超临界流体膨胀减压过程制备药物超细微粒工艺研究
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摘要
近年来,利用超临界流体技术制备药物超细微粒受到众多研究者的广泛关注。该类技术具有操作条件温和、操作参数可调与制备微粒粒径及形态可控等优点。其中颇具应用前景的是超临界流体膨胀减压(Supercritical fluid expansion depressization process,简称SFED)过程。它克服了传统方法制备药物微粒粒径较大,粒径分布较宽的缺点;弥补了RESS和SAS及其衍生技术分别在最终产物产量和水溶性药物微粒制备方面的不足;承接了CAN-BD和SAA过程的优点;既可用于脂溶性药物微粒的制备,也可用于水溶性药物的微粒化。但目前国内外有关SFED过程的报道较少,且多以针对性较强的实验研究为主,缺少系统和深入的理论及实验研究。本论文针对SFED过程的工艺基础和工艺过程进行了研究。通过研究有机溶剂/CO_2系统的液相体积膨胀,给出了确定SFED过程可行范围的方法;通过研究SFED过程的三相相行为,确定了各组分含量随操作参数的变化规律;通过研究喷嘴内液体的雾化过程,确定了液滴直径随操作参数的变化规律;通过研究水溶性药物、脂溶性药物和药物载体超细微粒的SFED过程制备工艺,给出了制备各类药物微粒的适宜工艺条件。本论文的主要研究工作及所形成的主要结果与结论如下:
(1)计算了有机溶剂/CO_2系统的液相体积膨胀率,考察了液相体积膨胀与CO_2在液相中溶解度的关系。结果表明,无论有机溶剂/CO_2系统的温度、压力和有机溶剂是否相同,只要液相中溶解了相同量的CO_2,液相体积膨胀就相差不大。液相体积膨胀率在500%以下时,其变化趋势平缓;液相体积膨胀率超过500%时,继续增加液相中CO_2的含量,液相体积膨胀率急剧增大。定义液相体积膨胀率500%对应液相中CO_2的含量0.9作为有机溶剂/CO_2系统适于进行SFED过程和SAS过程的转变点,此定义经实验验证与实验结果吻合良好。
(2)采用PR方程结合范德华-1混合规则,对气-液-固三相系统相平衡进行了计算,考察了液相中各组分含量随压力的变化规律。结果表明:随压力的增加,CO_2含量逐渐增大,而有机溶剂和固体含量逐渐降低;相同压力下,温度较高更适于进行SFED过程;对于同一原始溶剂,相同温度压力下,固体在液相中的含量越高越适于以SFED过程制备该物质的微粒。
(3)针对纯CO_2通过喷嘴的流动,建立了超临界流体通过喷嘴快速膨胀模型,利用流体力学计算软件FLUENT对该膨胀过程进行了数值模拟,得到了压力、温度、密度、速度沿喷嘴轴线的变化曲线.结果表明:CO_2的温度、压力在喷嘴内即急剧降低,而流速快速升高。
(4)以乙醇为模型材料,利用流体力学计算软件FLUENT中的气体辅助雾化模型对液膜通过喷嘴雾化成液滴的过程进行了模拟计算,得到了SFED过程液滴直径随入口压力、温度及溶液流量的变化规律,将液滴直径和利用SFED过程制备微粒粒径随操作参数的变化归一化后比较,两者变化规律基本一致。
(5)建立和形成了SFED过程实验装置和实验技术,分别针对水溶性药物(四环素、头孢羟氨苄),脂溶性药物(红霉素、灰黄霉素)和药物载体(聚甲基丙烯酸甲酯)超细微粒的SFED过程制备工艺进行了实验研究,确定了混合器温度、压力、溶液浓度、进液速率和析出器温度对微粒形态、粒径及粒径分布的影响规律,给出了制备各类材料超细微粒的适宜工艺条件。
In recent years,the supercritical fluid techniques for preparing drug microparticles have attracted great attention.They have many advantages such as mild operation conditions, adjustable parameters and controllable particle diameters.Among these techniques,the supercritical fluid expansion depressurization(SFED) process has shown greater application potential in preparing micro- and nano-particles with controlled size.It can overcome the distadvantages of the conventional techniques such as large particle diameters and wide diameter distribution,make up for the deficiency of RESS and SAS processes and its derivative techniques in the yield of the final product and the micronization of the water-soluble drug,and takeover the advantages of the CAN-BD and SAA processes.Both lipid-soluble and water-soluble drug microparticles can be prepared by this new technique. However,at present little research work on this process has been done.The previous work focused only on the experimental research for some special cases.A systemically theoretical and experimental research has not been reported.This dissertation is aimed to study the technological foundation and operation characteristics of SFED process.By the study on the liquid volume expansion of organic solvent/CO_2 systems,the method to determine feasible range of SFED process is given.By the study on the ternary phase behavior of SFED process, the realationship between the content of each component and the operation pressure is determined.By the study on the atomization process through the nozzle,the realationship between the droplet diameters and the operation parameters is presented.By the study on the preparation process of lipid-soluble drug microparticles,water-soluble drug microparticles and drug carrier microparticles,the optimal operation conditions are given.The main research work and achievements are as following.
(1) The liquid volume expansion ratios of the organic solvent/CO_2 system are calculated and the relationship of the liquid volume expansion ratio and the CO_2 solubility in liquid phase is investiaged.The results show that the liquid volume expansion ratios have little defference as long as the content of CO_2 in the liquid phase is same whether the temperature, pressure and organic solvent itself of the organic solvent/CO_2 system are same or not.When the liquid volume expansion ratio is below 500%,the change tendency of liquid volume expansion ratio is mild;when it is above 500%,the liquid volume expansion ratio increases sharply with the increase of the CO_2 content.The CO_2 content of 0.9,corresponding to liquid volume expansion ratio of 500%,can be defined as transition point of organic solvent/CO_2 system from SFED to SAS process.This definition is verified by experiments and it is in good agreement with the experimental results.
(2) The ternary gas-liquid-solid phase equilibrium is calculated by PR state equation with vdW-1 mixing rule and the relationship between the content of each component and the operation pressure is investiaged.The results show that,with the increase of pressure,CO_2 content increases while the contents of solid and organic solvent decrease;at the same pressure,a higher temperature is more favorable for SFED process;for the same original organic solvent,with same temperature and pressure,a higher solid content in liquid phase is more favorable for SFED process.
(3) For the flow of pure CO_2 through the nozzle,a simulating model of supercritical fluid rapid expansion through the nozzle is established.The rapid expansion process is simulated using the fluid calculation software of FLUENT and the evolution of pressure,temperature, density and flow rate along the nozzle axis are obtained.The results show that,the temperature and pressure of CO_2 decreases in the nozzle,while the flow rate increases rapidly.
(4) With ethanol as model material,the liquid film atomization process through the nozzle is simulated and calculated by the air-assisted atomization model in the fluid calculation software of FLUENT and the relationship between the droplet diameter and the operation pressure,temperature and the solution flow rate is investiaged.Compared with the relationship between the microparticles prepared by SFED process and the operation paremeters,the calculation results are in good agreement with the experiment ones after the normalization of the droplet diameters and particle diameters.
