DE4011956A1 - METHOD AND DEVICE FOR PRESENTING STERILE INJECTABLE ANTIBIOTIC POWDERS - Google Patents

Abstract

Sterile powder forms of antibiotics (penicillins and cephalosporins) for reconstitution for injection, are prepared by spray-drying an aqueous-alcoholic solution of the antibiotic and a salt-forming agent therefor, in an inert gas (e.g. nitrogen).

Description

The invention relates to a method and the associated Device for the preparation of sterile injectable antibiotic powders.

It is known to use pharmaceuticals with the aid of lyophilization or Freeze drying and by crystallization processes and facilities to represent. In the lyophilization process, the active Component frozen while separating from a solution and that Purification of the active ingredient in the crystallization process is performed.  

The main disadvantage of the lyophilization process is the fact that the stability of the pharmaceutical compounds changed or deteriorates due to the strict treatment of the active ingredient. In fact, the quality and the Stability of the lyophilized compounds due to the high Temperatures, the pH values, the large number of resolutions of the active ingredient, freezing and sublimation levels in the Lyophilization procedures are changed. This disadvantage occurs frequently when, as in the present invention, organic compounds are shown, their therapeutic purpose even by small Changes or modifications in the structure can be endangered.

In the crystallization process for the production of antibiotics always a cleaning stage for the crystals of the final product needed. The solvents used in the cleaning step represent additional costs for the main process. These Solvents must also be separated and disposed of so that a pure final connection is obtained. The extraction of the the latter from the solution of the solvent and reuse and the drain of the same solvent pose further problems the crystallization process.

Both methods of lyophilization and crystallization show that Disadvantage on that they need a large number of steps, such as e.g. B. the filtration of the crystals of the antibiotic and the steps grinding and drying the product. Consequently, the yield of the entire process is reduced, production times are increased, and the pharmaceuticals become at risk of bacterial poisoning and exposed to particle poisoning. These disadvantages of the known The method and the device are not negligible because they are sterile Pharmaceuticals for injection according to the present invention in the case any contamination cannot be used.

It is therefore an object of the invention to eliminate the above-mentioned restrictions and disadvantages of the known methods and devices for the preparation of sterile injectable antibiotic powders. It is a particular object of the invention to carry out a process for the continuous or batchwise preparation of injectable powders of β- lactam antibiotics, in particular the sodium derivatives of ampicillin, piperazillin, cefoperazone, cefazolin, cefuroxime and their solid derivatives with the aid of a dry spray process, the process it is suitable that the stability and sterility conditions of the sprayed product are not changed.

As it is known in fact, it is intended for the representation of Antibiotics do not use active substances in a process of Subject to change in their structure or pharmaceutical activity will. The conventional dry spray device does not process correctly the antibiotics according to the invention. For this reason, a proposed new dry spray process, in which, in contrast to the known method shown sterile injectable antibiotic powder will; due to the fact that no critical or harsh Treatments made of the products can be antibiotic Stability and quality are thus guaranteed, and there is no Problem with drainage or solvent recovery on.

According to the invention is a method for the production of sterile Injectable antibiotic powders provided this is characterized in that a solution of the active ingredient is atomized and dried in the presence of a salt-forming By means of, the sprayed solution in the presence of a cycle an inert gas is treated.  

After the method according to the invention has been developed, the antibiotics are β- lactam antibiotics, in particular antibiotics, which are selected from the group formed from the sodium salts of the following compounds:
- Ampicillin with the general formula:

- Piperazillin with the general formula:

- Cefazolin with the general formula:

- Cefuroxime with the general formula:

- Cefoperazone with the general formula:

and their solid derivatives.

According to a further development of the invention, there is a dry spray method with the stages of continuous atomization and dissolution of the active Component provided.

According to another development of the method according to the invention exhibits the solution of the active component in the dry spray reactor a temperature range from 50 to 550 ° C, preferably from 150 to 240 ° C on, the antibiotic powder the dry spray reactor at a Temperature from 90 to 200 ° C, preferably from 95 to 130 ° C, taken will.

According to another development of the method according to the invention the solution in the dry spray reactor for 10 seconds and  preferably treated no more than 2 seconds, taking the concentration the active component in the solution in the range from 1 to 50% by weight, is preferably in the range from 8 to 25% by weight.

