SE462014B - BUSH GRANULATES AND PROCEDURES FOR ITS PREPARATION - Google Patents

Description

15 20 25 30 462 014 become some unreasonably long dissolution times and whereby the manufacturable effervescent tablets must be stable and storable.

The invention as well as embodiments thereof are set out in the appended claims.

Preferably, the binder layer covers at least 80, in particular at least 95% of the surface of the acid crystals. Due to this complete coating, the adhesion of the calcium carbonate to the surface takes place in the unexpectedly rapid reaction between acid, for example citric acid, and calcium carbonate, which would otherwise have been much slower. In addition, this far-reaching covering of the acid crystals achieves a safe passivation of them against ambient moisture. A particular effect which results from this feature is that no foreign binders need be added for the construction of this system. The adhesion of the components is thus achieved only through the aforementioned bonding layer.

The grain size of the calcium carbonate is approximately in an order of magnitude which is smaller than that of the acid crystals and thus there is the most possible coherent coating on the acid crystals.

Preferably, the binder layer consists of a maximum of 5% by weight, in particular a maximum of 2% by weight of calcium carbonate in the form of acid salt, in order thereby to have as much calcium carbonate as possible available for the noise reaction.

The calcium carbonate component of the noise mixture preferably has a particle size of at most 20 micrometers, since the reaction surface of the calcium carbonate thereby becomes very large and a reaction rate is achieved which is comparable to that of the sodium carbonate.

In addition, although the coating material preferably consists exclusively of calcium carbonate, it may also contain sodium and / or potassium bicarbonate. According to a further feature of the invention, one layer contains mainly potassium and / or sodium salt and the other layer mainly calcium salts.

According to the invention, it is further provided that the coating has a calcium carbonate layer reacted on the surface of the acid crystals over the bonding layer and a potassium bicarbonate layer adhering thereto.

As the binder layer in the noise mixture according to the invention replaces the binders commonly used in powder technology, this also results in the possibility of using this binder layer for storage of minerals and / or vitamins.

The effervescent tablet proposed according to the invention can be prepared using the effervescent granulate.

According to a further feature, the effervescent tablet also contains vital minerals and / or vitamins.

The invention further discloses the use of the effervescent granulate for the manufacture of effervescent beverages or effervescent tablets.

The effervescent tablets can be used to advantage for mineralization of so-called Soft Drinks, since an increasing depletion of the organism in terms of vital minerals occurs due to the very highly sugared and partially mineral-poor Soft Drinks as well as the increased use of table salt (sodium chloride). The invention makes it possible, in the event of a faulty or very low content of sodium ions, to conveniently introduce large amounts of calcium, magnesium, potassium and other vital ions into a Soft Drink.

The effervescent tablet may also have a content of acetylsalicylic acid and a content of an effervescent mixture with a sodium ion-free coating, which consists of a first calcium carbonate-containing, a second potassium bicarbonate-containing and a third fumaric acid-containing layer.

Furthermore, an effervescent tablet is proposed which has a construction of several, preferably two layers of different composition.

It can be arranged in such a way that only one of the tablet layers contains the noise granulate according to the invention. It can also be arranged so that an effervescent granulate-free layer of the tablet layers contains at least one of the active substances.

One of the tablet layers may contain paracetamol and one of the tablet layers acetylsalicylic acid.

The basis for the invention is the surprising finding that it is possible to accelerate the noise reaction between organic acids, e.g. citric acid and calcium carbonate by coating the acid crystals with calcium carbonate and thus creating a very intimate contact between calcium carbonate and citric acid on the surface of the crystals. This achieves a reaction rate between acid and calcium carbonate which is comparable to the reaction with carbonates or the hydrogen bicarbonates of the alkalis. In this case, it is necessary to use a binder, which in this case constitutes the product of a reaction of approximately 5 - 10% calcium carbonate on the surface of the acid, e.g. the surface of the citric acid, forming the acid corresponding to the calcium salt. The surface reaction between calcium carbonate and acid, e.g. citric acid, then serves to anchor the calcium carbonate firmly on the surface of the acid, so that even in later mixing no separation of this structure can take place.

