Process and device for handling processing material and the reaction product manufactured with the aid of the process and/or device

The invention further relates to a method according to the preamble of claim 1. The invention also relates to a device according to the preamble of claim 10, as well as a reactive product produced by means of the method and / or the device.

In the pharmaceutical industry in particular, it is frequently necessary to mix, heat, moisten and dry powders and granules, or the like. These treatment steps often require different methods depending on the type and quantity of the raw materials. Some raw materials may only be moved and / or heated, others moisten and dry to form lumps and / or a skin which prevents the complete drying; Frequently even the uniform distribution of solvents or wetting agents, relatively small amounts of auxiliaries or active substances, etc., is difficult or at least time-consuming.

Therefore, a wide variety of methods and devices have been proposed which should solve these problems, but this is still unsatisfactory in many cases. Thus, the granulation of powders still requires a multi-stage treatment, and the drying of, in particular, larger batches requires an often long-lasting treatment. This also applies to drying processes in which hot air is sucked through or over the bed of a moistened material and / or the moisture is to be removed by the application of a vacuum. In this case, it is often the case that the mixture particles are heated superficially in the bed and dry, but, for example, existing binders, as mentioned above, form a skin which makes further drying more difficult or even impossible.

According to the state of the art, for example, the process material is mixed with liquid treatment agent and then freed from this or its evaporable parts by heating and / or pressure reduction. As already mentioned, the exact dosing and uniform distribution of the treatment agent can, in particular for comparatively small treatment agent proportions, for example those which are insufficient for embedding or forming a flowable dispersion, with a large surface area of ​​the bulk material and / or with large differences in density - to cause problems; Also the removal of the vaporizable portions of the treatment agent is not always easy, in particular if the process material can be separated off only poorly or only with a high energy or a large process expenditure. In the case of polar solvents including water as treatment agents, these problems are usually particularly pronounced because of the great chemical and physical reactivity of these agents, the boundaries between "chemical" and "physical" bonds or binding agents often becoming blurred in systems with comparatively large surfaces. It is therefore often necessary to dispense with the use of an effective and advantageous, because inexpensive and ecologically problem-free treatment agent and either to replace or "dilute" it by another means;

The theoretical processes involved in the processing and processing of powders had not yet been mastered, but had been mainly subjected to long-standing procedures. For example, in the production of medicaments, starch is still used as a binder, a specific amount of starch being hydrolyzed with considerable amounts of water for each batch, which must then be removed again in lengthy drying processes; Thus agglomerating or granulating the mass, which is subsequently comminuted to the desired grain size. For this reason, the automation of these process steps has not yet advanced very far.

However, if one proceeds from a process which has been solved in individual steps and ensures that, on the one hand, sufficient heat and / or on the other hand the treatment agent is introduced into these stages at the desired concentration, an optimum and, above all, reproducible solution of the initially mentioned is obtained Tasks.

If a carbohydrate, such as, for example, lactose or sugar, is to be granulated with an active ingredient, the powder mixture is treated with water, some parts dissolve and, after drying, show coarse-grained structures. A complete uniformity of composition and grain size is by no means assured.

A particular example for the particular tasks of the treatment of pourable solid process material is the special field of the agglomeration of pulverulent mixtures with or without chemical conversion in the interface area, such as, in particular, the production or processing of the water in the presence of water under the development of CO₂ Reactive formulations, hereinafter referred to simply as "reactive products".

However, the preparation of such reactive products is only one of many examples of the problems of the treatment of finely divided process material; Another example is the granulation of spray-dried or fine-grinding substances or the performance of chemical surface reactions.

SUMMARY OF THE INVENTION The object of the invention is to provide a method and a device by means of which it is possible, in a comparatively short time, to treat a batch of powder or granules very evenly and to dry them if necessary, Or substances susceptible to interferences.

The method is intended to allow an accurate control of the treatment process as well as the rapid and simple attainment of an almost arbitrarily uniform treatment or distribution of treatment agents even if their proportion relative to the process material is very small or the tendency to undesirable or undesirably strong interactions between the treatment agent and process material Particularly large or the removal of the treatment agent is normally very energy-consuming.

These objects are surprisingly achieved by a method according to the characterizing part of claim 1. Preferred embodiments of this method are described in the features of claims 2 to 9.

