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Engineering Crystallography: From Molecule to Crystal to Functional Form pp 247–260Cite as

Preparation, Stabilisation and Advantages of Metastable Polymorphs

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Abstract

This chapter examines the challenges faced by the pharmaceutical industry in developing metastable polymorphs of an API, and discusses some key advantages with examples. The new perspective of polymorph-directing crystallization using functionalised templates is also discussed. The basic principles and examples of heterogeneous template crystallisation are given.

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References

  1. Storey RA, Ymen I (eds) (2011) Solid state characterisation of pharmaceuticals. Wiley-Blackwell, London

    Google Scholar 

  2. Leppanen J, Wegelius E, Nevalainen T et al (2001) Structural studies of acyl esters of entacapone. J Mol Struct 562:129–135

    Article  CAS  Google Scholar 

  3. Kwokal A, Nguyen TH, Roberts KJ (2009) Polymorph-directing seeding of entacapone crystallization in aqueous/acetone solution using a self-assembled molecular layer on Au (100). Cryst Grow Des 4:4324–4334

    Article  Google Scholar 

  4. Kwokal A, Roberts KJ (2014) Direction of the polymorphic form of entacapone using an electrochemical tuneable surface template. CrystEngComm 16:3487–3493

    Article  CAS  Google Scholar 

  5. Kwokal A, Čavužić D, Roberts KJ (2013) Surface adsorbed templates for directing the crystal growth of entacapone as monitored using process analytical techniques. Cryst Grow Des 13:5324–5334

    Article  CAS  Google Scholar 

  6. Singhal D, Curatolo W (2004) Drug polymorphism and dosage form design: a practical perspective. Adv Drug Deliv Rev 56:335–347

    Article  CAS  Google Scholar 

  7. Chen X, Morris KR, Griesser UJ et al (2002) Reactivity differences of indomethacin solid forms with ammonia gas. J Am Chem Soc 124:15012–15019

    Article  CAS  Google Scholar 

  8. Guillory JK, Poust RI (2002) Chemical kinetics and drug stability. In: Banker GS, Rhodes CT (eds) Modern pharmaceutics, drugs and the pharmaceutical sciences. Marcel Dekker, New York, pp 111–138

    Google Scholar 

  9. Summers MP, Enever RP, Carless JE (1976) The influence of crystal form on the radial stress transmission characteristics of pharmaceutical materials. J Pharm Pharmacol 28:89–99

    Article  CAS  Google Scholar 

  10. Di Martino P, Guyot-Hermann AM, Conflan P et al (1996) A new pure paracetamol for direct compression: The orthorhombic form. Int J Pharm 128:1–8

    Article  CAS  Google Scholar 

  11. Joiris E, Di Martino P, Berneron C et al (1998) Compression behavior of orthorhombic paracetamol. Pharm Res 15:1122–1130

    Article  CAS  Google Scholar 

  12. Liang K, White G, Wilkinson D et al (2004) An examination into the effect of stirrer material and agitation rate on the nucleation of l-glutamic acid batch crystallized from supersaturated aqueous solutions. Cryst Growth Des 2:1039–1044

    Article  Google Scholar 

  13. Liang K, White G, Wilkinson D et al (2004) Examination of the process scale dependence of l-glutamic acid batch crystallized from supersaturated aqueous solutions in relation to reactor hydrodynamics. Ind Eng Chem Res 43:1227–1234

    Article  CAS  Google Scholar 

  14. Jones F, Jones P, De Marco R et al (2008) Understanding barium sulfate precipitation onto stainless steel. Appl Surf Sci 254:3459–3468

    Article  CAS  Google Scholar 

  15. Borissova A, Khan S, Mahmud T et al (2009) In situ measurement of solution concentration during the batch cooling crystallization of l-glutamic acid using ATR-FTIR spectroscopy coupled with chemometrics. Cryst Growth Des 9:692–706

    Article  CAS  Google Scholar 

  16. Chadwick K, Chen J, Myerson AS et al (2012) Toward the rational design of crystalline surfaces for heteroepitaxy: role of molecular functionality. Cryst Growth Des 12:1159–1166

    Article  CAS  Google Scholar 

  17. Hiremath R, Basile JA, Varney SW et al (2005) Controlling molecular crystal polymorphism with self-assembled monolayer templates. J Am Chem Soc 127:18321–18327

