IE872841L - Effervescent granular material containing on organic acid - Google Patents

Description

40 45 50 60120 P4382.IE METHOD OF PRODUCING AN EFFERVESCENT GRANULAR MATERIAL. EFFERVESCENT GRANULAR MATERIAL PREPARED BY SUCH METHOD AMD USE OF SAME The invention relates -to a method, of producing an effervescent granulate containing at least one solid crystalline edible organic acid, more particularly ci-tric acid, and at least one alkal i-metal or alkaline-earth metal carbonate which spl its off COa on reacting with the organic acid in aqueous solution. The invention also relates to an effervescent granulate produced by the method, and to use thereof.

DE-OS 34 34 774 discloses an effervescent granulate of the aforementioned kind and a method of producing it, in which organic acid crystals, more particularly citric acid crystals, are provided with a multi-layer coating containing calcium carbonate, by surface reaction in a vacuum. The process is as follows: In a vacuum mixing machine, in a first addition-reaction step, the acid crystals are wetted with a solvent for the acid, e.g. water or alcohol or a mixture thereof, and then, in order to form a first coating layer stuck to the surface of the respective acid crystal by a bonding layer formed by reaction, between the acid and carbonate, are Intensively and thoroughly mixed with a first pulverized coating subtance containing at least one alkal i-metal or alkaline-earth metal carbonate, and after the first coating layer has formed, in at least one additional addition-reaction step at least one additional solid pulverized- coating substance, identical with the first if required and containing at least one alkali-metal or alkaline-earth metal carbonate, is added and is reacted with vigorous agitation on,the previous coating layer formed in the preceding addition-reaction step and wet with the water of crystallization split off during the addition reaction, in order to form at least one additional coating layer, followed by final drying after interrupting the coating formation; the aforementioned procedure according to DE-OS 34 34 774 is hereinafter also called the "method according to the preamble".

The above—decrlbed effervescent granulate and the method of producing it according to the preamble have given excellent results in practice, but it would also be desirable to Improve the method of production, which in the prior art is carried out in a vacuum mixer, so that effervescent granulates of the desired quality can be produced even without a vacuum mixer, and so that even when the known vacuum mixing process is used, there are advantages as regards speeding up the process and the stability of the resulting effervescent granulates, particularly when the granulates are particularly reactive alkali-metal or alkal ine-earth metal carbonates or contain them in very high concentration, since in these cases. 6C1 20 under certain conditions, when the method according to the preamble is used, difficulties are caused by excessively violent reactions in the vacuum mixer. If too much carbonate is reacted with the organic acid and/or too much solution is used in the vacuum mixer in any step of the method, the result will be an excessive, undesired agglomeration inside the vacuum-mixer boiler, resulting In the formation of lumps and possibly clogging the agitator in the boiler, so that the acid crystal particles will not be reliably coated In the desired manner with the carbonate layers.

The object of the invention therefore Is to improve the method according to the preamble so that even without using a vacuum mixer, effervescent granulates of high quality and stability can be produced and the process as a whole can be carried out more quickly even when the substances for the acid crystals react violently with the substances for the coating layers.

According to the invention, this problem is solved by a development of the method according to the Invention by means of the features set out in claim 1.

Particularly preferred embodiments of the method according to the invention are disclosed in claims 2 to 15. The effervescent granulate according to the invention is the subject of claim 16, whereas its use is the subject of claims 17r 18 and 19.