This binding mechanism is preferably achieved by e.g. Moisten the citric acid crystals, which have different sizes, for example from 50 μm to 500 μm, with a mixture of alcohol and water and then evacuate in a vacuum mixer to 500 mbar, suck in the calcium carbonate and start mixing at 500 mbar vacuum in a stirrer , which preferably pivots about its horizontal axis and each time moves towards gravity. Through the three-dimensional mixing movement, all pre-moistened citric acid crystals are brought into contact with calcium carbonate, whereby the resulting reaction can be measured on the pressure drop of the vacuum meter on the vacuum machine. After the evolution of a certain amount of gas, the reaction is stopped by applying a full vacuum, and the monocalcium citrate layer formed now serves as a binder for the calcium carbonate adhered to the surface by the moisture. Due to the subsequent removal of the moisture, the system becomes mechanically and chemically stable.

In this way it is possible to introduce such amounts of calcium carbonate which approximately correspond to the stoichiometric amount of 1 mole of citric acid to 1 mole of calcium carbonate, whereby only 5 - 10% of the mole of calcium carbonate were reacted. 462 014 6 10 15 20 25 30 35 The production in vacuo enables for the first time a precise control and at any arbitrary time an exact termination of the reaction as well as an exact reproducibility of the process, whereby a corresponding slow stirring speed leads to an unobstructed construction of the system, but not to the destruction of the same, as would be the case with other procedures, e.g. vortex drying. In particular, the preparation in vacuo ensures that, as already mentioned, the finished sodium-free or sodium-poor effervescent tablet is as fast in solution as a traditional sodium-hydrogen-carbonate tablet and, in addition, significantly less sensitive to moisture.

This system can now be used as a noise system, to which certain amounts of potassium bicarbonate or potassium carbonate can be added. It is also possible to add a small amount of sodium carbonate depending on the amounts needed for the term "low sodium" or "very low sodium".

When choosing the organic acids, it must be taken into account that one does not choose such acids which give insoluble calcium salts, such as e.g. tartaric acid. On the other hand, malic acid, fumaric acid and adipic acid are useful, among others.

It is obvious that the effervescent tablet according to the invention may contain further customary additives such as, for example, inert fillers, e.g. mannitol or the like.

Particularly suitable methods and devices for the manufacture of the noise systems according to the invention are described in AT-PS 376 147.

Further features and advantages with regard to the invention appear from the claims and from the following description, in which exemplary embodiments are explained in detail.

Example 1: 22 parts of citric acid with a grain size between 0.4 and 0.6 mm and 43 parts of citric acid with a grain size of 0.1 mm are mixed, heated to 400 and added with 10 parts of 50%. ethanol.

After 5 minutes of vibrating mixing, evacuate to 500 mbar and 20 parts of micronized calcium carbonate are added. Without stirring, evacuate once more and when 500 mbar is reached, mix under vibration and the valve to the vacuum pump is switched off. The resulting reaction has the effect that the vacuum slowly decreases and when the 200 mbar is reached, a full vacuum is applied. The difference in the space located above, when calculating the pressure difference, gives a turnover of approximately 4% of the corresponding amount of calcium carbonate in monocalcium citrate.

After reaching 800 mbar, stirring is stopped and during temporary stirring / stopping to 10 mbar, drying takes place.

Up to 80 parts of potassium bicarbonate and up to 30 parts of sodium carbonate can be mixed into this system.

However, the system also provides individually usable effervescent tablets.

This base is particularly suitable for the preparation of high-dose acetylsalicylic acid effervescent tablets, which on repeated ingestion contain a well-balanced amount of alkali and alkaline earth ions, while a very large amount of sodium ions has hitherto been necessary for the effervescent effect. . 462 014 8 10 15 20 25 30 Example 2: 22 parts of citric acid in the order of 0.5 mm are mixed with 88 parts of citric acid 0.1 mm and moistened with 20 parts of ethanol / water. 22 parts of calcium carbonate are added and after drying 60 parts of potassium bicarbonate and 10 parts of sodium carbonate are added.

Depending on the desired acetylsalicylic acid addition, up to 40 parts of lactose can also be added, diluting the corresponding noise system to increase the stability of the acetylsalicylic acid. According to this seed composition, effervescent tablets of 4 g can be prepared, which as a separate dose may contain up to 1 g of acetylsalicylic acid.

Example 3: 40 parts of citric acid with a grain size of 0.7 mm are mixed with 30 parts of ascorbic acid and another 45 parts of powdered citric acid are added.

