Process for preparing microcapsules and microcapsule compositions

Abstract

A process for encapsulating an agrochemical in a biodegradable capsule comprising the complex coacervation of gelatin and a carboxylated polysaccharide. The process comprises forming an emulsion of an aqueous phase comprising at least one Pickering emulsifier and an oil phase comprising the agrochemical. The process is particularly suitable for forming biodegradable microcapsules of prosulfocarb which exhibit delayed release of the agrochemical.

Description

[0001] 111636-FF (83209) 1

[0002] Process for preparing microcapsules and microcapsule compositions

[0003] Technical Field

[0004] This invention relates to a process for preparing biodegradable microcapsules and the uses of the prepared microcapsules.

[0005] Microencapsulation is known in many fields of technology. In the agrochemical field, microencapsulation can be beneficial for example for controlling the rate of release of the active ingredient, to ensure chemical stability of the active ingredient, and to protect the operators from exposure to the active ingredients. The commonly employed process for preparing microcapsules in the agrochemical field is the use of oil-soluble monomers selected from diisocyanates and polyisocyanates and then reacting these with water or with water-soluble diamines and polyamines at the oil-water interface of oil-water emulsions. This leads then to the formation of polyurea capsule walls. Such encapsulation technology in the formulation of agrochemical active ingredients is well known to those skilled in the art (see, for example, P.J. Mulqueen in "Chemistry and Technology of Agrochemical Formulations", D.A. Knowles, editor, Kluwer Academic Publishers, 1998, pages 132-147).

[0006] Sustainability of agrochemical formulations has become an important target in the agrochemical field. The target is to develop products with low environmental impact. As part of this, the biodegradability of microplastics has become an important topic. Polyurea based microcapsules, as used in many agrochemical formulations, are not biodegradable and pose an environmental challenge. Hence, there is a need to provide new processes for preparing microcapsules which are biodegradable.

[0007] The present inventors have identified prosulfocarb as an example of an agrochemical for which a reduction in volatility by encapsulation can be beneficial to reduce loss of this agrochemical from soil and plants during field applications and moreover, which needs to be of a biodegradable microcapsule type for some markets beyond 2030. WO2023 / 094236 seeks to address some of the above issues identified in the art. Inter alia, the application discloses encapsulating an agrochemical in a biodegradable capsule comprising the complex coacervation of gelatin and a carboxylated polysaccharide.

[0008] However, the present inventors have found that the process of WO2023 / 094236 is less effective for forming microcapsules comprising certain active ingredients such as prosulfocarb and S-metolachlor. In particular, the failure to effectively encapsulate all of the prosulfocarb during the complex coacervation process leads to the loss of the capsule structure upon drying and subsequently, the sub-optimal capsule formation provides no benefit to volatility control and as a result, rapid release rates of the prosulfocarb active ingredient.

[0009] It is the purpose of this invention to provide an improved process for preparing biodegradable microcapsules e.g. starting from oil-in-water emulsions. This process enables the preparation of biodegradable microcapsules by forming a barrier at the oilwater interface of an emulsion. A further purpose of the invention is to provide biodegradable microcapsule compositions with desirable properties, such as the size distribution, storage stability, ease of handling etc.

[0010] The term "biodegradable" is defined as meaning a compound which passes the OECD Guidelines for the Testing of Chemicals, test no. 301 (OECD 301 test). In particular, a compound which is "biodegradable" is defined as a compound which demonstrates at least 30%, preferably more than 40%, more preferably more than 50% and most preferably more than 60% mineralisation measured as evolved CO2 or consumed O2 in 28 days, wherein the mineralisation is measured according to test methods OECD TG 301 B, C, D, F, or OECD TG 310.

[0011] ‘Carboxylated polysaccharide' includes both polysaccharides that naturally contain carboxylic acid groups and those that have been chemically modified to contain the same.

[0012] The terms "agrochemical" and "agrochemically active ingredient" and “active ingredient” are used herein interchangeably, and include herbicides, insecticides, nematicides, molluscicides, fungicides, plant growth regulators and safeners; preferably herbicides, insecticides and fungicides. "Complex coacervation" itself is defined as the complexation between two oppositely charged polyelectrolytes. of Invention

[0013] Accordingly, a first aspect of the invention provides a process for encapsulating an agrochemical in a biodegradable capsule comprising the complex coacervation of gelatin and a carboxylated polysaccharide. The process may comprise forming an emulsion of an aqueous phase comprising at least one Pickering emulsifier and an oil phase comprising the agrochemical.

[0014] The agrochemical may comprise one or more of herbicides, insecticides, nematicides, molluscicides, fungicides, plant growth regulators and safeners. Preferably, the agrochemical comprises one or more of herbicides, insecticides, and fungicides and is present in an amount of 0.01 to 60% by weight of the final formulation. The agrochemical may comprise at least 0.1%, 0.5%, 1 %, 2%, 4%, 5%, 6%, 8%, 10%, 12%, 14%, 15%, 16%, 18%, 20%, 22%, 24%, 25%, 26%, 28%, 30%, 32%, 34%, 35%, 36%, 38%, 40%, 42%, 44%, 45%, 46%, 48%, 50%, 52%, 54%, 55%, 56%, or 58% by weight of the final formulation. The agrochemical may comprise less than 60%, 58%, 56%, 55%, 54%, 52%, 50%, 48%, 46%, 45%, 44%, 42%, 40%, 38%, 36%, 35%, 34%, 32%, 30%, 28%, 26%, 25%, 24%, 22%, 20%, 18%, 16%, 15%, 14%, 12%, 10%, 8%, 6%, 5%, 4%, 2%, or 1% by weight of the final formulation. In one series of embodiments, the agrochemical comprises 20% to 40% by weight of the final formulation.

[0015] The agrochemical may comprise one or more of Prosulfocarb, S-metolachlor, Lambda- cyhalothrin, and / or Tefluthrin. In a preferred series of embodiments, the agrochemical comprises Prosulfocarb.

[0016] The emulsion may be an oil-in-water emulsion.

[0017] The oil phase may comprise a solvent and / or carrier fluid. The solvent and / or carrier fluid may be an aromatic solvent or carrier fluid. The solvent and / or carrier fluid may comprise benzyl benzoate and / or an alkylated naphthalene. The benzyl benzoate may comprise one or more of Ascabin™, Ascabiol™, Ascarbin™, and / or Tenutex™. The alkylated naphthalene may comprise Solvesso™ 200 and / or Aromatic™ 200 (ExxonMobil™ Corporation). The solvent and / or carrier fluid may comprise up to 30% by weight of the oil phase. For example, the solvent and / or carrier fluid may comprise at least 5%, 10%, 15%, 20% or 25% by weight of the oil phase. The solvent and / or carrier fluid may comprise less than 30%, 25%, 20%, 15%, 10% or 5% by weight of the oil phase. In a preferred series of embodiments, the solvent and / or carrier fluid may comprise 20% to 30% by weight of the oil phase.

[0018] The Pickering emulsifier may be present in an amount of 0.01 to 5% by weight of the emulsion. As used herein, the term Pickering emulsifier is intended to refer to surface active particulate materials. The Pickering emulsifier may comprise at least 0.01%, 0.05%, 0.1 %, 0.2%, 0.4%, 0.5%, 0.6%, 0.8%, 1%, 1.2%, 1.4%, 1.5%, 1.6%, 1.8%, 2.0%, 2.2%, 2.4%, 2.5%, 2.6%, 2.8%, 3%, 3.5%, 4%, or 4.5% by weight of the emulsion. The Pickering emulsifier may comprise less than 5%, 4.5%, 4%, 3.5%, 3%, 2.8%, 2.6%, 2.5%, 2.4%, 2.2%, 2%, 1.8%, 1.6%, 1.5%, 1.4%, 1.2%, 1 %, 0.8%, 0.6%, 0.5%, 0.4%, 0.2% or 0.1% by weight of the emulsion.