The invention is based on the surprising discovery that the desired addition reaction of one or more coating layers containing alkali—metal or alkal Ine-earth metal carbonates can be obtained e.g. on citric acid crystals even without using a vacuum mixer as described e.g. in AT-PS 37 61 47, if a part of the e.g. citric acid is reacted with a part of the e.g. calcium carbonate in a suitable solvent, I.e. water, alcohol or a water-alcohol mixture before being applied to the acid crystals, and if the resulting pre-reaction solution Is then applied to the acid crystals. This is an unexpectedly advantageous development of the procedure known e.g. from DE-OS 34 34 774, according to which addition reactions with alkali-metal or alkalIne—earth metal bicarbonates or carbonates can be brought about on the surface of the e.g. citric acid crystals using varying polar solvents and the resulting reaction products, i.e. mainly mono- or, if required dl—salts of citric acid In the present case, serve as binders for the subsequent layers or for incorporation of salts or the like. The difficulties of the previously-known procedure can be completely avoided 40 45 50 by -the teaching according to the invention even when using vacuum mixers, since there is no longer the difficulty -that if the reaction is too violent, i.e. if too much 1iquid is introduced Into the vacuum mixer, excessive undesirable agglomeration occurs Inside the boiler therein, resulting in lump formation and also possibly jamming the agitator in the boiler and falling completely to achieve the desired object of coating the acid crystals. According to the invention, therefore, at least part of this reaction is brought about outside the boiler, e.g. in the case of calcium products or potassium products citric acid is reacted with calcium carbonate or potassium bicarbonate in sufficiently concentrated form for the final concentrated solution to be clear and for no visible crystallization to occur, at least for some time. The very concentrated pre—reaction solution is then sucked into the vacuum mixer, with the advantage that it Initiates a very slight reaction, or none, with the acid crystals therein, depending In the present example on whether a solution of dl-calclum citrate or mono-calcium citrate Is made. Production of a tri-calcium citrate solution is of course impossible, because it is Insoluble in water. If, at the beginning of a first addition-? reaction step or in subsequent steps or stages, citric acid is sucked in, not with a solvent but as an already pre-reacted solution only, i.e. the pre-reactlon solution according to the invention, the resulting reactant is an excellent binder for additional calcium carbonate or potassium bicarbonate or sodium bicarbonate coating layers. After the corresponding coating layers have been made, it may be advantageous to add relatively large quantities of alcohol, preferably lsopropanol. The alcohols then precipitate the inorganic salts of the organic acid, more particularly citric acid, of course in anhydrous form, since no crystallization Incorporating water of crystallization can occur in the presence of alcohol. Before the alcohol evaporates, starch or e.g. neutral salts such as calcium lactate can be introduced and be "stuck on", and then and only then all the water can be removed with the alcohol as an exclpient. This process is particularly advantageous because solutions particularly of potassium citrates, which are in any case concentrated, have a very low vapour pressure, i.e. the solution will not boll at 100*C but at 150*C or even 180"C, and therefore cannot easily be evaporated in vacuo at e.g. 70*C. If however the salts are precipitated by adding alcohol as proposed according to the Invention, and If the water is simultaneously dissolved in alcohol, the vapour-pressure conditions will be normal, so that the water and the alcohol can be evaporated or both together <azeotropically in the case of lsopropanol> in the vacuum mixing process. Also, the process can be repeated a number of times if required.

The specially preferred embodiment of the Invention, in which anhydrous starch on the one hand and anhydrous calcium salts of the claimed kind on the other hand are added to at least one coating layer containing calcium carbonate, has the special advantage that the concentration of calcium in the effervescent granulate can be Increased without reducing the rate of dissolving, but actually with a dramatic increase thereof and a further marked improvement in the durabllity of the effervescent granulate. Since the additives are used in anhydrous form, they also act as additional drying agents when storing the granulate or an effervescent tablet, in that they prevent a chain reaction occurring between the calcium carbonate and the citric acid and liberating water which will cause premature ageing and deterioration of the effervescent granulate or tablet. The starch also serves as an effervescing agent for the additional calcium salts, which are in any case difficultly soluble and/or cannot react with the edible organic acid, so that when the effervescent granulate dissolves, the salts are distributed In the water particularly quickly, using the mechanical effervescents effect. Effervescent granulates produced in accordance with this preferred embodiment of the invention are particularly suitable as Instant preparations which dissolve in about 20 to 30 seconds at about 5*C, as contrasted with the calcium carbonate preparation, which takes unacceptably long times (several minutes) to dissolve at these low temperatures.

For the purpose of the Invention it is particularly Important to use the starch In a completely anhydrous state, since this is the only way of achieving a quasi-mechanical effervescing effect guaranteeing the short dissolving times as previously described. Effervescent granulates produced by the method according to the invention are so durable that they can be kept practically in open bottles, owing to the synerglstlcal 1 y obtained "drying-agent properties" of anhydrous starch on the one hand and the anhydrous calcium salts on the other hand, which are difficult to dissolve or do not react with the edible organic acid.

In all cases it should be remembered that the inventive idea of using pre—reacted "buffer granulating solutions", though preferably suitable for the vacuum mixing method according to the preamble, also leads to the aforementioned considerable advantages in the case of "atmospheric granulation", i.e. granulation without using vacuum mixers, in which, case granulation can be brought about on a large industrial scale e.g. in mixers or the like, and the final drying can be on belt dryers or the like.

According to the invention also, as claimed, isotonic and hypertonic effervescent granulates can be produced, characterised in that they can be mixed with instant sugar in a proportion up to about 1 : 5 and, owing to the density of the granulate and its surprisingly high local capacity to effervesce, are capable of producing turbulence In and simultaneously dissolving up to five times the quantity of Instant sugar. It is thus possible to prepare instant soft drinks which, like conventional soft drinks, contain 8 to 10 wt.% sugar but also contain the required amount of citric acid and mineral salts such as calcium, magnesium, sodium and potassium, of course with flavouring additives. These instant products differ in an extremely advantageous manner from the hitherto-known similar instant products, which dissolve very slowly in water with agitation and also taste relatively flat.

