METHOD FOR THE PRODUCTION OF FREE-FLOWING GRANULES

Abstract

The present invention refers to a method for the production of granules comprising surface-reacted calcium carbonate, granules comprising a surface-reacted calcium carbonate having a bulk density ranging from 0.25 to 0.70 g/mL, preferably from 0.28 to 0.65 g/mL, more preferably from 0.30 to 0.60 g/mL, and most preferably from 0.35 to 0.60 g/mL and the use of the granules n a nutraceutical product, agricultural product, veterinary product, cosmetic product, preferably in a dry cosmetic and/or dry skin care composition, home product, food product, packaging product or personal care product, preferably in an oral care composition, or as excipient in a pharmaceutical product.

Claims

1. Method for the production of granules comprising surface-reacted calcium carbonate, the method comprising the steps of a) providing an aqueous suspension comprising a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural ground or precipitated calcium carbonate with carbon dioxide and one or more acids, wherein the carbon dioxide is formed in situ by the acid treatment and/or is supplied from an external source; b) homogenizing the aqueous suspension comprising a surface-reacted calcium carbonate of step a), and c) removing the liquid from the aqueous suspension comprising a surface-reacted calcium carbonate of step b) by means of spray drying for obtaining granules comprising surface-reacted calcium carbonate.

2. The method according to claim 1, wherein the natural ground calcium carbonate is selected from calcium carbonate containing minerals selected from the group comprising marble, chalk, limestone and mixtures thereof and that or the precipitated calcium carbonate is selected from the group comprising precipitated calcium carbonates having amorphous, aragonitic, vateritic or calcitic mineralogical crystal forms and mixtures thereof.

3. The method according to claim 1, wherein the surface-reacted calcium carbonate in the aqueous suspension of step a) has a) a volume median grain diameter d.sub.50 of 0.5 to 50 μm, measured by using laser diffraction, and/or b) a BET specific surface area of from 1 m.sup.2/g to 200 m.sup.2/g, measured using nitrogen and the BET method according to ISO 9277:2010.

4. The method according to claim 1, wherein the aqueous suspension of step a) has a solids content in the range from 1 to 40 wt.-%, based on the total weight of the aqueous suspension.

5. The method according to claim 1, wherein at least one disintegrant is added before and/or during and/or after step b).

6. The method according to claim 5, wherein the at least one disintegrant is added before and/or during and/or after step b) in an amount ranging from 0.3 to 10 wt.-%, based on the total dry weight of the surface-reacted calcium carbonate.

7. The method according to claim 1, wherein the homogenizing in step b) is carried out at least once.

8. The method according to claim 1, wherein the homogenizing in step b) is carried out by milling.

9. The method according to claim 1, wherein the homogenizing in step b) is carried out at a) a pressure ranging from 50 to 900 bar, and/or b) an initial temperature ranging from 5 to 95° C.

10. The method according to claim 1, wherein the spray drying in step c) is carried out at a) a pressure ranging from 0.1 to 300 bar, and/or b) a temperature measured as inlet temperature ranging from 150 to 950° C.

11. Granules comprising a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural ground or precipitated calcium carbonate with carbon dioxide and one or more acids, wherein the carbon dioxide is formed in situ by the acid treatment and/or is supplied from an external source, the granules having a bulk density ranging from 0.25 to 0.70 g/mL.

12. The granules according to claim 11, wherein the granules have a) a volume particle size d.sub.90 of from 50 to 500 μm, as measured dry at 0.1 bar dispersion pressure by laser diffraction, b) a volume median particle size d.sub.50 of from 5 to 300 μm, as measured dry at 0.1 bar dispersion pressure by laser diffraction, and c) a volume particle size d.sub.10 of from 1 to 100 μm, as measured dry at 0.1 bar dispersion pressure by laser diffraction, and/or d) a spherical shape.

13. The granules according to claim 11, wherein the granules comprise particles of surface-reacted calcium carbonate having a) a BET specific surface area of from 1 m.sup.2/g to 200 m.sup.2/g, measured using nitrogen and the BET method according to ISO 9277:2010, and/or b) a volume median grain diameter d.sub.50 of from 0.5 to 50 μm, measured by using laser diffraction, and/or c) an intra-particle intruded specific pore volume within the range from 0.15 to 1.60 cm.sup.3/g, calculated from a mercury intrusion porosimetry measurement.

14. The granules according to claim 11, wherein the granules comprise at least one disintegrant.

15. The granules according to claim 14, wherein the granules comprise the at least one disintegrant in an amount ranging from 0.25 to 35 wt.-%, based on the total dry weight of the granules.