Moisten again with 25 parts of a mixture of 70% ethanol and 30% water and carry out a reaction with 25 parts of calcium carbonate as in Example 1 {After drying to 10 mbar, 80 parts of potassium bicarbonate and 60 parts of lactose with a grain size of 0.2 mm are added. and compressed into tablets.

The sodium-poor vitamin C effervescent tablets have approximately the same dissolution rate as those which have been prepared with sodium bicarbonate. <1 10 15 20 25 30 462 014 Exemoel 4: 22 parts by weight of citric acid with a grain size between 0.4 and 0.6 mm and 30 parts by weight of citric acid with a grain size of 0.1 mm are mixed, up; heated to 40 ° C and added with a solution of 13 parts by weight of gluconic acid-delta-lactone in 5 parts by weight of water. A reaction according to Example 1 is carried out and dried as in Example 1.

The addition of gluconic acid-delta-lactone, whereby 1 part by weight of lactone is converted to gluconic acid, has the advantage that the dissolution rate of this system is accelerated, in that reaction-retarding surface buffers are prevented by different citric acid and gluconic acid PHI Example 5: 200 parts 5 parts ethanol and 5 parts water and heated to 60 ° C.

Then 30 parts of calcium carbonate are sucked in and the mixture is allowed to react, first evacuating to approximately 100 mbar and at 900 mbar allowing the void in the vacuum mixer to be filled with formed CO gas. 2 The gas evolution is repeated a second time and then stopped by applying the vacuum.

Then add 10 parts of potassium bicarbonate and another 20 parts of citric acid and repeat the passivation with 2 parts of ethanol and 1 part of water.

In this way a passivated noise mixture is obtained, which consists of reacted calcium carbonate and potassium bicarbonate and possesses a remarkable stability against moisture. 462 014 10 10 15 20 25 30 To this basic noise mixture can also be added the actual amounts of sodium bicarbonate legally permitted for lack of sodium. Together with a conventional multi-vitamin mixture, the mixture results in an easily compressible effervescent tablet mixture with an extremely low content of sodium ions.

Example 6: 105 parts of ascorbic acid (vitamin C), 130 parts of citric acid oppneeaee with 5 parts of ethanol and 3 parts of water to 60 ° C and treated with 22 parts of calcium carbonate as in Example 1. In this case the ascorbic acid is also allowed to surface to reaction with calcium carbonate, because the durability of the system is thereby greatly increased, as the ascorbic acid with its low pH and its low water solubility has already been passivated on the surface and thereby made weak to react.

It is then reacted once more with 10 parts of potassium bicarbonate and 10 parts of citric acid, so that all free spots on the acids were passivated with calcium and potassium salts, respectively, by surface reaction. Here, too, you dry to a final allowable value of at least 20 mbar and can add flavors and colors and squeeze in a known manner.

Example 7: A certain difficulty prepares the preparation of sodium-poor acetylsalicylic acid-containing effervescent tablets: 68 parts of citric acid are moistened with 2 parts of ethanol and 1 part of water, heated to 60 ° C and reacted with 20 parts of calcium carbonate. Immediately following this, 40 parts of potassium bicarbonate are reacted, but only once, in that 2 parts of 70% ethanol are preferably added for 2 starts of reaction.

After the partial drying, however, 20 parts of fumaric acid in micronized form must be added to cover the possibly still open sites on the reaction partner with fumaric acid. This is achieved particularly elegantly if the previous reactions are dried only up to a certain vacuum value, for example 90 mbar, so that less moisture remains, which keeps the micronized fumaric acid fixed on the surface.

This mixture is miscible with acetylsalicylic acid in a ratio of 2: 1 and gives hard, rapidly decomposing effervescent tablets, which contain no sodium ion at all and which are characterized by a slight saponification of the free salicylic acid even with longer storage.

Of course, in order to improve the rate of decomposition, small amounts of sodium hydrogen carbonate can be added according to the relevant regulations. It is also possible to fill the effervescent tablet with inert substances, such as mannitol, which here leads to faster disintegration times and better stability. A ratio of mannitol to noise mixture in the size of 1: 1 still leads to rapidly decaying and stable noise systems. 462 014 12 Example 8: i? According to the process of the invention, it is also possible to produce even more complicated effervescent tablets, which is particularly suitable in the case of incompatible substances. For example, it is possible to combine the incompatible paracetamol / acetylsalicylic acid system in a bilayer effervescent tablet in the following manner. 68 parts of citric acid are moistened with 2 parts of ethanol and 1 part of water, heated to 60 ° C and reacted with 20 parts of calcium carbonate as in Example 6.

