RU2288594C2 - Method of preparing powderlike water-soluble sparkling composition (options) - Google Patents

Abstract

FIELD: food and chemical-pharmaceutical industries.

SUBSTANCE: invention concerns preparation of quick-dissolving powders, granules, and tablets of drugs, biologically active additives, and dry drink concentrates. Method provides for mixing initial powderlike acidic and carbonate components. Acidic components are selected from solid water-soluble acid, solid acid salts, and mixtures thereof. Carbonate components are selected from alkali and alkali-earth metal bicarbonates, carbonates, basic carbonates, and mixtures thereof. Mixture of initial powderlike components are subjected to mechanical treatment by way of percussion-cutting action to form agglomerates of disintegrated particles of treated components 30-300 μm in size. Alternatively, mixing of all above-mentioned components may be performed simultaneously with mechanical treatment in the same manner to form agglomerates 30-300 μm in size.

EFFECT: enabled preparation of compositions stable on storage, which does not separate into initial substances during further processing.

12 cl, 10 dwg, 2 tbl

Description

The invention relates to food and chemical-pharmaceutical industries and for the production of instant powders, granules and tablets of medicines (PM), biologically active food additives (BAA) and "dry" beverage concentrates.

In recent decades, a significant part of drugs and dietary supplements is available in the form of instant, so-called "effervescent" tablets, granules and powders. Before taking these drugs are dissolved in water with intense release of carbon dioxide (hence the term "effervescent") and are used in the form of a carbonated drink. This form of release allows you to increase the effectiveness of drugs and dietary supplements and avoid some undesirable side effects during their use.

Typically, these products are multicomponent mixtures of solids containing biologically active and medicinal substances for the intended purpose, "effervescent" composition, as well as technological and flavoring additives. The "effervescent" component interacts vigorously with water, releasing carbon dioxide, which ensures the disintegration of the tablet or granules and creates favorable conditions for the formation of a solution of the active ingredients. The "effervescent" composition includes at least two solids - a metal carbonate or bicarbonate, as well as an organic solid water-soluble acid or its acid salt. During hydration, these substances enter into a neutralization reaction, accompanied by gas evolution.

Upon receipt of "effervescent" tablets, granules and powders, it is necessary to combine at least two rather conflicting requirements:

1. To provide high reactivity of acidic and carbonate components during hydration of the compositions;

2. Ensure the chemical stability of the compositions during their preparation and storage.

The first task can be solved if you create the most developed contact of the solid phases of the reagents (carbonate and acidic), or use highly soluble solid reagents (at least one of them). To solve the second problem, it is necessary to achieve thorough removal of free water from the finished compositions and to prevent its ingress during storage.

In the known technical solutions for the preparation of "effervescent" compositions, four main approaches are used:

1. Acidic and carbonate components are separately mixed with excipients and granulated or encapsulated in a wet manner. Then, the obtained two types of granules (capsules) are mixed with each other and tableted, or used in a mixture [1, 2].

2. Acidic and carbonate components are mixed and moistened with a small amount of water or alcohol. After the start of the neutralization reaction, avoiding intense interaction, the mixture is quickly dried and granulated. Further, it can be tabletted, etc. [3-8].

3. Acidic and carbonate components are incorporated into an inert water-soluble matrix or coated with an inert water-soluble substance, and then mixed with each other. Further, tableting, etc. is also possible. [9-13].

4. Acidic and carbonate components are mixed together with auxiliary substances and active components without adding moisture, then the mixture is tableted or subjected to “dry” granulation [14-17].

The choice between different methods depends on the reactivity of the carbonate and acid components, the physicochemical properties of the target biologically active substances, and the desired characteristics of the final product. Thus, the bicarbonates and carbonates of alkali and alkaline earth metals used as carbonate components have different solubilities and react with acids at different rates. Of these, the most reactive are potassium and sodium bicarbonates, and "the least active is calcium carbonate, practically insoluble in water. Acids and acid salts also vary in solubility and activity. In cases 1 and 3, highly reactive components - sodium and potassium bicarbonates are most often used. as well as citric, ascorbic and tartaric acids, in case 2 - active acid (citric) and insoluble calcium carbonate.

