WO2019145731A1

WO2019145731A1 - Microcapsules

Info

Publication number: WO2019145731A1
Application number: PCT/GB2019/050217
Authority: WO
Inventors: Zhibing Zhang; Cong SUI; Jon Preece
Original assignee: The University Of Birmingham
Priority date: 2018-01-25
Filing date: 2019-01-25
Publication date: 2019-08-01

Abstract

A microcapsule (1), the microcapsule (1) comprising a hydrophilic core (11), preferably containing a water-soluble species and/or a suspended species (11a), a first wall (12) surrounding the aqueous core (11) and comprising an inner-most first layer, a second wall (14) comprising an outer-most second layer, and an intervening layer (13) situated between the first wall (12) and the second wall (14).

Description

MICROCAPSULES

This invention relates generally to microcapsules. More specifically, although not exclusively, this invention relates to microcapsules for the encapsulation of hydrophilic materials, methods of making said microcapsules, and uses of said microcapsules.

Encapsulation technology provides a means to entrap active ingredients, which may then be delivered to a target location upon release. A particular example of encapsulation technology is the use of microcapsules. Microcapsules are spherical particles with a diameter of between 50 nm to 2 mm having a peripheral wall (or shell) containing a core substance (Res Pharm Sci. 2010 Jul-Dec; 5(2): 65-77). The core substance may contain active ingredients that may be released, for example, upon fracture or dissolution of the peripheral wall material used to encapsulate the core substance.

Microcapsules generally find use in applications wherein the stability or the life of the core substance may be increased by encapsulation, or wherein controlled release of the core substance is sought, for example, for temporal release, or for release once the microcapsule has reached a specific location. Industrial applications include the use of microcapsules in the pharmaceutical industry, e.g. in drug delivery systems, or alternatively in fast moving consumer goods (FMCGs), e.g. in the controlled release of fragrances or actives in, for example, personal care products, or additionally in the food industry, e.g. for the release of flavour compounds.

It is useful in many industrial applications to be able to control the release profile of the core substance by using different microcapsule designs. The microcapsule may be designed to comprise an encapsulation material that is stable in particular environments, but degrades upon exposure to a particular stimulus, for example, one or more of heat, sheer stress, or change in pH, to release the core substance.

The encapsulation of hydrophobic ingredients is well known. For example, Pan et. al. (Powder Technology, Volume 227, September 2012, Pages 43-50) described the encapsulation of oil-based active ingredients in microcapsules. Additionally, EP1533415A1 describes the encapsulation of fragrance compounds in melamine formaldehyde microcapsules. The microcapsules comprised polymeric walls that are rupturable to allow the fragrance to be released over time. The fragrance components have a ClogioP of between 2.5 and 8 (where P is the n-octanol/water partition coefficient), meaning that the fragrance components are not water soluble.

However, the encapsulation of hydrophilic ingredients, and particularly hydrophilic ingredients with low molar mass, remains a challenge. Specifically, it is difficult to prevent the release of hydrophilic ingredients with low molar mass in an aqueous environment, e.g. pure water. The encapsulation of low molecular weight and hydrophilic compounds would be advantageous for a number of applications, including their use as delivery agents in foods, dentifrices and other personal care products or household products. For example, in cleaning products and detergents such as laundry detergent, it would be advantageous for the active ingredients to be released due to fracture caused by shear stress during the laundry cycle, but for active ingredients contained within intact microcapsules (i.e. those that have not fractured) to remain encapsulated post-wash to prevent skin irritation and damage to the clothes.

Accordingly, a first aspect of the invention provides a microcapsule, the microcapsule comprising an aqueous core containing a water-soluble species, a first wall surrounding the core and comprising an inner-most first layer, a second wall comprising an outer-most second layer, and an intervening layer situated between the first wall and the second wall.

A further aspect of the invention provides a microcapsule, the microcapsule comprising a core, the core comprising a hydrophilic material, for example an aqueous core, for example an aqueous core comprising a water soluble or suspended species, a first wall surrounding the core and comprising an inner-most first layer, a second wall comprising an outer-most second layer, and an intervening layer situated between the first wall and the second wall.

Hydrophilic compounds have tendency to mix with, dissolve in, or be wetted by water. IUPAC defines“hydrophilic” to mean“water loving” and the capacity of a species, e.g. a molecular entity or of a substituent to interact with polar solvents, in particular with water, or with other polar groups.

The core may consist of a hydrophilic material. In embodiments, the core may consist of a first hydrophilic material and may further contain a second species, e.g. a second hydrophilic, i.e. water-soluble species dissolved therein or a species suspended therein. The hydrophilic core may be a solid or a liquid at ambient temperature.

It has been surprisingly found that provision of an intervening layer that is situated between the first wall and the second wall of the microcapsule of the present invention provides a barrier to prevent release of water-soluble species that are situated within the aqueous core, particularly when the water-soluble species comprise one or more low molar mass hydrophilic compounds.

A further aspect of the invention provides a microcapsule, the microcapsule comprising a liquid core and a shell, the shell having at least three layers in an ABC structure, wherein the first and third layers each have a thickness of greater than 0.1 microns.

Advantageously, the use of self-assembly of precursor materials to form the walls, e.g. the first and third layers, enables wall thicknesses of desired thicknesses to be provided without the necessity to use ionically-driven layer-by-layer build up techniques which are time- consuming and thickness limited.

The liquid core may be an aqueous solution or a non-aqueous solution.

The microcapsule comprises an ABC structure with three layers: i.e. or e.g. (i) the first wall; (ii) the intervening layer; and (iii) the second wall. In embodiments, A = C, i.e. the material of the first wall and the material of the second wall are the same type of material. In embodiments, the first wall and the second wall may comprise any suitable material or species that is hydrophilic and capable of forming an interaction with the intervening layer, which may be and preferably is hydrophobic.

The first wall and/or the second wall may comprise a polymer. The polymer of the first wall and the polymer of the second wall may each comprise the same type of polymer, i.e. a polymer comprising the same repeating units. Alternatively, the first wall may comprise a first polymer and the second wall may comprise a second, different, polymer to that of the first wall.

Where the first wall and/or the second wall comprise a polymer, the polymer of the first wall and/or second wall may comprise repeating units of melamine or a melamine derivative, e.g. melamine-formaldehyde polymer. Additionally or alternatively, the polymer of the first wall and/or second wall may comprise one of, or a mixture of, an inorganic material, for example a calcium-based inorganic material, e.g. calcium carbonate, calcium phosphate, calcium silicate, calcium oxide, or a montmorillonite, an attapulgite (APT), a magnetic inorganic material, e.g. FesCU, nickel, and/or copper, carbon, silica, cellulose, a polypeptide, a polyester, a polyamide, a polysaccharide (e.g. chitosan), a polyacrylic acid, a polyacrylate, melamine and/or urea.

In embodiments, the first wall and/or the second wall comprise a polymer that is biocompatible, e.g. a biopolymer. For example, the biocompatible polymer may comprise one or more of a polypeptide and/or a polysaccharide (e.g. chitosan). Preferably, the biocompatible polymer is approved for use in human and non-human animals, for example a biopolymer approved for use by the FDA (US Food and Drugs Administration).

The first wall and/or second wall may comprise a monolayer, e.g. a single chain of polymer. Alternatively, the first wall and/or the second wall may comprise several layers of material, e.g. several polymer chains, which may be cross-linked, for example.

The first wall may be between 0.1 to 0.3 micrometres in thickness. The second wall may be between 0.1 to 0.3 micrometres in thickness. The third wall may be between 0.005 to 0.05 micrometres.

In embodiments, the intervening layer may comprise any suitable material that is hydrophobic. The intervening layer may form, and/or may be capable of forming, an interaction with the first wall and/or the second wall, both of which may be hydrophilic. For example, the intervening layer may be capable of forming an electrostatic interaction, e.g. a hydrogen bonding interaction, with the first wall and/or the second wall. Additionally or alternatively, the intervening layer may be capable of forming a chemical bonding interaction, e.g. an ionic interaction or bond and/or covalent interaction or bond, with the first wall and/or the second wall.

In embodiments, the intervening layer may be capable of forming a chemical bonding interaction with the first wall and/or the second wall when microcapsule is heated to a temperature above ambient temperature, e.g. above 30 °C, 40 °C, 50 °C, 60 °C or above In embodiments, the first wall and the intervening layer, and/or the second wall and the intervening layer, are bonded by one or more of an electrostatic interaction, a covalent bond, and/or an ionic bond.

For example, the intervening layer may comprise a layer of one or more of 1 H,1 H,2H,2H- perfluorodecanethiol (PFDT), palmitic acid, sodium oleate, polyvinylpyrrolidone (PVP), plasma polymerized 1 ,7-octadiene, octadecyltrimethylammonium bromide (ODTMA), dodecyldimethylammonium bromide (DDDMA), dehydrogenated tallow)dimethylammonium chloride, carbon nanotube, stearic acid, octadecylphosphonic acid, trichloromethylsilane (TCMS), dodecanethiol, monoalkyl phosphonic acid, polystyrene, polydimethylsiloxane (PDMS), 3-aminopropyl-triethoxysiloxane (APS), dodecyltrimethoxysilane (DTMS), methyltrimethoxysilane (MTMS), trimethylchlorosilane (TMCS), graphene, graphene oxide, reduced graphene oxide, polydimethylsiloxane (PDMS), polydopamine (PDA) & PFDT, fluoroalkylsilane (FAS), octadecylthiol, T1O2 & n- octadecylthiol, fluorinated-polyacrylate (PFA) & hydrophobic S1O2, PDA & octadecylamine (ODA), methyltrichlorosilane and polypropylene (PP).

The intervening layer may comprise a silane, for example an alkylsilane and/or an arylsilane. The alkylsilane and/or arylsilane may comprise an alkyl group. The alkyl group may comprise a hydrocarbon, e.g. an aliphatic hydrocarbon or a fluorohydrocarbon, the hydrocarbon comprising between 1 to 30 carbon atoms.

The alkylsilane may comprise the structure R^Si-(CH3)_y(Z)4-_x-y where R represents an alkyl group comprising one of a hydrocarbon, an aliphatic hydrocarbon, or a fluorohydrocarbon, of 1 to 30 carbons, and Z is selected from at least one of Br, Cl, F, an alkoxy group having from 1 to 3 carbon atoms or chlorine atoms, or a combination thereof, x is 1 or 2, and y is 0, 1 , or 2.

