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 gelatin and a co-surfactant and an oil phase comprising the agrochemical wherein the co-surfactant comprises an anionic surfactant. The process is particularly suitable for forming biodegradable microcapsules of prosulfocarb which exhibit delayed release of the agrochemical.

Description

[0001] 111628-FF (83362)

[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] Background

[0006] 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).

[0007] 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.

[0008] 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 the agrochemical from soil and plants during field applications and moreover, which needs to be of a biodegradable microcapsule for some markets beyond 2030.

[0009] PCT application WO2023 / 094236 by the present Applicant 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.

[0010] The present inventors have found that the process of WO2023 / 094236 is ineffective for forming microcapsules comprising prosulfocarb and S-metolachlor. In particular, the failure to effectively encapsulate all of the prosulfocarb leads to the loss of the capsule structure upon drying and subsequently, the sub-optimal capsule formation provides no benefit to volatility control and rapid release rates of the prosulfocarb active ingredient.

[0011] 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.

[0012] 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.

[0013] ‘Carboxylated polysaccharide' includes both polysaccharides that naturally contain carboxylic acid groups and those that have been chemically modified to contain the same.

[0014] 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.

[0015] "Complex coacervation" itself is defined as the complexation between two oppositely charged polyelectrolytes. of Invention

[0016] 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 gelatin and a co-surfactant and an oil phase comprising the agrochemical wherein the co-surfactant comprises an anionic surfactant.

[0017] The co-surfactant preferably comprises a sulphur-containing moiety. Advantageously, the co-surfactant may comprise a sulphonate or sulphate functional group, preferably sulphonate. The co-surfactant may comprise more than one ethoxylate sulphate, naphthalene sulphonate, sulfosuccinate or benzene sulphonate. For example, the cosurfactant may comprise one or more of Soprophor® 4D 384, Morwet® IP, Aerosol OT- 100, Morwet® D425, Agnique® PG8107 and / or Nansa EVM / 60B, preferably Morwet® IP.

[0018] The co-surfactant may comprise a salt of naphthalene sulphonate or a salt of a substituted naphthalene sulphonate. In one series of embodiments, the co-surfactant may comprise more than one salts of naphthalene sulphonates or salts of a substituted naphthalene sulphonates. In one series of embodiments, the co-surfactant may comprise one or more alkyl naphthalene sulphonate salts. For example, the co-surfactant may comprise a sodium iso-, di-iso-, and / or tri-isopropyl naphthalene sulphonate (e.g. Morwet® IP), a sodium salt of methylated dibutylnaphthalene sulphonate, a sodium salt of naphthalene sulfonate condensate (e.g. Morwet® D-245), sodium dioctyl sulfosuccinate (e.g. Aerosol OT-100) or mixtures thereof. In one series of embodiments, the co-surfactant may comprise one or more of Morwet® DB, Morwet® IP, Morwet® D425, Morwet® EFW (Nouryon Chemicals Ltd.), Agnique® ANS 3DNP-U (BASF), Aerosol OT-100 and / or Alkanol® XC (DuPont).

[0019] The co-surfactant may act as an emulsifier and / or wetting agent and / or dispersant.

[0020] The amount of co-surfactant may comprise 0.01-1% wt% of the emulsion. The co-surfactant may comprise at least 0.01%, 0.025%, 0.05%, 0.075%, 0.1 %, 0.125%, 0.15%, 0.175%, 0.2%, 0.3% 0.4%, 0.5%, 0.6%, 0.8%, by weight of the emulsion. The co-surfactant may comprise less than 1%, 0.8%, 0.6%, 0.5%, 0.4%, 0.3% 0.2%, 0.175%, 0.15%, 0.125%, 0.1 %, 0.075%, 0.05%, or 0.025% by weight of the emulsion. The amount of co-surfactant may be 1-50% w / w of the amount of gelatin. For example, the co-surfactant may comprise 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 15%, 16%, 18%, 20%, 22%, 24%, 25%, 26%, 28%, 30%, 32%, 34%, 35%, 36%, 38%, 40%, 42%, 44%, 45%, 46%, 48%, or 50% w / w of the amount of gelatin.