The disadvantage of processes 1-3 is multi-stage, the need to use a fairly wide range of technological equipment, low productivity of equipment for granulation, discreteness of technological processes, high cost of equipment. For example, drying the moistened mixture according to claim 2 should take place in a vacuum. It is possible to delaminate granules and powders of different compositions (processes 1, 4) during technological operations to obtain finished products, as well as during storage. In the used technological equipment, it is very difficult to completely remove moisture during drying, which negatively affects the stability during storage of the finished composition. In all cases, the resulting compositions are overloaded with auxiliary substances - granulating agents, fillers, binders.

Process 4 can be used only for water-soluble carbonate components (bicarbonates) and chemically stable target active substances and requires dilution of the "effervescent" components with a large (> 50%) amount of filler.

An analogue of the present invention is [4] (US Pat., Effervescent composition and method of making same, US 4,678,661, publ. 05.21.1986, Cl. A 61 K 033/10), describing a method for producing an "effervescent" composition, including solid organic acid (e.g. citric acid), calcium carbonate and sodium or potassium bicarbonates. To obtain a composition, acid crystals are moistened and mixed with much smaller particles of calcium carbonate. There is a “dusting" of large particles of acid with small particles of carbonate, accompanied by a partial interaction. The resulting composition is dried and, if necessary, sodium and potassium bicarbonates are added, which accelerate the interaction with the acid during hydration, as well as auxiliary substances, also under pre-wetting conditions followed by drying. The disadvantage of the prototype invention is the multi-stage process, including the operation of wetting, mixing, drying, as well as restrictions on the particle size of the powders of the starting components. In this case, the composition is dried under relatively mild temperature conditions to avoid a thermal reaction between the acid and carbonates. As a result of this, complete removal of moisture does not occur, which negatively affects the stability of the composition during prolonged storage under normal conditions.

The closest analogue selected for the prototype of the present invention is [17] (US Pat. RF No. 2189228, "Pharmaceutical composition in the form of effervescent soluble tablets and a method for its preparation" publ. September 20, 2002, class A 61 K 9/46, A 61 K 9/20, A 61 K 31/714, A 61 K 31/60, A 61 K 31/375, A 61 K 31/7004, A 61 K 31/195, A 61 K 31/095), describing the method of obtaining "effervescent" soluble tablets containing a therapeutic agent in combination with a biologically active substance, sodium bicarbonate, citric acid, frame material, binders and filler. The method includes operations of mixing, sieving, tabletting, characterized in that all operations are carried out at low humidity in the range of 5-30%. The disadvantage of this method is the congestion of the composition with excipients - at least 70% by weight. Another important disadvantage is the possible delamination of the components of the mixture during its transportation and handling before tableting.

The objective of the present invention is to develop a new method for producing "effervescent" compositions with the following advantages:

- reduction in the number of technological operations;

- reduction in the amount of excipients;

- simplification of technological equipment and increase productivity.

The final technical result is the reduction in the cost of the compositions and the creation of improved consumer characteristics.

The problem is solved thanks to the claimed method for producing a powdery water-soluble effervescent composition based on solid water-soluble acid or solid acid salts or a mixture thereof — acidic components, as well as bicarbonate, carbonate or basic carbonate of an alkali or alkaline earth metal, or mixtures thereof — carbonate components, including mixing the initial powdery components, characterized in that a mixture of the original powder components, including the required amount of excipients purpose substances is machined by impact and abrasive agglomerates impacts to ground particles treated component size 30-300 microns.

The above acidic and carbonate components, as well as excipients, adjuvants — water-soluble polymers and / or cyclodextrins that do not chemically interact with the above components — are taken as a mixture of the starting powder components.

The above acidic and carbonate components, as well as water-soluble medicinal and biologically active substances, dry extracts that do not chemically interact with the above components are taken as a mixture of the starting powder components.

The above acidic and carbonate components, as well as medicinal and biologically active substances capable of forming water-soluble salts with metals of carbonate components or residues of acidic components, are taken as a mixture of the starting powder components.

