DD252003B1 - METHOD FOR PRODUCING A DRY ORBITOL WITH IMPROVED APPLICATION-TECHNICAL PROPERTIES - Google Patents

Description

For this 2 pages drawings

Field of application of the invention

Dry sorbitol is used in various products as sucrose substitute for diabetics and in confectionery for caries prophylaxis. Very widespread is the use for sorbitol pellets and for the Talbettierung pharmaceutical active ingredients.

Characteristic of the known state of the art

Sorbitol is prepared by catalytic pressure hydrogenation of glucose in aqueous solution (1). After hydrogenation and optionally after separation of the catalyst, the sorbitol solution is subjected to various purification operations such as fillers, filtration and deionization. Thereafter, the purified solution is concentrated to about 70% by evaporation of water and either marketed in this form or further worked up dry sorbitol (2).

As a material that is difficult to crystallize, sorbitol tends to form supersaturated solutions, retarded crystallization, and partial or complete glassy solidification of the melts. It crystallizes in three different crystal forms (α, β and γ sorbitol), of which the first two are unstable and only the γ form is characterized by resistance. In general, a v-fraction of 90% is aimed for to produce a defined, stable dry sorbitol (3). The crystallization behavior of sorbitol is negatively influenced by isomeric hexites, which can be introduced with the glucose or can be formed by secondary reactions.

For the production of dry sorbitol, a variety of methods have been proposed, which can be divided essentially into the following 3 process principles.

According to the most obvious procedure, the sorbitol solution is evaporated to the nearly anhydrous melt in vacuo.

On cooling, possibly with the addition of crystalline sorbitol, this melt solidifies and, by breaking and grinding, granular to dust-fine dry sorbitol is obtained (4, 5). The product thus produced has a very broad grain spectrum and the proportion of v-sorbitol is subject to great fluctuations. In addition to crystalline sorbitol, considerable amounts of amorphous sorbitol are included. Oas trickle is bad. When stored, this dry sorbitol clumps to a hard mass after slight absorption of moisture. This is a problem-free and easy handling for the processor or the consumer is not given.

According to a second method principle, a highly concentrated sorbitol solution is dropped onto a mechanically agitated bed of crystallized sorbitol or coarsely sprayed (6, 7). The agitated and wetted crystal bed is kept at a temperature of 60 to 30 ⁰ C to evaporate the water while passing air or inert gas. After a corresponding crystallization time, part of the dry sorbitol is continuously removed by cooling.

The dry sorbitol thus obtained again has a very broad particle size spectrum. Partially must by grinding

be prepared in a user-friendly way. Due to its very compact structure, this sorbitol has a relatively high bulk density. The γ-sorbitol content is usually over 90%. The specific surface area is 0.1 m ² / g. A disadvantage of dry sorbitol prepared according to this process principle is that the individual sorbitol particles cake with low moisture absorption from the air quickly to hard masses and that the dissolution time in water is relatively high. Due to the poor trickling behavior, processing on high-speed tabletting machines is only possible with restrictions and frequent malfunctions.

The third process principle is a modified spray drying process. In this process, SO-80% purified sorbitol solution is continuously broken down into very fine droplets by means of a spraying device and at the same time airborne finely divided crystallized sorbitol is introduced into a spray tower so that the sprayed sorbitol solution covers the crystalline sorbitol particles with a thin film. For water evaporation, a hot air stream is additionally injected (8.9). The residual moisture can be varied by the hot air temperature and by the ratio of warm air to sorbitol solution in relatively wide limits (11). After a crystallization time of 20 to 90 minutes, the dry sorbitol is cooled to a temperature of <40 ° C. One part is then removed, while the other part is returned to the spray tower in finely divided form. Dry sorbitol produced by this process has a γ sorbitol content of up to 98%. The bulk density is 0.35 to 0.45 g / ml. As a result of large internal surfaces, this sorbitol tends to be less likely to clump together with low moisture absorption than dry sorbitol produced by other methods. On the other hand, because of the large surface area accessible, the dissolution time in water for dry sorbitol prepared by spray-drying is extremely short. A disadvantage of this dry sorbitol is the low bulk density, by which much larger packaging volumes are required and the preparations which are to be compressed during processing (eg lozenges) require substantially larger punch paths on the pressing tools than in the case of processing dry sorbitol produced by other processes.

Furthermore, this dry sorbitol has a structure that results in a relatively poor trickling and this in turn has a negative impact on the speed and reproducibility of filling in small packages and in tableting on fast tableting machines.