[0019] The Pickering emulsifier may comprise at least 0.01%, 0.05%, 0.1 %, 0.2%, 0.4%, 0.5%, 0.6%, 0.8%, or 1% of the final formulation. The Pickering emulsifier may comprise less than 1%, 0.8%, 0.6%, 0.5%, 0.4%, 0.2%, 0.1 %, or 0.05% by weight of the final formulation. In one series of embodiments, the Pickering emulsifier comprises 0.3% to 0.6% by weight of the final formulation.

[0020] The Pickering emulsifier may comprise a Ci6-silyl-coated fumed silica and / or amine- modified kaolin clay. The amine-modified kaolin clay may comprise an amino-silane modified kaolin clay e.g. in ultrafine tabular form. The Pickering emulsifier may comprise Aerosil® R816 and / or Imerys® RLO 7645. Preferably, the Pickering emulsifier may comprise Aerosil® R816.

[0021] The gelatin may be present within, or added to, the aqueous phase prior to the formation of the emulsion. Alternatively, the process may comprise adding the gelatin to the emulsion. The process may comprise adding an aqueous solution of gelatin to aqueous phase or the emulsion. The gelatin may comprise gelatin B.

[0022] The gelatin may be present in an amount of 0.5% to 6% by weight of the final formulation. The gelatin may comprise at least 0.5%, 0.6%, 0.8%, 1%, 1.2%, 1.4%, 1.5%, 1.6%, 1.8%, 2.0%, 2.2%, 2.4%, 2.5%, 2.6%, 2.8%, 3%, 3.5%, 4%, 4.5%, 5%, or 5.5% by weight of the final formulation. The gelatin may comprise less than 6%, 5.5%, 5%, 4.5%, 4%, 3.5%, 3%, 2.8%, 2.6%, 2.5%, 2.4%, 2.2%, 2%, 1.8%, 1.6%, 1.5%, 1.4%, 1.2%, 1%, 0.8%, or 0.6% by weight of the final formulation. In one series of embodiments, the gelatin comprises 0.5% to 2% by weight of the final formulation. As used herein, the weight percentages refer to the dry weight of the gelatin, excluding any water or organic solvent.

[0023] Forming the emulsion may comprise combining the oil phase and the water phase under high-shear mixing. For example, forming the emulsion may comprise adding the oil phase to the water phase under high-shear mixing. As used herein, the term high-shear is intended to refer to shear rates of 100s'1or greater, for example 100-10,000s'1. In some embodiments, the shear rate may be at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350s'1or greater. In some embodiments, the high-shear mixing may be performed at 6000rpm or greater, and / or having a mixer tip speed of at least 5m / s. In some embodiments, the high-shear mixing may be performed at 6, 000-21 , OOOrpm e.g. at 7,000- 20,000rpm, 8,000-15, OOOrpm, and / or 9, 000-10, OOOrpm. In some embodiments, the high- shear mixing may have a mixer tip speed of 5-19ms'1, for example, 6-19, 7-15, and / or 8-12 ms'1. The high-shear mixing may be carried out for 1-120 seconds, for example, 10-110, 20-100, 30-90, 40-80, 50-70 or for 60 seconds. In some embodiments, the high-shear mixing may be carried out for 30-60 seconds e.g. 40-50 seconds. In some embodiments, the high-shear mixing speed, tip speed, time, and / or shear-rate may be varied throughout the process depending on the physical properties of the composition being mixed. It will be understood that end points of ranges herein are intended to be combined in any manner.

[0024] The process may further comprise adding a carboxylated polysaccharide to the emulsion. The process may further comprise adding a crosslinker. The process may thereby form a polymer microcapsule at the oil-water phase boundary.

[0025] The carboxylated polysaccharide may be present in an amount of 0.1% to 3% by weight of the final formulation. The carboxylated polysaccharide may comprise at least 0.1%, 0.2%, 0.4%, 0.5%, 0.6%, 0.8%, 1%, 1.2%, 1.4%, 1.5%, 1.6%, 1.8%, 2.0%, 2.2%, 2.4%, 2.5%, 2.6%, or 2.8% by weight of the final composition. The carboxylated polysaccharide may comprise less than 3%, 2.8%, 2.6%, 2.5%, 2.4%, 2.2%, 2%, 1.8%, 1.6%, 1.5%, 1.4%, 1.2%, 1%, 0.8%, 0.6%, 0.5%, 0.4%, or 0.2% by weight of the emulsion. As used herein, the weight percentages refer to the dry weight of the carboxylated polysaccharide, excluding any water or organic solvent. The carboxylated polysaccharide may be selected from one or more of: gum Arabic, sodium alginate, and carboxymethyl cellulose. Preferably only one carboxylated polysaccharide is used. In a preferred series of embodiments, the carboxylated polysaccharide comprises carboxymethyl cellulose.

[0026] The carboxylated polysaccharide may comprise an aqueous solution e.g. adding a carboxylated polysaccharide to the emulsion may comprise adding an aqueous solution of carboxylated polysaccharide to the emulsion. The addition of the carboxylated polysaccharide to the emulsion may be carried out under acidic conditions. In some embodiments, the pH of the emulsion may be adjusted after the addition of the carboxylated polysaccharide e.g. to enable the complex coacervation. In some embodiments, the pH may be reduced. The process may comprise adding the carboxylated polysaccharide and subsequently acidifying the conditions.

[0027] The process may comprise a high-shear homogenisation step after adding the carboxylated polysaccharide. As used herein, the term high-shear is intended to refer to shear rates of 100s-1or greater, for example 100-10,000s-1. The high-shear homogenisation may be performed at 6000rpm or greater, and / or having a mixer tip speed of at least 5m / s. In some embodiments, the shear rate may be at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350s-1or greater. In some embodiments, the high-shear mixing may be performed at 6000rpm or greater, and / or having a mixer tip speed of at least 5m / s. In some embodiments, the high-shear mixing may be performed at 6, 000-21 , OOOrpm e.g. at 7,000- 20,000rpm, 8,000-15, OOOrpm, and / or 9,000-10, OOOrpm. In some embodiments, the high- shear mixing may have a mixer tip speed of 5-19ms-1, for example, 6-19, 7-15, and / or 8-12 ms-1. The high-shear mixing may be carried out for 1-120 seconds, for example, 10-110, 20-100, 30-90, 40-80, 50-70 or for 60 seconds. In some embodiments, the high-shear mixing may be carried out for 30-60 seconds e.g. 40-50 seconds. In some embodiments, the high-shear mixing speed, tip speed, time, and / or shear-rate may be varied throughout the process depending on the physical properties of the composition being mixed. It will be understood that end points of ranges herein are intended to be combined in any manner.

[0028] The crosslinker may be selected from polyaldehydes, polyacids, polyphenols, and aldose sugars. In a preferred embodiment, the crosslinker comprises glutaraldehyde. The crosslinker may be present in an amount of 0.0001 to 2% by weight of the final formulation. The crosslinker may comprise at least 0.0001%, 0.001 %, 0.01 % 0.1%, 0.2%, 0.4%, 0.5%, 0.6%, 0.8%, 1%, 1.2%, 1.4%, 1.5%, 1.6%, 1.8%, or 2.0% by weight of the final composition. The crosslinker may comprise less than 2%, 1.8%, 1.6%, 1.5%, 1.4%, 1.2%, 1%, 0.8%, 0.6%, 0.5%, 0.4%, 0.2%, 0.1 %, 0.01 % or 0.001 % by weight of the final composition.

[0029] The capsules may have an average diameter of less than 30pm, 25 pm, 20 pm, 15 pm, 10 pm, or 5 microns. The average diameter may comprise the Dso diameter, or more preferably, the D(4,3) diameter. The average diameter may be between 10 pm and 30 pm e.g. 15 pm and 25 pm. The capsules may exhibit controlled release e.g. of the agrochemical.

[0030] According to a second aspect of the invention there is provided a composition comprising a microcapsule prepared by the method described herein and / or with reference to the first aspect.