16. The granules according to claim 11, wherein the granules are obtained by a method comprising the steps of: a) providing an aqueous suspension comprising a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural ground or precipitated calcium carbonate with carbon dioxide and one or more acids, wherein the carbon dioxide is formed in situ by the acid treatment and/or is supplied from an external source; b) homogenizing the aqueous suspension comprising a surface-reacted calcium carbonate of step a), and c) removing the liquid from the aqueous suspension comprising a surface-reacted calcium carbonate of step b) by means of spray drying for obtaining granules comprising surface-reacted calcium carbonate.

17. A nutraceutical product, agricultural product, veterinary product, cosmetic product, home product, food product, packaging product, personal care product, or pharmaceutical product comprising the granules according to claim 11.

18. The method according to claim 5, wherein the at least one disintegrant is selected from the group comprising sodium croscarmellose, modified cellulose gums, insoluble cross-linked polyvinylpyrrolidones, starches, modified starches, starch glycolates, micro crystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, homopolymers of N-vinyl-2-pyrrolidone, alkyl-, hydroxyalkyl-, carboxyalkyl-cellulose esters, alginic acid, microcrystalline cellulose and its polymorphic forms, ion exchange resins, gums, chitin, chitosan, clays, gellan gum, crosslinked polacrilin copolymers, agar, gelatine, dextrines, acrylic acid polymers, carboxymethylcellulose sodium/calcium, hydroxypropyl methyl cellulose phthalate, shellac, effervescent mixtures in combination with one or more acids, and mixtures thereof.

19. The granules according to claim 14, wherein the at least one disintegrant is selected from the group comprising sodium croscarmellose, modified cellulose gums, insoluble cross-linked polyvinylpyrrolidones, starches, modified starches, starch glycolates, micro crystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, homopolymers of N-vinyl-2-pyrrolidone, alkyl-, hydroxyalkyl-, carboxyalkyl-cellulose esters, alginic acid, microcrystalline cellulose and its polymorphic forms, ion exchange resins, gums, chitin, chitosan, clays, gellan gum, crosslinked polacrilin copolymers, agar, gelatine, dextrines, acrylic acid polymers, carboxymethylcellulose sodium/calcium, hydroxypropyl methyl cellulose phthalate, shellac, effervescent mixtures in combination with one or more acids, or mixtures thereof.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0347] FIG. 1 shows the SEM results for the granules obtained for SRCC1 by using a homogenizer for homogenizing and a fountain nozzle for spray drying.

[0348] FIG. 2 shows the SEM results for the granules obtained for SRCC2 by using a homogenizer for homogenizing and a fountain nozzle for spray drying.

[0349] FIG. 3 shows the SEM results for the granules obtained for SRCC3 by using a homogenizer for homogenizing and a fountain nozzle for spray drying.

[0350] FIG. 4 shows the SEM results for the granules obtained for SRCC4 by using a homogenizer for homogenizing and a fountain nozzle for spray drying. FIG. 5 further shows the SEM results for a cross-section through the granules obtained for SRCC2 by spray drying in a fountain nozzle.

[0351] FIG. 6 shows the SEM results for the granules obtained for SRCC5 by using a mill for homogenizing and a rotary atomizer for spray drying.

[0352] FIG. 7 shows the SEM results for the granules obtained for SRCC6 by using a mill for homogenizing and a rotary atomizer for spray drying.

[0353] FIG. 8 shows the results for the tablet hardness [N] as a function of the main compression force [kN] for tablets prepared from the granules prepared according to the present invention by spray drying in a rotary atomizer compared to two commercial filler samples.

[0354] FIG. 9 shows the results for the disintegration time [sec] as a function of the tablet hardness [N] for tablets prepared from the granules prepared according to the present invention by spray drying in a rotary atomizer compared to the two commercial filler samples.

EXAMPLES

Measurement Methods

[0355] In the following, measurement methods implemented in the examples are described.

Particle Size Distribution

[0356] Volume determined median particle size d.sub.50(vol) and the volume determined top cut particle size d.sub.98(vol) as well as the volume particle sizes d.sub.90(vol) and d.sub.10(vol) were evaluated in a wet unit using a Malvern Mastersizer 2000 or 3000 Laser Diffraction System (Malvern Instruments Plc., Great Britain). The d.sub.50(vol) or d.sub.98(vol) value indicates a diameter value such that 50% or 98% by volume, respectively, of the particles have a diameter of less than this value. The raw data obtained by the measurement was analyzed using the Mie theory, with a particle refractive index of 1.57 and an absorption index of 0.005. The methods and instruments are known to the skilled person and are commonly used to determine particle size distributions of fillers and pigments. The sample was measured in dry condition without any prior treatment.

