SI8611694A8 - Method for simultaneous extract of dry substance from calf's blood extract acqueous solution devoited of proteins. - Google Patents

Description

HORMON-CHEMIE MUNCHEN GMBH

Process for simultaneous extraction of dry matter from aqueous solutions of calf extracts from which protein has been removed

FIELD OF THE INVENTION

IPC: A 61 K 35/14.

The invention relates to the preparation of medicaments containing blood constituents and relates to a process in a fluidized bed for simultaneous extraction of dry matter from aqueous solutions of extracts of calf blood from which proteins have been removed and preparation of a granulate which can be compressed into solids formulations and contains at least 50% by weight of extracts based on the total dry weight of the granulate. According to this process, the obtained granulate can be used to prepare pharmaceutical preparations containing as an effective substance an extract substance from

1a veal blood from which protein was removed.

A technical problem

It is therefore a technical object of the invention to improve both the process for the extraction of dry matter from aqueous solutions obtained from the isolation of extracts, as well as the preparation of granules which can be compressed into solid drug forms, avoiding the defects of the prior art and in addition to the economic benefits, a decisive requirement is the consistent improved product quality. In particular, dry matter should be obtained during the entire preparation process under conditions of leniency, and a high-content extract granulate can be prepared for compression, which can be converted into solid formulations of high stability, which do not show staining even at prolonged storage at room temperature and have improved consistency of quality parameters.

The state of the art

Extracts from the blood of young calves from which proteins have been removed and containing lower molecular constituents of calf blood are known to cause poor healing in the healing of poorly healing wounds, thereby accelerating wound healing. Furthermore, extracts are also used in disorders of cerebral blood flow and metabolism, cf. Schnellen, Med. Welt, aka 19, p. 198 (1968). Pharmaceutical preparations containing such extracts are marketed under the name Actovegin 'of Hormonchemie, Munich, or under the Actihaemyl mark of Solko, Basel.

The calf extracts from which the proteins have been removed are extremely heat sensitive as a dry matter. A longer thermal load above 30 ° C results in a brown discoloration which is probably caused by the reaction of glucose with amino acids and peptides (Maillard reaction), with a particularly unfavorable content of residual water in the dry matter above 4 wt. % and leads to the formation of brown dense mass.

When isolated from calf blood, extracts are obtained in aqueous solutions of varying concentrations. DE-PS 1,076,888 describes only the preparation of injection preparations with a concentration of 30 to 60 mg of dry matter / ml of solution by evaporation of solutions of extracts. Due to the high thermolability of the extracts, only a desiccant drying method is used to obtain solids for the preparation of solid drug forms.

AT-PS 330.953 discloses a process for the preparation of dry preparations of calf extracts in which the extracts are mixed with an adsorbent, e.g. high-dispersed silica

- 3 the resulting thixotropic gel is dried under vacuum. This procedure has the disadvantage that the aqueous solution of the extracts must be added to the extract of the foreign accompanying substance before drying, since without such additives the preparation of the undisturbed dry matter is thus impossible.

An improved alternative for the adsorption of active substances from blood extracts on solids exists according to AT-PS 330.953 in that they obtain freeze-dried (freeze-drying) dry matter of about 5 to 10% aqueous solutions of extracts. In addition to the fact that the lyophilization of large quantities of aqueous solutions is very time consuming and requires a lot of energy, lyophilization has the disadvantage that the lyophilisates obtained are a very fine and highly hygroscopic powder, which is not suitable for the preparation of solid forms of drugs by direct tableting or by dry granulation and subsequent pressing. appropriate.

The lyophilisate is now prepared for tabletting by suitable wet granulation with subsequent wet granulation with polyvinylpyrrolidone as a binder and carboxymethyl starch as a filler, whereby they cannot use water as granulating liquids but have to cut through organic solvents, e.g. isopropanol. Due to their toxicity, organic solvents are only reluctant to be used in the preparation of oral medications. In addition, the hygroscopic lyophilisate extracts moisture from the ambient air during the granulation process, so that either working under air-conditioned conditions at low relative humidity or the finished granulate undergoes a multi-drying process at about 40 ° C, with the extracts exposed to further temperature stress , which decreases the quality and causes the coloring of the finished preparations during storage.

