Polymeric prodrugs, 5. Dextran‐bound antirheumatic agent naproxen

The dextran-bound antirheumatic agent, Naproxen [(+)-2-(6-methoxy-2-naphtyl)propionic acid] (3) was synthesized by linking the 2-aminoethyl ester of Naproxen to the oxydized dextran via an alkylamine bond. The hydrolytic stabilities of modified dextrans were examined viscometrically. The drug release from polymeric prodrug samples containing 68–172 mg of Naproxen per g product was followed at 37°C by automatic titration at pH 8,4. The first order kinetic constant of hydrolysis, k1, was determined to be 2,46(±0,4) · 10−6 s−1. Acute toxicity tests showed no toxic effect on CFLP mice administered intraperitoneally 300 mg/kg of dextran-bound Naproxen.