[0031] According to a third aspect of the invention, there is provided an agrochemical composition comprising an oil-in-water emulsion. The oil-in-water emulsion may comprise 20 to 70wt% of an oil phase. The oil phase may comprise an agrochemical active ingredient. The oil-in- water emulsion may comprise 30 to 80 wt% of an aqueous phase. The aqueous phase may comprise a Pickering emulsifier. The Pickering emulsifier may be a Ci6-silyl-coated fumed silica and / or amine-modified kaolin clay.

[0032] The oil phase may comprise at least 20%, 30%, 40%, 50%, or 60% by weight of the final composition. The oil phase may comprise less than 70%, 60%, 50%, 40%, or 30% by weight of the final composition. The aqueous phase may comprise at least 30%, 40%, 50%, 60% or 70% by weight of the final composition. The aqueous phase may comprise less than 80%, 70%, 60%, 50%, or 40% by weight of the final composition. The Pickering emulsifier may comprise any emulsifier discussed with respect to the first aspect. In a preferred embodiment, the Pickering emulsifier may comprise Aerosil® R816 and / or Imerys RLO 7645.

[0033] The oil-in-water emulsion may comprise the emulsion formed by the process described herein and with reference to the first aspect of the invention. According to a fourth aspect of the invention, there is provided an agrochemical composition. The agrochemical composition may comprise microcapsules of a biodegradable polymer suspended in an aqueous continuous phase. The microcapsules may contain an oil phase. The oil phase may comprise an agrochemical active ingredient. The agrochemical active ingredient may comprise Prosulfocarb.

[0034] According to a fifth aspect of the invention, there is provided an agrochemical composition. The agrochemical composition may comprise microcapsules of a biodegradable polymer suspended in an aqueous continuous phase. The aqueous phase may comprise a Pickering emulsifier. The microcapsules may contain an oil phase. The oil phase may comprise an agrochemical active ingredient. The agrochemical active ingredient may comprise one or more of Prosulfocarb, S-metolachlor, Lambda-cyhalothrin, and / or Tefluthrin.

[0035] According to either of the fourth or fifth aspects, the biodegradable polymer may comprise a complex coacervation of gelatin and a carboxylated polysaccharide. The biodegradable polymer may be as described herein with reference to the first aspect of the invention.

[0036] The aqueous phase may comprise a Pickering emulsifier. The Pickering emulsifier may comprise any emulsifier discussed with respect to the first aspect. In a preferred embodiment, the Pickering emulsifier may comprise Aerosil® R816 and / or Imerys RLO 7645.

[0037] The agrochemical compositions of the third, fourth, or fifth aspect may be formed by the process of the first aspect.

[0038] According to a sixth aspect of the invention, there is provided the use of a composition according to the second, third, fourth or fifth aspects in the treatment of weeds, pests, nematodes, molluscs and / or fungi.

[0039] According to a seventh aspect of the invention, there is provided the use of a biodegradable microcapsule prepared by the method of the first aspect.

[0040] According to an eighth aspect of the invention, there is provided the use of a biodegradable microcapsule for the delayed release of prosulfocarb. As used herein throughout, the weight percentages refer to the dry weight of the compound (e.g. for gelatin, carboxylated polysaccharide, crosslinkers etc.) excluding any water or organic solvent.

[0041] Brief Description of the Figures

[0042] The invention will now be described with reference to the following Figures, wherein:

[0043] Figure 1 is a micrograph of an undiluted oil-in-water emulsion EE13;

[0044] Figure 2 is a micrograph of example composition EC4 after drying from a sprayable diluted state;

[0045] Figure 3 is a micrograph of oil-in-water emulsion EE17 in a sprayable diluted state;

[0046] Figure 4a is a micrograph of example composition EC1 in a sprayable diluted state after 1 week of storage at 50°C;

[0047] Figure 4b is a micrograph of example composition EC1 after drying from a sprayable diluted state;

[0048] Figure 5a is a micrograph of example composition EC2 in a sprayable diluted state;

[0049] Figure 5b is a micrograph of example composition EC3 in a sprayable diluted state; and

[0050] Figure 6 is a graph showing the thermogravimetric analysis results of three different samples.

[0051] Experiments and examples

[0052] A series of experiments was carried out to identify methods and systems for encapsulating an active ingredient in an agrochemical product. The active ingredient selected was prosulfocarb, a commercial pre-emergent herbicide used for control of grass weeds.

[0053] WO2023 / 094236 discloses a potential method and system for microencapsulation of active ingredients. The method comprises: forming an oil-in water emulsion consisting of an oil phase comprising an active ingredient (lambda-cyhalothrin or S-Metolachlor) and a solvent; and a water phase comprising gelatin, by high-shear mixing of the two phases; mixing an aqueous carboxylated polysaccharide with the emulsion and adding acetic acid to reduce the pH to 3.9-4.5 to induce complex coacervation; crosslinking the microcapsules formed using a crosslinking agent to stabilise the microcapsules.

[0054] 1 - initial emulsion formations

[0055] The method of WO2023 / 094236 was followed to assess whether the active ingredient prosulfocarb could be encapsulated using this method and system.

[0056] 16.9g of an 6% aqueous solution of gelatin (type B) was added to 22.85g of water and heated to 45°C to form an aqueous gelatin solution for use as the aqueous phase in an emulsion. The oil phase was prepared by mixing approximately 27.0g of prosulfocarb with 6.8g of benzyl benzoate as a co-solvent by placing both in a vial and manually inverting the vial.

[0057] The oil phase was then added to the aqueous phase and subjected to high shear mixing for 45 seconds at 13,000 rpm in a glass beaker using an I KA Ultra Turrax® T25 mixer having a 17mm diameter rotor head while maintaining a temperature of 45°C for the mixture.

[0058] The mixture initially showed a good emulsion quality and approximately 80g were recovered of a white, flowable colloidal liquid (included as example emulsion EE13 in Table 2b). The mixture was found to gel when stored overnight at approximately 18°C but could be homogenised easily by warming and shaking.

[0059] The mixture was analysed by microscopy and despite the initial positive indications, was found to produce an unacceptable emulsion. Figure 1 is a micrograph of this emulsion without any further dilution showing a broad distribution of droplet sizes, including many substantially greater than 20 microns. The target droplet size was 10 microns, due to the physical requirements of the sprayers for which this invention is intended. Increasing droplet sizes e.g. above 20 microns, causes increasing issues with sprayer effectiveness such as sprayer nozzle clogging. Very small droplets, e.g. 1 micron, tend to form stable emulsions but have previously been found to form unstable microcapsules which are prone to breaking down and leaking, and are thus undesirable. On visual inspection after a few days storage at 40°C, the sample was found to have an off-white colour and showed clear separation of the oil and water phases due to significant coalescence of the oil droplets. The mixture was thus deemed unsuitable for attempting to form coacervated microcapsules.

[0060] Subsequently, a second attempt at using the above gelatin-only-based emulsion precursor system to encapsulate prosulfocarb was attempted to establish the effect on the final encapsulated composition. An aqueous phase was formed by prewarming 40.01g of a 6% aqueous solution of gelatin (type B) to 45°C and combining with 31 ,88g of deionised water in a 250ml temperature-controlled stainless steel jacketed vessel. The aqueous phase was homogenised using an IKA Eurostar 40 mixer at 200rpm for 8 minutes. Next, 47.99g of prosulfocarb and 11 ,998g of benzyl benzoate were blended together and added to the jacketed vessel containing the aqueous phase while mixing continued and was allowed to mix for a further couple of minutes. The mixture was transferred to an IKA UltraTurrax T25 high shear mixer with a 17mm mixer head and then mixed under high shear at 11 ,000 rpm (tip speed 9.79m / s) at 45°C for 90 seconds. This produced a very coarse and unsatisfactory oil-in-water emulsion - the particle size distribution (PSD) was measured by laser diffraction giving the following results: D(4,3): 74.5 pm, D : 38.7 pm, D5o: 71.5 pm & D90: 117 pm. The mixture was then subjected to a further 90 seconds of mixing at 15,000 rpm (tip speed 13.35 m / s), and then finally 18,600 rpm (tip speed 16.55m / s) for 90 seconds. The mixture remained an unacceptable emulsion, with the final PSD observed as: D(4,3): 83.6 pm, D : 35.0 pm, D5O: 76.1 pm & D90: 139 pm. Lastly, the mixture was returned to the IKA Eurostar 40 mixer and stirred at 350rpm.