Description of solution to a technical problem with implementation examples

The object of the invention is solved by a process for simultaneously extracting solids from aqueous solutions of extracts of calf blood from which proteins have been removed, and with the right granules which can be compressed into solid drug forms and containing at least 50 wt. % of the extracts based on the total dry weight of the granulate, binder and pharmaceutically acceptable fillers and carriers, the process being characterized by spraying a quantity of concentrated aqueous solution in a fluidized bed granulator _{on a} previously given amount of fillers and carriers in a fluidized state containing the desired amount of extracts and which at 10 wt. parts of the extracts additionally contains 0.2 to 2 wt. of the binder in a dissolved state, adjusting the temperature of the inlet fluidizing gas and the rate of spray during the spraying of the entire amount of the solution, or at least a large portion thereof, such that at a temperature of the fluidized bed of 25 to 30 ° C and a water content of the material in the fluidized bed of 15 to 20 wt. % sprayed water and the amount of evaporated water roughly correspond to each other, does not form and remains material in the vortex powder form, to agglomerate and granulate the resulting milling even during or after the end of the spraying of the extracts the water content in the vortex increase the layer to 35 to 45 wt. %, and then the granulate formed, after reaching the desired granulate size, is subjected to short-term drying at a temperature of 30 to maximum 45 ° C by swirling the inlet fluidizing gas.

The advantages of the process of the invention, on the one hand, are to increase the quality of the product, i.e. the resulting granulate, which can be compressed into solid, well-stored, solid formulations with high stability, high mass stability and excellent galenic properties upon exit from the fluidized bed granulator, either directly or after the addition of further pharmaceutically acceptable auxiliaries. On the other hand, the process of the invention provides both the gentle extraction of dry matter from large quantities of aqueous solutions of calf extracts from which proteins have been removed, as well as the preparation for compressing the prepared granulate in a single continuous process in a substantially simpler and more economical way than so far this has been the case with the known process.

For the purpose of carrying out the process according to the invention, a whirling layer commercial granulator is suitable. Such a fluidized bed granulator is essentially made of a material container into which fluidizing gas flows from the bottom or bottom, regulating both the flow velocity and the temperature of the incoming fluidizing gas. Further, these apparatus have one or more spray heads in the form of single or double-base doses through which pure liquids and solutions can be sprayed by means of a pump with adjustable spray rate into a material container and arranged so that the sprayed liquid or solution flows directly into the well. layer. A mechanical mixer or chopper at the bottom of the pan or shaker ensures additional mixing effect as needed.

For the practical implementation of the process, a pre-specified amount of fillers and carriers is provided in the material container, which is based on the desired weight fraction of these additives in the finished granulate and in each case is less than 50 wt. %, preferably 25 to 45 wt. %, based on the total dry weight of the finished granulate, and a fluidized gas stream produces a uniform vortex layer. For the preparation of the granulate according to the invention, conventional fillers and carriers with small particle size, which have at the same time a large surface area and are insoluble or hardly soluble in water, are particularly suitable in galenics. As

- 7 suitable fillers and carriers with the above described characteristics, e.g. microcrystalline cellulose (commercially available, eg under the name Avicel PH 101), cross-linked sodium carboxymethylcellulose (commercially available, eg under the name Ac-DI-Sol), cross-linked polyvinylpyrrolidone (commercially available, e.g., under the name Polyplasdone) or mixtures of these substances, the mixing ratios being arbitrarily chosen over a wide range, and again mixtures of equal weight parts of these substances are again preferred here. For this purpose, particularly the use of ricrocrystalline cellulose or cross-linked sodium carboxymethylcellulose.

Dry air can be used as a fluidizing gas in the simplest possible way without fear of quality, persistence of extracts. Of course, other gases which are inert to the extracts, such as e.g. nitrogen. The total amount of fluidizing gas per hour depends on the size of the fluidized bed granulator and, at a nominal volume of the material container 60 1, e.g. 500 to 3000 m ³ / h. As soon as a uniform vortex layer is formed due to the flow pressure, the aqueous solution of the extracts can be sprayed. Concentrated aqueous solutions containing up to 50% by weight are used for this purpose. %, preferably 15 to 25 wt. % of the extracts and whose volume is so calculated that the total quantity of the sprayed substances is at least 50% by weight. %, preferably 55 to 70 wt. %, based on the total dry weight of the finished granulate.

These solutions contain 10 wt. parts of extracts additional 0.2 to 2 wt. parts of a water-soluble binder, preferably 0.5 to 1 wt. del. The weight of the binder in the finished granulate is then e.g. 1 to 10 wt. %, preferably 2 to 6 wt. % based on the total dry weight of the granulate.

