DE3009875A1 - METHOD FOR COMPRESSING SORBITE AND PRODUCT OBTAINED THEREOF - Google Patents

Description

ROQUETTE FRERES, F-62136 Lestrem / France

description

METHOD OF COMPRESSING SORBITE AND ITS RECEIVED

PRODUCT

The invention relates to a method for compressing sorbitol.

The product obtained in this way, as well as the uses thereof, are also objects of the invention

The use in compressed form of solid, finely mashed, ground or crushed substances, In other words of powders, it is widely used in the pharmaceutical industry, where it is particularly the dilution of very strong active ingredients in the corresponding vehicles and consequently the administration of these active ingredients simplified.

The powdery substances used in this context are, for example, in the group including dextrose, lactose and sucrose.

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In contrast, this form of application is not very widespread in the food industry, and in particular in the sugar confectionery industry, although this is the area where the recent great development of "sugar-free" products in the production of which polyols of the sorbitol, mannitol and the like are used, great sales opportunities should have done.

Now it is the case that only some sugars and polyols or certain crystal forms of these products are used Compress suitable.

In this context, for example, not all forms of sorbitol - its polymorphism in the crystallized state is known, as well as its difficulties in crystallizing - which are commercially available for compressing, whereby, on the other hand, from the ever larger Quantities of crystallized sorbits that are used in the sugar confectionery industry indicate that the food industry Sorbitol needs one that is suitable for compression.

Now, after long research, the applicant has succeeded in determine that a crystallized sorbitol suitable for compression

- More than 90% by weight from the stable crystallized Must exist in gamma form,

- Has to be present in the form of particles with a slightly angular shape or with little cutting edges, these particles or particles having rounded circumferential shapes or lines have good flow opportunities,

- Has a surface condition with oriented microneedles, the interpenetration of these Needles allows the surfaces that are in contact with one another to be entangled at the time of compression,

- The applicant was also able to determine that a crystallized sorbitol produced with the help of a certain process meets these requirements, this process being characterized in that melted, finely divided sorbitol with a dry matter content of over 98% is continuously at a temperature of ^{over 95 ° C}

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ORIGINAL INSPECTED

⁶ '300987S

lying temperature, which is generally 10O ⁰ C, is mixed with an approximately equivalent amount of powdered sorbitol with a grain size that is less than 5 mm, namely on the surface of a mass kept in motion, which is located inside an open rotating container, which rotates about an axis that may be inclined with respect to the horizontal, the one being kept in motion. The mass consists of grains, which come from the mixture of the melted, finely divided sorbitol and the powdery sorbitol, whereby these grains, which are continuously collected at the exit of the rotating container, after a ripening treatment consist of more than 90% sorbitol of the crystallized, stable gamma form .

Accordingly, the method according to the invention for compressing sorbitol is characterized in that crystallized, powdered sorbitol is used, which,

- consists of more than 90% by weight of the permanent gamma form,

- which is in the form of particles which have only a few corners or cutting edges and which are in contrast in addition with rounded forms or lines award,

- these particles or particles having a surface state with oriented microneedles.

According to a preferred embodiment, the method according to the invention is characterized in that a powdery, crystallized sorbitol is used for compression, which was produced with the aid of a method known per se, corresponding to the melted, finely divided sorbitol, with a dry matter content of over 98% continuously at a temperature above 95 ° C temperature, which is generally carried out at 100 ⁰ C, is mixed with an approximately equivalent amount of powdered sorbitol with a particle size that is less than 5 mm and that at the surface of a mass kept in motion, the is located inside an open rotating container, which rotates around an axis that may be inclined with respect to the horizontal, whereby the moving

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ORIGINAL INSPECTED

Holding mass is made up of grains obtained from the mixture the melted, finely divided sorbitol and the powdery Sorbitol, these grains, which are continuously collected at the exit of the rotating container, after a ripening treatment consist of more than 90% sorbitol of the crystallized, stable gamma form.