[0021] 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.

[0022] 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.

[0023] The emulsion may be an oil-in-water emulsion.

[0024] 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 50% 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. 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.

[0025] In one series of embodiments, the aqueous phase may comprise 1-10wt% of gelatin and / or 0.01-2.5wt% of co-surfactant. For example, the aqueous phase may comprise from 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, or 9 wt% to 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, or 10 wt% of gelatin. The aqueous phase may comprise from 0.01 wt%, 0.025 wt%, 0.05%, 0.075%, 0.1 %, 0.125%, 0.15%, 0.175%, 0.2%, 0.3% 0.4%, 0.5%, 0.6%, 0.8%, 1 wt%, 1.5 wt%, or 2 wt% to 0.025 wt%, 0.05%, 0.075%, 0.1%, 0.125%, 0.15%, 0.175%, 0.2%, 0.3% 0.4%, 0.5%, 0.6%, 0.8%, 1 wt%, 1.5 wt%, 2 wt% or 2.5 wt% of co-surfactant.

[0026] 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. 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.

[0027] 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.

[0028] 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.

[0029] 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.

[0030] 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.

[0031] 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.

[0032] 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.

[0033] According to a second aspect of the invention there is provided a composition comprising a microcapsule prepared by the method described herein and with reference to the first aspect.

[0034] 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 co-surfactant.

[0035] 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.

[0036] The aqueous phase may comprise from 0.01 wt%, 0.025 wt%, 0.05%, 0.075%, 0.1 %, 0.125%, 0.15%, 0.175%, 0.2%, 0.3% 0.4%, 0.5%, 0.6%, 0.8%, 1 wt%, 1.5 wt%, or 2 wt% to 0.025 wt%, 0.05%, 0.075%, 0.1%, 0.125%, 0.15%, 0.175%, 0.2%, 0.3% 0.4%, 0.5%, 0.6%, 0.8%, 1 wt%, 1 .5 wt%, 2 wt% or 2.5 wt% of co-surfactant.

[0037] 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.

[0038] 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.

[0039] The aqueous phase may comprise a co-surfactant.

[0040] 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 cosurfactant. 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.

[0041] 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.

[0042] According to either of the fourth or fifth aspects, the co-surfactant may comprise one or more emulsifiers and / or wetting agents. The co-surfactant may comprise a salt of naphthalene sulphonate or a salt of a substituted naphthalene sulphonate. In one series of embodiments, the co-surfactant may comprise an alkyl naphthalene sulphonate salt. For example, the co-surfactant comprises a sodium isopropyl naphthalene sulphonate e.g. Morwet® IP. The agrochemical compositions of the third, fourth, or fifth aspect may be formed by the process of the first aspect.

[0043] 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.

[0044] 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.

[0045] According to an eighth aspect of the invention, there is provided the use of a biodegradable microcapsule for the delayed release one or more of Prosulfocarb, S-metolachlor, Lambda- cyhalothrin, and / or Tefluthrin, preferably Prosulfocarb.

[0046] 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.

[0047] Brief Description of the Figures

[0048] The invention will now be described with reference to the following Figures, wherein:

[0049] Figure 1 is a micrograph of an undiluted oil-in-water emulsion EE13;

[0050] Figure 2 is a micrograph of example composition EC5 after drying from a sprayable diluted state;

[0051] Figure 3 is a micrograph of oil-in-water emulsion EE17 in a sprayable diluted state; Figure 4 is a micrograph of example composition EC3 after drying from a sprayable diluted state;

[0052] Figures 5a is a graph showing a particle size distribution of example composition EC4;

[0053] Figures 5b and 5c are micrographs of example composition EC4 in a sprayable diluted state and after drying respectively; and

[0054] Figure 6 is a graph showing the thermogravimetric analysis results of four different samples.

