pH Sensitive Polymeric Prodrugs Containing Ibuprofen, Ketoprofen and Naproxen as Pendent Groups

Abstract

Polymeric prodrugs were prepared by copolymerization of methacrylic acid (MA) with 2-hydroxyethyl methacrylate (HEMA) covalently linked with ibuprofen (HI), ketoprofen (HK) and naproxen (HN). Varying the monomer compositions in the copolymers afforded water-soluble polymeric prodrugs. The dissolution of these polymeric prodrugs was assayed by measuring the absorbance of the drug moiety in the parent prodrug (including the moieties, which were hydrolytically cleaved) after immersing for 3 h in buffer solutions at various pHs. The dissolution profiles were dependent on the copolymer composition. Both ester bonds were cleaved in pH 7.4 as well as pH 10 buffer solutions. The hydrolyzed products, hydroxyethyl ester of ibuprofen (Ibu-EtOH), ketoprofen (Keto-EtOH) and naproxen (Nap-EtOH) were synthesized. The free drugs and their drug-EtOH were qualitatively and quantitatively analyzed by high performance liquid chromatography (HPLC).