FI90937C - A method for producing effervescent granulate, an effervescent granulate prepared therefrom and its use - Google Patents

Description

90937

A method for producing effervescent granulate, an effervescent granulate prepared therefrom and its use

The invention relates to a process for the preparation of effervescent granulate. This effervescent granulate contains at least one solid, crystalline corrosive organic acid, in particular citric acid, and at least one alkali or alkaline earth metal carbonate which, on reaction with the organic acid in aqueous solution, decomposes to form a CC> 2. effervescent granulate and its use.

DE-OS 3434774 discloses a effervescent granulate as described above and a process for its preparation. Organic acid crystals, especially citric acid crystals, are coated with a multilayer calcium carbonate-containing coating in a vacuum reaction. In the first reaction step, the acid crystals are moistened in a vacuum mixer with a suitable solvent such as water, alcohol or a mixture thereof. The reaction is then carried out efficiently and a first binder layer and a first powder coating containing at least one alkali or alkaline earth metal carbonate are attached to the surface of each acid crystal by the reaction of the acid and the carbonate. After the first coating has been formed, at least one further solid powder-like additional coating, similar to the first layer, which also contains at least one alkali metal or alkaline earth metal, is added in at least one step, while still stirring vigorously. This reacts with the 30 volatile crystalline wet coating formed in the first stage. After the formation of paving roads, final drying follows. The process method described above is hereinafter referred to as DE-OS 3434744 with reference to a known method.

The effervescent granulate described above, as well as the process 35 for its preparation, have proven to be excellent in practice. However, it has proved desirable to further improve the method. This is done according to the invention either in such a way that a vacuum mixer is not required, 2 or that when the vacuum mixer is used in a known manner, the production method according to the invention both speeds up production and improves the durability of the foamed granules produced. This is especially the case when the effervescent granules are particularly sensitive to alkali or alkaline earth metal carbonates or contain them in high concentrations, since then, under certain conditions, the use of a known method in a vacuum mixer causes the reaction to take place. This is the case if too much carbonate is fed to the vacuum mixer at a certain stage of the reaction or if too much solution is used. In this case, too much agloro separation occurs inside the boiler of the vacuum mixer, which results in a certain agglomeration. The boiler stirrer can also become stuck, so the desired result of coating the crystal particles with carbonate-containing layers is not obtained.

The object of the invention is to improve the known process on the one hand so that high-quality and durable effervescent granules can be prepared without the use of a vacuum mixer and on the other hand a faster process is obtained when using highly reactive combinations of substances for acid crystallization and coating. According to the invention, this object can be solved by improving the known method as set out in the characterizing part of claim 1.

Particularly preferred embodiments of the method according to the invention are included in claims 2 to 15. The effervescent granulate according to the invention is the subject of claim 30 and its use as claimed in claims 17, 18 and 19.

The invention is based on the surprising finding that the desired reaction to obtain one or more coating layers containing alkali or alkaline earth metal carbonate, e.g. for citric acid crystals, can also be carried out without the use of a vacuum mixture, if necessary. As described, for example, in AT-PS 376147, this is possible when, before coating the citric acid crystals, a part of e.g. 3,90937 of an acid and a portion of e.g. calcium carbonate are reacted with each other in a suitable solvent such as water, alcohol or an aqueous-alcoholic solution, and the pre-reaction solution thus prepared is then applied to the surface of the acid crystals. Tate provides an unexpectedly advantageous development of, for example, the mode of operation known from DE-OS 3434744. For example, on the surface of citric acid crystals, reactions with more or less polar solvents with alkali or alkaline earth metal bicarbonate or also carbonates can be effected. In this case, the reaction products formed by Tate are essentially mono- or di-salts of citric acid, and in each case act as a binder for the following layers or act as salt or the like.

