Harnessing the Complexity of EC Formulations with Solvay: Solvents Performance and Sustainability at Heart

Modern high performance fungicides Emulsifiable Concentrates (EC) formulations are challenging to design with the need to identify non-toxic, sustainable solvents to solubilize high loading of actives.

In order to achieve an optimal biological efficacy and avoid the emergence of pest resistance, agricultural practices strategies involve the combination of different chemical classes of agrochemical actives for a patchwork of modes of action. For fungicides, it is for example very common to associate in the same emulsifiable concentrate (EC), triazoles with strobilurins and/or carboxamides and/or picolinamides. However, such molecules display different physico-chemical characteristics and solubility profiles, and the identification of a suitable solvency system is fastidious, and time consuming. For adequate solvents selection, formulators should consider the solubilization performance at various temperatures for the targeted active(s) loadings, but also specific physico-chemical and olfactory characteristics (high flash point, chemical stability, water miscibility threshold to avoid crystallization issues upon dilution in water, low smell characteristics, packaging compatibility etc.), as well as regulatory compliance for the targeted regions of use and low hazards considerations. In this respect, the toolbox of versatile polar aprotic or protic solvents has shrunk considerably over the last ten years in Europe, with the ban of reproductive toxicity cat.1B solvents such as N-methyl-2-pyrrolidone (NMP) or Tetrahydrofurfuryl alcohol (THFA) for use as co-formulants in plant protection products, and potential future restrictions for additional traditional solvents emerging.

In addition, sustainability and eco-friendly considerations are gaining more and more importance: an ideal solvent should be readily or at least inherently biodegradable, with no or low ecotoxicity, and with a high level of circularity (high renewable carbon index (RCI) [1], low carbon emission footprint). Figure 1 describes the general matrix of desired characteristics for an ideal solvent system.

Figure 1. Summary of the relevant characteristics to consider for the selection of a suitable solvent, for EC development

Introducing Solvay toolbox: a large solvents portfolio

Solvay has developed over the last 20 years a dedicated large portfolio of aprotic and protic solvents with low tox-ecotox profile, various polarity and water miscibility, enabling to tackle most challenging EC developments. Table 1 describes the main grades and their corresponding characteristics.

Table 1. Characteristics of Rhodiasolv^® solvents grades. All products are REACH and EPA registered.

High throughput methodologies and modeling tools to identify relevant solvents associations.

High throughput methodologies were developed at Solvay Laboratory of Future (LOF) in order to identify in a very fast way new sustainable solvents associations of interest for a targeted active, by combining Hansen approach HSPiP [2], robotic experiments, quantum mechanics thermodynamics simulations (COSMO-RS) [3], and machine learning approaches.

Hansen's approach is the most popular solubility theory wherein solvents and active ingredients are described by 3 parameters corresponding to dispersion (dD), polar (dP) and hydrogen bonding (dH) interactions. The approach consists in the first step to determine experimentally the Hansen solubility parameters and sphere of active ingredients (in solo or combo) by testing their solubility into a set of 46 conventional solvents well located in the Hansen space at a given temperature and concentration. Then, in a second phase, a proprietary algorithm is applied to optimize, generate and evaluate experimentally more than one hundred blends of solvents located inside the solubility sphere of the active ingredient or close to its boundaries.    
 
In addition to HSPiP, purely theoretical and in silico methods were applied to study liquid systems and physico-chemical properties of molecules in solution. Solvent effects are pertinently described by continuum solvation models that simulate the solvent medium by a dielectric continuum within the frame of quantum mechanics. The COnductor-like Screening MOdel for Real Solvents (COSMO-RS) is a refinement of one of these models combined with statistical thermodynamics. Only based on molecular structures, COSMO-RS provides an a priori prediction of thermodynamic data such as partition coefficients, vapor pressures and activity coefficients. This purely predictive approach is especially used for a theoretical screening of pure and blend of solvents to solubilise active ingredients for complex Emulsifiable Concentrates (EC).