The dimensions, the possible inclination relative to the horizontal and the speed of rotation mentioned above Container are selected such that the mixture obtained at the outlet of the container with a grain size of 5 to 20 mm is present, this grain size later except for the values required for compression can be reduced.

The product according to the invention is characterized in that it consists of crystallized, compressed sorbitol, more than 90% by weight of which consists of the stable gamma form, this sorbitol being in the form of particles with only a few angular shapes or cutting edges and which, in contrast, are characterized by rounded enclosing shapes, these particles or particles having a surface condition with oriented microneedles, this sorbitol being expediently produced with the aid of a process according to which melted, finely divided sorbitol with a dry matter content of over 98% continuously at a temperature above 95 ° C temperature, which is generally carried out at 100 ⁰ C, is mixed with an approximately equivalent amount of powdered sorbitol with a particle size that is less than 5 mm and that at the surface of a mass kept in motion, the is located inside an open rotating container, which is around an event uell rotates with reference to the horizontal inclined axis, the mass kept in motion consisting of grains resulting from the mixture of the melted finely divided sorbitol and the powdery sorbitol, these grains, which are continuously collected at the exit of the rotating container, after a ripening treatment more than 90% sorbitol consists of the crystallized permanent gamma form.

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INSPECTS)

3003875

The application of the compressed according to the invention Sorbits are in the field

- the food industry and in particular the sugar confectionery industry, the dietetic food industry, especially for diabetics, for example in the production of "sugarless candies"

- the pharmaceutical industry.

The compression of the sorbitol used according to the invention takes place immediately and without prior granulation instead, which gives a significant advantage over conventional compression methods in which the preceding Granulating is necessary.

Seen from the practical point of view and according to the invention Production of a compressed product based on sorbitol is that used according to the invention crystallized sorbitol for use, this sorbitol being intimate with the necessary quantities of ingredients, such as lubricants, Aromatics, dyes, acidification products and possibly active ingredients, is mixed and this mixture is immediately compressed.

It is emphasized that in some cases the aromatics, dyes, acidification products and other possible Ingredients can be incorporated into the sorbitol used according to the invention at the time of Making the same.

The grain size of the sorbitol used according to the invention is generally less than 10 mm.

The flowability of the powdered sorbitol particles used according to the invention enables

- regular feeding of the compression machines with powdered sorbitol

- an even distribution of the powdery Sorbits in the matrices of the compression machines.

It can therefore be seen that the compressed tablets obtained in this way have a remarkable evenness from the Point of view of the weight and that, moreover, the powdery starting orbit does not have the sinking phenomena which otherwise occur and by which

030039/0797 ORIGINAL INSPECTED

Pilling irregularities occur during normal machine operation.

The compressibility of the according to the invention for use Coming sorbitol is far higher than that of the sorbitol used according to the prior art. Hence is the hardness of the tablets obtained in this way is higher at the same level of compression, the surface condition being with oriented microneedles enables a cohesion between the particles, which is very high, with identical Sliding effect. -

The rounded shape of the particles also affects the hardness; in fact are the points of friction less numerous and the surfaces to be lubricated smaller, which means that less lubricant is required is and whereby a greater hardness of the tablets is achieved, this hardness in inverse proportion to Sliding effect lies.

The significant reduction in the amount of lubricant used continues to yield significant advantages from the standpoint of taste properties.

Advantageous embodiments of the invention are illustrated with the aid of the following examples and the superiority of the process according to the invention and the products thus obtained over the prior art are shown with the aid of comparative experiments. EXAMPLE 1

Comparison of the results obtained with the aid of sorbitol powder according to the state of the art on the one hand and with the aid of the other of sorbitol, having the properties of the sorbitol used according to the invention.

The, the prior art sorbitol, was prepared by evaporation under vacuum at 12O ⁰ C a solution containing 70% dry matter, wherein said evaporation is performed up to a dry matter content of 99%; This sorbitol is poured into molds and then mixed an impalpable crystallized sorbitol powder at a temperature somewhat lower than 100 ⁰ C with 25 wt.% and that to initiate the crystallization.