Object of the invention

The aim of the invention is a process for the preparation of dry sorbitol by spray drying, which is characterized by improved performance properties.

Explanation of the essence of the invention

The object was therefore to find a dry sorbitol and a process for its preparation, in particular by increasing the bulk density and flow rate, reducing the angle of repose, reducing the particle size and improving the tableting properties, expressed by increasing the bending and breaking strength of the Sorbitol produced tablets and a better energy ratio E _v in the tableting over known Trockensorbitoltypen distinguished and largely retains the achieved by the spray drying advantageous properties.

The object has been achieved by improving the performance properties by mechanical or pneumatic aftertreatment of dry sorbitol and thereby achieving a dry sorbitol having the following special properties:

- a bulk density of at least 0.5 g / ml

- a repose angle of max. 33 °

- a flow rate of at least 12 g / s

- a specific surface area of at least 0.9 m ² / g

- a melting point of about 95 ° C.

- a residual moisture content of less than 1%

- An energy ratio E _v in the tableting of at least 0.2

a flexural strength resulting from the sorbitol at max. Pressing of 120 MPa produced tablets of at least 8 N / mm ²

- a breaking strength resulting from the sorbitol at max. Pressing of 120 MPa produced tablets of at least 120 N.

To prepare this dry sorbitol according to the invention, purified 50-80% sorbitol solution containing isomeric sugar alcohols <2% and residual sugar <0.2% is sprayed through a spray device in a spray tower and the sprayed solution is intimately mixed with crystallized sorbitol particles finely distributed in a stream of air mixed. At the same time, another air stream with a temperature of 120 to 150 ° C for water evaporation is introduced into this spray tower so that the residual moisture of the resulting dry sorbitol is less than 1%. The primarily produced dry sorbitol is left for further crystallization for 20 to 90 minutes at temperatures of 40 to 80 ° C and then cooled to a temperature below 40 ° C. Part of this crystallized dry sorbitol is fed back to the spray tower in a finely divided manner in a stream of air, while the other part is removed and subjected to a mechanical treatment according to the invention. This mechanical treatment must be designed so as to reduce the sorbitol particles, increase the bulk density and smooth the outer surface to improve the trickle behavior. It has been found that suitable mechanical treatments are passage through a disintegrator or conveyance through a baffled pneumatic conveyor.

In the disintegrator, the sorbitol particles are spun at speeds of 1500 to 4500 min ^-1 at high speed against each other and against stationary or moving baffles. Here, a comminution of agglomerates and there are structural changes to the sorbitol particles. The mean grain size drops to 40 to 80% of the initial value. Similar effects can be achieved during transport via a pneumatic conveying line provided with baffles. The optimum gas velocity is 15 to 50 m / s. As a result of the mechanical treatment, there is a reduction in the mean grain size of 20 to 60% and a rounding of the previously highly branched sorbitol particles. Figure 1 shows an enlarged photograph of dry sorbitol before mechanical treatment and Figure 2 shows the same image

Surprisingly, the βΕΤ-surface of the sorbitol does not change significantly, so that the flowability remain unchanged with low moisture absorption and the dissolution time in water.

On the other hand, the bulk density increases by 30% to 0.6 g / ml. The trickle behavior improves considerably, which is expressed by a reduction of the angle of repose by about 5 ° and the increase of the flow rate up to 60%.

As a user advantage results in an increase in the operating speed and the reproducibility of the filling in small packages and the Tablettierfähigkeit of sorbitol added. In order to quantify this effect, in addition to the determination of the flexural and compressive strength of the tablets, the pressure curve during the entire pressing process is measured as a function of the upper punching path (FIG. 3). Curve 1 in Figure 3 results on the way back of the press ram (relax). The area 3 enclosed by the curves 1 and 2 is proportional to the work for the plastic deformation of the sorbitol, while the area 4 corresponds to the work for the elastic recovery (10). The energy ratio E _v E _v = area 3 / (area 3 + area 4)

gives the percentage of plastic deformation in the entire compression work and is a measure of the tablettability of a substance. In the interest of a good energy utilization and a low burden of tablet presses E _v should approach the maximum value 1 as possible. E _v is a function of the maximum pressing pressure during the measurement. A comparison of the E _v values of yeschiedener products therefore requires the maintenance of a constant maximum pressing pressure in the measurement.

