were poured into glass bottles of amber-colored cholecalciferol concentrate with a volume of 200 ml and into tubes of transparent 1.0 ml. MO/g 0.24mMg of glass, which were closed with lids. Bottles and tubes of nicotinamide 17 bmg were placed in the following conditions: 1) at 7"C and thiamine nitrate 1.28mg relative humidity of the environment in riboflavin 1.32mg refrigerator, 2) at 25"C and relative humidity pyridoxine hydrochloride 1.32mg 6090 and 3) at 30"C and relative humidity of 60905. cyanocobalamin 3.75 mg

The test tubes were examined for the presence of any ascorbic acid 78.0mg destruction or coalescence of the dispersed phase dexpanthenol 4.31mMg after 30 days. The samples were also examined to sodium benzoate 15.0mg determine whether any syneresis had occurred. sucrose 6500 mg

Syneresis is a phenomenon that can occur in liquid invert syrup 70905 1720mg formulations containing a gelling agent. It is believed that agar 31.3mMg it is the result of changes that occur in the polymer gum igadapiy 25.0mg mesh and which cause gel shrinkage, causing lecithin 1.58mg to release a clear aqueous phase devoid of sta- peanut oil 0.98mg bilising gelling agents and thickeners . Samples citric acid monohydrate 46.9mMg that show syneresis change to a normal orange oil 15.0mg small homogeneous appearance when the samples are slightly orange concentrate 97.5mMg shaken or when the bottles are turned with their neck rosehip fruit extract 85.0mg down. malt extract 200 mg

Observations were recorded by digitally photographing test tubes in a cabinet with regulated light conditions. mg or

The tests were carried out with test tubes, each of which contained a lipophilic drug and O-o-tocopheryl acetate 11.0 mg of an oil phase consisting of 5 or 2095. Medicinal palmitate of vitamin A, 1.7 mln. IU/g 1.20 mg agent, which was chosen as an example, was carbama - cholecalciferol concentrate, zepin. 1.0 million IU/g 0.24 mg

The composition and results of the analyzes are given below. thiamine nitrate 1.28 mg riboflavin 1.32 mg pyridoxine hydrochloride 1.32 mg cyanocobalamin 3.75 mg; ascorbic acid T8, Omg dexpanthenol 4.31 mg sodium benzoate 15.0 mg lactose 2000 mg

Polysorbate 8b0. dream 5 bbmg | 500mg aspartame 5.BMg agar Z1.3Mg igadapi gum 25.0mMg peanut oil b.avm citric acid monohydrate 16.μm ' ' orange concentrate 97.5mMg after 30 days (μm ' ' malt extract 200mg

Both Examples 17 and 18 showed purified water (C tosoMmg) satisfactory stability with respect to the average particle size. The composition containing 595 oleic O-o-tocopheryl acetate 9.39 phase was homogeneous and no degradation was observed. emulsion or syneresis with palmitate of vitamin A, T, 7 million IU/g, 1 mg cholecalciferol concentrate, 0.3 mg

1.0 million MO/g of emulsions (A), (B) and (C) were stored at room temperature in dry conditions. thiamine nitrate 1.22mg In order to restore emulsions, concentrates of riboflavin 110mg of emulsions (A), (B) and (C) are suspended in 4 g of purified pyridoxine hydrochloride 1.53mg of water. folic acid 90.Omkg Example 25 ascorbic acid 56.3mMg Preparation of liquid emulsion containing lidexpanthenol 412mM folinic medicinal substances Composition: potassium sorbate 7.00mg Ingredients maltodextrin 1000mg probucol 6b, aspartame 2.5Mg long-chain triglycerides (co- agar 8.12mg eva oil) 137g galactomannan mixture 34 8mg beta-carotene suspension 30905 1g lecithin 1.60mg polysorbate 80bg triglycerides, medium chain 1.20mg agar 1.83g citric acid monohydrate 40bmg potassium sorbate 2y1g orange oil b6.90mg polysorbate 80 500mg purified water 4350mg galactomannan mixture 7.83g

Emulsions (A), (B) and (C) were prepared as described - non-crystalline sorbitol 7090 2.13 kg but in Example 1. sorbitol powder 33.6 g

