Solid Forms of Pharmaceutical Molecules

  • Bohumil KratochvílEmail author
Part of the Hot Topics in Thermal Analysis and Calorimetry book series (HTTC, volume 8)


A drug discovery is characterized by two stages. The first in terms of time is called “lead structure”, followed by a so called “drug candidate” stage. The lead structure stage involves selecting the optimum molecule of the pharmaceutical, while drug candidate stage means selecting the optimum solid form. Usually, five to ten candidates pass to the drug candidate stage and the result is the selection of the final solid API (Active Pharmaceutical Ingredience) for the ensuing formulation of the solid dosage form. The lead structure stage concerns only the discovery of the original drug, the drug candidate stage may concern also generics (a drug which is bioequivalent with original and is produced and distributed after the patent protection of the original).


Ergot Alkaloid Mandelic Acid Pharmaceutical Substance Stable Polymorph Patent Litigation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This chapter was written in the framework of the project MSM 2B08021 of the Ministry of Education of the Czech Republic.


  1. 1.
    Hájková M, Kratochvíl B, Rádl S (2008) Atorvastatin – the world’s best selling drug. Chem Listy 102:3–14Google Scholar
  2. 2.
    Childs SL, Hardcastle KI (2007) Cocrystals of piroxicam with carboxylic acid. Cryst Growth Des 7:1291–1304CrossRefGoogle Scholar
  3. 3.
    Bingham AL, Hughes DS, Hursthouse MB, Lancaster RW, Tavener S, Threlfall TL (2001) Over one hundred solvates of sulfathiazole. Chem Commun 7:603–604CrossRefGoogle Scholar
  4. 4.
  5. 5.
  6. 6.
    Bernstein J (2002) Polymorphism in molecular crystals. Oxford University Press, New York, p 298Google Scholar
  7. 7.
    Bauer J, Sponton S, Henry R, Quick J, Dziki W, Porter W, Morfia J (2001) Ritonavir: an extraordinary example of conformational polymorphism. Pharm Res 18:859–866CrossRefGoogle Scholar
  8. 8.
    Pudipeddi M, Serajuddin ATM (2005) Trends in solubility of polymorphs. J Pharm Sci 94:929–939CrossRefGoogle Scholar
  9. 9.
    Bond AD, Boese R, Desiraju GR (2007) On the polymorphism of aspirin. Angew Chem Int Ed 46:615–617CrossRefGoogle Scholar
  10. 10.
    Steiner T, Kellner G (1994) Crystalline beta-cyclodextrin hydrate at various humidites - fast, continuous, and reversible dehydration studies by X-ray diffraction. J Am Chem Soc 116:5122–5128CrossRefGoogle Scholar
  11. 11.
    Etter MC, Urbanczyk-Lipkowska Z, Zia-Ebrahimi M, Panunto TW (1990) Hydrogen bond directed cocrystallization and molecular recognition properties of diarylureas. J Am Chem Soc 112:8415–8426CrossRefGoogle Scholar
  12. 12.
    Hušák M, Kratochvíl B, Císařová I, Cvak L, Jegorov A, Böhm S (2002) Crystal forms of semisynthetic ergot alkaloid terguride. Collect Czech Chem Commun 67:479–489CrossRefGoogle Scholar
  13. 13.
    Stahl PH, Wermuth CG (eds) (2002) Handbook of pharmaceutical salts: properties, selection, and use. Wiley-VCH, WeinheimGoogle Scholar
  14. 14.
  15. 15.
    Vishweshwar P, McMahon JA, Bis JA, Zaworotko MJ (2006) Pharmaceutical co-crystals. J Pharm Sci 95:499–516CrossRefGoogle Scholar
  16. 16.
    Childs SL, Stahly PG, Park A (2007) The salt-cocrystal continuum: the influence of crystal structure on ionization state. Mol Pharm 4:323–338CrossRefGoogle Scholar
  17. 17.
    Schultheiss N, Newman A (2009) Pharmaceutical cocrystals and their physicochemical properties. Cryst Growth Des 9:2950–2967CrossRefGoogle Scholar
  18. 18.
    Morissete SL, Almarsson Ő, Peterson ML, Remenar J, Read M, Lemmo A, Ellis S, Cima MJ, Gardner CR (2004) High-throughput crystallization: polymorphs, salts, co-crystals and solvates of pharmaceutical solids. Adv Drug Deliv Rev 56:275–300CrossRefGoogle Scholar
  19. 19.
    Hickey MB, Peterson ML, Scoppettuolo LA, Morisette SL, Vetter A, Guzman H, Remenar JF, Zhang Z, Tawa MD, Haley S, Zaworotko MJ, Almarsson O (2007) Performance comparison of a co-crystal of carbamazepine with marketed product. Eur J Pharm Biopharm 67:112–119CrossRefGoogle Scholar
  20. 20.
    Zaworotko MJ (2008) Crystal engineering of cocrystals and their relevance to pharmaceuticals and solid-state chemistry. In: XXI congress of the international union of crystallography, Book of Abstracts C11. OsakaGoogle Scholar
  21. 21.
    Jones W (2009) Multicomponent crystals in the development of new solid forms of pharmaceuticals. In: 25. European Crystallographic Meeting (ECM 25), Abstracts p. 102. IstanbulGoogle Scholar
  22. 22.
    Hilfiker R (ed) (2006) Polymorphism in the pharmaceutical industry. Wiley-VCH Verlag, WeinheimGoogle Scholar
  23. 23.
    Křen V et al (1997) Glycosylation of silybin. J Chem Soc, Perkin Trans 17:2467–2974Google Scholar
  24. 24.
    Nagarajan R (1993) Structure-activity relationship of vancomycin-type glycopeptide antibiotics. J Antibiot 46:1181–1195CrossRefGoogle Scholar
  25. 25.
    Hancoek BC, Zografi G (1997) Characteristics and significance of amorphous state in pharmaceutical systems. J Pharm Sci 86:1–12CrossRefGoogle Scholar
  26. 26.
    Teva Pharmaceutical Industries Ltd Patent WO 01/36384 A1Google Scholar
  27. 27.
    Accolate (2008)
  28. 28.
    Accupro (Accupril) (2008)
  29. 29.
  30. 30.
  31. 31.
  32. 32.
  33. 33.
    Parthasaradhi et al Novel polymorphs of imatinib mesylate. Patent US2005/0234069A1Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Prague Institute of Chemical TechnologyPraha 6Czech Republic

Personalised recommendations