The above acidic and carbonate components, as well as medicinal and biologically active substances capable of forming water-soluble complexes with excipients, are taken as a mixture of the starting powder components.

As a mixture of the starting powder components, the above acidic and or carbonate components are taken, as well as vitamins, carbohydrates, amino acids, sweeteners and flavorings.

The mixture of all the components indicated in the previous ones occurs simultaneously with their mechanical processing by impact-abrasion effects.

The basis of our invention is the phenomenon of aggregation (agglomeration) of particles of solids discovered by us under intensive mechanical treatment by impact-abrasion, for example, in ball mills [18]. Moreover, if a mixture of various powdered substances is processed, then the initial particles are ground first and then aggregated to form agglomerates of a composite composition. Thus, it is possible to obtain a solid dispersed system of substances - reagents prepared for accelerated interaction under the influence of external influences, in particular during hydration. In the present invention, we use this aggregation phenomenon to produce effervescent compositions of water-soluble solid acids (or their acid salts) and metal carbonates and bicarbonates. For this, mixtures of these substances are subjected to mechanical treatment by impact-abrasion in mills, where there is a simultaneous mixing, grinding and afegration of crushed particles of the starting components. Not only two substances can be used - one acid and one carbonate - but also any solid multicomponent mixtures of different acids and carbonates. As a rule, solid organic acids of "food" purpose are used as acids - citric, malic, succinic, glutamic, grape and ascorbic, etc. However, it is possible to use solid inorganic acids and, in particular, their acid salts. It is desirable that the solubility of the acid and carbonate components of the salts formed after the neutralization reaction exceed the solubility of the starting materials. If necessary, the introduction of auxiliary substances - sugars, polysaccharides, soluble polymers, flavors, etc. The starting material powders can have particle sizes of up to several millimeters. In the following examples, their particle sizes are of the order of 10 ² microns, see FIGS. 1-6. As a result of machining, a polydisperse powder is formed with particle sizes from ~ 1 to 300 microns, see Figs. 7-10. Large particles (30-300 microns) are mainly composite agglomerates of smaller particles. In this case, the fraction of unmilled crystalline particles of the starting materials is acceptable (~ <25% by weight). The fine fraction mainly consists of non-aggregated ground particles of the components. The fraction of large particles (30-300 microns) contains at least 50% of the calculated mass of the powder.

Due to the formation of strong particle agglomerates, the resulting powder is not subject to delamination into the starting components during storage, refusal, and tabletting. At the same time, due to aggregation (sticking together) of acid and carbonate particles, their accelerated interaction during hydration is ensured with the formation of solutions of the corresponding salts. In fact, the neutralization reaction proceeds simultaneously with the dissolution process, significantly accelerating the latter due to the equilibrium shift of the solid phase-solution:

solid phase ← → solution → neutralization reaction → products

In the case of dissolution of the “non-agglomerated” mixture of reagent powders, the particles are individually dispersed in water and the neutralization reaction occurs in the volume of the solution. In this case, sparingly soluble components precipitate, their dissolution in the absence of intensive mixing takes a considerable time. Under conditions of a close arrangement of soluble particles in their composite agglomerate, a higher concentration of interacting substances is ensured, the neutralization reaction is accelerated, and, therefore, their dissolution rate increases. In addition, particles of carbonate and acid components dissolve almost simultaneously, regardless of their initial solubility in water.

The machining process is carried out without adding water, in "dry" conditions. It is advisable to use substances that do not contain crystallization water, since it may be released in the processes of preparation and storage of compositions. It is also desirable to use acids and acid salts having a melting point of at least + 100 ° C, which ensures the grindability of these substances. However, if refrigerated mills are used, this limitation is not significant. During machining, a partial solid-phase neutralization reaction between the acidic and carbonate components can occur in the particle contact zone. However, the depth of this interaction should be small in order to avoid the release of water.

The obtained powdery "effervescent" compositions can be mixed with other substances of the intended purpose and used in a dosage form - "sprinkling" of powders and granules, as well as tablets.