As water binders, conventional water-soluble binders are suitable for the preparation of the granulate of the invention, e.g. pregelatinised starch, water-soluble cellulose, such as methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, or other water-soluble high molecular weight compounds such as polyvinyl alcohol, polyvinylpyrrolidone and the like. Particularly preferably, binders of 1-vinyl-2-pyrrolidone commercially available e.g. under the name Kollidon K 25 or Kollidon 90.

The temperature of the inlet fluidizing gas during the spraying process and the spray rate at which the aqueous solution of the extractants is sprayed together with the binder on the fluidized fillers and supports depend on the amount of auxiliaries provided and the nominal volume of the fluid bed granulator container. In this phase of the process, the temperature and the spray rate are thus aligned with one another in order to achieve a stationary water content of 15 to 20 wt.% In the material in the swirling layer at a fluidized bed temperature of 25 to 30 ° C. % by weight, and the amount of water sprayed and the amount of water vaporized correspond approximately to each other.

For this purpose, depending on the amount of fillers and carriers provided, and the size of the material container, the temperatures of the fluidizing gas from about 30 to 80 ° C are required.

Under these conditions no design is yet to be done. Fillers and carriers remain capable of absorbing extracts which are advantageously exposed to no significant temperature load in the vortex layer while removing most of the water, yielding a fine granular powder which remains powdery during this first stage of the process and hardly tends to agglomerate.

Agglomeration of the powder material to produce a granulate of the desired size is achieved by the process of the invention by increasing the water content of the vortex to 35 to 45 wt. %, preferably at 33 to 40 wt. %. To this end, the water content can be increased either during the spraying process, when a large part of the desired amount of extracted substances is already sprayed, or after the spraying of the extracted substances. In a particularly advantageous embodiment of the process, spray a large portion of the solution containing the extracts and a binder, e.g. depending on the concentration of extracts 75 to 85 vol. % of the total volume of the solution to be sprayed under the above conditions, which do not lead to agglomeration of the mill, while spraying the remainder of the volume of the solution, lower the temperature of the inlet fluidizing gas and / or increase the spray rate by spraying more water, as it may evaporate at the same time, the consequence is that the water content of the vortex layer increases to the value required for agglomeration and granulation.

However, it is also possible to spray the whole volume of the solution under conditions that do not lead to agglomeration and then

- 10 The water content of the fluidized bed is increased by spraying clean water to the value required for granulation.

As soon as the water content of the fluidized bed exceeds the value of about 35 wt. %, agglomeration begins and a uniform uniform granulate is formed.

Throughout the granulation process, the water content of the above mentioned boundaries is maintained in the material of the fluidized bed. Depending on the adjustment of the water content, granules having a diameter in the range of 0.03 to 2 mm, preferably 0.05 to 1 mm, can be obtained in a reproducible manner according to the process of the invention.

When a granulate of the desired size is formed, a drying phase is introduced by increasing the temperature of the fluidizing gas. The temperature of the fluidizing gas is appropriately selected so that, for the gentle treatment of the extracts, the temperature of the granulate in the vortex layer does not exceed 30 to 32 ° C. Drying is complete as soon as the granulate temperature rises. To remove residual water, the temperature of the granulate may be allowed to rise for a short time, e.g. 5 to 15 minutes, without compromising the stability of the extracts and the quality of the granulate at 40 to 45 ° C, preferably 40 to 43 ° C. This gives granules with a maximum water content of about 1.5 to 3 wt. % by weight.

The process of the invention is rational, simple and well reproducible. For the preparation of 58 kg of dry, pressed granulate from aqueous concentrate of calf extracts, which have been removed, protein is required in a continuous mode of operation, e.g. only about 7 hours, whereas only the prior art lyophilization of the same amount requires about 7 to 9 days.

According to the invention, the prepared granulate has a high content by weight of extracts and has an excellent flowability at a uniform grain size, which enables its processing into solid drug forms with high mass constancy and high stability. A useful use is to use a granulate of the invention for the preparation of solid forms of medicaments containing as an effective substance an extract of calf blood from which proteins have been removed. Preferably, we prepare compresses, such as tablets, dragees, cores or other compresses of any shape and size. According to the invention, the prepared granulate can be compressed directly or after mixing further auxiliary substances known in the art, such as tablet binders, fillers, preservatives, tablet disintegrators and the like. The nature and quantity of these excipients is governed by the desired mechanical strength and dissolution rate of the presses.