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The suspension thus obtained is kneaded until it starts to solidify, and then the suspension thus obtained becomes Mass after crystallization at normal temperature or ripening process, crushed.

The crystallized sorbitol which corresponds to that which is used according to the invention, its features in of the description above was produced using the method defined in the description.

The sorbitol powder according to the prior art and the sorbitol used according to the invention were used up to Grind to a grain size spectrum, according to the

- 13.5% of the particles are between 800 and 1000 microns

- 46.9% of the particles are between 500 and 800 microns

- 34.3% of the particles are between 315 and 500 microns

- 5.3% of the particles are below 315 microns.

Starting from these two sorbitol powders, tablets are produced with a weight of 1.15 g Addition of 0.3% by weight magnesium stearate; this is a Laboratory compressor used, expediently of the MILCOTT K 55 type (sold by Edmond FROGERAIS); four different compression values are used, which correspond to four positions of the ram and which are in the The following description is identified by the information items 1 to 4.

The tablets obtained in this way are considered first, and then their resilience becomes in one Crush test measured with the help of an apparatus, with which increasing pressure values can be achieved, whereby this apparatus is expediently an apparatus of the INSTRON type, Model 1122 (sold by INSTRON).

Twelve tablets were tested; the mean value of the crushing resistance is calculated without taking it into account the highest and the lowest value.

The results obtained in this way are summarized qualitatively in Table I and quantitatively in Table II; the latter corresponds to the graphic representation of the Figure 1, which shows the variation in crush strength,

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ORIGINAL INSPECTED

«■ 3 OO 9 S ^r * 5

in kg / cm2, in relation to the manufacturing compression value, i.e. in relation to positions 1, 2, 3 and 4 of the punch illustrated. The curve I corresponds to the sorbitol used according to the invention; corresponds to curve II the sorbitol according to the state of the art.

TABLE I.

Compression value
at the manufacturer
treatment of the tablets Tablets on the base
of the invention
used sorbitol Tablets on the ba
sis of sorbitol after the
State of the art position 1 broken edges
grainy appearance nosed edges
very grainy appearance Position 2 nice edges
grainy appearance broken edges
very grainy appearance Position 3. nice edges
slightly grainy end
see broken edges
grainy appearance Position 4 sharp edges
smooth surface broken edges
Lich grainy appearance

TABLE II

Compression value Crush resistance
(kg / cm ² ) Tablets on the ba
sis of sorbitol after the
State of the art position 1 Tablets on the base
of the invention
used sorbitol 7.4 Position 2 14.5 21.2 Position 3 39.2 67.5 Position 4 98.9 150 288

From the results summarized in the two tables it can be seen that the cohesion of the tablets produced according to the invention is almost twice better than that of the tablets, manufactured with the help of sorbitol according to the state of the art

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became.

These two samples of crystallized sorbitol were subjected to the analyzes given below to characterize their crystal state, the particle shape and the micro-surface condition.

a) Determination of the characteristics regarding the crystal state

1. The diffraction spectra obtained with the aid of X-rays of the two powders are recorded in Figures 2 and 3, the intensity I in the ratio is given for the angle Θ (curves C · ^ for according to the invention applicable sorbitol or, D, for sorbitol accordingly the state of the art).

The diffraction spectrum obtained in connection with the sorbitol used according to the invention corresponds to that the constant gamma form of sorbitol- This sorbitol can absorb moisture and thermal, as well as mechanical Treatments are undergone without any changes in structure.

The spectrum of the prior art sorbitol is very different from the previous one and corresponds to one inconsistent crystallized form of sorbitol.

2. A differential thermal analysis was then carried out of the two powders carried out using a thermoanalytical apparatus from METTLER from Type TA 2000.

