Method for producing capsules comprising at least one water-soluble or hydrophilic substance, and resulting capsules

Abstract

The present invention relates to a method for preparing solid microcapsules that comprises of the following steps: a) the preparation of a composition C1, comprising at least one water-soluble or hydrophilic substance dispersed in a hydrophobic phase; b) the addition, under stirring, of the said composition C1 in a polymeric composition C2, the compositions C1 and C2 being immiscible with each other, whereby an emulsion (E1) is obtained; c) the addition, under stirring, of the emulsion (E1) in a composition C3, the compositions C2 and C3 being immiscible with each other, whereby a double emulsion (E2) is obtained; d) the application of a shear to the emulsion (E2), whereby a double emulsion (E3) is obtained; and e) the polymerisation of the composition C2, whereby solid microcapsules dispersed in the composition C3 are obtained.

Claims

1. A method for preparing solid microcapsules that comprises of the following steps: a) the preparation of a composition C1, comprising at least one water-soluble or hydrophilic substance dispersed in a hydrophobic phase; b) the addition, under stirring, of said composition C1 in a polymeric composition C2, the compositions C1 and C2 being immiscible with each other; the composition C2 comprising at least one monomer or polymer, at least one crosslinking agent, and optionally at least one photoinitiator or a crosslinking catalyst; the viscosity of the composition C2 being comprised between 500 mPa.Math.s and 100 000 mPa.Math.s at 25° C., whereby an emulsion (E1) is obtained comprising droplets of the composition C1 dispersed in the composition C2; c) the addition, under stirring, of the emulsion (E1) in a composition C3, the compositions C2 and C3 being immiscible with each other; the viscosity of the composition C3 being comprised between 500 mPa.Math.s and 100,000 mPa.Math.s at 25° C.; whereby a double emulsion (E2) is obtained comprising droplets dispersed in the composition C3; d) the application of a shear to the emulsion (E2); whereby a double emulsion (E3) is obtained comprising size controlled droplets dispersed in the composition C3; and e) the polymerisation of the composition C2, whereby solid microcapsules dispersed in the composition C3 are obtained.

2. The method according to claim 1, wherein the water-soluble or hydrophilic substance is in solid form at ambient temperature and atmospheric pressure.

3. The method according to claim 2, wherein the composition C1 is prepared, either by dispersing, in the hydrophobic phase, at least one solid water-soluble or hydrophilic substance in powder form or by preparing a nanoemulsion of water droplets in the hydrophobic phase.

4. The method according to claim 2, wherein the composition C1 is obtained by means of grinding at least one solid water-soluble or hydrophilic substance and then dispersing the said ground substance in the hydrophobic phase.

5. The method according to claim 2, wherein the water-soluble or hydrophilic substance is selected from the group consisting of the following compounds: ascorbic acid and its biologically compatible salts, enzymes, antibiotics, components with tensor effect, alpha-hydroxy acids and their salts, polyhydroxylated acids, sucroses and their derivatives, urea, amino acids, oligopeptides, water-soluble plant extracts, and yeasts, protein hydrolysates, hyaluronic acid, mucopolysaccharides, vitamins B2, B6, H, PP, panthenol, folic acid, acetyl salicylic acid, allantoin, glycyrrhetic acid, kojic acid, hydroquinone, dihydroxyacetone, EUK 134, semi-crystalline polymers, and mixtures thereof.

6. The method according to claim 1, wherein the water-soluble or hydrophilic substance is selected from the group consisting of the following compounds: ascorbic acid and its biologically compatible salts, enzymes, antibiotics, components with tensor effect, alpha-hydroxy acids and their salts, polyhydroxylated acids, sucroses and their derivatives, urea, amino acids, oligopeptides, water-soluble plant extracts, and yeasts, protein hydrolysates, hyaluronic acid, mucopolysaccharides, vitamins B2, B6, H, PP, panthenol, folic acid, acetyl salicylic acid, allantoin, glycyrrhetic acid, kojic acid, hydroquinone, dihydroxyacetone, EUK 134, semi-crystalline polymers, and mixtures thereof.

7. The method according to claim 1, wherein the hydrophobic phase comprises at least one oil whose interfacial tension with water is comprised between 25 mN/m and 50 mN/m.

8. The method according to claim 7, in which the oil is selected from among plant, animal or synthetic oils.

9. The method according to claim 1, wherein the composition C2 comprises from 0.001% to 70% by weight of crosslinking agent(s) in relation to the total weight of said composition.

10. The method according to claim 1, wherein the step d) consists in applying a homogeneous controlled shear to the emulsion (E2), with the said shear rate applied comprised between 1000 s.sup.−1 and 100,000 s.sup.−1.

11. The method according to claim 1, wherein when the viscosity of the composition C3 is greater than 2000 mPa.Math.s at 25° C., the step d) consists in applying to the emulsion (E2) a shear rate of less than 1000 s.sup.−1.

12. The method according to claim 1, wherein, when the composition C2 comprises a photoinitiator, the step e) is a step of photopolymerisation consisting in exposing the emulsion (E3) to a light source that is capable of initiating the photopolymerisation of the composition C2.

13. The method according to claim 1, wherein, when the composition C2 does not comprise a photoinitiator, the step e) is a polymerisation step, without exposure to a light source.

14. The method according to claim 1, wherein the composition C3 comprises in addition at least one branched polymer and/or at least one polymer having a molecular weight greater than 5000 g.Math.mol.sup.−1, and/or solid particles.