As such, pre-compression adjuvants are suitable e.g. stearates such as magnesium stearate, calcium stearate, etc. or other commonly used sliding means for tableting, e.g. talc or glycerin esters of saturated natural fatty acids such as those on the market e.g. under the name Precirol, in an amount of from 1 to 10 wt. % based on the total weight of the finished preparation.

The finished preparations contain per dosage unit e.g. 150 to 250 mg of extracts over the total weight of the tablet or core 12 to 300 mg.

Solid drug formulations prepared using the granules of the invention do not show any coloration even at prolonged storage at room temperature and have an improved consistency in quality parameters.

The following examples further illustrate the invention.

a) Granulate preparation

EXAMPLE 1

3000 g of a mixture of equal weight parts of Avicel PH 101 (microcrystalline cellulose) and Polyplasdon (cross-linked polyvinylpyrrolidone) are submitted to a vortex material container with a nominal volume of 7 1 and a dry air stream with a flow rate of 500 m ³ per hour and temperature. 80 ° C to create a uniform vortex layer.

1 20% aqueous solution of extracts is mixed with 1 1 20% aqueous solution of Collidon K 25 (polymer 1-vinyl

2-pyrrolidone) is fed into a double-base nozzle by means of a tubular pump and sprayed into a fluidized bed. The spray velocity is controlled by setting the temperature of the fluidized bed 28 to 30 ° C and the stationary water content of the material in the fluidized bed at about 15 wt. %, where the spray water volume and the evaporating water volume are balanced and no agglomeration is observed.

To maintain these conditions, the average spray rate is 70 g of solution per minute. After spraying about 3/4 of the total volume of the solution, the supply air temperature is reduced to 30 ° C and the remaining volume of the solution is sprayed at the same spray rate. The stationary water content of the vortex layer is now increasing and at a water content of 38 to 40 wt. % agglomeration of dust begins. At this water content, granulate until a granulate of 0.06 mm to 0.8 mm in diameter is formed from the total amount of dust. After spraying is completed, the temperature of the supply air is again raised to 60 to 80 ° C, thereby introducing a drying phase. The temperature of the granules ranges from 30 to 32 ° C during drying. Drying is complete when the granulate temperature rises. To remove the remaining water, the granulate temperature is kept at 43 ° C for 15 minutes. This gives 7350 g of granulate with the following properties:

content of extracts 544.2 rag / g granulate Collidon K 25 27.3 mg / g granulate Avicel PH 101 204.0 mg / g granulate Polyplasdone 204.0 mg / g granulate the residual water content about 20 mg / g of granulate, equivalent to about 2% diameter from 0.08 to 0.8 mm

EXAMPLE 2 Experiment 1 is repeated, taking as filler and carrier

Use 3000 g of microcrystalline cellulose (Avicel PH 101) and add 1 to 20% aqueous solution of 1-vinyl-2-pyrrolidone polymer Collidone 90 as a binder.

This gives a granulate with the following properties:

content of extracts 544.2 mg / g granulate Collidon 90 21.3 mg / g granulate Avicel PH 101 408 mg / g granulate the residual water content about 20 mg / g of granulate, equivalent to about 2%

diameters from 0.08 to 0.8 mm

- 15 EXAMPLE 3

15,000 g of Avicel PH 101 (microcrystalline cellulose) and 10,000 g of Ac-Di-Sol (cross-linked sodium carboxymethylcellulose) are placed in a fluid bed granulator container with a nominal volume of 60 1. With an airflow of 800 m ³ / h and a temperature of 80 ° C is maintained by a uniform swirling layer. 166.6 1 20% aqueous solutions of the extracts are mixed with a solution of 1660 g of Kollidon K 25 and 16.6 1 water, piped (3 nozzles with a nozzle opening of 1.2 mm) and sprayed into a swirling layer. At a spray rate of about 600 g of Actovegin-Collidon / min solution, a steady water content of about 15% and a temperature of 30 to 32 ° C is adjusted in the vortex layer.

After spraying under these conditions of 140 l, the supply air temperature is lowered to room temperature, the water content is thus increased and the agglomeration phase introduced. After spraying is complete, the resulting granulate is dried in a fluidized bed granulator at an inlet air temperature of 80 ° C.

