Journal of Thermal Analysis and Calorimetry

, Volume 73, Issue 2, pp 397–408 | Cite as

Crystal polymorphism of local anaesthetic drugs

  • A. C. Schmidt
  • N. Senfter
  • U. J. Griesser


Crystal polymorphs of pramocaine hydrochloride (PRCNC) and pramocaine (PRCN) free base were produced and characterized by means of thermomicroscopy, differential scanning calorimetry (DSC), FTIR- and FT-Raman-spectroscopy as well as X-ray-powder diffractometry. The relative thermodynamic stabilities of all forms were determined and are represented in semi-schematic energy/temperature diagrams. PRCN, which is a viscous liquid at room temperature and insoluble in water, was found to exist in two different crystal forms with the melting points 23.5°C (mod. I°) and 12.5°C (mod. II). The water-soluble PRCNC crystallizes in three different crystal modifications. Mod. II° is the thermodynamically stable form at room temperature and is present in commercial products. This form is obtained by crystallization from solvents and transforms on heating at about 95°C into the high temperature form mod. I which melts at 171.0°C. Both compounds show conformational polymorphism with forms of low kinetic stability.

crystal forms local anaesthetics pramocaine hydrochloride thermal analysis conformational polymorphism pramocaine pramoxine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Martindale, The complete Drug reference 32nd Ed., The Pharmaceutical Press, London 1999, p. 1281.Google Scholar
  2. 2.
    M. Kuhnert-Brandstätter and H. Grimm, Mikrochim. Acta, (1957) 427.Google Scholar
  3. 3.
    A. Wickstrøm, J. Pharm. Pharmacol., 5 (1953) 158.Google Scholar
  4. 4.
    H. Grimm, PhD Thesis, Innsbruck 1954.Google Scholar
  5. 5.
    D. Giron, M. Draghi, C. Goldbronn, S. Pfeffer and P. Piechon, J. Thermal Anal., 49 (1997) 913.CrossRefGoogle Scholar
  6. 6.
    M. Gruno, H. Wulff and P. Pflegel, Pharmazie, 48 (1993) 834.Google Scholar
  7. 7.
    L. Borka and J. Haleblian, Acta Pharm. Jugosl., 40 (1990) 71.Google Scholar
  8. 8.
    H. Kreider and A. Menotti, J. Am. Chem. Soc., 64 (1942) 1227.CrossRefGoogle Scholar
  9. 9.
    Abbott, U.S. pat 2, 870 (1959) 151.Google Scholar
  10. 10.
    A. C. Schmidt, N. Senfter and U. J. Griesser, PhandTA 6 (6th Symposium and Workshops on Pharmacy and Thermal Analysis), Eurostar meeting, Ascona, Switzerland, May 26-29, 2002. Abstract: PhandTA 6 Workbook (2002), PO 20.Google Scholar
  11. 11.
    A. Burger and U. J. Griesser, Sci. Pharm., 60 (1992) 3.Google Scholar
  12. 12.
    U. J. Griesser and A. Burger, Int. J. Pharm., 120 (1995) 83.CrossRefGoogle Scholar
  13. 13.
    A. Burger and R. Ramberger, Mikrochim. Acta II, (1979) 259.Google Scholar
  14. 14.
    L. Yu, J. Pharm. Sci., 84 (1995) 968.Google Scholar

Copyright information

© Kluwer Academic Publishers/Akadémiai Kiadó 2003

Authors and Affiliations

  • A. C. Schmidt
    • 1
  • N. Senfter
    • 1
  • U. J. Griesser
    • 1
  1. 1.Institute of Pharmacy, Department of Pharmaceutical TechnologyUniversity of InnsbruckInnsbruckAustria

Personalised recommendations