SYNTHESIS AND THERAPEUTIC POTENTIAL OF A MACROMOLECULAR PRODRUG OF DIFLUNISAL

A macromolecular prodrug of diflunisal was synthesised by linking this anti-inflammatory agent to an alpha,beta-poly(N-hydroxyethyl)-DL-aspa rtamide (PHEA) polymeric carrier via an ester bond. The resulting PHEA -diflunisal conjugate, containing a quantity of linked drug of 16% (w/ w) is, like the polymeric carrier, water-soluble. The delayed drug rel ease from the conjugate, in simulated gastric juice, indicates that th e adduct PHEA-diflunisal is suitable for peroral applications. Moreove r, it was shown that this conjugate subjected to enzymatic hydrolysis releases all the linked drug in the active form, within 24 h. Finally, it was experimentally ascertained that neither PHEA-diflunisal nor PH EA induced platelet aggregation at least up to a polymer concentration of 2% (w/v) in platelet-rich plasma. According to these consideration s, the PHEA-diflunisal conjugate can also be employed for parenteral a pplications.