Emulsions (A), (B) and (C) were spray-dried Etypor 100mg in a laboratory device for citric acid dismonohydrate 12.18g spray-drying Mori! Mipog (Migo M5, Denmark). purified water up to: 300 Oml

The drying device works in one direction. The composition is prepared by a method similar to the centrifugal atomizer and the flow of the drying sob of Example 1, while the probucol is dissolved in air at a productivity of about 135 in the oil phase by applying ultra- kg/hour. The temperature of the intake air is static. vit 120"C, the temperature of the exhaust air is maintained at 75"C, and the speed of rotation Preparation of a liquid emulsion containing lividdent sprayer is 31,000 obe-pophilic medicinal substances Composition: mouths per minute. During spray drying, the crystals of the solid carrier are introduced into the zone of spray-diazepam 3, bologization. After spray-drying, medium-chain triglycerides 140 g of the emulsion are stored at room temperature in dry conditions. The relative humidity polysorbate 80 bg of the room where the process of spray-agar 1.83g spray drying takes place, and the inlet air that enters the spray drying device is polysorbate 80 500mg so low that the emulsion could be a mixture of galactomannans 7 .83g to dry so that the water content in it is less non-crystalline sorbitol 7090 2.13kg 195 by weight. sorbitol powder 33.6 bg

In order to restore the emulsion, the emulsion concentrates (A), (B) and (C) are suspended in approximately 12.18 g of citric acid monohydrate and 4 g of purified water. purified water up to: 300 Oml

Examples 22, 23 and 24: Freeze-drying - The composition is prepared by a method similar to the preparation of liquid emulsions of Example 1, while diazepam is dissolved

Emulsions (A), (B) and (C) underwent drying in the oil phase by applying ultrasound in a laboratory sonic drying device. freezing-drying devices Example 27 SOZ8 (Neo, Denmark). Emulsions were poured into Preparation of liquid emulsion containing li- test tubes (one ml in each test tube). Test tubes of disintegrating medicinal substances were placed on shelves in a drying device and emulsions were frozen to minus 807С Ingredients and stored at this temperature for 5 hours. Primary drying is carried out by keeping triglycerides with a long chain of belching emulsions for 72 hours at a pressure (soybean oil) of 143 g 0.04 hPa, a storage temperature of minus 557 C and a temperature of minus 90 "C in the evaporator. Secondary drying - polysorbate 80 bg is carried out by increasing the pressure to agar 1.83 g 0 1 hPa and increasing the temperature of holding potassium sorbate 21 g to 25 "С. The duration of secondary drying is polysorbate 80 500 mg 12 hours. Freeze-drying of a mixture of galactomannans 7.83 g was stopped by ventilating the drying chamber with dry non-crystalline sorbitol 7090 2.13 kg nitrogen. After freeze-drying, 33.6 g of sorbitol powder concentrate

Etsure 100mg citric acid monohydrate 12.18g agar 1.83g purified water to: 300Oml potassium sorbate 2y1g

The composition is prepared according to a method similar to the polysorbate 80 50 ОмМг sobu of Example 1, while danazol is dissolved in a mixture of galactomannans 7.83 g in the oil phase by using ultrasound. non-crystalline sorbitol 7090 2.13 kg

Example 28 sorbitol powder 33.6 g

Preparation of a liquid emulsion containing Li-Etsure 100 mg polyphenolic medicinal substances Composition: citric acid monohydrate 12.18 g

Ingredients purified water up to: 300 Oml halofantrine base 15.0 g The composition is prepared according to a method similar to the long-chain triglycerides of Example 1, while halofantrine (soybean oil) 128 g is dissolved in the oil phase by using ultra-suspension of beta-carotene 30905 1 year of education. polysorbate 80 bg

Computer typesetting by T. Chepelev Signature Circulation 26 approx.

Ministry of Education and Science of Ukraine

State Department of Intellectual Property, str. Urytskogo, 45, Kyiv, MSP, 03680, Ukraine

SE "Ukrainian Institute of Industrial Property", str. Glazunova, 1, Kyiv - 42, 01601