The difficulties of the hitherto known process method can also be avoided in the process according to the invention when using a vacuum mixer. There are no longer any difficulties due to too vigorous a reaction if too much liquid is fed into the vacuum mixer and the resulting undesired excessive agglomeration in the boiler, which in turn can lead to agglomeration and even jamming of the boiler mixer, so that the acid crystals do not. since part of this reaction is now carried out outside the boiler. In both calcium products and also in potassium products, citric acid is reacted with calcium carbonate or potassium bicarbonate in such a concentrated form that the final concentrated solution is clear and at least shows no signs of crystallization. This well-concentrated pre-reaction solution is then sucked into a vacuum mixer, where no or very little reaction now occurs with the acid crystals, depending on whether the solution in the above example is made into monocalcium citrate or dicalcium citrate. It is known that the preparation of tricalcium neurositrate is impossible because it is insoluble in water. If, already at the beginning of the first reaction step or in subsequent reaction steps or steps, citric acid is also used as a reactant as a pre-reaction solution according to the invention, instead of a single solvent, it acts as a significant .

After preparation of the coating layers, it may be advantageous to add relatively large amounts of alcohol, preferably isopropanol. Alcohols remove inorganic salts of organic acids, especially lemon skin, in a naturally anhydrous form, because when alcohol is present, crystallization by crystal water formation is not possible. Before the alcohol evaporates, it is possible to add, for example, starch or neutral salts such as calcium lactate or the like and in a way "glue" the said salts, and only then remove all the water present with the aid of the alcohol.

This process is particularly advantageous because excessively concentrated solutions, especially calcium citrates, generate only a very low vapor pressure. Such a solution 20 does not start to boil at 100 ° C, but at 150 ° C or even at 180 ° C, so that evaporation in a vacuum, e.g. at 70 ° C, is not automatically possible. But when, according to the invention, the removal of salts is effected by the addition of alcohol and at the same time the existing water 25 dissolves in the alcohol, normal vapor pressure formation is again formed. Thus, when the pressure is reduced by using the vacuum mixing method, both water and alcohol or both together (azeotropic with isopropanol) are made to evaporate. The Tarna process can also be repeated several times if desired.

In a particularly preferred embodiment of the invention, in which anhydrous starch is added to one of the calcium carbonate-containing coating layers and the necessary anhydrous calcium salts are added to the other, there is an advantage that the Because these additives are used anhydrous, they act as additional desiccants in the storage of granules or effervescent tablets, respectively. They prevent a water-releasing chain reaction between calcium carbonate and citric acid, which would lead to premature aging and unusability of effervescent granulate and effervescent tablets, respectively. Furthermore, starch as a disintegrant with otherwise sparingly soluble and / or corrosive organic acids acts on unreactive calcium salts. Thus, these are distributed rapidly up to -10 as the effervescent granulate dissolves mechanically in water. The effervescent granules prepared according to the invention in this preferred embodiment are excellently suitable, especially as instant preparations, because the dissolution time is about 20 to 30 seconds at a temperature of about 5 ° C. In contrast, calcium carbonate preparations require too long, several minutes, to dissolve at such low temperatures.

It is particularly important for the invention that the starch is used completely anhydrous, since only then is a mechanical disintegration effect achieved, which guarantees the short dissolution time described above. The effervescent granules prepared according to the process of the invention are so durable that they can be stored in open bottles on the one hand due to the synergistically achieved "drying property" of anhydrous starch and on the other hand with sparingly soluble or edible organic acids. It can be seen that the idea of using the pre-reacted "buffer granulation solutions" according to the invention also suits excellently in the known vacuum mixing method, in addition to the fact that it is also suitable for "free air granulation", i.e. granulation without a vacuum mixer. In both cases, the significant advantages described above are achieved. Granulation can take place, for example, in pie-35 mixing plants or on a large-scale scale. The final drying can also be performed with a belt dryer or the like.

