药物晶型转化与控制的研究进展

doi:10.3969/j.issn.0438-1157.2013.02.001

摘要/Abstract

摘要： 药物晶型可显著影响药品质量、安全性和有效性,国家"医药工业十二五发展规划"将药物晶型研究列为提升药物质量安全的主要任务和重点技术。本文介绍了药物多晶型的溶解度行为以及晶型转化的液相和固相介导机理,溶剂、添加剂/模板剂对药物晶型的控制有着重要的作用,而物理场效应(超声波、微波、超重力场等)对晶型转化过程起强化效应;过程分析技术的快速发展为晶型转化机理的研究以及过程优化、控制提供了先进手段。未来药物晶型转化与控制的研究将聚焦分子的组装与调控行为、过程分析以及药物的构效关系等方面。

关键词: 药物多晶型, 转化, 控制

Abstract: The drug polymorphism has a profound effect on the quality, safety and efficiency of the drug product.The Twelfth Five-Year Development Plan of China's Pharmaceutical Industry puts forward one of the major development tasks and technologies focused on the improvement in drug polymorphism study to enhance the quality and safety of the drugs.In this paper, the solubility behavior coupled with the solid state and solution mediated transformation of drug polymorphs are introduced and analyzed.In addition, solvent and additive/template play a critical role in the manipulation of drug crystal form.In many cases, physical field (ultrasound, microwave and high gravity-field)-assisted crystallization gives different results for the manipulation of drug crystal form by specific mechanism.Meanwhile, with the rapid development of process analytical technologies, process optimization and control are enhanced through getting more knowledge of drug polymorphism transformation.In the future, the research of transformation and manipulation of pharmaceutical drug polymorphism will focus on the molecular assembly and regulation, process analysis and structure-activity relationship of drugs.

Key words: drug polymorphism, transformation, manipulation

中图分类号:

TQ460.6

龚俊波, 王琦, 董伟兵, 王静康. 药物晶型转化与控制的研究进展[J]. 化工学报, 2013, 64(2): 385-392.

GONG Junbo, WANG Qi, DONG Weibing, WANG Jingkang. Progress on transformation and manipulation of drug polymorphism[J]. CIESC Journal, 2013, 64(2): 385-392.