(5) The experiment apparatus and the related experiment technique of SFED process are established.The microparticles of different materials,namely water-soluble drug(cefadroxil, tetracycline),lipid-soluble drug(erythromycin,griseofulvin) and drug carrier(Poly-methyl methacrylate),are successfully prepared by SFED process.The influences of the operation parameters,including mixing vessel pressure,mixing vessel temperature,solution feed rate, solution concentration and precipitator temperature,on the particle morphology,size and size distribution are investigated.The optimal process conditions for these materials are obtained.
(1)计算了有机溶剂/CO_2系统的液相体积膨胀率,考察了液相体积膨胀与CO_2在液相中溶解度的关系。结果表明,无论有机溶剂/CO_2系统的温度、压力和有机溶剂是否相同,只要液相中溶解了相同量的CO_2,液相体积膨胀就相差不大。液相体积膨胀率在500%以下时,其变化趋势平缓;液相体积膨胀率超过500%时,继续增加液相中CO_2的含量,液相体积膨胀率急剧增大。定义液相体积膨胀率500%对应液相中CO_2的含量0.9作为有机溶剂/CO_2系统适于进行SFED过程和SAS过程的转变点,此定义经实验验证与实验结果吻合良好。
(2)采用PR方程结合范德华-1混合规则,对气-液-固三相系统相平衡进行了计算,考察了液相中各组分含量随压力的变化规律。结果表明:随压力的增加,CO_2含量逐渐增大,而有机溶剂和固体含量逐渐降低;相同压力下,温度较高更适于进行SFED过程;对于同一原始溶剂,相同温度压力下,固体在液相中的含量越高越适于以SFED过程制备该物质的微粒。
(3)针对纯CO_2通过喷嘴的流动,建立了超临界流体通过喷嘴快速膨胀模型,利用流体力学计算软件FLUENT对该膨胀过程进行了数值模拟,得到了压力、温度、密度、速度沿喷嘴轴线的变化曲线.结果表明:CO_2的温度、压力在喷嘴内即急剧降低,而流速快速升高。
(4)以乙醇为模型材料,利用流体力学计算软件FLUENT中的气体辅助雾化模型对液膜通过喷嘴雾化成液滴的过程进行了模拟计算,得到了SFED过程液滴直径随入口压力、温度及溶液流量的变化规律,将液滴直径和利用SFED过程制备微粒粒径随操作参数的变化归一化后比较,两者变化规律基本一致。
(5)建立和形成了SFED过程实验装置和实验技术,分别针对水溶性药物(四环素、头孢羟氨苄),脂溶性药物(红霉素、灰黄霉素)和药物载体(聚甲基丙烯酸甲酯)超细微粒的SFED过程制备工艺进行了实验研究,确定了混合器温度、压力、溶液浓度、进液速率和析出器温度对微粒形态、粒径及粒径分布的影响规律,给出了制备各类材料超细微粒的适宜工艺条件。
In recent years,the supercritical fluid techniques for preparing drug microparticles have attracted great attention.They have many advantages such as mild operation conditions, adjustable parameters and controllable particle diameters.Among these techniques,the supercritical fluid expansion depressurization(SFED) process has shown greater application potential in preparing micro- and nano-particles with controlled size.It can overcome the distadvantages of the conventional techniques such as large particle diameters and wide diameter distribution,make up for the deficiency of RESS and SAS processes and its derivative techniques in the yield of the final product and the micronization of the water-soluble drug,and takeover the advantages of the CAN-BD and SAA processes.Both lipid-soluble and water-soluble drug microparticles can be prepared by this new technique. However,at present little research work on this process has been done.The previous work focused only on the experimental research for some special cases.A systemically theoretical and experimental research has not been reported.This dissertation is aimed to study the technological foundation and operation characteristics of SFED process.By the study on the liquid volume expansion of organic solvent/CO_2 systems,the method to determine feasible range of SFED process is given.By the study on the ternary phase behavior of SFED process, the realationship between the content of each component and the operation pressure is determined.By the study on the atomization process through the nozzle,the realationship between the droplet diameters and the operation parameters is presented.By the study on the preparation process of lipid-soluble drug microparticles,water-soluble drug microparticles and drug carrier microparticles,the optimal operation conditions are given.The main research work and achievements are as following.
(1) The liquid volume expansion ratios of the organic solvent/CO_2 system are calculated and the relationship of the liquid volume expansion ratio and the CO_2 solubility in liquid phase is investiaged.The results show that the liquid volume expansion ratios have little defference as long as the content of CO_2 in the liquid phase is same whether the temperature, pressure and organic solvent itself of the organic solvent/CO_2 system are same or not.When the liquid volume expansion ratio is below 500%,the change tendency of liquid volume expansion ratio is mild;when it is above 500%,the liquid volume expansion ratio increases sharply with the increase of the CO_2 content.The CO_2 content of 0.9,corresponding to liquid volume expansion ratio of 500%,can be defined as transition point of organic solvent/CO_2 system from SFED to SAS process.This definition is verified by experiments and it is in good agreement with the experimental results.
(2) The ternary gas-liquid-solid phase equilibrium is calculated by PR state equation with vdW-1 mixing rule and the relationship between the content of each component and the operation pressure is investiaged.The results show that,with the increase of pressure,CO_2 content increases while the contents of solid and organic solvent decrease;at the same pressure,a higher temperature is more favorable for SFED process;for the same original organic solvent,with same temperature and pressure,a higher solid content in liquid phase is more favorable for SFED process.
(3) For the flow of pure CO_2 through the nozzle,a simulating model of supercritical fluid rapid expansion through the nozzle is established.The rapid expansion process is simulated using the fluid calculation software of FLUENT and the evolution of pressure,temperature, density and flow rate along the nozzle axis are obtained.The results show that,the temperature and pressure of CO_2 decreases in the nozzle,while the flow rate increases rapidly.
(4) With ethanol as model material,the liquid film atomization process through the nozzle is simulated and calculated by the air-assisted atomization model in the fluid calculation software of FLUENT and the relationship between the droplet diameter and the operation pressure,temperature and the solution flow rate is investiaged.Compared with the relationship between the microparticles prepared by SFED process and the operation paremeters,the calculation results are in good agreement with the experiment ones after the normalization of the droplet diameters and particle diameters.
(5) The experiment apparatus and the related experiment technique of SFED process are established.The microparticles of different materials,namely water-soluble drug(cefadroxil, tetracycline),lipid-soluble drug(erythromycin,griseofulvin) and drug carrier(Poly-methyl methacrylate),are successfully prepared by SFED process.The influences of the operation parameters,including mixing vessel pressure,mixing vessel temperature,solution feed rate, solution concentration and precipitator temperature,on the particle morphology,size and size distribution are investigated.The optimal process conditions for these materials are obtained.
引文
[1]李凤生,姜炜,付廷明,杨毅等.药物粉体技术.北京:化学工业出版社.2007.
