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 degrees C) and k=0.0177 h(-1) (t=37 degrees 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 (E(a)=100.6 kJ mol(-1)). The concentration of the released fenoprofen was determined by high performance liquid chromatography (HPLC).
van der Merwe
T
T
Department of Pharmaceutical Chemistry, Potchefstroom University for CHE, P.B. X6001, Potchefstroom 2520, South Africa.
Boneschans
B
B
Zorc
B
B
Breytenbach
J
J
Zovko
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005279:Fenoprofen / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011102:Polyhydroxyethyl Methacrylate / Q000031:analogs & derivatives* / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D011102:Polyhydroxyethyl Methacrylate; C023037:poly(2-hydroxyethyl acrylate); D005279:Fenoprofen