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

The kinetics of fenoprofen release from poly[alpha,beta-(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 degreesC) and k = 0.0177 h (-1) (t = 37 degreesC) 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 (E-a = 100.6 kJ mol (-1)) The concentration of the released fenoprofen was determined by high performance liquid chromatography (HPLC). (C) 2002 Elsevier Science B.V. All rights reserved.