GB2046743A

GB2046743A - Compressible sorbitol

Info

Publication number: GB2046743A
Application number: GB8008745A
Authority: GB
Original assignee: Roquette Freres SA
Current assignee: Roquette Freres SA
Priority date: 1979-03-16
Filing date: 1980-03-14
Publication date: 1980-11-19
Also published as: NO800748L; AU5646580A; IT8020671A1; FI800807A7; FR2451357A1; JPS55132628A; DE3009875A1; BE882216A; NL8001528A; IT8020671A0; SE8002013L; DK110680A; IT1149912B

Abstract

A preparation of sorbitol which can be compressed has at least 90% by weight of the sorbitol in gamma form and comprises blunt-shaped particles with an orientated micro- needles surface state. The sorbitol is manufactured by mixing finely divided molten sorbitol, of dry matter content greater than 98%, with essentially the same amount of pulverulent sorbitol of particle size less than 5 mm at a temperature above 95 DEG C in an open rotating vessel to form grains which when ripened contain at least 90% by weight of gamma sorbitol. These grains, if necessary reduced in size, can be compressed to provide tablets comprising sorbitol for dietetic or pharmaceutical use.

Description

SPECIFICATION Compressible sorbitol The invention relates to a preparation of sorbitol which can be compressed, to a process for putting sorbitol into a compressible form, and to the use of such compressible sorbitol.

The bringing of finely ground, crushed or pulverised solid substances, e.g. powders, into compressed form is widespread in the pharmaceutical industry where it notably allows the dilution of very potent active principles with excipients and, consequently, the formulation of suitable unit dosage forms. The pulverulent substances used in this context are, for example, dextrose, lactose and saccharose.

This procedure, however, is seldom practised in the food industry where, especially in the making of confectionary, there has been considerable recent development of so-called "sugarless" products comprising polyols of the sorbitol or mannitol type and the like, which should provide important avenues open to the adoption of this procedure. This is because it so happens that only certain sugars and polyols or certain crystalline types of these materials are suitable for compression.

In the case of sorbitol, the polymorphism of which in the crystalline state as well as the difficulties of crystallising it are known, all of the grades which are to be found on the market are not suitable for compression. However, in view of the increasing tonnages of crystalline sorbitol being used in confectionary, there is clearly a need in the food industry for a preparation of sorbitol giving good results on compression.

We have now found surprisingly that, to have optimal compressibility, the crystalline sorbitol must: - be in the gamma-crystalline form to a proportion of at least 90% by weight; - be present in the form of particles including few angular shapes or sharp edges and distinguished but blunt contours, which confers on it good flow characteristics, a higher number of points of contact and, hence, better interpenetration of the particles; - have a surface state with orientated micro-needles, whose interpenetration enables "felting" of the surfaces present during compression.

We have moreover found that such crystalline sorbitol, may be prepared by the application of a process known in itself and characterised by the fact that finely divided molten sorbitol of dry matter content higher than 98%, is mixed continuously at a temperature above 950C, generally close to 1 00 C, with an approximately equivalent amount of pulverulent sorbitol of granulometry less than 5 mm, at the surface of a mass kept in motion inside an open rotating container e.g. rotating around an axis which may be inclined to the horizontal, said mass being constituted by grains derived from the mixing of the finely divided molten sorbitol and the pulverulent sorbitol, the grains being collected continuously at the outlet of the rotary container, and being constituted after ripening by more than 90% of sorbitol in gamma stable crystalline form.

Accordingly, in the present invention sorbitol for putting into compressed form is characterised by the fact that it is pulverulent crystalline sorbitol: - which is of gamma form to more than 90% by weight; - which is in the form of particles comprising few angular shapes or sharp edges and having blunt contours; and - the constituent particles have a surface state of orientated micro-needles.

