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Effect of particle size on the bioavailability of digoxin


The bioavailability of digoxin in three tablets prepared from materials with different particle sizes was measured in healthy volunteers in a cross-over study using an alcoholic solution of digoxin as a reference standard. Its bioavailability in tablets with particle sizes of 7 µ or 13 µ was 78–97% of that of digoxin in solution. The tablet with largest particle size (102 µ) showed markedly lower bioavailability than the reference solution, namely 39%. It is obvious that particle size is an important determinant of the dissolution rate and bioavailability of digoxin.

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  1. 1.

    Binnion, P.F., McDermott, M.: Bioavailability of digoxin. Lancet1972 II 592

  2. 2.

    Johnson, B.F., Fowle, A.S.E., Lader, S., Fox, J., Munro-Faure, A.D.: Biological availability of digoxin from Lanoxin produced in the United Kingdom. Brit. med. J.1973 IV 323–326

  3. 3.

    Lindenbaum, J., Mellow, M.H., Blackstone, M.O., Butler, V.P.Jr.: Variation in biologic availability of digoxin from four preparations. New Engl. J. Med.285 1344–1348 (1971)

  4. 4.

    Manninen, V., Melin, J., Härtel, G.: Serumdigoxin concentrations during treatment with different preparations. Lancet1971 II 934–935

  5. 5.

    Shaw, T.R.D., Howard, M.R., Hamer, J.: Variation in the biological availability of digoxin. Lancet1972 II 303–307

  6. 6.

    Shaw, T.R.D., Raymond, K., Howard, M.R., Hamer, J.: Therapeutic non-equivalence of digoxin tablets in the United Kingdom: Correlation with tablet dissolution rate. Brit. med. J.1973 IV 763–766

  7. 7.

    Fraser, E.J., Leach, R.H., Poston, J.W., Bold, A.M., Culank, L.S., Lipede, A.B.: Dissolution and bioavailability of digoxin tablets. J. Pharm. Pharmacol.25 968–973 (1973)

  8. 8.

    Johnson, B.F., Greer, H., McCrerie, J., Bye, C., Fowle, A.: Rate of dissolution of digoxin tablets as a predictor of absorption. Lancet1973 I 1473–1475

  9. 9.

    Lindenbaum, J., Butler, V.P., Murphy, J.E., Cresswell, R.M.: Correlation of digoxin-tablet dissolution-rate with biological availability. Lancet1973 I 1215–1217

  10. 10.

    Notari, R.E.: Biopharmaceutics and Pharmacokinetics. New York: Marcel Dekker 1971

  11. 11.

    Jounela, A.J., Sothmann, A.: Bioavailability of digoxin. Lancet1973 I 201–202

  12. 12.

    Shaw, T.R.D., Carless, J.E., Howard, M.R., Raymond, K.: Particle size and absorption of digoxin. Lancet1973 II 209–210

  13. 13.

    Florence, A.T., Salole, E.G., Stenlake, J.P.: The effect of particle size reduction on digoxin crystal properties. J. Pharm. Pharmacol.26 479–480 (1974)

  14. 14.

    Lachman, L., Lieberman, H.A., Kanic, J.L. (eds.): The theory and practice of industrial pharmacy, p. 112. Philadelphia: Lea & Febiger 1970

  15. 15.

    Smith, T.W., Butler, V.P., Haber, E.: Determination of therapeutic and toxic serum digoxin concentrations by radio-immunoassay. New Engl. J. Med.281 1212–1216 (1969)

  16. 16.

    Duncan, D.B.: Multiple range and multiple F tests. Biometrics11 1–42 (1955)

  17. 17.

    Sorby, D.L., Tozer, T.N.: On the evaluation of biologic availability of digoxin from tablets. Drug Intell. clin. Pharm.7 78–83 (1973)

  18. 18.

    Brock, A., Christensen, E.: Dag til dag variationen af digoxinkoncentrationen i serum hos digitaliserade indlagte patienter. Ugeskr. Laeg.136 37–39 (1973)

  19. 19.

    Greenblatt, D.J., Duhme, D.W., Koch-Weser, J., Smith, T.W.: Evaluation of digoxin bioavailability in single-dose studies. New Engl. J. Med.289 651–654 (1973)

  20. 20.

    Sanchez, N., Sheiner, L.B., Halkin, H., Melmon, K.L.: Pharmacokinetics of digoxin: Interpreting bioavailability. Brit. med. J.1973 IV 132–134

  21. 21.

    Huffman, D.H., Azarnoff, D.L.: Absorption of orally given digoxin preparations. J. Amer. med. Ass.222 957–960 (1972)

  22. 22.

    Steiness, E., Christensen, V., Johansen, H.: Bioavailability of digoxin tablets. Clin. Phar Ther.14 949–954 (1973)

  23. 23a

    U.S. Pharmacopoeia. New York, U.S.: Pharmacopoeia Convention Inc. 1970

  24. 23b

    British Pharmacopoeia. London: Pharmaceutical Press 1968

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Jounela, A.J., Pentikäinen, P.J. & Sothmann, A. Effect of particle size on the bioavailability of digoxin. Eur J Clin Pharmacol 8, 365–370 (1975).

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Key words

  • Particle size
  • bioavailability
  • digoxin