The aforementioned process can be repeated a number of times, and the concentrations of the solution or pre— reaction solution can of course be varied within wide limits. If for example "ready-made" calcium salts such as calcium lactate and/or calcium heptagluconate, are introduced e.g. in a coating step, these already neutral salts reduce the speed of the reaction, thus reducing the need for strongly neutralized or pre-reacted -solutions. When on the other hand starch is Incorporated, it may be advantageous to use more highly concentrated solutions, to prevent the incorporation of residual moisture in the starch. As before, subsequent treatment with alcohol, preferably lsopropanol, likewise in vacuo, can be a very elegant method of removing residual moisture from the starch also, with a corresponding advantageous influence on the stability of the resulting effervescent granulate.

Example 1; The procedure according to the invention is particularly advantageous in the treatment of hygroscopically difficult potassium salts. To this end, 250 parts by weight of crystallized citric acid having a particle size of 0.4 to 0.6 mm was reacted in a solution of 20 parts by weight of citric acid in 15 parts by weight of water, to which 20 parts by weight of potassium bicarbonate had been added. The solution was agitated in a high—speed agitator and heated to 31*C, thus giving a pre-reactlon solution.

Next, 210 parts by weight of pulverized potassium 4 bicarbonate were added. The pre—reaction solution, which consisted substantially of di-potasslum citrate, served as a binder and buffer between the citric acid and the potassium bicarbonate, preventing a violent reaction, 5 since di—potassium citrate in any case reacts very slowly and sluggishly with potassium bicarbonate. It is thus possible to obtain granules, I.e. a uniformly pourabl e structure, and also ensure that a passivation layer is Incorporated between the citric acid crystals on the one 10 hand and the very strongly hygroscopic potassium bicarbonate on the other hand. In this procedure it is advisable and advantageous, after one or two coating processes of the previously-described kind, to add a larger quantity of alcohol, preferably three to four times 15 the amount of water hitherto used, in order to precipitate the potassium salts, which are insoluble in alcohol, in anhydrous form and remove the aqueous solvent with water, a process which particularly advantageously may be azeotropic in the case of lsopropanol.

This procedure yields extremely pourable granulates which can be compressed to form very hard effervescent tablets which have greatly reduced sensitivity to atmospheric moisture, since dl-potassium citrate can also Incorporate water of crystallization, in contrast to mono-potassium 25 citrate. There is the same possibillty in the case of tri-potassium citrate, In which case the pre-reactlon solution contains 30 parts by weight of potassium bicarbonate instead of 20 parts as described previously. In this case, therefore, granulates are produced by means 30 of a solution of tri-potassium citrate which as before is precipitated in anhydrous form by alcohol and forms a passivation layer between the individual reactants, I.e. between the acid crystals and the first coating layer or between two successive coating layers. , In practice, however, di-potasslum citrate has given better results, because the adhesive power of this salt, which probably later becomes a mixture of mono-, dl- and tri—potassium citrates during the reaction, has much better binding properties than even a defined tri-40 potassium citrate, to name only one example.

Example 2; The procedure was the same as in Example 1, except that a coating layer of magnesium oxide was also applied. To this end, the di-potasslum citrate solution was added to 45 90 parts by weight of crystallized citric acid. The pre- reactlon solution, prepared as in Example 1, was then distributed among the citric acid crystals by mixing, after which. 20 parts by weight of potassium bicarbonate were applied. Additional pre—reaction solution was then Introduced, after which 11 parts by weight of magnesium oxide were anchored as an intermediate layer. Finally, an additional amount of pre-reaction solution and 25 parts by weight of potassium bicarbonate were added, thus giving a final coating layer which was finally dried with agitation.

In short, the procedure according to the invention can avoid the necessity of prolonged heat-treatment of effervescent tablets and also effervescent granulates after the granulates have been wet pressed and even when a vacuum mixer is not used and granulation is brought about under atmospheric conditions. During such heat treatment, as conventionally used In the prior art, the water partly evaporates and reactions of the previously-described kind, of the sort brought about in vacuo in the end product, may of course occur without it being possible to remove water of crystallization. In the prior-art procedure also, added constituents and especially vitamins and flavourings may be destroyed by the moisture and the acid or strongly alkaline reactants, so that this procedure Is unsuitable for sensitive active principles. This is another considerable advantage of the procedure according to the invention over the process described as "curing", especially In the American literature, i.e. wet-pressing of tablets and subsequent final drying by prolonged heat treatment <e. g. Herbert A. Liebermann .and Leon .Lachmann "Pharmaceutical dosage forms - tablets". Vol. 1, pages 232 - 243>.

