A METHOD OF PREPARING A HYBRID CAPSULE AND RELATED PRODUCTS

Abstract

There is provided a method of preparing a hybrid capsule, the method comprising heterocoagulating organic polymer latex particles with a primary capsule to form an organic polymer coating layer over a shell of the primary capsule.

Claims

1. A method of preparing a hybrid capsule, the method comprising: heterocoagulating organic polymer latex particles with a primary capsule to form an organic polymer coating layer over a shell of the primary capsule.

2. The method of claim 1, wherein the hybrid capsule is an organic-inorganic capsule and the primary capsule is an inorganic capsule.

3. The method of claim 1, of wherein the heterocoagulating step is at least partly carried out at a temperature that is no less than the glass transition temperature (T.sub.g) of the organic polymer latex particles.

4. The method of claim 3, wherein the heterocoagulating step is at least partly carried out at a temperature of from 10° C. to 80° C. and/or at a pH from 2 to 11.

5. The method of claim 1, wherein the heterocoagulating step is carried out in the presence of two opposing charges, a first charge being associated with the organic polymer latex particles and a second charge being associated with the primary capsule, the second charge having a polarity that is opposite to that of the first charge.

6. The method of claim 1, further comprising introducing the primary capsule into a larger volume of the polymer latex particles prior to the heterocoagulating step.

7. The method of claim 6, wherein the step of introducing the primary capsule comprises introducing a plurality of primary capsules until the concentration of the primary capsules in the mixture of primary capsules and organic polymer latex is from 10% to 40% by weight of the entire mixture.

8. The method of claim 1, wherein the heterocoagulating step to form a polymer coating layer over a shell of the primary capsule is substantially devoid of a polymerization reaction and, optionally, wherein the heterocoagulating step is carried out in the absence of an organic solvent.

9. (canceled)

10. The method of claim 1, wherein the organic polymer latex particles comprises poly-N-isopropyl acrylamide (PNIPAM) latex particles, poly-methyl-methacrylate-co-poly-styrene-co-polyethyl-hexyl-acrylate-co-poly-acrylic acid latex particles, poly caprolactone (PCL) latex particles, poly valerolactone latex particles, poly butyrolactone latex particles, polyurethane latex particles, polyamide latex particles, polyacrylic acid-containing latex particles or combinations thereof.

11. The method of claim 1, wherein the primary capsule comprises a silica capsule, a zirconia capsule, a titania capsule or combinations thereof.

12. The method of claim 1, wherein the polymer latex particles have an average particle size in the range of from 50 nm to 1000 nm and the primary capsule has an average particle size in the range of from 1 μm to 100 μm.

13. The method of claim 5, wherein the heterocoagulating step is carried out in the presence of at least two different surfactants comprising at least one cationic surfactant and at least one anionic surfactant and, optionally, wherein the at least two different surfactants are independently selected from the group consisting of a primary amine surfactant, a secondary amine surfactant, a tertiary amine surfactant, a quaternary amine surfactant, cetyl trimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), carboxylic acid salt, sulfonic acid salt, phosphoric acid ester, alcohol sulfate, alkylbenzene sulfonate, and a combination thereof.

14. (canceled)

15. A hybrid capsule comprising: a primary capsule having a shell; and an organic polymer coating layer over the shell of the primary capsule.

16. The hybrid capsule of claim 15, wherein the hybrid capsule is an organic-inorganic capsule and the primary capsule is an inorganic capsule.

17. The hybrid capsule of claim 15, wherein the shell of the primary capsule is substantially hermetically sealed by the polymer coating layer.

18. The hybrid capsule of claim 15, wherein the hybrid capsule is micron- or submicron-sized.

19. The hybrid capsule of claim 15, wherein the hybrid capsule is substantially resistant to breaking under scanning electron microscopy (SEM) vacuum conditions.

20. The hybrid capsule of claim 15, wherein the hybrid capsule comprises one or more actives loaded in a core of the primary capsule that is encapsulated by the shell of the primary capsule.

21. The hybrid capsule of claim 15, wherein the organic polymer coating comprises poly-N-isopropyl acrylamide (PNIPAM), poly-methyl-methacrylate-co-poly-styrene-co-polyethyl-hexyl-acrylate-co-poly-acrylic acid, poly caprolactone (PCL), poly valerolactone, poly butyrolactone, polyurethane, polyamide, polyacrylic acid or combinations thereof and the primary capsule comprises a silica capsule, a zirconia capsule, a titania capsule or combinations thereof.