[0061] To prepare the microcapsules, 57.12g of sodium carboxymethylcellulose (Na-CMC) (2.1% aqueous solution) was added gradually over 15 minutes to the mixture with mixing. The speed of the mixer was increased from the initial 350rpm to 550rpm as the viscosity of the fluid increased. The bottom and sides of the vessel were scraped to ensure no gelled or highly viscous material remained unmixed. The mixture was then returned to the IKA UltraT urrax T25 for high shear mixing at 11 ,4k rpm and 45°C for 90 seconds (tip speed = 10.14 m / s). The PSD of the resulting mixture was D(4,3): 50.5 pm, D : 3.5 pm, Dso: 50.1 pm & D9O: 111 pm. Visually, the sample looked identical to the initial emulsion prior to the addition of the Na-CMC.

[0062] The batch was returned to the Eurostar 40 mixer at 500 rpm, 40°C for the pH adjustment.

[0063] The initial pH was 5.89 - 2.15g of acetic acid (25wt% aqueous solution) was added to achieve a final pH of 4.26. The mixture was then cooled for approximately 30 minutes to 10°C in the 250 ml jacketed vessel using a chiller system. The mixture was quite viscous, almost paste-like, but was still able to be mixed. 3.98g of glutaraldehyde (25wt% aqueous solution) was added and the mixture was left to react overnight with continuous stirring. The following morning, the mixture was judged to be much less viscous following the reaction with gluteraldehdye. A sample (shown as example composition EC4 in Table 5) was taken, diluted in water and dried for 2 hours onto a glass slide as shown in Figure 2. Drying the mixture revealed a wide emulsion size distribution via light microscopy, which visually indicated an unsatisfactory coacervated capsule. In Figure 2 the regions of ‘shadow’ (10) around capsules which did form (i.e. the oily residues) are indicative of ineffective polymer barrier properties, poor capsule wall formation, and breaching of the capsule.

[0064] Then 4.99g of Morwet D425 (40wt% aqueous solution) was added with mixing to stabilise the mixture and temperature was increased from 10°C to 20°C. The final sample was decanted and bottled after 2 hours further mixing. Thermogravimetric analysis was carried out on the sample and the results shown in Table 1 :

[0065] Table 1

[0066] Overall, the full coacervation process was deemed a failure in the case of prosulfocarb. The method of WO2023 / 094236 was found to not produce a suitable microcapsule.

[0067] Without wishing to be bound by theory, it was believed that the difference in polarity between prosulfocarb and lambda-cyhalothrin (as described in WO2023 / 094236) may be responsible for the inadequate emulsion formation, and failure to form an effective emulsion formation was believed to prevent the possibility of effective microcapsule formation. Experiment 2 - Alternative emulsion formations

[0068] A series of experiments was carried out to identify alternative systems for forming stable emulsions comprising prosulfocarb in the oil phase having a suitable particle size distribution. A range of Pickering emulsifiers were selected for testing as set out below.

[0069] The process of Experiment 1 was repeated according to the compositions in Table 2 below - all values except emulsion score are in grams. The oil phase components were prepared by adding the prosulfocarb and benzyl benzoate to a vial and manually inverting the vial to mix them till homogenous. The aqueous phase components were mixed together in a vessel at ambient temperatures with the exception of experimental emulsions EE13 which was carried out at 45°C to ensure good mixing of the gelatin. As in Experiment 1 , the oil phase was then added to the aqueous phase and subjected to high shear mixing for 45 seconds at 13,000 rpm in a glass beaker using an IKA Ultra Turrax® T25 mixer having a 17mm diameter rotor head while maintaining a temperature of 45°C for the mixture. For the unheated examples, the temperature of the mixture increased naturally due to the high- shear mixing to approximately 25-30°C.

[0070] The quality of the emulsion was inspected visually and by microscope and scored according to Table 2 below. The scores for each of the emulsions formed are shown in Table 3a-b.

[0071] Table 2 - assessment criteria for emulsions 111636-FF (83209) 14

[0072] Table 3a

[0073] Table 3b

[0074] Benzyl Benzoate - Lanxess Deutschland GmbH. Laponite EP, Laponite RD -synthetic phyllosilicates; BYK Additives & Instruments GmbH. Aerosil® 300, Aerosil® R805, Aerosil® R711 , Aerosil® R972, Aerosil® 0X50, Aerosil® R812 S, Aerosil® R816 - modified fumed silicas; Evonik Degussa GmbH. Polyfon® H - kraft lignin sulphonate; Ingevity Ltd. Gelatin B - Gel systems Ltd. Morwet® IP - sodium isopropyl naphthalene sulfonate; Nouryon Chemicals Ltd. Imerys®

[0075] RLO 7645 - amino-silane modified kaolin clay; Imerys S.A.

[0076] 111636-FF (83209) 16

[0077] Compositions EE12 and EE15 were all found to provide high quality, stable emulsions with desirable PSDs. Composition EE12 in particular was identified as a promising emulsion system and selected for further testing. The compositions tested are listed in T able 4 below- all values except emulsion score are in grams.

[0078] All three of the emulsions EE12, EE16 and EE17 were found to produce high quality, stable emulsions with desirable PSDs, showing that the Pickering agent selected (Aerosil® R816) was effective at stabilising the emulsion system even at very low concentrations. Aerosil® R816 is a fumed silica after-treated with hexadecylsilane.

[0079] A micrograph of the experimental emulsion EE17 after further dilution in water is shown in Figure 3. EE17 formed a stable water-in-oil emulsion with a good particle size distribution and was deemed a satisfactory composition for progressing to microcapsule formation through complex coacervation.

[0080] Experiment 3 - Prosulfocarb loading tests

[0081] Experimental emulsions EE12, EE16 and EE17 each comprised an oil phase of 30%, 31%, and 30.8% respectively (see Table 3). A further test was carried out to determine whether higher loadings of prosulfocarb oil might be feasible with the same emulsifier system tested in Experiment 2.

[0082] 0.606g of Aerosil® R816 was added to 39.99g DI water in a 125 mis secured Pyrex® glass beaker and mixed for 45 seconds at a high shear of 11 ,000 rpm using the I KA Ultra-Turrax T25 mixer. 60.02g of oil phase (comprising only prosulfocarb oil) was then added into the existing aqueous phase and mixed together for a further 45 seconds at a high shear of 13,000 rpm. The result was a viscous oil-in-water emulsion stabilised by the Pickering emulsifier and comprising 59.7% w / w prosulfocarb oil phase in the 100.6g of the total mass of the emulsion at this stage in the processing.

[0083] 30.1 g of DI water was then added to the vessel and the mixture was mixed under high shear for another 45 seconds at 13,000 rpm to give 46% w / w prosulfocarb oil phase. A final addition of 19.5g of DI water was added to the vessel and the mixture was then transferred to a glass vial for storage & inspection. This produced a satisfactory Pickering-type example emulsion (EE20). The total mass was 150.13g giving a prosulfocarb oil phase of 40%wt (assuming a liquid density ~ 1 g / litre). Samples EE12, EE16 and EE17 from Experiment 2 each had an oil phase content of 30-31wt%.

[0084] Experiment 4 - Capsule formation

[0085] A further round of testing was carried out to assess the viability of microcapsules formed from the emulsions generated according to Table 5 below and the process described above.

