Development and evaluation of an inhibitor-releasing matrix for intrauterine devices

Antifibrinolytic agents when released into the uterine cavity decrease menorrhagia associated with IUD use. Our objective was to develop a matrix that could be incorporated onto an IUD and release anti-fibrinolytic agents. The copolymer ethylene-vinyl acetate (EVA) was selected for detailed study because it has the advantage over other materials in that it can release large molecular weight substances for more than 100 days, and allows incorporation of large amounts of anti-fibrinolytic agents with different molecular weights. Two compounds, tranexamic acid (AMCA, MW=157) and Trasylol (Kunitz pancreatic trypsin inhibitor, (MW=6,500) were incorporated into the EVA matrix and their release rates measured. In vitro studies with AMCA showed that after the initial burst, a constant high release rate was obtained over a prolonged period of time. The in utero release rate of AMCA from the EVA matrix in rabbits was similar to that obtained in vitro. By contrast, the release rate of Trasylol decreased to low levels during incubation in vitro. The release rate of Trasylol in utero however, appeared to be higher than that in vitro.