[0055] 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.

[0056] 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.

[0057] 1 - initial emulsion formations

[0058] The method of WO2023 / 094236 was followed to assess whether the active ingredient prosulfocarb could be encapsulated using this method and system.

[0059] 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 27g of prosulfocarb with 6.8g of benzyl benzoate as a co-solvent by placing both in a vial and manually inverting the vial.

[0060] 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.

[0061] 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. 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 oil droplets, e.g. around 1 micron average size, tend to form acceptable emulsions stable to physical separation but when coacervated with natural polymers they have previously been found to form unstable microcapsules which are for example prone to breaking down and leaking their contents at that relatively small size range, and thus such emulsions are generally undesirable as precursors to the coacervated capsules described herein. 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.

[0062] 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 I KA 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 I KA 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, Dso: 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. 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, D50: 50.1 pm & D90: 111 pm. Visually, the sample looked identical to the initial emulsion prior to the addition of the Na-CMC.

[0063] The batch was returned to the Eurostar 40 mixer at 500 rpm, 40°C for the pH adjustment. 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 EC5 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.

[0068] Experiment 2 - Alternative emulsion formations

[0069] 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 emulsifier systems were selected for testing as set out below.

[0070] 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 and EE16 which were 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 I KA 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. 111628-FF (83362)

[0071] Table 2a

[0072]

[0073] Table 2b

[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] 111628-FF (83362)

[0077] The quality of the emulsion was inspected visually and by microscope and scored according to Table 3 below. The scores for each of the emulsions formed are shown in Table 2a-b.

[0078] Table 3 - assessment criteria for emulsions

[0079] Compositions EE12, EE15, and EE18 were all found to provide high quality, stable emulsions with desirable PSDs. Composition EE12 and EE18 in particular were identified as a promising emulsion system and selected for further testing. The compositions tested are listed in Table 4 below- all values except emulsion score are in grams.

[0080] Table 4

[0081] All three of the emulsions EE12, EE16 and EE17 were found to produce high quality, stable emulsions with desirable PSDs, showing that the Pickering emulsifier 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.

[0082] 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. formation

[0083] 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.

[0084] Example Composition EC1

[0085] 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.

[0086] 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.

[0087] 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 D5o = 11.4 pm, D90of 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, D9o 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 Dso 10.0 pm, D9o 56.0 pm and D(4,3) 20.1 pm. The pH of the emulsion at this stage was measured to be 5.59.

[0088] 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 Dso 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) dispersing agent was added whilst mixing at 425rpm, the temperature was increased on the heaterchiller 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.

[0089] 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.

[0090] Example Composition EC2

[0091] A first test was carried out to assess whether the example emulsion EE18, comprising Morwet® IP as a co-surfactant in combination with gelatin B in a 1 :1 ratio as the emulsifier system, offers a benefit over the coacervation process described in WO2023 / 094236.

[0092] The initial emulsion was prepared using the same process as described previously according to the formulation shown in Table 5. After addition of the oil phase to the aqueous phase at 43°C, the composition was mixed under high shear at 11 ,000rpm for 90 seconds yielding a PSD (measured by laser diffraction) of: Dm: 1.4 pm, D50: 2.2 pm, D90: 3.9 pm, D(4,3): 2.4 pm. The composition was returned to the Eurostar mixer and 57.17g of Na- CMC (2.1wt% aqueous solution) was added gradually over 15 minutes, with the mixer speed increasing from 300-650 rpm. The sample was mixed again at 8,400 rpm for 120 seconds (tip speed = 7.5 m / s), giving a PSD of: Dm: 1.2 pm, D50: 1.8 pm, D90: 2.7 pm, D(4,3): 1.9 pm. The pH was measured to be 6.49 initially, before 2.76g of acetic acid (25wt% aqueous solution) was added dropwise giving an adjusted pH of 4.24. The composition was cooled down to 10°C over 30 minutes before 4.00g of glutaraldehyde (25% aqueous solution) was added and was left to react overnight while mixing at 625 rpm. The composition was observed to be noticeably more viscous the following morning, and was difficult to pipette up into a 3ml plastic pipette. The batch was heated up to 20°C, and 5.01g of Morwet® D425 (40wt% aqueous solution) was added and allowed to mix in for around 1 hour before decanting into a plastic bottle for storage to form example composition EC2. Upon diluting into water, flocculated particles were visible to the naked eye. Final PSD was: Dw: 7.5 pm, Dso: 31.1 pm, D90: 65.0 pm, D(4,3): 34.1 pm. This was a substantial increase in particle size and aligned with the flocculation seen with microscopy.

[0093] A sample of EC2 was dried for one hour and assessed via microscope. The capsule walls were ill-defined visually and large amounts of oil leakage can be seen. Without wishing to be bound by theory, it is suspected that the small, negatively charged Morwet® IP interfered with the coacervation process and as a result has negatively affected the wall formation and capsule robustness.

[0094] Example Composition EC3

[0095] A second example composition EC3 was prepared with Morwet® IP in combination with gelatin B in 1 :10 ratio respectively as the emulsifier system. The process for forming EC2 was replicated with a lower shear rate and duration due to the very small particle size obtained initially with the emulsion precursor for EC2.

[0096] EC3 was prepared according to the formulation in Table 5. The emulsion was initially stirred at 10,000rpm for 45 seconds at 43°C, yielding a PSD of: D10: 3.2 pm, D50: 6.8 pm, D90: 12.8 pm, D(4,3): 7.5 pm. The PSD appeared to contain a population of small particles (<1-2 pm diameter) versus the remainder being around 2-25 pm diameter, confirmed via microscopy. The addition of Na-CMC was carried out over 10 minutes with mixer speed increasing from 250-475 rpm as the viscosity rose. The sample was then high-sheared again, but at 8,000 rpm for 60 seconds (tip speed = 7.1 m / s), giving a PSD of Dw: 2.7 pm, D50: 5.5 pm, D90: 10.3 pm, D(4,3): 6.9 pm. The PSD trend was similar to the first measurement. The composition was returned to the Eurostar 40 mixer at 400 rpm where the initial pH was measured to be 6.46. Acetic acid was added and the adjusted pH was measured to be 4.24. Microscopy was carried out and it was noticed that small flocculated assemblies of particles up to 35 pm in length had begun to form. The composition was cooled to 10°C and 1.77g of DI water was added to make up for the un-needed acetic acid. Once at 10°C, the stirrer speed was set to 450 rpm and glutaraldehyde was added dropwise before leaving the composition to react overnight. The following day, the composition was warmed back up to room temperature and a PSD measurement was taken giving a PSD of: D : 2.6 pm, Dso: 5.5 pm, D90: 60.1 pm, D(4,3): 72.2 pm. The PSD graph produced in this way indicated a small proportion of particles between 30-200 pm which skewed the D90 and D(4,3) results, however these implied larger particles in the distribution were not visible by eye with light microscopy. 5.01g of 40wt% Morwet<R) D425 aqueous solution was added and allowed to mix in for 2 hours before decanting. PSD measurement after Morwet<R) D425 addition yielded: D10: 2.5 pm, D50: 5.1 pm, D90: 11.9 pm, D(4,3): 20.1 pm, although the PSD graph still indicated a small population of particles with diameters of 30 pm.

[0097] After two hours of drying, the sample appeared acceptable as shown in Figure 4 with a good proportion of robust, intact capsules visible. After around 20 hours drying, there were still a significant proportion of the capsules that had persisted intact. Figure 6 shows the TGA data where sample EC3 performs well against the control emulsion sample.

[0098] Example Composition EC5

[0099] Finally, example Composition EC5 is as described in Experiment 1.