[0086] Example Composition EC1

[0087] Microcapsules were then prepared starting from an emulsion formed according to EE17. In a first 250mL jacketed vessel 0.80g Aerosil® R816 was added to 31.09g DI water and mixed under high shear using an I KA UltraTurrax T25 with a 17mm mixer head at 11 ,000 rpm for 45 seconds. Then, 60.66g of an oil phase consisting of 80wt% prosulfocarb blended with 20%wt benzyl benzoate was added to the vessel and mixed under high shear with the same mixer at 9,000 rpm for 45 secs (tip speed 8.0 m / s) before increasing the speed to 11 ,000 rpm for 90 secs.

[0088] To a second 250mL jacketed stainless steel vessel, 40g of gelatin B (6wt% aqueous solution) was added and heated to 43°C to fluidise and homogenise. Subsequently, the gelatin B solution was added to the first vessel containing the emulsion whilst simultaneously beginning to heat the vessel to 48C to avoid the gelatin B from gelling upon addition.

[0089] The vessel was mixed at high shear at 9,600 rpm for 60 secs (tip speed 8.5m / s) producing an oil-in-water emulsion with Dso = 11.4 pm, D90 of 30.0 pm and D(4,3) = 19.0 pm as measured by laser diffraction. The mixture was high sheared again at a lower speed of 5,600rpm (tip speed 5.0 m / s) for 5 mins to further comminute the emulsion. The Dso was measured as 10.9 pm, D90 35.2 pm, and D(4,3) 30.6 pm. The sample was high sheared again at 8,600 rpm for 60 secs (tip speed = 7.7 m / s) resulting in a PSD of D50 10.0 pm, D90 56.0 pm and D(4,3) 20.1 pm. The pH of the emulsion at this stage was measured to be 5.59.

[0090] 57.15g of Na-CMC (2.1 % aqueous solution) was added over 10 mins whilst stirring at 450- 500 rpm using an IKA Eurostar 40 with 4-pronged stirrer while maintaining the composition at 48°C). The pH increased after Na-CMC addition to 6.10. The composition was then high sheared at 7,000 rpm for 120 seconds using the 17mm head (tip speed = 6.2 m / s) to disperse the Na-CMC polymer solution. PSD measurements gave a D50 of 6.3 pm, D90 of 10.8 pm and D(4,3) of 8.4 pm. The composition was transferred back to low shear mixer and mixed at 550 rpm, whereby pH had changed slightly to 5.95. Then 2.12g of acetic acid (25wt% aqueous solution) was added dropwise until pH = 4.25 was reached. The composition was cooled to 10°C in the jacketed vessel using a chiller system over approximately 30mins. Material which had dried around the surface of the preparation was mixed back into solution with a spatula. Then, 4.01g of glutaraldehyde (25wt% aqueous solution) was added to the composition and left stirring at 400 rpm overnight at 10°C. Approximately 15hrs later, 4.99g of Morwet® D425 (40wt% aqueous solution) was added whilst mixing at 425rpm, the temperature was increased on the heater-chiller unit to 20°C, and any residues that had dried around the surface of the preparation overnight were scraped back into the solution with a spatula. The composition was left at 20°C for one hour before decanting.

[0091] Figure 4a is a micrograph of a diluted sample of Example Composition EC1 taken via optical light microscopy showing the effective formation of microcapsules. The sample was allowed to dry on the slide for 1 hour and a further micrograph taken as shown in Figure 4b. Figure 4b shows clearly visible microcapsules remaining intact after drying with minimal ‘shadow’, indicating that the microcapsules were effective at containing the oil phase within and thus likely to be effective for the delayed release of the agrochemical active ingredient.

[0092] Example Composition EC2 and EC3

[0093] Two further tests were carried out with higher prosulfocarb loadings. The process of example composition EC1 was replicated but according to the formulations in Table 5. In both EC2 and EC3, the cosolvent benzyl benzoate was omitted and PSC loadings of 66.3 wt% and 69.2 wt% were attempted for the initial emulsion. A higher concentration of gelatin B was used to achieve an increased polymer content forming the microcapsules, and the Pickering emulsifier content was reduced from approx. 0.6wt% to approx. 0.5wt%.

[0094] The final PSD of EC2 was measured by laser diffraction to be: D10: 3.6 pm, D50: 7.4 pm, D90: 38.8 pm, D(4,3): 14.0 pm, thus indicating good sizing of microcapsules by complex coacervation.

[0095] The final PSD of EC3 was measured by laser diffraction to be: D10: 3.1 pm, D50: 6.1 pm, D90: 15.8 pm, D(4,3): 10.4 pm, thus indicating good sizing of microcapsules by complex coacervation.

[0096] Figure 5a is a micrograph of the example composition EC2 showing clear well-formed microcapsules of the oil phase. Figure 5b is a micrograph of the initial emulsion formed in EC3 prior to the addition of Na-CMC, showing a small amount of flocculation but otherwise the emulsion was well-formed with a desirable particle size.

[0097] In summary, it appears again as though the use of Aerosil® R816 is highly effective at stabilising the initial emulsions at a range of compositions, and the combination of gelatin B and Aerosil® R816 work effectively at the start of the Pickering complex coacervate process even when the relative oil phase loading and polymer loading is changed.

[0098] Example Composition EC4

[0099] Finally, example Composition EC4 is as described in Experiment 1.

[0100] Table 5 shows the various coacervate microcapsule compositions formed.

[0101] Na-CMC - sodium carboxymethyl cellulose; Texturecel™ 2000 PA 07. GA - glutaraldehyde; Sigma- Aldrich Company Ltd. Acetic acid - Sigma-Aldrich Company Ltd. Morwet® D425 - sodium salt of naphthalene sulfonate condensate; Nouryon Chemicals Ltd.

[0102] Experiment 5 - Capsule analysis

[0103] The coacervated micro-capsule compositions produced by the above processes were further tested by thermogravimetric analysis (TGA) in order to determine the release rate of the active ingredient and thus determine the quality of the microcapsules formed. The tests were carried out using a Netzsch TG 209 F1 Libra thermogravimetric analyser.

[0104] The analysis process was as follows:

[0105] - A sample was loaded into an open pan alumina crucible. - The gas was helium.

[0106] - The sample was warmed to 30°C and allowed to equilibrate by losing water to the atmosphere.

[0107] - The temperature of the sample was then ramped from 30°C at 5°C per minute to 350°C, and subsequently at 20°C per minute to 550°C. - The sample was held at 550°C for 20 minutes - 10 minutes under helium and 10 minutes under air.

[0108] - The loss of mass was monitored and any vapour emitted was also analysed by GC- MS, with GC-MS injections every two minutes.

[0109] - the results were plotted on the graph shown in Figure 6 and Table 6 below to show differential performance of the samples.

[0110] Table 6 below shows the TGA results for four samples: Example Emulsion EE17; Comparative Emulsion CE19; Example Composition EC1 and Example Composition EC4.

[0111] A sample of Example Emulsion EE17 was selected as a Control reference to provide a baseline against which the microcapsule compositions could be benchmarked. Example Emulsion EE17 comprised an Aerosil® R816 stabilised emulsion prior to any polymerisation steps being carried out and is thus considered to represent a ‘free emulsion’ providing no barrier to loss of the agrochemical oil phase. Preliminary testing found that the TGA data for EE17 was comparable to the data for the pure oil phase i.e. the blend of prosulfocarb and benzyl benzoate.

[0112] Comparative Emulsion CE19 (15.2g prosulfocarb, 3.89 benzyl benzoate, 23.61g DI water, 7.48 PVA Mowiol 4-88 [Kuraray Spec. Europe GmbH]) was selected as a further example of a stable emulsion but using PVA as an emulsifier in the aqueous phase. CE19 did not comprise either a Pickering agent nor microcapsules and thus should also not slow the loss of the oil phase. PVA is known to effectively stabilise emulsions as an interfacial surfaceactive agent but does not form any type of effective microcapsules since it does not undergo any cross-linking reactions or any other chemical change at the interface. On drying of CE19, microscopy confirmed that no polymer-like interfacial microcapsules were formed. Both EE17 and CE19 were deemed suitable for use as control references to compare effectiveness of various microcapsule compositions.

