• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

无定形态药物结晶行为的研究进展

施秦, 蔡挺

施秦, 蔡挺. 无定形态药物结晶行为的研究进展[J]. 中国药科大学学报, 2017, 48(6): 654-662. DOI: 10.11665/j.issn.1000-5048.20170604
引用本文: 施秦, 蔡挺. 无定形态药物结晶行为的研究进展[J]. 中国药科大学学报, 2017, 48(6): 654-662. DOI: 10.11665/j.issn.1000-5048.20170604
SHI Qin, CAI Ting. Recent progress on crystallizations of amorphous pharmaceutical solids[J]. Journal of China Pharmaceutical University, 2017, 48(6): 654-662. DOI: 10.11665/j.issn.1000-5048.20170604
Citation: SHI Qin, CAI Ting. Recent progress on crystallizations of amorphous pharmaceutical solids[J]. Journal of China Pharmaceutical University, 2017, 48(6): 654-662. DOI: 10.11665/j.issn.1000-5048.20170604

无定形态药物结晶行为的研究进展

基金项目: 国家自然科学基金资助项目(No.81402877);江苏省双创团队计划;天然药物活性组分与药效国家重点实验室优秀青年人才基金项目(No.SKLNMZZYQ201604);江苏省高校研究生科研创新计划项目(No.KYLX16_1180)