[0357] The weight determined median particle size d.sub.50(wt) was measured by the sedimentation method, which is an analysis of sedimentation behaviour in a gravimetric field. The measurement was made with a Sedigraph™ 5120 of Micromeritics Instrument Corporation, USA. The method and the instrument are known to the skilled person and are commonly used to determine particle size distributions of fillers and pigments. The measurement was carried out in an aqueous solution of 0.1 wt.-% Na.sub.4P.sub.2O.sub.7. The samples were dispersed using a high speed stirrer and supersonicated.

[0358] The processes and instruments are known to the skilled person and are commonly used to determine grain sizes of fillers and pigments.

[0359] If not otherwise indicated in the following example section, the volume particle sizes were evaluated in a wet unit using a Malvern Mastersizer 2000 Laser Diffraction System (Malvern Instruments Plc., Great Britain).

Specific Surface Area (SSA)

[0360] The specific surface area was measured via the BET method according to ISO 9277:2010 using nitrogen, following conditioning of the sample by heating at 110° C., when using disintegrant(s), or at 250° C., when the sample is free of disintegrant(s), for a period of 30 minutes. If the sample was in the form of an aqueous suspension, the sample was filtered within a Büchner funnel, rinsed with deionised water and dried at 110° C. in an oven for at least 12 hours prior to such measurement.

Intra-Particle Intruded Specific Pore Volume (in Cm.SUP.3./g)

[0361] The specific pore volume was measured using a mercury intrusion porosimetry measurement using a Micromeritics Autopore V 9620 mercury porosimeter having a maximum applied pressure of mercury 414 MPa (60 000 psi), equivalent to a Laplace throat diameter of 0.004 μm (˜nm). The equilibration time used at each pressure step was 20 seconds. The sample material was sealed in a 5 cm.sup.3 chamber powder penetrometer for analysis. The data were corrected for mercury compression, penetrometer expansion and sample material compression using the software Pore-Comp (Gane, P. A. C., Kettle, J. P., Matthews, G. P. and Ridgway, C. J., “Void Space Structure of Compressible Polymer Spheres and Consolidated Calcium Carbonate Paper-Coating Formulations”, Industrial and Engineering Chemistry Research, 35(5), 1996, p1753-1764).

[0362] The total pore volume seen in the cumulative intrusion data can be separated into two regions with the intrusion data from 214 μm down to about 1-4 μm showing the coarse packing of the sample between any agglomerate structures contributing strongly. Below these diameters lies the fine inter-particle packing of the particles themselves. If they also have intra-particle pores, then this region appears bi-modal, and by taking the specific pore volume intruded by mercury into pores finer than the modal turning point, i.e. finer than the bi-modal point of inflection, the specific intra-particle pore volume is defined. The sum of these three regions gives the total overall pore volume of the powder, but depends strongly on the original sample compaction/settling of the powder at the coarse pore end of the distribution.

[0363] By taking the first derivative of the cumulative intrusion curve the pore size distributions based on equivalent Laplace diameter, inevitably including pore-shielding, are revealed. The differential curves clearly show the coarse agglomerate pore structure region, the inter-particle pore region and the intra-particle pore region, if present. Knowing the intra-particle pore diameter range it is possible to subtract the remainder inter-particle and inter-agglomerate pore volume from the total pore volume to deliver the desired pore volume of the internal pores alone in terms of the pore volume per unit mass (specific pore volume). The same principle of subtraction, of course, applies for isolating any of the other pore size regions of interest.

Bulk Density

[0364] 100±0.5 g of the respective material were carefully filled through a powder funnel into the 250 mL measuring cylinder and the volume was read off to the nearest 1 mL. The loose bulk density was the calculated according the formula:

Loose bulk density [g/mL]=weighed sample [g]/bulk volume [mL] and the result was recorded to the nearest 0.01 g/mL.

Brookfield Viscosity

[0365] The Brookfield viscosity is measured by a Brookfield (type RVT) viscometer at 25° C.±1° C. at 100 rpm after 30 seconds using an appropriate spindle and is specified in mPas.

Weight Solids (Wt.-%) of a Material in Suspension

[0366] The weight solids were determined by dividing the weight of the solid material by the total weight of the aqueous suspension. The weight of the solid material is determined by weighing the solid material obtained by evaporating the aqueous phase of the slurry and drying the obtained material to a constant weight.

Granule Stability and Granule Particle Size Distribution

[0367] A Malvern Mastersizer 3000 (Malvern Instruments Plc., Great Britain) in combination with Malvern Aero S dry dispersion unit and dry cell was used to determine the particle size distribution of the granules within the fineness range of d.sub.50 of from 5 to 300 μm by means of laser diffraction. The methods used are described in the Mastersizer 3000 Basic Guide, Mastersizer 3000 Manual and the Manual for Aero Series Dry dispersion unit available by Malvern Instruments Ltd. Approximately 10 ml of sample was loaded into the Aero S through the corresponding sieve. The sample was measured dry. The results are expressed in V.-% (volume %). The feed rate was done at 0.1 bar, 0.5 bar, and 1.5 bar to show granule stability.