The dried granulate has the following characteristics:

bulk density bulk density bulk density water content grain size

0.53 g / cm ³ 0.63 g / cm ³ 12.30 g / cm ² sec 1.6%

- 500 / Um

- 16 EXAMPLE 4

22,000 g of microcrystalline cellulose (Avicel PH 101) is presented in a fluid bed granulator container with a nominal volume of 60 1. By maintaining air at a flow rate of 800 m ³ / h and a temperature of 70 ° C, a uniform borehole is maintained throughout the layer. 166.6 1 20% aqueous solution of Actovegin (a protein extract of calf blood from which proteins have been removed) is mixed with a solution of 1660 g of Collidone 90 (polymer of 1-vinyl-2-pyrrolidone) in 16.6 1 of water. pump (3 nozzles with a nozzle opening of 1.2 mm) and spray into a swirling layer. At an initial spray rate of about 600 g of the Actovegin-Collidone 90 / min solution. a stationary water content of about 15% and a temperature of 30 to 32 ° C is established in the vortex layer.

After 2.5 hours, the spray rate increases to 900 g / min at the same supply air temperature. and agglomeration phase is strengthened. After spraying, the resulting granulate is dried in a fluidized bed granulator at a supply air temperature of 70 ° C.

The dried granulate has the following characteristics:

bulk density bulk density bulk density water content grain size

0.53 g / cm ³ 0.63 g / cm ³ 12.30 g / cm ³ sec 1.6%

- 500 ^ um

b) Use of granulate for the preparation of solid drug forms

EXAMPLE 5

Dragee sails

7200 g of Example 1 of the obtained granulate is mixed with 60 g of magnesium stearate and 40 g of talc, and in a rotary pelletizing machine at a compression pressure of 78.5 to 150 N / mm ^2, pressed into a dragee core with a mass of 365 mg. Thus, we obtain dragee kernels that have the following properties:

Grain properties: Composition:

diameter 10,0 mm extract substances 200 mg thickness 5.5 mm Poljrplasdone 75 mg tensile strength 115 N Avicel PH 101 75 mg wear (4 min.) 20,1% Collidon K 25 10 mg breakup 8 - 10 min. talc 2 mg Mg stearate 3 mg

These dragee cores have a constant content of extracts and do not show any deterioration in quality or staining when stored at room temperature for 24 months.

EXAMPLE 6

Pills

7200 g of Example 1 of the obtained granulate is mixed with 60 g of magnesium stearate and 40 g of talc and in a rotary pelletizing machine at a compression pressure of 98 "1 to 196.2 N / mm ^2, compressed into 730 mg tablets. This gives tablets that have the following properties:

Tablet features:

Rectangular tablet 18 mm long 7 mm thick 6.7 mm tensile strength 180 N wear (4 min.) 0.1% decay 10 min.

Composition:

extract substances 400 mg Polyplasdone 150 mg Avicel PH 101 150 mg Collidon K 25 20 mg talc 4 mg Mg stearate 6 mg

The best way to make economic use of the invention

3000 g of a mixture of equal weight parts of Avicel PH 101 (microcrystalline cellulose) and Polyplasdon (cross-linked polyvinylpyrrolidone) are submitted to a vortex material container with a nominal volume of 7 1 and a dry air stream with a flow rate of 500 m ³ per hour and temperature. 80 ° C to create a uniform vortex layer.

1 20% aqueous solution of extracts is mixed with 1 1 20% aqueous solution of Collidon K 25 (polymer 1-vinyl

2-pyrrolidone) is fed into a double-base nozzle by means of a tubular pump and sprayed into a fluidized bed. The spray velocity is controlled by setting the temperature of the fluidized bed 28 to 30 ° C and the stationary water content of the material in the fluidized bed at about 15 wt. %, where the spray water volume and the evaporating water volume are balanced and no agglomeration is observed.

To maintain these conditions, the average spray rate is 70 g of solution per minute. After spraying about 3/4 of the total volume of the solution, the supply air temperature is reduced to 30 ° C and the remaining volume of the solution is sprayed at the same spray rate. The stationary water content of the vortex layer is now increasing and at a water content of 38 to 40 wt. % agglomeration of dust begins. At this water content, granulate until a granulate of 0.06 mm to 0.8 mm in diameter is formed from the total amount of dust. After spraying is completed, the temperature of the supply air is again raised to 60 to 80 ° C, thereby introducing a drying phase. The temperature of the granules ranges from 30 to 32 ° C during drying. Drying is complete as the granulate temperature rises. To remove the remaining water, the granulate temperature is kept at 15

minutes at 43 ° C. That's how we get it nostmi: 7350 g of granulate with the following properties content of extracts 544.2 mg / g granulate Collidon K 25 27.3 mg / g granulate Avicel PH 101 204.0 mg / g granulate Polyplasdone 204.0 mg / g granulate the residual water content about 20 mg / g of granulate, equivalent to about 2% diameter from 0.08 to 0.8 mra

