PLGA implant tablet of ketoprofen: comparison of in vitro and in vivo releases.
An implant tablet of ketoprofen (KP) was developed in order to achieve its sustained supply for approximately one week, and its release was evaluated in vitro and in vivo. Implant tablets (30 mg) containing 1 and 5 mg of ketoprofen, prepared using poly(DL-lactic acid-co-glycolic acid) copolymer (PLGA; MW 10000; lactic acid : glycolic acid=1 : 1 (mol/mol)) as a matrix, exhibited similar week-long sustained release in vitro. Plasma concentration was monitored after the implant tablet (5 mg of KP) and a KP solution (0.5 mg of KP) were administered subcutaneously to rats, and in vivo release rate was analyzed by deconvolution. The release rate from the implant tablet was faster in vivo than in vitro in the initial phase, but much lower in vivo than in vitro in the later phase. The plasma level decreased to the level less than the minimal effective concentration at 96 h after administration. However, the calculated plasma concentration given by convolution based on in vitro release rate was more than 7 times greater than the minimal effective concentration even at 96 h after administration. As the implant displayed the discrepancy between in vitro and in vivo release rates, the improvement of the in vivo release rate is required.
Onishi
Hiraku
H
Department of Drug Delivery Research, Hoshi University; Tokyo 142-8501, Japan. onishi@hoshi.ac.jp
Takahashi
Mari
M
Machida
Yoshiharu
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004343:Drug Implants; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000008:administration & dosage* / Q000097:blood; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013607:Tablets
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004343:Drug Implants; D011108:Polymers; D013607:Tablets; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007660:Ketoprofen