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

Chinese Journal of Chemical Engineering ›› 2012, Vol. 20 ›› Issue (4): 803-813.

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. Star Lake Bioscience Co., Inc., Zhaoqing 526040, China;
2. School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China

收稿日期:2012-04-01 修回日期:2012-07-03 出版日期:2012-08-28 发布日期:2012-09-15
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

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. 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:2012-08-28 Published:2012-09-15
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

摘要/Abstract

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

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

李文锋, 刘贵金, 李黎仙, 伍娟, 吕扬效, 江燕斌. Effect of Process Parameters on Co-precipitation of Paclitaxel and Poly(L-lactic Acid) by Supercritical Antisolvent Process[J]. Chinese Journal of Chemical Engineering, 2012, 20(4): 803-813.

LI Wenfeng, LIU Guijin, LI Lixian, WU Juan, LÜ Yangxiao, JIANG Yanbin. Effect of Process Parameters on Co-precipitation of Paclitaxel and Poly(L-lactic Acid) by Supercritical Antisolvent Process[J]. Chin.J.Chem.Eng., 2012, 20(4): 803-813.

参考文献

1 Orr,G.A.,Verdier-Pinard,P.,McDaid,H.,Horwitz,S.B.,"Mechanisms of taxol resistance related to microtubules",Oncogene,22 (47),7280-7295(2003).
2 Singla,A.K.,Garg,A.,Aggarwal,D.,"Paclitaxel and its formulations",Int.J.Pharm.,235(1-2),179-192(2002).
3 Rowinsky,E.K.,Cazenave,L.A.,Donehower,R.C.,"Taxol:A novel investigational antimicrotubule agent",J.Natl.Cancer I.,82(15),1247-1259(1990).
4 Lee,J.,Lee,S.C.,"Hydrotropic solubilization of paclitaxel:Analysis of chemical structures for hydrotropic property",Pharm.Res.,20(7),1022-1030(2003).
5 Greenwald,R.B.,Pendri,A.,Bolikal,D.,"Highly water soluble taxol derivatives:7-polyethylene-glycol carbamates and carbonates", J.Org.Chem.,60(2),331-336(1995).
6 Kang,B.K.,Chon,S.K.,Kim,S.H.,Jeong,S.Y.,Kim,M.S.,Cho, S.H.,Lee,H.B.,Khang,G.,"Controlled release of paclitaxel from microemulsion containing PLGA and evaluation of anti-tumor activity in vitro and in vivo",Int.J.Pharm.,286(1-2),147-156(2004).
7 Gupte,A.,Ciftci,K.,"Formulation and characterization of paclitaxel,5-FU and paclitaxel+5-FU microspheres",Int.J.Pharm.,276(1-2),93-106(2004).
8 Dong,Y.,Feng,S.S.,"Poly(D,L-lactide-co-glycolide)(PLGA) nanoparticles prepared by high pressure homogenization for paclitaxel chemotherapy",Int.J.Pharm.,342(1-2),208-214(2007).
9 Kim,S.C.,Kim,D.W.,Shim,Y.H.,Bang,J.S.,Oh,H.S.,Kim,S.W., Seo,M.H.,"In vivo evaluation of polymeric micellar paclitaxel formulation:Toxicity and efficacy",J.Control.Release,72(1-3),191-202(2001).
10 Pasquali,I.,Bettini,R.,Giordano,F.,"Solid-state chemistry and particle engineering with supercritical fluids in pharmaceutics",Eur.J. pharm.Sci.,27(4),299-310(2006).
11 Mishima,K.,"Biodegradable particle formation for drug and gene delivery using supercritical fluid and dense gas",Adv.Drug Delivery Rev.,60(3),411-432(2008).