After a further development of the method according to the invention a solution of the active component is represented in water, Methanol or aqueous mixtures containing up to 80 vol% ethanol, 70 vol% Acetone and 50 vol% isopropyl alcohol are formed in the Presence of a salt-forming agent, preferably sodium hydroxide, Sodium bicarbonate or the sodium salt of the for the solution of the active Component alcohol used, the ratio of sodium equivalents is in the range of 1 to 1.15.

The dissolution of the active component is carried out in a continuous or batch-wise process carried out, the active component in the solution remains for 10 to 30 minutes at the longest.

As the inert gas used in the process according to the invention preferably nitrogen, the solution being the active Component also an ultrasound and degassing treatment is subjected.

The device according to the invention is characterized in that a Reactor is provided in which the sprayed solution of the active Component in contact with a flow of hot and inert gas comes with a collector for the powder at the bottom of the reactor is attached and a separator for the powder at the outlet of the inert gas from the reactor is attached.

According to a further development, the device has a vacuum line for the reactor, the device still having a return line of the inert gas at the outlet of the powder separator is provided.  

According to another development of the device according to the invention is a condenser to separate the solvents from the gas phase the separator of the powder is provided, with a return line for the condensed phase and a heater for the recycled inert gas are still provided.

In comparison with the known methods of producing The method according to the invention has the advantage of pharmaceuticals that there are only a few stages of treatment of the products, which contrasts the quality and stability of antibiotics to the conventional methods not by the inventive Procedure to be changed. As already stated, the invention is particularly suitable for the presentation of sterile injectables Antibiotic powders.

The yield of the process according to the invention is also higher, and the number of solutions of the active component is compared with the traditional methods of crystallization lower. The Stability and purity of the process according to the invention Antibiotics achieved is also compared to conventional ones Lyophilization process improved.

According to the invention is a continuous display method of sterile antibiotic powders and the solution of the active component given in the form of non-sterile salts. The antibiotics can also by salt formation of the corresponding acids from solid Mixtures of these acids and the salt-forming agents are obtained.

The active component is in a solution of the salt-forming agent, such as solutions of sodium hydroxide, sodium bicarbonate or the sodium salt the alcohol used to dissolve the active component and other sodium agents of salt formation.  

The batch process is used to achieve a stable solution in the presence of small volumes of solution at low temperatures (generally from -10 to 45 ° C, preferably at 0 to 35 ° C) carried out.

The duration of the solution step of the continuous and batch mode Process is achieved by using a reactor with a Ultrasonic device reduced, in addition to a stirrer and a degassing system is provided. So that the stability of the End products is increased, the presence of oxygen in the Solution for the continuous as well as the batch Procedure excluded. The pH of the solution is made up of special pH values are selected for each product, causing the deterioration and polymerization reactions are excluded.

The solutions of the dry spray process are water solutions from Isopropyl, methyl and ethyl alcohols or water-acetone mixtures, pure methanol or similar solvents in which the active Component is resolved.

The batch work according to the invention takes place at one Temperature instead, to prevent the failure of the active Component from their solution is suitable. The active component is first dissolved in water, and then the solvent is added, or alternatively, the active component directly becomes the mixture of Added solvents.

The concentration of the active component in the solution is normally 5 to 50% by weight, preferably 8 to 20% by weight. These Concentrations of the active component and the percentages mentioned the solvents result in a solution with higher stability.  

So that the antibiotic does not deteriorate, the active one Component for a maximum of 2 to 10 minutes (continuous process) or leave in solution for 20 to 30 minutes (batch procedure).

The physical parameters of the dry spray process according to the Invention does not deteriorate or scorch the products, the solvents are easy to remove and the final product is the same the international official medical or pharmaceutical Standards (BP, USP, FU, Ph.Eur.).

These results are obtained by the dry spray method according to the invention achieved, the process normally in the presence one cycle or cycle of a flow of nitrogen the temperature of the solution at the inlet of the reactor is 50 to 500 ° C., preferably 150 to 240 ° C and at the outlet 90 to 200 ° C, preferably 95 to Is 130 ° C.

These temperatures of the solution at the inlet of the reactor reduce this Risk of deterioration of the antibiotic. The temperature of the same pharmaceuticals at the outlet is suitable for complete drying the powder of the antibiotic.