Before stopping the reaction, in this case 20 parts of paracetamol are added, which immediately accumulate on the surface due to the sticky binding force of the resulting calcium nitrate. Only then is the product dried in vacuo and the reaction is carried out in this connection, in which 40 parts of potassium hydrogen carbonate are reacted once with 2 parts of 20% ethanol. Here, too, after the partial drying, only 20 parts of fumaric acid in micronized form are added to, for example, only 100 mbar.

The resulting substrate for a paracetamol effervescent tablet can be compressed in the form of a bilayer tablet with a final mixture in a given ratio as in Example 7 (acetylsalicylic acid effervescent tablet), whereby with the two-layer tablet only about 0.8% of the acetylsalicylic acid is lost. such as free salicylic acid, referred to as the pressed boundary layer between the two phases of the bilayer tablet. Due to the chemical properties of the paracetamol base, it is also possible to proceed so that a two-layer tablet is prepared, in which, for example, the base mixture is prepared so as to obtain an effervescent tablet of 2.89, which contains it against the corresponding amount of paracetamol, after which a second layer, an acetylsalicylic acid mixture, consisting of 200 mg acetylsalicylic acid and 500 mg ordinary lactose, is applied, whereby a two-layer tablet of a total of 3.5 g is formed. Although the aspirin here is in a non-effervescent form, the effervescent effect of the paracetamol-containing layer is sufficient to achieve a complete release of the acetylsalicylic acid in the total tablet. The outstanding advantage of this system is that the paracetamol is completely resistant in the Na-poor noise phase, however, the system is not exposed to the saponifying effect of both the paracetamol and the Na-free noise mixture on the aspirin. In this way it is possible by means of a simple two-layer tablet press to produce hitherto non-manufacturable effervescent tablets with incompatible constituents up to and including

Na-poor.

Example 9: In the manner described, it is also possible to prepare sodium-free or sodium-poor effervescent tablets, which are enriched with minerals and vitamins, for example from the B group. 500 parts of citric acid, preferably with a grain size of 0.2 - 0.3 mm, are heated with 30 parts of magnesium oxide and 150 parts of calcium carbonate: in so ° c.

A solution of 40 parts of citric acid in 20 parts of water is added and the mixture is allowed to react until the evacuated space located above, which generally corresponds in volume to the double parts of citric acid, has once been filled with CO2. 462 014 10 15 20 25 30 14 Then a high vacuum is applied and dried to a value of 100 mbar. To this still residual moist mixture are now added, for example, 20 parts of ferrous sulphate, 40 parts of potassium citrate, 10 parts of potassium chloride and a corresponding amount of the vitamin group B1, B2, Bp and B6.

Through the residual moist but passivated well mixture, a clinging of additives takes place, so that - after the evacuation of the pulp to 10 - 20 mbar, a uniform, very well flowable and above all very humid product is very stable.

This product can either be used as granules in Sachets for the production of Instant sports drinks or can be compressed into effervescent tablets with the addition of 2 - 5% micronized fumaric acid.

Example 10: 70 parts of citric acid with grain sizes of about 0.3 - 0.5 mm are mixed with 30 parts of citric acid with grain sizes of 0.1 mm, 45 parts of calcium carbonate are added and heated under temporary vacuum to 50 ° C.

Then the valve to the vacuum pump is closed as in Example 1 after evacuation to 500 mbar, but this time a mixture of 5 parts levulinic acid, 3 parts citric acid and one part lactic acid in 2 parts water and 2 parts alcohol is added slowly with rotary stirring. This time the upper compartment of the vacuum vessel is filled twice and evacuated twice and then dried by applying full vacuum. RW 10 15 462 014 This further example of the multiple formulation possibilities shows that even with elevated calcium carbonate content through the use of different acids surface reactions are possible, which when dissolved in water can delay the formation of tricalcium citrate as solvent. - remained for 10 to 12 hours.

The features of the invention disclosed in the above description and in the claims may, individually or in arbitrary combinations, be essential for the realization of the invention in its various embodiments.