According to the invention, 6 isotonic and hypertonic effervescent granules can also be prepared if required. They are characterized in that they can be mixed with instant sugar up to a ratio of 1: 5 and that, due to the density of the granulate and the surprisingly high local frothing capacity, they are able to thoroughly mix with instant sugar and at the same time dissolve up to 5 times. Thus, instant soft drinks can be prepared which, like ordinary soft drinks, contain 8-10% by weight of sugar and in addition 10 necessary essential amounts of citric acid, mineral salts such as calcium, magnesium, sodium and potassium, and naturally. These instant products differ in advantage from the instant products known to date, which dissolve in water very slowly and taste in addition to the cooled ones.

Example 1:

Particularly preferred is the process 20 of the invention when using hygroscopically heavy potassium salts.

In this case, 250 parts by weight of crystallized citric acid having a grain size of 0.4 to 0.6 mm are mixed with a solution of 20 parts by weight of citric acid in 15 parts by weight of water, and 20 parts by weight of potassium bicarbonate are added thereto. The solution is stirred in a high-speed stirrer, which is heated to 35 ° C at the same time. A pre-reaction is thus obtained. 210 parts by weight of ground potassium bicarbonate are then added to the pre-reaction solution. In practice, the pre-reaction solution consisting of dipotassium citrate then acts as a binder and buffer between citric acid and potassium bicarbonate, so that a violent reaction cannot take place because dipotassium citrate already reacts very slowly and lazily with potassium bicarbonate. Thus, not only granulation is achieved, i.e. a uniform granular substance, but rather it is ensured that a passivating layer is formed between the citric acid crystals on the one hand and the very strongly hygroscopic potassium bicarbonate on the other.

II

90937 7 In this procedure it is advisable and advantageous to add a relatively large amount of alcohol after one or two coats as described above, preferably three to four times the amount of water added beforehand. The alcohol-insoluble potassium salts of Tate can be removed anhydrous and the water used as a solvent can be removed with the aid of alcohol, using isopropanol in a particularly advantageous manner azeotropically.

This procedure yields granules which can be compressed into very hard effervescent tablets, the sensitivity of which to air humidity is significantly reduced because dipotassium citrate is also capable of forming crystalline water, in contrast to monopotassium citrate.

A similar possibility is obtained with tripotassium citrate, in which case the pre-reaction solution does not contain, as described above, 20 parts by weight of potassium bicarbonate, but 30 parts by weight of potassium bicarbonate. Thus, in this case, the 20 is granulated with a tripotassium citrate solution, from which, as before, the water is removed with alcohol and forms a passivation layer between the different parties, i.e. between the acid crystals and the first coating layer or two successive coating layers.

However, experience has shown that dipotassium citrate is superior because the adhesion of this salt, which is later present in the reaction as a mixture of mono-, di- and tri-potassium citrates, provides substantially better binding properties than tri-potassium citrate: to name one example.

Example 2:

The procedure is as in Example 1, but in addition an additional coating layer of magnesium oxide is made. 90 parts by weight of crystalline citric acid are then mixed with the di-calcium solution. The pre-reaction solution prepared as in Example 1 is subjected to citric acid crystals with stirring. Thereafter, 20 parts by weight of potassium carbonate are added. An additional pre-reaction solution is then introduced, after which 11 parts by weight of magnesium oxide are anchored as an intermediate layer. Finally, the pre-reaction solution and 25 parts by weight of potassium carbonate are added again to obtain a final coating layer, before final drying with the same mixing.

All in all, the process according to the invention makes it possible to avoid the prolonged heat treatment of the still wet effervescent tablets and also of the effervescent granulate by means of the mark granulation of the wet granulate. This is also the case when the vacuum mixing method is not used, but the granulation takes place under atmospheric conditions. In the current state of the art, during the general heat treatment 15, the water partially evaporates. This results in reactions as described above in the final product of the product conventionally treated under vacuum, since removal of water of crystallization is not possible under vacuum. The prior art treatment also destroys additives, especially vitamins, but also aromatics. This is due to moisture and acidic or strongly alkaline reactants, so such a process is not suitable for sensitive biologically active substances.