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

[0101] Table 5

[0102] Na-CMC - sodium carboxymethyl cellulose; Texturecel™2000 PA 07. GA- glutaraldehyde; Sigma- Aldrich Company Ltd. Acetic acid; Sigma-Aldrich Company Ltd. Morwet® IP - sodium isopropyl naphthalene sulfonate & Morwet® D425 - sodium salt of naphthalene sulfonate condensate; Nouryon Chemicals Ltd.

[0103] Experiment 4 - Alternative agrochemical test

[0104] A further experiment was carried out to assess viability of the gelatin and co-surfactant emulsifier system with an alternative agrochemical active ingredient.

[0105] An aqueous phase was formed according to Table 6 by adding the gelatin B, Morwet IP and an antifoam additive (SAG™ 1572; Momentive Performance Materials Inc.) to 166.05ml of water in a 500ml jacketed vessel warmed to 45°C. The aqueous solution was stirred at low shear until everything had dissolved, and subsequently transferred to a Silverson high- shear mixer.

[0106] An oil phase was formed of lambda-cyhalothrin as a technical pre-mix comprising 119.81g of a 1 :1 combination of 100% lambda-cyhalothrin (an insecticidal agrochemical) and Solvesso® 200 solvent. The aqueous phase formed above was sheared slowly at 1500rpm while the oil phase was pipetted into the aqueous phase over a period of 5 minutes. The mixer speed was increased to 7,000rpm for 5 minutes, followed by 8,000rpm for 5 minutes to yield an adequate oil-in-water emulsion. The PSD was measured indicating a Dso of 3.6 microns and D90 of 7.6 microns. Visually, the emulsion appeared well formed and was physically stable upon stirring for the 2 hours tested.

[0107] The vessel was returned to low shear mixing at 200 rpm and 90.01g of carboxylated polysaccharide (Na-CMC) was added while ramping up the stirring speed to 500rpm as the mixture increased in viscosity. Once mixed, the particle size was assessed and large peaks at 200 microns were observed. Optical microscopy was used to identify the cause of the peaks, but no flocculation of the particles could be observed - it was thus concluded that the peaks were caused by Na-CMC aggregates. The vessel was returned to the high-shear mixer and sheared at 7,000rpm for 5 minutes. The resulting particle size distribution still indicated significant large peaks which were thus assumed to be air bubbles, which are an artefact of the laser diffraction sample preparation methodology i.e. a dilution and stirring.

[0108] The vessel was cooled to 10°C while mixing at 500rpm. Once 10°C was reached, the 2.39g of crosslinker (glutaraldehyde, 25% aqueous solution) was added and left to react overnight. The following day, the composition was warmed to 20°C and 16g of Morwet® D425 (25% aqueous solution) dispersing agent was added to yield the final example composition EC4 as shown in Table 6 below.

[0109] Table 6

[0110] The PSD for EC4 was measured and graphed as shown in Figure 5a. The composition had a majority of particles in the 1-10 micron range, which indicated good capsule formation. A peak was also observed at a larger size range which were confirmed to be due to flocculation of the particles as confirmed by optical spectroscopy.

[0111] Figures 5b and 5c are micrographs taken of the composition EC4 in a dilute sprayable form and after 90 minutes of drying from a dilute sprayable form respectively. Figure 5b showed some visible flocculations of the particles, but which could not be identified after drying (Fig 5c). The clear presence of capsules in Figure 5c shows that the capsule polymer system is robust and capable of containing lambda-cyhalothrin and other agrochemicals.

[0112] 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.

[0113] The TGA process was as follows:

[0114] - A sample was loaded into an open pan alumina crucible.

[0115] - The gas was helium.

[0116] - The sample was warmed to 30°C and allowed to equilibrate by losing water to the atmosphere.

[0117] - 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.

[0118] - The sample was held at 550°C for 20 minutes - 10 minutes under helium and 10 minutes under air.

[0119] - The loss of mass was monitored and any vapour emitted was also analysed by GC- MS, with GC-MS injections every two minutes.

[0120] - the results were plotted on the graph shown in Figure 6 and Table 7 below to show differential performance of the samples.