The storage stability of the resulting effervescent compositions is reduced if crystallization water is present in the composition of the substances used. On the other hand, stability increases in a row: alkali metal bicarbonates - alkali metal carbonates - alkaline earth metal carbonates. In a similar way, the rates of direct solid-phase mechanochemical reactions of the interaction of acids and the corresponding carbonates change (decrease).

The molar ratios of acidic and carbonate components can vary over a wide range, with the pH of the aqueous solution of the compositions varying from acidic to alkaline. However, when insoluble carbonates are used in the composition of carbonate components, incomplete solubility of the composition is possible due to a lack of ratio of acid components

The resulting powdery composition can be mixed with other components for various purposes, subjected to "dry" granulation, tableted by direct compression, or used in dosage form. During hydration of the compositions, the carbonate and acid components react rapidly with their simultaneous dissolution, accompanied by abundant evolution of carbon dioxide. In this case, there is also a quick dissolution or dispersion in the solution of other substances - medicinal, biologically active or flavoring and other additives introduced into the composition.

To improve the wettability and accelerate the dissolution processes of the compositions, additives of solid water-soluble polymers of the classes of polyvinylpyrrolidone, polyethylene glycol, polyethylene oxide, water-soluble cellulose ethers and oligosaccharides, including cyclodextrins. These substances are mixed with acidic and carbonate components before they are machined or can be added to an already prepared effervescent composition.

The composition of the compositions can be introduced water-soluble medicinal and biologically active substances, amino acids, vitamins, sweeteners and flavorings, as well as dry extracts. In this case, an increase in the dissolution rate of these additives due to the intense dispersion of the mixture during gas evolution due to the interaction of acidic and carbonate components will also be achieved.

The composition of the compositions can also be introduced sparingly soluble drug or biologically active substances of acidic or basic nature - forming water-soluble salts with acidic residues of the acidic components or with the corresponding metal ions of the carbonate components. In the case of the acidic nature of the additives, an excess (relative to the stoichiometry of the interaction of the acid and carbonate effervescent components) of the carbonate components should be used. In the case of the basic nature of the additives, an excess of the acid component is required. In general, the balance of acidic and basic components is selected in order to achieve complete dissolution of the corresponding additives.

The composition of the compositions can also be added sparingly soluble medicinal or biologically active substances - forming water-soluble complexes with polymers used as adjuvants (see above). During the dissolution of the "effervescent" composition, intense dispersion and mixing of the components will occur, contributing to the accelerated formation of the above water-soluble complexes. This will ensure the dissolution of sparingly soluble additives.

The mixing operations with the above additives can be carried out simultaneously with the process of obtaining the composition, i.e. at the stage of machining. This method is applicable for discrete-action mills, when the required quantities of powdered starting materials are loaded into the mill’s working volume and their mechanical processing occurs, accompanied by mixing, grinding and the formation of agglomerates of ground particles. In the case of using continuous flow mills, thorough preliminary mixing of the initial powders is required to obtain a product with a uniform composition.

As apparatuses for machining, ball rolls, planetary, vibrational, vibrocentrifugal, etc. can be used. mills with shock abrasion. It is possible to use grinding media other than balls. The process scales from ball roll laboratory mills with a load of 20 g to flow vibrocentrifugal mills with a capacity of up to 100 kg / h or more [19]. There are no special requirements for controlling the humidity of the premises, since the substances are processed in the sealed internal volume of the mills. In all cases, the process is carried out in virtually one stage, does not require expensive equipment and is easy to implement. The specific parameters of technological processes depend on the physicochemical and physico-mechanical properties of the components used.

The effervescent compositions obtained according to our invention can be used without additives (based on ascorbic, citric or succinic acids, etc.), as well as when mixed with medicinal substances, vitamins, amino acids, sugars, dry extracts, flavorings and sweeteners, etc. .d. for the production of medicines, dietary supplements and food products (dry drinks) of a wide spectrum of action.

Thus, our proposed method allows us to achieve previously stated advantages, compared with the prototype and analogues.

In relation to the selected prototype, the claimed technical solution has a combination of distinctive essential features set forth in the claims and allowing to solve the problem. Therefore, the claimed technical solution meets the criterion of "novelty" according to the current legislation.