The process according to the invention is also obviously advantageous compared, in particular, in the process known in the American literature as "curing", in which the final drying of the compressed tablets takes place by a long heat treatment (e.g. Herbert A. Lie-30 bermann and Leon Lachmann "Pharmaceutical dosage forms tablets ", Part 1, pages 232-243).

II

Claims (19)

90937 9 A process for the preparation of effervescent granules using at least one solid, crystalline, corrosive organic acid and at least one alkali or alkaline earth metal carbonate which, on reaction with an organic acid in aqueous solution, decomposes to form CO 2, known from the following steps: a) part of the acid a portion of the alkali metal carbonates (s) as the first powder-like coating agent, containing at least one alkali or alkaline earth metal carbonate, is dissolved in an acid solvent and reacted with each other; b) those acid crystals which have not been used in the first reaction step (a) to prepare the pre-reaction solution are moistened with the pre-reaction solution prepared in reaction step (a); c) in step (b), the acid crystals has not been used to prepare the pre-reaction solution, so that a first coating layer is formed on the acid crystals, which adheres to the upper surface of the acid crystals as a bonding layer when the acid and carbonate react with each other. D) after the coating layer formed on the surface of the acid crystals in the first step (c), at least one solid powder coating layer is added to the surface of the crystals in at least one reaction step at the same time. , after the reaction from the dispersed crystal water still moist crystals. e) final drying takes place after the formation of the coating layers. Process according to Claim 1, characterized in that after the formation of the first coating layer and / or at least one of the subsequent coating layers, intermediate wetting is carried out with an additional reaction solution Process according to Claim 1 or 2, characterized in that the solvent is heated to about 35 to 40 ° C before the addition of the acid and / or the alkali or alkaline earth metal carbonate. Process according to one of the preceding claims, characterized in that the pre-reaction solution (s) is (are) heated to 30-40 ° C before it is contacted with acid crystals. Process according to one of the preceding claims, characterized in that the pre-reaction solution (s) is (are) prepared in such a concentration that the substance (s) is (are) clear and that no visible crystallization occurs during the time required for the preparation process. Method according to one of the preceding claims, characterized in that the solid powder coating agent (s) contain (in each case) a part of the total acid content. Method according to one of the preceding claims, characterized in that at least one, preferably after the addition of the last coating layer, alcohol is added at least once, followed by drying. Process according to Claim 7, characterized in that isopropanol is used as the alcohol. Process according to one of the preceding claims, characterized in that the at least one coating agent contains an alkali and / or alkaline earth metal salt which is insoluble and / or difficult to dissolve and / or reacts with a corrosive organic acid. Process according to one of the preceding claims, characterized in that the at least one pre-reaction solution contains an alkali and / or alkaline earth metal salt which is non-reactive with starch and / or difficult-to-dissolve and / or corrosive organic acid. Process according to Claim 9 or 10, characterized in that calcium lactate is used as the unreactive salt. Process according to Claim 9 or 10, characterized in that calcium levulate is used as the unreactive salt. Process according to Claim 9 or 10, characterized in that calcium gluconate, preferably calcium hepatucluconate, is used as the unreactive salt. Process according to one of Claims 11 to 13, characterized in that the respective coating layer with non-reactive calcium salts contains from 5 to 30% by weight relative to the respective alkali and / or alkaline earth metal carbonate content. Process according to one of Claims 9 to 14, characterized in that the respective starch-containing coating layer containing anhydrous starch contains from 2 to 8% by weight relative to the respective alkali and / or alkaline earth metal carbonate. Foam granulate prepared according to any one of the preceding claims. Use of an effervescent granulate according to claim 16 as an instant granulate for the preparation of effervescent beverages or the like. Use of an effervescent granulate 30 according to claim 16 for the preparation of effervescent tablets. Use according to Claim 17 or 18, characterized in that instant sugar is mixed into the effervescent granulate in a ratio of up to 1: 5. 12