22. The hybrid capsule of claim 21, wherein the hybrid capsule is configured to release at least a portion of one or more actives from the core when stimulated by a change in one or more of a salt concentration, a pH, a temperature or a mechanical pressure.

Description

BRIEF DESCRIPTION OF FIGURES

[0106] FIG. 1 is a schematic flowchart 100 for illustrating a method of preparing a hybrid capsule in accordance with various embodiments disclosed herein.

[0107] FIG. 2 is a schematic diagram 200 for illustrating a method of preparing a hybrid capsule in accordance with various embodiments disclosed herein.

[0108] FIG. 3 is a schematic diagram 300 of a hybrid capsule in accordance with an example embodiment disclosed herein.

[0109] FIGS. 4A and 4B are scanning electron microscopy (SEM) images of poly(N-isopropylacrylamide) (PNIPAM) polymer latex prepared via emulsion polymerization with 1% acrylic acid (AA) and 1% N,N′-Methylenebis(acrylamide) (BIS) crosslinker by weight of the monomer latex particles in the absence of a SDS surfactant, and dried at an elevated temperature (e.g. at 90° C.), in accordance with an example embodiment disclosed herein. FIG. 4A shows an SEM image taken at 5,000× magnification, with the scale bar representing 1 μm. FIG. 4B shows an SEM image taken at 10,000× magnification, with the scale bar representing 1 μm.

[0110] FIG. 5 is a dynamic light scattering Z-average particle size (DLS Z-ave) vs. temperature graph showing the temperature response of PNIPAM polymer latex synthesized for heterocoagulation studies, in accordance with an example embodiment disclosed herein. As shown, a higher temperature led to decreased particle size, thereby demonstrating the temperature responsiveness of the latex.

[0111] FIG. 6A is a dark field microscopic image of silica capsule dispersion in water and FIG. 6B is a dark field microscopic image of hetero-coagulated silica capsules with poly-NIPAM latex particles prepared from a method in accordance with an example embodiment disclosed herein. The scale bar in both figures represents 50 μm.

[0112] FIG. 7 is a graph showing the particle size distribution of a silica capsule obtained after heterocoagulation.

[0113] FIG. 8A is a thermogravimetric analysis (TGA) graph of silica capsules and FIG. 8B is a thermogravimetric analysis (TGA) graph of hetero-coagulated silica capsules with poly-NIPAM latex particles prepared from a method in accordance with an example embodiment disclosed herein.

[0114] FIGS. 9A-9C are scanning electron microscopy (SEM) images of sub-20 micron silica capsules stabilised by cetyltrimethylammonium bromide (CTAB) in accordance with an example embodiment disclosed herein, taken at various stages of polymer coating. These images are captured after 2-3 hours after heterocoagulation and film formation under SEM conditions. FIG. 9A shows an SEM image taken at 5,000× magnification, with the scale bar representing 1 μm. FIG. 9B shows an SEM image taken at 5,000× magnification, with the scale bar representing 1 μm. FIG. 9C shows an SEM image taken at 1,000× magnification, with the scale bar representing 10 μm.

[0115] FIG. 10A is a scanning electron microscopy (SEM) image of original silica capsules and FIG. 10B is a scanning electron microscopy (SEM) of polycaprolactone particles coated on silica capsules after hetero-coagulation in accordance with an example embodiment disclosed herein. FIG. 10A shows an SEM image taken at 1,000× magnification, with the scale bar representing 10 μm. FIG. 10B shows an SEM image taken at 2,000× magnification, with the scale bar representing 10 μm.

EXAMPLES

[0116] Example embodiments of the disclosure will be better understood and readily apparent to one of ordinary skill in the art from the following examples, tables and if applicable, in conjunction with the figures. It should be appreciated that other modifications related to structural, and chemical changes may be made without deviating from the scope of the invention. Example embodiments are not necessarily mutually exclusive as some may be combined with one or more embodiments to form new example embodiments. The example embodiments should not be construed as limiting the scope of the disclosure.

Example 1: Method of Preparing A Hybrid Capsule

[0117] FIG. 1 is a schematic flowchart 100 for illustrating a method of preparing a hybrid capsule in accordance with various embodiments disclosed herein. At step 104, the organic polymer latex particles in a suspension/dispersion/mixture are heterocoagulated with at least one primary capsule such as an inorganic capsule so that an organic polymer film can be eventually formed over the shell of the primary capsule (e.g. inorganic shell).