参考文献 47

[1]	Tang Sufang(唐素芳).Research on pharmaceutical polymorphs and the influence of efficacy and physicochemical properties[J].Tianjin Pharmacy(天津药学),2002, 14(2): 12-14
[2]	Zhang Weiguo(张伟国),Liu Changxiao(刘昌孝).The bioavailability research of pharmaceutical polymorphs[J].Tianjin Pharmacy(天津药学),2007, 19(2): 59-61
[3]	Ma Tingsheng(马廷升),Zhu Lancui(朱兰翠).Study on the effective factors of bioavailability[J].Journal of Huaihua University(怀化学院学报),2006, 25(2): 76-77
[4]	Zheng Lili(郑丽莉).The effect of pharmaceutical polymorph for the quality of drugs[J].China Pharmacist(中国药师),2008, 11(3): 347-349
[5]	Jiang Shanfeng, Pieter J Jansens,Joop Hter Horst. Control over polymorph formation of o-aminobenzoic acid[J].Cryst.Growth Des., 2010, 10: 2541-2547
[6]	Martínez-Ohárriz M C,Martín C, Goi M M, Rodríguez-Espinosa C,Tros De Ilarduya-Apaolaza M C,Sánchez M.Polymorphism of diflunisal: isolation and solid-state characteristics of a new crystal form[J].J.Pharm.Sci., 1994, 83(2): 174-177
[7]	Damir Kralj, Ljerka Bre?evi?, Jasminka Kontrec.Vaterite growth and dissolution in aqueous solution(Ⅲ):Kinetics of transformation [J].J.Cryst.Growth, 1997, 177: 248-257
[8]	Davey R J, Blagden N, Righini S, Alison H, Ferrari E S.Nucleation control in solution mediated polymorphic phase transformations: the case of 2,6-dihydroxybenzoic acid[J].The Journal of Physical Chemistry B, 2001, 106(8): 1954-1959
[9]	Kostas Saranteas, Roger Bakale, Hong Yaping, Hoa Luong, Reza Foroughi,Stephen Wald.Process design and scale-up elements for solvent mediated polymorphic controlled tecastemizole crystallization[J].Org.Process Res., Dev., 2005, 9: 911-922
[10]	Shoji Maruyama, Hiroshi Oshima, Jyoji Kato.Crystal structure and solvent-mediated transformation of taltireline polymorphs[J].Chem.Eng.J., 1999, 75: 193-200
[11]	Shoji Maruyama,Hiroshi Oshima.Mechanism of the solvent-mediated transformation of taltirelin polymorphs promoted by methanol[J].Chem.Eng.J., 2001, 81(1/2/3): 1-7
[12]	Jiang Shanfeng, Pieter J Jansens,Joop Hter Horst. Mechanism and kinetics of the polymorphic transformation of o-aminobenzoic acid[J].Cryst. Growth Des., 2010, 10: 2123-2128
[13]	Naba K Nath, Himanshu Aggarwal,Ashwini Nangia. Crystal structure of methyl paraben polymorph(Ⅱ)[J].Cryst.Growth Des., 2011, 11: 967-971
[14]	Saikat Roy, Prashant M Bhatt, Ashwini Nangia,Gert J Kruger.Stable polymorph of venlafaxine hydrochloride by solid-to-solid phase transition at high temperature[J].Cryst.Growth Des., 2007, 7(3): 476-480
[15]	Mo Yuxin,Dang Leping,Wei Hongyuan.L-Glutamic acid polymorph control using amino acid additives[J].Ind. Eng. Chem.Res., 2011, 50: 10385-10392
[16]	Christopher P Price, Adam L Grzesiak,Adam J Matzger. Crystalline polymorph selection and discovery with polymer heteronuclei[J].J.Am.Chem.Soc., 2005, 127: 5512-5517
[17]	Scott C McKellar, Andrew J Urquhart, Dimitrios A Lamprou, Alastair J Florence.Polymer templating of supercooled indomethacin for polymorph selection[J].ACS Comb.Sci., 2012, 14: 155-159
[18]	Norihito Doki, Hiroya Seki, Kiyoteru Takano, Haruki Asatani, Masaaki Yokota, Noriaki Kubota.Process control of seeded batch cooling crystallization of the metastable α-form glycine using an in-situ ATR-FTIR spectrometer and an in-situ FBRM particle counter[J].Cryst. Growth Des., 2004, 4(5): 949-953
[19]	Corker D,Hodnett B K.Mechanistic features of polymorphic transformation:the role of surfaces[J].Cryst. Growth Des., 2010, 10: 2806-2816
[20]	Masahiro Kurotani, Izumi Hirasawa.Polymorph control of sulfamerazine by ultrasonic irradiation[J].Journal of Crystal Growth, 2008, 3(10): 4576-4580
[21]	Rizzuti A, Leonelli C.Crystallization of aragonite particles from solution under microwave irradiation[J].Powder Technology, 2008, 186: 255-262
[22]	Zbigniew A Dreger, Yogendra M Gupta.Raman spectroscopy of high-pressure-high-temperature polymorph of hexahydro-1,3,5-trinitro-1,3,5-triazine (ε-RDX)[J].J.Phys.Chem.A, 2010, 114(26): 7038-7047
[23]	Lee Eun Hee, Stephan X M Boerrigter, Alfred C F Rumondor,Sai P Chamarthy,Stephen R Byrn.Formation and solid-state characterization of a salt-induced metastable polymorph of flufenamic acid[J].Cryst.Growth Des., 2008, 8(1): 91-97
[24]	Scott L Childs, Leonard J Chyall, Jeanette T Dunlap, David A Coates, Barbara C Stahly,Patrick Stahly G.A metastable polymorph of metformin hydrochloride: isolation and characterization using capillary crystallization and thermal microscopy techniques[J].Cryst.Growth Des., 2004, 4(3): 441-449
[25]	Julien Zaccaro, Jelena Matic, Allan S Myerson, Bruce A Garetz.Nonphotochemical, laser-induced nucleation of supersaturated aqueous glycine produces unexpected polymorph[J].Cryst. Growth Des., 2001, 1(1): 5-8