Information about the fame of the distinguishing features in the totality of the features of the known technical solutions with the achievement of the same positive result as the proposed method, is not available. Based on this, we can conclude that the claimed technical solution meets the criterion of "inventive step".

The proposed method is as follows.

Table 1 shows the compositions of "effervescent" compositions based on various acids, their "acidic" salts, metal bicarbonates and carbonates, as well as their mixtures in various ratios. In all cases, the compositions were obtained by machining by impact-abrasion in a ball roller mill for 1-3 hours before the formation of agglomerates of crushed particles of components with a size of 30-300 μm, observed under an optical microscope.

Microscopic studies showed that the starting materials are powders of crystal particles. However, after machining by impact-abrasion, agglomerates of 30-300 microns in size are formed. Micrographs of some of the starting powders and the resulting effervescent compositions described in Table 1 are shown in FIGS. 1-10.

Comparison of X-ray diffraction patterns indicates the presence in the obtained "effervescent" compositions of crystalline phases of only the starting materials.

The dissolution of 1 g of the compositions in 200 ml of distilled water at + 20 ° C took place over a period of several seconds to 5 minutes with the formation of a clear solution.

At the same time, the dissolution of similar in composition mixtures of components preliminarily ground under similar conditions occurred significantly (5–10 times) more slowly and often required intensive mixing. So, when using calcium and magnesium carbonates in their composition, these substances precipitated and their dissolution in the absence of mixing required several hours.

Table 2 shows the compositions of "effervescent" compositions, including additives:

- auxiliary substances - adjuvants (polyvinylpyrrolidone, cyclodextrin);

- biologically active and medicinal substances, soluble in water (paracetamol, licorice extract);

- biologically active and medicinal substances capable of forming water-soluble salts with metals of carbonate components or residues of acid components (indomethacin, azaleptin);

- biologically active and medicinal substances capable of forming water-soluble complexes with water-soluble polymers and cyclodextrin (bufenox, sibazon);

- vitamins, carbohydrates, amino acids, sweeteners and flavorings (ascorbic acid, fructose, glutamic acid, glycine, sodium saccharin, acesulfame, dry fruit flavoring).

All the compositions shown in table 2 were also obtained by machining by impact-abrasion in a ball mill for 1-3 hours.

Similarly to the compositions of table 1 and the figures 1-10 after mechanical processing by impact-abrasion, agglomerates of 30-300 microns in size are formed. Comparison of X-ray diffraction patterns also indicates the presence in the obtained effervescent compositions of crystalline phases of only the starting materials.

The dissolution of 1 g of the compositions in 200 ml of distilled water at + 20 ° C took place from 1 to 10 minutes with the formation of a clear solution.

At the same time, the dissolution of similar in composition mixtures of the components preliminarily ground under similar conditions occurred significantly (> 5–10 times) more slowly and required intensive mixing. So, when using poorly soluble or water-insoluble components in their composition, these substances precipitated and their dissolution in the absence of mixing required several hours.

In all the examples cited, the powders of the starting components were weighed and loaded into a ball mill drum. A homogeneous mixture of powders was formed at the initial stage of machining, namely in its first minutes. Thus, when using discrete action mills, it is not necessary to pre-mix the powdered components.

When using flowing mills, the material continuously fed into the grinding zone must be constant in composition. Simultaneous continuous dosing of several powdered components with the required high accuracy is practically inconvenient and difficult to implement. Therefore, it is necessary to carry out preliminary thorough mixing of the components, which is a separate technological operation. Then, the mixture already obtained is fed into the mill’s working volume with the necessary speed. We also implemented this method. For this, 19.48 kg of ascorbic acid and 5.52 kg of calcium carbonate were loaded into a special discrete discrete turbo mixer (composition 1, table 1). After mixing in a special turbo mixer, the mixture was supplied by a screw feeder to a flow-mill vibrocentrifugal mill VTsM-10 m of shock-abrasive type. The rotation frequency and feed rate of the material were varied and selected in order to obtain in the final product agglomerates of crushed particles of components with a size of 30-300 μm, observed under an optical microscope. A comparison of X-ray diffraction patterns indicates the presence of only ascorbic acid and calcium carbonate in the obtained effervescent crystalline compositions.