The alkylsilane may be octadecyltrichlorosilane (OTS), dodecyltrichlorosilane, octyltrichlorosilane, butyltrichlorosilane or a combination thereof.

The intervening layer may comprise a monolayer, for example, a self-assembled monolayer. Wherein the intervening layer comprises a silane, the intervening layer may comprise siloxane moieties, e.g. a self-assembled monolayer of alkylsilane or aryly silane molecules bound by siloxane bonds. The intervening layer may be from 0.5 to 100 nm thick. For example the intervening layer may be from 1 to 10 nm thick.

In embodiments, the first wall may comprise a first moiety, the intervening layer may comprise a second moiety, the first moiety and the second moiety may be capable of interacting with one another, e.g. bonding through intermolecular interactions such as hydrogen bonding, and/or ionic and/or covalent bonding.

Additionally or alternatively, the second wall may comprise a third moiety, the intervening layer may comprise a second moiety. In embodiments, the third moiety of the second wall, and the second moiety of the intervening layer, may be capable of interacting with one another, e.g. bonding through intermolecular interactions such as hydrogen bonding, and/or ionic and/or covalent bonding.

For example, the second moiety of the intervening layer may be capable of forming an electrostatic interaction, e.g. a hydrogen bonding interaction, with the first moiety of the first wall and/or the third moiety of the second wall. Additionally or alternatively, the second moiety of the intervening layer may be capable of forming a chemical bonding interaction, e.g. an ionic interaction or bond and/or covalent interaction or bond, with the first moiety of the first wall and/or the third moiety of the second wall.

Advantageously, the electrostatic interactions and/or the chemical bonding interactions formed between the first wall and the intervening layer act to prevent molecules within the aqueous core containing a water-soluble species of the microcapsule from diffusing out of the microcapsule by providing a barrier, e.g. a polymer-bound hydrophobic barrier. In this way, the aqueous core containing a water-soluble species is released only when the microcapsule is fractured.

The chemical bonding interaction may be formed by heating the microcapsule comprising the first wall and the intervening layer and optionally the second wall to a temperature above ambient temperature.

The first moiety may comprise an amine, and/or an aniline moiety, and/or an alcohol, and/or phenol moiety. The second moiety may comprise a silanol (Si-OH) moiety, and/or an alcohol moiety. Alternatively, the first moiety may comprise a silanol (Si-OH) moiety, and/or an alcohol moiety and the second moiety may comprise an amine, and/or an aniline moiety, and/or an alcohol, and/or phenol moiety.

In embodiments, the microcapsule comprises more than three layers, e.g. a third, fourth, or fifth wall, or a second, third, or fourth intervening layer. The second intervening layer may be situated, for example, between the second wall and the third wall.

The water-soluble species in the aqueous core may be selected from one or more of a bleaching compound, e.g. a hypochlorite salt such as NaOCI, and/or peroxide such as hydrogen peroxide; a flavour and/or fragrance compound, e.g. a water-soluble organic flavour or fragrance compound, or an inorganic salt, for example, NaCI; a pharmaceutical compound, i.e. a drug; an active agent or ingredient for use in household products, such as a cleaning product, or a personal care product, for example, an antimicrobial agent, e.g. zinc chloride (ZnCh) or cetylpyridinium chloride (CPC); a colourant and/or ink; an agrochemical agent such as a herbicide, e.g. glyphosate, and/or a pesticide, and/or a fertiliser, e.g. one or more plant nutrient(s), plant additives, and/or plant food; a phase change material; and/or liquid crystals.

The microcapsule may have a diameter of between 50nm and 1000 micrometres, for example from 500 nm to 500 micrometres, for example, between 2 and 500 micrometres.

The intervening layer of the microcapsule may be hydrophobic, for example, the water contact angle may be 130° or above, for example 140° and above and in embodiments may be 144° or above.

A further aspect of the invention provides a method of fabricating a microcapsule, the method comprising the steps of:

i. fabricating a first wall to encapsulate an aqueous core;

ii. fabricating an intervening layer to encapsulate the first wall;

iii. fabricating a second wall to encapsulate the intervening layer.

Step (i) may comprise emulsifying a polymer starting material in a water-in-oil emulsion and initiating polymerisation to fabricate the first wall. The polymer starting material may be melamine formaldehyde precondensate. The oil in the water-in-oil emulsion may be selected from one or more of a vegetable oil, an organic oil comprising hydrocarbons, and/or a synthetic oil. The water-in-oil emulsion may further comprise an emulsifier, e.g. polyglycerol polyricinoleate (PGPR), Span 80, and/or lecithin.

Initiating the polymerisation reaction to fabricate the first wall may comprise heating the solution and/or changing the pH, e.g. heating the solution to 65 °C, and/or lowering the pH so that the water-in-oil emulsion becomes more acidic. For example, the pH may be lowered by addition of acetic acid to pH 4.3 to initiate polymerisation.

Step (ii) may comprise addition of a hydrophobic compound to the water-in-oil emulsion. The hydrophobic compound may be capable of being hydrolysed in the water-in-oil emulsion. The hydrophobic compound may be capable of forming a monolayer that interacts with, and encapsulates, the first wall to form an intervening layer. For example, the hydrophobic compound may be octadecyltrichlorosilane.

