SILICA WITH ULTRA-FAST DISSOLUTION PROPERTIES

Abstract

The current invention concerns a mesoporous silica with ultra-fast dissolution properties prepared by (i) forming a silica comprising an amphiphilic glycoside; and (ii) subsequently subjecting said silica comprising said amphiphilic glycoside to a heat-treatment above 400 C.

Claims

1. Mesoporous silica prepared by (i) forming a clogged mesoporous silica comprising an amphiphilic glycoside; and (ii) subsequently subjecting said clogged mesoporous silica comprising said amphiphilic glycoside to a heat-treatment above 400 C.

2. The mesoporous silica according to claim 1, whereby said silica clogged mesoporous is subjected to a heat-treatment between 450 C. and 950 C.

3. The mesoporous silica according to claim 1, whereby said amphiphilic glycoside is saponin.

4. The mesoporous silica according to claim 1, wherein said clogged mesoporous silica comprises an amphiphilic glycoside and a cationic load, wherein said cationic load consists of cations chosen from the list of Na+, K+, Ca2+ and Mg2+.

5. The mesoporous silica according to claim 1, whereby said clogged mesoporous silica is formed by (i-a) mixing a silica precursor in presence of said amphiphilic glycoside and (i-b) subsequently filtrating or drying.

6. The mesoporous silica according to claim 1, whereby said silica has mesopores having an average pore size of at least 1 nm.

7. The mesoporous silica according to claim 1, whereby said silica has a porous volume of at least 0.1 cm3/g.

8. The mesoporous silica according to claim 5, whereby said silica precursor is represented by the formula Si(OR1)(OR2)(OR3)(OR4) or R1-Si(OR2)(OR3)(OR4) whereby R1, R2, R3 and R4 are independently selected from hydroxyl, alkyl, glycols, trimethyl-1, 2, 3, 4-tetrahydronaphthalene, 1,1,1,3,3,3-hexafluoropropan-2-yl, dimethylsilyl, trimethylsilyl, ethoxysilyl, tributoxysilyl, diethoxy(methoxy)silyl, trimethoxysilyl, ethoxy(dimethoxy)silyl, butoxy(dipropoxy)silyl, tripropoxysilyl, diethoxy(trimethylsilyloxy)silyl, ethoxy-bis(trimethylsilyloxy)silyl, methyl-bis(trimethylsilyloxy)silyl, butoxy-bis(trimethylsilyloxy)silyl, diethoxy(triethoxysilyloxy)silyl, dimethyl(vinyl)silyl, trimethylsilyloxy, (3-methylpentoxy)silyl, 4,7,7-trimethyl-3-bicyclo[2.2.1]heptanyl, 2,2,4-trimethyl-3-bicyclo[2.2.1]heptanyl, propan-2-yloxy-bis(trimethylsilyloxy)silyl, dibutoxy(trimethylsilyloxy)silyl, trimethyl trimethoxysilyl, dibutoxy(ethenyl)silyl, diethyl bis(trimethylsilyl), (butan-2-yloxy)silyl, diacetyloxy-[(2-methylpropan-2-yl)oxy]silyl, acetyloxy(diethoxy)silyl, 4-(dimethylamino)phenyl, 4-(dimethylamino)phenyl, 2-(diethylamino)ethyl, pyridin-3-yl, 2-methylpropan-2-yl)oxy, 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptyl, trichloro-2-ethylbutoxy, cyclononyl, 1-methoxypropan-2-yl, 2-(2-methoxyethoxy)ethyl, 2-butoxyethyl, 2-ethoxyethyl, 2-methoxyethyl, acetyl, acetyloxy(dipropoxy)silyl, 5-methyl-2-propan-2-ylcyclohexyl, butan-2-yloxy, methylphenyl, cyclohexyl, 2-aminoethyl, phenyl, prop-2-enyl, 2-fluoroethyl, acetate or trihydroxysilyloxy; or by the formula xSiO2:MyO whereby M is one or more metal atoms, one or more transition metal atoms, one or more non-metals, or ammonium, and whereby y=1, 2, 3 or 4 and x is the ratio of SiO2/MyO.

9. The mesoporous silica according to claim 8, whereby R1, R2, R3 and R4 are independently selected from methyl, ethyl, propyl and butyl, preferably from methyl or ethyl, and whereby preferably R1, R2, R3 and R4 are equal.

10. The mesoporous silica according to claim 1, whereby said clogged mesoporous silica comprising an amphiphilic glycoside is formed by mixing a silica precursor in presence of said amphiphilic glycoside at a pH between 8 and 13.

11. An oral dosage form comprising a mesoporous silica prepared by (i) forming a clogged mesoporous silica comprising an amphiphilic glycoside; and (ii) subsequently subjecting said clogged mesoporous silica comprising said amphiphilic glycoside to a heat-treatment above 400 C.