[0368] The feed rate of 0.1 bar was used for determining the particle size distribution of the granules.

Scanning Electron Microscope (SEM)

[0369] The samples were prepared by diluting 50 to 150 μl slurry samples with 5 ml water. The amount of slurry sample depends on solids content, mean value of the particle size and particle size distribution. The diluted samples were filtrated by using a 0.8 μm membrane filter. A finer filter was used when the filtrate is turbid. A doubled-sided conductive adhesive tape was mounted on a SEM stub. This SEM stub was then slightly pressed in the still wet filter cake on the filter. The SEM stub was then sputtered with 8 nm Au. The investigation under the FESEM (Zeiss Sigma VP) was done at 5 kV (Au). Subsequently, the prepared samples were examined by using a Sigma VP field emission scanning electron microscope (Carl Zeiss AG, Germany) and a secondary electron detector (SE2) at high vacuum (<10.sup.−2 Pa).

Mechanical Sieving

[0370] The mechanical sieving was carried out in a vibratory sieve shaker RETSCH AS200 equipped with Easy Sieve Software, sieves according to ISO 3310 incl. sieve pan and a balance (0.1 g). 120 g were used for sieving. The measured sample is made homogeneous to ensure the reproducibility of the sieving at a maximum. The measured sample material was put in the upper test sieve. The sieving was carried out with the following method: sieving time: 3 min/amplitude: 1.0/interval: 10 s.

2. Materials Used

Surface-Reacted Calcium Carbonate (SRCC1)

[0371] SRCC was obtained by preparing 350 litres of an aqueous suspension of ground calcium carbonate in a mixing vessel by adjusting the solids content of a ground limestone calcium carbonate from Omya SAS, Orgon having a weight based median particle size d.sub.50(wt) of 1.3 as determined by sedimentation, such that a solids content of 10 wt.-%, based on the total weight of the aqueous suspension, is obtained.

[0372] Whilst mixing the slurry at a speed of 6.2 m/s, 11.2 kg phosphoric acid was added in form of an aqueous solution containing 30 wt.-% phosphoric acid to said suspension over a period of 20 minutes at a temperature of 70° C. After the addition of the acid, the slurry was stirred for additional 5 minutes, before removing it from the vessel.

[0373] The slurry obtained (SRCC1) had a solids content of 25.7 wt.-%, based on the total weight of the slurry, and a Brookfield viscosity of 554 mPas.

[0374] The characteristics of the surface-reacted calcium carbonate are summarized in the following Table 1.

TABLE-US-00001 TABLE 1 Intra particle intruded specific pore volume [cm.sup.3g.sup.−1] Bulk (for the range density d.sub.98(vol) d.sub.90(vol) d.sub.50(vol) d.sub.10(vol) 0.004 − d* d* [kg/L] [μm] [μm] [μm] [μm] [μm]) [μm] 1.193 8.8 6.9 3.9 2.1 0.869 0.8

[0375] Other Materials

[0376] Sodium croscarmellose-Ac-di-sol, from JRS

3. Homogenizing and Drying SRCC by Spray Drying

A. Homogenizing

[0377] SRCC2

[0378] The slurry of the surface-reacted calcium carbonate (SRCC1) was then diluted down to a solids content of about 20.1 wt.-%, based on the total weight of the slurry. Subsequently, 500 L of the slurry was pumped twice through the homogenizer GEA Ariete NS3055 of GEA Mechanical Equipment Italia S.p.A. at a pressure of 500 bar, a temperature of 50 to 70° C. and a feed flow of 400 L/h at closed screw position and small nozzle.

[0379] The slurry obtained (SRCC2) had a solids content of 23.4 wt.-%, based on the total weight of the slurry.

[0380] After 2 passes through the homogenizer, the surface-reacted calcium carbonate had the characteristics as set out in the following Table 2.

TABLE-US-00002 TABLE 2 Intra particle intruded specific pore volume [cm.sup.3g.sup.−1] d.sub.98(vol) d.sub.90(vol) d.sub.50(vol) d.sub.10(vol) (for the range 0.004-d* d* [μm] [μm] [μm] [μm] [μm]) [μm] 8.8 6.2 3.0 1.5 0.722 0.8

[0381] SRCC3

[0382] The slurry of the surface-reacted calcium carbonate (SRCC1) was diluted down to a solids content of about 18.9 wt.-%, based on the total weight of the slurry. Subsequently, 500 L of the slurry was pumped three times through the homogenizer GEA Ariete NS3055 of GEA Mechanical Equipment Italia S.p.A. at a pressure of 500 bar, a temperature of 50 to 70° C. and a feed flow of 400 L/h at closed screw position and small nozzle.

