超临界流体构筑微粒技术作为药物制剂研发平台的应用

摘要

在药物递送系统的研发和应用过程中,制备结构可控的微粒药物制剂是重要且有效的方式。本论文阐述了超临界流体构筑微粒技术在药物递送系统创新的应用,包括纳微米级药物微粒、药物多晶型控制和复合粒子制剂。总结了不同类型的超临界流体工艺特点及其粒子微观结构调控的机理。基于热力学和流体动力学两因素,利用超临界流体构筑微粒技术调控构筑药物活性成分的微观结构,包括粒度、晶型、晶习和粒度分布。

	Service

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	Email Alert
	RSS
	作者相关文章
	朱彬
	洪鸣凰
	任福正
	任国宾

关键词：药物传递系统；超临界流体构筑微粒技术；粒子微观结构；纳微米级微粒；药物多晶型；复合粒子制剂

Abstract：

Preparation of particulate drug delivery systems with some controlled structure is an important and efficious way in the research, development and application of pharmaceuticals. This paper summarized the novel application of supercritical fluid-based particle technology in drug delivery system, including preparation of nano-micron grade drug particles, control of drug polymorphism and formation of composite particles. The characteristics of different types of supercritical fluid technology and the mechanism of particle microstructure regulation were summerized. Based on the principles of thermodynamics and fluid dynamics, supercritical fluid-based particle technology is able to tune and construct the microstructure of active pharmaceutical ingredients, including grain size, crystal habit, polymorph, particle size distribution and so on.

Keywords： drug delivery system； supercritical fluid-based particle technology； microstructure； nano-micron grade drug particles； drug polymorphism； composite particle

Received 2015-07-10;

Fund:

国家自然科学基金青年基金(81102391)、上海科学技术委员会(12DZ1930702)。

Corresponding Authors: 洪鸣凰,E-mail:mhhong@ecust.edu.cn。 Email: mhhong@ecust.edu.cn

About author: 朱彬(1989-),男,博士研究生,现从事药物晶体工程方面的研究。

引用本文:

朱彬, 洪鸣凰, 任福正, 任国宾.超临界流体构筑微粒技术作为药物制剂研发平台的应用[J]. 化学工业与工程, 2015,32(5): 52-61

Zhu Bin, Hong Minghuang, Ren Fuzheng, Ren Guobin.The Application of Supercritical Fluid-Based Particle Technology as the Platform for Pharmaceutical Preparations Research and Development[J]. Chemcial Industry and Engineering, 2015,32(5): 52-61