[0121] Table 7 below shows the TGA results for five samples:

[0122] Comparative Emulsion CE19;

[0123] (Control) - Example Emulsion EE17, comprising an emulsion system stabilised by Aerosil® R816;

[0124] Example Composition EC5, formed as described in Experiment 1. Example Composition EC1 comprising coacervated polymer microcapsules formed from an emulsion system stabilised by Aerosil® R816.

[0125] Example Composition EC3 comprising coacervated polymer microcapsules formed from an emulsion system stabilised by gelatin B and Morwet IP in a 10:1 ratio.

[0126] 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.

[0127] 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 surface-active 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.

[0128] Table 7

[0129] As expected, the Control sample (Example Emulsion EE17) was found to lose 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.

[0130] Example Composition EC5 was found to exhibit very similar properties to comparative emulsion CE19, confirming that the gelatin-only system of WO2023 / 094236 failed to form microcapsules and that any small improvements were likely due to the behaviour of the gelatin in the bulk continuous phase, similar to the PVA in CE19. EC5 was deemed ineffective at delaying the release of prosulfocarb.

[0131] EC1 was found by TGA to lose prosulfocarb mass at a slower rate than both the emulsions CE19 and EE17 and the example composition EC5. 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). Example Composition EC3 showed an even greater improvement over the control and over the Pickering emulsifier-stabilised EC1.

[0132] Similarly, Figure 6 shows the TGA results for the three samples A to C plotted against the Control sample listed in Table 7. Sample B, consisting of the Example Composition EC1 shows a modest ‘shift to the right’ on the x-axis, which relates to the extended time and hence elevated temperature experienced by the capsule material for a given %loss of the prosulfocarb, as compared to the gelatin-only Example Composition EC5 (sample A). This demonstrates delayed release of the prosulfocarb-containing composition, and thus the effectiveness of the glutaraldehyde cross-linked coacervated polymer walls of the microcapsules formed. However, sample C (Example Composition EC3) shows a significantly greater ‘shift to the right’ on the x-axis, supporting the findings in Table 7 above and supporting the conclusion of the system forming highly physically stable microcapsules with an enhanced diffusion barrier and thus indicating a further improvement over both free emulsions and Pickering emulsifier system of EC1.

[0133] Experiment 6 - further emulsification work

[0134] Further PSC data was generated to study the effect of a broader range of co-surfactants to be used with gelatin B. Hence various examples of gelatin B combined with a variety of coemulsifiers were prepared in order to form an initial emulsion of PSC technical grade oil as a starting point, which could then be assessed for suitability.

[0135] The first step was to assess the nature of the pre-emulsions suitable for step 2 of coacervation process to make PSC-based capsules with the aim of reducing volatility primarily. This was done with a 10: 1 ratio of gelatin B : co-surfactant by using example EC3 as the template for all such exploratory emulsifications.

[0136] Preparatory work:

[0137] A 6%wt aqueous solution (stock) of gelatin was prepared (gelatin B (11.35 g) and de-ionised water (177.56 g)) and allowed to roll in a 250 ml PET bottle and placed in 50 °C oven for 1 hour, to dissolve the gelatin B fully into water solution. A light brown colouration as expected was achieved.

[0138] Preparing Prosulfocarb (PSC) : Benzyl Benzoate (BB) technical stock 4 : 1 oil mixture

[0139] An 80: 20 blended Al stock liquid (prosulfocarb (PSC) (99.6% at 384 grams) and Benzyl benzoate (BB) (95.98 grams)) was left rolling in 1 litre glass bottle and then used as the stock liquid for experiment 6.

[0140] Preparing the ten selected emulsions with varying co-surfactant:

[0141] Gelatin B was used as the primary emulsifier for 36% PSC oil-in-water type emulsions (EWs) with varied co-surfactants as the secondary emulsifier (9 different examples as shown in Table 8). The sequence of co-surfactants is given in the order in which they were screened to give a set of samples #1 to #10 within Experiment 6.

