Macromolecular prodrugs: X. Kinetics of fenoprofen release from PHEA-fenoprofen conjugate

The kinetics of fenoprofen release from poly[α,β-(N-2-hydroxyethyl-dl-aspartamide)]-fenoprofen conjugate (PHEA-Fen) in aqueous buffer solutions (pH 10 and 1.1), simulated gastric (SGF) and intestinal fluids (SIF) was studied. In borate buffer pH 10, the following rate constants were obtained: k=0.2659 (t=60 °C) and k=0.0177 h−1 (t=37 °C) and in glycine buffer solution pH 1.1 k=0.0036 h−1. In SGF and SIF fenoprofen release did not occur in significant extend within 12 h. The hydrolysis of the ester bond between the polymeric carrier and fenoprofen followed the pseudo first-order kinetics, with activation energy indicative for the breakage of a sigma bond (Ea=100.6 kJ mol−1). The concentration of the released fenoprofen was determined by high performance liquid chromatography (HPLC). [Copyright &y& Elsevier]