[2]罗付生,韩爱军,杨毅等.超细粉体技术在中药行业中的应用.中草药,2001,32(10):941-942.
[3]Gonda T I.Controlled drug delivery system.Marcel Dekker,Inc.,New York,1998.
[4]Hickey A J.Thomposon D C.Physiology of the airways.In:Pharmaceutical Inhalation Aerosol Technology,Hickey A J Ed.,Marcel Dekker,Inc.,New York,1992.
[5]Smith P L.Peptide delivery via the pulmonary route:a valid approach for local and systemic delivery.J Controlled Release,1997,46(1):99-106.
[6]朱自强,关怡新,姚善泾.超临界辅助雾化制备适于气溶胶给药的药物微粒.化工学报,2005 56(2):187-196.
[7]马喆坤,邹亚萍,周云高.超细粉碎技术在制药工业中的应用.江西化工,2003,4(2):174-175.
[8]葛晓陵.药物超细粉碎技术的研究.中国粉体技术,2002,8(6):19-23.
[9]王喜忠,于才渊,周才君.喷雾干燥.北京:化学工业出版社.2003.
[10]张更超,应富强.超细粉碎技术现状及发展趋势.中国非金属矿业导刊,2003,9(2):44-48.
[11]邓政兴,张润,李立华等.生物材料制备新方法-超临界流体技术.化学世界,2004,(2):99-102.
[12]刘燕,王威强,李爱菊.超临界流体技术制备超微材料应用.化学工程,2004,32(6):47-51.
[13]朱自强.超临界流体技术.北京:化学工业出版社,2000.18-23.
[14]V.Krukonis.Supercritical Fluid Nucleation of Difficult-to-Comminute Solids.Paper at Annual Meeting AIChE,San Francisco,November 1984.
[15]Meziani MJ,Rollins HW,Allard LF,et al.Protein-protected nanoparticles from rapid expansion of supercritical solution into aqueous solution.J Phys Chem B,2002,106(43):11178-11182.
[16]M.Turk,P.Hils,B.Helfgen.Micronization of pharmaceutical substances by the Rapid Expansion of Supercritical Solutions(RESS):a promising method to improve bioavailability of poorly soluble pharmaceutical agents.J.Supercrit Fluids,2002,22:75-84.
[17]D.Kayrak,U.Akman,O.Hortacsu.Micronization of Ibuprofen by RESS.J.Supercrit.Fluids,2003,(26):17-31.
[18]P.Debenedetti,J.W.Tom,S.D.Yeo et al.Application of Supercriticai Fluids for the Production of Sustained Delivery Devices.J.Controlled Release.,1993,24:27-44.
[19]P.Pallado,L.Benedetti,L.Callegaro.WO Patent 96/29998,1996
[20]P.Pathak,M.J.Meziani,Y.-P.Sun,Supercritical fluid technology for enhanced drug delivery,Expert Opin.Drug Deliv.,2005,2:4-7.
[21]P.Pathak,M.J.Meziani,T.Desai,Y.-P.Sun,Nanosizing drug particles in supercritical fluid processing.J.Am.Chem.Soc.,2004,126:10-42.
[22]Pankaj Pathak,Mohammed J.Meziani,Tarang Desai,Ya-Ping Sun.Formation and stabilization of ibuprofen nanoparticles in supercritical fluid processing.J.Supercrit Fluids.,2006,37:279-286.
[23]陈鸿雁,蔡建国.超临界流体溶液快速膨胀法制备灰黄霉素微细颗粒.化工学报,2001,52(1):56-60.
[24]陈兴权,赵天生,于慧杰,等.用超临界CO-2制备α2细辛醚及布洛芬微细颗粒.宁夏大学学报:自然科学版,2001,22(2):1552157.
[25]蒋思嫒,赵亚平,于文利,等.超临界快速膨胀法制备植物甾醇超细微粒.精细化工,2004,21(2):129-132.
[26]P.M.Gallagher,M.P.Coffey,V.J.Krukonis,Gas Anti-Solvent Recrystallization of RDX:Formation of Ultrafine Particles of a Difficult-to-Comminute Explosive.J.Supercrit Fluids.,1992,5,130-142.
[27]B.Subramaniam,S.Saim,RA.Rajewski,V.Stella.Method for particle precipitation and coating using near-critical and supercriticai anti solvents.US Patent 5,833,891,1997.
[28]M.Hanna,P.York.WO Patent 95/01221,1994.
[29]M.Moneghini,I.Kikic,D.Voinovich et al.Processing of carbamazepine-PEG4000 solid dispersions with supercritical carbon dioxide:Preparation,characterisation,and in vitro dissolution.Int J Pharm.,2001,222:129-138.
[30]OI.Corrigan,AM.Crean.Comparative physicochemical properties of hydrocortisobe- PVP composites prepared using supercritical carbon dioxide by the gas anti-solvent recrystallization process by coprecipitation and by spray drying.Int J Pharm.,.2002,245:75-82.
[31]MJ.Cocero,S.Ferrero.Crystallization of β-carotene by a GAS process in batch.E.ect of operating conditions.J Supercrit Fluids.,2002,22:237-245.
[32]Eivassore N,Bertucco A,Caliceti P.Production of insulin-loaded poly(ethyleneglycol)/poly(l-lactide)(PEG/PLA) nanoparticles by gas antisolvent techniques.J.Pharm Sci.,2001,90:1628-1636.
[33]Rantakyla M,Jantti M,Aaltonen O et al.The e.ect of initial drop size on particle size in the supereritical antisolvent precipitation(SAS) technique.J.Supercrit Fluids.,2002,24:251-263.
[34]Winters M A,Knutson B L,Debenedetti P G,et al.Precipitation of proteins in supercritical carbon dioxide[J].J Pharm.Sci.,1996,85:586-594.
[35]Sang-Do Yeo,Min-Su Kim,Jong-Chan Lee.Recrystailization of sulfathiazole and chlorpropamide using the supercritical fluid antisolvent process.J Supercrit Fluids.,2003,25(2):143-154.
[36]E.Reverchon,I.De Marco,G.Della Porta.Rifampicin microparticles production by supercritical antisolvent precipitation.Int.J Pharm.,2002,243:83-91.
[37]E.Reverchon,I.De Marco,G.Caputo,G.Della Porta.Pilot scale micronization of arnoxicillin by supercritical antisolvent precipitation.J Supercrit Fluids.,2003,26:1-7.
[38]R.Bodmeier,H.Wang,DJ.Dixon et al.Polymeric Microspheres Prepared by Spraying into Compressed Carbon Dioxide.Pharm Res.,1995,12(8):1211-1217.
[39]TJ.Young,KP.Johnston,K.Mishima et al.Encapsulation of lysozyme ina biodegradeable polymer by precipitinon with a vapor-over-liquid antisolvent.J Pharm Sci.,1999,88(6):640-650.
[40]H.Krober,U.Teipel.Materials processing with supercritical antisolvent precipitation:Process parameters and morphology of tartaric acid.J Supercrit Fluids.,2002,22:229-235.