15. The method according to claim 14, wherein solid particles are silicates.

Description

EXAMPLES

Example 1: Manufacture of Solid Capsules According to the Invention

(1) A mechanical agitator (Ika Eurostar 20) equipped with a deflocculating type propeller stirrer is used to carry out all the stirring/agitation steps.

(2) Step a): Creation of the Dispersion of Particles (Composition C1) by Means of Nanoemulsion

(3) TABLE-US-00001 Raw materials INCI % Composition A Paraffin oil Paraffinum liquidum 48 Abil Em 90 (Evonik) Cetyl PEG/PPG-10/1 2 Dimethicone Composition B Vitamin C Ascorbic acid 16.5 L-Glutathione Glutathione 1 Phosphate buffer (PBS) Disodium Phosphate 32.5 Potassium Chloride Sodium Chloride Total 100

(4) The composition A (hydrophobic phase) is placed under agitation at 1000 rotations per minute (rpm) until complete homogenisation is obtained.

(5) Composition B is stirred at 1000 rpm in a bath thermostated at 40° C. until complete homogenization and then allowed to cool to room temperature.

(6) The composition B is subsequently added dropwise to the composition A under agitation at 2000 rpm. The agitation is maintained for a period of 5 minutes after the addition and the mixture is thereafter subjected to sonication (Vibra-cell 75042, Sonics) for a period of 3 minutes (pulse 10 s/5 s) for a period of 3 minutes at 20% amplitude.

(7) The nanoemulsion obtained is then placed in a desiccator under reduced pressure until complete evaporation of the water occurs. The composition C1 is thus obtained.

(8) Step b): Preparation of the First Emulsion (E1)

(9) TABLE-US-00002 % for Ratio Raw materials INCI C2 C1-C2 Composition C1 — 3 Composition CN 9800 (Sartomer) silicone acrylate 85 7 C2 urethane oligomer, CN381 (Sartomer) modified amine 12 polyether oligomer Darocur 1173 2-Hydroxy-2- 3 (photoinitiator, BASF) methyl-1- phenyl-propan- 1-one Total 100 10

(10) Alternatively, the CN9800 (Sartomer) may be replaced by CN2035 (Sartomer) (polyester acrylate oligomer).

(11) The composition C1 is added dropwise to the composition C2 under agitation at 2000 rpm in a ratio of 3:7. This results in the first emulsion (E1).

(12) Step c): Preparation of the Second Emulsion (E2)

(13) TABLE-US-00003 Raw materials INCI % First emulsion 5 Composition C3 Sodium alginate Algin 9.5 (Sigma Aldrich) Deionized water Aqua 85.5 Total 100

(14) The composition C3 is placed under agitation at 1000 rotations per minute (rpm) until complete homogenisation is obtained and then allowed to stand for a period of one hour at ambient temperature. The first emulsion (E1) is then added dropwise to the composition C3 under agitation at 1000 rpm. The second emulsion (E2) is thus obtained.

(15) Step d): Size Refinement of the Second Emulsion

(16) The second polydisperse emulsion (E2) obtained in the previous step is agitated at 1000 rpm for a period of 10 minutes. A monodisperse emulsion (E3) is thus obtained.

(17) Step e): Cross-Linking of the Enveloping Shell of the Capsules

(18) The second monodisperse emulsion (E3) obtained in the previous step is irradiated for a period of 15 minutes by using a UV light source (Dymax LightBox ECE 2000) having a maximum luminous intensity of 0.1 W/cm.sup.2 at a wavelength of 365 nm.

(19) The solid microcapsules according to Example 1 have a good size distribution, namely an average size of 3.4 μm and a standard deviation of 1 μm.

(20) Furthermore, the quality of encapsulation of vitamin C with the microcapsules according to Example 1 was studied by incubating the microcapsules at 50° C. for 20 days.

(21) There is no yellow coloration, synonymous with oxidation of vitamin C. The solid microcapsules according to Example 1 are therefore particularly suitable for effectively encapsulating a water-soluble or hydrophilic substance.

Example 2: Manufacture of Solid Capsules According to the Invention

(22) Example 2 differs from Example 1 only in the nature of composition C2, as described below.

(23) All the other parameters, protocols, steps, compositions described in Example 1 therefore remain identical.

(24) TABLE-US-00004 % for Ratio Raw materials C2 C1-C2 Composition C1 — 2.5 Composition CN 981 77 7.5 C2 (aliphatic polyester/ether urethane acrylate oligomer, Sartomer) SR238 (1,6-hexanediol diacrylate, Sartomer) 20 Darocur 1173 3 (2-Hydroxy-2-methyl-1-phenyl-propan-1- one, photoinitiator, BASF) Total 100 10

Example 3: Manufacture of Solid Capsules According to the Invention

(25) Example 3 differs from Examples 1 and 2 in the nature of composition C1, as described below. All the other parameters, protocols, steps, compositions described in example 1 remain identical.

(26) TABLE-US-00005 MatiérRaw materials INCI % Composition Vitamin C Ascorbic acid 26.4 C1 L-Glutathione Glutathione 1.6 Phosphate buffer (PBS) Disodium Phosphate 52 Potassium Chloride Sodium Chloride Aculyn 44 PEG-150/Decyl Alcohol/ 20 SMDI Copolymer Total 100