The aim of the present study is to investigate and compare the solubilizing effect of Pluronic F127 toward leflunomide in biorelevant media FaSSGF and FaSSIF simulating the gastrointestinal fluids and in the standard pharmacopoeia buffers. More pronounced reduction of leflunomide solubilization by Pluronic F127 was observed in FaSSIF. The influence of various micellar species, which are present in the dissolution media under study, on the leflunomide solubilization was considered in detail. Selectivity of leflunomide interactions with primary and secondary micelles of taurocholate was revealed. Formation of the mixed micelles and their interactions with leflunomide molecules were considered. According to the obtained results, it is suggested that binding of taurocholate with the polymeric micelles results in the weakening of solubilization capability of Pluronic F127 to leflunomide in the biorelevant media.