On the coupling between ionic conduction and dipolar relaxation in deep eutectic solvents: Influence of hydration and glassy dynamics.

We have studied the ionic conductivity and the dipolar reorientational dynamics of aqueous solutions of a prototypical deep eutectic solvent (DES), ethaline, by dielectric spectroscopy in a broad range of frequencies (MHz-Hz) and for temperatures ranging from 128 to 283 K. The fraction of water in the DES was varied systematically to cover different regimes, starting from the pure DES and its water-in-DES mixtures to the diluted electrolyte solutions. Depending on these parameters, different physical states were examined, including low viscosity liquid, supercooled viscous liquid, amorphous solid, and freeze-concentrated solution. Both the ionic conductivity and the reorientational relaxation exhibited characteristic features of glassy dynamics that could be quantified from the deviation from the Arrhenius temperature dependence and non-exponential decay of the relaxation function. A transition occurred between the water-in-DES regime (<40 wt. %), where the dipolar relaxation and ionic conductivity remained inversely proportional to each other, and the DES-in-water regime (>40 wt. %), where a clear rotation-translation decoupling was observed. This suggests that for a low water content, on the timescale covered by this study (∼10-6 to 1 s), the rotational and transport properties of ethaline aqueous solutions obey classical hydrodynamic scaling despite these systems being presumably spatially microheterogeneous. A fractional scaling is observed in the DES-in-water regime due to the formation of a maximally freeze-concentrated DES aqueous solution coexisting with frozen water domains at sub-ambient temperature.

Manipulating the physical states of confined ibuprofen in SBA-15 based drug delivery systems obtained by solid-state loading: Impact of the loading degree.

Using the Milling-Assisted Loading (MAL) solid-state method for loading a poorly water-soluble drug (ibuprofen, IBP) within the SBA-15 matrix has given the opportunity to manipulate the physical state of drugs for optimizing bioavailability. The MAL method makes it easy to control and analyze the influence of the degree of loading on the physical state of IBP inside the SBA-15 matrix with an average pore diameter of 9.4 nm. It was found that the density of IBP molecules in an average pore size has a direct influence on both the glass transition and the mechanism of crystallization. Detailed analyzes of the crystallite distribution and melting by Raman mapping, x-ray diffraction, and differential scanning calorimetry have shown that the crystals are localized in the core of the channel and surrounded by a liquid monolayer. The results of these complementary investigations have been used for determining the relevant parameters (related to the SBA-15 matrix and to the IBP molecule) and the nature of the physical state of the confined matter.

Extension and Limits of Cryoscopy for Nanoconfined Solutions.

This work investigates the phase behavior of aqueous solutions of glycerol confined in MCM-41 and SBA-15 nanoporous matrixes by calorimetry. Limitations due to overfilling and eutectic freezing are prevented by the absence of an external liquid reservoir and by the glass-forming property of glycerol. Consequently, the stability of nanoconfined ice in equilibrium with aqueous solutions is studied over a wide range of compositions. In confinement, a large temperature depression of the liquidus line is observed. A thermodynamic model accounting simultaneously for the cryoscopic and the Gibbs-Thomson effects gives a consistent view of the phase diagram for large pores (Rp = 4.15 nm). For smaller pores (Rp = 1.8 nm), it reveals that the water activity strongly deviates from the bulk solution with the same composition, indicating the possible role of concentration heterogeneities in determining the onset of ice freezing in strongly nanoconfined solutions.

Trehalose or Sucrose: Which of the Two Should be Used for Stabilizing Proteins in the Solid State? A Dilemma Investigated by In Situ Micro-Raman and Dielectric Relaxation Spectroscopies During and After Freeze-Drying.

The bioprotective properties of 2 disaccharides (sucrose and trehalose) were analyzed during the freeze-drying (FD) process and at the end of the process, to better understand the stabilization mechanisms of proteins in the solid state. In situ Raman investigations, performed during the FD process, have revealed that sucrose was more efficient than trehalose for preserving the secondary structure of lysozyme during FD, especially during the primary drying stage. The lower bioprotective effect of trehalose was interpreted as a consequence of a stronger affinity of this disaccharide to water, responsible for a severe phase separation phenomenon during the freezing stage. Dielectric spectroscopy investigations on the freeze-dried state of protein formulations have shown the capabilities of trehalose assisted by residual water to reduce the molecular mobility of the vitreous matrix, suggesting that trehalose is more efficient to preserve the protein structure during long-term storage.