[0118] It will be appreciated that in some embodiments, the method may also include steps before and after step 104. For example, prior to step 104, at least one primary capsule may be introduced into a volume of organic polymer latex particles to form the suspension/dispersion/mixture at step 102. Likewise, subsequent to step 104, the organic polymer latex particles may be further physically cured by using at least one of temperature or pH as a curing means to form an organic polymer coating layer over a shell of the primary capsule, thereby obtaining a hybrid capsule at step 106. In addition, at step 108, the hybrid capsule is further purified to remove any impurities such as excess/free polymer particles and/or further concentrated to obtain a desired concentration.

[0119] While in various embodiments, the method relies on the use of preformed organic polymer latex particles and primary capsules, it will also be appreciated that optional steps to prepare the polymer latex particles and primary capsules may also be incorporated in various embodiments of the method. For example, prior to step 102, the method may optionally comprise step 110 for synthesizing the primary capsule and may also optionally comprise step 112 for synthesizing the organic polymer latex particles. The dotted lines of boxes containing steps 110 and 112 emphasise that these steps may be absent in some embodiments of the present disclosure as the primary capsule(s) and/or organic polymer latex particles may be preformed or purchased/obtained commercially. For example, preformed silica capsules may be used as the primary capsule(s) and preformed (responsive) polymer latex may be used as the organic polymer latex.

[0120] FIG. 2 is a schematic diagram 200 for illustrating a method of preparing a hybrid capsule in accordance with various embodiments disclosed herein. A primary capsule 202 is introduced into a volume of organic polymer latex particles 204a, 204b and 204c, collectively known as organic polymer latex 204 as shown by arrow 203 to form a suspension/dispersion/mixture 206. The organic polymer latex particles 204a, 204b and 204c then undergo heterocoagulation as shown by arrow 205 and physical curing as shown by arrow 207 to form an organic polymer coating layer 208 over a shell of the primary capsule 202, thereby forming a hybrid capsule 210. In other words, in various embodiments, the steps may include resuspension/dispersion of the polymer latex particles with the primary capsule followed by heterocoagulation such that fusion of the organic polymer latex particles will occur thereby forming film around the shell of the primary capsule. Thereafter, post processing steps such as purification and concentration of the capsules may take place. It will be appreciated that although not shown in the figure, the interior/core of the primary capsule 202 may be empty or may be filled/loaded with cargo such as active molecules.

[0121] FIG. 3 is a schematic diagram of a hybrid capsule in accordance with various embodiments disclosed herein. The hybrid capsule 300 comprises a primary capsule having a shell 302 encapsulating an empty or a loaded/filled core 304 and an organic polymer coating layer 306. In this example, the hybrid capsule has a size/diameter/particle size/particle size distribution/average particle size in the range of from about 5 μm to about 50 μm.

Example 2: Primary Capsule(s)

[0122] Prior to the synthesis of hybrid capsules/polymer reinforced structures, primary capsules stabilised by a surfactant were synthesized. In this example, the primary capsules synthesized were silica hollow microspheres stabilised by cetyltrimethylammonium bromide (CTAB) as the surfactant.

[0123] 36.4 mg of CTAB was dissolved in 100 mL of deionised (DI) water in a 250 mL reaction vessel. The solution was stirred at 600 rpm for thirty minutes to ensure that all of the surfactant was dissolved. 10 mL of n-pentane was injected into the solution and was stirred for thirty minutes at 600 rpm. Before the addition of TEOS, light microscopy was taken to ensure that the particles have an average particle size of 30 μm. 4 mL of TEOS was added via a programmed syringe pump at 80 μL/min to the solution. After the addition of TEOS was completed, the stirring speed was lowered to 400 rpm. A sample of the solution was taken for analysis using brightfield microscopy. Microscopic images were recorded for four days. SEM analysis was done on day 4. The resultant silica capsules were post processed for other applications.

Example 3: Organic Polymer Latex Particles

[0124] Prior to performing heterocoagulation of organic polymer latex particles with primary capsule(s), organic polymer latex particles were synthesized using emulsion polymerization. In this example, the organic polymer latex particles synthesized were poly(N-isopropylacrylamide) (PNIPAM) latex particles having an average particle size of about 200 nm.

