Morgan Durand

Panorama of sustainable solvents using the COSMO-RS approach

Recent regulations have banned numerous common organic solvents that have been recognized as hazardous to human health and environment. There is thus a pressing need for alternatives, often called “green” or “sustainable” solvents, which have a good HSE (Health Safety Environment) profile and are preferably obtained from the biomass feedstock. A number of such green solvents are already on the market or under advanced development and have been listed in this work. To use this set of solvents as effective alternatives, a tool is needed to compare their physico–chemical properties to the ones of the solvents they are supposed to replace. The COnductor-like Screening MOdel for Real Solvents (COSMO-RS) approach was used to model the solvents, which were located in a pseudo 3D-space thanks to Principal Components Analysis and clustering procedures. This approach had already been successfully applied to the classification of classical organic solvents into ten families in which the green solvents have been positioned. This pseudo 3D-representation of green solvents helps in the search of potential alternatives to a questionable solvent. It also sheds light on paucity or even a complete lack of green solvents in some families (e.g. strong electron pair donor bases). There is thus a need to develop new green solvents with the prerequisite properties. As the COSMO-RS approach can be applied to almost any potential candidate, it could be a powerful tool for the design in silico of new sustainable solvents.

Solid-State Amorphization of Linaprazan by Mechanical Milling and Evidence of Polymorphism

In this paper, we study the thermodynamic and structural changes of crystalline linaprazan (a proton pump inhibitor) upon high-energy ball milling at room temperature. The investigations have been performed by differential scanning calorimetry and powder X-ray diffraction. The results indicate that this drug undergoes a direct crystal-to-glass transformation upon milling. Moreover, upon heating, the amorphous material obtained by milling is shown to recrystallize toward two different polymorphs that appear to form a monotropic set.

In Silico Search for Alternative Green Solvents

The selection of the most appropriate alternative solvents requires efficient predictive tools that avoid resorting to time-consuming trial and error experiments. Several classifications of organic solvents exist but they most often require the knowledge of one or more experimental characteristics, which might be an obstacle in the case of emerging candidates. This chapter gives an overview of existing tools for the characterisation and classification of organic solvents and particular attention is given to purely predictive methods, such as the COnductor-like Screening MOdel for Real Solvents (COSMO-RS). A panorama of the currently available sustainable solvents is given, and these “green” alternatives are compared to the classical organic solvents, thanks to a completely in silico approach. Examples of substitutions are given to illustrate the methodology that can also be used to design new alternatives.

Toward the Rationalization of Facilitated Hydrotropy: Investigation with the Ternary Dimethyl Isosorbide / Benzyl Alcohol / Water System

Solubility enhancement has been achieved by facilitated hydrotropy for the dimethyl isosorbide (DMI) / benzyl alcohol / water system. Facilitated hydrotropy has been studied via three different approaches: the solubilization in water of a hydrophobic dye, the evolution of the surface tension and dynamic light scattering, all as a function of the benzyl alcohol concentration. The facilitated hydrotropy has been rationalized from the solubilization properties of the system according to the ratio between the insoluble hydrotrope (here benzyl alcohol, a preservative used in parenteral injections) and the bio-sourced co-solvant (here the dimethyl isosorbide ether, DMI, a solvent used in pharmaceutical formulation). The presence of self-associated nanostructures has been detected by dynamic light scattering (DLS). It appears that the cosolvent, DMI, has an antagonistic action: DMI increases the facilitated hydrotrope (benzyl alcohol) solubility in the aqueous solution (favoring solute solubilization) but simultaneously decreases the hydrotropic efficiency of benzyl alcohol.