[41]WK.Snavely,B.Subramaniam,RA.Rajewski et al.Micronization of insulin from halogenated alcohol solution using supercritical carbon dioxide as an antisolvent.J Pharm Sci.,2002,91:2026-2039.
[42]B.Warwick,F.Dehghani,NR.Foster et al.Regtop.Micronization of copper indomethacin using gas antisolvent processes.Ind Eng Chem Res.,2002,41:1993-2004.
[43]TL.Sze,F.Dehghani,NR.Foster.Micronization and microencapsulation of pharmaceuticals using a carbon dioxide antisolvent.Powder Technol.,2002;126:134-149.
[44]P.Chattopadhyay,RB.Gupta.Production of griseofulvin nanoparticles using supercritical CO_2antisolvent with enhanced mass transfer.Int J Pharm 2001;228:19-31.
[45]A.Kordikowski,T.Shekunov,P.York.Polymorph control of sulfathiazole in supercritical CO_2.Pharm Res 2001;18:682-688.
[46]HHY.Tong,BY.Shekunov,P.York et al.Characterization of two polymorphs of salmeterol xinafoate crystallized from supercritical fluids.Pharm.Res.2001,18:852-858.
[47]S.Bristow,T.Shekunov,BY.Shekunov et al.Analysis of the supersaturation and precipitation process with supercritical CO_2.J.Supercrit.Fluids.2001,21:257-271.
[48]AD.Edwards,BY.Shekunov,A.Kordikowski et al,P.York.Crystallization of pure anhydrous polymorphs of carbamazepine by solution enhanced dispersion with supercritical fluid(SEDSTM).J Pharm.Sci.2001,90:1115-1124.
[49]SP.Velaga,R.Ghaderi,J.Carlfors.Preparation and characterization of hydrocortisone particles using a supercritical fluids extraction process.Int.J.Pharm.,2002;231:155-166.
[50]H.Okamoto,S.Nishida,H.Todo et al.Pulmonary gene delivery by chitosan-pDNA complex powder prepared by a supercritical carbon dioxide process.J Pharm.Sci.,2003,92:371-380.
[51]陈岚,张岩,李保国等.压力对超临界流体技术制备药物微粒的影响.上海理工大学学报,2004,26(3):220-223.
[52]陈岚,张岩,李保国等.超临界流体增强溶液分散度法制备阿莫西林缓释微囊.化学工程,2006,34(1):70-73,78
[53]李冬兵,王家炜,杨基础.超临界抗溶剂技术制备对乙酰氨基酚-PEG4000固体分散体.中国抗生素杂志,2005,30(4):1982203.
[54]李志义,刘学武,金良安等 超临界反溶剂过程制备四环素超细微粒.大连理工大学学报,2006,46(4):491-494.
[55]李志义,李文秀,刘学武等.超临界反溶剂过程制备灰黄霉素超细微粒.化学反应工程与工艺,2006,22(2):156-161.
[56]刘学武,李志义,夏远景等.超临界反溶剂过程制备银杏叶提取物超细微粒.高校化学工程学报,2005,19(4):550-553.
[57]刘学武,李志义,韩冰等.超临界反溶剂过程制备槲皮素超细颗粒.林产化学与工业,2004,24(2):73-76.
[58]Liu Xue-wu,Li Zhi-yi,Han Bing et al.Supercritical Antisoivent Precipitation of Microparticles of Quercetin.China J.Chem.Eng.2005,13(1):128-130.
[59]F.Graser,G.Wickenhaeuser.US Patent 4,451,654.
[60]R.E.Sievers,U.Karst.Patent EP 0,677,332,1995;US Patent 5,639,441,1997.
[61]E.Reverchon.Supercritical-assisted atomaization to produce micro-and/or nanoparticles of controlled size and distribution.Ind.Eng.Chem.Res.2002,41:2405-2411.
[62]Sievers,R.E.,Karst,U.,Milewski,P.D et al.Formation of Aqueous Small Droplet Aerosols Assisted by Supercritical Carbon Dioxide.Aerosol Sci.Technol.1999,30,3-10.
[63]N.Ventosa,S.Sala,J.Veciana.DELOS process:a crystallization technique using compressed fluids 1.Comparison to the GAS crystallization method.J.Supererit.Fluids.2003,26:33-45.
[64]M.Rodrigues,N.Peirico,H.Matos,E.Gomes de Azevedo,MR.Lobato,AJ.Almeida Microcomposites theophylline/hydrogenated palm oil from a PGSS process for controlled drug delivery systems.J Supercrit.Fluids,2004,29:175-184
[65]Sethia S.,Squillante.Physicochemical characterization of solid dispersions of carbamazepine formulated by supercritical carbon dioxide and conventional evaporation method.J.Pharm.Sci.2002,91,1948-1957.
[66]RE.Sievers,ETS.Huang,JA.Villa,et al Brauer.Micronization of water-soluble or alcohol-soluble pharmaceuticals and model compounds with a low-temperature bubble dryer.J.Supercrit Fluids.2003,26:9-16.
[67]SP.Sellers,GS.Clark,RE.Sievers,JF.Carpenter.Dry powders of stable protein formulations from aqueous solutions prepared using supercritical CO_2-assisted aerosolization.J Pharm.Sci.2001,90(6):785-797.
[68]E.Reverchon,G.Delia Porta.Micronization of antibiotics by supercritical assisted atomization.J.Supercrit.Fluids,2003,26:243-252.
[69]E.Reverchon,G.Delia Porta.Terbutaline microparticles suitable for aerosol delivery produced by supercritical assisted atomization.Inter J Pharm,2003,258:1-9.
[70]E.Reverchon,A.Spada.Erythromycin micro-particles produced by supercritical fluid atomization [J].Powder Technol.,2004,14:100-108.
[71]G.Delia Porta,C.De Vittori,E.Reverchon.Supercritical assisted atomization:a novel technology for microparticles preparation of an asthma-controlling drug.AAPS Pharm.Sci.Tech.,2005,6 (3):421-428.
[72]E.Reverchon,A.Antonacci.Cyclodextrins micrometric powders obtained by sypercritical fluid processing.Biotechnol.Bioeng.2006,94(4):753-761.
[73]Ernesto Reverchon and Alessandra Antonacci.Chitosan Microparticles Production by Supercritical Fluid Processing.Ind.Eng.Chem.Res.,2006,45:5722-5728.
[74]E.Reverchon,A.Antonacci.Polymer microparticles production by supercritical assisted atomization.J.Supercrit.Fluids.,2007,39:444-452.
[75]Peng D,Robinson D.A new two-constant equation of state.Ind.Eng.Fund.1976,15:59-60
[76]Shariati A.,Peters C.J.Measurements and modeling of the phase behavior of ternary systems of interest for the GAS process:Ⅰ.The system carbon dioxide + 1-propanol + salicylic acid.J.Supercri.Fluids,2002,23(3):195-208.
