The alchemical free energy method was used to determine the solubility of the following species in selected solvents at the atomistic and coarse-grained level: a) a dimeric PLGA unit in acetone, octanol and water solvents; b) DTXL in octanol and water solvents; c) PEG chains with degree of polymerization N = 10 and 20 in a polymer matrix consisting of PLGA chains with N = 10 and in water. In alchemical simulations, the solute explores a series of nonphysical intermediates generated by progressively turning off the interactions with the solvent using a coupling parameter lambda λ (λ = 0, 0.1,...,1). For atomistic models with partial atomic charges, Coulomb and Lennard-Jones components of the λ vector were turned off sequentially (20 λ windows in total), whereas for the uncharged coarse-grained systems, only the Lennard-Jones potential was considered (10 λ windows in total). Soft-core (sc) potentials were selected to smooth interactions at the cut-off distance to avoid large fluctuations deriving from the superposition of particles when the interaction energy is weak (near the end points λ = 0, and λ = 1). Each window was sampled for 20 ns at 300K using the stochastic dynamics (SD) integrator. The Multistate-Bennetts-Acceptance-Ratio (MBAR) method was employed to estimate the solvation free energy differences between 𝜆=0 and 𝜆=1 and statistical errors.