The invention also provides a process for the preparation of sorbitol as defined above, which process comprises continuously mixing finely divided molten sorbitol, of a dry matter content higher than 90%, at a temperature above 950C, generally close to 1 000C, with an approximately equivalent amount of pulverulent sorbitol of granulometry less than 5 mm, at the surface of a mass held in motion inside an open rotary container, rotating around an axis if necessary inclined to the horizontal, said mass being constituted by grains derived from the mixing of finely divided molten sorbitol and pulverulent sorbitol, these grains, which are collected continuously at the outlet of the rotary container, being constituted after ripening by more than 90% by weight of sorbitol in gamma stable crystalline form.

The dimensions, the possible inclination and the speed of rotation of the above said container are selected so that the mixture collected at the outlet shows a granulometry of 5 to 20 mm which may be brought back subsequently to the values required for compression.

The applications of the sorbitol according to the invention belong to the fields of: -the food industry, in particular confectionary and dietetic foods, notably for diabetics, for example, "sugarless sweets"; and -the pharmaceutical industry.

The manufacture of compressed products using the sorbitol according to the invention takes place by the direct compression route without prior granulation, which constitutes a considerable advantage with respect to the traditional methods of compression for which said granulation step is necessary.

From the practical point of view and to manufacture a compressed product base on sorbitol according to the invention, the sorbitol is mixed intimately with any necessary amounts of lubricating ingredients, flavourings, colourings, acidulants and/or active principles, the mixture thus obtained being directly subjected to compression.

In certain cases, flavourings, colourings, acidulants and other possible ingredients may be intimately incorporated with the sorbitol according to the invention, during the manufacture of the latter.

The granulometry of the sorbitol according to'the invention is generally less than 10 mm.

In the examples which follow, advantageous embodiments of the invention are illustrated and it is demonstrated, by means of comparative tests, that there is a superiority of the sorbitol according to the invention with respect to the prior art.

EXAMPLE 1.

This Example compares the results obtained employing sorbitol powder according to the prior art and sorbitol having the characteristics of that provided according to the invention.

The sorbitol of the prior art is obtained by evaporation under vacuum from a solution with 70% of dry matter at 1 200C to a dry matter content of 99%; it is cast into moulds then, at a temperature slightly below 1 000 C, there is added to it 25% by weight of an impalpable powder of crystalline sorbitol, for the purpose of initiating crystallisation. This suspension is triturated until the beginning of solidification then, after crystallisation at ordinary temperature'oi ripening, the mass thus obtained is ground.

The crystalline sorbitol complying with the characteristics of that according to the invention, defined in the description, was prepared by the application of the process described above.

The sorbitol powders of the prior art and of sorbitol according to the invention were brought by grinding to the following granulometric spectrum: - 13.5% of particles comprise between 800 and 1000 microns; - 46.9% of particles comprised between 500 and 800 microns; - 34.3% of particles comprised between 31 5 and 500 microns; - 5.3% of particles less than 31 5 microns.

Tablets of a weight of 1.1 5 g were prepared from these two sorbitols to which was added 0.3% by weight of magnesium stearate, in a laboratory compression apparatus advantageously of the MILCOTT K 55 type (marketed by Ets Edmond FROGERAIS) using four different compression ratios, corresponding to four positions of the piston, called Position 1 to Position 4.

The tablets obtained were observed visually, then their resistance to crushing was measured on an apparatus adapted to subject them to increasing pressures, advantageously of the INSTRON, MODELE 1122 type (marketed by the INSTRON Company).

Twelve tablets were prepared and tested, the average value of the crushing strength indicated being obtained after putting aside the maximum value and the minimum value.

The results obtained are summarised qualitatively in Table I and quantitatively in Table II to which the graph shown in Figure 1 corresponds and in which the variation in the crushing strength, expressed in kg/cm2, is represented as a function of the compression ratio on manufacture, that is to say of the positions 1, 2, 3 and 4 of the piston. Curve I is that corresponding to the sorbitol according to the invention, curve Il that corresponding to the sorbitol according to the prior art.