For

HORMON-CHEMIE MUNCHEN GMBH:

PATENT APPLICATIONS

A process for the simultaneous extraction of a dry substance from aqueous solutions of extracts of calf blood from which protein has been removed and the preparation of a granulate which can be compressed into solid drug forms and containing at least 50% by weight. % of extracts based on the total dry weight of the granulate, binder and pharmaceutically acceptable fillers and carriers, characterized in that, in a continuous process in a fluidized bed granulator, the amount of concentrated aqueous solution containing the sprayed liquid is sprayed on to a previously given amount of fillers and carriers the desired amount of extracts and which at 10 wt. parts of the extracts additionally contains 0.2 to 2 wt. of the binder in the dissolved state, adjusting the temperature of the inlet fluidizing gas and the spray rate during the spraying of the entire amount of the solution or at least a large part thereof, such that at the temperature of the swirl layer 25 to 30 ° C and the water content of the material in the swirl layer 15 to 20 wt. % sprayed water and the amount of water that vaporizes roughly correspond to each other, does not form and remains material in the powder form, in order to agglomerate and granulate the resulting milling material even during or after the end of the spraying of the extract substances increase the layer to 35 to 45 wt. % and then the granulate formed, after reaching the desired granulate size, is subjected to short-term drying at a temperature of 30 to maximum 45 ° C by blowing the fluidizing gas inlet.

- 2 ^ 2. Process according to claim 1, characterized in that 25 to 45 wt. % of fillers and carriers by total dry weight of granulate.

Process according to claims 1 or 2, characterized in that microcrystalline cellulose or cross-linked sodium carboxymethylcellulose is used as filler and carrier.

Process according to Claims 1 or 2, characterized in that a mixture of equal weight portions of microcrystalline cellulose and cross-linked polyvinylpyrrolidone is used as fillers and carriers.

5. Procedure after one of the claims 1 to 4, marked with that as fluidizing we use gas. 6. Procedure after one of the claims 1 to 5, marked by this to spray the solution, containing 15 to 25 wt. % of extracts substances. 7. Procedure after one of the claims 1 to 6, marked by this

to spray a solution containing 10 wt. parts of extract substances 0.5 to 1 wt. part of the binder.

Process according to any one of claims 1 to 7, characterized in that the polymers of 1-vinyl-2-pyrrolidone are used as the binder.

Method according to one of Claims 1 to 8, characterized in that after spraying a large part of the volume of the solution, the water content in the vortex layer for agglomeration and granulation is increased by reducing the temperature of the inlet fluidizing gas and / or increasing the spray rate.

Method according to one of Claims 1 to 8, characterized in that the water content after the end of the spraying of the extracts

- ² 2 in the vortex layer for agglomeration and granulation is increased by spraying pure water.

Process according to claims 9 or 10, characterized in that the water content of the vortex layer is increased to 38 to 40 wt. %.

Process according to one of Claims 1 to 11, characterized in that the granulate is dried at a temperature of 30 to 35 ° C in the whirlpool layer and the residual water content is removed by briefly increasing the temperature to 40 to 43 ° C.

Process according to one of Claims 1 to 12, characterized in that a granulate with an extract content of 53 to 70% by weight is prepared. % based on the total dry weight of the granulate.

Process according to one of Claims 1 to 13, characterized in that a granulate having a diameter in the range of 0.05 to 1 mm is prepared.

For

HORMON-CHEMIE MUNCHEN GMBH:

19748-ΙΧ-86 / KA

Claims (1)

SUMMARY The invention relates to a fluidized bed process for the simultaneous extraction of dry matter from aqueous solutions of calf extracts from which protein has been removed and the preparation of a granulate which can be compressed into solid drug forms and containing at least 50% by weight. % of the extracts based on the total dry weight of the granulate, the binder and the pharmaceutically acceptable fillers and carriers, by spraying the aqueous solution of the extracts and binders on the fillers and carriers and granulating the milling agent at a certain water content in the fluid bed. After drying, a compressed granulate is obtained for use in the preparation of solid forms of medicaments of high stability and constant quality.