USE OF SURFACE-REACTED CALCIUM CARBONATE FOR PREPARING SUPERSATURATED AQUEOUS SYSTEMS

Abstract

The present invention relates to the use of a loaded particulate carrier comprising surface-reacted calcium carbonate loaded with an active ingredient, characterized in that the loaded particulate carrier is used for preparing an aqueous system comprising said active ingredient in dissolved form, wherein the mass concentration of dissolved active ingredient in said aqueous system corresponds to a supersaturated state. The surface-reacted calcium carbonate is a reaction product of calcium carbonate treated with CO.sub.2 and one or more H.sub.3O.sup.+ ion donors, wherein the CO.sub.2 is formed in situ by the H.sub.3O.sup.+ ion donors treatment and/or is supplied from an external source.

Claims

1. Use of a loaded particulate carrier comprising surface-reacted calcium carbonate loaded with an active ingredient, said active ingredient having a solubility limit in water of less than 10 g/l, measured at 20 C. and 1 bar, characterized in that the loaded particulate carrier is used for preparing an aqueous system comprising said active ingredient in dissolved form, wherein the mass concentration of dissolved active ingredient in said aqueous system corresponds to a supersaturated state.

2. The use according to claim 1, characterized in that the surface-reacted calcium carbonate is a reaction product of ground natural calcium carbonate (GNCC) or precipitated calcium carbonate (PCC) treated with CO.sub.2 and one or more H.sub.3O.sup.+ ion donors, wherein the CO.sub.2 is formed in situ by the H.sub.3O.sup.+ ion donors treatment and/or is supplied from an external source.

3. The use according to claim 2, characterized in that the one or more H.sub.3O.sup.+ ion donor is selected from a strong acid, medium-strong acid, weak acid, or acidic salts thereof or mixtures thereof.

4. The use according to claim 1, characterized in that the surface-reacted calcium carbonate is obtained by a process comprising the steps of: (a) providing a suspension of natural or precipitated calcium carbonate, (b) adding at least one acid having a pK.sub.a value of 0 or less at 20 C. or having a pK.sub.a value from 0 to 2.5 at 20 C. to the suspension of step (a); and (c) treating the suspension of step (a) with carbon dioxide before, during or after step (b).

5. The use according to claim 4, characterized in that said acid having a pK.sub.a value of 0 or less at 20 C. is selected from sulphuric acid, hydrochloric acid or mixtures thereof.

6. The use according to claim 4, characterized in that said acid having a pK.sub.a value from 0 to 2.5 at 20 C., the acid is selected from H.sub.2SO.sub.3, H.sub.3PO.sub.4, oxalic acid or mixtures thereof.

7. The use according to claim 1, characterized in that the surface-reacted calcium carbonate is obtained by a process comprising the steps of: (a) providing a ground natural calcium carbonate (GNCC) or precipitated calcium carbonate (PCC); (b) providing at least one acid; (c) providing gaseous CO.sub.2; and (d) contacting said GNCC or PCC provided in step (a), the at least one acid provided in step (b) and the gaseous CO.sub.2 provided in step (c); characterized in that (i) the at least one acid provided in step (b) has a pK.sub.a of greater than 2.5 and less than or equal to 7 at 20 C., associated with the ionisation of its first available hydrogen, and a corresponding anion is formed on loss of this first available hydrogen capable of forming a water-soluble calcium salt; and (ii) following contacting the at least one water-soluble acid provided in step (b) and the GNCC or PCC provided in step (a), at least one water-soluble salt, which in the case of a hydrogen-containing salt has a pK.sub.a of greater than 7 at 20 C., associated with the ionisation of the first available hydrogen, and the salt anion of which is capable of forming water-insoluble calcium salts, is additionally provided.

8. The use according to claim 1, characterized in that the surface-reacted calcium carbonate has: (i) a specific surface area of from 15 m.sup.2/g to 200 m.sup.2/g, preferably from 27 m.sup.2/g to 180 m.sup.2/g, more preferably from 30 m.sup.2/g to 160 m.sup.2/g, even more preferably from 45 m.sup.2/g to 150 m.sup.2/g, most preferably from 48 m.sup.2/g to 140 m.sup.2/g, measured using nitrogen and the BET method. measured using nitrogen and the BET method according to ISO 9277:2010; (ii) a volume median grain diameter d.sub.50(vol) of from 1 to 75 m, preferably from 2 to 50 m, more preferably 3 to 40 m, even more preferably from 4 to 30 m, and most preferably from 5 to 15 m; (iii) a grain diameter d.sub.98(vol) of from 2 to 150 m, preferably from 4 to 100 m, more preferably 6 to 80 m, even more preferably from 8 to 60 m, and most preferably from 10 to 30 m; and/or (iv) an intra-particle intruded specific pore volume in the range from 0.1 to 2.3 cm.sup.3/g, more preferably from 0.2 to 2.0 cm.sup.3/g, especially preferably from 0.4 to 1.8 cm.sup.3/g and most preferably from 0.6 to 1.6 cm.sup.3/g, calculated from mercury porosimetry measurement.

