MECHANOCHEMICAL SOLID-STATE POLYMERIZATION - VIII - NOVEL COMPOSITE POLYMERIC PRODRUGS PREPARED BY MECHANOCHEMICAL POLYMERIZATION IN THE PRESENCE OF PHARMACEUTICAL AIDS

We carried out the mechanochemical polymerization of methacryloyl deri vatives of acetoaminophen and 5-fluorouracil in the presence of lactos e. The reaction proceeded readily and the polymeric prodrugs were quan titatively produced. This method produces powdered polymeric prodrugs in which fine particles of lactose are homogeneously dispersed, since the reaction proceeds quantitatively through a totally dry process. It is difficult to prepare such a powdered polymeric prodrug by conventi onal solution polymerization. The rate of drug release of polymeric pr odrugs increases with increasing content of lactose, as is shown to be true of the specific surface of polymeric prodrugs, These results sug gest that lactose is homogeneously dispersed in powdered polymeric pro drugs. The present method seems applicable to a wide variety of pharma ceutical aids, If one takes the physicochemical property of pharmaceut ical aids into consideration, novel polymeric prodrugs with a variety of drug release rates can be synthesized simultaneously with mixing.