    Article  CAS  Google Scholar 

  18. Singh A, Lee IS, Myerson AS (2009) Concomitant crystallization of ROY on patterned substrates: Using a high throughput method to improve the chances of crystallization of different polymorphs. Cryst Growth Des 9:1182–1185

    Article  CAS  Google Scholar 

  19. Ward MD (2001) Bulk crystals to surfaces: combining X-ray diffraction and atomic force microscopy to probe the structure and formation of crystal interfaces. Chem Rev 101:1697–1725

    Article  CAS  Google Scholar 

  20. Hamilton BD, Weissbuch I, Lahav M et al (2009) Manipulating crystal orientation in nanoscale cylindrical pores by stereochemical inhibition. J Am Chem Soc 131:2588–2596

    Article  CAS  Google Scholar 

  21. Diao Y, Harada T, Myerson AS et al (2011) The role of nanopore shape in surface-induced crystallization. Nat Mater 10:867–871

    Article  CAS  Google Scholar 

  22. Nicholson CE, Chen C, Mendis B et al (2011) Stable polymorphs crystallized directly under thermodynamic control in three-dimensional nanoconfinement: a generic methodology. Cryst Growth Des 11:363–366

    Article  CAS  Google Scholar 

  23. Parambil JV, Poornachary SK, Tan RBH et al (2014) Template-induced polymorphic selectivity: the effects of surface chemistry and solute concentration on carbamazepine crystallisation. Cryst Eng Comm 16:4927–4930

    Article  CAS  Google Scholar 

  24. Ward MD (2005) Snapshots of crystal growth. Science 308:1566–1567

    Article  CAS  Google Scholar 

  25. Mitchell CA, Yu L, Ward MD (2001) Selective nucleation and discovery of organic polymorphs through epitaxy with organic single crystal substrates. J Am Chem Soc 123:10830–10839

    Article  CAS  Google Scholar 

  26. Dressler DH, Mastai Y (2007) Controlling polymorphism by crystallization on self-assembled multilayers. Cryst Growth Des 7:847–850

    Article  CAS  Google Scholar 

  27. Cox JR, Dabros M, Shaffe JA et al (2007) Selective crystal growth of the anhydrous and monohydrate forms of theophylline on self-assembled monolayers. Angew Chem Int Edit 46:1988–1991

    Article  CAS  Google Scholar 

  28. Frenette M, Cosa C, Friščić T (2013) Characterisation of organic solid forms and real-time in situ monitoring of their transformations using solid-state fluorescence. Cryst Eng Comm 15:5100–5106

    Article  CAS  Google Scholar 

  29. Jiang S, Jansens PJ, ter Horst JH (2010) Mechanism and kinetics of the polymorphic transformation of o-aminobenzoic acid. Cryst Growth Des 10:2123–2128

    Article  CAS  Google Scholar 

  30. Mukuta T, Lee AY, Kawakami T et al (2005) Influence of impurities on the solution-mediated phase transformation of an active pharmaceutical ingredient. Cryst Growth Des 5:1429–1436

    Article  CAS  Google Scholar 

  31. Khawam A, Flanagan DR (2006) Solid-state kinetic models: basics and mathematical fundamentals. J Phys Chem B 110:17315–17328

    Article  CAS  Google Scholar 

  32. Urakam K, Beezer AE (2003) A kinetic and thermodynamic study of seratrodast polymorphic transition by isothermal microcalorimetry. Int J Pharm 257:265–271

    Article  Google Scholar 

  33. Laird T (2004) Polymorphism and impurities. Org Process Res Dev 8:301–302

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. GlaxoSmithKline, R&D, New Frontiers Science Park, Third Avenue, Harlow, UK

    Ana Kwokal

Authors
  1. Ana Kwokal
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Correspondence to Ana Kwokal .

Editor information

Editors and Affiliations

  1. School of Chemical & Process Engineering, University of Leeds, Leeds, United Kingdom

    Kevin J. Roberts

  2. Pfizer Global R&D, Pharmaceutical Sciences, Pfizer Global R&D, Sandwich, Kent, United Kingdom

    Robert Docherty

  3. Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto, Japan

    Rui Tamura

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Kwokal, A. (2017). Preparation, Stabilisation and Advantages of Metastable Polymorphs. In: Roberts, K., Docherty, R., Tamura, R. (eds) Engineering Crystallography: From Molecule to Crystal to Functional Form. NATO Science for Peace and Security Series A: Chemistry and Biology. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1117-1_14

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