[0125] 150 mL of D.I. water was heated to 90° C. in the 1 L-jacketed reactor at the stirring speed of 200 rpm. 1.5 g of ammonium persulfate and 1.5 g of sodium hydrogen carbonate was added. 30 g of N-Isopropylacrylamide (NIPAM) and 0.3 g of N,N′-methylenebis (acrylamide) (BIS) dissolved in 750 mL of water was added into the reactor at the feed rate of 25 mL/min for 30 min. The mixture was stirred for another 30 min after the second feed of 0.3 g NIPAM, 0.03 g BIS and 0.3 g acrylic acid (AA) dissolved in 7.5 mL water was fed into the reactor at the rate of 1.5 mL/min. The total 900 mL mixture was allowed to stir at 90° C. for another 3 hr. The final latex was then filtered to remove aggregates and stored in glass bottle in 60° C. oven.

[0126] Latex particles were prepared in a few different batches to evaluate their stability against aggregation as well as their thermal response (i.e. response to temperature). The latex particles were characterized by scanning electron microscopy (SEM) and by performing dynamic light scattering (DLS) experiments.

Scanning Electron Microscopy (SEM) of Latex Particles

[0127] FIG. 4A and FIG. 4B are SEM images of PNIPAM latex particles taken at different degree of magnifications (i.e. 5,000× and 20,000× respectively). The latex particles were prepared via emulsion polymerization with 1% acrylic acid (AA) and 1% N,N′-methylenebis (acrylamide) (BIS) crosslinker by weight of the monomer latex particles in the absence of a SDS surfactant, and dried at an elevated temperature. As shown in FIG. 4A and FIG. 4B, the PNIPAM latex particles were stable against aggregation. The acrylic acid on the surface of the latex particles provided sufficient charge for latex particles to stabilize in aqueous system and prevented aggregation. Therefore, as demonstrated, a surfactant may not be required if an acid such as an acrylic acid is used as a monomer in the system.

Dynamic Light Scattering (DLS) of Latex Particles

[0128] PNIPAM latex particles samples were prepared with varying concentrations of crosslinker (i.e. N,N′-methylenebis(acrylamide) (BIS)) and surfactant (i.e. sodium dodecyl sulfate (SDS)). A summary of the composition present (wt % based on the monomer latex particles) in the samples and their corresponding aggregation percentage (Aggr %) is provided in Table 1 below. The z-average particle size (DLS Z-Ave) and polydispersity index (PDI) results of the latex particles obtained from DLS experiments are also provided in Table 1. To test for reversibility in temperature response, the measurements were first taken at (i) a temperature of about 40° C., then at (ii) a temperature of about 20° C. and finally (iii) at a temperature of about 40° C. As shown in Table 1, the average particle size recorded at temperature (iii) for the samples remains relatively similar to those recorded at temperature (i). Therefore, the temperature response was proven to be reversible.

TABLE-US-00001 TABLE 1 Summary of composition and DLS results of PNIPAM samples synthesized for hetero-coagulation studies Temperature 40° C. 20° C. 40° C. % (wrt to BIS SDS Aggr DLS Z- DLS Z- DLS Z- monomer) (%) (%) (%) ave (nm) PDI ave (nm) PDI ave (nm) PDI Sample A 1 0.267 0 203.7 0.038 453.6 0.086 204.7 0.010 (PNIPAM 3) Sample B 0.2 0.267 0 207.2 0.014 494.6 0.144 209.6 0.031 (PNIPAM 4) Sample C 0 0.267 0 210.9 0.025 513.3 0.151 212.4 0.024 (PNIPAM 5) Sample D 1 — 48.1 553.5 0.104 20230.0 1.000 806.5 1.000 (PNIPAM 6)

[0129] DLS measurements were also performed at varying temperatures from 10° C. to 60° C. and the results obtained on the average particle size of the PNIPAM samples are provided in FIG. 5. It is shown that a higher temperature led to decreased particle size (as expected), thereby demonstrating the temperature responsiveness of the latex particles.

Example 4: Hetero-Coagulation of Organic Polymer Latex Particles (i.e. poly-NIPAM) with Primary Capsule(s)

[0130] In this example, hetero-coagulation experiments were carried out using poly-NIPAM latex particles as the organic polymer latex particles and CTAB stabilized silica capsules as the primary capsule(s).

[0131] Silica capsules dispersion 20.0 mL (10% w/w) was left to stand/allowed to cream in a sealed bottle over a day and then, the water dispersant was removed. The cream was then topped up with D.I. water and redispersed to the initial total volume of 20.0 mL. This process was repeated for another 2 cycles to remove free dissolved CTAB.

[0132] Under the working temperature of 60° C., the washed silica capsules dispersion was then added slowly over 1 min into 20.0 mL of PNIPAM latex dispersion (5% w/w) for heterocoagulation. For this step, the pH of the latex solution is alkaline (around 8.5) and pH of the silica capsule solution is acidic (around 3.2). Therefore, it will be appreciated that the pH of the heterocoagulation step can fluctuate between about 3 to about 9.5. The resulting mixture was then filtered and dispersed in 20.0 mL of D.I water.