Step (iii) may comprise providing an oil-in-water emulsion to the intervening layer. Step (iii) may further comprise addition of melamine formaldehyde and/or a copolymer, e.g. poly(acrylamide-acrylic) acid to form the second wall. The melamine formaldehyde and/or the copolymer may react in a polymerisation reaction to form the second wall, the second wall encapsulating the intervening layer. The polymerisation reaction may be initiated by heating the solution and/or changing the pH, e.g. heating the solution to 65 °C, and/or lowering the pH so that the oil-in-water emulsion becomes more acidic. Lowering the pH may comprise addition of acetic acid to lower the pH to 4.3 to initiate polymerisation. The polymerisation reaction may be terminated by a change in pH, e.g. an increase in pH by addition of sodium hydroxide.

Advantageously, in some embodiments, heating the solution, e.g. to 65 °C, for example to initiate polymerisation to form the second wall, may additionally initiate one or more chemical bonds, e.g. covalent bonds, to form between the first wall and the intervening layer, and/or initiate one or more chemical bonds, e.g. covalent bonds, to form between the second wall and the intervening layer.

Within the scope of this application it is expressly intended that the various aspects, embodiments, examples and alternatives set out in the preceding paragraphs, in the claims and/or in the following description and drawings, and in particular the individual features thereof, may be taken independently or in any combination. That is, all embodiments and/or features of any embodiment can be combined in any way and/or combination, unless such features are incompatible. For the avoidance of doubt, the terms“may”,“and/or”,“e.g.”,“for example” and any similar term as used herein should be interpreted as non-limiting such that any feature so-described need not be present. Indeed, any combination of optional features is expressly envisaged without departing from the scope of the invention, whether or not these are expressly claimed. The applicant reserves the right to change any originally filed claim or file any new claim accordingly, including the right to amend any originally filed claim to depend from and/or incorporate any feature of any other claim although not originally claimed in that manner.

Embodiments of the invention will now be described by way of example only with reference to the accompanying drawings in which:

Figure 1 is microcapsule, according to an embodiment of the invention;

Figure 2 is a method of fabricating the microcapsule of Figure 1 , according to a further embodiment of the invention;

Figure 3A is a schematic chemical structure of the interaction between a first wall and an intervening layer of a microcapsule, according to embodiments of the invention; Figure 3B is a schematic chemical structure of an alternative interaction between a first wall and an intervening layer of a microcapsule, according to embodiments of the invention;

Figure 4 is a series of SEM images taken during different steps of the method of Figure 2 to fabricate the microcapsules of Example 1 ;

Figure 5 is a series of TEM (HAADF-STEM) and EDS images according to the microcapsules of Example 1 ;

Figure 6 is a series of spectra for the characterisation of the microcapsules of Example 1.

Referring now to Figure 1 , there is shown a microcapsule 1 , according to a first embodiment of the invention. The microcapsule 1 comprises a liquid core 1 1 , preferably an aqueous core 11 , a first wall 12, an intervening layer 13, and a second wall 14. The liquid core 11 may be a solution of an active in a solvent. For example, the core 11 may be an aqueous core 1 1 comprising a water-soluble or suspended substance 1 1a. The microcapsule 1 is round, and may be sphere like or spherical, and comprises successive encapsulated layers, i.e. the first wall 12 is encapsulated by the intervening layer 13, and the intervening layer 13 is encapsulated by the second wall 14. The encapsulated core 11 is encapsulated, i.e. completely enclosed, by the first wall 12. The first wall 12 represents the innermost layer of the microcapsule 1. The intervening layer 13 encapsulates the first wall 12. The second wall 14 encapsulates the intervening layer 13 so that the intervening layer 13 is situated between the first wall 12 and the second wall 14. In this embodiment, the second wall 14 represents the outermost layer.

The encapsulated core 11 comprises a volume of liquid, e.g. water, or a substantially aqueous medium, which is entrapped within the first wall 12. The water-soluble substance 11 a is dissolved or suspended in the volume or water or the substantially aqueous medium of the encapsulated core 11.

Referring now to Figure 2, there is shown a method 2 of fabricating the microcapsule 1 , according to an embodiment of the invention. The method 2 comprises Step (a), Step (b), Step (c), and Step (d). There is shown a water-in-oil emulsion 20, which comprises a polymer starting material 21 and an active ingredient 22 to be encapsulated, an unripened microcapsule 23, which comprises the encapsulated core 11 and an unripened first wall 12a, a first intermediate microcapsule 24, which comprises the first wall 12, a second intermediate microcapsule 25, which comprises the intervening layer 13, and the microcapsule 1 of the present invention, which comprises the second wall 14. In Step (a), the unripened microcapsule 23 is synthesised by self-assembly of the polymer starting material 21 at the interface of the water-in-oil emulsion to form the unripened first wall 12a. This encapsulates the active ingredient 22 within the encapsulated core 11 of the unripened microcapsule 23. In Step (b), the first intermediate microcapsule 24 is formed from the unripened microcapsule 23 by polymerisation of the unripened first wall 12a to form the first wall 12. In Step (c), the second intermediate microcapsule 25 is formed from the first intermediate microcapsule 24 by addition of a hydrophobic compound (not shown) to form the intervening layer 13. The hydrophobic compound (not shown) is added dropwise to form the intervening layer 13, which encapsulates the first wall 13. In Step (d), the microcapsule 1 is formed from the second intermediate microcapsule 25 by polymerisation of further polymer starting material 22 to form the second wall 14, which encapsulates the intervening layer 13.

