Abstract
Purpose. We prepared injectable microspheres for controlled release of TAK-029, a water-soluble GPIIb/IIIa antagonist and discussed the characteristics of controlled release from microspheres.
Methods. Copoly(dl-lactic/glycolic)acid (PLGA) microspheres were used for controlled release of TAK-029 [4-(4-amidinobenzoylglycyl)-3-methoxycarbonyl-2-oxopiperazine-l-acetic acid]. They were prepared with a solid-in-oil-in-water (S/O/W) emulsion solvent evaporation technique using either a crystalline form or an amorphous form of the drug.
Results. An amorphous form of TAK-029 gave more homogeneous S/O dispersion and higher viscosity than its crystalline form when added to dichloromethane solution of PLGA, resulting in a high drug entrapment into microspheres and a well-controlled release of the drug. Additions of sodium chloride into an external aqueous phase and L-arginine into an oil phase also increased entrapment of the drug, and reduced initial burst of the drug from the microspheres. The micro-spheres demonstrated a desirable plasma level profile in therapeutic range (20−100 ng/ml) for 3 weeks in rats after single subcutaneous injection.
Conclusions. A well-controlled release of TAK-029, a water-soluble neutral drug, with small initial burst was achieved by utilizing its amorphous form as a result of possible interaction with PLGA and L-arginine.
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Takada, S., Kurokawda, T., Miyazaki, K. et al. Utilization of an Amorphous Form of a Water-Soluble GPIIb/IIIa Antagonist for Controlled Release from Biodegradable Microspheres. Pharm Res 14, 1146–1150 (1997). https://doi.org/10.1023/A:1012190304074
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DOI: https://doi.org/10.1023/A:1012190304074