It has been found that the E _v values of sorbitol prepared according to the invention are 0.16 to 0.34 at maximum molding pressures of 128 MPa, while non-mechanically treated sorbitol after spraying at the same maximum molding pressures has Ev values of 0.06 to 0.34 0.11 results.

embodiments example 1

A 70% aqueous sorbitol solution with a temperature of 50 ° C is finely sprayed in a spray tower by a mechanical atomizer and intimately mixed with finely divided in a stream of air crystallized sorbitol particles. In the spray tower, a hot air flow of 120 to 150 ° C is injected so that the residual moisture content of the resulting Trockensorbitols <1% at the same time for water evaporation. Only post-crystallization is left sorbitol 40 minutes at about 5O ⁰ C and then cooled in a cooling drum at 25 ° C. Part of the dry sorbitol is recycled back to the spray tower in the manner described with the air flow, while the other part is removed from the system.

Table 1 summarizes the properties of dry sorbitol. The properties of the tablets prepared from the dry sorbitol result after a pressure of 120 MPa. For the determination of the E _v values, a maximum pressure of 128 MPa was chosen.

The tablet diameter was 10 mm.

Table 1

Properties of spray-dried dry sorbitol without mechanical stress

melting point CC) 95 residual moisture (%) 0.6 bulk density (G / ml) 0.38 angle of repose (Degree) 37 flow rate (G / s) 8.1 mean grain size (Mm) 0.52 spec. surface K / g) 1.1 Tableting properties: Energy ratio E _v 12:09 flexural strength (N / mm ¹ ) 7.5 breaking strength (N) 116

The data in Table 1 were determined as follows:

- Melting point by means of a heating microscope to AB of the GDR

- Residual moisture with moisture absolute FAS 1/2 of the VEB Mytron

Bulk density according to DIN 53912

- Schüttwinkel according to R. Voigt, Textbook of Pharmaceutical Technology, 5th edition, Berlin 1984

- Flow rate according to C. Schaffner, diploma thesis, Halle 1981

- Mean particle size calculated from sieve analysis

, _ (% Sieve fraction mesh size) ^dm "100

- specific surface according to Schwab, Handbook of Catalysis Bd. V, Vienna 1957

- Energy ratio EV to Dürr, M., Hanssen. D., u. Harwalik, H., Pharm. Ind. 34, 905 (1972)

- Flexural strength according to P. H. List, Pharmaceutical Theory, 3rd edition, Stuttgart 1982

- Breaking strength Beyer, B., u. White, G., Diploma Thesis, Halle 1980

Example 2

Dry sorbitol obtained according to Example 1 is passed through a disintegrator at a rotational speed of the impeller of 3200 min ^-1 In the disintegrator, the sorbitol particles are spun against one another and against baffles at high speed

Rounding off the sorbitol particles (Fig. 2) compared to the previous state (Fig. 1). Table 2 summarizes the properties of sorbitol after loading in the disintegrator. The measuring conditions were the same as in Example 1.

Table 2 Properties of spray-dried dry sorbitol after mechanical stress in the disintegrator

melting point ( 'C) 95 residual moisture (*) 0.6 bulk density (G / ml) 0.54 angle of repose (Degree) 32 flow rate (G / s) 12.1 Miner particle size (Mm) 0.36 spec. surface (MVG) 1.08 Tableting properties: Energy ratio E _v 0.34 flexural strength (N / mm ² ) 8.6 breaking strength (N) 126

The comparison of the properties in Tables 1 and 2 shows that the mechanical loading of the dry sorbitol in the disintegrator increased the bulk density by 42% and at the same time improved the trickling behavior, expressed as a 5 ° lower angle of repose and a 49% higher flow rate , The mean grain size has dropped by 39%. The energy ratio E _v in the tabletting and thus the Tablettierbarkeit par excellence are significantly increased. This is also reflected in a higher bending and breaking strength of the tablets made from the sorbitol. In fact, the specific surface remains unchanged and thus the desired behavior against moisture influences.

Example 3 Dry sorbitol obtained according to Example 1 is transported via a pneumatic conveyor line provided with baffles. The

average air velocity is 35 m / s. This mechanical loading of the dry sorbitol results in size reduction looseners, irregularly shaped agglomerates and an optically recognizable rounding off of the sorbitol particles.

Table 3 summarizes the properties of sorbitol after pneumatic delivery. The measuring conditions

were the same as in Example 1.