[1] Allen T M, Cullis P R. Drug delivery systems: Entering the mainstream[J]. Science, 2004, 303: 1 818-1 822
[2] Fahr A, Liu X. Drug delivery strategies for poorly water-soluble drugs[J]. Expert Opin Inv Drug, 2007, 4: 403-416
[3] Loira-Pastoriza C, Todoroff J, Vanbever R. Delivery strategies for sustained drug release in the lungs[J]. Adv Drug Deliver Rev,2014, 75: 81-91
[4] Cansell F, Aymonier C. Design of functional nanostructured materials using supercritical fluids[J]. J Supercrit Fluid, 2009, 47: 508-516
[5] Jain A, Bollinger J A, Truskett T M. Inverse methods for material design[J]. AIChE J, 2014, 60(3): 2 732-2 740
[6] Yasuji T, Takeuchi H, Kawashima Y. Particle design of poorly water-soluble drug substances using supercritical fluid technologies[J]. Adv Drug Deliv Rev, 2008, 60 (3): 388-398
[7] Jung J, Perrut M. Particle design using supercritical fluids: Literature and patent survey [J]. Journal of Supercritical Fluids, 2001, 20: 179-219
[8] Krukonis V. Supercritical fluid nucleation of difficult to comminute solids [C]. San Francisc Annual Meeting A IChE, 1984: 11
[9] Smith R D. Supercritical fluid molecular spray film deposition and powder formation: US, 4582731[P]. 1986-04-15
[10] Graser F, Wickenhaeuser G. Conditioning of finely divided crude organic pigments: US, 4451654 [P]. 1984-05-29
[11] Gallagher P M, Coffey M P, Krukonis V J. Gas anti-solvent recrystallization of RDX: Formation of ultrafine particles of a difficult-to-comminute explosive [J]. J Supercrit Fluids, 1992, 5: 130-142
[12] Hanna M, York P. Method and apparatus for formation of particles: WO, 1995/01221 [P]. 1994-06-30
[13] Chattopadhyay P, Gupta R B. Production of griseofulvin nanoparticles using supercritical CO₂ antisolvent with enhanced mass transfer[J]. Int J Pharm, 2001, 228: 19-31
[14] Gupta R B, Shim J J. Solubility in supercritical carbon dioxide[M].USA: CRC Press, 2006
[15] Skerget M, Knez Z, Knez-Hrncic M. Solubility of solids in sub-and supercritical fluids: A review[J]. J Chem Eng Data, 2011, 56: 694-719
[16] Jiang Y, Liu M, Sun W, et al. Phase behavior of poly (lactic acid)/poly (ethylene glycol)/poly (lactic acid)(PLA-PEG-PLA) in different supercritical systems of CO₂+dichloromethane and CO₂+C₂H₅OH+dichloro methane[J]. J Chem Eng Data, 2010, 55: 4 844-4 848
[17] Diefenbacher A,Türk M. Phase equilibria of organic solid solutes and supercritical fluids with respect to the RESS process[J]. Journal of Supercritical Fluids, 2002, 22(3): 175-184
[18] Reverchon E, Caputo G, De Marco I. Role of phase behavior and atomization in the supercritical antisolvent precipitation[J]. Ind Eng Chem Res, 2003, 42: 6 406-6 414
[19] Weber M, Russell L M, Debenedetti P G. Mathematical modeling of nucleation and growth of particles formed by the rapid expansion of a supercritical solution under subsonic conditions[J]. J Supercritical Fluid, 2002, 23: 65-80
[20] Martín A, Cocero M J. Micronization processes with supercritical fluids: Fundamentals and mechanisms[J]. Adv Drug Deliver Rev, 2008, 60: 339-350
[21] Martín A, Cocero M J. Numerical modeling of jet hydrodynamics, mass transfer, and crystallization kinetics in the supercritical antisolven(SAS) process[J]. J Supercritical Fluid, 2004, 32: 203-219
[22] Lengsfeld C S, Delplanque J P, Barocas V H, et al. Mechanism governing microparticle morphology during precipitation by a compressed ntisolvent: Atomization vs nucleation and growth[J]. J Phys Chem B, 2000, 104: 2 725-2 735
[23] Werling J O, Debenedetti P G. Numerical modeling of mass transfer in the supercritical antisolvent process[J]. J Supercrit Fluid, 1999, 16: 167-181
[24] Chattopadhyay P, Gupta R B. Protein nanoparticles formation by supercritical antisolvent with enhanced mass transfer[J]. AIChE J, 2002, 48: 235-244
[25] Bahrami M, Ranjbarian S. Production of micro-and nanocomposite particles by supercritical carbon dioxide[J]. J Supercritical Fluids, 2007, 40: 263-283
[26] Zarena A S, Sankar K U. Design of submicron and nanoparticle delivery systems using supercritical carbon dioxide-mediated processes: An overview[J]. Therapeutic Delivery, 2011, 2: 259-277
[27] Domingo C, Saurina J. An overview of the analytical characterization of nanostructured drug delivery systems: Towards green and sustainable pharmaceuticals: A review[J]. Anal Chim Acta, 2012, 744:8-22
[28] Sun Y. Supercritical fluid particle design for poorly water-soluble drugs[J]. Current Pharmaceutical Design, 2014,20: 349-368
[29] Chen W, Hu X, Hong Y, et al. Ibuprofen nanoparticles prepared by a PGSS^TM-based method[J]. Powder Technol, 2013, 245: 241-250
[30] Dalvi S V, Azad M A, Dave R. Precipitation and sta-bilization of ultrafine particles of Fenofibrate in aqueous suspensions by RESOLV[J]. Powder Technol, 2013, 236: 75-84
[31] Kim M S, Jin S J, Kim J S, et al. Preparation, characterization and in-vivo evaluation of amorphous atorvastatin calcium nanoparticles using supercritical antisolvent (SAS) process[J]. Eur J Pharm Biopharm, 2008, (69): 454-465
[32] Esfandiari N, Ghoreishi S M. Synthesis of 5-fluorouracil nanoparticles via supercritical gas antisolvent process[J]. J Supercrit Fluid, 2013, 84: 205-210