Both of the measures according to the invention already produce more heat alone and lead to a more uniform treatment than would be the case without one of the measures. Of course, their simultaneous application is even better.

In the treatment according to the invention, for example, for the granulation of an effervescent mixture, the hot air is charged with steam, which then condenses; Then the steam can be switched off, the carbon dioxide and moisture formed are removed with hot air and then dried under vacuum. Preferably, the hot air stream is therefore forced in at a pressure of 1.5 bar because, in order to prevent the resistance of the heat exchanger, too high vacuums are necessary. This would prevent or at least reduce the condensation of the steam.

In EP-A-151 782, which is a priority but not prepublished, the single treatment of a bulk material in a vacuum drum is disclosed with a hot-air stream, which may be charged with steam, which is passed through the bed. There are several disadvantages:<ul><li>- when passing through the mixture, the nozzles can easily become blocked with still moist, fine-grained material;</li><li>- in order to achieve the treatment in one pass, the temperature and / or steam concentration must be relatively high; But this leads to local overheating and / or uneven condensation.</li></ul>

In the same way, the one-off process described in DE-B-1 060 093, in which, by the way, not necessarily heating is carried out, a vaporous solvent is suctioned once for the granulation of a powder, and is removed again after condensation by vacuum.

A drying method has now been described in GB-A-2 031 570, in which liquid or paste-like products are subjected intermittently to a vacuum and then again to a heated, dry gas stream; However, even with comparatively few moisture-containing products, such as yeast or onions, extremely long drying times occur, which appear to be advantageous only in comparison with the still much longer freeze-drying times. This is due to the fact that the air stream is circulated and freed of solvent vapor via an absorber bed, resulting in a considerable pressure drop. Therefore, on the one hand, the intake phase lasts too long; On the other hand, the air stream carries only a small amount of heat in order to re-heat the material, which has been cooled too far by the application of vacuum.

A conventional heat exchanger for air preheating has a certain flow resistance. If this is now overcome in a conventional manner by a suction process, a relatively high vacuum is created in the boiler and thus a strong cooling of the material or a high heat loss occurs. Compressed air, on the other hand, compensates for the loss of friction in the heat exchanger by a compressor.

By virtue of the fact that hitherto the hot air was sucked essentially only through or over the material, the temperature to be dried was evidenced by the evaporation of the moisture to be dried, which could only be compensated slowly by the hot air flowing in; A large part of the heat energy was lost. If, however, a lower heat loss was obtained by pre-heating the mixture, the above-mentioned problems arose which could only be solved with the method according to the invention or which do not occur at all until the mentioned disadvantages are avoided.

The usual treatment processes between, for example, a powdery processing material and a liquid, for example a solvent, are separated into individual steps, which can be controlled and controlled more easily and, if appropriate, even programmable in the direction of automation. This has hitherto not been possible for a person skilled in the art in connection with such treatment processes, since many liquids, such as, for example, binder solutions or even water alone, are still far too viscous to achieve a uniform distribution in the micro-range of process material particles of a size of between 10 and 100 microns allow. So far, a very large excess of solvent had always to be added in order to achieve a secure wetting of all particles.

If, on the other hand, the binder, the filler and the active ingredient are mixed in powder form and then treated step by step with very small amounts of the solvent whose viscosity drops drastically when diluted in the vapor phase and by hot air, Solved the seemingly insurmountable problems.

Water vapor alone does not lead to usable results in all cases because the condensation of the water vapor takes place much too quickly at the point of its entry on a cooler surface, ie on the particles to be granulated, and leads to the formation of clumps. If, for example, 10 liters of air of 120 degrees C contains only 100 ml of water, the condensation takes place significantly slower before the water becomes liquid. The slow condensation of a liquid from the vapor phase in the finest droplets (mist formation) is also unequally more effective and energetically more economical than the treatment with liquid in many other processes.

The parameters required for a reproducible and programmable procedure are the temperature of the process material and the air supplied, the proportion of the vaporous reaction partner, or treatment agent in the dilution phase, and the optionally selected negative pressure. With this procedure, the wetting of the process material particles can be separated into several stages and the structure of a granulate, ie, the grain enlargement can be precisely set, and the process can be terminated in a timely manner.