[0113] Example Composition EC1 represents a composition formed according to the present invention and formed using Aerosil® R816 as a Pickering emulsifier before successfully forming microcapsules. Example Composition EC4 was formed as set out above but was deliberately without a Pickering emulsifier and thus used solely gelatin B to stabilise the emulsion prior to coacervation.

[0114] Table 6

[0115] As expected, the Control sample (Example Emulsion EE17) was found to lose its mass of oil phase at the fastest rate and offered no barrier to loss of the oil phase. Comparative Emulsion CE19 showed a very slight improvement over the Control EE17, which was consistent across all repeats. Without wishing to be bound by theory, it is believed that the PVA as a polymer had a small inhibiting effect to loss of the oil phase, whereas the Pickering stabilised EE17 behaves essentially as a ‘free oil’, but that the presence of polymer alone (i.e. non-capsule polymer) was insufficient to prevent the loss of the oil phase.

[0116] EC1 was found by TGA to lose prosulfocarb mass at a slower rate than both the free emulsions EE17 and CE19, and the ‘non-Pickering’, gelatin-only emulsifier stabilised EC4. On drying of sample EC1 , microscopy confirmed the presence of capsules, and the TGA results show the effectiveness of the microcapsules in delaying the release of the agrochemical active ingredient contained within the oil phase (i.e. prosulfocarb). In the absence of the Pickering emulsifier, EC4 demonstrated a mass loss roughly equivalent to the free emulsion CE19, thus indicating that the microcapsules had failed to form in an effective manner. This was confirmed by microscopy after drying of the EC4 sample, whereby intact capsules could not be identified within the sample to the same extent as sample EC1 (see Figure 4b as compared to Figure 2).

[0117] Similarly, Figure 6 shows the TGA results for three samples: example composition EC1 (A), comparative emulsion CE19 (B) and a sample of EC1 prior to the cross-linking reaction (C). The lines plotted for samples B and C are comparable and show that in the absence of the cross-linking reaction, any coacervated polymer formation during the complex coacervation step is ineffective at encapsulating the oil phase. EC1 shows a clear ‘shift to the right’ on the x-axis, which relates to the extended time and hence elevated temperature experienced by the capsule material, thus demonstrating delayed release of the prosulfocarb-containing composition, and thus the effectiveness of the glutaraldehyde cross-linked coacervated polymer walls of the microcapsules formed.

[0118] Experiment 6 - Capsule (CS) formation with tefluthrin (TFT)

[0119] Samples were prepared using the active ingredient tefluthrin (TFT) of a Pickering oil-in- water type emulsion as a starting point followed by coacervation (where Aerosil® R816 is claimed as the Pickering stabilising agent) in order to compare to the results obtained for prosulfocarb (PSC).

[0120] Four TFT formulations were prepared in this sixth experiment including a Pickering emulsion type :

[0121] EC5 - TFT coacervation microcapsule using a Pickering type emulsifier (namely, Aerosil R816) in the first processing step, known as the emulsification of the oil phase into water.

[0122] EC6 - TFT coacervation microcapsule using only gelatin B as an emulsifier system in the first processing step as a non-Pickering comparator.

[0123] EC7 - TFT standard type emulsion as another non-Pickering comparator where moreover ‘gelatin B I Na-CMC’ type polymeric material was not added.

[0124] EC8 - TFT commercialised product (FORCE® 20CS) (= 200 g / litre TFT microcapsule product).

[0125] Table 7 shows the coacervate microcapsule compositions formed.

[0126] Table 7

[0127] Na-CMC - sodium carboxymethyl cellulose; Texturecel™ 2000 PA 07. GA - glutaraldehyde; Sigma-Aldrich Company Ltd. Acetic acid - Sigma-Aldrich Company Ltd. Morwet® D425 - sodium salt of naphthalene sulfonate condensate; Nouryon Chemicals Ltd.

[0128] Additional testing was carried out to assess the viability of TFT based microcapsules using the Pickering emulsion approach according to this invention.

[0129] Preparation of stock chemicals:

[0130] • Gelatin B was added to water in a sealed glass bottle and left on the oven rollers to dissolve for 1 hour prior to the processing work.

[0131] • Na-CMC, Xanthan gum, PVA were individually added to water and left overnight on the rollers to dissolve & used as stock solutions when required for a given experiment.

[0132] • These were all stored in the fridge at 5 °C between preparations to ensure minimal change in chemical identity.

[0133] • Na-CMC and Gelatin B solutions were warmed in the oven for approximately 45 minutes prior to planned usage to give them fluidity in order to aid dispensing.

[0134] • Benzyl benzoate (BB) as the solvent for TFT was checked for acceptability prior to addition. Example Composition EC5

[0135] 200mls of a TFT formulation as a Pickering type (using Aerosil® R816) coacervate capsule (CS) according to this invention, with D(v, 50) and D(4, 3) not greater than 15 microns and not smaller than 12 microns.

[0136] Equipment setup:

[0137] • I KA Ultra-Turrax® EC Digital Control system, fitted with a type ‘S25 10G’ disperser blade as a high shear emulsification device.

[0138] • I KA Nanostar® 7.5 digital mixer fitted with pitched 4-blade turbine blade. Effective mixing was sustained during all process steps giving good homogenisation of the formulation.

[0139] • A 200ml stainless steel jacketed vessel allowing effective temperature control between 10C and 40C using a heater-chiller unit purchased from Huber® (model: Pilot One, Ministat 125).

[0140] Procedure for melting of the active ingredient technical material Tefluthrin (TFT), a pyrethroid insecticide & preparation of the required oil premix with benzyl benzoate (BB): The water bath filled with water, and clamp stands placed around the bath to hold chemical containers, then the water bath turned on to a set temperature of 60 degrees. This is then left for 30 minutes to equilibrate and after confirming that the temperature control is working as expected, TFT containers are immersed ensuring that they are ‘double bagged’ in durable plastic bags, individually sealed with tape. The TFT was then left for 3 hours to fully melt, and the correct amount of benzyl benzoate was then added. The resulting container (with the TFT & BB mixture) was ‘double bagged’, the lid loosened, the placed back into the water bath to aid continued fluidity.

[0141] The microcapsules preparation sequence was started as follows from an emulsion where Aerosil R816 was the Pickering stabilizing agent. Using a first 250mL jacketed vessel, 1 ,0012g Aerosil® R816 was added to 75.39g de-ionised (DI) water and mixed under high shear conditions using an I KA Ultra-Turrax T25 with a 10mm mixer head at 11 ,000 rpm for 45 seconds. Then, 42.298g of oil phase (pre-prepared & pre-warmed as described above) consisting of 33wt% tefluthrin (TFT) blended with 67%wt benzyl benzoate (BB) was added to the vessel and mixed under high shear with the same mixer at 9,000 rpm for 45 secs before increasing the speed to 11 ,000 rpm for 90 secs. At this point 0.128g of NaOH (as 10%wt aqueous solution) was added, increasing the initial pH from 5.78 to 7.57 (where target was pH 7.5) in order to combat the known benzoic acid impurity from the TFT / BB mixture addition.

[0142] To a second 250mL jacketed stainless steel vessel, 26.697g of gelatin B (of 7.5wt% aqueous solution) was added and heated to 43°C to fluidise and homogenise. Subsequently, the gelatin B solution was added to the first vessel containing the initial Pickering emulsion whilst simultaneously beginning to heat the vessel to 48C to avoid the gelatin B from gelling upon its addition into the mixture. Furthermore, SAG® 1572 antifoam was added at 0.1 grams to combat any foam generated at this stage.

