The free energy translocation of the drugs (DTXL) and prodrugs (DTXL-OA, PEG10-DTXL, PEG25-DTXL) from an equilibrated PLGA matrix to the aqueous solution (the reaction coordinate representing the release progress), was computed at CG level by the umbrella sampling (US) approach. The PLGA matrix consisted of chains with degree of polymerization N=10 to ensure reasonable mobility and relaxation time. The US method allows to improve the sampling of rare events (e.g., a hydrophobic compound visiting the water phase) through the use of a bias potential that forces the compound of interest to explore regions that would otherwise not be energetically accessible. The unbiased free energy profile can be recovered by subtracting the known bias potential from the biased probability distribution obtained from simulations.