[0383] The slurry obtained (SRCC3) had a solids content of 18.9 wt.-%, based on the total weight of the slurry.

[0384] After 3 passes through the homogenizer, the surface-reacted calcium carbonate had the characteristics as set out in the following Table 3.

TABLE-US-00003 TABLE 3 Intra particle intruded specific pore volume [cm.sup.3g.sup.−1] d.sub.98(vol) d.sub.90(vol) d.sub.50(vol) d.sub.10(vol) (for the range 0.004- d* [μm] [μm] [μm] [μm] d* [μm]) [μm] 8.2 5.9 2.8 1.4 0.667 0.5

[0385] SRCC4

[0386] The slurry of the surface-reacted calcium carbonate (SRCC1) was mixed with sodium croscarmellose in an amount of 3 wt.-%, based on the total weight of the surface-reacted calcium carbonate (SRCC1), and then diluted down to a solids content of about 20.5 wt.-%, based on the total weight of the slurry. Subsequently, 500 L of the slurry was pumped twice through the homogenizer GEA Ariete NS3055 of GEA Mechanical Equipment Italia S.p.A. at a pressure of 500 bar, a temperature of 50 to 70° C. and a feed flow of 400 L/h at closed screw position and small nozzle.

[0387] The slurry obtained (SRCC4) had a solids content of 20.5 wt.-%, based on the total weight of the slurry.

[0388] After 2 passes through the homogenizer, the surface-reacted calcium carbonate had the characteristics as set out in the following Table 4.

TABLE-US-00004 TABLE 4 Intra particle intruded specific pore volume [cm.sup.3g.sup.−1] d.sub.98(vol) d.sub.90(vol) d.sub.50(vol) d.sub.10(vol) (for the range 0.004- d* [μm] [μm] [μm] [μm] d* [μm]) [μm] 145 87.2 4.3 1.8 —

[0389] SRCC5

[0390] The slurry of the surface-reacted calcium carbonate (SRCC1) was diluted down to a solids content of about 20.1 wt.-%, based on the total weight of the slurry. Subsequently, the slurry was milled in a 25 L vertical stirred media mill of Siegmund Linder containing 33 kg silibeads ZY-E 0.4/0.6 mm at a feed flow of 82 L/h, a tip speed of 5.0 m/s and a specific energy of about 55 kWh/t.

[0391] The slurry obtained (SRCC5) had a solids content of 20.2 wt.-%, based on the total weight of the slurry.

[0392] After milling, the surface-reacted calcium carbonate had the characteristics as set out in the following Table 5.

TABLE-US-00005 TABLE 5 Intra particle intruded specific pore volume [cm.sup.3g.sup.−1] d.sub.98(vol) d.sub.90(vol) d.sub.50(vol) d.sub.10(vol) (for the range 0.004- d* [μm] [μm] [μm] [μm] d* [μm]) [μm] 5.8 4.10 1.65 0.063 0.868 0.83

[0393] SRCC6

[0394] The slurry of the surface-reacted calcium carbonate (SRCC1) was diluted down to a solids content of about 22.6 wt.-%, based on the total weight of the slurry. Subsequently, the slurry was milled in a 25 L vertical stirred media mill of Siegmund Linder containing 33 kg silibeads ZY-E 0.4/0.6 mm at a feed flow of 82 L/h, a tip speed of 5.0 m/s and a specific energy of about 55 kWh/t.

[0395] The slurry obtained (SRCC6) had a solids content of 22.9 wt.-%, based on the total weight of the slurry.

[0396] After milling, the surface-reacted calcium carbonate had the characteristics as set out in the following Table 6.

TABLE-US-00006 TABLE 6 Intra particle intruded specific pore volume [cm.sup.3g.sup.−1] d.sub.98(vol) d.sub.90(vol) d.sub.50(vol) d.sub.10(vol) (for the range 0.004-d* d* [μm] [μm] [μm] [μm] [μm]) [μm] 5.9 4.63 2.54 1.38 0.895 0.83

[0397] SRCC7

[0398] SRCC7 was obtained by preparing 350 litres of an aqueous suspension of ground calcium carbonate in a mixing vessel by adjusting the solids content of a ground limestone calcium carbonate from Omya SAS, Orgon having a weight based median particle size d.sub.50(wt) of 1.3 as determined by sedimentation, such that a solids content of 10 wt.-%, based on the total weight of the aqueous suspension, is obtained.

