<P>Objectives??To avoid the major adverse effects induced by Cremophor EL formulated in the commercial paclitaxel products of Taxol. Methods??An injectable paclitaxel solid dispersion free of Cremophor was prepared by a supercritical antisolvent...
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https://www.riss.kr/link?id=A107564361
2011
-
SCI,SCIE,SCOPUS
학술저널
491-499(9쪽)
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P>Objectives??To avoid the major adverse effects induced by Cremophor EL formulated in the commercial paclitaxel products of Taxol. Methods??An injectable paclitaxel solid dispersion free of Cremophor was prepared by a supercritical antisolvent...
<P>Objectives??To avoid the major adverse effects induced by Cremophor EL formulated in the commercial paclitaxel products of Taxol. Methods??An injectable paclitaxel solid dispersion free of Cremophor was prepared by a supercritical antisolvent process and then was fully characterized and investigated with regard to its short-term and long-term stability. Pharmacokinetics in rats was also evaluated compared with the commercial product. Key findings??The solid dispersion system at a 1/20/40 weight ratio of paclitaxel/HP-관-CD/HCO-40 had a paclitaxel solubility of about 10?g/ml, an almost 10??00-fold increase over its aqueous solubility. This system was physically stable for at least six months or four weeks in accelerated conditions (40??2°C; RH: 75??5%) and stress conditions (60°C), respectively. The precipitation time of paclitaxel solid dispersion in 0.9% sodium chloride injection at a concentration of 1000?/ml was above 70? at room temperature. Intravenous administration of paclitaxel solid dispersion at a dose of 6?g/kg revealed no significant differences when compared with the commercial product. However, our results obtained at a dose of 12?g/kg showed a striking non-linear increase in the plasma Cmax and AUCall with increased dose. In addition, the concentrations of paclitaxel in various organs in the solid dispersion group were found to be higher than those of Taxol at 6?g/kg, and the paclitaxel levels in these organs increased proportionately with increasing dose. Conclusions??Nano-scale paclitaxel solid dispersion without Cremophor EL provided advantageous results over Taxol with respect to the physicochemical properties, safety, clinic convenience and pharmacokinetic behaviour in rats.</P>