Preferential solvation of apremilast in some (Transcutol® plus water) mixtures

Shakeel et al. reported the equilibriumsolubility of apremilast (3) in some {transcutol (1)+ water (2)} mixtures at several temperatures with some numerical correlation analysis. Nevertheless, no attempt wasmade to evaluate the preferential solvation of this compound by the solvents. In this communication the preferential solvation of apremilast in the saturated mixtures at 298.15 K was analyzed based on the inverse Kirkwood-Buff integrals as described in the literature. Apremilast is preferentially solvated bywater in water-rich mixtures (0.00 < x(1) < 0.12) but preferentially solvated by transcutol in mixtures with composition 0.12 < x(1) < 1.00. These results could be interpreted as a consequence of hydrophobic hydration around the non-polar groups of the solute in the former case. Moreover, in the last case, the observed trend could be a consequence of the acid behavior of apremilast in front to transcutol molecules because this cosolvent is more basic than water as described by the respective solvatochromic parameters. (C) 2020 Elsevier B.V. All rights reserved.