[26]	Gianluca Di Profio, Selene Tucci, Efrem Curcio, Enrico Drioli.Selective glycine polymorph crystallization by using microporous membranes[J].Cryst. Growth Des., 2007, 7(3): 526-530
[27]	Masahiro Kurotani, Izumi Hirasawa.Effect of ultrasonic irradiation on the selective polymorph control in sulfamerazine[J].Chemical Engineering Research and Design, 2010, 9(88): 1272-1278
[28]	Narducci O, Jones A G.Seeding in situ the cooling crystallization of adipic acid using ultrasound[J].Cryst. Growth Des., 2012, 12: 1727-1735
[29]	Marcus A O'Mahony, Anthony Maher, Denise M Croker, ke C Rasmuson, Benjamin K Hodnett.Examining solution and solid state composition for the solution-mediated polymorphic transformation of carbamazepine and piracetam[J].Cryst.Growth Des., 2012, 12(4): 1925-1932
[30]	Debra S Hausman, Thomas Cambron R, Adel Sakr. Application of on-line Raman spectroscopy for characterizing relationships between drug hydration state and tablet physical stability[J].International Journal of Pharmaceutics, 2005, 299: 19-33
[31]	Wang Fang, Wachter John A, Antosz Frederick J, Berglund Kris A.An investigation of solvent-mediated polymorphic transformation of progesterone using in situ Raman spectroscopy[J].Org.Process Res., Dev., 2000, 4: 391-395
[32]	Starbuck Cindy,Spartalis Angela,Wai Lawrence,Wang Jian,Fernandez Paul,Lindemann Christopher M, Zhou George X,Ge Zhihong.Process optimization of a complex pharmaceutical polymorphic system via in situ Raman spectroscopy[J].Cryst.Growth Des., 2002, 2(5): 515-522
[33]	Kougoulos E,Jones A G, Jennings K H, Wood-Kaczmar M W.Use of focused beam reflectance measurement (FBRM) and process video imaging (PVI) in a modified mixed suspension mixed product removal (MSMPR) cooling crystallizer [J].Journal of Crystal Growth, 273(2005): 529-534
[34]	Zhang Haitao(张海涛).Research on crystallization technique of cefotaxime sodium .Tianjin:Tianjin University, 2008
[35]	Tian Jing(田静).Research on cooling crystallization process of irbesartan.Tianjin:Tianjin University,2008
[36]	Doris E Braun, Panagiotis G Karamertzanis, Jean-Baptiste Arlin, Alastair J Florence, Volker Kahlenberg, Derek A Tocher, Ulrich J Griesser, Sarah L Price.Solid-state forms of β-resorcylic acid: how exhaustive should a polymorph screen be? [J].Cryst. Growth Des., 2011, 11(1): 210-220
[37]	Chong-Hui Gu, Victor Young Jr, David J W Grant. Polymorph screening: influence of solvents on the rate of solvent-mediated polymorphic transformation[J].Journal of Pharmaceutical Sciences, 2001, 90(11): 1878-1890
[38]	Haiyan Q, Marjatta L K, Juha K.Additive effects on the solvent-mediated anhydrate/hydrate phase transformation in a mixed solvent[J].Cryst. Growth Des., 2007, 7(4): 724-729
[39]	Shan G,Igarashi K, Noda H, Oshima H.Control of solvent-mediated transformation of crystal polymorphs using a newly developed batch crystallizer (WWDJ-crystallizer)[J].Chemical Engineering Journal (Amsterdam,Netherlands), 2002, 85(2/3): 169-176
[40]	Li Tonglei, Paul W Ayers, Liu Shubin, Matthew J Swadley, Clare Aubrey-Medendorp.Crystallization force—a density functional theory concept for revealing intermolecular interactions and molecular packing in organic crystals[J].Chem.Eur.J., 2009, 15: 361-371
[41]	Gaetano Angelici, Nicola Castellucci, Simone Contaldi, Giuseppe Falini, Hans-Jrg Hofmann, Magda Monari,Claudia Tomasini.A network of small molecules connected by cross-linked NH bonds[J].Cryst. Growth Des., 2010, 10(1): 244-251
[42]	Jie Chen,Bernhardt L Trout.Computational study of solvent effects on the molecular self-assembly of tetrolic acid in solution and implications for the polymorph formed from crystallization[J].J.Phys.Chem.B, 2008, 112: 7794-7802
[43]	Kawakami Kohsaku, Asami Yasuo, Takenoshita Itsuro. Calorimetric investigation of solvent-mediated transformation of sulfamerazine polymorphism [J].Journal of Pharmaceutical Sciences, 2010, 99(1): 76-81
[44]	Alejandro J Alvarez, Aniruddh Singh, Allan S Myerson. Polymorph screening comparing a semi-automated approach with a high throughput method[J].Cryst. Growth Des., 2009, 9: 4181-4188
[45]	Aniruddh Singh, In Sung Lee, Allan S Myerson. Concomitant crystallization of ROY on patterned substrates: using a high throughput method to improve the chances of crystallization of different polymorphs[J].Cryst. Growth Des., 2009, 9(2):1182-1185
[46]	Julius F Remenar, Michael MacPhee J, Bridget K Larson, Viraj A Tyagi, Jason H Ho, David A McIlroy, Magali B Hickey, Paul B Shaw,rn Almarsson.Salt selection and simultaneous polymorphism assessment via high-throughput crystallization: the case of sertraline[J].Organic Process Research & Development, 2003, 7: 990-996
[47]	Nicholas Blagden, Roger J Davey.Polymorph selection:challenges for the future? [J].Cryst.Growth Des., 2003, 3(6): 873-885

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