Pharmaceutical Research

, 36:151 | Cite as

Assessing the Utility of In Vitro Screening Tools for Predicting Bio-Performance of Oral Peptide Delivery

  • Prajakta GadgilEmail author
  • Candice Alleyne
  • Kung-I Feng
  • Mengwei Hu
  • Marian Gindy
  • Alexei V. Buevich
  • Scott Fauty
  • Gino Salituro
  • Jianzhong Wen
  • Ying Li
  • Rebecca Nofsinger
  • Tomi K. Sawyer
  • Nicole Buist
Research Paper



In this study we evaluated the utility of in-vitro screening tools for predicting the in-vivo behavior of six cyclic peptides with different solubility and permeability properties (BCS class II and III), intended for oral delivery in presence of permeation enhancer Labrasol.


An in vitro flux assay was used to assess peptide permeation across a biomimetic, lipid-based membrane and in vivo studies in rats were used to determine oral peptide bioavailability in the presence of Labrasol.


The in vitro flux was significantly increased for BCS class III peptides, while it significantly decreased or remained unchanged for BCS class II peptides with increasing Labrasol concentrations. The different flux responses were attributed to the combination of reduced effective free peptide concentration and increased membrane permeability in the presence of Labrasol. In vivo studies in male Wistar-Hans rats indicated improved oral bioavailability at different extents for all peptides in presence of Labrasol. On comparing the in vitro and in vivo data, a potential direct correlation for BCS class III peptides was seen but not for BCS class II peptides, due to lower free concentrations of peptides in this class.


This study assessed the utility of in vitro screening tools for selecting peptides and permeation excipients early in drug product development.

Graphical Abstract Graphical Abstract and Figure 1 contains small text.Graphical Abstract text is made larger. The Figure 1 text cannot be made larger.

Key words

flux oral delivery peptides permeation enhancer 



Area under the Curve


Biopharmaceutics Classification System


Correlation spectroscopy




Ethylenediaminetetraacetic acid


Heteronuclear Multiple Bond Correlation


Heteronuclear Single Quantum Coherence/Correlation Spectroscopy






Nuclear Magnetic Resonance


Nuclear Overhauser Enhancement Spectroscopy


Parallel Artificial Membrane Permeability Assay


Phosphate Buffered Saline


Acknowledgments and Disclosures

This research was performed as a part of MRL Postdoctoral Research Program.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Prajakta Gadgil
    • 1
    Email author
  • Candice Alleyne
    • 1
  • Kung-I Feng
    • 1
  • Mengwei Hu
    • 1
  • Marian Gindy
    • 1
  • Alexei V. Buevich
    • 2
  • Scott Fauty
    • 3
  • Gino Salituro
    • 4
  • Jianzhong Wen
    • 4
  • Ying Li
    • 4
  • Rebecca Nofsinger
    • 5
  • Tomi K. Sawyer
    • 6
  • Nicole Buist
    • 1
  1. 1.Department of Discovery Pharmaceutical SciencesMerck & Co., Inc.RahwayUSA
  2. 2.Department of NMR Structure ElucidationMerck & Co., Inc.KenilworthUSA
  3. 3.Department of Safety Assessment and Laboratory Animal ResourcesMerck & Co., Inc.KenilworthUSA
  4. 4.Department of Pharmacokinetics, Pharmacodynamics and Drug MetabolismMerck & Co., Inc.KenilworthUSA
  5. 5.Department of Biopharmaceutics and Specialty Dosage FormMerck & Co., Inc.KenilworthUSA
  6. 6.Department of Discovery Chemistry ModalitiesMerck & Co., Inc.KenilworthUSA

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