In embodiments, the first wall 12 and the second wall 14 each comprise a cross-linked network of melamine formaldehyde, and the intervening layer 13 comprises a layer of alkylsilane. The intervening layer 13 is formed by dropwise addition of octadecyltrichlorosilane into the emulsion, which hydrolyses to form a mixture of silanol compounds, which may also oligomerise to form the intervening layer 13, which is a hydrophobic layer, around the first wall 12.

Without wishing to be bound by theory, it is thought that the octadecylsilanetriol of the intervening layer 13 is able to form hydrogen bonds with the melamine formaldehyde of the first wall 12. This creates a hydrophobic barrier to the encapsulated core 11 , wherein water, the water-soluble substance 11a, and other hydrophilic species are repelled. This causes the water-soluble substance 11a to be entrapped within the microcapsule 1 without leakage into the external environment.

Referring now to Figure 3A and 3B, there is shown a schematic chemical structure 3A of a hydrogen bonding interaction 33 between a first wall 31 and an intervening layer 32 of a microcapsule, and a schematic chemical structure 3B of a covalent bond 34 between a first wall 31 and an intervening layer 32 of a microcapsule, according to embodiments of the invention. There is shown a first wall 31 , and intervening layer 32, a hydrogen bonding interaction 33, and a covalent bond 34. In this embodiment, the first wall 31 comprises a layer of melamine formaldehyde polymer, the intervening layer 32 comprises a polymerised layer of alkylsilane. The alkylsilane of the intervening layer 32 comprises an R group, which is an alkyl chain.

In the schematic chemical structure 3A, the first wall 31 and the intervening layer 32 are intermolecularly bonded through the hydrogen bonding interaction 33. In contrast, in the schematic chemical structure 3B, the first wall 31 and the intervening layer 32 are bonded through the covalent bond 34. The covalent bond 34 may be formed from the hydrogen bonding interaction 33 by hydrolysis, i.e. the removal of water. Both bonding mechanisms may be possible in different embodiments of the invention. In embodiments, the intervening layer 32 may form one or more bonds, e.g. a hydrogen bonding interaction, and/or a covalent bond with the second wall, in a like-manner to that described for Figures 3A and 3B.

To further exemplify the invention, reference is also made to the following non-limiting Example.

Example 1 : Synthesis of Microcapsules T

To further exemplify Step (a) and Step (b) shown in Figure 2, the following method was followed.

KCI (0.2 g) and melamine formaldehyde precondensate (MFP, 1 .0 g) were dispersed homogeneously in deionised water (DIW, 2 ml). The pH of the solution was adjusted to 4.3 by addition of acetic acid, which was then emulsified into vegetable oil (200 ml) with polyglycerol polyricinoleate (PGPR, 0.2 g) at 800 rpm overnight. The temperature was raised to 60 °C for 1 h at the same stirring conditions and the temperature was then increased to 65 °C, heating for 4 h at a stirring speed of 1000 rpm. The polymerisation process was finally terminated by adding NaOH solution (1 M, 1 ml) at a stirring speed of 2000 rpm for 30 min. First intermediate microcapsule 24’ was produced (MF-KCI microcapsules).

To further exemplify Step (c) shown in Figure 2, the following method was followed.

Octadecyltrichlorosilane (OTS, 1 ml) was added dropwise into the above emulsion at a stirring speed of 2000 rpm for 30 min. The microcapsules were harvested by removing the free oil via centrifugation (8000 rpm, 2 min). Second intermediate microcapsule 25’ was produced (MF-OTS- KCI microcapsules).

To further exemplify Step (d) shown in Figure 2, the following method was followed.

The melamine formaldehyde precondensate (5.0 g), formaldehyde solution (37% (aq.) w/w, 3 ml) and copolymer (poly(acrylamide-acrylic acid), 1 .16 g) were dissolved in DIW (140 ml) at a stirring speed of 600 rpm for 105 min at pH 4.3 adjusted by acetic acid at room temperature. Half amount of the formed MF-OTS-KCI microcapsules oil slurry was poured into the above aqueous solution and homogenized at a speed of 2100 rpm for 30 min, forming an oil/water emulsion. The formed emulsion was then stirred at 600 rpm for 30 min before raising the temperature to 65 °C for 4 h. The microcapsules dispersion was then cooled down to room temperature and the polymerisation was terminated by changing pH to 12 via adding NaOH solution (1 M). The obtained microcapsules were harvested by centrifugation (8000 rpm, 2 min) and washed by DIW for 3 times. The formed microcapsules T were dried in vacuum drier (MF-OTS-MF-KCI microcapsules). In the Example, Potassium chloride (KCI) was used as a model active ingredient for encapsulation within microcapsule T.

