SUSTAINED-RELEASE OF A WATER-SOLUBLE GP IIB IIIA ANTAGONIST FROM COPOLY(DL-LACTIC/GLYCOLIC)ACID MICROSPHERES/

Sustained release of TAK-029 glycyl)-3-methoxycarbonyl-2-oxopiperazine -1-acetic acid], a glycoprotein (GP) IIb/IIIa antagonist, from injecta ble microspheres was achieved by a W/O/W emulsion solvent evaporation technique using copoly(DL-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-arg inine to an internal water phase dose-dependently reduced initial burs t 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 u sing sodium chloride and L-arginine demonstrated sustained plasma leve ls of TAK-029 for 3 weeks after subcutaneous injection in rats, while causing a slight increase of its plasma levels in 2-3 weeks. (C) 1997 Elsevier Science B.V.