12. The oral dosage form according to claim 11, comprising said silica in an amount of at least 1 wt. %, relative to the total weight of said oral dosage form.

13. The oral dosage form according to claim 12, comprising said silica in an amount of at least 50 wt. %.

14. Method for producing a mesoporous silica, comprising the steps of: i. forming a clogged mesoporous silica comprising an amphiphilic glycoside; and ii. subsequently subjecting said clogged mesoporous silica comprising said amphiphilic glycoside to a heat-treatment above 400 C.

15. Use of a mesoporous silica according to claim 1 in nutrition or food supplements for humans or animals, in cosmetics or pharmaceuticals.

Description

EXAMPLES 1-6 AND COMPARATIVE EXAMPLES 1-6

[0124] The invention is further described by the following non-limiting examples which further illustrate the invention, and are not intended to, nor should they be interpreted to, limit the scope of the invention.

[0125] Preparation

[0126] In a reactor, under agitation, saponin solution is added to water and pH is adjusted to 10 with adequate quantity of NH.sub.4OH. Triethoxysilane (TEOS) is then added with a peristaltic pump at a rate of 1.8 g/min and the formulation is aged under agitation for 24 hours. The amounts of tetraethoxysilane, saponin, water and ammonium hydroxide used for the preparation of mesoporous silica according to Examples 1 to 6 and Comparative Examples 1 to 6 is summarized in Table 1.

TABLE-US-00001 TABLE 1 Amounts of tetraethoxysilane, saponin, water and ammonium hydroxide used for the preparation of mesoporous silica. tetraethoxy Example silane (g) saponin (g) water (g) NH.sub.4OH (g) Ex. 1 9.94 13.24 325.92 0.9 Ex. 2 19.9 26.48 651.82 1.8 Ex. 3 9.94 13.24 325.92 0.9 Ex. 4 28400 50100 919200 2300 Ex. 5 25.56 45.09 827.3 2.07 Ex. 6 25.56 45.09 827.3 2.07 Comp. Ex. 1 17.04 22.72 559.8 0.44 Comp. Ex. 2 39.8 52.96 1303.64 3.6 Comp. Ex. 3 19.9 26.48 651.82 1.8 Comp. Ex. 4 39.8 52.96 1303.64 3.6 Comp. Ex. 5 39.76 79.48 1277.2 3.56 Comp. Ex. 6 39.76 79.48 1277.2 3.56

[0127] The formulation is sprayed under the conditions presented in Table 2 and a clogged mesoporous silica comprising silica and saponin is collected as a powder.

TABLE-US-00002 TABLE 2 Spray conditions. T in 140 C. Inlet gaz flow 0.3 m.sup.3/min Pressure drop cyclone (AP) 60 mbar Nozzle Bi-fluid 0.4 mm Nozzle air flow 7 l/min Nozzle air 0.6 bar Spray rate 6.0 g/min

[0128] The powder obtained after spray drying of the mixtures according to Examples 1 to 6 is calcined at 550 C. for 2 hours.

[0129] The powder obtained after spray drying of the mixtures according to Comparative Examples 1, 2 and 5 is washed and subsequently calcined at 550 C. for 2 hours. The powder obtained after spray drying of the mixtures according to Comparative Examples 3, 4 and 6 is washed and not calcined.

[0130] Dissolution Tests

[0131] The dissolution method is as followed. 100 mg of silica powder is placed in 900 mL of water in a type II USP dissolution apparatus. Samples are taken at different times and filtered with a 0.45 m nylon membrane. The Si concentration is determined either by ICP-OES (total Si content) or by molybdate complexation (monomeric Si). The results of the two dosages were the same for every tested sample.

[0132] The silicon dissolution percentages after 6 hours in water are presented in Table 3. The results clearly show that the mesoporous silica according to the invention show a distinctly higher dissolution compared to mesoporous silica known in the art.

TABLE-US-00003 TABLE 3 Amount of Si dissolved in water, as a weight percent of the amount of Si in the mesoporous silica. Example wt. % Si dissolved Ex. 1 31.2 Ex. 2 28.76 Ex. 3 11.01 Ex. 4 49.06 Ex. 5 43.08 Ex. 6 46.74 Comp. Ex. 1 3.69 Comp. Ex. 2 4.94 Comp. Ex. 3 1.42 Comp. Ex. 4 2.25 Comp. Ex. 5 9.55 Comp. Ex. 6 3.21

EXAMPLES 7-11: INFLUENCE OF CATIONS ON THE DISSOLUTION RATE

[0133] In a beaker, 22.5 grams of saponin-water mixture (15 w % saponin in water) is introduced. Approximately 850 grams of additional water are added, and the resulting mixture is kept under vigorous agitation with a magnetic stirrer set at 550 rpm for 2 minutes. Approximately 1.2 grams of a 25 w % ammonium hydroxide solution is added until a pH of 9.5 is reached. After 5 minutes of stirring at 550 rpm, 25.6 grams of TEOS is added dropwise via a peristaltic pump. The rate of addition is set at 1.76 g/min.