TABLE I

Compression ratio Tablets based on Tablets based on in the manufacture sorbitol according sorbitol according of the tablets to the invention to the prior art broken edges broken edges Position 1 grainy appearance very grainy appea rance fine edges broken edges Position 2 grainy appearance very grainy appea rance fine edges broken edges Position 3 slightly grainy grainy appearance appearance sharp edges broken edges Position 4 smooth surface fairly grainy ap pearance TABLE II

Crushing strength (kg/cm2) Compression ratio Tablets based on Tablets based on sorbitol according sorbitol according to the invention to the prior art Position 1 14.4 7.4 Position 2 39.2 21 2 Position 3 98.9 87.5 Position 4 288 150 As can be seen the cohesion of the tablets prepared from sorbitol according to the invention is almost twice as good as that of tablets prepared from the sorbitol of the prior art.

The two specimens of crystalline sorbitol were also subjected to the following analyses to characterize their crystallinity, the form of the particles and the micro-state of the surface of the latter.

a) Determination of the characteristics relating to crystallinity: 1. The X-ray diffraction spectra of the two powders are shown in Figures 2 and 3, intensity I as a function on the scanning angle 0 (curves respectively C1 for sorbitol according to the invention and D1 for sorbitol according to the prior art).

The spectrum obtained for the sorbitol according to the invention is characteristic of the gamma stable crystalline form. This sorbitol can take up moisture again and undergo heat or mechanical processing without undergoing structural changes.

The sorbitol spectrum according to the prior art is very different and corresponds to an unstable crystalline form of sorbitol.

2. A differential thermal analysis was carried out on the two powders using a my METTLE thermoanalytic device of the TA 2 000 type.

The recordings shown by curves C2 (sorbitol according to the invention) and D2 (sorbitol asccording to the prior art) in Figures 4 and 5 were obtained. Curve C2 is characteristic of the fusion of a pure crystalline form, the curve D2 of that of a polymorphous state (the latter is characterized by the presence of two peaks, that is to say a form with low melting point followed by a transformation, followed itself by a form with a higher melting point).

The sorbitol according to the invention has a melting temperature of 98.560, a heat of fusion of 179.5 Joules/g and a percentage of stable gamma crystalline form of 95.7% (data provided by the thermoanalytic device).

Curve D2 is typical of the melting of unstable crystalline forms, the unstable form with low melting point being transformed into a stable form with high melting point.

b) The shape of the particles: The two specimens of sorbitol powder examined were sifted and the fraction corresponding to a granulometry comprised between 350 and 500 microns was observed and photographed by means of a lens of the "BBT KRAUSS" type, with a magnification of 16. The particles P1 shown in Figure 6 correspond to the sorbitol according to the invention and the particles P2 shown in Figure 7 correspond to the sorbitol of the prior art.

As seen in Figures 6 and 7, the shape of the particles P2 is far more angular (probably due to the non-negligible percentage of amorphous sorbitol present in this specimen) than that of particles P which are blunt and include practically no sharp angles.

The particles P1 are agglomerates of small "nuclei" with a blunt shape and with "undulating" surfaces.

c) The micro-state of the surfaces: The constituent particles of the two specimens examined, have under the sweep electron miscroscope with a magnification of 1 500, the appearance shown in Figure 8 (sorbitol according to the invention) and 9 (sorbitol according to the prior art).

It clearly appears that the micro-state of the surface of these two powders is very different, the sorbitol according to the invention having a distinctly orientated surface structure, in the form of "dendrites" with micro-needles M, whereas the specimen of sorbitol according to the prior art is in the form of "filaments" F, entangled and unorientated.

EXAMPLE 2.

Comparative tests were carried out on a sorbitol according to the invention with finer granulometry than in Example 1 and on a crystalline sorbitol according to the prior art available on the market, of granulometry comparable with the sorbitol according to the invention.

