In drug delivery systems, mathematical modeling plays an important role in elucidating the release mechanisms, the potential applications of a determinate system matrix drug, or the design of new delivery systems. In this work, we have modeled porous biodegradable foams based on polylactide (PLA) and poly(lactide-co-glycolide) (PLGA) impregnated with a hydrophobic drug (indomethacin) through a single-step process using supercritical CO2 as foaming agent. The modeling of indomethacin in vitro release was based on a previous model developed to describe accurately the process of release of a hydrophilic drug and consisting of three simpler and more comprehensible stages: external and internal mass transfer as well polymer degradation. It has been modified considering the low aqueous solubility of indomethacin and the variations in the mechanism produced, consequently improving its physical signification. Finally, the solubility of different drugs impregnated and their response in the release profiles were evaluated.