If, for example, a mixture of 80 parts of lactose, 15 parts of a pharmaceutical active substance and 5 parts of a binder is treated approximately 10 times successively with in each case only 3 parts of water in approximately 15 parts of inflowing hot air, and dried after each treatment by applying vacuum, Then the aforementioned desirable control of the method is achieved and, in the programmed circuit of the device described below, only three control parts, namely the inflow valve for the pre-set steam-air mixture, the vacuum pump to change from a low constant vacuum for The condensation to a full vacuum for drying, and finally the control of the stirring speed, which is to be high during condensation, but during drying should be low.

The hot air laden into the drum and / or steam which has a much higher specific heat than the air gives off its heat to the material, resulting in the desired treatment effect, for example, an evaporation of the moisture at the respective one Grain surface. Since negative pressure has prevailed in the bed before, the hot air penetrates into all areas of the bed.

This inflow is important and, according to the invention, is highly superior to the conventional suction through the material. Even a secondary air circulation in the cavity above the bed in the vacuum mixing boiler gives rise to turbulence only in the same airspace, or even to dust it.

Of course, in simple drying processes you have to optimize the steam content of the air. More steam gives more heat to the material, but for balance reasons prevents more moisture from evaporating. This is, however, a variable which can be easily ascertained by a person skilled in the art as a function of the material to be treated, or the action to be taken.

In the subsequent phase, in which vacuum is applied, this moisture is sucked off. Due to the fact that the vacuum phase generally represents only a fraction of the hot-air pressure phase, only the minimal, absolutely necessary heat quantity is lost. The heat loss can be further reduced if the hot air supply is interrupted during at least one part of the extraction phase.

If, in this phase, a skin is formed on the grain surface, the moisture content inside the grains during the subsequent hot-air pressure phase is again given the opportunity to diffuse outwards ("migration"), to dissolve the skin formed there and to enter the skin Hot air to evaporate.

The temperature of the hot air and the cycle times can easily be adjusted to the product to be treated. With the method according to the invention, it is also possible to dispense 100 or more kg of fine powders such as, for example, milk sugar, dust sugar, paracetamol, naproxen etc., which contain, for example, 10 to 20% moisture, within 30 to 60, often even only Of 20 minutes to dry. The control of the cycle time and the termination of the method can be carried out, for example, after a running moisture measurement.

If the pressure difference between the hot air inlet and the suction in the vacuum phase is too great, the above-mentioned disadvantages of the prior art result at least in part, albeit to a lesser extent.

Despite the mentioned penetration of the bed with hot air or vacuum, it has proved to be expedient in many cases to prevent agglomeration, at least from time to time, to move the bed by means of a drum rotation and / or the movement of a stirrer. However, an excessively intense movement should be avoided, since the granulate formed or formed in this process can be destroyed and undesirable dust can be formed especially for the vacuum pump.

For carrying out the process according to the invention, the particulate material, for example, having a particle size of from 0.01 to 1.5 mm or more, may be introduced into the process chamber, for example a vacuum chamber, if necessary as a premixing of the components or in the form of the individual components With mechanical and / or pneumatic means for moving the process material.

Suitable means of movement are those which exert a slight shearing force on the material, preferably those which effect a movement of the material counter to the gravity, such as in particular the two- or three-dimensionally vibrating mixing devices. Mixtures which also trigger a mechanical as well as a pneumatic movement of the process material, for example hollow mixing arms, through whose openings hot gas can be blown in, are also preferably used.

In the context of the invention, the term "hot gas" or "hot gas" means a gas or a gas mixture which is ideal in comparison with the treatment medium vapor, such as nitrogen, air, noble gas or carbon dioxide, provided no undesirable reactions are caused thereby.

The temperature of the hot gas in the process according to the invention must be higher than the evaporation or boiling temperature of the treatment agent at normal pressure of about 1 bar, typically by at least 10 ° C. and preferably by at least 20 ° C. higher. The upper limit of the temperature of the hot gas is not particularly critical but, for reasons of heat sensitivity of the process material as well as to avoid an unnecessary thermal load on the equipment used and for reasons of minimizing energy consumption, is not increased beyond the stated minimum values ​​without special reason.

Treatment agents which are suitable for the process according to the invention must evaporate (or sublime) practically without residue in the hot gas at normal pressure and condense at normal pressure and temperatures of typically between zero and 200 ° C., preferably between room temperature and 100 ° C.