9. The use according to claim 1, characterized in that the active ingredient has a solubility limit in water, measured at 20 C. and 1 bar, of less than 5 g/l, preferably less than 1 g/l, and most preferably less than 0.1 g/l.

10. The use according to claim 1, characterized in that the surface-reacted calcium carbonate is used in a weight ratio of from 100:1 to 1:10, preferably 50:1 to 1:2, and most preferably 20:1 to 1:1 on a dry weights basis relative to the weight of the active ingredient.

11. The use according to claim 1, characterized in that the loaded particulate carrier is used in an amount such that the theoretical mass concentration of dissolved active ingredient in the aqueous system is at most 10 times, preferably at most 5 times, and most preferably at most 3 times higher than the solubility limit of said active ingredient under identical conditions.

12. The use according to claim 1, characterized in that the mass concentration of dissolved active ingredient in the aqueous system is at least 1.1 times, preferably at least 1.5 times, and most preferably at least 2 times higher than the solubility limit of said active ingredient under identical conditions.

13. The use according to claim 1, characterized in that the aqueous system has a pH value in the range of from 1.5 to 10, preferably from 3 to 9, more preferably from 4 to 8 and most preferably from 6.5 to 7.5.

14. The use according to claim 1, characterized in that the active ingredient is selected from pharmaceutical drugs, agrochemical compounds including pesticides and fertilizers, biocides, micronutrients, antimicrobial agents including antifungal agents and antibacterial agents, and mixtures thereof; preferably the biocide is selected from the group consisting of phenols, halogenated phenols, halogen-containing compounds, halogen-releasing compounds, isothiazolinones, aldehyde-containing compounds, aldehyde-releasing compounds, biguanides, sulfones, thiocyanates, pyrithiones, antibiotics such as -lactam antibiotics, quaternary ammonium salts, peroxides, perchlorates, amides, amines, heavy metals, biocidal enzymes, biocidal polypeptides, azoles, carbamates, glyphosates, sulphonamides and mixtures thereof; more preferably the active ingredient is selected from L-carvone, chloramphenicol, curcumin, 2-phenylphenol, vanillin and mixtures thereof; most preferably the active compound is chloramphenicol or 2-phenylphenol.

15. An aqueous system, obtainable by contacting water and a loaded particulate carrier comprising surface-reacted calcium carbonate loaded with an active ingredient, said active ingredient having a solubility limit in water of less than 10 g/l, measured at 20 C. and 1 bar, characterized in that the aqueous system comprises said active ingredient in dissolved form, wherein the mass concentration of dissolved active ingredient in said aqueous system corresponds to a supersaturated state.

16. A method for preparing an aqueous system comprising an active ingredient in dissolved form, the method comprising the steps of: (a) providing surface-reacted calcium carbonate; (b) providing an active ingredient having a solubility limit in water of less than 10 g/l, measured at 20 C. and 1 bar; (c) loading the surface-reacted calcium carbonate provided in step (a) with the active ingredient provided in step (b) to obtain a loaded particulate carrier; (d) providing water; (e) contacting the loaded particulate carrier obtained in step (c) and the water provided in step (d); and (f) mixing the loaded particulate carrier and the water contacted in step (e); characterized in that the mass concentration of dissolved active ingredient in said aqueous system corresponds to a supersaturated state.

Description

DESCRIPTION OF THE FIGURES

[0212] FIG. 1: Supersaturation observed with surface-reacted calcium carbonate (SRCC) loaded with chloramphenicol (CAM)

[0213] FIG. 2: Supersaturation observed with surface-reacted calcium carbonate (SRCC) loaded with chloramphenicol (CAM)

[0214] FIG. 3: Supersaturation observed with surface-reacted calcium carbonate (SRCC) loaded with 2-phenylphenol (OPP)

EXAMPLES

[0215] The scope and interest of the invention may be better understood on basis of the following examples which are intended to illustrate embodiments of the present invention.

(A) ANALYTICAL METHODS

[0216] All parameters defined throughout the present application and mentioned in the following examples are based on the following measuring methods:

Particle Size Distributions

[0217] The particle size of surface-reacted calcium carbonate herein is described as volume-based particle size distribution d.sub.x(vol). The volume-based median particle size d.sub.50(vol) and the volume-based top cut particle size d.sub.98(vol) were evaluated using a Malvern Mastersizer 2000 Laser Diffraction System (Malvern Instruments Plc., Great Britain). 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.