The products are in the dry spray reactor for 0.5 to 3 seconds, preferably left for 1 or 2 seconds. The solution to be dried will opposite to the current or with the current (in relation to the Flow direction of the inert gas) in the dryer with the help of Rotating nozzles or atomizers sprayed, the physical Parameters of the method described below to a refer to rotating atomizers and the directions of flow of the solution and of the inert gas are the same (co-current). The surface of the spray generated by the atomizer is 800 to 1500 m² / l.  The solution for the presentation of antibiotics is with the help filtered by sterilizing cartridges. The powdery product will first in a chilled cyclone separator and then in a sterile one cooled mixer, creating an even batch of the final product is collected.

Further features and advantages of the method according to the invention and the device according to the invention result from the Description of the following embodiments with reference to the figure.

The device according to FIG. 1 essentially has a reactor 1 , which is connected by means of lines 2 and 3 to a supply 4 for hot inert gas or to a cyclone or dust catcher 5 . The solution of the active component is fed from the mixer 14 to the reactor 1 through the line 6 and a plurality of nozzles 7 .

So that the atomization of the solution is improved, it is mixed with an inert gas which is fed in the same direction or in the opposite direction from the line 2 . A powder of the active component is thus generated in the reactor 1 , the powder being collected at the bottom 8 of the reactor. The flow of the outflowing gas is discharged from the line 3 and led to the cyclone or dust separator 5 , in which the remaining powders are collected at the bottom 9 .

A flow of the inert gases and vapors of the solvent which are free of the powder is released from the cyclone 5 and returned via line 10 . The condensing solvent separates from the inert gas in a condenser 11 : the condensates are fed to the mixer or stirrer 14 for preparing the solution of the active component, the inert gas passes through a heater 12 and is then introduced into the reactor 1 . The return line is connected to a vacuum line 13 , which is suitable for creating vacuum conditions in the reactor 1 . The active component powders are taken from the collectors or collectors 8 and 9 and subsequently treated for packaging, etc.

Example 1 Presentation of sodium ampicillin

This example relates to the representation of injectable Powder of sodium salts of ampicillin with the general formula:

300 g ampicillin trihydrate are in a mixture of water for injectable compounds and isopropanol (910 ml or 400 ml) suspended and in one with an ultrasonic resolution device, a stirrer and a degassing system equipped reactor collected. This solution was 380 ml of 2 N sodium hydroxide, the Correspond to 1.02 gram equivalents of sodium. The Solution was presented 5 consecutive games.

So that the dwell time of the product in the solution is kept low lot # 2 was ready for atomization after filtration at the time when lot # 1 was just atomized. The Batch Nos. 3, 4 and 5 were processed in the same way, with the product remains in the solution for a maximum of 10 minutes was and the temperature was in a range of -5 to 5 ° C.  

These solutions were spray dried at an inlet temperature in the reactor from 190 to 195 ° C and an outlet temperature of 95 to 120 ° C. The dry spray reactor was with one atomizer Provided speed of 45,000 revolutions per minute, the flow rate nitrogen was 80 kg / h. Under these conditions, 10 games represented by sterile sodium ampicillin, and the practical average conversion yield of that described below Product was 99.8%:

Ratio 92.5% acid
Water (KF) 0.4%
Degradation products 1.1%
Dimers and polymers 0.7%
Isopropyl alcohol 90 ppm
particulate matter <10 µ 130 / g
<25 µ 15 / g
specific rotation (FU IX) + 280 °
Aspect of the solution <Solution I FU IX.

The estimated duration of stability was 5 years.

The same example was repeated and the same results achieved with a solution of sodium ampicillin of 5 to 50% by weight, preferably 9 to 20% by weight. The solvents were water solutions from Methanol (0-100 vol%), ethanol (0-60 vol%), isopropanol (0-40 vol%) and acetone (0-40 vol%).

The sodium salt of ampicillin to be atomized can be shown be by the pure ampicillin (at a rate of preferably more than 97% in the dry material) in a water-alcohol or Water-acetone mixture is suspended, as stated above, the salt-forming agent slowly in such a manner is added that the pH of the solution is within the limits lies in which the stability of the ampicillin is given.  

As previously described, the dissolution can be in a continuous or batch-wise processes are carried out at temperatures of 5 up to 20 ° C. Usually 1.02 to 1.15, preferably 1.05, sodium equivalents added. The temperature when atomizing the solution active component normally ranged from 150 to 550 ° C, preferred from 150 to 240 ° C. The temperature at the outlet was 90 to 200 ° C, preferably 95 to 130 ° C.

