Overview

The Conductor-like Screening Model for Realistic Solvation (COSMO-RS) is the theoretical basis for the BIOVIA COSMOtherm tool. Fundamentally, COSMO-RS predicts the standard state chemical potential of small to medium-sized molecules in liquids. Leveraging thermodynamics and other principles of physical chemistry, COSMO-RS has been successfully used to predict various macroscopic properties of interest, such as solubility, volatility and solvent miscibility. However, the expert in consumer product formulation may initially dismiss COSMO-RS as a useful tool because of the complexity of real-life mixtures. After all, consumer products, such as shampoos, cosmetics, or detergents, often contain highly structured dispersions, as well as complex substances engaging in intricate and diverse interactions, such as polymers, salts or bio-molecules.

Tackling Consumer Product Formulations

COSMO-RS, though, can and has been used to aid in resolving consumer product formulation challenges. In a recent two-part report, we have provided a comprehensive overview of the application of COSMO-RS in various consumer product formulations [1, 2].

The trick is properly scoping COSMO-RS’s use, in terms of “Step, Setup, Score”:

1. Step: formulation typically requires several workflow steps, and COSMO-RS will be more relevant for some than for others;
2. Setup: in some steps, the system is simple enough to be directly simulated with COSMO-RS, and in others, coming up with a simplified model system will allow use of COSMO-RS;
3. Score: which properties are we optimizing?

Back to Basics

Even though nowadays COSMO-RS enables to predict many different properties of and in liquids, such as activity/partition/diffusion/Henry coefficients as well as vapor pressure, boiling point, viscosity, dielectric constant, the core strength of this theory is to provide a quantitative measure of the affinity of an ingredient for a medium, through the standard state chemical potential. Because of the complexity of real-life formulations, applying the sophisticated theoretical frameworks coming with COSMO-RS to predict these endpoint properties, which require full knowledge of the molecular structure of each component of the liquid, is often impractical.

Thus, a beautiful paradox is that the simplest application of COSMO-RS (predicting the chemical potential) is also the most useful for complex media such as consumer product formulations. The best success has been found for consumer products by simply:

1. Defining a relevant model system, such as Natural Deep Eutectic Solvents (NADES);
2. Predicting the chemical potential of an active ingredient of interest (such as an antioxidant) in various compositions for this model system;
3. Rank ordering predictions to short list candidate compositions that dissolve this active ingredient of interest best, and can be good vehicles to disperse it in the target formulation.

A Success Story

Antioxidants play a critical role in preserving product quality and prolonging the shelf life of consumer goods. Rutin (cf. Figure 1) is a powerful antioxidant, also investigated for potential health benefits and as a skincare ingredient. It can be extracted from biomass.

Figure 1. Rutin (left), and Aspartic acid / Proline NADES (right)

Thus, there is interest in the formulation industry to dissolve rutin in various consumer products. However, rutin dissolves poorly in water, making its dispersion in formulations challenging.

NADES are solvent preparations based on a mixture of bio-compatible molecules, classified as Hydrogen-Bond Acceptor (HBA) and Hydrogen Bond Donor (HBD). The HBA and HBD are typically solid when in their pure form, but liquid when mixed, opening the way to numerous innovative solvent combinations. They are ideal solvent candidates when it comes to dispersing an active ingredient of interest such as rutin, but finding the right combination for the right ingredient is a needle-in-a-haystack problem.

Such a challenge is perfectly suited for computational methods, and in particular, COSMO-RS, which has proven to be a method of choice to screen NADES [1, 2].

 In this context, Jeliński & Cysewski [3] have screened a number of different NADES with BIOVIA COSMOtherm, following-up with experimental solubility measurements on shortlisted NADES, minimizing the chemical potential in the NADES. They found that the aspartic acid/proline combination provided an 80% increase in solubility over the state-of-the-art, using amino-acids that combine moderate cost with high bio-compatibility. Their judicious use of BIOVIA COSMOtherm (see Table 1) has delivered a sustainable and efficient solution to improve the quality and shelf-life of consumer products.

Step	Setup	Score
Dispersion of antioxidant in formulation	Antioxidant dissolved in the dispersion solvent	Minimizing chemical potential of antioxidant in dispersion solvent

Table 1. Step, setup, score approach adopted by Jeliński & Cysewski [3]

👉 Explore COSMO-RS on 3ds.com

References

[1] Gaudin & Aubry, COCIS, 2025, 75 (101874), doi: 10.1016/j.cocis.2024.101874

[2] Gaudin & Aubry, COCIS, 2025, 75 (101876), doi: 10.1016/j.cocis.2024.101876

[3] Jeliński & Cysewski, J. Mol. Model., 2018, 24 (180), doi: 10.1007/s00894-018-3700-1

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