Claims (18)

462 614 10 15 20 25 30 35 P a t e n t k r a v A process for preparing an effervescent granulate wherein at least one solid crystalline edible organic acid is moistened with a solvent for the acid in a vacuum mixing machine at about 60 ° C and then, with stirring, mixed with solid powdered calcium carbonate to carry out a reaction of calcium carbonate on the acid crystals surface during the formation of a calcium carbonate layer on the crystals during the decomposition of reaction water, characterized in that, after the formation of the calcium carbonate layer, powdered crystalline acid is incorporated with stirring and reacted with the layer of calcium carbonate carbonate moistened by the reaction water. alkali bicarbonate is applied and reacted by the water of reaction formed on the acid powder layer, after which additional carbonate layers are similarly formed and the layering process is interrupted by the application of a vacuum. Process according to Claim 1, characterized in that a solid organic acid from the group adipic acid, malic acid, ascorbic acid, fumaric acid and citric acid is introduced into the vacuum mixing machine, the latter having a grain size of between 50 and 700 μm, and at a temperature of approx. 60 ° C, at citric acid 40 ° C - 60 ° C, after application of an initial vacuum of about 0,1 bar or less and moistened with a mixture of alcohol and water, then calcium carbonate with a grain size of about order less than that of the acid crystals is added and the mixture is stirred while shutting off the vacuum until the pressure rises to 800 - 900 mbar, with final drying at about 10 - 20 mbar, using 50 - 70% by weight of alcohol and the weight ratio of organic acid, alcohol and calcium carbonate are set at 1: 0.013 - 0.385: 0.085 - 0.042 and in connection with the pressure increase again at least one more time organic acid is added and after Qi 10 15 20 25 30 462 014 F; Injection of additional powdered calcium carbonate during intermediate evacuation, by stirring is reacted using the water formed in the previous reaction step, after which finally the drying takes place. Process according to Claims 1 to 2, characterized in that a calcium carbonate with a grain size of at most 20 μm is used. Process according to Claims 1 to 3, characterized in that the organic acid is mixed with gluconic acid-delta-lactone before mixing with the calcium carbonate. 5. A method according to claims 1 - 4, characterized in that after reaction of a calcium carbonate-containing layer a drying is carried out to a pressure of about 10 mbar and that then the minerals and / or vitamins are added and applied to the calcium carbonate-containing layer. Effervescent granules comprising at least one solid crystalline edible organic acid and at least one carbonate which cleaves on reaction with the organic acid CO 2, the acid crystals having a calcium carbonate-containing coating which adheres to their surface by means of a binder layer formed by the reaction between a calcium carbonate surface layers of the present acid crystals, specially prepared according to the process according to any one of claims 1 to 5, characterized in that the coating is built up in several layers and has at least two carbonate layers of which at least the layer bound to the acid crystal consists of calcium carbonate and the the following layers adhere to the presently underlying carbonate layer via a bonding layer formed by a reaction between acid and carbonate. 462 014 10 15 20 25 30 18 Noise granules according to claim 6, characterized in that the coating has at least two calcium carbonate layers. Noise granules according to claims 6 - 7, characterized in that the coating also contains sodium and / or potassium bicarbonate. Noise granules according to claims 6 - 8, characterized in that the coating has at least one layer consisting essentially of potassium and / or sodium salts and a layer consisting essentially of calcium salts. Noise granules according to Claims 6 to 9, characterized in that the coating has a potassium bicarbonate layer adhering to a calcium carbonate layer. Noise granules according to claims 6 - 10, characterized in that the respective bonding layer covers at least 80%, preferably at least 95% of the surface of the acid crystal. Noise granules according to claim 6 4 11, characterized in that the grain size of the calcium carbonate is approximately one order of magnitude smaller than that of the acid crystals. Noise granules according to claims 6 to 12, characterized in that the adhesive layer (s) adjacent to a calcium carbonate-containing coating layer contains a maximum of 5% by weight, preferably up to 2% by weight of the calcium carbonate present in the form of acid salt. Noise granules according to claims 6 - 13, characterized in that the calcium carbonate has a particle size of at most 20 μm. 10 15 462 014 19 Noise granules according to claims 6 - 14, characterized in that the coating has at least one calcium-gluconate-containing layer. Noise granules according to claims 6 - 15, characterized in that the coating has at least one enriched additive layer with minerals such as magnesium oxide and / or ferrous sulphate and / or vitamins, such as those belonging to the B group. Use of the soda granulate according to claims 6 - 16 as an "Instant" mixture for the production of soft drinks. Use of the effervescent granulate according to claims 6 - 16 for the preparation of effervescent tablets.