12 Davies,O.R.,Lewis,A.L.,Whitaker,M.J.,Tai,H.,Shakesheff,K.M., Howdle,S.M.,"Applications of supercritical CO₂ in the fabrication of polymer systems for drug delivery and tissue engineering",Adv. Drug Delivery Rev.,60(3),373-387(2008).
13 Kang,Y.Q.,Yin,G.F.,Ouyang,P.,Huang,Z.B.,Yao,Y.D.,Liao, X.M.,Chen,A.Z.,Pu,X.,"Preparation of PLLA/PLGA microparticles using solution enhanced dispersion by supercritical fluids (SEDS)",J.Colloid Interface Sci.,322(1),87-94(2008).
14 Kim,M.S.,Lee,S.,Park,J.S.,Woo,J.S.,Hwang,S.J.,"Micronization of cilostazol using supercritical antisolvent(SAS)process:Effect of process parameters",Powder Technol.,177(2),64-70 (2007).
15 Chang,Y.P.,Tang,M.,Chen,Y.P.,"Micronization of sulfamethoxazole using the supercritical antisolvent process",J.Mater.Sci.,43 (7),2328-2335(2008).
16 Kang,Y.Q.,Wu,J.,Yin,G.F.,Huang,Z.B.,Liao,X.M.,Yao,Y.D., Ouyang,P.,Wang,H.J.,Yang,Q.,"Characterization and biological evaluation of paclitaxel-loaded poly(L-lactic acid)microparticles prepared by supercritical CO₂",Langmuir,24(14),7432-7441 (2008).
17 Lee,L.Y.,Wang,C.H.,Smith,K.A.,"Supercritical antisolvent production of biodegradable micro-and nanoparticles for controlled delivery of paclitaxel",J.Control.Release,125(2),96-106(2008).
18 Kalogiannis,C.G.,Pavlidou,E.,Panayiotou,C.G.,"Production of amoxicillin microparticles by supercritical antisolvent precipitation",Ind.Eng.Chem.Res.,44(24),9339-9346(2005).
19 Mattea,F.,Martin,A.,Cocero,M.J.,"Co-precipitation ofβ-carotene and polyethylene glycol with compressed CO₂ as an antisolvent:Effect of temperature and concentration",Ind.Eng.Chem.Res.,47 (11),3900-3906(2008).
20 Luo,N.,Lu,Y.M.,Jiang,Y.B.,"Solubility of paclitaxel in mixtures of dichloromethane and supercritical carbon dioxide",Chin.J.Chem. Eng.,19(4),558-564(2011)
21 Jiang,Y.B.,Sun,W.L.,Wang,W.,"Recrystallization and micronization of 10-hydroxycamptothecin by supercritical antisolvent process",Ind.Eng.Chem.Res.,51(6),2596-2602(2012).
22 Liu,J.,Meisner,D.,Kwong,E.,Wu,X.Y.,Johnston,M.R.,"A novel trans-lymphatic drug delivery system:Implantable gelatin sponge impregnated with PLGA-paclitaxel microspheres",Biomaterials,28 (21),3236-3244(2007).
23 Wang,Y.M.,Sato,H.,Adachi,I.,Horikoshi,I.,"Preparation and characterization of poly(lactic-co-glycolic acid)microspheres for targeted delivery of a novel anticancer agent,taxol",Chem.Pharm. Bull.,44(10),1935-1940(1996).
24 Jin,H.,Xia,F.,Jiang,C.,Zhao,Y.,He,L.,"Nanoencapsulation of lutein with hydroxypropylmethyl cellulose phthalate by supercritical antisolvent",Chin.J.Chem.Eng.,17(4),672-677(2009).
25 Kalani,M.,Yunus,R.,"Application of supercritical antisolvent method in drug encapsulation:A review",Int.J.Nanomed.,6,1429-1442(2011).
26 Davies,O.R.,Lewis,A.L.,Whitaker,M.J.,Tai,H.,Shakesheff,K.M., Howdle,S.M.,"Applications of supercritical CO₂ in the fabrication of polymer systems for drug delivery and tissue engineering",Adv. Drug Delivery Rev.,60(3),373-387(2008).
27 Elvassore,N.,Bertucco,A.,Caliceti,P.,"Production of protein-loaded polymeric microcapsules by compressed CO₂ in a mixed solvent",Ind.Eng.Chem.Res.,40(3),795-800(2001).
28 Kikic,I.,"Polymer-supercritical fluid interactions",J.of Supercritical Fluids,47(3),458-465(2009).