Dissolution of 1 g of the composition in 200 ml of distilled water at + 20 ° C took place over a period of not more than 1 minute with the formation of a clear solution. At the same time, upon dissolution of the untreated mixture in the mill, a precipitate of calcium carbonate precipitated and its dissolution in the absence of mixing required 0.5-2 hours.

Thus, the above examples of obtaining "effervescent" compositions confirm the claims.

Literature

1. US Patent, Effervescent mixture characterized by protracted release of gas and the use of this mixture in the preparation of carbonated drinks, US 4,579,742.

2. United States Patent, Effervescent ibuprofen preparations, US 5445827.

3. US Patent, Process for manufacturing effervescent granules and tablets, US 4,614,648.

4. US Patent, Effervescent composition and method of making same, US 4,678,661.

5. US Patent, Effervescent ranitidine formulations, US 5728401.

6. US Patent, Effervescent composition and its production, US 5824339.

7. US Patent, Effervescent granules and process for their preparation, US 5759575.

8. US Patent, Process for manufacturing effervescent granules and tablets and high efficiency granulation tower for such process, RE 33086.

9. U.S. Patent, Method to make effervescent calcium tablets and calcium tablets produced thereby, US 4,650,669.

10. US Patent, Effervescent composition, its production and use, US 5223246.

11. US Patent, Effervescent granules and methods for their preparation, US 6071539.

12. US Patent, Effervescent granules and methods for their preparation, US 6649186.

13. U.S. Patent, Method to make effervescent calcium tablets and calcium tablets produced thereby, US 4,650,669.

14. U.S. Patent, A direct compression process for forming an effervescent tablet containing an active chemical compound is enhanced by the addition to the composition to be compressed of an alkali metal carbonate, US 4265847.

15. U.S. Patent, Pharmaceutical compositions containing an effervescent acid-base couple, US 6,667,056.

16. U.S. Patent, Pharmaceutical compositions containing an effervescent acid-base couple, US 6284272.

17. RF patent, Pharmaceutical composition in the form of effervescent soluble tablets and method for its preparation, RF 2189228.

18. Dushkin A.V., Rykova Z.U., Botdyrev V.V., Shaktshneider T.P. // int. J. Mechanochem. Mechanochem. Alloying 1994. No. 1. C.1; Dushkin A.V., Possibilities of the mechanochemical technology of organic synthesis and the production of new materials, Chemistry for Sustainable Development, 12 (2004), p.1.

19. Internet site of the Institute of Solid State Chemistry and Mechanochemistry SB RAS. http://www.solid.nsc.ru/

Table 1.
The compositions of the "effervescent" compositions obtained by processing acidic and carbonate components in a ball mill No. p. Acid components, wt.% Carbonate components, wt.% Apple acid Lemon acid Vitamin C succinic acid Glutamic acid Potassium dihydrogen phosphate Bicarbonate of soda Sodium carbonate Calcium carbonate Basic magnesium carbonate one - - 77.9 - - - - 22.1 - 2 - - 78.0 - - - - - 22.0 3 73.0 - - - - - - 27.0 four - - - 44.05 - 55.95 - - 5 - 79.5 - - - - - - 20.5 - 6 73.0 - - - - - - - 27.0 - 7 - - - - 74.5 - - - 25.5 - 8 - 80.0 - - - - - - - 20,0 9 55.85 - - - - - - 44.15 - - 10 - - - 54.5 - - - - - 45.5 eleven - 50,0 - - 5 - 45.0 - - 12 - - - - - - - - 13 fifteen fifteen fifteen fifteen 3 - - 22 10 - fourteen - - 70 - - - 5 5 fifteen - fifteen - - - - - fifteen - 85 - - table 2
The compositions of the "effervescent" compositions (in wt.%) With the addition of auxiliary substances, flavors, medicinal and biologically active substances  No.p Acidic components Carbonate components pvp 12000 Beta cd Paracetamol Licorice extract Indomethacin Azaleptin Bufwnox Sibazon Fructose Glycine Saccharinate Na Acesulfame Fruit flavor one AK-66.2 CaCO ₃ -18.8 - - - 5,0 - - - - - 10.0 - 0.01 2 AK-58.0 CaCO ₃ - 16.5 5 - twenty - - - - - - - 0.3 - 0.01 3 AK - 44.61 CaCO ₃ -25.1 10 10 - - - - - 0.1 10 - 0.1 0.1 - four Yak-54.44 Basic carbonate Mg-15.36 - - 5 - - - twenty 5 0.1 0.1 0.01 5 AK-50.0 Na ₂ CO ₃ -30.0 5 10 - - 5,0 - - - - - - - - 6 LK-68.6 CaCO ₃ -17.1 2 - - - - 7 - - - 5 0.1 0.1 0.02 7 LK-63.28 CaCO ₃ -16.32 10 10 - - - 0.2 - - - 0.1 0.1 - AK - ascorbic acid;
LC - citric acid;
YAK - succinic acid;
PVP - polyvinylpyrrolidone;
Beta - CD - Beta-Cyclodextrin