The granulometry of the two sorbitol powders was: - 3.8% of particles larger than 3-1 5 microns; - 28.2% of particles comprised between 200 and 315 microns; - 57.5% of particles comprised between 80 and 200 microns; - 10.5% of particles larger than 80 microns.

Tablets were prepared after addition of 0.3% of magnesium stearate, the average weight of the tablets obtained being 1.1 5 gram. Tablets were manufactured with the same apparatus as in Example 1 and for five positions of the piston marked by Position 5 to Position 9.

Observations and measurements identical with those of Example 1 were carried out on the tablets so-obtained and the results are summarized in Tables Ill and IV below.

TABLE III

Tablets based on Tablets based on Compression ratio sorbitol according sorbitol according to the invention to the prior art slightly grainy sticks to the slightly grainy sticks to the Position 5 appearance piston sharp edges broken edges rather grainy ap pearance slightly grainy slightly grainy Position 6 appearance appearance sharp edges sticks to the piston very 7 very slightly very slightly Position 7 grainy appearance grainy appearance sticks to the piston smooth and bright impossible to Position 8 tablets eompress sharp edges sticks to the piston gmooth - bright impossible to Position 9 compress sticks to the piston TABLE IV

Crushing strength (k9/cm2) Compression ratio Tablets based on Tablets based on sorbitol according sorbitol according to the invention to the prior art Position 5 30 5.35 Position 6 58.7 25.0 Position .7 140 50 Position 8 271 Position 9 386 It emerges clearly from these results that the sorbitol according to the invention leads to the production of tablets which are much more resistant to crushing.

These two specimens of sorbitol powders were subjected to the other analyses and examinations described in Example 1 and the results are collected in Table V.

TABLE V

Sorbitol according Sorbitol according to the invention to the prior art' X rays gamma spectrum complex spectrum DTA (differential 95% of gamma polymorphism thermal analysis) crystalline form Appearance of the blunt powder cleavage planes powder sharp edges Micrnstate of the dendritic crystal- fibrous appearance surface (sweep lization amorphous masses electron micros- fine microcrystal copy) lization in needles The above results confirm those of Example 1.

EXAMPLE 3.

The prior art sorbitol used was that used in Exampie 2, and the two specimens of crystalline sorbitol used had a granulometry as given in Example 1.

The density of the two products was identical to within 2% and the average weight of the tablets obtained was 1.02 gram.

The compression tests were carried out at increasing compression ratios, obtained by variation of the stroke of the piston, on powders to which 0.2% of magnesium stearate was added. The values of the pressure in the five pressure tests were the same as in Example 2 (positions 5 to 9).

The results are summarized in Table VI and VII below.

TABLE Vl

Tablets based on Tablets based on Compression ratio sorbitol according . sorbitol according to the invention to the prior art Position 5 broken edges broken edges grainy appearance grainy appearance Position 6 broken edges broken edges grainy appearance grainy appearance smooth edges I smooth edges Position 7 slightly grainy slightly grainy appearance appearance Position 8 smooth and bright slightly grainy appearance appearance Position 9 smooth and very very 'slightly bright appearance grainy appearance TABLE VII

Crushing strength (kg/cm2) Compression ratio Tablets based on Tablets based on sorbitol according sorbitol according to the invention to the prior art Position 5 8.8 5.7 Position 6 22.4 13.9 Position 7 65.3 37.7 Position 8 148.3 89.7 Position 9 288 155 The differences in behaviour between the two specimens of crystalline sorbitol are hence still as distinct.

EXAMPLE 4.

Tablets were manufactured at a pressure corresponding to position 8 of Example 2 from various specimens of crystalline sorbitol of different origins.

These specimens were previously brought to the same granulometry, identical with that of Example 1; the density of each powder was similar to within 2% and the average weight of the tablets prepared was also identical to within less than 4%.