[0133] The hybrid capsules obtained after the heterocoagulation step were also further purified. Purification was achieved by allowing the heterocoagulated, film formed hybrid capsules to cream, separating the aqueous layer containing no capsule from below, resuspending again in water by adding water and gentle stirring, stopping the stirring and allowing the hybrid capsules to cream again. This process was repeated 2-3 times to get pure heterocoagulated capsules with no free silica capsule or latex articles. Most of the personal care actives and perfume capsules are lower density and hence this method of creaming may work better for such lower density capsules.

[0134] For capsules that are denser than water, the capsules could be allowed to settle, and a similar procedure could be adopted by removing the top layer and repeating the washing steps.

Dark Field Microscopy of (i) Silica Capsule and (ii) Hetero-Coagulated Silica Capsules With Poly-NIPAM Latex Particles

[0135] Evidence of temperature responsive poly-NIPAM latex particles adsorbing on CTAB stabilized silica capsules was demonstrated by careful optical microscopic analysis at various stages of the adsorption and poly-NIPAM film formation on the surface of the silica capsule.

[0136] In the case of silica microspheres, SEM cannot be used as a characterization tool as microcapsules (e.g. having a size above 50 micrometer (>50 μm)) do not stay/remain stable under high vacuum conditions employed during measurement (e.g. SEM imaging) Therefore, the adsorption and film formation of poly-NIPAM latex particles on silica hollow spheres were demonstrated by dark field microscopy (see FIG. 6B).

[0137] FIG. 6A shows a dark field microscopic image of silica capsule dispersion in water. After heterocoagulation of poly-NIPAM latex particles with silica capsules, a dark field microscopic image was captured for the hetero-coagulated silica capsules with poly-NIPAM latex particles as shown in FIG. 6B. Particle size analysis of the hetero-coagulated silica capsules with poly-NIPAM latex particles using laser scattering shows a monomodal size distribution. This is indicative of a good nano-film formation of poly-NIPAM around the silica capsule structures.

[0138] For the current measurement method, the refractive index of silica was used for determination of the particle size distribution. FIG. 7 shows the particle size distribution of a silica capsule obtained after heterocoagulation. Exact values of the particle size distribution of the heterocoagulated sample shown in FIG. 7 are provided in Table 2 below. A bimodal size distribution is shown, indicating some percentage of aggregation.

TABLE-US-00002 TABLE 2 Particle size distribution of a heterocoagulated sample shown in FIG. 7 Size Volume (μm) in % 0.100 0.111 0.00 0.123 0.00 0.136 0.00 0.151 0.00 0.167 0.00 0.186 0.00 0.206 0.00 0.228 0.00 0.253 0.00 0.280 0.00 0.311 0.00 0.345 0.00 0.382 0.00 0.423 0.00 0.469 0.00 0.520 0.00 0.577 0.00 0.577 0.640 0.00 0.709 0.00 0.786 0.00 0.871 0.00 0.966 0.00 1.071 0.00 1.187 0.00 1.316 0.00 1.459 0.01 1.617 0.06 1.793 0.25 1.988 0.50 2.204 0.76 2.443 1.10 2.708 1.51 3.002 1.97 3.328 2.49 3.328 3.690 3.05 4.090 3.63 4.535 4.20 5.027 4.72 5.573 5.18 6.178 5.54 6.849 5.78 7.593 5.87 8.417 5.80 9.331 5.56 10.344 5.22 11.468 4.74 12.713 4.19 14.093 3.59 15.624 3.01 17.321 2.49 19.201 2.05 19.201 21.286 1.66 23.598 1.37 26.160 1.11 29.001 0.90 32.151 0.75 35.642 0.63 39.512 0.55 43.803 0.50 48.559 0.47 53.832 0.46 59.678 0.45 66.159 0.45 73.343 0.45 81.307 0.46 90.136 0.46 99.924 0.47 110.775 0.49 110.775 122.804 0.50 136.140 0.51 150.923 0.52 167.312 0.53 185.481 0.52 205.622 0.50 227.951 0.47 252.704 0.42 280.145 0.36 310.566 0.29 344.291 0.22 381.678 0.13 423.125 0.06 469.072 0.01 520.009 0.00 576.477 0.00 639.077 0.00 639.077 708.475 0.00 785.406 0.00 870.696 0.00 965.246 0.00 1070.062 0.00 1186.261 0.00 1315.078 0.00 1457.883 0.00 1616.196 0.00 1791.700 0.00 1986.251 0.00 2201.951 0.00 2441.062 0.00 2706.139 0.00 3000.000 0.00