Liquid and, in particular, polar treatment agents which are liquid at normal temperature are generally preferred for the process according to the invention. Water is preferred, but organic solvents are not excluded. A treating agent suitable for the process according to the invention must be able to condense in the form of very fine particles on the optionally warm process material and can be easily removed from the process material which has been heated if the pressure prevailing in the process space is reduced.

When using water as a treating agent, the hot gas, for example air, has a temperature of more than 100 ° C., preferably at least 110 ° to 150 ° C., the condensation being carried out on the typically approximately 50 ° C. process material at 200-900 mbar and The evaporation takes place at approximately the same process material temperature and, for example, at 10-30 mbar.

The concentration of the treating agent vapor in the hot gas can be varied within wide limits, for example from 0.1 to 50% by volume or more; The use of mixtures with higher treatment agent vapor contents is possible, but is usually not preferred; Typical hot air / water vapor mixtures contain, for example, 1 to 5, preferably 2 to 4, volumes of hot air per volume of water vapor. Before and / or after treatment of the process material with the treatment agent or water, hot gas or, if desired, cold carrier gas can be passed through the process material in order to achieve a desired heating or cooling effect.

The treatment agent can be metered into the heat exchanger, which is also used for heating the gas, to produce the mixture of hot gas and treatment medium steam (hereinafter called the gas / steam mixture).

Preferably, the material presented in the process chamber is preheated before introduction of the gas / vapor mixture, for example to a temperature which is clearly below the normal pressure boiling temperature of the treatment agent, for example by 30 to 60 degrees lower.

This preheating of the process material can be carried out with hot gas and / or by heating the wall of the process chamber from the outside (heating jacket). The heat transfer between the chamber wall and process material can thereby be effected directly, ie, by contacting the process material with the heated wall or, if there is not a markedly reduced gas pressure, indirectly via the gas / steam mixture located in the chamber.

In order to effect the condensation of the treating agent vapor on the solids particles forming the process material in as finely uniform, finely divided form, the gas / steam mixture is generally brought to the preferably moved and heated process material at a normal or slightly reduced pressure The process material particles does not form a liquid phase; For many applications, the process is preferably carried out in such a way that the process material particles are not "wet" in the sense that a continuous liquid film is formed on each particle or the space between the particles is practically filled with liquid. For an optimal distribution of the treatment agent on or in the process material particles, it is preferred that the treatment agent is in the form of very fine, ie Normally sluggish droplets ("mist") are condensed on the process material particles and are absorbed, ie, absorbed, or virtually reacted by the surface of the process material as it condenses on them. The choice of the pressure, temperature and quantity values ​​for the condensation and the adaptation to a given process product can be optimized by means of simple tests.

The step described hereinafter as a condensation phase can be terminated after the introduction of the gas / steam mixture or extended beyond this time for the distribution of the condensate in the material and / or for the interaction between the components of the material; The duration of this phase consisting of the actual condensation and, if appropriate, treatment agent action is typically only a few seconds to several minutes, eg 10 seconds to 10 minutes, rarely longer.

The condensation phase is terminated by reducing the pressure in the process chamber to such an extent that the boiling point of the treatment agent is reached at least at the prevailing temperature of the process material and the reduced pressure and is preferably exceeded.

With this pressure reduction, for example from 10 to 50 mbar, the treatment agent removal phase begins, which can lead to a partial and typically at least 50% or practically complete removal of the treatment agent; Also this phase can typically be completed in seconds to minutes, for example 30 seconds to 30 minutes.

A condensation phase with a subsequent removal phase is here referred to as a "treatment cycle"; As indicated above, the treatment according to the invention is carried out at least with two, preferably with five or more cycles, until a certain final state, for example a desired agglomeration and / or reaction and / or diffusion degree of the process material, is achieved.

In contrast to the present invention, a solvent is also sucked in AT-A-372 299, but a defined reaction is allowed to proceed to a defined pressure increase and then dried with a vacuum. In the present case, however, the vapor / air mixture is pressurized with steam at 600-900 mbar at an overpressure of 0.5 bar, ie 1500 mbar, and is condensed, always under reduced pressure, and then either the resulting C0₂ Or H₂0 is filtered off with hot air at the same 600-900 mbar or vacuum dried and the entire process is repeated cyclically, ie the free volume in the reaction vessel is not allowed to pass through the C0 formed by reaction₂ And water, but is simultaneously suctioned off during the pressure of the steam / air mixture. The advantage of this is that the product remains at temperature, since the exothermic process is condensed with steam by the added hot air; By the fine distribution of the fog, the reaction is not so violent, but can easily be carried out several times.