The specimens of crystalline sorbitol tested were the following: - sorbitol according to the invention, identical to that of Example 1 (Product X); -four commercial sorbitols of various origins (denoted by the names Product X2, Product X3, Product X4 and Product X5); - sorbitol manufactured as described in Example 1 (Product Xe); As in the preceding examples, the tablets obtained from these various specimens were observed and tested from the point of view of their compression strength.

The results are presented in Tables VIII and IX.

TABLE VIII

Product X1 Product X2 Product X3 Product X4 Product X5 Product smooth very 1 grainy ap- grainy ap- grainy ap- slightly bright ap- slightly pearance pearance pearance grainy ap pearance grainy ap- sticks to sticks to pearance pearance the piston the piston difficult to \ to compress TABLE IX Crushing strength (kg/cm2)

Product X1 Product X2 Product X3 Product X4 Product.X5 Product X6 287 155 169 65 85 150 The results of the examinations and analyses. identical with those of Example 1 and carried out on the abovesaid specimens, are combined in Table X.

TABLE X

Crystallinity Appearance Micro-state of the of the X rays DTA powder surface Product X1 gamma purity = blunt spectrum 9S h shape microcrys tallization Product X2 gamma poly- sharp fibrous spectrum morphism edges appearance gamma purity = sharp beginning Product X3 spectrum 86% edges beginning of micro crystalli zation Product X4 -- sharp Product X4 edges gamma purity = sharp beginning Product X5 spectrum 85% edges of micro crystalli crystalli- zation Product X6 gamma poly sharp fibrous spectrum morphism edges appearance It can be observed, in view of these results, that only the sorbitol according to the invention.

enables the production of excellent compression characteristics.

Two other specimens, among those analysed and tested (namely the product X3 and X5) have a relatively high purity in gamma stable form, but lead however to results which are rather mediocre in compression, which demonstrates the superiority of the sorbitol according to the invention.

Claims

1. A preparation of sorbitol which can be brought to a compressed state, the preparation comprising pulverulent crystalline sorbitol to which at least 90% by weight is in gamma form and which is in the form of blunt-shaped particles having few shapes or sharp edges and with an orientated micro-needles surface state.

2. A preparation according to claim 1, wherein 95% by weight or more of the sorbitol is in gamma form.

3. A preparation according to claim 1 or claim 2, which includes one or more of lubricating agents, flavouring agents, colouring agents and acidulants.

4. A preparation according to any one of the preceding claims which includes a nutritive agent.

5. A preparation according to any one of the preceding claims which includes a pharmaceutically active agent.

6. A preparation according to claim 1 substantially as hereinbefore described with reference to the specific Examples.

7. A continuous process for the manufacture of a sorbitol preparation which can be brought to a compressed state, which process comprises mixing at a temperature above 950C finely divided sorbitol, of dry matter content greater than 98%, with the same or substantially the same amount of pulverulent sorbitol of particle size less than 5 mm, the mixing being effected in an open rotating container whereby under steady state conditions the mixing takes place at the surface of a moving mass of grains derived from said mixing of finely divided sorbitol and pulverulent sorbitol, the grains being continuously removed and ripened to a gamma sorbitol content of at least 90% by weight.

8. A process according to claim 7, wherein the grains have a particle size of from 5 to 20 mm and are subsequently reduced to a particle size suitable for compression.

9. A process according to claim 7 or claim 8, wherein the mixing is carried out at a temperature of about 1 000C.

1 0. A sorbitol preparation when made by a process according to any one of claims 7 to 9.

1 A compressed product when made from a sorbitol preparation according to any one of claims 1 to 6 and 10 without prior granulation.

12. A tablet when made form a sorbitol preparation according to any one of claims 1 to 6 and 10 without prior granulation.

13. A compressed product according to claim 11 or a tablet according to claim 12 for dietetic use.

14. A compressed product according to claim 11 or a tablet according to claim 12 for use in the prevention or cure of disease.

1 5. Sorbitol in compressible particulate form in which the sorbitol particles comprise at least 90% gamma sorbitol.