Curves C ~ (from sorbitol according to the invention) and D2 (according to the prior art), which appear on drawings 4 and 5, were obtained. Curve C2 corresponds to the melting of a pure crystallized sorbitol form, whereas curve D ^ corresponds to that of a polymorphic state (D2 is characterized by the presence of two maxima or peaks s /; it is therefore a form with a low melting point, which undergoes a transformation followed by a second mold with a higher melting point).

The present invention next apply sorbitol has a melting point of 98.56 ⁰ C, a heat of fusion of 179.5 joules / g and a proportion of 95.7 wt.% Of

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ORIGINAL INSPECTED

Th

stable crystallized gamma form (these values are obtained by the above-mentioned thermoanalytical apparatus) -

Curve D ₂ is typical of the melting process of volatile crystallized forms, the volatile, low melting point form being transformed into the stable high melting point form.

b) The shape of the particles

The two tested sorbitol powder samples were sieved and the fraction, which corresponds to a particle size of 350 to 500 microns, was observed and photographed with a magnifying glass of the type BBT "KRÄUSS", at a magnification of 16, the particles Ρ * according to FIG correspond to the sorbitol used according to the invention and the particles P ₂ according to FIG. 7 correspond to the sorbitol of the prior art.

As can be seen from FIGS. 6 and 7, the particles P _{2 have} a much more angular shape (probably due to a not insignificant proportion of amorphous sorbitol) than that of the particles P ₁ , which are rounded and have practically no acute angles.

The particles P, are agglomerates of small "nuclei" with a rounded shape and with "wave-like" surfaces.

c) The microsurface condition

The particles of both samples look like under the electron microscope and at a magnification of 1500 on FIGS. 8 (sorbitol used according to the invention) and 9 (prior art sorbitol).

It is clear that the micro-surface condition of both powders is very different from each other. The sorbitol used according to the invention has a clearly oriented surface structure in the form of "dendrites" with microneedles M, the sorbitol according to the prior art being in the form of "threads" F which are not oriented and are matted with one another.
EXAMPLE 2

Comparative experiments were carried out, on the one hand with a sorbitol used according to the invention with a finer one Grain size than that of Example 1, and on the other hand with a commercially available crystallized sorbitol according to the

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State of the art, the grain size of which is that of the invention sorbitol used.

The grain size of both powders is as follows: 3.8% particles with a grain size of over 315 microns 28, 2% particles with a grain size between 200 and 315 microns 57.5% particles with a grain size between 80 and 200 microns 10.5% Particles with a grain size below 80 microns

The tablets were made after adding 0.3% magnesium stearate The tablets were produced with the mean weight of the tablets obtained being 1.15 g the same apparatus produced as in Example 1, with five positions of the stamp, those with position 5 to Position 9 are designated.

The same observations and measurements were made on the tablets thus obtained, and the results are in the. Tables III and IV summarized.

TABLE III

Compression value Tablets on the base
of the invention
used sorbitol Tablets on the base
of sorbitol after the
.State of the art Position 5 slightly grainy
Appearance
sharp edges sticks to the stamp
broken edges
quite grainy appearance Position 6 slightly grainy
Appearance
sharp edges . slightly grainy end
see
sticks to the stamp Position 7 very slightly grainy
Appearance very slightly grainy
Appearance
sticks to the stamp Position 8 smooth and shiny
Tablets
sharp edges unprimeable
sticks to the stamp Position 9 smooth-glossy uncompressible
sticks to the stamp

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/ S "

TABLE IV

Compression
value Crushing strength (kg / cm ² ) Tablets on the ba
sis of sorbitol after
the state of the art Position 5 Table killing on the ba
sis of the invention
used sorbitol 5.35 Position 6 30th 25.0 Position 7 58.7 50 Position 8 140 - Position 9 271 - 386

From these results it is clear that the sorbitol used according to the invention leads to tablets which are much more pressure-resistant.

Both powder samples were then subjected to the same analyzes and tests as in Example 1, the corresponding results are summarized in Table V.