[0143] The vessel was mixed again with the I KA Ultra-Turrax T25 at high shear of 9,600 rpm for 60 secs maintaining the oil-in-water emulsion with Dso = 21.6 pm and D(4,3) = 23.0 pm as measured by Malvern Mastersizer 3000 laser diffraction. The mixture was high sheared again at a lower speed of 5,600rpm (tip speed 5.0 m / s) for 5 mins to further comminute the emulsion. The D5o was measured as 15.4 pm and D(4,3) as 16.6 pm. The sample was high sheared again at 8,600 rpm for 60 secs resulting in a PSD of D5o of 14.6 pm and D(4,3) of 15.6 pm. This was the pre-arranged target for the particle size, so the next step could now be carried out towards the coacervation. The pH of the gelatin-containing emulsion at this stage was measured to be 5.02.

[0144] The Na-CMC (pre-heated in the 50C oven) was then added as 38.044g of Na-CMC (2.625% aqueous solution) over 10 mins whilst stirring at 450-500 rpm using an I KA Eurostar 40 with 4-pronged stirrer while maintaining the composition at 48°C. The pH was then re-adjusted to 6.52 whereby a further 0.4656 g of 10%wt NaOH solution was added increasing the pH from 5.02 to 6.53 end-point.

[0145] The composition was then high sheared again at 7,000 rpm for 120 seconds using the 10mm head to disperse the Na-CMC polymer solution fully. PSD measurements gave a Dso of 14.6 pm and D(4,3) of 15.6 pm. The composition was transferred back to an IKA ‘Eurostar 60’ low shear mixer and mixed at 550 rpm, whereby the pH had changed slightly to 6.40. Then 2.075g of acetic acid (as 25wt% aqueous solution) was carefully added dropwise until pH = 4.31 was reached, that is, the pH was adjusted from 6.40 to 4.31 (where target was pH 4.30). The composition was cooled to 10°C in the jacketed vessel using a Huber® chiller system over approximately 30 mins. Then, 4.012g of glutaraldehyde (GA as 25wt% aqueous solution) was added to the composition and left stirring at 400 rpm overnight at 10°C. Approximately 15 hours later, 10.304g of Morwet® D425 (as 40wt% aqueous solution) was added whilst mixing at 425rpm, the temperature was increased on the heater-chiller unit back to 20°C. The composition was left at 20°C for one hour before decanting & then assessing. The total mass of the batch was 200.52 grams including 13.96 grams TFT ai at 7%wt Al loading approx, in the overall formulation (and 21%wt of total oil phase by mass).

[0146] A storage experiment was performed to check the robustness of this coacervate capsule formulation using a storage period: (A) 4weeks / 50 °C and (B) 4weeks / 20 °C.

[0147] Table 8

[0148] Table 8 demonstrates the Malvern Mastersizer 3000 particle size data. Hence, the particle size of the coacervated capsules sample known as EC5 containing TFT has not changed significantly in this regard, hence this formulation is considered satisfactory in conjunction with other observations such as appearance, colour (light brown) and fluidity.

[0149] Example Composition EC6

[0150] Further work was carried out to make a TFT CS (60 grams I litre) standard coacervated capsule Gelatin B & Na-CMC as follows:

[0151] A comparison sample EC6 was made without the Pickering emulsion step i.e. using gelatin B as the sole emulsifier. Overall, the full coacervation process was carried out for tefluthrin according to the method of WO2023 / 094236. This was found to produce a suitable microcapsule (EC6) for measurement of release rate of TFT into hexane by a standard method as will be shown later in comparison to other TFT-based samples EC5, EC7 and EC9.

[0152] Set up is an I KA ‘Eurostar 60’ mixer with a standard turbine blade and built-in thermometer, an IKA Ultra-Turrax T25 fitted with an ‘S25-KV-18G’ dispersing element, in a 3-litre jacketed vessel. Subsequently, an attempt at using the above gelatin-only-based emulsion precursor system to encapsulate tefluthrin (TFT) was attempted to establish the effect on the final encapsulated composition. An aqueous phase was formed by adding 20.4g of 100% powder of gelatin (type B) raw material and combining with 822.0g of de-ionised water in a 3-litre temperature-controlled stainless steel jacketed vessel heated liquid contents to 45°C. Furthermore, SAG 1572 antifoam was added at 1.7 grams to combat any foam generated at this stage. The aqueous phase was homogenised using an I KA Eurostar 40 mixer at 200rpm for 8 minutes. Next, 102.0g of tefluthrin (TFT) and 207.1g of benzyl benzoate were blended together and added to the jacketed vessel containing the aqueous phase while mixing continued and was allowed to mix for a further couple of minutes. The mixture was transferred to an IKA Ultra-Turrax T25 high shear mixer with a 10mm mixer head and then mixed under high shear at 11 ,000 rpm (tip speed 9.79m / s) at 45°C for 90 seconds. This produced an oil-in-water emulsion - the particle size distribution (PSD) was measured by laser diffraction giving the following results: D(4,3): 28 pm, D50: 11.4 pm. The mixture was then subjected to a further 90 seconds of mixing at 15,000 rpm (tip speed 13.35 m / s), and then finally 18,600 rpm (tip speed 16.55m / s) for 90 seconds. The mixture remained an unacceptable emulsion, with the final PSD observed as: D(4,3): 13.9 pm, D50: 11 pm. Lastly, the mixture was returned to the IKA Eurostar 40 mixer and stirred at 350rpm.

[0153] Next the pH of the formulation so far measured at pH 4.8 : this is much lower than with equivalent prosulfocarb (PSC) experiments, indicating the tefluthrin technical material (TFT / BB “technical grade” mixture) likely contains more acidic impurities than PSC mixtures. Therefore, the pH was brought back up to 7.5 with 8.5g of 10w / w% NaOH. This was done so that the gelatin was negatively charged when the Na-CMC was added (i.e. was above its so-called iso-electric point).

[0154] To prepare the microcapsules, 510.0g of sodium carboxymethylcellulose (Na-CMC) (as freshly made 2% aqueous solution) was added gradually over 15 minutes to the mixture with mixing. The speed of the mixer was increased from the initial 350rpm to 550rpm as the viscosity of the fluid increased. The bottom and sides of the vessel were scraped to ensure no gelled or highly viscous material remained unmixed. The mixture was then returned to the IKA Ultra-Turrax T25 for high shear mixing at 11.4k rpm and 45°C for 90 seconds. The PSD of the resulting mixture was D(4,3): 14 pm, D50: 11 pm. Visually, the sample looked identical to the initial emulsion prior to the addition of the Na-CMC.

[0155] The batch was returned to the Eurostar 40 mixer at 500 rpm, 40°C for the pH adjustment. The pH was remeasured at 6.21. This is typical and occurs because the Na-CMC is slightly basic in nature. Hence the initial slightly acidic pH of 6.21 was adjusted by adding 23.8g of acetic acid (as a 25wt% aqueous solution) to achieve a final pH of 4.27. The mixture was then cooled for approximately 30 minutes to 10°C in the 250 ml jacketed vessel using a chiller system. The mixture was quite viscous, almost paste-like, but was still able to be mixed. 34.0g of glutaraldehyde (as a 25wt% aqueous solution) was added and the mixture was left to react overnight with continuous stirring. The following morning, the mixture was judged to be much less viscous following the reaction with gluteraldehdye.

[0156] Then 42.5g of Morwet D425 (as a 40wt% aqueous solution) was added with mixing to stabilise the mixture and temperature was increased from 10°C to 20°C. The final sample was decanted and bottled after 2 hours further mixing.

[0157] The total mass of the batch known as sample EC6 was 1772 grams including 102 grams TFT ai at 5.75%wt approx, in the overall formulation (and 17.4% total oil phase by mass).