Referring now to Figure 4, there is shown a series of SEM (scanning electron microscope) images 4 taken during different steps of the method 2 of Figure 2, according to Example 1 of the invention. There is shown a first SEM image 4A of the unripened microcapsule 23’, a second SEM image 4B of the first intermediate microcapsule 24’, a third SEM image 4C of the second intermediate microcapsule 25’, and a fourth SEM image 4D of the microcapsule T, according to examples of the invention. All SEM images were recorded on a Zeiss Merlin Compact instrument. As this is a specific example of the invention, the same numeric indicators will be used but distinguished by use of a prime Q.

The unripened microcapsules 23’ shown in the first SEM image 4A were formed during Step (a) of Figure 2 and via self-assembly of melamine formaldehyde precondensate after being emulsified overnight. The first intermediate microcapsule 24’ shown in the second SEM image 4B was formed during Step (b) of Figure 2. The first intermediate microcapsule 24’ comprises the first wall 12’, and the first wall 12’ comprises polymerised or‘ripened’ melamine formaldehyde, which displayed a spherical shape with a smooth surface.

The second intermediate microcapsule 25’ shown in the third SEM image 4C was formed during Step (c) of Figure 2. The second intermediate microcapsule 25’ comprises the intervening layer 13’, which in this example is a layer of self-assembled octadecyltrichlorosilane.

Without wishing to be bound by theory, it is thought that octadecyltrichlorosilane is hydrolysed by the water in the emulsion, which enables self-assembly of a monolayer onto the surface of the first intermediate microcapsule 24’ via self-condensation reactions and/or intermolecular interactions, e.g. hydrogen bonding and/or covalent bonding, with moieties of the melamine formaldehyde polymer of the first wall 12’, to form the intervening layer 13’ of the second intermediate microcapsule 25’.

The second intermediate microcapsule 25 comprises a relatively rough surface, as shown in the third SEM image 4C. A water contact angle of 144° was recorded (shown in image 4C as an inset image 40) for the second intermediate microcapsule 25’ as a measurement of the hydrophobicity of the intervening layer 13’ of the second intermediate microcapsule 25’.

The microcapsule T shown in the fourth SEM image 4D was formed during Step (d) of Figure 2. The microcapsule T comprises the second wall 14’, which was formed during polymerisation of melamine formaldehyde precondensate. The fourth SEM image 4D shows that the microcapsules T were well dispersed in water.

Referring now to Figure 5, there is shown a series of images 5 according to Example 1 of the invention. There is shown an image 5A from a high-angle annular dark field scanning TEM (HAADF-STEM). There is also shown a series of images 5B (carbon), 5C (nitrogen), 5D (silicon), 5E (chlorine), 5F (potassium), and 5G (oxygen) from an energy dispersive spectrometer (EDS) mapping performed on a field emission high resolution transmission electron microscope (FEI, Talos F200X). The series of images 5 confirm the element distributions of the microcapsules T according to Example 1 of the invention.

The images 5B (carbon), 5C (nitrogen), and 5G (oxygen) represent the formation of the melamine formaldehyde polymer of the second wall 14’ (shown in Figure 4), and the images 5D (silicon) and 5E (chlorine) reveal the embedded hydrolysed octadecyltrichlorosilane of the intervening layer 13’ (shown in Figure 4). As shown in image 5D, the widespread Si element indicates the attached, i.e. bound, hydrolysed octadecyltrichlorosilane of the intervening layer 13’. As shown in image 5F, the concentrations of K⁺ ions are below the minimum detection limit.

Referring also to Figure 6, there is shown a series of spectra 6 for the characterisation of the microcapsules T of Example 1. There is shown a Fourier-transform infrared (FT-IR) spectra 6A, a series of thermogravimetric analysis (TGA) curves 6B, and an X-ray photoelectron spectroscopy (XPS) spectra 6C.

The FT-IR spectra 6A was recorded on a Thermo Nicolet 8700 instrument, from 4000 to 400 cm ¹. The TGA curves 6B were recorded at a heating rate of 10 °C min ¹ under nitrogen flow by thermogravimetric analysis (TGA, SDT Q600) equipment. The XPS spectra 6C was measured on a Thermo ESCALAB 250 high-performance electron spectrometer equipped with monochromatized Al Ka (hv = 1486.7 eV) as the excitation source. Referring first to the FT-IR spectra 6A, there is shown an FT-IR spectrum 61 of the first intermediate microcapsule 24’ of Example 1 , an FT-IR spectrum 62 of the second intermediate microcapsule 25’ of Example 1 , and an FT-IR spectrum 63 of the microcapsule T according to Example 1.

The FT-IR spectrum 63 shows absorption bands of N-H stretching vibration at around 3400, 1560 and 813 cm^-1 , the C-N stretching at around 1358 cm^-1 , the C-H stretching at around 2925 and 1 164 cm^-1 and the methylol at roughly 1010 cm^-1 , which are the characteristic stretches of melamine formaldehyde and the copolymer (poly(acrylamide-acrylic acid). The FT-IR spectrum 62 shows bands at around 1630, 2850 and 2920 cm^-1 represent the presence of the C-H groups of the octadecyltrichlorosilane of the second intermediate microcapsule 25’.

