S. Takada et al., SUSTAINED-RELEASE OF A WATER-SOLUBLE GP IIB IIIA ANTAGONIST FROM COPOLY(DL-LACTIC/GLYCOLIC)ACID MICROSPHERES/, International journal of pharmaceutics, 146(2), 1997, pp. 147-157
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.