In this work, the combination of two solubilizing agents, methyl-beta-cyclodextrin and Pluronic F68, is proposed and analyzed for a sparingly water soluble drug, fenbufen. Despite the large solubility enhancement achieved, ca. 70-fold, the synergistic effect promoted by the combination of these agents, is only effective over a narrow concentration range, being replaced by a competition between the drug and hydrophobic blocks of the copolymer when the concentration of the latter increases. Moreover, the detailed analysis of the release profiles, resorting to a model dependent approach, shows that the combination of these agents is a strong modulator of the overall profile and also of the total amount of drug that is released. Molecular dynamics simulation indicates a significant change in the cyclodextrin behavior, when alone in solution, situation in which the collapse of the conical structure is relatively frequent, or in the presence of each of the other components, and also shows that copolymer extension is decreased upon introduction of the drug, while there is an increase in extension when the cyclodextrin is added. Inclusion complexes are detected for both drug and copolymer. These play a definite role in solubilization by cyclodextrins, but are also responsible for the competitive behavior observed when polymeric micelles are present. Hydrophobic block copolymers compete with the drug for the cyclodextrin cavity through the formation of polypseudorotaxanes, which in turn modulates drug release. From the fundamental point of view, this work presents an in depth analysis of the molecular behavior in these systems, focusing on the cyclodextrin, inclusion complexes, polymeric micelles and supramolecular systems.