Acrylic type polymers containing ibuprofen and indomethacin with difunctional spacer group: Synthesis and hydrolysis

Acryloyl- and methacryloyloxyethyl ester and amide of ibuprofen and indomethacin, two kinds of non-steroidal anti-inflammatory drugs, were prepared under mild conditions. A difunctional spacer group was introduced between the drug and acrylic moiety of the monomer through an hydrolyzable ester or amide linkage. Free radical polymerization of the resulting monomers were carried out in DMF, DMSO or dioxane solution, using AIBN as initiator at the temperature range 60-70 degrees C. The polymers were characterized by FT-IR, H-1 NMR and C-13 NMR spectroscopies. Stereochemical configuration of monomeric units along the polymer chain had been analysed by NMR spectroscopy. Gel permeation chromatography (GPC) was used for determination of average molecular weights of drug pendent polymers. Glass transition temperature (Tg) of the polymers was determined calorimetrically. The hydrolysis of drug-polymer conjugates was carried out in cellophane membrane dialysis bags containing aqueous buffer solutions (pH 8 and pH 1) at 37 degrees C. Detection of hydrolysis solution by UV spectroscopy showed that the drug can be released by hydrolysis of ester or amide bonds between the drug and spacer group. The acryloyloxyethyl type polymers having a polar amide group were hydrolyzed rather easily.