[1]	Xiaobin Chen, Yuting Tang, Chuncheng Ke, Chaoyue Zhang, Sichun Ding, Xiaoqian Ma. CO₂ capture by double metal modified CaO-based sorbents from pyrolysis gases[J]. 中国化学工程学报, 2022, 43(3): 40-49.
[2]	Marwa M. Ibrahim. An efficient nano-adsorbent via surfactants/dual surfactants assisted ultrasonic co-precipitation method for sono-removal of monoazo and diazo anionic dyes[J]. 中国化学工程学报, 2021, 40(12): 225-236.
[3]	Adewale Adewuyi, Adole I. Ogagbolo, Woei Jye Lau, Rotimi A. Oderinde. Synthesis of spinel ferrite and its role in the removal of free fatty acids from deteriorated vegetable oil[J]. 中国化学工程学报, 2021, 40(12): 78-87.
[4]	Junqi Tian, Yanqin Li, Xia Zhou, Yongbin Yao, Denghao Wang, Jianming Dan, Bin Dai, Qiang Wang, Feng Yu. Overwhelming low ammonia escape and low temperature denitration efficiency via MnO_x-decorated two-dimensional MgAl layered double oxides[J]. 中国化学工程学报, 2020, 28(7): 1925-1934.
[5]	Zhenhua Li, Mengyao Si, Li Xin, Renjie Liu, Runxue Liu, Jing Lü. Cobalt catalysts for Fischer-Tropsch synthesis: The effect of support, precipitant and pH value[J]. Chinese Journal of Chemical Engineering, 2018, 26(4): 747-752.
[6]	Qi Zhang, Xuhua Yan, Peng Zheng, Zhengbao Wang. Influence factors on activity of Ru-Zn catalysts in selective hydrogenation of benzene[J]. , 2017, 25(3): 294-300.
[7]	张志斌, 李艺, 魏垒垒, 吕育锋, 王猛, 高宝玉. Effect of Ferric Chloride on the Properties of Biological Sludge in Co-precipitation Phosphorus Removal Process[J]. Chinese Journal of Chemical Engineering, 2013, 21(5): 564-568.
[8]	韩爱军, 廖娟娟, 叶明泉, 李燕, 彭新华. Preparation of Nano-MnFe₂O₄ and Its Catalytic Performance of Thermal Decomposition of Ammonium Perchlorate[J]. , 2011, 19(6): 1047-1051.
[9]	罗宁, 卢英妹, 江燕斌. Solubility of Paclitaxel in Mixtures of Dichloromethane and Supercritical Carbon Dioxide [J]. , 2011, 19(4): 558-564.
[10]	焦真, 陈志明, 吴有庭, 马少玲. Determination of Paclitaxel Solubility in Carbon Dioxide Using Quartz Crystal Microbalance[J]. , 2011, 19(2): 227-231.
[11]	温亮, 辛忠. Effect of a Novel Nucleating Agent on Isothermal Crystallization of Poly(L-lactic acid)[J]. , 2010, 18(6): 899-904.
[12]	金鹤阳, 夏菲, 江翠兰, 赵亚平, 何琳. Nanoencapsulation of Lutein with Hydroxypropylmethyl Cellulose Phthalate by Supercritical Antisolvent[J]. , 2009, 17(4): 672-677.
[13]	未作君, 元英进, 吴兆亮, 吴金川. 有机溶剂原位萃取法提高悬浮培养中国红豆杉细胞紫杉醇产量[J]. , 2003, 11(2): 224-226.

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

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

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 13

编辑推荐

Metrics

本文评价