[0399] Whilst mixing the slurry at a speed of 6.2 m/s, 11.2 kg phosphoric acid was added in form of an aqueous solution containing 30 wt.-% phosphoric acid to said suspension over a period of 20 minutes at a temperature of 70° C. After the addition of the acid, the slurry was stirred for additional 5 minutes, before removing it from the vessel.

[0400] The slurry obtained (SRCC7) had a solids content of 25.2 wt.-%, based on the total weight of the slurry, and a Brookfield viscosity of 365 mPas.

[0401] The characteristics of the surface-reacted calcium carbonate are summarized in the following Table 7.

TABLE-US-00007 TABLE 7 Intra particle intruded specific pore volume [cm.sup.3g−.sup.1] Bulk (for the range density d.sub.98(vol) d.sub.90(vol) d.sub.50(vol) d.sub.10(vol) 0.004 − d* d* [kg/L] [μm] [μm] [μm] [μm] [μm]) [μm] — 9.2 — 3.9 — — —

[0402] SRCC8

[0403] A slurry of the surface-reacted calcium carbonate (SRCC7) was milled in a 200 L vertical stirred media mill of Siegmund Linder containing 250 kg silibeads ZY-E 0.4/0.6 mm at a feed flow of 1775 L/h, a tip speed of 10.0 m/s and a specific energy of about 65.8 kWh/t.

[0404] The slurry obtained (SRCC8) had a solids content of 21.7 wt.-%, based on the total weight of the slurry.

[0405] After milling, the surface-reacted calcium carbonate had the characteristics as set out in the following Table 8.

TABLE-US-00008 TABLE 8 Intra particle intruded specific pore volume [cm.sup.3g.sup.−1] d.sub.98(vol) d.sub.90(vol) d.sub.50(vol) d.sub.10(vol) (for the range 0.004-d* d* [μm] [μm] [μm] [μm] [μm]) [μm] 5.3 — 1.75 — — —

[0406] SRCC9

[0407] A slurry of the surface-reacted calcium carbonate (SRCC7) was milled in a 200 L vertical stirred media mill of Siegmund Linder containing 250 kg silibeads ZY-E 0.4/0.6 mm at a feed flow of 2010 L/h, a tip speed of 10.0 m/s and a specific energy of about 58.1 kWh/t.

[0408] The slurry obtained (SRCC8) had a solids content of 20.1 wt.-%, based on the total weight of the slurry.

[0409] After milling, the surface-reacted calcium carbonate had the characteristics as set out in the following Table 9.

TABLE-US-00009 TABLE 9 Intra particle intruded specific pore volume [cm.sup.3g.sup.−1] d.sub.98(vol) d.sub.90(vol) d.sub.50(vol) d.sub.10(vol) (for the range 0.004-d* d* [μm] [μm] [μm] [μm] [μm]) [μm] 5.2 — 1.67 — — —

B. Drying

[0410] The slurries obtained, i.e. SRCC1, SRCC2, SRCC3, SRCC4, SRCC5, SRCC6, SRCC8 and SRCC9 were than dried by removing the liquid from the slurries comprising the surface-reacted calcium carbonate by means of spray drying using a rotary atomizer, a bi-fluid nozzle or a fountain nozzle of GEA-Niro, Denmark.

[0411] The settings used for spray drying are set out in the following Table 10.

TABLE-US-00010 TABLE 10 Solids Atomizer content speed Nozzle SRCC [wt.- [%- con- Pressure used %] Device rpm] figuration [bar] SRCC1 25.7 rotary 5-9660 Slurry*: 2.8 atomizer bi-fluid 12.9/44/28 Air: 1.05 nozzle Slurry*: 9.0 fountain 1.7SE Slurry: 14.5 nozzle SRCC2 23.4 rotary 5- Slurry*: atomizer 9660 3.4 bi-fluid 12.9/44/28 Air: 2.53 nozzle Slurry*: 12.0 12.9/44/28 Air: 1.50 Slurry*: 11.8 12.9/44/28 Air: 1.30 Slurry*: 11.5 fountain 1.7SF Slurry*: nozzle 13.5 SRCC3 18.9 rotary 5- Slurry*: atomizer 9660 3.1 bi-fluid 12.9/44/28 Air: 1.25 nozzle Slurry*: 11.5 fountain 1.7SF Slurry*: nozzle 13.0 SRCC4 20.5 rotary 5- Slurry*: atomizer 9660 3.0 bi-fluid 12.9/44/28 Air: 1.25 nozzle Slurry*: 12.0 fountain 1.7SF Slurry*: nozzle 15.0 SRCC5 20.3 rotary Slurry*: atomizer 3.6 SRCC6 22.9 rotary Slurry*: atomizer 4.2 SRCC8 21.7 rotary Slurry*: atomizer 4.4 SRCC9 20.1 rotary Slurry*: atomizer 3.5 *refers to the pressure of the feed that goes to the drier

[0412] The results for the obtained granules are set out in the following Table 11.