[0218] The particle size of particulate materials other than surface-reacted calcium carbonate is described herein as weight-based particle size distribution d.sub.x (wt). The weight determined median particle size d.sub.50 (wt) and top cut d.sub.98 (wt) were 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 sonicated.

BET Specific Surface Area (SSA)

[0219] Throughout the present document, the specific surface area (in m.sup.2/g) was determined using the BET method (using nitrogen as adsorbing gas), which is well known to the skilled man (ISO 9277:2010). The total surface area (in m.sup.2) of the filler material was then obtained by multiplication of the specific surface area and the mass (in g) of the corresponding sample.

Porosimetry

[0220] The specific pore volume is 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 m. The equilibration time used at each pressure step is 20 s. The sample material is sealed in a 3 cm.sup.3 chamber powder penetrometer for analysis. The data are corrected for mercury compression, penetrometer expansion and sample material elastic 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, 1996, 35(5), 1753-1764).

[0221] The total pore volume seen in the cumulative intrusion data can be separated into two regions with the intrusion data from 214 m down to about 1 to 4 m showing the coarse packing of the sample between any agglomerate structures contributing strongly. Below these diameters lies the fine interparticle packing of the particles themselves. If they also have intraparticle pores, then this region appears bimodal, and by taking the specific pore volume intruded by mercury into pores finer than the modal turning point, i.e. finer than the bimodal point of inflection, we thus define the specific intraparticle pore volume. 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.

[0222] 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 interparticle pore region and the intraparticle pore region, if present. Knowing the intraparticle pore diameter range it is possible to subtract the remainder interparticle and interagglomerate 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.

Mass Concentration

[0223] The mass concentration of a solute (e.g. dissolved active ingredient) present in a solution or solvent system can be determined according to methods generally known to the skilled person. Suitable methods according to the present invention include UV-VIS spectroscopy, chromatographic methods as well as gravimetric or volumetric methods. Preferably, UV-VIS spectroscopy may be used to determine the mass concentration.

Thermogravimetric Analysis (TGA)

[0224] Thermogravimetric analysis was performed on a Mettler-Toledo TGA/DSC1 (TGA 1 STARe System) instrument with a method as follows: 30-80 C. and hold 5 min (10 K/min), 80-110 C. and hold 5 min (10 K/min), 10-570 C. and hold 10 min (20 K/min).

Solubility Limit

[0225] The solubility limit is determined by the shake flask method known to the skilled person. According to this method, excess compound (e.g. active ingredient) is added to the solvent (e.g. water, preferably deionized water) and shaken at 20 C. and 1 bar ambient pressure for at least 24 h. The saturation is confirmed by observation of the presence of undissolved material. After filtration of the slurry, a sample of the solution for analysis is taken. Both filtration and analysis is performed under the conditions used during dissolution (20 C., 1 bar) to minimize loss of volatile components. If necessary, the sample may be diluted to prevent crystallization. The mass concentration of solute contained in the sample is then determined by an appropriate known method which depends on the nature of the solute/solvent and on the concentration.

[0226] In many cases, solubility limits of active ingredients are available in public databases, for example GESTIS Gefahrstoffdatenbank. In case of any differences or inconsistencies, the solubility limit determined according to the method described hereinabove shall be preferred.

(B) EXAMPLES

[0227] The following examples are not to be construed to limit the scope of the claims in any manner whatsoever.

Example 1: Preparation of Surface-Reacted Calcium Carbonate

[0228] In a mixing vessel, 330l of an aqueous suspension of calcium carbonate-containing mineral was prepared by adjusting the solids content of a ground limestone calcium carbonate from Omya SAS, Orgon, having a weight based median particle size of 1.3 m, as determined by sedimentation, such that a solids content of 10 wt %, based on the total weight of the aqueous suspension, was obtained.

[0229] Whilst mixing the suspension at a mixer tip speed of 12.7 m/s, 10.6 kg of an aqueous solution containing 30 wt % phosphoric acid, based on the total weight of the aqueous solution, was added to said suspension over a period of 12 min at a temperature of 70 C. After the addition of the acid, the slurry was stirred for additional 5 min, before removing it from the vessel and drying. During acid treatment, carbon dioxide was formed in situ in the aqueous suspension.

[0230] The resulting surface-reacted calcium carbonate SRCC1 had an intraparticle intruded specific pore volume of 0.871 g/cm.sup.3 for the pore diameter range of 0.004 to 0.4 m (using a Micromeritics Autopore IV 9500 mercury porosimeter having a maximum applied pressure of 414 MPa with a equilibration time used at each pressure step of 20 seconds; the sample material was sealed in a 5 ml chamber powder penetrometer for analysis), a volume median grain diameter (d.sub.50) of 7.3 m and a d.sub.98 of 16.6 m as measured by laser diffraction (Malvern Mastersizer 2 000) and a specific surface area of 52.1 m.sup.2/g.