TABLE V

according to the invention
Sorbitol more conventional
Sorbitol. X-rays Gamma spectrum complex spectrum thermal special
analysis
(Appearance of the Pul
verse) 95% crystallizes
te gamma form Polymorphism Appearance of the powder rounded
powder Split planes
sharp edges Micro-surfaces
State
(under the electron
microscope) crystallization
with dendrites
Fine microcrystalline
sizing with needles fibrous out
see
amorphous masses

These results confirm those after

Example 1.

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EXAMPLE 3

This example is identical to example 2.

The two crystallized sorbitol samples correspond to those of Example 2 and demonstrate the grain size Example 1 on.

The density of both products is identical except for 2% and the average weight of the tablets obtained is 1.02 g.

Compression tests were carried out with different compression values, the gradually higher compression values being achieved with the help of the variation of the ram stroke, namely with powders to which 0.2% magnesium stearate was previously added - the pressure values in the five tests are the same as in Example 2 (Position 5 to Position 9).

The results are summarized in Tables VI and VII.

TABLE VI

Compression
value Tablets on the base
of the invention
.used sorbitol Tablets on the base
of sorbitol after the
State of the art Position 5 broken edges
grainy appearance broken edges
grainy appearance Position 6 broken edges
. grainy appearance. . broken edges
. .grainy appearance Position 7 smooth edges
slightly grainy
Appearance... smooth edges
slightly grainy
Appearance Position 8 smooth and shiny
of appearance slightly grainy
Appearance. . . Position 9 smooth and very
shiny appearance. very slightly grainy
Appearance... . .

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TABLE VII

Compression
value Crush strength (kg / arr) Tablets on the ba
sis of sorbitol after
the state of the art Position 5 Tablets on the ba
sis from inventions
used sorbitol 5.7 Position 6 8.8 13.9 Position 7 22.4 .37.7 Position 8 65.3 89.7 Position 9 148.3 155. 288

The differences in the behavior of the two samples are clear from the comparison of the above results. EXAMPLE 4

Tablets were produced at the same compression pressure, the pressure being that of item 8 Example 2 corresponds to and wherein samples of crystallized sorbitol from various sources have been tested are.

The samples are previously brought to the same grain size, which corresponds to that of Example 1; the density of the powders is identical to 2% and the average weight of the tablets is identical to less than 4%.

The following samples were tested:

- Sorbitol used according to the invention is identical with that of Example 1 (product X,).

Four commercially available sorbitos of various origins (referred to as product X2, product X3, product X4 and product X ₅ ),

- Sorbitol according to the prior art identical to that whose production is described in Example 1 (product X ₆ ).

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** - 3009375

As in the previous examples, the tablets prepared with the aid of the samples mentioned above are on the compressive strength tested. Their appearance is also noted.

The results are summarized in Tables VIII and IX :

TABLE VIII

product product product product product product ^X 2 ^X 3 X ₄ ^X 5 ^X 6 smooth and very easy grainy grainy grainy easy shiny grainy Appearance Appearance Appearance grainy Appearance Appearance sticks dm sticks to Appearance rubber stamp rubber stamp hard to compressie_ ren

JX

Crushing strength (kg / cm ² )

product
^X l product
^X 2 product
^X 3 product
^X 4 ^ product
^X 5 product
^X 6 287 155 169 65 85
150

The results of the tests and analyzes according to Example 1, which were carried out on the above samples, are shown in
Table X summarized.

ORIGINAL INS
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TABLE X

product product product product product product ^X l X ₂ * 3 ^X 4 ^X 5 X Crystal! - · gamma complex Ganttia— Ganna— complex nity spectral Spectrum Spectrum spectrum spectrum roentgen purity Polymor purity purity Polymor shine = 95% phism = 86% = 85% phism T.D.A. Appearance rounded down sharp sharp sharp sharp sharp the dete edge edge edge edge edge powder shape micro- perfect fiber- Beginning Beginning fiber- Upper micro- formal- one one formal- area- crystal total micro- micro- ges off State lisie- the end crystal crystal see tion see lisie- lisie- tion tion

From these results it can be seen that only the sorbitol used according to the invention is excellent Properties when compressing leads.

