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