Claims (12)

1. A method of obtaining a powdery water-soluble effervescent composition based on solid water-soluble acid or solid acid salts or a mixture thereof — acidic components, as well as alkali or alkaline earth metal bicarbonate, carbonate or basic carbonate, or a mixture thereof — carbonate components, including mixing the initial powdery acidic and carbonate components, characterized in that the mixture of the original powder components is subjected to mechanical treatment by impact-abrasion to form anija agglomerates crushed particle size of the processed components of 30-300 microns. 2. The method according to claim 1, characterized in that the above acidic and carbonate components, as well as excipients, water-soluble polymers and / or cyclodextrins that do not chemically interact with the above components, are taken as a mixture of the starting powder components. 3. The method according to claim 1, characterized in that the above acidic and carbonate components, excipients, as well as target substances — water-soluble medicinal and biologically active substances, dry extracts that do not chemically interact with the above components — are taken as a mixture of the starting powder components. 4. The method according to claim 1, characterized in that as the mixture of the starting powder components take the above acidic and carbonate components, excipients, as well as target substances - medicinal and biologically active substances capable of forming water-soluble salts with metals of carbonate components or acid residues components. 5. The method according to claim 1, characterized in that the above acidic and carbonate components, excipients, as well as medicinal and biologically active substances capable of forming water-soluble complexes with excipients are taken as a mixture of the starting powder components. 6. The method according to claim 1, characterized in that the above acidic and carbonate components, excipients, target substances — biologically active substances and, in addition, vitamins, carbohydrates, amino acids, sweeteners and flavorings are taken as a mixture of the starting powder components. 7. A method of obtaining a powdery water-soluble effervescent composition based on solid water-soluble acid or solid acid salts or a mixture thereof — acidic components, as well as alkali or alkaline earth metal bicarbonate, carbonate or basic carbonate, or mixtures thereof — carbonate components, characterized in that the initial powdery components subjected to simultaneous mixing and machining by impact-abrasion to form agglomerates of crushed particles of the processed components 30-300 microns in size. 8. The method according to claim 7, characterized in that the above-mentioned acidic and carbonate components, as well as excipients, water-soluble polymers and / or cyclodextrins that do not chemically interact with the above components, are taken as starting powder components. 9. The method according to claim 7, characterized in that the initial acidic powder components are the aforementioned acidic and carbonate components, excipients, as well as the target substances — water-soluble medicinal and biologically active substances, dry extracts that do not chemically interact with the above components. 10. The method according to claim 7, characterized in that the initial acidic powder components are the aforementioned acidic and carbonate components, excipients, as well as the target substances are medicinal and biologically active substances capable of forming water-soluble salts with metals of carbonate components or residues of acidic components . 11. The method according to claim 7, characterized in that the above-mentioned acidic and carbonate components, excipients, as well as medicinal and biologically active substances capable of forming water-soluble complexes with excipients are taken as starting powder components. 12. The method according to claim 7, characterized in that the starting acidic components are the aforementioned acidic and / or carbonate components, excipients, target substances - biologically active substances and additionally vitamins, carbohydrates, amino acids, sweeteners and flavorings.

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