Sustained release of a water-soluble GP IIb/IIIa antagonist from copoly(dl-lactic/glycolic)acid microspheres

Abstract Sustained release of TAK-029 [4-(4-amidinobenzoylglycyl)-3-methoxycarbonyl-2-oxopiperazine-l-acetic acid], a glycoprotein (GP) IIb/IIIa antagonist, from injectable microspheres was achieved by a W/O/W emulsion solvent evaporation technique using copoly( d -lactic/glycolic)acid (PLGA). Entrapment of the drug into microspheres increased with addition of sodium chloride into an external aqueous polyvinyl alcohol solution. Addition of l -arginine to an internal water phase dose-dependently reduced initial burst of the drug from the microspheres in vitro and in vivo, probably by forming hydrophobic diffusion barriers with rigid inner structure and increased glass transition temperature ( T g ). Microspheres obtained using sodium chloride and l -arginine demonstrated sustained plasma levels of TAK-029 for 3 weeks after subcutaneous injection in rats, while causing a slight increase of its plasma levels in 2–3 weeks.