TABLE-US-00011 TABLE 11 Intra particle intruded specific pore volume [cm.sup.3g.sup.−1] (for the range Granules d.sub.98(vol) d.sub.90(vol) d.sub.50(vol) d.sub.10(vol) 0.004 − d* d* density SRCC Device [μm] [μm] [μm] [μm] [μm]) [μm] [g/mL] Granules rotary 205 158 91.2 51.1 0.588 0.3 0.32 SRCC1 atomizer bi-fluid 438 325 164 63.9 0.577 0.3 0.31 nozzle fountain 340 271 168 101 0.602 0.3 0.31 nozzle Granules rotary 162 125 72.3 40.8 0.681 0.8 0.51 SRCC2 atomizer bi-fluid 150 106 52.5 27.0 0.698 0.9 0.49 nozzle fountain 279 224 145 92.9 — — 0.52 nozzle Granules rotary 162 123 70.4 39.3 0.636 0.8 0.53 SRCC3 atomizer bi-fluid 313 221 110 50.0 0.658 0.8 0.54 nozzle fountain 285 226 139 83.5 0.647 0.4 0.57 nozzle Granules rotary 176 135 76.7 41.5 0.683 0.8 0.58 SRCC4 atomizer bi-fluid 293 210 106 49.0 0.712 0.9 0.49 nozzle fountain 304 237 147 83.4 0.709 0.7 m0.49 nozzle Granules rotary 171 136 82 47.9 0.854  0.83 0.43 SRCC5 atomizer Granules rotary 183 146 89.1 52.9 0.894  0.83 0.42 SRCC6 atomizer Granules rotary 181 161 83.6 47.4 — — 0.43 SRCC8 atomizer Granules rotary 180 140 82.9 47.1 — — 0.44 SRCC9 atomizer *refers to the pressure of the feed that goes to the drier

[0413] The following table 12 summarizes the granule stability determined by the ratio d.sub.50 and d.sub.10 for (0.5 bar) vs. (0.1 bar) and for (1.5 bar) vs. (0.1 bar). From table 12, it can be gathered that granules prepared by a method comprising a step of homogenizing the aqueous suspension comprising the surface-reacted calcium carbonate, i.e. Granules SRCC2, Granules SRCC3, Granules SRCC4, Granules SRCC5, Granules SRCC6, Granules SRCC8 and Granules SRCC9, are more stable compared to granules obtained by the same method but missing the step of homogenizing the aqueous suspension comprising the surface-reacted calcium carbonate, i.e. Granules SRCC1. Furthermore, FIGS. 1 to 4 show a comparison of the SEM results for granules obtained by homogenizing in a homogenizer and by spray drying in a fountain nozzle, i.e. Granules SRCC1, Granules SRCC2, Granules SRCC3, and Granules SRCC4. It is to be noted that the SEM results for the granules obtained by spray drying in a rotary atomizer or bi-fluid nozzle are similar. FIG. 5 further shows a cross-section through the granules obtained by spray drying in a fountain nozzle, i.e. Granules SRCC2. FIGS. 6 and 7 show a comparison of the SEM results for granules obtained by homogenizing in a mill and by spray drying in a rotary atomizer, i.e. Granules SRCC5 and Granules SRCC6. It is to be noted that the SEM results for the granules obtained by spray drying in a fountain nozzle or bi-fluid nozzle are similar. Furthermore, it is to be noted that granules prepared by a step of homogenizing, which is carried out in an industrial scale, i.e. Granules SRCC8 and Granules SRCC9, show the same granule stability as granules prepared by a step of homogenizing, which is carried out in a lab scale, i.e. Granules SRCC2, Granules SRCC3, Granules SRCC4, Granules SRCC5 and SRCC6. It is to be noted that samples after milling may be slightly inferior in physical data (friability/bulk density) but they are equal in performance.