[0158] Next a TFT oil-in-water conventional emulsion (EW at approx. 60 grams per litre of TFT) with PVA as emulsifier was prepared as follows:

[0159] Example Composition EC7

[0160] A comparison sample EC7 was made with neither the Pickering emulsion methodology nor the polymer addition steps i.e. using PVA as the sole emulsifier & then adding water and then Morwet D425 as the only other co-formulants. The TFT I BB technical mixture was prepared in advance as described in previous sections and also the PVA solution was prepared in advance of the experiment as a 20%wt stock solution.

[0161] The experimental equipment set-up was an I KA Eurostar 60 with turbine blade and thermometer, an IKA Ultra-Turrax 25 high shear mixing device fitted with an S25-KV-18G dispersing element, working in a 3-litre jacketed vessel.

[0162] The Mowiol® 4-88 ( = PVA grade) as a 20%wt aqueous solution at 255 grams was added to the 3-litre jacketed vessel followed by 1149g exactly of de-ionised water. The stirrer operated under low shear was sufficient to homogenise this emulsifier solution. Then 309.1 grams of the tefluthrin (TFT) I benzyl-benzoate (BB) mixture (as 33% TFT Al loading; and 67% BB carrier solvent) was added to the jacketed vessel under low shear mixing. Once all the chemicals had been transferred, high shear mixing was enabled for 2 minutes at 10 000 rpm, and particle size measurements taken via Malvern Mastersizer 3000 laser diffraction: D(4,3) = 12.8 microns. Further shearing for 3 minutes at 10 000 rpm gave rise to the following emulsion : D(4,3) = 11.4 microns.

[0163] Once this desired droplet size had been reached, then Morwet D425 (42.5g) and antifoam (SAG antifoam 1572, 1.7g) were added, mixed in, and then the formulation was transferred to 2L glass bottle via peristaltic pump. This sample was labelled as EC7 where total mass @ 1613.1 grams including 102 grams TFT ai at 6.3%wt approx, in the overall formulation (and 19.2% total oil phase by mass).

[0164] These four formulations were then tested according to Analytical Method “X” which is a common methodology for PP321 , S-metolachlor & TFT as described on page 12 of WO2023 1094236 (Syngenta).

[0165] The method is followed and data taken for the 48-hour time period showing the resulting release rate of TFT into the hexane phase whereby TFT starts at zero concentration (time = zero) and increases gradually over time up to 48 hours.

[0166] The release rate data at 48 hours time-point for samples EC5, EC6, EC7 and EC8 is shown in Table 9, showing the release rate of TFT into the hexane phase.

[0167] Table 9

[0168] Table 9 shows that the TFT - based coacervation sample EC5 made using the Pickering approach of this invention is superior to the standard coacervation sample EC6, which is the conventional gelatin B based emulsion approach of the prior art. Sample EC5 is also far superior as expected to the negative control sample EC7, which is a simple PVA-based emulsion without any polymeric barrier wall material.

[0169] The superiority amongst the biodegrading coacervation samples (that is, coacervated samples EC5 and EC6 as determined by OECD-301 F) is judged by which sample is closest in reducing the release rate over a 48 hour period from the aqueous phase (“donating” fluid) made by diluting the TFT based formulation and then transferring TFT into the adjacent hexane based solvent phase (“receptor” fluid). The commercial FORCE® 200 g / litre CS product has the lowest release rate into hexane but contains polyurea polymeric wall material.

[0170] Hence, the Pickering technical approach sample EC5 for Tefluthrin (TFT) is technically viable. The invention is defined by the claims.

Claims

CLAIMS1. A process for encapsulating an agrochemical in a biodegradable capsule comprising the complex coacervation of gelatin and a carboxylated polysaccharide, wherein the process comprises: forming an emulsion of an aqueous phase comprising at least one Pickering emulsifier and an oil phase comprising the agrochemical.

2. The process according to claim 1 , wherein the agrochemical comprises one or more of herbicides, insecticides, and fungicides and is present in an amount of 0.01 to 60% by weight of the final formulation.

3. The process according to either preceding claim, wherein the agrochemical is Prosulfocarb, S-metolachlor, Lambda-cyhalothrin, and / or Tefluthrin.

4. The process according to any one of the preceding claims, wherein the oil phase comprises a solvent and / or carrier fluid, and optionally, wherein the solvent and / or carrier fluid is an aromatic solvent or carrier fluid.

5. The process according to any one of the preceding claims, wherein the Pickering emulsifier is present in an amount of 0.01 to 5% by weight of the emulsion.

6. The process according to any one of the preceding claims, wherein the Pickering emulsifier is a Ci6-silyl-coated fumed silica and / or amine modified kaolin clay.

7. The process according to any one of claims 1 to 6, wherein the gelatin is present within, or added to, the aqueous phase prior to the formation of the emulsion.

8. The process according to any one of claims 1 to 6, comprising adding the gelatin to the emulsion.

9. The process according to any one of the preceding claims, wherein the gelatin is present in an amount of 0.5% to 6% by weight of the final formulation.

10. The process according to any one of the preceding claims, wherein forming the emulsion comprises adding the oil phase to the water phase under high-shear mixing.

11. The process according to any one of the preceding claims, comprising: adding a carboxylated polysaccharide to the emulsion; and adding a crosslinker to thereby form a polymer microcapsule at the oil-water phase boundary.

12. The process according to claim 11 , wherein the carboxylated polysaccharide is present in an amount of 0.1% to 3% by weight of the final formulation.

13. The process according to claim 11 or 12, wherein the carboxylated polysaccharide is selected from one or more of gum Arabic, sodium alginate, and carboxymethyl cellulose, and wherein preferably only one carboxylated polysaccharide is used.

14. The process according to any one of claims 11 to 13, wherein the carboxylated polysaccharide comprises an aqueous solution of carboxylated polysaccharide prior to addition to the emulsion and / or wherein the addition of the carboxylated polysaccharide is carried out under acidic conditions and / or wherein the process comprises adding the carboxylated polysaccharide and subsequently acidifying the conditions.

15. The process according to any one of claims 11 to 14, comprising a high-shear homogenisation step after adding the carboxylated polysaccharide.

16. The process according to any of claims 11 to 15, wherein the crosslinker is selected from polyaldehydes, polyacids, polyphenols, and aldose sugars.

17. The process according to any of claims 11 to 16, wherein the crosslinker is present in an amount of 0.0001 to 2% by weight of the final formulation18. The process according to any of the preceding claims, wherein the capsules have a diameter of less than 15 microns, less than 10 microns, less than 5 microns; and / or exhibit controlled release.

19. A composition comprising a microcapsule prepared by the method of any of claims 1 to 18.

20. An agrochemical composition comprising an oil-in-water emulsion, comprising 20 to 70wt% of an oil phase comprising an agrochemical active ingredient;30 to 80 wt% of an aqueous phase comprising a Pickering emulsifier; wherein the Pickering emulsifier is a C16-silyl-coated fumed silica and / or amine-modified kaolin clay.

21. An agrochemical composition comprising: microcapsules of a biodegradable polymer suspended in an aqueous continuous phase; wherein the microcapsules contain an oil phase comprising an agrochemical active ingredient, the agrochemical active ingredient comprising Prosulfocarb,22. The agrochemical composition of claim 21, wherein the biodegradable polymer comprises a complex coacervation of gelatin and a carboxylated polysaccharide23. The agrochemical composition of either claim 21 or 22, wherein the aqueous phase comprises a Pickering emulsifier.

24. An agrochemical composition comprising: microcapsules of a biodegradable polymer suspended in an aqueous continuous phase comprising a Pickering emulsifier; wherein the microcapsules contain an oil phase comprising an agrochemical active ingredient, the agrochemical active ingredient comprises one or more of Prosulfocarb, S-metolachlor, Lambda-cyhalothrin, and / or Tefluthrin.

25. Use of a composition according to any one of claims 19 to 24 in the treatment of weeds, pests, nematodes, molluscs and / or fungi.

26. Use of a biodegradable microcapsule prepared by the method of any of claims 1 to 18.

27. Use of a biodegradable microcapsule for the delayed release of prosulfocarb.

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