Example 2: Preparation of sodium piperazillin

This example relates to the representation of injectable Powder of sodium salts of piperazillin with the general formula:

350 g of anhydrous acid piperazillin are made in a mixture Water for injectable compounds and isopropanol (1350 ml or 400 ml) suspended in a with an ultrasound resolution device, a stirrer and a degassing system equipped reactor collected. 60 g of sodium bicarbonate were correspondingly added to this solution Added 1.06 gram equivalents of sodium. The solution was in 5 successive games.

So that the dwell time of the product in the solution is kept low lot # 2 was ready to be atomized after filtering the time when lot 1 was just atomized. The  Batch Nos. 3, 4 and 5 were treated in the same manner, with the product remains in the solution for a maximum of 10 minutes was and the temperature was in a range of -5 to 10 ° C.

These solutions were spray dried at an inlet temperature in the reactor from 195 to 200 ° C and an outlet temperature of 110 to 115 ° C. The spray dry reactor was with a rotary atomizer of 45,000 revolutions provided per minute, the flow rate of nitrogen was 80 kg / h. Under these conditions, 8 batches of sterile Sodium piperazillin, and the practical average yield the conversion of the product described below was 99.9%:

Ratio 93.2% acid
Water (KF) 0.4%
Degradation products 0.1%
Dimers and polymers 0.7%
Isopropyl alcohol 130 ppm
particulate matter <10 µ 150 / g
<25 µ 13 / g
specific rotation (FU IX) + 187 °
Aspect of the solution <Solution I FU IX
Duration of the solution
(50% water solution PPI) <30 seconds.

The estimated stability period was 3 years.

The same example was repeated and the same results were achieved with a solution of sodium piperazillin of 5 to 50% by weight, preferably 10 to 25% by weight. The solvents were water solutions of methanol (0-100 vol%), ethanol (0-60 vol%), Isopropanol (0-40 vol%) and acetone (0-40 vol%).  

The solution of piperazillin sodium salt to be atomized can are represented by suspending the acid piperazillin or another form of pure piperazillin (preferred at a rate higher than 98% of the dry matter) in a water-alcohol or Water-acetone mixture, as stated above, which salt-forming agents are gradually added in such a way that the pH of the solution is within the limits of the stability of the Piperazillins lies.

As previously described, the resolution can be in a continuous or a batch process at temperatures from 5 to 20 ° C are carried out. Usually 1.00 to 1.10 are preferred Added 1.02 equivalents of sodium. The temperature of the Atomization of the active component solution usually ranges from 150 to 550 ° C, preferably from 155 to 200 ° C. The temperature at that Outlet was 95 to 220 ° C, preferably 95 to 115 ° C.

Example 3: Preparation of sodium cefazolin

This example relates to the representation of injectable Powders of the sodium salts of cefazolin with the general formula:

390 g of anhydrous acid cefazolin become homogeneous with 75 g of sodium bicarbonate mixed, which corresponds to 1.04 sodium equivalents, so that  A mixture is quickly achieved in a mixture of water for injectable compounds and methanol (1210 ml or 405 ml) is solvable, in one with an ultrasound resolution device, one Stirrer and a degassing reactor equipped, where the solution is kept at 35 ° C. This solution was in five consecutive Lots shown.

So that the dwell time of the product in the solution is kept low After filtering, lot # 2 was ready to be atomized the time when lot 1 was already atomized. The games Nos. 3, 4 and 5 were treated in the same way, with the Residence time of the product in the solution was at most 7 minutes.

These solutions were spray dried at an inlet temperature in the reactor from 195 to 200 ° C and an outlet temperature of 110 to 115 ° C. The spray dry reactor was with a rotary atomizer of 44,000 revolutions provided per minute, the flow rate of nitrogen Was 80 kg / h. Under these conditions, 13 batches of sterile Sodium cefazolin presented, and the practical average Yields of the conversion of the product described below were 99.7%:

Ratio 93.1% acid
Water (KF) 1.3%
Degradation products 0.1%
Dimers and polymers 0.3%
Methyl alcohol 30 ppm
particulate matter <10 µ 133 / g
<25 µ 9 / g
specific rotation (FU IX) -23 °
Aspect of the solution <Solution I FU IX.

The estimated stability period was 4 years.  

The same example was repeated and the same results were obtained achieved with a solution of sodium cefazolin of 5 to 50% by weight, preferably 8 to 24% by weight. The solvents were water solutions from Methanol (0-50 vol%), ethanol (0-50 vol%), isopropanol (0-50 vol%) and acetone (0-55 vol%).