Gravimetric Analysis and Thermogravimetric Analysis of (i) Silica Capsule and (ii) Hetero-Coagulated Silica Capsules With Poly-NIPAM Latex Particles

[0139] There are many ways to utilize the hetero-coagulated silica capsules with poly-NIPAM latex particles and one (ideal) way is to use the material in the form of dispersion in formulations. In this example, the solid content of the material (estimated gravimetrically) is 0.013 g/mL (or 0.014 g/g).

[0140] To determine the content of poly-NIPAM latex layer adsorbed on the silica capsules, thermogravimetric analysis (TGA) was performed on both (i) silica capsule and (ii) hetero-coagulated silica capsules with poly-NIPAM latex particles.

[0141] In FIG. 8A, the TGA result of silica micro capsules shows that the residual amount is 82.5%. After hetero-coagulation of poly-NIPAM latex particles with silica capsules, it is shown in FIG. 8B that the residual amount decreased to 61%. Therefore, this indicated that the content of poly-NIPAM latex adsorbed on the silica capsules is approximately 20%.

[0142] Analysis of the silica capsules vs. poly-NIPAM coated silica capsules using dark field microscopy and TGA proved that the hetero-coagulated silica capsules with poly-NIPAM latex particles synthesized in the examples are spherical micro-capsules having uniform size distribution with approximately 20% temperature responsive poly-NIPAM coating. Poly-NIPAM is also reported to be salt-responsive.

Scanning Electron Microscopy of Sub-20 Micron Hetero-Coagulated Silica Capsules With Poly-NIPAM Latex Particles

[0143] To further prove that the hetero-coagulation was successfully achieved, the inventors performed synthesis of sub-20 micron silica capsules using CTAB as the surfactant, which are not breakable under SEM, i.e. able to withstand the vacuum condition used for SEM imaging

[0144] SEM images were obtained at various stages of the polymer coating process (see FIG. 9A, FIG. 9B and FIG. 9C). Based on the SEM images, it is shown very clearly that the inventors were able to coat a uniform layer of polymer around the silica capsules.

Example 5: Hetero-Coagulation of Organic Polymer Latex Particles (i.e. Polycaprolactone) with Primary Capsule(s)

[0145] In this example, hetero-coagulation experiments were carried out using polycaprolactone particles as the organic polymer latex particles and silica capsules as the primary capsule(s).

[0146] Silica capsules dispersion 20.0 mL (10% w/w) was left to stand/allowed to cream in a sealed bottle over a day and then, the water dispersant was removed. The cream was then topped up with D.I. water and redispersed to the initial total volume of 20.0 mL. This process was repeated for another 2 cycles to remove free dissolved CTAB.

[0147] The washed silica capsules dispersion was then added slowly over 1 min into 20.0 mL of PCL latex dispersion (5% w/w), which may be purchased or made using conventional techniques such as that described in “Nano-emulsion formulation using spontaneous emulsification: solvent, oil and surfactant optimisation”, Fessi, H. et al. Int. J. Pharm. 2004, 280(1-2), 241-251”, the contents of which are fully incorporated by reference. The resulting mixture was then heated at 70° C. for 10 min with stirring and cooled to room temperature. For this step, the pH of the latex solution is alkaline (around 8.5) and pH of the silica capsule solution is acidic (around 3.2). Therefore, it will be appreciated that the pH of the heterocoagulation step can fluctuate between about 3 to about 9.5. It was then filtered and dispersed in 20.0 mL of D.I water.

[0148] The hybrid capsules were also purified using similar methods that were described in Example 4.

Scanning Electron Microscopy of (i) Silica Capsule and (ii) Hetero-Coagulated Silica Capsules With Polycaprolactone Particles

[0149] FIG. 10A shows the SEM image of original silica capsules. The silica capsules were fragile and break under vacuum conditions used for SEM imaging Therefore, only broken films were observed.

[0150] On the other hand, the SEM image of hetero-coagulated silica capsules with polycaprolactone particles (FIG. 10B) shows that the hybrid capsule did not break. As shown, capsules with spherical morphology were observed under SEM conditions, which is indicative of the robustness and stability of the hybrid capsule.