TABLE-US-00004 TABLE 4 summary of the formulation. Products Weight (g) % w Saponin mixture 22.5 2.50 TEOS 25.6 2.84 NH.sub.4OH 1.2 0.13 Water 850 94.4

[0134] The mixture is kept under agitation (550 rpm) at room temperature for 24 h before being spray dried.

[0135] The spray drying process is performed with the settings below on ProCept 4M8Trix spray-dryer.

TABLE-US-00005 TABLE 5 parameters of the spray drying process Temperature inlet gaz 140 C. Inlet gaz flow 0.3 m.sup.3/min Cyclone air flow 47 L/min Cyclone Medium Nozzle Bi-fluid-0.4 mm Nozzle air flow 7 l/min Spray rate 6.0 g/min

[0136] The powder recovered after spray-drying is calcinated in order to remove the organic template. The heat treatment parameters are as follows: From ambient temperature to 500 C. with a heat rate ramp of 10 C./min. The product stays 2 hours at 500 C. before being taken off at this temperature.

[0137] Table 6 below summarizes the cations identified and their concentrations for six batches of saponin mixture, measured by ICP-OES:

TABLE-US-00006 TABLE 6 Concentration of alkali and earth alkaline cations in the saponin mixture Ca K Mg Na Cationic Example (ppm) (ppm) (ppm) (ppm) load (ppm) Example 7 1866 2183 686 3235 7970 Example 8 1906 2216 694 3277 8093 Example 9 1140 3574 1119 614 6446

[0138] The cationic load in this example is expressed as the sum of the molar concentrations of the alkali and earth alkali cations detected and quantified by ICP-OES in ppm. These concentrations are with respect to the cation-saponin mixture. It does not include the silica-based material and thus is not representative of the concentrations in the final mesoporous silica product.

[0139] The cations identified and quantified in the saponin mixture such as sodium, potassium, magnesium, and calcium form inorganic compounds during the spray drying step. These compounds are not eliminated during the heat treatment process at 500 C.

[0140] The concentrations of alkali and earth alkali cations of the saponin mixture can be modified by a demineralization process. For that, the saponin water solution is treated by an ion exchange resin (Dowex MB Mixed) with supplies H.sup.+/OH.sup. ions.

[0141] Using this process of demineralization, we have obtained [0142] a completely demineralized saponin (example 11) [0143] a 50% demineralized saponin by mixing the completely demineralized and the non-demineralized saponins (example 10)

TABLE-US-00007 TABLE 7 The concentration of the alkali and earth alkaline metals in the saponin mixture as measured by ICP-OES before and after treatment: Demin- Cat- eraliza- ionic tion Ca K Mg Na load Example (%) (ppm) (ppm) (ppm) (ppm) (ppm) Example 9 0 1140 3574 1119 614 6446 Example 10 50 563 1693 555 333 3143 Example 11 99.2 23 0 13 19 55

[0144] The rate of demineralization expressed in percent is determined by the ratio between the cationic load after and before the demineralization treatment of Saponin-water mixture.

[0145] Using these 3 batches of saponin mixture with differing degree of demineralization, three mesoporous silica's have been produced (examples 9, 10 and 11 in table 7.) We have consequently analyzed the dissolution properties thereof.

[0146] The dissolution rate of the mesoporous silica-based materials is expressed in a percentage of silicium dissolved in water after 8 hours of test. The dissolution test is performed at 37 C. in ultra-pure water in a Sotax apparatus. The dissolution rates measured from samples of examples 9, 10 and 11 in function of the initial cationic load of the Saponin-water mixture are represented in graph 1.

[0147] It is clear that the dissolution properties are linked to the cationic load present in the saponin-water mixture used during the synthesis process. When the cationic load increases, the dissolution rate of silicium increases. This allows the present process to be used to optimize the dissolution rate of a mesoporous silica.

[0148] The porosity of the silica-based materials obtained from the examples 9 and 11 have been analyzed by BET method and the sorption isotherm are represented in graph 2.

[0149] Example 11 has a specific surface area S.sub.s of 417 m.sup.2/g, an maximum absorbed volume of 0.49 cm.sup.3/g and an estimated pore diameter of 4.3 nm.

[0150] Example 11 has a specific surface area S.sub.s of 696 m.sup.2/g, an maximum absorbed volume of 0.55 cm.sup.3/g and an estimated pore diameter of 3.3 nm.

[0151] The cationic load in Saponin-water mixture influences the specific surface area and pore volume of the final silica material. When the cationic load of the saponin at the beginning of the synthesis process increases the specific surface area and the pore volume decrease.