The solution of atomized sodium salt of cefazolin can are represented by suspending the pure acid cefazolin (at a rate preferably higher than 97% of the dry material) in one Water-alcohol or water-acetone mixture, as described above, at a temperature of 15 to 40 ° C, the salt-forming agent is gradually added in such a way that the pH of the solution is within the limits of the stability of the cefazoline.

As previously described, the dissolution can be done by a continuous or batch-wise process. Typically, 1.02 to 1.09, preferably 1.03 equivalents of Sodium added. The temperature of atomizing the solution of the active component normally ranged from 150 to 550 ° C, preferred from 160 to 200 ° C. The temperature at the outlet was 95 to 220 ° C, preferably 95 to 115 ° C.

Example 4: Preparation of sodium cefuroxime

This example relates to the representation of injectable Powder of sodium salts of cefuroxime with the general formula:

140 g of anhydrous acid cefuroxime are mixed evenly with 29 g of sodium bicarbonate, which correspond to 1.05 equivalents of sodium, mixed, so that a mixture is achieved which quickly in a 1400 ml Mixture of water for injectable compounds is soluble in one with an ultrasonic dissolver, a stirrer and a Gassing equipped reactor collected, the solution at Is kept 10 to 20 ° C. 150 ml of ethanol were added to this solution added. This solution was divided into 5 consecutive lots shown.

So that the dwell time of the product in the solution is kept low lot # 2 was ready for atomization after filtering the time when lot 1 was already atomized. The games Nos. 3, 4 and 5 were treated in the same way, with the Residence time of the product in the solution was at most 7 minutes.

These solutions were spray dried at an inlet temperature in the reactor from 195 to 200 ° C and an outlet temperature of 110 to 115 ° C. The spray dry reactor was with a rotary atomizer of 44,000 revolutions provided per minute, the flow rate of nitrogen was 80 kg / h. Under these conditions, 15 batches of sterile Sodium cefuroxime and the practical average yield the conversion of the product described below was 99.9%:

Ratio 92.5% acid
Water (KF) 1.6%
Degradation products <0.1%
Dimers and polymers 0.1%
Methyl alcohol 110 ppm
particulate matter <10 µ 190 / g
<25 µ 21 / g
specific rotation (FU IX) + 65 °
Aspect of the solution <Solution I FU IX.

The estimated stability period was 4 years.

The same example was repeated and the same results were achieved with a solution of sodium cefuroxime of 1 to 12% by weight, preferably 8 to 10% by weight. The solvents were water solutions of methanol (0-60 vol%), ethanol (0-80 vol%), Isopropanol (0-50 vol%) and acetone (0-70 vol%).

The solution of the sodium salt of cefuroxime to be atomized can by by suspending the pure acid cefuroxime (preferred at a rate higher than 97% of the dry matter) in a water-alcohol or Water-acetone mixture can be prepared as described above at a temperature of 15 to 40 ° C, the means for salt formation is gradually added in such a way that the pH of the solution is within the limits of the stability of the cefuroxime.

As previously described, the dissolution can be done by a continuous or a batch-wise procedure. Usually become 1.02 to 1.10, preferably 1.04 equivalents of sodium added. The temperature of atomization of the solution of the active Component normally ranged from 150 to 550 ° C, preferably from 180 up to 220 ° C. The temperature at the outlet was 95 to 200 ° C., preferably 105 up to 115 ° C.

Example 5: Representation of sodium cefoperazone

This example relates to the representation of injectable Powder of sodium salts of cefoperazone with the general formula:

440 g of anhydrous acid cefoperazone become even with 59 g Sodium bicarbonate, which corresponds to 1.03 equivalents of sodium, mixed so that a mixture is achieved which is quickly in water for Injectable compounds soluble with isopropanol (1540 ml or 150 ml) is, in one with an ultrasonic dissolving device, a stirrer and a reactor provided with a degassing system, the Solution is kept at 10 to 20 ° C. This solution was developed in 5 successive games.

So that the residence time of the product in the solution is as short as was held possible, lot # 2 was finished after filtering for atomization at the moment when the game No. 1 already was atomized. Lots 3, 4 and 5 were made in the same way processed, the residence time of the product in the solution was at most 7 minutes.