TABLE-US-00012 TABLE 12 d.sub.50(vol)* d.sub.10(vol)* d.sub.50(vol)* d.sub.10(vol)* Granules 0.5 bar 0.5 bar 1.5 bar 1.5 bar SRCC Device vs 0.1 bar vs 0.1 bar vs 0.1 bar vs 0.1 bar Granules rotary atomizer 22.7 36.8 6.4 23.7 SRCC1 bi-fluid nozzle 7.4 50.0 4.7 38.0 fountain nozzle 37.9 35.1 4.3 23.9 Granules rotary atomizer 93.5 65.2 64.7 8.9 SRCC2 bi-fluid nozzle 83.1 27.8 43.5 8.8 fountain nozzle 82.9 42.6 38.6 18.3 Granules rotary atomizer 86.6 36.8 52.4 7.3 SRCC3 bi-fluid nozzle 90.8 56.6 62.1 6.5 fountain nozzle 97.2 88.0 82.4 10.8 Granules rotary atomizer 76.7 21.8 48.0 6.3 SRCC4 bi-fluid nozzle 84.3 32.8 53.2 6.4 fountain nozzle 91.8 56.7 74.1 7.9 Granules rotary atomizer 94.9 69.1 70.2 6.8 SRCC5 Granules rotary atomizer 91.6 45.6 65.8 5.7 SRCC6 Granules rotary atomizer 92.0 44.6 68.7 8.3 SRCC8 Granules rotary atomizer 89.3 48.3 66.8 7.2 SRCC9 *evaluated in a wet unit using a Malvern Mastersizer 3000 Laser Diffraction System (Malvern Instruments Plc., Great Britain)

[0414] The granules prepared according to the present invention were further analysed with regard to their compactability. For the testing, tablets were prepared in that the obtained granules of SRCC2, SRCC3, SRCC5 and SRCC6 were first mixed with croscarmellose in a Turbula Mixer (Willy A. Bachofen, Turbula T10B) for 5 minutes. Subsequently, a lubricant (Magnesium stearate, Ligamed MF-2-V, Cas #557-04-0, Peter Greven) was added and the obtained mixture was again mixed in a Turbula Mixer (Willy A. Bachofen, Turbula T10B) for 5 minutes. Tablets of two comparative filler samples, one filler is based on tribasic calcium phosphate and the other one is based on dibasic calcium phosphate, were prepared the same way. Contrary thereto, the granules of SRCC4 were mixed with a lubricant (Magnesium stearate, Ligamed MF-2-V, Cas #557-04-0, Peter Greven) only in a Turbula Mixer (Willy A. Bachofen, Turbula T10B) for 5 minutes. The mixes were then used to prepare tablets in a Fette 1200i using EU1″ tooling, a 10 mm fill cam, 8 standard convex round 10 mm punches and a tableting speed of 10 000 tablets/hour. The fill depth was adjusted to obtain compression forces of 2 kN up to 20 kN and the tablet weight was fixed at 160 mg. Tablets of two comparative filler samples, one filler is based on tribasic calcium phosphate and the other one is based on dibasic calcium phosphate, were prepared the same way.

[0415] The following Table 13 sets out the amounts [in wt. %] of the single ingredients in the tablets prepared.

TABLE-US-00013 TABLE 13 Ingredient/Amount [wt. %] Granules Magnesium Sodium SRCC stearate croscarmellose Granules SRCC2 95 2 3 Granules SRCC3 95 2 3 Granules SRCC4 95 2 3 Granules SRCC5 95 2 3 Granules SRCC6 95 2 3 tribasic calcium 95 2 3 phosphate dibasic calcium 95 2 3 phosphate

[0416] The tablet hardness [N] of the tablets as a function of the main compression force [kN] is shown in FIG. 8. FIG. 8 shows the results for tablets prepared from the granules prepared according to the present invention by spray drying in a rotary atomizer compared to two commercial filler samples, i.e. one filler is based on tribasic calcium phosphate and the other one is based on dibasic calcium phosphate. It can be gathered that the tablets prepared from the granules prepared according to the present invention shows a better relation of hardness versus main compression force and thus a better compactability compared to the commercial filler samples. It is to be noted that the compactability results for the granules obtained by spray drying in a fountain nozzle or bi-fluid nozzle are similar to the results obtained by spray drying in a rotary atomizer.

[0417] The granules prepared according to the present invention were further analysed with regard to their disintegration properties.

[0418] The disintegration time was determined by using a DisiTest 50 Automatic Tablet Disintegration Tester of Pharmatron. For the testing, a beaker was filled with 700 mL tap water. The water was heated to 37.0° C., and then 6 tablets of each sample as prepared and described above were placed in a robust basket. The apparatus automatically detects and records the disintegration time. In addition, the disintegration time was also monitored visually.

[0419] FIG. 9 shows the disintegration time [sec] as a function of the tablet hardness [N] for tablets prepared from the granules prepared according to the present invention by spray drying in a rotary atomizer compared to the two commercial filler samples, i.e. one filler is based on tribasic calcium phosphate and the other one is based on dibasic calcium phosphate. It can be gathered that the tablets prepared from the granules prepared according to the present invention show a favourable relation of disintegration time versus hardness. It is to be noted that the results of the relation of disintegration time versus hardness for the granules obtained by spray drying in a fountain nozzle or bi-fluid nozzle are similar to the results obtained by spray drying in a rotary atomizer.