Recently, Solvay developed an interactive internal web-app, compiling a large number of external and internal sources of solubility and physicochemical properties data of solvents and active ingredients. In addition to the smart visualization and filtration options (hazard statements, regulatory criteria (EPA, REACH), water miscibility, flash point, boiling point etc.), our researchers can also optimize blends of solvents to solubilise active ingredients by using Hansen, COSMO-RS approaches and proprietary algorithms integrated in the web-app, which also includes deep learning models to predict solubility parameters of solvents and solutes without bench work.

Figure 2.  Strategy used to identify new solvents associations, by combining Hansen approach HSPiP, HTP experiments, quantum mechanics thermodynamics simulations (COSMO-RS), and machine learning approaches.

A practical example based on identifying safer solvents for the development of full formulation EC Prothioconazole/Azoxystrobin 125/75gr/L is described: synergistic behavior was highlighted, with the use of a specific polar aprotic ester amide solvent (Rhodiasolv^Ⓡ Polarclean) enabling to achieve a good solubility spectrum for the targeted active(s), in presence of other biobased non water-miscible solvents (A and B) displaying a poor intrinsic solubility performance for such active(s). Interestingly the solvents blend of interest has a high renewable carbon index (55%), with a mild classification, and displays a good solubilization potential for classical modern fungicides families.

Figure 3. Positioning of the pure solvents (stars) and the blend of solvents (blue square) compared to the Hansen solubility sphere of the combo Prothioconazole/Azoxystrobin at 125/75g/l at 0°C (Black sphere).

Creation of high performance solvents associations with better renewable carbon index

This general approach was enlarged to a large variety of classical fungicides belonging to triazoles, strobilurins, to design new solvent blends with a large solubilization spectrum, with a specific attention on their low tox-ecotox profile and a high renewable carbon index. Table 2 describes 3 solvent blends of interest, designed thanks to the methodology detailed above.

Table 2. Solubilizing performances of 3 bio-based blends for triazole and strobilurin actives (gr of solubilized active / 100 gr of solvent, 25°C)

The associations of such sustainable solvents blends and considered active ingredients were found to be easy to emulsify. A practical example of complete EC development is given in Table 3 with Soprophor^Ⓡ S/25 and Rhodacal^Ⓡ 60B/E as classical emulsifiers.

Table 3. Composition of Emulsifiable Concentrate (EC), 250gr/L prothioconazole with blend T and its characteristics.

Under the increasing pressure to accelerate its transition towards more sustainable practices, the agriculture industry is striving to effectively protect crops and enhance the efficiency of food production without compromising on the environment or food safety. Rising to the challenge, Solvay is accelerating its innovation to find more sustainable and safer solutions, and thereby broaden the agrochemical formulators’ options, in particular in terms of solvent systems. New Solvay solutions, developed thanks to the association of the latest company's innovations with high throughput methodologies and deep learning models, will help formulators to efficiently identify the best and safest solvents with a high renewable carbon index for a targeted active(s) system.

We would be very happy to propose our technical support for your solubility challenges and formulations development, please do not hesitate to contact us at monique.adamy@solvay.com, claire.darre@solvay.com

[1] The Renewable Carbon Index, or RCI, measures sustainability by dividing the number of carbons derived from renewable sources (from biomass or from recycling of already existing plastics & other organic materials) by the total number of carbons in an active ingredient. A high RCI substance contains a high percentage of carbon atoms from renewable sources.
Calculations in table 2 are based on information in our possession and reflect our current knowledge and experience of the products. This information is offered solely for your consideration. We disclaim all liabilities in relation to the use of the present information.

[2] C.M. Hansen, The three dimensional solubility parameter – key to paint component affinities I, J. Paint Technol. 39 (1967) 104–117.

[3] A. Klamt, Conductor-like screening model for real solvents: a new approach to the quantitative calculation of solvation phenomena, J. Phys. Chem. 99 (1995)2224–2235.

This article will be published in AgroPages '2023 Formulation & Adjuvant Technology ' magazine to be published this May.

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