Table 3 Properties of spray-dried dry sorbitol after mechanical loading by pneumatic conveying

melting point ro 96 residual moisture (%) 0.6 bulk density (G / ml) 0.59 angle of repose (Degree) 32.5 flow rate (G / s) 12.9 mean grain size (Mm) 0.28 spec. surface K / g) 1.16 Tableting properties Energy ratio E _v 0.21 flexural strength (N / mm ² ) 8.9 breaking strength (N) 130

The comparison of the properties in Tables 1 and 3 shows that by the mechanical loading of the dry sorbitol in pneumatic conveying over a baffled line the bulk density increased by 55% and at the same time the trickle behavior, expressed by a 4.5 ° lower angle of repose and a 59% higher flow rate, is improved. The grain size has dropped to 54% of the initial value. The energy ratio E _v in the tabletting and thus the Tablettierbarkeit par excellence are significantly increased. This is also reflected in a higher bending and breaking strength of the tablets made from the sorbitol. In fact, the specific surface and thus the desired behavior towards moisture remain unchanged.

Example 4

According to Example 1 obtained Trockensorbitol is by a disintegrator with a rotational speed of the impeller of 4200 min ^"1. Guided. In the disintegrator the Sorbitolpartikeln at high speed against each other and thrown against baffles. In this mechanical load, a crushing agglomerates present and an optically recognizable rounding of the carried Sorbitol particles versus the previous state Table 4 summarizes the properties of sorbitol after loading

 The measuring conditions were the same as in Example 1.

Table 4

Properties of spray-dried sorbitol after mechanical stress in the disintegrator

melting point ( ⁰ C) 95 residual moisture (%) 0.6 bulk density (G / ml) 0.54 angle of repose (Degree) 32.5 flow rate (G / s) 12 mean grain size (Mm) 0.21 specific surface (MVG) 1.1 Tableting properties: Energy ratio Ev 0.29 flexural strength (N / mm ² ) 8.7 breaking strength (N) 120

The comparison of the properties in Tables 1 and 4 shows that the mechanical density of the dry sorbitol in the disintegrator increased the bulk density by 42% and at the same time the flow behavior, expressed by a 4.5 ° lower angle of repose and by 48% higher flow rate , is improved. The mean grain size has dropped to 40%. The energy ratio E _v in the tabletting and thus the Tablettierbarkeit par excellence are significantly increased. This is also reflected in the higher bending and breaking strength of the tablets made from the sorbitol. In fact, the specific surface and thus the desired behavior towards moisture remain unchanged.

Example 5

Trockensorbitol obtained according to Example 1 is passed through a disintegrator at a speed of the impeller of 2950 min " ¹ .

In the disintegrator, the sorbitol particles are hurled against each other and against baffles at high speed.

Be this mechanical stress is a crushing of existing agglomerates and a visually recognizable rounding of the sorbitol particles compared to the previous state. Table 5 summarizes the properties of sorbitol after loading.

The measuring conditions were the same as in Example 1.

Table 5

Properties of spray-dried sorbitol after mechanical stress in the disintegrator

melting point ( ⁰ C) 96 residual moisture (%) 0.6 bulk density (G / ml) 0.50 angle of repose (Degree) 33 flow rate (G / s) 12 mean grain size (Mm) 0.41 specific surface (Nv7g) 1.12 Tableting properties: Energy ratio E _v 0.24 flexural strength (N / mm ² ) 0.7 breaking strength (N) 125

The comparison of the properties in Tables 1 and 5 shows that the mechanical loading of the dry sorbitol in the disintegrator increased the bulk density by 32% and at the same time improved the trickling behavior, expressed as a 4 ° lower angle of repose and 48% higher flow rate ,

The mean grain size has dropped to 79%. The energy ratio E _v in the tabletting and thus the Tablettierbarkeit par excellence are significantly increased. This is also reflected in the higher bending and breaking strength of the tablets made from the sorbitol. In fact, the specific surface and thus the desired behavior towards moisture remain unchanged.

Examples

Dry sorbitol obtained according to Example 1 is transported via a pneumatic conveyor line provided with baffles. The average air speed is 15m / s. This mechanical stress results in a comminution of loose, irregularly shaped agglomerates and in an optically recognizable rounding off of the sorbitol particles compared with the previous state. Table 6 summarizes the properties of sorbitol after loading. The measuring conditions were the same as in Example 1.

