SCI和EI收录∣中国化工学会会刊

Chin.J.Chem.Eng. ›› 2012, Vol. 20 ›› Issue (4): 803-813.

• MATERIALS AND PRODUCT ENGINEERING • Previous Articles     Next Articles

Effect of Process Parameters on Co-precipitation of Paclitaxel and Poly(L-lactic Acid) by Supercritical Antisolvent Process

LI Wenfeng1, LIU Guijin2, LI Lixian2, WU Juan2, LÜ Yangxiao2, JIANG Yanbin2   

  1. 1. Star Lake Bioscience Co., Inc., Zhaoqing 526040, China;
    2. School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China
  • Received:2012-04-01 Revised:2012-07-03 Online:2012-09-15 Published:2012-08-28
  • Supported by:
    Supported by the National Natural Science Foundation of China (21076084);the Fundamental Research Funds for the Central Universities (2011ZZ0006);the Open Project Program of Provincial Key Laboratory of Green Processing Technology and Product Safety of Natural Products

Effect of Process Parameters on Co-precipitation of Paclitaxel and Poly(L-lactic Acid) by Supercritical Antisolvent Process

李文锋1, 刘贵金2, 李黎仙2, 伍娟2, 吕扬效2, 江燕斌2   

  1. 1. Star Lake Bioscience Co., Inc., Zhaoqing 526040, China;
    2. School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China
  • 通讯作者: JIANG Yanbin, E-mail:cebjiang@scut.edu.cn
  • 基金资助:
    Supported by the National Natural Science Foundation of China (21076084);the Fundamental Research Funds for the Central Universities (2011ZZ0006);the Open Project Program of Provincial Key Laboratory of Green Processing Technology and Product Safety of Natural Products

Abstract: Paclitaxel(PTX) is an effective anticancer drug with poor solubility in water.Recently,much effort has been devoted into alternative formulations of PTX for improving its aqueous solubility.In this study,PTX and poly(L-lactic acid)(PLLA) were co-precipitated by a supercritical antisolvent(SAS) process using dichloromethane(DCM) and the mixtures of DCM/ethanol(EtOH) or DCM/dimethyl sulfoxide(DMSO) as the solvent,with super-critical carbon dioxide as the antisolvent.The effects of solvent,solvent ratio,temperature,pressure,polymer concentration and solution flow rate on particle morphology,mass median diameter(Dp50) and PTX loading were investigated using single-factor method.The particle samples were characterized using X-ray diffraction(XRD),scanning electron microscopy(SEM),laser diffraction particle size analyzer and high pressure liquid chromatography(HPLC).XRD results indicate that the micronized PTX is dispersed into the PLLA matrix in an amorphous form.SEM indicates that the solvent and the solvent ratio have great effect on the particle morphologies,and particle morphology is good at the volume ratio of DCM/EtOH of 50/50.For the mixed DCM/EtOH solvent,Dp50 increases with the increase of the temperature,pressure,PLLA concentration and solution flow rate,and PTX loading increases with pressure.Suitable operating conditions for the experimental system are as follows:DCM/EtOH 50/50(by volume),35℃,10-12 MPa,PLLA concentration of 5 g·L-1 and solution flow rate of 0.5 ml·min-1.

Key words: supercritical antisolvent, paclitaxel, poly(L-lactic acid), co-precipitation, drug delivery system

摘要: Paclitaxel(PTX) is an effective anticancer drug with poor solubility in water.Recently,much effort has been devoted into alternative formulations of PTX for improving its aqueous solubility.In this study,PTX and poly(L-lactic acid)(PLLA) were co-precipitated by a supercritical antisolvent(SAS) process using dichloromethane(DCM) and the mixtures of DCM/ethanol(EtOH) or DCM/dimethyl sulfoxide(DMSO) as the solvent,with super-critical carbon dioxide as the antisolvent.The effects of solvent,solvent ratio,temperature,pressure,polymer concentration and solution flow rate on particle morphology,mass median diameter(Dp50) and PTX loading were investigated using single-factor method.The particle samples were characterized using X-ray diffraction(XRD),scanning electron microscopy(SEM),laser diffraction particle size analyzer and high pressure liquid chromatography(HPLC).XRD results indicate that the micronized PTX is dispersed into the PLLA matrix in an amorphous form.SEM indicates that the solvent and the solvent ratio have great effect on the particle morphologies,and particle morphology is good at the volume ratio of DCM/EtOH of 50/50.For the mixed DCM/EtOH solvent,Dp50 increases with the increase of the temperature,pressure,PLLA concentration and solution flow rate,and PTX loading increases with pressure.Suitable operating conditions for the experimental system are as follows:DCM/EtOH 50/50(by volume),35℃,10-12 MPa,PLLA concentration of 5 g·L-1 and solution flow rate of 0.5 ml·min-1.

关键词: supercritical antisolvent, paclitaxel, poly(L-lactic acid), co-precipitation, drug delivery system