These solutions were spray dried at an inlet temperature in the reactor from 185 to 190 ° C and an outlet temperature of 110 to 115 ° C. The dry spray reactor was with a rotary atomizer of 44,000 revolutions provided per minute, the flow rate of nitrogen was 80 kg / h. Under these conditions, 17 lots of sterile Sodium cefoperazone and the practical average yield was the conversion of the product described below 99.6%:

Ratio 92.1% acid
Water (KF) 1.0%
Degradation products 0.6%
Dimers and polymers 0.7%
Isopropyl alcohol 230 ppm
particulate matter <10 µ 152 / g
<25 µ 17 / g
Aspect of the solution <Solution I FU IX.

The estimated stability period was 2 years.

The same example was repeated and the same results were achieved with a solution of sodium cefoperazone of 5 to 50% by weight, preferably 8 to 25% by weight. The solvents were water solutions of methanol (0-60 vol%), ethanol (0-80 vol%), Isopropanol (0-25 vol%) and acetone (0-50 vol%).

The solution of the sodium salt of cefoperazone to be atomized can by suspending the acid or pure hydrogenated cefoperazone (at a rate preferably higher than 97% of the dry material) in one Water-alcohol or water-acetone mixture can be represented as is carried out above, at a temperature of 15 to 40 ° C, which salt-forming agent is gradually added in such a way that the pH of the solution within the limits of the stability of the Cefoperazons lies.

As previously described, the dissolution can be in a continuous or a batch-wise procedure. Usually 1.02 to 1.10, preferably 1.05 equivalents of sodium are added. The temperature of atomization of the active component solution normally ranged from 150 to 550 ° C, preferably from 180 to 220 ° C. The temperature at the outlet was 95 to 200 ° C, preferably 105 to 115 ° C.

Claims (13)

1. A process for the preparation of sterile injectable powders of antibiotics, characterized in that a solution of the active component is atomized and dried in the presence of a salt-forming element, the sprayed solutions being treated in the presence of a circuit of an inert gas. 2. The method according to claim 1, characterized in that the antibiotics are β- lactam antibiotics. 3. The method according to claim 2, characterized in that the antibiotics are selected from the group formed from the sodium salts of the following compounds:

• - Ampicillin with the general formula:
• - Piperazillin with the general formula:
• - Cefazolin with the general formula:
• - Cefuroxime with the general formula:
• - Cefoperazone with the general formula:

and their solid derivatives. 4. The method according to any one of claims 1 to 3, characterized in that a dry spray process with the steps of continuous Atomizing and dissolving the active component is provided.   5. The method according to any one of claims 1 to 4, characterized in that the solution of the active component in the spray dry reactor Temperature of 50 to 550 ° C, preferably from 150 to 240 ° C, the antibiotic powder from the spray dry reactor at a Temperature taken from 90 to 200 ° C, preferably from 95 to 130 ° C. will. 6. The method according to any one of claims 1 to 5, characterized in that that the solution in the dry spray reactor at most 10 seconds and is preferably treated for at most 2 seconds. 7. The method according to any one of claims 1 to 6, characterized in that that the concentration of the active component in the solution from 1 to 50% by weight, preferably from 8 to 25% by weight. 8. The method according to any one of claims 1 to 7, characterized in that a solution of the active component in water, methanol or aqueous mixtures consisting of up to 80 vol% ethanol, up to 70 vol% Acetone and up to 50 vol% isopropyl alcohol are formed. 9. The method according to any one of claims 1 to 8, characterized in that the solution of the active component in the presence of a salt-forming By means, preferably sodium hydroxide, sodium bicarbonate or that Sodium salt of the used for the solution of the active component Alcohol is carried out, the ratio of the equivalent of Sodium is in the range of 1 to 1.15. 10. The method according to any one of claims 1 to 9, characterized featured, that dissolving the active component in a continuous or a batch-wise process takes place, whereby the active component in the solution for a maximum of 10 or 30 minutes is left and in both cases the temperature of the solution is -10 to 45 ° C, preferably 0 to 35 ° C.   11. The method according to any one of claims 1 to 10, characterized characterized in that the inert gas is nitrogen and that the solution the active component still an ultrasound and one Degassing treatment is suspended. 12. Device for carrying out the method according to one of the claims 1 to 11, characterized in that a reactor is provided in which the atomized solution of the active component with a flow of a hot and inert gas comes into contact, a collector for the Powder is attached to the bottom of the reactor, a separator Powder is attached to the outlet of the inert gas from the reactor, a vacuum line is provided for the reactor, with further one Return line for the inert gas at the outlet of the separator Powder is provided, a capacitor for the separation of the solvents from the gas phase of the separator the powder is provided, one Return line for the condensed phase and a heating element for the recycled inert gas are provided.