[77]Liu Zhimin,Wang Jiaqiu,Song Liping et al.Study on the phase behavior of cholesterol-acetone-CO_2 system and recrystallization of cholesterol by antisolvent CO_2.J.Supercri.Fluids,2002,24(1):1-6.
[78]Chang C.J.,Randolph A.D.Solvent expansion and solute solubility predictions in gas-expanded liquids.AIChE J.,1990,36(6):939-942.
[79]Dixon D.J.,Johnston K.P.Molecular thermodynamics of solubilities in gas antisolvent crystallization.AIChE J.,1991,37(10):1441-1449.
[80]Lele A K,Shine A D.Morphology of polymers precipitated from a supercritical solvent.AIChE J.1992,385:742-751.
[81]Kwauk,X,Debenedetti,P.G.Mathematical modeling of aerosol formation by rapid eapansion of supercritical solution in a converging nozzle.J.Aerosol Sci,1993,24(4):445-469.
[82]B.Helfgen,P.Hils,Ch.Hoizknecht et al.Schaber.Simulation of particle formation during the rapid expansion of supercritical solution.Aerosol Science,2001,32:295-319.
[83]Song Y;Hino T,Lambert S et al.Liquid-liquid equilibria for polymer solutions and blends including copolymers.Fluid Phase Equilibria,1996,117:69-76.
[84]邓小亮,超临界反溶剂过程相行为研究,硕士论文,大连:大连理工大学.2004.
[85]Li Y.H.,Dillard K.H.,Robinson R.L.Vapor-liquid phase equilibrium for carbon dioxide- n-Hexane at 40,80 and 120℃.J.Chem.Eng.Data,1981,26(1):53-55.
[86]Ng H.J.and Robinson D.B.Equilibrium phase properties of the toluene-carbon dioxide system.J.Chem.Eng.Data,1978,23(4):325-327.
[87]Chang C.J.,Day C.Y.,Ko C.M.,Chiu K.L.Densities and P-x-y diagrams for carbon dioxide dissolution in methanol,ethanol,and acetone mixtures.Fluid Phase Equilibria,1997,131:243-258.
[88]Silva M.V.,Barbosa D.,Ferreira P.O.et al.High pressure phase equilibrium data for the systems carbon dioxide/ethyl acetate and carbon dioxide/isoamyl acetate at 295.2,302.2 and 313.2K.J.Chem.Eng.Data,1992,37(2):249-251.
[89]Li Zhiyi,Xia Yuanjing,Liu Xuewu,et al.Study of the liquid phase volume expansion for CO_2/Organic Solvent Systems.Chinese J.Chem.Eng.,2005,13(4) 504-509.
[90]Liu Zhimin,Li Dan,Yang Guanying et al.Solubility of hydroxybenzoic acid isomers in ethyl acetate expanded with CO_2..J.Supercrit.Fluids,2000,18(2):111-119.
[91]Singh H,Yun S,Macnaughton S et al.Solubility of cholesterol in supercritical ethane and binary gas mixtures containing ethane.Ind.Eng.Chem.Res,1993,32(11):2841-2848.
[92]Lee HK,Kim CH.Solid Solubilities of Methoxyphenylacetic Acid Isomer Compounds in Supercritical Carbon Dioxide.J.Chem.Eng.Data.,1994,39(1):163-165.
[93]Trabelsi F,Kikic I.Predicting the approximate solubilities of solids in dense carbon dioxide.J.Supercritical Fluid.,1999,14(2):151-161.
[94]Huang C,Tang M,Tao W et al.Calculation of the solid solubilities in supercritical carbon dioxide using a modified mixing model.Fluid phase equilibria,2001,179:67-84.
[95]Angus S,Amstrong B,Renk KM.Carbon dioxide international thermodynamic tables of fluid state.IUPAC Project Center,Imperial College,London.Pergamon Press 3:P385.
[96]童景山,李敬编著.流体热物理性质的计算.北京:清华大学出版社.1982.
[97]Chapman S,Cowling T G.The mathematical Theory of Nonuniform Gas,Cambride,New York,1939
[98]陶文铨.数值传热学.西安:西安交通大学出版社,2001.
[99]葛晓陵.药物超细粉碎技术的研究.中国粉体技术,2002,8(6):19-23.
[100]葛建国.四环素的非抗感染用途.中国临床医生,2002,30:50-53.
[101]张建成,四环素类抗生素研究进展.河北医药,2005,27(7):710-712.
[102]朱虎刚,田宜灵,陈丽等,超临界CO_2+CH_3OH及C_2H_5OH二元系的气液平衡.高等学校化学学报,2002,23(8):1588-1591.
[103]Zhu Hugang,Tian Yiling,Chen Li et al.High-pressure Phase Equilibria for Binary Ethanol System Containing Supereritical CO_2.Chin.J.of Chem.Eng,2001,9(3):322-325.
[104]张伦.红霉素市场现状与发展趋势.中国药房,2003,14(12):713-715.
[105]杨帆,林茵,谭载友.肺靶向红霉素聚乳酸微球的研究.中国药科大学学报,2002,33(3):211-215.
[106]Atkinson,R.M.,Bedford,C.,Child,K.J.,Tomich,E.G.,effect of particle size on blood-griseofulvin levels in man,Nature February 10.1962.
[107]Kraml,M.,Dubuc,J.,Guadry,R.,Proc.R.Soc.London 12,239,1962.
[108]刘晓峰,邓修,沈中华.提高灰黄霉素溶解度的研究.中国抗生素杂志,1999,24(6):417-418,452
[109]Barbara De Gioannis,Arlette Vega Gonzalez,Pascale Subra.Anti-solvent and co-solvent effect of CO_2 on the solubility of griseofulvin in acetone and ethanol solutions.J.Supercrit Fluids,2004,29:49-57.
[110]Chiehming J.Chang,Chany-Yih Day,Ching-Ming Ko et al.Densities and P-x-y diagrams for carbon dioxide dissolution in methanol,ethanol,and acetone mixtures.Fluid Phase Equilibria,1997,131:243-258.
[111]V.Bulmus,H.Ayhan,E.Piskin.Modified PMMA monosize microbeads for glucose oxidase immobilization.Chem.Eng.J.,1997,65:71-76.
[112]E.Waddell,Y.Wang,W.Stryjewski,S.McWhorter,A.C.Henry,D.Evans,R.L.McCarley,S.A.Soper,High-resolution near-infrared imaging of DNA microarrays with time resolved acquisition of fluorescence lifetimes.Anal.Chem.,2000,72:5907-5913.
[113]F.Fixe,M.Dufva,P.Telleman,C.B.V.Christensen,Functionalization of poly(methyl methacrylate)(PMMA) as a substrate for DNA microarrays.Nucleic Acids Res.,2004,32:1-8.
[114]Fang Han,Yuan Xue,Yiling Tian,Xuefeng Zhao,and Li Chen.Vapor-Liquid Equilibria of the Carbon Dioxide + Acetone System at Pressures from(2.36 to 11.77)MPa and Temperatures from (333.15 to 393.15) K.J.Chem.Eng.Data,2005(50):36-39
[2]罗付生,韩爱军,杨毅等.超细粉体技术在中药行业中的应用.中草药,2001,32(10):941-942.