[0151] The examples above demonstrate the successful synthesis of a hybrid capsule by heterocoagulating organic polymer latex particles with a primary capsule. The examples also show that stability of the capsules is enhanced by having an additional layer of polymer around the micron sized capsules such as silica capsules. The results therefore show that the common drawbacks of micron sized capsules (such as capsule breakability and porosity etc.) can be addressed by embodiments of the method disclosed herein.

APPLICATIONS

[0152] Embodiments disclosed herein provide a method that involves applying a heterocoagulation approach and creating a polymer film to impart stability to primary capsules such as silica capsules with actives (which normally have lot of instability issues such as capsule breakability, settling or creaming in water depending on the density of the active).

[0153] The inventors have surprisingly found out that desirable capsules may be produced via a simple heterocoagulation approach to obtain a film of polymer on a shell of a primary capsule such as a silica shell without using any chemical modification, notwithstanding that the primary capsule used may be considered one that is originally unstable (e.g. fragile inorganic capsules such as silica capsules). This is surprising as there was no prior knowledge or indication that such a film coating is possible on a primary capsule surface to reinforce a primary capsule shell, without breaking the micron or submicron sized primary capsule.

[0154] Embodiments of the method are capable of producing hollow capsules (contrast with solid nanoparticles) that are biocompatible, degradable, environmentally benign, chemically and physically stable. For example, hybrid capsules produced by embodiments of the methods disclosed herein are advantageously stable under high vacuum such as the vacuum conditions used for SEM measurements.

[0155] Advantageously, embodiments of method involve the deposition of a polymer film on a primary capsule such as a silica capsule using polymer particles, particularly polymer latex particles, without a crosslinking chemistry or curing agent or organic solvent. For example, embodiments of the methods disclosed herein do not involve free radical chemistry which limits application potential and do not require a chemical reaction such as polymer grafting or surface functionalization (such as surface initiated ATRP) of a silica capsule. As such, embodiments of the methods disclosed herein do not need any block co-polymer (which is more expensive and require synthetically more steps to produce as compared to the polymer latex particles used in embodiments of the method) or controlled radical polymerization. Special silane monomers such as organo alkoxy silanes to render the silica surface hydrophobic are also not required in embodiments of the methods disclosed herein.

[0156] In this regard, as embodiments of the methods disclosed herein do not use coupling chemistry and are based on physical phenomena, sensitive actives can be encapsulated and applied. Advantageously, embodiments, of the methods disclosed herein are suitable encapsulating a wide variety of active compounds, oils, hydrophobic actives/formulations and also for sensitive actives e.g. actives that react with free radicals. As such, embodiments of the methods disclosed herein are suitable for cosmetic/consumer-based applications such as for perfumes or aromatic oils or other consumer-based product encapsulation.

[0157] As compared to chemical-based methods, embodiments of the disclosed method rely primarily on water-based technology without the need to use organic solvents. For example, water-based chemistry may be employed for both silica capsule and latex synthesis. Advantageously, the water-dispersed polymer latex used do not require chemical curing but instead rely on physical curing (e.g. by making use of temperature or pH) of a polymer layer on a primary capsule shell such as silica shell. The water-based polymer latex nanoparticles may then be heterocoagulated on a primary capsule e.g. silica capsule surface and allowing polymer chains to interpenetrate to seal the pores and create a polymer shell on top of the silica hollow sphere. As such, embodiments of the methods disclosed herein are capable of blocking porous channels in primary capsules by coating polymer leading to longer and better protection of the encapsulated material. The hybrid capsules may thus be hermetically sealed unlike in the case of pure silica capsules.

[0158] Embodiments of the methods disclosed herein also versatile. For example, embodiments of the methods disclosed herein are compatible with polymers having favorable film forming properties and wide-ranging polydispersity indexes (including degradable/biodegradable, bioresorbable and/or non-toxic polymers). In one particular example, embodiments of the disclosed method are capable of coating polycaprolactone latex around otherwise breakable silica capsules. Given that polycaprolactone is biodegradable, bioresorbable and non-toxic, cosmetic and even cosmeceutical applications become easy with this approach.

[0159] In embodiments of the disclosed method, the polymer can be varied to generate different properties including stimuli responsive and degradable nature. Embodiments of the method disclosed herein make it possible to introduce multiple functionalities to a capsule easily which allows the method to be adapted as one that has a modular approach. This is possible as embodiments of the disclosed methods do not involve stabilization of droplets by pickering emulsion and thus allow for a variety of functionalities to be possible to be present on the capsule through the ability to use different polymers (including stimuli responsive polymers). As such, the capsules produced by embodiments of the methods disclosed herein may be customised to release their actives at certain predetermined conditions. The benefits offered by embodiments of the disclosed methods in terms of protection of the active and versatility of the release options, make the approach valuable.