Example 2: Supersaturated Solution of Chloramphenicol

Loading:

[0231] 1.100 g of surface-reacted calcium carbonate prepared as described above (d.sub.50(vol) 7 m, d.sub.98(vol)16 m, SSA55 m.sup.2/g) were shaken in a 1 l Erlenmeyer flask using a Heidolph Uni 2010 orbital shaker at 300 rpm. A stock solution of 133 g/ml chloramphenicol (dry, purchased from Merck, #1.02366.0050) in absolute ethanol was added dropwise at a speed of 1.5 drops/second using a burette until the SRCC powder was loaded with 8.65% w/w of chloramphenicol. The sample was dried at room temperature. The percentage of loading and absence of ethanol was confirmed by TGA.

Calibration Curve:

[0232] The following standard solutions of chloramphenicol in water were prepared and analyzed by UV-VIS: 0.013 mg/ml, 0.083 mg/ml, 0.113 mg/ml, 0.167 mg/ml, and 0.333 mg/ml. The absorbance of each 3 l of standard was measured at 280 nm in a Nanodrop 2000c device and was taken as a reference to determine a calibration curve mg/ml chloramphenicol vs. absorbance (280 nm). A linear fit analysis was performed (R.sup.2=0.9982).

Solubility Measurements:

[0233] 1. The SRCC loaded with chloramphenicol as prepared above was mixed with water at a theoretical mass concentration of 5 mg/ml which is higher than the solubility limit reported in the product datasheet (2.5 mg/ml). The identical amount of pure chloramphenicol was taken as a reference. [0234] 2. After shaking, 0.1 ml of the solution were removed and centrifuged at 16 000 rcf (relative centrifugal force) for 1 min. The supernatant was then diluted with water at a ratio of 1:20 (5 l+95 l), mixed by pipetting five times (95 l volume) and absorbency was then measured immediately as described above. [0235] 3. The linear fit analysis was used to calculate the concentration of dissolved chloramphenicol in water. [0236] 4. Steps 2 and 3 were repeated at different time points.

[0237] The results of the concentration measurements are shown in FIG. 1 and FIG. 2 and clearly indicate the presence of a supersaturated aqueous system as the concentration of active ingredient (chloramphenicol) dissolved in the supernatant solution exceeds the reported solubility limit (2.5 mg/ml).

Example 3: Supersaturated Solution of 2-Phenylphenol

Loading:

[0238] 50 g of surface-reacted calcium carbonate prepared as described above (d.sub.50(vol)7 m, d.sub.98(vol)16 m, SSA55 m.sup.2/g) were shaken in a 1 l Erlenmeyer flask using a Heidolph Uni 2010 orbital shaker at 300 rpm. A stock solution of 75 w/w 2-phenylphenol in absolute ethanol (purchased from Lanxess, Preventol O Extra) was added dropwise at a speed of 1.5 drops/s using a burette until the SRCC powder was loaded with 17.2% w/w of 2-phenylphenol. The sample was dried at room temperature. The percentage of loading and absence of ethanol was confirmed by TGA.

Calibration Curve:

[0239] The following standard solutions of 2-phenylphenol in water were prepared and analyzed by UV-VIS: 0.025 mg/ml, 0.05 mg/ml, 0.1 mg/ml, 0.2 mg/ml, 0.4 mg/ml, 0.6 mg/ml and 0.8 mg/ml. The absorbance of each 3 l of standard was measured at 283 nm in a Nanodrop 2000c device and was taken as a reference to determine a calibration curve mg/ml 2-phenylphenol vs. absorbance (283 nm). A linear fit analysis was performed (R.sup.2=0.9996).

Solubility Measurements:

[0240] 1. The SRCC loaded with 2-phenylphenol as prepared above was mixed with water at a theoretical mass concentration of 4.8 mg/ml which is higher than the solubility limit reported in the product datasheet (0.5 to 0.6 mg/ml). The identical amount of pure 2-phenylphenol was taken as a reference. [0241] 2. After shaking, 0.1 ml of the solution were removed and centrifuged at 16 000 rcf for 1 minute. A dilution of 1:10 in water of the supernatant was performed to measure absorbency. Absorbency was then measured immediately as described above. [0242] 3. The linear fit analysis was used to calculate the concentration of dissolved 2-phenylphenol in water. [0243] 4. Steps 2 and 3 were repeated at different time points.

[0244] The results of the concentration measurements are shown in FIG. 3 and clearly indicate the presence of a supersaturated system as the concentration of active ingredient (2-phenylphenol) dissolved in the supernatant solution exceeds the reported solubility limit (0.5 to 0.6 mg/ml).