Drug Excipient Interactions

  • Ajit S. NarangEmail author
  • Aaron Yamniuk
  • Limin Zhang
  • S. Nilgun Comezoglu
  • Dilbir S. Bindra
  • Sailesh A. Varia
  • Michael Doyle
  • Sherif Badawy


Unintended physicochemical interaction of an excipient with a drug substance in a dosage form can result in the complexation or binding of the drug, resulting in slow and/or incomplete drug release in a dissolution medium. It is important to assess the risk whether such interactions would reduce oral bioavailability of a drug from its dosage form. This chapter describes the development of a methodology to assess the biorelevance of the drug release impact of drug-excipient binding interactions using a model compound, brivanib alaninate. This methodology was developed using a combination of modeling and simulation tools as well as experimental data generated in vitro and in vivo. In addition, general application of this principle and methodology to other drug substances and binding affinities of drugs with excipients as a function of dose is described.


Adsorption Bioavailability Binding Brivanib alaninate Croscarmellose sodium Excipient Isothermal titration calorimetry Langmuir adsorption isotherm Wet granulation 



Area under the plasma concentration-time curve from dosing till time of last sampling (72 h)


Brivanib alaninate


Croscarmellose sodium


Maximum concentration reached in plasma


High performance liquid chromatography


Hydroxypropyl methyl cellulose


Isothermal titration calorimetry


Nuclear magnetic resonance


Sodium starch glycollate


Plasma half life


The time of maximum plasma concentration


United States National Formulary


Volume of distribution





We thank our biostatistics colleague, James Bergum, for help with statistical analyses of data. The majority of this chapter and illustrations are reprinted from Journal of Pharmacy and Pharmacology, Vol 64 (© 2012) pp 553–565, with permission from John Wiley and Sons.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Ajit S. Narang
    • 1
    Email author
  • Aaron Yamniuk
    • 3
  • Limin Zhang
    • 2
  • S. Nilgun Comezoglu
    • 4
  • Dilbir S. Bindra
    • 1
  • Sailesh A. Varia
    • 1
  • Michael Doyle
    • 3
  • Sherif Badawy
    • 1
  1. 1.Drug Product Science and TechnologyBristol-Myers Squibb, Co.New BrunswickUSA
  2. 2.Analytical and Bioanalytical DevelopmentBristol-Myers Squibb, Co.New BrunswickUSA
  3. 3.Gene Expression and Protein Biochemistry DepartmentBristol-Myers Squibb, Co.PrincetonUSA
  4. 4.Biotransformation DepartmentBristol-Myers Squibb, Co.PrincetonUSA

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