Recent progress on crystallizations of amorphous pharmaceutical solids

  • 摘要: 无定形态药物与其晶态形式相比较,通常具有更高的溶解度和更快的溶出速率,并有效地改善部分难溶性药物的口服生物利用度。但由于无定形态药物处于热力学不稳定的高自由能状态,容易自发转变为其热力学稳定的晶态形式,从而丧失其原有优势。本文简述了无定形态药物中存在的多种快速结晶行为,并介绍近几年来该领域的研究进展。通过对无定形药物结晶内在机制的研究,有助于人们更好地理解、控制和预测无定形态药物的物理稳定性,为合理有效的开发无定形药物制剂提供理论基础。
    Abstract: Compared to their crystalline form, amorphous drugs exhibit higher solubility and faster dissolution rate and thus enhancing oral bioavailability of poorly water soluble drugs. However, since the amorphous form is thermodynamically unstable relative to the crystalline form, amorphous solids tend to crystallize over time and subsequently negate their advantages. This review briefly describes fundamental aspects of amorphous substances and highlights the recent advances of fast crystallization behaviors. Understanding the inherent crystallization mechanisms of amorphous materials is of utmost importance in order to control the physical stability and lead to efficient formulation development of amorphous pharmaceutical solids.
  • [1] Datta S,Grant DJ.Crystal structures of drugs:advances in determination,prediction and engineering[J].Nat Rev Drug Discov,2004,3(1):42-57.
    [2] Hilfiker R.Polymorphism-In the Pharmaceutical Industry[M].Weinheim:Wiley-VCH,2006.
    [3] Bai ZH,Fang XL.Development of preparation for orally administreted insoluble drugs[J].Chin Pharm J(中国药学杂志),2005,40:1124-1127.
    [4] Ying J,Lü Y,Du GH.Progress in the research of amorphous pharmaceuticals[J].Acta Pharm Sin(药学学报),2009,44:443-448.
    [5] Zallen R.The physics of amorphous solids[M].J Wiley:New York,1983.
    [6] Stillinger FH,Weber TA.Packing structures and transitions in liquids and solids[J].Science,1984,225(4666):983-989.
    [7] Murdande SB,Pikal MJ,Shanker RM,et al.Solubility advantage of amorphous pharmaceuticals:I.A thermodynamic analysis[J].J Pharm Sci,2010,99(3):1254-1264.
    [8] Alonzo DE,Zhang GGZ,Zhou D,et al.Understanding the beha-vior of amorphous pharmaceutical systems during dissolution[J].Pharm Res,2010,27(4):608-618.
    [9] Bhugra C, Pikal MJ. Role of thermodynamic, molecular, and kinetic factors in crystallization from the amorphous state[J].J Pharm Sci,2008,97(4):1329-1349.
    [10] Debenedetti PG,Stillinger FH.Supercooled liquids and the glass transition[J].Nature,2001,410(6825):259-267.
    [11] Wang WH,The nature and properties of amorphous matter[J].Prog Phys(物理学进展),2013,33:177-351.
    [12] Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems[J].J Pharm Sci,1997,86(1):1-12.
    [13] Wang XL,Wang P,Yin DD.The progress of research on the formation mechanism and preparation process of amorphous drug delivery system[J].Chin Pharm J(中国药学杂志),2013,13:1538-1544.
    [14] Qi S,Craig D.Recent developments in micro- and nanofabrication techniques for the preparation of amorphous pharmaceutical dosage forms[J].Adv Drug Deliv Rev,2016,100:67-84.
    [15] Yu L.Amorphous pharmaceutical solids:preparation,characterization and stabilization[J].Adv Drug Deliv Rev,2001,48(1):27-42.
    [16] Wanapun D,Kestur US,Taylor LS,et al.Single particle nonlinear optical imaging of trace crystallinity in an organic powder[J].Anal Chem,2011,83(12):4745-4751.
    [17] Swallen SF,Kearns KL,Mapes MK,et al.Organic glasses with exceptional thermodynamic and kinetic stability[J].Science,2007,315(5810):353-356.
    [18] Trasi NS,Baird JA,Kestur US,et al.Factors influencing crystal growth rates from undercooled liquids of pharmaceutical compounds[J].J Phys Chem B,2014,118(33):9974-9982.
    [19] Baird JA,Van EB,Taylor LS.A classification system to assess the crystallization tendency of organic molecules from undercooled melts[J].J Pharm Sci,2010,99(9):3787-3806.
    [20] Nunes C,Mahendrasingam A,Suryanarayanan R.Quantification of crystallinity in substantially amorphous materials by synchrotron X-ray powder diffractometry[J].Pharm Res,2005,22(11):1942-1953.
    [21] Naito K.Quantitative relations between glass transition temperatures and thermodynamic parameters for various materials:molecular design for nonpolymeric organic dye glasses with thermal stability[J].Chem Mater,1994,6(12):2343-2350.
