Synthesis, characterization and in-vitro evaluation of novel polymeric prodrugs of mefenamic acid

In this research work, a serious of novel polymeric prodrugs of mefenamic acid was prepared in order to minimize of the mefenamic acid side effects. Glycidyl methacrylate was first copolymerized with acrylamide and methyl methacrylate by free radical solution polymerization method, using α,ά-azobisisobutyronitrile as an initiator at 70±2 oC. Mefenamic acid, as a non-steroidal anti-inflammatory drug, was then attached to the synthesized copolymers via the hydrolysable ester bonds by transesterification procedure in the presence of N,N'-dicyclohexylcarbodiimide to give polymeric prodrugs. The synthesized copolymers and polymeric prodrugs were characterized by various techniques such as FT-IR, 1HNMR and 13CNMR to confirm their structures. These polymeric prodrugs were hydrolyzed in cellophane membrane dialysis bags containing aqueous buffer solutions (pH 1, 7.4 and 8.5) at 37 oC. Analysis of the hydrolyzing solutions by UV spectrophotometer at selected intervals showed that the drug could be released by selective hydrolysis of the ester bond from side chain of drug moiety. The release profiles of drug indicated that the hydrolytic behavior of polymeric prodrugs strongly depends on the hydrophilicity of polymer and the release rate of mefenamic acid at alkaline medium is higher than other mediums. These developed systems would be useful for the development of pH-sensitive polymeric prodrugs in controlled release systems.