Reactive products according to the invention consist, for example, of a normally solid, approximately crystalline carboxylic acid, such as citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, ascorbic acid, or mixtures of such acids with finely divided reaction partners, for example carbonates or bicarbonates of alkali metal salts Alkaline earth metal, zinc or iron oxides or hydroxides, or other salts of acids which are weaker than the carboxylic acid used, for example zinc glycerophosphate, iron gluconate, calcium lactate, etc.

An optimized interface between the acid and the carbonate particles is achieved when practically every acid particle is surrounded by carbonate particles; It is understood that an agglomerate may also contain a plurality of acid particles, but each of which is practically encased in carbonate particles, as will be explained further below.

Additional binders and fillers such as sugars, mannitol, starch or lactose can be used here; Preferably, as a binder between the acid particles and the carbonate particles, a compound formed by reaction in situ from the acid and the carbonate, for example calcium citrate, which accounts for approximately 1 to 5% of the weight of the components forming them.

By means of corresponding cycle repetition, additional components, for example colorants or active ingredients which have a solubility of at least about 5 g / liter in water at process temperature temperatures, can also be uniformly distributed in a particulate process product by the process according to the invention.

In particular, it is possible in this way to prepare new reactive products for instant or effervescent preparations, or with sparingly soluble carbonates, such as MgC0₃, CaC0₃ Or oxides, such as, for example, Mg oxide, as well as toxicologically permissible fluorine compounds, such as disodium fluorophosphate, in the absolutely uniform distribution which is absolutely necessary for such products, the carbonate particles being fixed or releasably fixed on the acid particles in a particularly simple and cost- In the surface thereof. A particularly close contact between the sparingly soluble reaction partners with the acid crystals is important; It is facilitated by the addition of powdered acid. For other solutions which are difficult to solubilize, for example, alkaline earth carbonates, it is expedient to ancharily more readily soluble alkali metal carbonates if it is desired to obtain effervescent mixtures.

It is surprising that a reactive product with calcium carbonate as C0₂And with a content of water-soluble fluorine compounds, for example in proportions of 0.05 to 10% of the weight, is available and useful; It would have been expected that the soluble fluorine compound would quantitatively react with the calcium carbonate or calcium citrate during the preparation to form the insoluble calcium fluoride and it can not be ruled out that the precise controllability of the process according to the invention preferably used for the production of such fluorine-containing reactive products is a decisive factor Plays.

Even sparingly soluble oxides such as, for example, magnesium oxide or magnesium oxide carbonate, iron oxide, zinc oxide, etc. and the like can be so anchored by this process on the surface of an acid by partially reacting with the organic carboxylic acids which are wetted by condensing mist, Are very uniformly fixed on the organic acid.

As a result, the process of conversion to magnesium citrate, iron citrate, zinc citrate, etc., initiated during the production process by means of water vapor can be continued during the introduction of the organic acid with the attached oxides in water, whether as an instant product or as a reactive effervescent product.

A device which is particularly suitable for carrying out the method according to the invention and the structure of certain reactive products are explained in more detail by way of example with reference to the appended drawings, show it:<ul><li>1 is a schematic diagram of an apparatus for carrying out the method according to the invention, and FIG</li><li>FIG. 2 is a schematic sectional view</li><li>And 3 of an agglomerate prepared according to the invention.</li></ul>

1 shows the schematically illustrated device 10; Which comprises a pump or compressor 11 which sucks a gas, for example air, at 110 and feeds it into the heat exchanger 13 through the line 111 with the optional valve 112. The conveying capacity is, for example, 10 to 100 liters / minute; The pressure at which the gas leaves the heat exchanger is adjusted, for example, to 1.5 bar, depending on the desired process parameters. The container 12 contains the treatment agent and can be delivered to the heat exchanger 13 via the line 121, metered through the valve 122, where it is evaporated, if desired, to form the mixture of the hot gas and the treating agent vapor.

