LAUSR

Graphical abstract Figure. No caption available. ABSTRACT Recent work demonstrated remarkable solubilization effects of methacrylate‐copolymer Eudragit EPO (EPO) not only with acidic drugs but interestingly also with poorly soluble basic compounds. The current work studied EPO‐mediated solubilization effects first in vitro using felodipine (FLP) and tamoxifen (TMX) as model compounds. EPO‐containing solutions were subsequently compared in a rat pharmacokinetic study against reference solutions and suspensions. Surprisingly, solution formulations with EPO did not result in an increased relative oral bioavailability. Exposure was reduced for both drugs and plasma‐profiles of the EPO solutions showed a delayed and lower maximum plasma concentration compared to the reference formulations. This sustained in vivo release was likely due to combined effects of strong drug‐polymer interactions and pH‐dependent precipitation of the polymer in the rat intestine. Remarkable was that in vitro drug‐polymer coprecipitates did not reveal crystalline drug by polarized light microscopy. Thus, such a formulation approach provides a rather simple opportunity to modify drug release in vivo. However, this may be rather an approach for preclinical formulations, if high peak‐to‐trough ratios of plasma levels are problematic regarding adverse effects related to Cmax or if plasma concentrations drop too fast below required pharmacological concentrations.