[0142] Table 8

[0143] Ten 36%wt PSC based emulsions (EWs) were made by using gelatin as the primary emulsifier and by varying the co-surfactant as the secondary emulsifier. The emulsion quality guide as seen in Table 3 was used to evaluate the emulsions so prepared.

[0144] Table 9

[0145] Table 10

[0146] Standardised emulsion processing used for all the 10 samples: Add de-ionised water, then the co-surfactant (e.g. Synperonic A7 surfactant in this example), and finally Gelatin B as pre-prepared 6%wt solution into a 125 ml pyrex glass beaker. Mix at approx. 200 rpm and heat gently using a magnetic flea and hotplate-stirrer plate to ensure a) the solution remains above 22 °C to avoid gelatin B forming a gel phase and b) that the Synperonic A7 has dissolved fully. Add the oil phase (PSC I BB mix) as 80: 20 blended Al stock liquid. Mix for 45 seconds at 13, 000 rpm using an IKA ULTRA- TLIRRAX T-25 high shear mixer with shear-head type ‘S25 10G’ with power setting #2. Once finished, then liquid emulsion was placed into a glass bottle, and an initial inspection made and then store sample at 50C for 10 days without any agitation.

[0147] All ten of these samples were prepared in sequence using the method indicated above and left in an oven at 50 °C (static) once prepared. All samples then were shaken to synchronise them ahead of the 10 days storage at 50 °C. It was expected that some sedimentation would occur whilst static in the oven as a result of different oil droplet sizes in the likely range from 1 to 100 microns.

[0148] All the final samples were tested by MM3000 and also all samples checked by light microscopy for comparative purposes.

[0149] Table 11

[0150] EE20 (gelatin only) was the poorest for making a PSC based emulsion pre-cursor at 36 wt% PSC oil loading. Hence, it is clear that a co-surfactant would be required.

[0151] The non-ionic surfactants (Tween 20, Agnique PG8107 and Emulsogen EL360) of EE21 , EE24 and EE27 do not work well to form the desired emulsions in combination with gelatin. However, the anionic surfactants (Soprophor 4D-384, Morwet IP, Aerosol OT-100 and Nansa EVM / 60B) of EE22, EE23, EE25, EE28 worked well.

[0152] Experiment 7 - complex coacervation with Aerosol QT-100 as co-surfactant- Composition EC6

[0153] Aerosol OT-100 was then compared with the previously established result for Morwet IP (refer to example EC3). This was performed with a 10:1 ratio of gelatin B:Aerosol OT-100.

[0154] Composition EC6 was prepared with Aerosol® OT-100 in combination with gelatin B in 1 :10 ratio respectively as the emulsifier system.

[0155] Formulation EC6 was prepared according to the formulation in Table 12, which also shows composition EC3 for reference purposes. The starting emulsion (Part 1) was composed of de-ionised water (61.54 grams), Aerosol OT-100 surfactant (0.25 grams) and gelatin B (2.41 grams).

[0156] This mixture was combined together in a stainless-steel jacketed vessel warmed to 40 °C and stirred by 4-way Teflon-coated paddle head for approximately 60 minutes to allow the Aerosol OT-100 to fully dissolve. Once fully dissolved, then to complete Part 1 of the processing this mixture was initially sheared at 10,000rpm for 45 seconds at 43 °C, yielding a PSD of: D50: 3.4 pm, D(4,3): 3.7 pm. The PSD appeared to contain a population of small particles (<1-2 pm diameter) versus the remainder being around 2-15 pm diameter, confirmed via light microscopy. The addition of Na-CMC (59.94 grams of a 2% aq. Solution) was carried out over 10 minutes with mixer speed increasing from 250-475 rpm as the viscosity rose. The sample was then high-sheared again, but at 8,000 rpm for 60 seconds (tip speed = 7.1 m / s), giving a PSD of D50: 2.8 pm, D(4,3): 3.0 pm. The PSD trend was similar to the first measurement and was considered satisfactory.