Two further samples (these are the products X ₃ and X5) have a relatively high content of stable gamma form, but lead to rather mediocre compression results, which again illustrates the superiority of the sorbitol used according to the invention.

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Claims (10)

Dr. F. Zumstein Sr. - Dr &. Assmann - Dr. R. Koenigsberger Dipl.-Phys. R. Holzbauer - Dipl.-Ing. F. Klingseisen - Dr. F. Zumstein jun. PATENTANWÄLTE 80OO Munich 2 ■ Bräuhausstraße 4 · Telephone collection no. 225341 ■ Telegrams Zumpat ■ Telex 529979 20 / Lb OO82-8O-Ö5 PATENT CLAIMS 1.) A method for compressing sorbitol, characterized in that that powdered, crystallized sorbitol is used, the - more than 90% by weight consists of gamma sorbitol, - Which is in the form of particles that have only slightly angular shapes or cutting edges and that are in contrast, are characterized by rounded outer lines - The surface condition of these particles is characterized by oriented micro-needles. 2. A method for compressing sorbitol, characterized in that crystallized powdered sorbitol is used, which has been produced by a process similar to that of melted, finely divided sorbitol with a dry matter content of over 98% continuously at a temperature above 95 ° C, which is generally 030039/0797 at 10O ⁰ C, is mixed with an approximately equivalent amount of powdered sorbitol with a grain size that is less than 5 mm, on the surface of a mass kept in motion, which is located within an open rotating container, which may be referred to rotates to the horizontal inclined axis, whereby the kept moving mass consists of grains, which result from the mixture of the melted finely divided sorbitol and the powdery sorbitol, whereby these grains, which are continuously collected at the exit of the rotating container, after a ripening treatment to more than 90 % consist of sorbitol of the crystallized permanent gamma form. 3. Product based on compressed, crystallized sorbitol, more than 90% by weight of sorbitol of the gamma form, present in the form of particles that have only slightly angular shapes and cutting edges, and that are in the On the contrary, they are characterized by rounded outer lines, whereby these particles have a surface condition with oriented Have microneedles. 4.Product based on crystallized, compressed sorbitol, this sorbitol being produced using a process according to which molten, finely divided sorbitol with a dry matter content of over 98% continuously at a temperature of over 95% C, which is generally 100 ⁰ C is mixed with an approximately equivalent amount of powdered sorbitol with a grain size that is less than 5 mm, on the surface of a mass kept in motion, which is located inside an open rotating container, which is possibly inclined with reference to the horizontal The axis rotates, the mass kept in motion consisting of grains that come from the mixture of the melted, finely divided sorbitol and the powdered sorbitol, these grains, which are continuously collected at the exit of the rotating container, after a ripening treatment to more than 90% sorbitol the crystallized persistent gamma form exist. 030039/0797 ³ 3009675 5. Application of compressed sorbitol, produced by the method according to any one of claims 1 and 2, in the The food industry, particularly the sugar confectionery and dietetic food industries, especially for diabetics. 6. Application of the product according to one of claims 3 and 4 in the food industry, in particular the ' The sugar confectionery industry and the dietary food industry, especially for diabetics. 7. Application of the compressed sorbitol, prepared using the method according to any one of claims 1 and 2 in the pharmaceutical industry. 8. Use of the Erzeungisses according to one of claims 3 and 4 in the pharmaceutical industry. 9. A method for producing the product according to any one of claims 3 and 4, characterized in that sorbitol directly, without prior granulating the sorbitol, is compressed, this sorbitol the necessary amounts of ingredients, such as lubricants, aromatics, colors, acidulants and contains other active substances. 10. A method for producing the product according to any one of claims 3 and 4, characterized in that Sorbitol is compressed immediately, without prior granulation, this sorbitol beforehand with the necessary Amounts of ingredients such as lubricants, aromatics, colorings, acidification products and possibly other active ingredients mixed together; will. 0 3 0 C5 9/0797