    [22] Ngai KL,Magill JH,Plazek DJ.Flow,diffusion and crystallization of supercooled liquids:revisited[J].J Chem Phys,2000,112(4):1887-1892.
    [23] Swallen SF,Ediger MD.Self-diffusion of the amorphous pharmaceutical indomethacin near Tg[J].Soft Matter,2011,7(21):10339-10344.
    [24] Sun Y,Zhu L,Wu T,et al.Stability of amorphous pharmaceutical solids:crystal growth mechanisms and effect of polymer additives[J].AAPS J,2012,14(3):380-388.
    [25] Greet RJ,Turnbull D.Glass transition in o-terphenyl[J].J Chem Phys,1967,46(4):1243-1251.
    [26] Ishida H,Wu T,Yu L.Sudden rise of crystal growth rate of nifedipine near Tg,without and with polyvinylpyrrolidone[J].J Pharm Sci,2007,96(5):1131-1138.
    [27] Musumeci D,Powell CT,Ediger MD,et al.Termination of solid-state crystal growth in molecular glasses by fluidity[J].J Phys Chem Lett,2014,5(10):1705-1710.
    [28] Wu T,Yu L.Surface crystallization of indomethacin below Tg[J].Pharm Res,2006,23(10):2350-2355.
    [29] Yu L.Surface mobility of molecular glasses and its importance in physical stability[J].Adv Drug Deliv Rev,2016,100:3-9.
    [30] HikimaT,Adachi Y,Hanaya M,et al.Determination of potentially homogeneous-nucleation-based crystallization in,o-terphenyl and an interpretation of the nucleation-enhancement mechanism[J].Phys Rev B Condens Matter,1995,52(6):3900-3908.
    [31] Shi Q,Cai T.Fast crystal growth of amorphous griseofulvin:relations between bulk and surface growth modes[J].Cryst Growth Des,2016,16(6):3279-3286.
    [32] Kestur US,Taylor LS.Evaluation of the crystal growth rate of felodipine polymorphs in the presence and absence of additives as a function of temperature[J].Cryst Growth Des,2013,13(10):4349-4354.
    [33] Shtukenberg A,Freundenthal J,Gunn E,et al.Glass-crystal growth mode for testosterone propionate[J].Cryst Growth Des,2014,11(10):4458-4462.
    [34] Gunn EM,Guzei IA,Yu L.Does crystal density control fast surface crystal growth in glasses? A study with polymorphs[J].Cryst Growth Des,2011,11(9):3979-3984.
    [35] Zhu L,Wong L,Yu L.Surface-enhanced crystallization of amorphous nifedipine[J].Mol Pharmaceutics,2008,5(6):921-926.
    [36] Zhu L,Jona J,Nagapudi K,et al.Fast surface crystallization of amorphous griseofulvin below Tg[J].Pharm Res,2010,27(8):1558-1567.
    [37] Sun Y,Xi H,Chen S,et al.Crystallization near glass transition:transition from diffusion-controlled to diffusionless crystal growth studied with seven polymorphs[J].J Phys Chem B,2008,112(18):5594-5601.
    [38] Powell CT, Paeng K, Chen Z, et al. Fast crystal growth from organic glasses:comparison of o-terphenyl with its structural analogs[J].J Phys Chem B,2014,118(28):8203-8209.
    [39] Powell CT,Xi H,Sun Y,et al.Fast crystal growth in o-terphenyl glasses:apossible role for fracture and surface mobility[J].J Phys Chem B,2015,119(31):10124-10130.
    [40] Konishi T,Tanaka H.Possible origin of enhanced crystal growth in a glass[J].Phys Rev B Condens Matter,2007,76(22):220201.
    [41] Zhu L,Brian CW,Swallen SF,et al.Surface self-diffusion of an organic glass[J].Phys Rev Lett,2011,106(25):256103.
    [42] Zhang W,Brian CW,Yu L.Fast surface diffusion of amorphous o-terphenyl and its competition with viscous flow in surface evolution[J].J Phys Chem B,2015,119(15):5071-5078.
    [43] Wu T, Sun Y, Li N, et al. Inhibiting surface crystallization of amorphous indomethacin by nanocoating[J].Langmuir,2007,23(9):5148-5153.
    [44] Capece M,Davé R.Enhanced physical stability of amorphous drug formulations via dry polymer coating[J].J Pharm Sci,2015,104(6):2076-2084.
    [45] Sun Y,Zhu L,Kearns KL,et al.Glasses crystallize rapidly at free surfaces by growing crystals upward[J].Proc Natl Acad Sci,2011,108(15):5990-5995.
    [46] Hasebe M,Musumeci D,Powell CT,et al.Fast surface crystal growth on molecular glasses and its termination by the onset of fluidity[J].J Phys Chem B,2014,118(27):883-889.
    [47] Musumeci D,Hasebe M,Yu L.Crystallization of organic glasses:how does liquid flow damage surface crystal growth[J]?Cryst Growth Des,2016,16(5):2931-2936.