The heat exchanger is connected to the process chamber 14 via the line 141 and the control valve 142, into which process material or process product components G are fed and can be withdrawn from the finished product P.

The process chamber 14 is supplied with heat W, for example by means of a heating jacket (not shown) and with movement energy E, for example by means of a mechanically and / or pneumatically acting stirrer (not shown) for moving the process material. The process chamber 14 is also connected via the line 151, the control valve 152, an optional condenser 15 and the line 161 to a suction or vacuum pump 16, which passes through the gas withdrawn from the chamber 14 and, if appropriate, the treatment agent not removed in the condenser 15 The conduit 160, if necessary via a cleaning plant, into the open air or recirculates (in a manner not shown) to the heat exchanger 13. The power of the pump 16 is preferably at least as great as that of the pump 11.

The optional condenser 15, which is not preferred when water is used as a treating agent, can be maintained in operation via the coolant lines 154, 155, the condensed treatment agent being discharged via the conduit 157 and, if appropriate, via the valve 158 and the return line 159, to the treatment agent container 12 .

For carrying out a preferred embodiment of the method according to the invention, the device 10 has a program controller 17 which in the simplest case only controls the opening / closing process of the valves 142, 152 as well as the instants of the valve actuation.

Provided that all parts of the device 10 are in operation, the condensation phase can be initiated by opening the valve 142 with the valve 152 fully or partially closed, and can be terminated by closing the valve 142 and opening the valve 152, ie the evaporation phase can be initiated.

FIG. 2 is a schematic sectional view of a stereospecific agglomerate having a plurality of cores; FIG. The cores represent, for example, the relatively coarse-particle acid particles of a reactive product which is referred to as CO₂Is a relatively finely divided calcium carbonate represented by the particles 23. Each core is covered by the particles 23 to at least 80% of its surface area.

Between the cores and the carbonate particles 23, the structurally simplified and proportionally exaggerated binder layers 22 are shown which can be formed in situ in a reproducible manner by reacting the acid with the calcium carbonate in the presence of small amounts of water according to the method according to the invention, eg In proportions of 1 to 5% of the weight of the acid and carbonate particles.

It is to be understood that the cores 21 are normally not spherical, but generally grained, as is typical of more or less crystalline substances. Otherwise, the acidic nuclei may have different sizes as long as they are relatively coarse relative to the carbonate particles.

FIG. 3 shows schematically and greatly enlarged parts of a citric acid crystal 21 'treated according to the invention with magnesium oxide and potassium carbonate. In a first cycle, a layer 22 'of magnesium oxide and citric acid powder is applied there, the magnesium oxide particles 23' being surrounded by a magnesium citrate layer (not shown). In a second cycle, a layer 22 "of the same constituents was applied, and in a third cycle, potassium carbonate crystals 25 were applied, a potassium citrate layer 24 being formed on the contact zone Individual particles and layers do not exist as such, but are at least partially blurred by diffusion.

In an analogous manner, a reactive product according to the invention can be constructed such that the particles 23 'contain a toxicologically permissible, water-soluble fluorine compound, such as, for example, alkali fluorophosphate, as will be explained later on with reference to Example 3.

Furthermore, the invention is further explained by the following examples, but not by way of limitation.

Example 1:

200 kg of a powder mixture consisting of 150 kg of naproxen, 22 kg of filler, 20 kg of water and 8 kg of polyvinylpyrrolidone are used in a 720 liter vacuum drum with a usable volume of 300 liters.

First, the vacuum valve is opened and a pressure of 200 mbar is obtained for about 50 seconds. The vacuum valve is then closed and hot air is pressed in for 30 to 120 seconds via the hot air generator until a pressure of about 1 bar prevails in the treatment drum. Subsequently, a vacuum is applied again for 50 seconds and the treatment is repeated cyclically. During the hot-air pressure phase the migration of the moisture from the interior of the grain takes place to the outside, and the discharge of the already outside moisture to the hot air takes place. There is also some convection. During the vacuum phase the discharge of the steam-laden air takes place. Within 20 minutes, the total amount of the powder deposit is dried to a residual moisture of 0.1 to 0.2%.

Example 2:

This example illustrates the preparation of a reactive product suitable for effervescent preparations.

