caa a22 4500 477126073 CHVBK 20180405111650.0 cr unu---uuuuu 170330e19970901xx s 000 0 eng 10.1023/A:1012190304074 doi (NATIONALLICENCE)springer-10.1023/A:1012190304074 Utilization of an Amorphous Form of a Water-Soluble GPIIb/IIIa Antagonist for Controlled Release from Biodegradable Microspheres [Elektronische Daten] [Shigeyuki Takada, Tomofumi Kurokawda, Keiko Miyazaki, Susumu Iwasa, Yasuaki Ogawa] 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. Plenum Publishing Corporation, 1997 amorphous nationallicence GPIIb/IIIa antagonist nationallicence controlled release nationallicence PLGA, microspheres nationallicence Takada Shigeyuki DDS Research Laboratories, Takeda Chemical Industries, Ltd., 2-IT-85, Juso-honmachi, 532, Yodogawa-ku, Osaka, Japan aut Kurokawda Tomofumi DDS Research Laboratories, Takeda Chemical Industries, Ltd., 2-IT-85, Juso-honmachi, 532, Yodogawa-ku, Osaka, Japan aut Miyazaki Keiko DDS Research Laboratories, Takeda Chemical Industries, Ltd., 2-IT-85, Juso-honmachi, 532, Yodogawa-ku, Osaka, Japan aut Iwasa Susumu DDS Research Laboratories, Takeda Chemical Industries, Ltd., 2-IT-85, Juso-honmachi, 532, Yodogawa-ku, Osaka, Japan aut Ogawa Yasuaki DDS Research Laboratories, Takeda Chemical Industries, Ltd., 2-IT-85, Juso-honmachi, 532, Yodogawa-ku, Osaka, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1146-1150 0724-8741 14:9<1146 1997 14 11095 https://doi.org/10.1023/A:1012190304074 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012190304074 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takada Shigeyuki DDS Research Laboratories, Takeda Chemical Industries, Ltd., 2-IT-85, Juso-honmachi, 532, Yodogawa-ku, Osaka, Japan aut NATIONALLICENCE 700 1- Kurokawda Tomofumi DDS Research Laboratories, Takeda Chemical Industries, Ltd., 2-IT-85, Juso-honmachi, 532, Yodogawa-ku, Osaka, Japan aut NATIONALLICENCE 700 1- Miyazaki Keiko DDS Research Laboratories, Takeda Chemical Industries, Ltd., 2-IT-85, Juso-honmachi, 532, Yodogawa-ku, Osaka, Japan aut NATIONALLICENCE 700 1- Iwasa Susumu DDS Research Laboratories, Takeda Chemical Industries, Ltd., 2-IT-85, Juso-honmachi, 532, Yodogawa-ku, Osaka, Japan aut NATIONALLICENCE 700 1- Ogawa Yasuaki DDS Research Laboratories, Takeda Chemical Industries, Ltd., 2-IT-85, Juso-honmachi, 532, Yodogawa-ku, Osaka, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1146-1150 0724-8741 14:9<1146 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer