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++ +-1-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 microspheres 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.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Takada S,Kurokawa T,Miyazaki K,Iwasa S,Ogawa Ydoi
10.1023/a:1012190304074subject
Has Abstractpub_date
1997-09-01 00:00:00pages
1146-50issue
9eissn
0724-8741issn
1573-904Xjournal_volume
14pub_type
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journal_title：Pharmaceutical research
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