[3]Gonda T I.Controlled drug delivery system.Marcel Dekker,Inc.,New York,1998.
[4]Hickey A J.Thomposon D C.Physiology of the airways.In:Pharmaceutical Inhalation Aerosol Technology,Hickey A J Ed.,Marcel Dekker,Inc.,New York,1992.
[5]Smith P L.Peptide delivery via the pulmonary route:a valid approach for local and systemic delivery.J Controlled Release,1997,46(1):99-106.
[6]朱自强,关怡新,姚善泾.超临界辅助雾化制备适于气溶胶给药的药物微粒.化工学报,2005 56(2):187-196.
[7]马喆坤,邹亚萍,周云高.超细粉碎技术在制药工业中的应用.江西化工,2003,4(2):174-175.
[8]葛晓陵.药物超细粉碎技术的研究.中国粉体技术,2002,8(6):19-23.
[9]王喜忠,于才渊,周才君.喷雾干燥.北京:化学工业出版社.2003.
[10]张更超,应富强.超细粉碎技术现状及发展趋势.中国非金属矿业导刊,2003,9(2):44-48.
[11]邓政兴,张润,李立华等.生物材料制备新方法-超临界流体技术.化学世界,2004,(2):99-102.
[12]刘燕,王威强,李爱菊.超临界流体技术制备超微材料应用.化学工程,2004,32(6):47-51.
[13]朱自强.超临界流体技术.北京:化学工业出版社,2000.18-23.
[14]V.Krukonis.Supercritical Fluid Nucleation of Difficult-to-Comminute Solids.Paper at Annual Meeting AIChE,San Francisco,November 1984.
[15]Meziani MJ,Rollins HW,Allard LF,et al.Protein-protected nanoparticles from rapid expansion of supercritical solution into aqueous solution.J Phys Chem B,2002,106(43):11178-11182.
[16]M.Turk,P.Hils,B.Helfgen.Micronization of pharmaceutical substances by the Rapid Expansion of Supercritical Solutions(RESS):a promising method to improve bioavailability of poorly soluble pharmaceutical agents.J.Supercrit Fluids,2002,22:75-84.
[17]D.Kayrak,U.Akman,O.Hortacsu.Micronization of Ibuprofen by RESS.J.Supercrit.Fluids,2003,(26):17-31.
[18]P.Debenedetti,J.W.Tom,S.D.Yeo et al.Application of Supercriticai Fluids for the Production of Sustained Delivery Devices.J.Controlled Release.,1993,24:27-44.
[19]P.Pallado,L.Benedetti,L.Callegaro.WO Patent 96/29998,1996
[20]P.Pathak,M.J.Meziani,Y.-P.Sun,Supercritical fluid technology for enhanced drug delivery,Expert Opin.Drug Deliv.,2005,2:4-7.
[21]P.Pathak,M.J.Meziani,T.Desai,Y.-P.Sun,Nanosizing drug particles in supercritical fluid processing.J.Am.Chem.Soc.,2004,126:10-42.
[22]Pankaj Pathak,Mohammed J.Meziani,Tarang Desai,Ya-Ping Sun.Formation and stabilization of ibuprofen nanoparticles in supercritical fluid processing.J.Supercrit Fluids.,2006,37:279-286.
[23]陈鸿雁,蔡建国.超临界流体溶液快速膨胀法制备灰黄霉素微细颗粒.化工学报,2001,52(1):56-60.
[24]陈兴权,赵天生,于慧杰,等.用超临界CO-2制备α2细辛醚及布洛芬微细颗粒.宁夏大学学报:自然科学版,2001,22(2):1552157.
[25]蒋思嫒,赵亚平,于文利,等.超临界快速膨胀法制备植物甾醇超细微粒.精细化工,2004,21(2):129-132.
[26]P.M.Gallagher,M.P.Coffey,V.J.Krukonis,Gas Anti-Solvent Recrystallization of RDX:Formation of Ultrafine Particles of a Difficult-to-Comminute Explosive.J.Supercrit Fluids.,1992,5,130-142.
[27]B.Subramaniam,S.Saim,RA.Rajewski,V.Stella.Method for particle precipitation and coating using near-critical and supercriticai anti solvents.US Patent 5,833,891,1997.
[28]M.Hanna,P.York.WO Patent 95/01221,1994.
[29]M.Moneghini,I.Kikic,D.Voinovich et al.Processing of carbamazepine-PEG4000 solid dispersions with supercritical carbon dioxide:Preparation,characterisation,and in vitro dissolution.Int J Pharm.,2001,222:129-138.
[30]OI.Corrigan,AM.Crean.Comparative physicochemical properties of hydrocortisobe- PVP composites prepared using supercritical carbon dioxide by the gas anti-solvent recrystallization process by coprecipitation and by spray drying.Int J Pharm.,.2002,245:75-82.
[31]MJ.Cocero,S.Ferrero.Crystallization of β-carotene by a GAS process in batch.E.ect of operating conditions.J Supercrit Fluids.,2002,22:237-245.
[32]Eivassore N,Bertucco A,Caliceti P.Production of insulin-loaded poly(ethyleneglycol)/poly(l-lactide)(PEG/PLA) nanoparticles by gas antisolvent techniques.J.Pharm Sci.,2001,90:1628-1636.
[33]Rantakyla M,Jantti M,Aaltonen O et al.The e.ect of initial drop size on particle size in the supereritical antisolvent precipitation(SAS) technique.J.Supercrit Fluids.,2002,24:251-263.
[34]Winters M A,Knutson B L,Debenedetti P G,et al.Precipitation of proteins in supercritical carbon dioxide[J].J Pharm.Sci.,1996,85:586-594.
[35]Sang-Do Yeo,Min-Su Kim,Jong-Chan Lee.Recrystailization of sulfathiazole and chlorpropamide using the supercritical fluid antisolvent process.J Supercrit Fluids.,2003,25(2):143-154.
[36]E.Reverchon,I.De Marco,G.Della Porta.Rifampicin microparticles production by supercritical antisolvent precipitation.Int.J Pharm.,2002,243:83-91.
[37]E.Reverchon,I.De Marco,G.Caputo,G.Della Porta.Pilot scale micronization of arnoxicillin by supercritical antisolvent precipitation.J Supercrit Fluids.,2003,26:1-7.
[38]R.Bodmeier,H.Wang,DJ.Dixon et al.Polymeric Microspheres Prepared by Spraying into Compressed Carbon Dioxide.Pharm Res.,1995,12(8):1211-1217.
[39]TJ.Young,KP.Johnston,K.Mishima et al.Encapsulation of lysozyme ina biodegradeable polymer by precipitinon with a vapor-over-liquid antisolvent.J Pharm Sci.,1999,88(6):640-650.
[40]H.Krober,U.Teipel.Materials processing with supercritical antisolvent precipitation:Process parameters and morphology of tartaric acid.J Supercrit Fluids.,2002,22:229-235.