43 kg of citric acid with grain sizes between 0.4 and 0.6 mm are mixed with 22 kg of citric acid with a grain size of 0.1 mm and heated to 45 ° C. in a vacuum mixing vessel (process chamber 14) with a jacket temperature of 65 ° C. 20 kg of micronized calcium carbonate are then introduced; After evacuation to remove possible residual moisture, the material is again allowed to warm to 45.degree.

A constant vacuum of 600 to 900 mbar) is then applied to the vacuum mixing boiler and the heating device (heat exchanger 13) for the air heating is set to 120 ° C. (gas outlet temperature).

The pumps 11, 16 and the valves 142, 152 are adjusted in such a way that approximately 600 to 800 liters of hot air per minute flow into the process chamber 14 at 700 mbar. An amount of 500 ml of water is then allowed to flow from the container 12 into the heat exchanger 13 within 2 minutes, a ratio of 1 volume of water vapor to 2 to 3 parts by volume of hot air being established. Since the boiling point of the water at 900 mbar is about 96 ° C., the water vapor condenses on the process material of about 45 ° C. Under three-dimensional mixing during the suction, the water vapor condenses in the process material in the form of very fine droplets. At the same time, the development of C0 begins₂, Which is withdrawn via the vacuum pump 16.

After introducing the said quantity of water, the reaction is allowed to run for one minute and then full vacuum is applied. With a sufficiently dimensioned vacuum pump (100-200 m³ Per hour) the water removal can be achieved at about 20 mbar within 2 to 5 min.

The following heat balance results:

The condensed water volume causes a caloric intake of about 10,500 kilojoules (2500 calories). A specific heat of 0.84 kilojoules (0.2 calories) per kilogram can be attributed to the process material as a matter of fact. Since the 85 kg of process material required requires only 71.2 kilojoules (17 calories) to heat them by 1 degree C, the temperature of the process material has increased by about 15 degrees C (from 45 degrees Celsius to 60 degrees Celsius) ).

By the application of the vacuum or the resulting evaporation, this energy is again consumed so that the original temperature of the material of 45 ° C. should be reached again after the water removal of the first cycle. However, since the jacket temperature of the process chamber is 65 ° C., a process material temperature of about 50 ° C. occurs after the first cycle because the convection of the incoming water vapor / hot air mixture at the chamber wall somewhat amplifies the heat transfer. The reaction temperature with calcium carbonate is still negligibly low at a process temperature of 50 ° C.

If this cycle is repeated, a process material temperature of about 55 ° C. is established after the removal of water, which already corresponds to the formation of a stable, dry end product when the residual moisture content is removed with about 10 mbar of vacuum. If the cycle is repeated a third time, the stability of the final product is even higher, but the effervescent effect is already somewhat reduced, since already about 20% of the initially introduced calcium carbonate has been converted into calcium citrate in the intermediate layer.

By changing the amount of water vapor, the temperatures and the vacuum used, the reactivity or effervescent temperature of the end product can be controlled as desired. The once defined method can, for example, be controlled programmatically with the device described as follows:

The control valve 142, which is controlled by a manometer, for example, and which maintains a pressure of, for example, 700 mbar in the process chamber 14, is closed at the selected program time, so that the pump 16 brings the process chamber 14 to full vacuum.

When the valve 142 is opened again, an amount of, for example, 500 ml of water arrives in the process chamber 14 for a given time unit of, for example, 2 minutes, with appropriate adjustment. After this time, the valve 142 is closed and, for example, The valve 152 is opened to achieve the full vacuum. If the vacuum in the process chamber reaches a final value of, for example, 20 mbar, the cycle can be repeated.

After two or three cycles, the process chamber can be kept to values ​​of less than 10 mbar for about 15 minutes to finally dry the process material, as a result of which the reactively formed calcium citrate is also dehydrated and thus stabilizes the product.

Example 3:

33 kg crystallized citric acid of the crystal size 0.3 to 0.6 mm, 10 kg of citric acid, 25 kg of micronized calcium carbonate, and 3 kg of sodium fluorophosphate and 200 g of food dye are introduced into the reaction chamber 14 and heated to 45 ° C. therein.

Under the conditions of Example 2, the cycle is carried out a total of three times. After the final drying, both the dyestuff and the sodium fluorophosphate are very evenly distributed by its slight water solubility under the action of the condensing vapor; No significant distribution differences can be observed both when looking at the individual particles under the microscope and in the analysis.

