Physicochemical Drug Interactions and Incompatibilities

  • A. T. Florence
  • D. Attwood


This chapter deals with some practical consequences of the physical chemistry of drugs- particularly their interactions with each other, with solvents and with excipients in formulations. Sometimes the interaction is beneficial and sometimes not. In reading this chapter you should appreciate that there are several causes of interactions and incompatibilities such as: pH effects, change of solvent characteristics on dilution, cation-anion interactions, salting-out and salting-in, chelation, ion-exchange interactions, adsorption to excipients and containers, interactions with plastics, protein binding. Equations can be written to describe most of these, but these formulae can be applied in vivo only as a first-line calculation because of the complexity of the body. Nevertheless the equations are important to allow some prediction of the magnitude of effects.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    C. L. J. Coles and K. A. Lees. Pharm. J. 206, 153 (1971)Google Scholar
  2. 2.
    B. Lynn. Pharm. J. 206, 154 (1971)Google Scholar
  3. 3.
    K. A. Fitzgerald and M. W. MacKay. Am. J. Hosp. Pharm. 43, 88 (1986)PubMedGoogle Scholar
  4. 4.
    A. J. Fairfax, J. Adam and F. S. Pagan. Br. Med. J. 1, 820 (1978)CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    G. Levy and B. A. Hayes. New Engl. J. Med. 262, 1053 (1960)CrossRefPubMedGoogle Scholar
  6. 6.
    J. H. Lipton, New Engl. J. Med. 268, 92 (1963)CrossRefGoogle Scholar
  7. 7.
    W. Jusko, M. Gretch and R. Gassett. J. Am. Med. Ass. 225, 176 (1973)CrossRefGoogle Scholar
  8. 8.
    D. E. Langdon et al. J. Am. Med. Ass. 223, 184 (1973)CrossRefGoogle Scholar
  9. 9.
    J. B. Crapper. Br. Med. J. 1, 33 (1975)CrossRefGoogle Scholar
  10. 10.
    E. Tomlinson. Pharm. Int. 1, 156 (1980)Google Scholar
  11. 11.
    G. M. Irwin, H. B. Kostenbauder et al. J. Pharm. Sci. 58, 313 (1969)CrossRefPubMedGoogle Scholar
  12. 12.
    T. R. Marshall, J. T. Ling, G. Follis and M. Russell. Radiology 84, 536 (1965)CrossRefPubMedGoogle Scholar
  13. 13.
    M.A. El-Nakeeb. Acta Pharm. Suec. 5, I (1968)Google Scholar
  14. 14.
    A. C. Barbara, C. Clemente and E. Wagman. New Engl. J. Med. 274, 1316 (1966)CrossRefPubMedGoogle Scholar
  15. 15.
    C. F. Bell. Metal Chelation, Clarendon Press, 1977Google Scholar
  16. 16.
    P. R. Clink and J. L. Colaizzi. J. Pharm. Sci. 62, 97 (1973)CrossRefGoogle Scholar
  17. 17.
    J. T. Doluisio and A. N. Martin. J. Med. Chern. 6, 16 (1963)CrossRefGoogle Scholar
  18. 18.
    A. E. Martell and M. Calvin. Chemistry of the Metal Chelate Compounds, Prentice-Hall, New York, 1952, p. 54Google Scholar
  19. 19.
    J. J. Ambre and L. T. Fischer. Clin. Pharmacol. Ther. 14, 231 (1973)CrossRefPubMedGoogle Scholar
  20. 20.
    M. A. Zoglio. J. Pharm. Sci. 58, 222 (1969)CrossRefPubMedGoogle Scholar
  21. 21.
    K. J. Ikeda. Chern. Pharm. Bull. 23, 201 (1975)CrossRefGoogle Scholar
  22. 22.
    K. J. Ikeda. J. Pharm. Sci. 63, 1168 (1974)CrossRefPubMedGoogle Scholar
  23. 23.
    D. E. Tutt and M. A. Schwartz. J. Am. Chern. Soc. 93, 767 (1971)CrossRefGoogle Scholar
  24. 24.
    L. Gross and M. Brotman. Ann. Intern. Med. 72, 95 (1970)CrossRefPubMedGoogle Scholar
  25. 25.
    A. Coronato and G. R. J. Glass. Proc. Exp. Bioi. Med. 142, 1341 (1973)CrossRefGoogle Scholar
  26. 26.
    G. Boman, P. Lundgren and G. Stjemstrom. Eur. J. Clin. Pharmacol. 8, 293 (1975)CrossRefPubMedGoogle Scholar
  27. 27.
    S. T. Anik and J.-Y. Hwang. Int. J. Pharm. 16, 181 (1983)CrossRefGoogle Scholar
  28. 28.
    A. W. Malik, A. H. Amman, D. M. Baske and R. G. Stohl. J. Pharm. Sci. 70, 798 (1981)CrossRefGoogle Scholar
  29. 29.
    L. Illum and H. Bundgaard. Int. J. Pharm. 10, 339 (1982)CrossRefGoogle Scholar
  30. 30.
    E. J. Lien, J. Kuwahara and R. T. Koda. Drug Intell. Clin. Pharm. 8, 470 (1974)Google Scholar
  31. 31.
    L. R. Peterson and D. N. Gerding. Lancet ii, 376 (1978)Google Scholar

Copyright information

© A. T. Florence and D. Attwood 1998

Authors and Affiliations

  • A. T. Florence
    • 1
  • D. Attwood
    • 2
  1. 1.The School of PharmacyUniversity of LondonUK
  2. 2.School of Pharmacy and Pharmaceutical SciencesUniversity of ManchesterUK

Personalised recommendations