Claims (20)

CLAIMS:

1. A method of producing an effervescent granulate containing at least one solid crystalline edible organic acid and at least one alkali-metal or alkaline-earth metal carbonate which spl its off COB on reacting with the organic acid in aqueous solution, characterised by the following steps:

<a) A part of the total quantity of acid and a part of the alkali—metal carbonate or carbonates in a first pulverized coating substance containing at least one alkali-metal or alkaline-earth metal carbonate are dissolved in a solvent for the acid and reacted together;

(b) The acid crystals not used in step <a) for producing the pre-reaction solution formed therein are wetted with the pre-reactlon solution produced in step <a);

<c> The acid crystals wetted with the pre-reaction solution in step <b> are intensively and thoroughly mixed with the part of the first pulverized coating substance not used for producing the pre-reactlon solution, with the result that a first coating layer Is formed on the acid crystals and is stuck to the surface thereof by a bonding layer formed by reaction between the acid' and carbonate;

<d) After the first coating layer has formed, at least one additional solid pulverized coating substance containing at least one alkali-metal or alkaline-earth metal carbonate is added, with vigorous agitation to the acid crystals provided with the first coating layer In step <c>, thus forming at least one additional coating layer on the previous coating layer, which is wet with split-off water of crystallization;

<e) The coating process Is stopped, followed by final drying.

2. A method according to claim 1, characterised in that after the first coating layer and/or at least one of the subsequent coating layers has formed, intermediate wetting is brought about with an additional prereaction solution formed by pre-reacting a (respective) additional part of the total amount of acid and a part of the alkali-

metal and/or al kal ine-earth metal carbonate of the next-following coating substance In an additional solvent.

3. A method according to claim 1 or 2, characterised in that the solvent Is heated to about 30 to 40*C before Introducing the acid and/or the alkali—metal or alkaline-earth metal carbonate or carbonates.

4. A method according to any of the preceding claims, characterised in that the pre-reaction solution or solutions are heated to about 30 to 40*C before applying to the acid crystals.

5. A method according to any of the preceding claims, characterised in that the pre-reaction solution or solutions are produced in a concentration such that they are still clear and no visible crystallization occurs in them during the time required for working the method.

6. A method according to any of the preceding claims, characterised in that the solid pulverulent coating substance or substances each contain a part of the total quantity of acid.

7. A method according to any of the preceding claims, characterised in that after at least one coating layer (the last if required) has been applied, alcohol is applied at least once followed by drying.

8. A method according to claim 7, characterised in that the alcohol used is lsopropanol.

9. A method according to any of the preceding claims, characterised by use of at least one coating substance containing starch and/or an alkali-metal and/or alkaline-earth metal salt which is difficultly soluble and/or does not react with the edible organic acid.

10. A method according to any of the preceding claims, characterised by use of at least one pre-reactlon solution containing starch and/or an alkali-metal and/or alkaline-earth metal salt which is difficultly soluble and/or does not react with the edible organic acid.

11. A method according to claim 9 or 10, characterised in that the non-reactive salt used is calcium lactate.

12. A method according to claim 9 or 10, characterised in that the non—reactive salt used is calcium laevulate.

- 10 -

^

13. A method according to claim 9 or 10, characterised

In that the non-reactive salt used is calcium gluconate, f preferably calcium heptagluconate.

2

.4

14. A method according to any of claims 11 to 13, 5 characterised in that the or each coating layer is produced with a content of 5 to 30 wt.% of non-reactive calcium salt relative to the respective content of alkali-metal and/or alkaline—earth metal carbonate.

15. A method according to any of claims 9 to 14, 10 characterised in that the or each starch-containing coating layer is manufactured with a content of 2 to 8 wt. % of anhydrous starch relative to the content of the respective alkali-metal and/or al kal ine-earth metal carbonate.

15 16. An effervescent granulate produced according to any of the preceding claims.

17. Use of the effervescent granulate according to claim 16 as an instant granulate for producing effervescent drinks or the like.

20 1®* Use of the effervescent granulate according to claim 16 for producing effervescent tablets.

19. Use according to claim 17 or 18, characterised in that the effervescent granulate is mixed with instant sugar in a proportion of up to 1 : 5.

25

20. A method according to Claim 1, substantially as herein described in the Examples.

MACLACHLAN & DONALDSON, Applicant's Agents, 47, Merrion Square, DUBLIN 2.