Example 4:

90 parts of cane sugar and 10 parts of vitamin C are brought to about 40 ° C. in a vacuum mixer; A constant vacuum of 600-900 mbar is then applied. Subsequently, within one minute, a quantity of water of one part is passed through the mixture in a quantity of air of about 20 parts, three-dimensionally (oscillating) being mixed at a high stirring speed. The process takes about 60 seconds. The valve for air supply is then closed and the low constant vacuum is replaced by a valve control by the full pump power. The drying process takes about 60 seconds. After these 60 seconds, a final value of about 30 mbar is reached.

At this time, the valve for air-to-steam supply is opened and, in turn, switched to the previous constant vacuum. These steps can be repeated 5 to 10 times, requiring a total of 30 minutes. The resulting granules are absolutely uniform, self-added dyes are absolutely evenly distributed, and the product can be discharged completely dust-free for further processing or packaging via a rotating screen.

Example 5:

95 parts of lactose are mixed with 4.5 parts of polyvinylpyrrolidone and 0.5 parts of a highly effective hormone and heated to 40 ° C. A constant vacuum of about 800 mbar is then established.

In this case, a solution of acetone is allowed to flow into the air as agglomeration agent. This solution can consist of 1 part of acetone in 5-10 parts of air. If, for example, lactose with a grain size of 0.2 mm is used here, a total clumping of the hormone with the lactose is obtained after a treatment of 5 steps, although no differences in the distribution of the individual particles can be determined even with the application of the most accurate analysis.

However, the process is of particular interest when substances which are difficult to distribute, such as colloids or pseudocolloids, polymetacrylic acid esters, shellac, waxes or the like are simultaneously presented.

If the inflow of the air-solvent mixture is repeated in several, optionally even 20 or even 30 stages, then any desired type of delayed release of the active substance is obtained in the simplest possible form and with the aid of easy-to-implement automation measures.

Example 6:

50 kg of crystallized citric acid having a crystal size of 0.3-0.6 mm, 15 kg of magnesium oxide powder and 15 kg of citric acid are introduced into the reaction vessel and heated to 50 ° C. A constant vacuum of 700 mbar is then established, and a steam / air mixture (1 part by volume of water vapor to 20 parts by volume of air) is passed through the mixture within a period of 2 minutes at a pressure of 500 mbar, Min three-dimensionally. Subsequently, the air supply is closed and the drying is carried out with a full pumping capacity of up to 20 mbar for approx. 2 min. The magnesium oxide, supported by the citric acid powder, clings to the surface of the citric acid crystals to form a magnesium citrate binding layer. This procedure is repeated cyclically four times, 15 kg of potassium carbonate being added anhydrous (70% under 0.2 mm grain size) at the fourth time, which now reacts partially with the still free surfaces of the citric acid and in turn is anchored there to form a potassium citrate layer. Subsequently, the mixture is stirred to 10 mbar, stirring at 2 rpm. Finally, natural flavor, sweeteners and fillers are added.

Example 7:

40 kg of citric acid of grain size 0.4-0.6 mm, 2.4 kg of sweetener and 18 kg of iron-2-gluconate are introduced into a vacuum granulator which has a jacket temperature of 65 ° C. The mass is heated to 50 ° C. A constant vacuum of 600 mbar is set at the vacuum mixing tank. The heater for air heating is set to 120 degrees Celsius; The pumps 11, 16 and the valves are controlled in such a way that 500 l of hot air flow into the process chamber at 600 mbar. An amount of 400 ml of water is then allowed to flow from the container into the heat exchanger within 2 minutes and evaporate. With this steam / air mixture, the iron gluconate is granulated onto the citric acid by condensing on the process material.

After introducing the water, a full vacuum is applied, dried to 20 mbar with occasional stirring, and the water is removed in about 5 minutes. 10 kg of sodium bicarbonate are then added to the process mixture and the process is repeated in the same manner, with an action being taken between the citric acid and the sodium bicarbonate.

After drying to 20 mbar, 10 kg of sodium bicarbonate are again added, and the cyclic treatment is repeated. The product is then finally dried at a temperature of 50 ° C. to 20 mbar. Then, 3 kg of flavor and 4 kg of fillers are added, and the granules are discharged through the screening machine.