    [48] Schmelzer J,Gutzow I,Möller J,et al.Surface induced devitrification of glasses:the influence of elastic strains[J].J Non-Cryst Solids,1993,162(1/2):26-39.
    [49] Farrance OE,Jones RAL,Hobbs JK.The observation of rapid surface growth during the crystallization of polyhydroxybutyrate[J].Polymer,2009,50(15):3730-3738.
    [50] Hasebe M, Musumeci D, Yu L. Fast surface crystallization of molecular glasses:creation of depletion zones by surface diffusion and crystallization flux[J].J Phys Chem B,2015,119(7):3304-3311.
    [51] Wyttenbach N,Kuentz M.Glass-forming ability of compounds in marketed amorphous drug products[J].Eur J Pharm Biopharm,2017,112:204-208.
    [52] Huang Y,Dai WG.Fundamental aspects of solid dispersion technology for poorly soluble drugs[J].Acta Pharm Sin B(药学学报),2014,4:18-25.
    [53] Cai T,Zhu L,Yu L.Crystallization of organic glasses:effects of polymer additives on bulk and surface crystal growth in amorphous nifedipine[J].Pharm Res,2011,28(10):2458-2466.
    [54] Kestur US,Taylor LS.Role of polymer chemistry in influencing crystal growth rates from amorphous felodipine[J].Crystengcomm,2010,12(8):2390-2397.
    [55] Trasi NS,Taylor LS.Effect of additives on crystal growth and nucleation of amorphous flutamide[J].Cryst Growth Des,2012,12(6):3221-3230.
    [56] Kothari K,Ragoonanan V,Suryanarayanan R.The role of drug-polymer hydrogen bonding interactions on the molecular mobility and physical stability of nifedipine solid dispersions[J].Mol Pharmaceutics,2014,12(1):162-170.
    [57] Powell C T,Cai T,Hasebe M,et al.Low-concentration polymers inhibit and accelerate crystal growth in organic glasses in correlation with segmental mobility[J].J Phys Chem B,2013,117(35):10334-10341.
    [58] Huang C,Powell C T,Sun Y,et al.Effect of low-concentration polymers on crystal growth in molecular glasses:a controlling role for polymer segmental mobility relative to host dynamics[J].J Phys Chem B,2017,121(8):1963-1971.
    [59] Shi Q, Zhang C, Su Y, et al. Acceleration of crystal growth of amorphous griseofulvin by low-concentration poly(ethylene oxide):aspects of crystallization kinetics and molecular mobility[J].Mol Pharmaceutics,2017,14(7):2262-2272.
    [60] Mao C,Chamarthy SP,Pinal R.Time-dependence of molecular mobility during structural relaxation and its impact on organic amorphous solids:an investigation based on a calorimetric approach[J].Pharm Res,2006,23(8):1906-1917.
    [61] Bhardwaj S P,Suryanarayanan R.Molecular mobility as a predictor of the water sorption by annealed amorphous trehalose[J].Pharm Res,2013,30(3):714-720.
    [62] Tian B,Zhang L,Pan Z,et al.A comparison of the effect of temperature and moisture on the solid dispersions:aging and crystallization[J].Int J Pharm,2014,475(1/2):385-392.
    [63] Vyazovkin S, DrancaI. Effect of physical aging on nucleation of amorphous indomethacin[J].J Phys Chem B,2007,111(25):7283-7287.
    [64] Bhattacharya S, Bhardwaj SP, Suryanarayanan R. Molecular motions in sucrose-PVP and sucrose-sorbitol dispersions-II.Implications of annealing on secondary relaxations[J].Pharm Res,2014,31(10):2822-2828.
    [65] Brian CW,Zhu L,Yu L.Effect of bulk aging on surface diffusion of glasses[J].J Chem Phys,2014,140(5):054509.
    [66] Mistry P, Suryanarayanan R. Strength of drug-polymer interactions:implications on crystallization in dispersions[J].Cryst Growth Des,2016,16(9):5141-5149.
    [67] Mehta M,Suryanarayanan R.Acceleratedphysical stabilitytestingofamorphous dispersion[J].Mol Pharmaceutics,2016,13(8):2661-2666.
    [68] Fung MH,Suryanarayanan R.Use of a plasticizer for physical stability prediction of amorphous solid dispersions[J].Crystal Growth Design,2017,17(8):4315-4325.
    [69] Descamps M,Willart JF,Perspectives on the amorphisation/milling relationship in pharmaceutical materials[J].Adv Drug Deliv Rev,2016,100:51-66.
  • 期刊类型引用(2)

    1. 王永健,郭明. 新型BCR-ABL抑制剂的设计合成与构效关系. 中国药科大学学报. 2024(03): 357-366 . 本站查看
    2. 关淑文,高博韬,肖将尉. 基于细胞薄膜技术构建可长期维持细胞色素P450活性的体外人类三维肝脏模型. 生物医学工程学杂志. 2022(04): 776-783 . 百度学术

    其他类型引用(0)

计量
  • 文章访问数:  1045
  • HTML全文浏览量:  7
  • PDF下载量:  4002
  • 被引次数: 2
出版历程
  • 刊出日期:  2017-12-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