[0157] For Part 2, the composition was returned to the Eurostar 40 mixer at 400 rpm where the initial Ph was measured to be 5.8. Acetic acid (2.26 grams) was added (as 25%wt aqueous solution) and the adjusted Ph was measured to be 4.21. The composition was cooled to 10°C and the mixer head was rinsed out with 2.44g of DI water to dislodge some of the emulsion residues that remained within. Once the mixing vessel was stabilised at 10°C, for Part 3 of the overall preparation, the stirrer speed was set to 450 rpm and 3.99 grams of glutaraldehyde (GA as 25% aqueous solution) was added dropwise before leaving the composition to react overnight. In the morning, the temperature of the preparation was raised to 20°C, stirring was changed to 225rpm. About an hour later, 5.05g of Morwet D425 powder was added, along with the remaining DI water (0.66g), and mixing was set to -500 rpm. When sub-sampling, it was noticed that the fluidity / flowability of the prep was vastly improved after Morwet D425 addition. The preparation was decanted around 5hrs after the Morwet D425 addition as sample EC6.

[0158] Sample EC6 was then characterised by:

[0159] 20) Dilution and light microscopy inspection ii) Dilution and Malvern Mastersizer 3000 particle sizing iii) Assessment of sample appearance and fluidity

[0160] After two hours of drying, the sample appeared acceptable with a good proportion of robust, intact capsules visible.

[0161] Sample EC6 was then compared to the previously made sample EC3 and a judgment made as to Morwet® IP versus Aerosol® OT-100 functioning as a co-surfactant to gelatin B in this invention.

[0162] Table 12

[0163] It has been shown that the present invention encapsulates otherwise difficult to formulate active ingredients in biodegradable microcapsules. The capsules have been found to have good size distribution for effective volatility control, storage stability, ease of handling and rapid release rates of the active ingredient.

[0164] 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 gelatin and a cosurfactant and an oil phase comprising the agrochemical wherein the co-surfactant comprises an anionic surfactant.

2. The process according to claim 1 , wherein the co-surfactant comprises a sulphur- containing moiety.

3. The process according to claim 1 or 2, wherein the co-surfactant comprises comprise a sulphonate functional group.

4. The process according to claims 1 to 3, wherein the co-surfactant comprises a salt of naphthalene sulphonate or a salt of a substituted naphthalene sulphonate and / or sodium dioctyl sulfosuccinate.

5. The process according to claim 4, wherein the co-surfactant comprises a salt of alkyl naphthalene sulphonate.

6. The process according to any one of the preceding claims, wherein the amount of co-surfactant is 1-50% w / w of the amount of gelatin.

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

8. 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.

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 emulsion.

10. 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.

11. The process according to claim 10, 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.

12. The process according to any one of claims 10 or 11, comprising a high-shear homogenisation step after adding the carboxylated polysaccharide.

13. The process according to any of the preceding claims, wherein the capsules have a diameter of less than 15 microns, than 10 microns, less than 5 microns; and / or exhibit controlled release.

14. A composition comprising a microcapsule prepared by the method of any of claims 1 to 13.

15. An agrochemical composition comprising an oil-in-water emulsion, comprising20 to 70wt% of an oil phase comprising an agrochemical active ingredient;30 to 80 wt% of an aqueous phase comprising gelatin and a co-surfactant.

16. An agrochemical composition comprising: microcapsules of a biodegradable polymer suspended in an aqueous continuous phase comprising a co-surfactant; 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.

17. Use of a composition according to any one of claims 14 to 16 in the treatment of weeds, pests, nematodes, molluscs and / or fungi.

18. Use of a biodegradable microcapsule prepared by the method of any of claims 1 to 13.

19. Use of a biodegradable microcapsule for the delayed release of one or more of Prosulfocarb, S-metolachlor, Lambda-cyhalothrin, and / or Tefluthrin.

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