Referring now to the TGA curves 6B, there is shown a TGA curve 64 of the first intermediate microcapsule 24’ of Example 1 , a TGA curve 65 of the second intermediate microcapsule 25’ of Example 1 , and a TGA curve 66 of the microcapsule T according to Example 1.

In TGA curves 64 and 65, the weight loss before 100 °C was attributed to the water evaporation and the weight loss between 300 °C and 370 °C was assigned to the degradation of the first wall 12’ comprising melamine formaldehyde polymer. The weight loss in the region 370-600 °C corresponded to the octadecyltrichlorosilane degradation as shown in the TGA curve 65 of the second intermediate microcapsules 25’. The TGA curve 66 of the microcapsule T displays an overlapping weight loss with the TGA curve 65, of melamine formaldehyde polymer, octadecyltrichlorosilane and copolymer poly(acrylamide- acrylic acid) from 300 °C to 700 °C.

Advantageously, the microcapsules T displayed a no release of K⁺ ions after they were immersed in water for a month under continuous stirring at room temperature, while the first intermediate microcapsules 24’ showed a comparatively faster release (<1 h) under the same condition. The embedded hydrophobic octadecyltrichlorosilane of the intervening layer 15’ offered a highly effective barrier to prevent the ions from releasing out in the aqueous environment.

Without wishing to be bound by theory, it is thought that the intervening layer 13, which is highly hydrophobic, prevents release of the low molar mass hydrophilic encapsulated substance, e.g. KCI from the microcapsule. The intermolecular bonding, e.g. the hydrogen bonding shown in Figure 3A, between in the first wall 12’ and the intervening layer 13’ enables the microcapsule T of the present invention to be robust towards sheer stress to prevent fracture, and also prevents osmotic movement of the low molar mass hydrophilic encapsulated substance from the encapsulated core 1 T of the microcapsule T, to the external environment. Additionally, the second wall 14’ provides an additional layer of protection to the microcapsule T, which prevent damage to the intervening layer 13’ and/or enhances the dispersibility of the microcapsule T.

Referring now to the XPS spectra 6C, there is shown an XPS spectrum 67 of the first intermediate microcapsule 24’ of Example 1 , an XPS spectrum 68 of the second intermediate microcapsule 25’ of Example 1 , and an XPS spectrum 69 of the microcapsule T according to Example 1.

The XPS spectrum 67 display peaks for C, N, O, K and Cl, representing the first wall 12’ comprising melamine formaldehyde, and the aqueous core containing potassium chloride. The XPS spectra 68 shows peaks for Si and strong C peaks, revealing the coating of hydrolysed octadecyltrichlorosilane of the intervening layer 13’ of the second intermediate microcapsule 25’. The XPS spectra 69 shows C, N and O peaks for the microcapsules T, which are present in the second wall 14’ comprising melamine formaldehyde and the copolymer (poly(acrylamide-acrylic acid).

It will be appreciated by those skilled in the art that several variations to the aforementioned embodiments are envisaged without departing from the scope of the invention. For example, the first wall and the second wall need not comprise the same material, e.g. the first wall may comprise a first polymer, and the second wall may comprise a second, different polymer. Additionally, the design of the microcapsule, for example, the first and second wall thickness, and the materials used to fabricate the microcapsule may be selected to prevent release of a specific active ingredient. The thickness of the first and/or second wall may be designed and selected according to the molar mass of the active ingredient and its release profile from the microcapsule. Alternatively, the microcapsule may be designed to enable release of the encapsulated active ingredient at a specific time, and/or in the presence of a specific stimulus. Additionally, the microcapsule may comprise a third wall, or a second intervening layer, depending upon the application. The microcapsules of the invention may be used in the food, personal care, cleaning product or other industries, depending upon the core material selected.

It will also be appreciated by those skilled in the art that any number of combinations of the aforementioned features and/or those shown in the appended drawings provide clear advantages over the prior art and are therefore within the scope of the invention described herein.

Claims

1. A microcapsule, the microcapsule comprising a hydrophilic core, for example an aqueous core containing a water-soluble or suspended species, a first wall surrounding the aqueous core and comprising an inner-most first layer, a second wall comprising an outer-most second layer, and an intervening layer situated between the first wall and the second wall.

2. A microcapsule according to Claim 1 , wherein the first wall and/or the second wall comprise(s) a polymer.

3. A microcapsule according to Claim 2, wherein the first wall and the second wall each comprise a polymer, and each polymer comprises the same repeating units.

4. A microcapsule according to Claims 2 or 3, wherein the first wall and/or the second wall comprise(s) repeating units of melamine/urea or a melamine derivative, e.g. melamine formaldehyde.

5. A microcapsule according to any preceding Claim, wherein the first wall is 0.1 to 0.3 micrometres in thickness.

6. A microcapsule according to any preceding Claim, wherein the second wall is 0.1 to 0.3 micrometres in thickness.

7. A microcapsule according to any preceding Claim, wherein the intervening layer comprises a layer of a hydrophobic species.

8. A microcapsule according to any preceding Claim, wherein the intervening layer comprises a monolayer, for example, a self-assembled monolayer.

9. A microcapsule according to any preceding Claim, wherein the intervening layer comprises an alkylsilane, the alkylsilane comprising an alkyl group, the alkyl group comprising a hydrocarbon, e.g. an aliphatic hydrocarbon or a fluorohydrocarbon, the hydrocarbon comprising between 1 to 30 carbon atoms.

