Pharmaceutical Research

, Volume 24, Issue 1, pp 73–80 | Cite as

A Modern View of Excipient Effects on Bioequivalence: Case Study of Sorbitol

  • M.-L. Chen
  • A. B. Straughn
  • N. Sadrieh
  • M. Meyer
  • P. J. Faustino
  • A. B. Ciavarella
  • B. Meibohm
  • C. R. Yates
  • A. S. Hussain
Research Paper



To examine the effect of common excipients such as sugars (sorbitol versus sucrose) on bioequivalence between pharmaceutical formulations, using ranitidine and metoprolol as model drugs.


Two single-dose, replicated, crossover studies were first conducted in healthy volunteers (N = 20 each) to compare the effect of 5 Gm of sorbitol and sucrose on bioequivalence of 150 mg ranitidine or 50 mg metoprolol in aqueous solution, followed by a single-dose, nonreplicated, crossover study (N = 24) to determine the threshold of sorbitol effect on bioequivalence of 150 mg ranitidine in solution.


Ranitidine Cmax and AUC(0–∞) were decreased by ∼50% and 45%, respectively, in the presence of sorbitol versus sucrose. Similarly, sorbitol reduced metoprolol Cmax by 23% but had no significant effect on AUC(0–∞). An appreciable subject-by-formulation interaction was found for ranitidine Cmax and AUC(0–∞), as well as metoprolol Cmax. Sorbitol decreased the systemic exposure of ranitidine in a dose-dependent manner and affected bioequivalence at a level of 1.25 Gm or greater.


As exemplified by sorbitol, some common excipients have unexpected effect on bioavailability/bioequivalence, depending on the pharmacokinetic characteristics of the drug, as well as the type and amount of the excipient present in the formulation. More research is warranted to examine other ‘common’ excipients that may have unintended influence on bioavailability/bioequivalence.

Key words

bioavailability bioequivalence excipient permeability sorbitol 



This work was supported, in part, by a contract from the Food and Drug Administration to the University of Tennessee, Memphis, Tennessee. The authors would like to thank Lawrence Lesko, Rabindra Patnaik and Lawrence Yu for their helpful discussion on the related topics during the early phase of this investigation.


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • M.-L. Chen
    • 1
  • A. B. Straughn
    • 2
  • N. Sadrieh
    • 3
  • M. Meyer
    • 4
  • P. J. Faustino
    • 3
  • A. B. Ciavarella
    • 3
  • B. Meibohm
    • 2
  • C. R. Yates
    • 2
  • A. S. Hussain
    • 3
    • 5
  1. 1.Office of Pharmaceutical Science, Center for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA
  2. 2.Health Science CenterUniversity of TennesseeMemphisUSA
  3. 3.Food and Drug AdministrationSilver SpringUSA
  4. 4.Boca RatonUSA
  5. 5.Sandoz, Inc.PrincetonUSA

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