[33] Zu Y, Wang D, Zhao X, et al. A novel preparation method for camptothecin (CPT) loaded folic acid conjugated dextran tumortargeted nanoparticles[J]. Int J Mol Sci 2011; 12: 4 237-4 249
[34] Huang Z, Guo Y, Miao H, et al. Solubility of progesterone in supercritical carbon dioxide and its micronization through RESS[J]. Powder Technol,2014, 258: 66-77
[35] Yim J H, Kim W S, Lim J S. Recrystallization of adefovir dipivoxilparticles using the aerosol solvent extraction system process[J]. Ind Eng Chem Res, 2014, 53: 1 663-1 671
[36] Todo H, Iida K, Okamoto H, et al. Improvement of insulin absorption from intratracheally administrated dry powder prepared by supercritical carbon dioxide process[J]. J Pharm Sci, 2003, 92: 2 475-2 486
[37] Bahrami M, Ranjbarian S. Production of micro-and nanocomposite particles by supercritical carbon dioxide[J]. J Supercritical Fluids, 2007, 40: 263-283
[38] Tandya A, Mammucari R, Dehghani F, et al.Dense gas processing of polymeric controlled release formulations[J]. Int J Pharm, 2007, 328: 1-11
[39] Reverchon E, De Marco I, Caputo G, et al.Pilot scale micronization of amoxicillin by supercritical antisolvent precipitation[J]. J Supercritical Fluids, 2003, 26: 1-7
[40] Steckel H, Thies J, Müller B W. Micronizing of steroids for pulmonary delivery by supercritical carbon dioxide [J]. Int J Pharm, 1997, 152: 99-110
[41] Todo H, Iida K, Okamoto H, et al. Improvement of insulin absorption from intratracheally administrated dry powder prepared by supercritical carbon dioxide process[J]. J Pharm Sci, 2003, 92: 2 475-2 486
[42] Rodriguez-Spong B, Price C P, Jayasankar A, et al.General principles of pharmaceutical solid polymorphism: A supramolecular perspective[J]. Adv Drug Del Rev, 2004, 56: 241-274
[43] Knapman K. Polymorphic predictions[J]. Modern Drug Discovery, 2000, 3: 53-57
[44] Kruger G J, Gafner G. The crystal structures of polymorphs I and III of sulphathiazole[J]. Acta Cryst, 1972, B28: 272-283
[45] Kordikowski A, Shekunov T, York P. Polymorph control of sulfathiazole in supercritical CO₂[J]. Pharm Res, 2001, 18: 682-688
[46] Varshosaz J, Hassanzadeh F, Mahmoudzadeh M, et al. Preparation of cefuroxime axetil nanoparticles by rapid expansion of supercritical fluid technology[J]. Powder Technol, 2009, 189: 97-102
[47] Kim M S, Jin S J, Kim J S, et al. Preparation, characterization and in vivo evaluation of amorphous atorvastatin calcium nanoparticles using supercritical antisolvent (SAS) process[J]. Eur J Pharm Biopharm, 2008, 69: 454-465
[48] Shekunov B Y, Bristow S, York P. Formation of composite crystals by precipitation in supercritical CO₂[J]. Crystal Growth and Design, 2003, 3(4): 603-610
[49] Luis P, Miguel A, de Azevedo E G, et al. Formation of indomethacin-saccharin cocrystals using supercritical fluid technology[J]. European Journal of Pharmaceutical Sciences, 2009, 38: 9-17
[50] Reverchon E, Volpe M C, Caputo G. Supercritical fluid processing of polymers: Composite particles and porous materials elaboration[J]. Current Opinion in Solid State and Materials Sci, 2003, 7: 391-397
[51] Lee L Y, Wang C H, Smith K A. Supercritical antisolvent production of biodegradable micro-and nanoparticles for controlled delivery of paclitaxel[J]. J Control Release, 2008, 125: 96-106
[52] Hu D, Lin C, Liu L, et al. Preparation, characterization, and in vitro release investigation of lutein/zein nanoparticles via solution enhanced dispersion by supercritical fluids[J]. J Food Eng, 2012, 109: 545-552
[53] Chattopadhyay P, Shekunov B Y, Yim D, et al. Production of solid lipid nanoparticle suspensions using supercritical fluid extraction of emulsions (SFEE) for pulmonary delivery using the AERx system[J]. Adv Drug Del Rev, 2007, 59: 444-453
[54] Salmaso S, Elvassore N, Bertucco A, et al.Production of solid lipid submicron particles for protein delivery using a novel supercritical gas-assisted melting atomization process[J]. J Pharm Sci, 2009, 98: 640-649
[55] Zu Y, Wang D, Zhao X, et al. A novel preparation method for camptothecin (CPT) loaded folic acid conjugated dextran tumortargeted nanoparticles[J]. Int J Mol Sci, 2011, 12: 4 237-4 249
[56] Vezzù K, Campolmi C, Bertucco A. Production of lipid microparticles magnetically active by a supercritical fluid-based process[J]. Int J Chem Eng, 2009, 2009: 1-9
[57] Sievers R E, Quinn B P, Cape S P, et al.Near-Critical fluid micronization of stabilized vaccines, antibiotics and anti-virals[J]. J Supercritical Fluids, 2007, 42: 385-391
[58] Burger J L, Cape S P, Braun C S, et al.Stabilizing formulations for inhalable powders of live-attenuated measles virus vaccine[J]. J Aerosol Med Pulm Drug Deliv, 2008, 21: 25-34
[59] Tservistas M, Levy M S, Lo-Yim M Y A, et al. The formation of plasmid DNA loaded pharmaceutical powders using supercritical fluid technology[J]. Biotechnol Bioeng, 2001, 72: 12-18
[60] Okamoto H, Nishida S, Todo H, et al. Pulmonary gene delivery by chitosan-pDNA complex powder prepared by a supercritical carbon dioxide process[J]. J Pharm Sci, 2003, 92: 371-380