The feasibility of a monolayer patch based on polydimethylsiloxane pressure sensitive adhesive containing ibuprofen (IB) in supersaturated condition was studied. The efficacy of three low molecular weight excipients (propylene glycol, PG, Cremophor EL and Cremophor RH) and of two copolymers of methacrylic acid (Eudragit((R)) E, EuE, and Eudragit((R)) RL, EuRL) as IB crystallization inhibitors was tested. The performances of the patches were evaluated in terms of drug release and human stratum corneum and epidermis (SCE) permeation profile. The interactions between IB and the other excipients were investigated by ATR-FT-IR spectroscopy. The stability of the patches, prepared without adding crystallization inhibitors, was unsatisfactory because crystals grew in less than 1 month. Among the low molecular weight molecules, only PG inhibited the IB crystallization up to 50 days without affecting the IB skin permeation profile. The addition of EuE or EuRL in the matrices prevented drug crystallization for more than 12 months. EuE significantly reduced the IB in vitro release rate and the IB permeated amount through the SCE compared to other formulations. These phenomena are attributed to a stronger association between IB and EuE than IB and EuRL.