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The AAPS Journal

, 21:19 | Cite as

PBPK Absorption Modeling: Establishing the In VitroIn Vivo Link—Industry Perspective

  • Cordula Stillhart
  • Xavier Pepin
  • Christophe Tistaert
  • David Good
  • An Van Den Bergh
  • Neil Parrott
  • Filippos KesisoglouEmail author
Commentary Theme: Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development
  • 271 Downloads
Part of the following topical collections:
  1. Theme: Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development

Abstract

The establishment of an in vitroin vivo correlation (IVIVC) is considered the gold standard to establish in vivo relevance of a dissolution method and to utilize dissolution data in the context of regulatory bioequivalence questions, including the development of dissolution specifications. However, several recent publications, including industry surveys and reviews from regulatory agencies, have indicated a low success rate for IVIVCs, especially for immediate-release formulations. In recent years, the use of physiologically based pharmacokinetics (PBPK) and absorption modeling, as a tool to facilitate formulation development, has been attracting increased attention. This manuscript provides an industry perspective on the current challenges with establishing IVIVCs and the potential PBPK and absorption modeling offer to increase their impact. Case studies across both immediate-release and extended-release formulations from five pharmaceutical companies are utilized to demonstrate how physiologically based IVIVC (PB-IVIVC) may facilitate drug product understanding and to inform bioequivalence assessment and clinically relevant specifications. Finally, PB-IVIVC best practices and a strategy for model development and application are proposed.

KEY WORDS

IVIVC oral absorption modeling physiologically based absorption modeling physiologically based biopharmaceutics modeling physiologically based pharmacokinetics 

Notes

Supplementary material

12248_2019_292_MOESM1_ESM.docx (54 kb)
ESM 1 (DOCX 54 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Cordula Stillhart
    • 1
  • Xavier Pepin
    • 2
  • Christophe Tistaert
    • 3
  • David Good
    • 4
  • An Van Den Bergh
    • 5
  • Neil Parrott
    • 6
  • Filippos Kesisoglou
    • 7
    Email author
  1. 1.Pharmaceutical Research & Development, Formulation & Process SciencesF. Hoffmann-La Roche Ltd.BaselSwitzerland
  2. 2.AstraZeneca, Pharmaceutical Technology & DevelopmentMacclesfieldUK
  3. 3.Pharmaceutical Sciences, Discovery, Product Development & Supply, Janssen Research and DevelopmentBeerseBelgium
  4. 4.Drug Product Science and TechnologyBristol-Myers Squibb Co.New BrunswickUSA
  5. 5.Pharmacodynamics, Pharmacokinetics, and Metabolism, Discovery, Product Development & SupplyJanssen Research and DevelopmentBeerseBelgium
  6. 6.Pharmaceutical Sciences, Pharmaceutical Research and Early DevelopmentRoche Innovation Center BaselBaselSwitzerland
  7. 7.Biopharmaceutics and Specialty Dosage Forms, Pharmaceutical SciencesMerck & Co., Inc.West PointUSA

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