[0160] Additionally, embodiments of the methods disclosed herein are also versatile in that they are compatible with primary capsules with or without the structural feature of a mesoporous shell and have the flexibility to work with both micron to submicron sized capsules to accordingly produce micron and submicron particles (e.g. from micro-sized to nano-sized capsule products) with relative ease. Advantageously, embodiments of the method are able to address or ameliorate the challenges faced by primary capsules such as silica microcapsules having nano pores and which typically have difficulty keeping small molecules (like perfume) actives inside the capsule. Advantageously, embodiments of the disclosed method are also able to produce reinforced/strengthened capsules over 50 μM, which are typically brittle and easily break when produced by conventional methods.

[0161] Advantageously, embodiments of the disclosed methods employ physical methods that are simple and scalable. Embodiments of the disclosed methods do not involve coacervation to create a polymer shell around a primary capsule such as a silica capsule to produce a hybrid capsule and do not require calcination to remove a template. Instead, embodiments of the methods disclosed herein use a single polymer latex (and not multiple polymers that is e.g. used in layer by layer polymer assembly around a particle). As this is unlike a layer-by-layer approach which requires several different layers to get the desirable thickness, embodiments of the method can achieve the desirable thickness in one single step and are easily scalable. Accordingly, embodiments of the disclosed method are simpler as compared to complex approaches using hydrogen bonding and layer by layer assembly. In addition, embodiments of the disclosed methods can be scaled up to kilograms and even tons since embodiments of the method depend mainly on shear force for breakdown of actives into droplets and surfactants such as cationic surfactants for stabilization of the droplets.

[0162] Furthermore, embodiments of the disclosed methods do not involve the more complex and less scalable steps of stabilization of droplets by pickering emulsion and then subsequently growing shell on the pickering stabilized emulsion to obtain hollow structures. Instead, embodiments of the disclosed methods involve creating a primary inner core such as an inorganic inner core, for example, a silica inner core, then producing a pickering emulsion using polymer particles, and then curing it on the surface to create a polymer shell, thus obtaining a hybrid capsule by simple steps.

[0163] As compared to known methods that involve in situ polymerization (which can be sort of classified as precipitation polymerization), embodiments of the disclosed method are able to use preformed commercially available functional polymers. As such, embodiments of the disclosed method are able to separate a polymer coating incorporation step from a primary capsule shell (e.g. silica) formation step, thus having more versatility and do not suffer from the shortcomings of an active reacting with the functional polymer. If desired, embodiments of the methods disclosed herein may optionally involve a polymerization step that is done separate in water to form latex particles which are adsorbed onto and cured to form a polymer shell around existing primary capsule shell such as silica shell. This allows a sufficiently distinct polymer layer around a first primary capsule shell such as a first silica shell to be formed and no cross-linking (chemical reaction) is involved in creating a second polymer shell/coating and hence only a physical approach is used for shell formation.

[0164] Advantageously, embodiments of the disclosed methods are capable of preparing an active loaded primary capsule e.g. silica capsule (as opposed to hard solid particle) whilst forming substantially uniform coating around the surface e.g. a silica surface using polymer latex particles (e.g. a reinforced silica shell by physical deposition of preformed polymeric nanoparticles on micron sized silica particles may be obtained). Accordingly, embodiments of the methods disclosed herein are capable of producing capsules with potentially higher stability to high shear compared to capsules in the art.

[0165] Embodiments of the disclosed methods also have high encapsulation efficiency since 20-30 wt % of actives in water can be emulsified and encapsulated in a primary capsule such as silica capsule with almost quantitative efficiency. Upon polymer coating, leakage of the encapsulated actives is substantially prevented and hence the efficiency is retained high.

[0166] Even more advantageously, embodiments of the disclosed methods have high reproducibility (the inventors have performed embodiments of the method reproducibly for more than 5 times in lab scale (1 L total volume)).

[0167] It will be appreciated by a person skilled in the art that other variations and/or modifications may be made to the embodiments disclosed herein without departing from the spirit or scope of the disclosure as broadly described. For example, in the description herein, features of different example embodiments may be mixed, combined, interchanged, incorporated, adopted, modified, included etc. or the like across different example embodiments. The present embodiments are, therefore, to be considered in all respects to be illustrative and not restrictive.