[41]WK.Snavely,B.Subramaniam,RA.Rajewski et al.Micronization of insulin from halogenated alcohol solution using supercritical carbon dioxide as an antisolvent.J Pharm Sci.,2002,91:2026-2039.
[42]B.Warwick,F.Dehghani,NR.Foster et al.Regtop.Micronization of copper indomethacin using gas antisolvent processes.Ind Eng Chem Res.,2002,41:1993-2004.
[43]TL.Sze,F.Dehghani,NR.Foster.Micronization and microencapsulation of pharmaceuticals using a carbon dioxide antisolvent.Powder Technol.,2002;126:134-149.
[44]P.Chattopadhyay,RB.Gupta.Production of griseofulvin nanoparticles using supercritical CO_2antisolvent with enhanced mass transfer.Int J Pharm 2001;228:19-31.
[45]A.Kordikowski,T.Shekunov,P.York.Polymorph control of sulfathiazole in supercritical CO_2.Pharm Res 2001;18:682-688.
[46]HHY.Tong,BY.Shekunov,P.York et al.Characterization of two polymorphs of salmeterol xinafoate crystallized from supercritical fluids.Pharm.Res.2001,18:852-858.
[47]S.Bristow,T.Shekunov,BY.Shekunov et al.Analysis of the supersaturation and precipitation process with supercritical CO_2.J.Supercrit.Fluids.2001,21:257-271.
[48]AD.Edwards,BY.Shekunov,A.Kordikowski et al,P.York.Crystallization of pure anhydrous polymorphs of carbamazepine by solution enhanced dispersion with supercritical fluid(SEDSTM).J Pharm.Sci.2001,90:1115-1124.
[49]SP.Velaga,R.Ghaderi,J.Carlfors.Preparation and characterization of hydrocortisone particles using a supercritical fluids extraction process.Int.J.Pharm.,2002;231:155-166.
[50]H.Okamoto,S.Nishida,H.Todo et al.Pulmonary gene delivery by chitosan-pDNA complex powder prepared by a supercritical carbon dioxide process.J Pharm.Sci.,2003,92:371-380.
[51]陈岚,张岩,李保国等.压力对超临界流体技术制备药物微粒的影响.上海理工大学学报,2004,26(3):220-223.
[52]陈岚,张岩,李保国等.超临界流体增强溶液分散度法制备阿莫西林缓释微囊.化学工程,2006,34(1):70-73,78
[53]李冬兵,王家炜,杨基础.超临界抗溶剂技术制备对乙酰氨基酚-PEG4000固体分散体.中国抗生素杂志,2005,30(4):1982203.
[54]李志义,刘学武,金良安等 超临界反溶剂过程制备四环素超细微粒.大连理工大学学报,2006,46(4):491-494.
[55]李志义,李文秀,刘学武等.超临界反溶剂过程制备灰黄霉素超细微粒.化学反应工程与工艺,2006,22(2):156-161.
[56]刘学武,李志义,夏远景等.超临界反溶剂过程制备银杏叶提取物超细微粒.高校化学工程学报,2005,19(4):550-553.
[57]刘学武,李志义,韩冰等.超临界反溶剂过程制备槲皮素超细颗粒.林产化学与工业,2004,24(2):73-76.
[58]Liu Xue-wu,Li Zhi-yi,Han Bing et al.Supercritical Antisoivent Precipitation of Microparticles of Quercetin.China J.Chem.Eng.2005,13(1):128-130.
[59]F.Graser,G.Wickenhaeuser.US Patent 4,451,654.
[60]R.E.Sievers,U.Karst.Patent EP 0,677,332,1995;US Patent 5,639,441,1997.
[61]E.Reverchon.Supercritical-assisted atomaization to produce micro-and/or nanoparticles of controlled size and distribution.Ind.Eng.Chem.Res.2002,41:2405-2411.
[62]Sievers,R.E.,Karst,U.,Milewski,P.D et al.Formation of Aqueous Small Droplet Aerosols Assisted by Supercritical Carbon Dioxide.Aerosol Sci.Technol.1999,30,3-10.
[63]N.Ventosa,S.Sala,J.Veciana.DELOS process:a crystallization technique using compressed fluids 1.Comparison to the GAS crystallization method.J.Supererit.Fluids.2003,26:33-45.
[64]M.Rodrigues,N.Peirico,H.Matos,E.Gomes de Azevedo,MR.Lobato,AJ.Almeida Microcomposites theophylline/hydrogenated palm oil from a PGSS process for controlled drug delivery systems.J Supercrit.Fluids,2004,29:175-184
[65]Sethia S.,Squillante.Physicochemical characterization of solid dispersions of carbamazepine formulated by supercritical carbon dioxide and conventional evaporation method.J.Pharm.Sci.2002,91,1948-1957.
[66]RE.Sievers,ETS.Huang,JA.Villa,et al Brauer.Micronization of water-soluble or alcohol-soluble pharmaceuticals and model compounds with a low-temperature bubble dryer.J.Supercrit Fluids.2003,26:9-16.
[67]SP.Sellers,GS.Clark,RE.Sievers,JF.Carpenter.Dry powders of stable protein formulations from aqueous solutions prepared using supercritical CO_2-assisted aerosolization.J Pharm.Sci.2001,90(6):785-797.
[68]E.Reverchon,G.Delia Porta.Micronization of antibiotics by supercritical assisted atomization.J.Supercrit.Fluids,2003,26:243-252.
[69]E.Reverchon,G.Delia Porta.Terbutaline microparticles suitable for aerosol delivery produced by supercritical assisted atomization.Inter J Pharm,2003,258:1-9.
[70]E.Reverchon,A.Spada.Erythromycin micro-particles produced by supercritical fluid atomization [J].Powder Technol.,2004,14:100-108.
[71]G.Delia Porta,C.De Vittori,E.Reverchon.Supercritical assisted atomization:a novel technology for microparticles preparation of an asthma-controlling drug.AAPS Pharm.Sci.Tech.,2005,6 (3):421-428.
[72]E.Reverchon,A.Antonacci.Cyclodextrins micrometric powders obtained by sypercritical fluid processing.Biotechnol.Bioeng.2006,94(4):753-761.
[73]Ernesto Reverchon and Alessandra Antonacci.Chitosan Microparticles Production by Supercritical Fluid Processing.Ind.Eng.Chem.Res.,2006,45:5722-5728.
[74]E.Reverchon,A.Antonacci.Polymer microparticles production by supercritical assisted atomization.J.Supercrit.Fluids.,2007,39:444-452.
[75]Peng D,Robinson D.A new two-constant equation of state.Ind.Eng.Fund.1976,15:59-60
[76]Shariati A.,Peters C.J.Measurements and modeling of the phase behavior of ternary systems of interest for the GAS process:Ⅰ.The system carbon dioxide + 1-propanol + salicylic acid.J.Supercri.Fluids,2002,23(3):195-208.