( ⁰ C) 96 (%) 8.6 (G / ml) 0.51 (Degree) 33 (G / s) 12 (Mm) 0.37 (MVG) 1.08 0.20 (N / mm ² ) 8.3 (N) 124

Table 6

Properties of spray-dried sorbitol after mechanical stress by pneumatic conveying

melting point

residual moisture

bulk density

angle of repose

flow rate

mean grain size

specific surface

Tableting properties:

Energy ratio E _v

flexural strength

breaking strength

The comparison in properties in Tables 1 and 6 shows that by the mechanical loading of the dry sorbitol in pneumatic conveying over a baffled line the bulk density increased by 34% and at the same time the trickling behavior, expressed and by a 4 ° lower angle of repose and by a 48% higher flow rate, is improved. The mean grain size has dropped to 71%. The energy ratio E _v in the tabletting and thus the Tablettierbarkeit par excellence are significantly increased. This is also reflected in the higher bending and breaking strength of the tablets made from the sorbitol. In fact, the specific surface and thus the desired behavior towards moisture remain unchanged.

Example 7

Dry sorbitol obtained according to Example 1 is transported via a pneumatic conveyor line provided with baffles. The average air speed is 50 m / s. The mechanical stress results in a comminution of loose, irregularly shaped agglomerates and an optically recognizable rounding off of the sorbitol particles compared to the previous state. Table 7 summarizes the properties of sorbitol after loading. The measuring conditions were the same as in Example 1.

Table 7

Properties of spray-dried sorbitol after mechanical stress by pneumatic conveying

melting point

residual moisture

bulk density

angle of repose

flow rate

mean grain size

specific surface

Tablettlereigenschaften:

Energy ratio E "

flexural strength

breaking strength

The comparison of the properties in Tables 1 and 7 shows that by the mechanical loading of the dry sorbitol in pneumatic conveying over a baffled line the bulk density increased by 47% and at the same time the trickling, expressed by a 4.5 ° lower angle of repose and by a 48% higher flow rate, is improved. The mean grain size has dropped to 40%. The energy ratio E _v in the tabletting and thus the Tablettierbarkeit par excellence are significantly increased. This is also reflected in the higher bending and breaking strength of the tablets made from the sorbitol. In fact, the specific surface and thus the desired behavior towards moisture remain unchanged

 Used literature (I) R. Albert, A. Streitz u. G. Vollheim; Chem. Ing. Techn. 52 (1980), pp. 582-587

(2) Ullmanns Enzyklopädie der Techn. Chemie, 4th Edition, Vol. 24, p. 773

(3) Ullmanns Enzyklopädie der Techn. Chemie, 4th Edition, Vol. 24, p. 774

(4) DD-PS 49 322

(5) DD-PS 76 487

(6) DD-PS 69 360

(7) OD-PS 83 341 (i) Dan. Pat. 133 603 (9) DE-OS 3 245 170

(10) strain, Α., U. Mathis, C,

Acta Pharm. Technol. Suppl. 1.7 (1976)

(11) Ullmann's Encyclopedia of Techn Chem, 4th Edition, Vol. 2, pp. 254-258

( ⁰ C) 96 (%) 0.5 (G / ml) 0.56 (Degree) 32.5 (G / s) 12 (Mm) 0.21 ImVg) 1.18 0.22 (N / mm ² ) 0.8 (N) 128

Claims (1)

Process for the preparation of dry sorbitol with improved performance properties, such as - a melting point of about 95 ⁰ C. - residual moisture below 1% - a bulk density of at least 33 " - a flow rate of at least 12 g / s - An energy ratio E _v in the tableting of at least 0.2 at pressing pressures of 128MPa - A Biefestigkeit of the tablets prepared from the sorbitol at pressing pressures of about 120 MPa of at least 8N / mm ² a breaking strength of the tablets of at least 120N produced from the sorbitol at pressing pressures of about 120 MPa, by spraying a 50 to 80% aqueous sorbitol solution, intimate mixing with air in a finely divided crystalline sorbitol, simultaneous drying with hot air of 120 to 150 ⁰ C, recrystallization at 40 to 80 ⁰ C and cooling to temperatures below 40 ⁰ C, characterized characterized in that the dry sorbitol is subjected to a mechanical treatment when passing through a disintegrator, in which the mean grain size of the sorbitol particles is reduced to 40 to 80% of the initial values, or by pneumatic demand via a baffled conveying line at average air velocities of 15 to 50 m / s is subjected.