10. A microcapsule according to any preceding Claim, wherein the intervening layer comprises an alkylsilane, the alkylsilane comprising the structure R^Si-(CH3)_y(Z)4-_x-y where R is the alkyl group comprising one of a hydrocarbon, an aliphatic hydrocarbon, or a fluorohydrocarbon, of 1 to 30 carbons, and Z is selected from at least one of Br, Cl, F, an alkoxy group having from 1 to 3 carbon atoms or chlorine atoms, or a combination thereof, x is 1 or 2, and y is 0, 1 , or 2.

11. A microcapsule according to any preceding Claim, wherein the first wall comprises a first moiety, the intervening layer comprises a second moiety, the first moiety and the second moiety being capable of chemically interacting with one another, e.g. bonding through intermolecular interactions such as hydrogen bonding, and/or ionic and/or covalent bonding.

12. A microcapsule according to any preceding Claim, wherein the second wall comprises a first moiety, the intervening layer comprises a second or third moiety, the first moiety and the second or third moiety being capable of chemically interacting with one another, e.g. bonding through intermolecular interactions such as hydrogen bonding, and/or ionic and/or covalent bonding.

13. A microcapsule according to any preceding Claim, wherein the water-soluble species is selected from one or more of a bleaching compound, e.g. a hypochlorite salt such as NaOCI, and/or peroxide such as hydrogen peroxide; a flavour and/or fragrance compound, e.g. a water-soluble organic flavour or fragrance compound, or an inorganic salt, for example, NaCI; a pharmaceutical compound, i.e. a drug.

14. A microcapsule according to any preceding Claim, wherein the diameter of the microcapsule is between 50 nm and 1000 micrometres, for example 500nm to 500 micrometres.

15. A microcapsule according to any preceding Claim, wherein the water contact angle of the intervening layer of the microcapsule is 130° or above, for example 140° or above, and preferably 144° or above.

16. A microcapsule according to any preceding Claim, wherein when located in water and subjected to continuous stirring for at least 1 week no release of the water soluble or suspended species is detected.

17. A method of fabricating a microcapsule, the method comprising:

i. fabricating a first wall to encapsulate a liquid core, preferably an aqueous core;

ii. fabricating an intervening layer to encapsulate the first wall;

iii. fabricating a second wall to encapsulate the intervening layer.

18. A method according to Claim 17, wherein step (i) comprises emulsifying a polymer starting material in a water-in-oil emulsion and initiating polymerisation to fabricate the first wall.

19. A method according to Claim 17 or 18, wherein the polymer starting material is melamine formaldehyde precondensate.

20. A method according to Claims 17, 18 or 19, wherein the oil is selected from one or more of a vegetable oil, an organic oil comprising hydrocarbons, and/or a synthetic oil.

21. A method according to any one of Claims 17 to 20, further comprising an emulsifier, e.g. polyglycerol polyricinoleate (PGPR), Span 80 and/or lecithin.

22. A method according to any one of Claims 17 to 21 , wherein initiating polymerisation comprises heating the solution and/or changing the pH, e.g. heating the solution to above 60°C, for example to 65 °C, and/or lowering the pH so that the water-in-oil emulsion becomes more acidic.

23. A method according to Claim 22, wherein lowering the pH comprises addition of acetic acid.

24. A method according to any one of Claims 17 to 23, wherein step (ii) comprises addition of a hydrophobic compound to the water-in-oil emulsion.

25. A method according to Claim 24, wherein the hydrophobic compound is capable of being hydrolysed in the water-in-oil emulsion.

26. A method according to Claim 24 or 25, wherein the hydrophobic compound is capable of forming a monolayer that interacts with, and encapsulates, the first wall.

27. A method according to Claim 26, wherein the hydrophobic compound is octadecyltrichlorosilane.

28. A method according to Claim 17 to 27, wherein step (iii) comprises providing an oil- in-water emulsion to the intervening layer.

29. A method according to any of Claims 17 to 28, wherein step (iii) comprises addition of melamine formaldehyde and/or a copolymer, e.g. poly(acrylamide-acrylic acid to form the second wall.

30. A method according to Claim 29, wherein the melamine formaldehyde and/or the copolymer react in a polymerisation reaction to form the second wall, the second wall encapsulating the intervening layer, the polymerisation reaction being initiated by heating the solution and/or changing the pH, e.g. heating the solution to 65 °C, and/or lowering the pH so that the oil-in-water emulsion becomes more acidic.

31. A method according to Claim 30, wherein lowering the pH comprises addition of acetic acid.

32. A method according to Claim 30 or 31 , wherein the polymerisation reaction is terminated by a change in pH, e.g. an increase in pH by addition of sodium hydroxide.

33. A method according to any of Claims 17 to 32, comprising forming or causing to form an interaction between the intervening layer and the first wall and/or second wall.

34. A microcapsule as claimed in any of Claims 1 to 16, wherein the intervening layer and the first wall and/or second wall are bonded together.

35. A microcapsule according to Claim 34, wherein the intervening layer and the first wall and/or second wall are hydrogen, ionically or covalently bonded together.