[77]Liu Zhimin,Wang Jiaqiu,Song Liping et al.Study on the phase behavior of cholesterol-acetone-CO_2 system and recrystallization of cholesterol by antisolvent CO_2.J.Supercri.Fluids,2002,24(1):1-6.
[78]Chang C.J.,Randolph A.D.Solvent expansion and solute solubility predictions in gas-expanded liquids.AIChE J.,1990,36(6):939-942.
[79]Dixon D.J.,Johnston K.P.Molecular thermodynamics of solubilities in gas antisolvent crystallization.AIChE J.,1991,37(10):1441-1449.
[80]Lele A K,Shine A D.Morphology of polymers precipitated from a supercritical solvent.AIChE J.1992,385:742-751.
[81]Kwauk,X,Debenedetti,P.G.Mathematical modeling of aerosol formation by rapid eapansion of supercritical solution in a converging nozzle.J.Aerosol Sci,1993,24(4):445-469.
[82]B.Helfgen,P.Hils,Ch.Hoizknecht et al.Schaber.Simulation of particle formation during the rapid expansion of supercritical solution.Aerosol Science,2001,32:295-319.
[83]Song Y;Hino T,Lambert S et al.Liquid-liquid equilibria for polymer solutions and blends including copolymers.Fluid Phase Equilibria,1996,117:69-76.
[84]邓小亮,超临界反溶剂过程相行为研究,硕士论文,大连:大连理工大学.2004.
[85]Li Y.H.,Dillard K.H.,Robinson R.L.Vapor-liquid phase equilibrium for carbon dioxide- n-Hexane at 40,80 and 120℃.J.Chem.Eng.Data,1981,26(1):53-55.
[86]Ng H.J.and Robinson D.B.Equilibrium phase properties of the toluene-carbon dioxide system.J.Chem.Eng.Data,1978,23(4):325-327.
[87]Chang C.J.,Day C.Y.,Ko C.M.,Chiu K.L.Densities and P-x-y diagrams for carbon dioxide dissolution in methanol,ethanol,and acetone mixtures.Fluid Phase Equilibria,1997,131:243-258.
[88]Silva M.V.,Barbosa D.,Ferreira P.O.et al.High pressure phase equilibrium data for the systems carbon dioxide/ethyl acetate and carbon dioxide/isoamyl acetate at 295.2,302.2 and 313.2K.J.Chem.Eng.Data,1992,37(2):249-251.
[89]Li Zhiyi,Xia Yuanjing,Liu Xuewu,et al.Study of the liquid phase volume expansion for CO_2/Organic Solvent Systems.Chinese J.Chem.Eng.,2005,13(4) 504-509.
[90]Liu Zhimin,Li Dan,Yang Guanying et al.Solubility of hydroxybenzoic acid isomers in ethyl acetate expanded with CO_2..J.Supercrit.Fluids,2000,18(2):111-119.
[91]Singh H,Yun S,Macnaughton S et al.Solubility of cholesterol in supercritical ethane and binary gas mixtures containing ethane.Ind.Eng.Chem.Res,1993,32(11):2841-2848.
[92]Lee HK,Kim CH.Solid Solubilities of Methoxyphenylacetic Acid Isomer Compounds in Supercritical Carbon Dioxide.J.Chem.Eng.Data.,1994,39(1):163-165.
[93]Trabelsi F,Kikic I.Predicting the approximate solubilities of solids in dense carbon dioxide.J.Supercritical Fluid.,1999,14(2):151-161.
[94]Huang C,Tang M,Tao W et al.Calculation of the solid solubilities in supercritical carbon dioxide using a modified mixing model.Fluid phase equilibria,2001,179:67-84.
[95]Angus S,Amstrong B,Renk KM.Carbon dioxide international thermodynamic tables of fluid state.IUPAC Project Center,Imperial College,London.Pergamon Press 3:P385.
[96]童景山,李敬编著.流体热物理性质的计算.北京:清华大学出版社.1982.
[97]Chapman S,Cowling T G.The mathematical Theory of Nonuniform Gas,Cambride,New York,1939
[98]陶文铨.数值传热学.西安:西安交通大学出版社,2001.
[99]葛晓陵.药物超细粉碎技术的研究.中国粉体技术,2002,8(6):19-23.
[100]葛建国.四环素的非抗感染用途.中国临床医生,2002,30:50-53.
[101]张建成,四环素类抗生素研究进展.河北医药,2005,27(7):710-712.
[102]朱虎刚,田宜灵,陈丽等,超临界CO_2+CH_3OH及C_2H_5OH二元系的气液平衡.高等学校化学学报,2002,23(8):1588-1591.
[103]Zhu Hugang,Tian Yiling,Chen Li et al.High-pressure Phase Equilibria for Binary Ethanol System Containing Supereritical CO_2.Chin.J.of Chem.Eng,2001,9(3):322-325.
[104]张伦.红霉素市场现状与发展趋势.中国药房,2003,14(12):713-715.
[105]杨帆,林茵,谭载友.肺靶向红霉素聚乳酸微球的研究.中国药科大学学报,2002,33(3):211-215.
[106]Atkinson,R.M.,Bedford,C.,Child,K.J.,Tomich,E.G.,effect of particle size on blood-griseofulvin levels in man,Nature February 10.1962.
[107]Kraml,M.,Dubuc,J.,Guadry,R.,Proc.R.Soc.London 12,239,1962.
[108]刘晓峰,邓修,沈中华.提高灰黄霉素溶解度的研究.中国抗生素杂志,1999,24(6):417-418,452
[109]Barbara De Gioannis,Arlette Vega Gonzalez,Pascale Subra.Anti-solvent and co-solvent effect of CO_2 on the solubility of griseofulvin in acetone and ethanol solutions.J.Supercrit Fluids,2004,29:49-57.
[110]Chiehming J.Chang,Chany-Yih Day,Ching-Ming Ko et al.Densities and P-x-y diagrams for carbon dioxide dissolution in methanol,ethanol,and acetone mixtures.Fluid Phase Equilibria,1997,131:243-258.
[111]V.Bulmus,H.Ayhan,E.Piskin.Modified PMMA monosize microbeads for glucose oxidase immobilization.Chem.Eng.J.,1997,65:71-76.
[112]E.Waddell,Y.Wang,W.Stryjewski,S.McWhorter,A.C.Henry,D.Evans,R.L.McCarley,S.A.Soper,High-resolution near-infrared imaging of DNA microarrays with time resolved acquisition of fluorescence lifetimes.Anal.Chem.,2000,72:5907-5913.
[113]F.Fixe,M.Dufva,P.Telleman,C.B.V.Christensen,Functionalization of poly(methyl methacrylate)(PMMA) as a substrate for DNA microarrays.Nucleic Acids Res.,2004,32:1-8.
[114]Fang Han,Yuan Xue,Yiling Tian,Xuefeng Zhao,and Li Chen.Vapor-Liquid Equilibria of the Carbon Dioxide + Acetone System at Pressures from(2.36 to 11.77)MPa and Temperatures from (333.15 to 393.15) K.J.Chem.Eng.Data,2005(50):36-39
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