Integrating Drug- and Formulation-Related Properties With Gastrointestinal Tract Variability Using a Product-Specific Particle Size Approach: Case Example Ibuprofen

Rodrigo Cristofoletti; Bart Hens; Nikunjkumar Patel; Valvanera Vozmediano Esteban; Stephan Schmidt; Jennifer Dressman

doi:10.1016/j.xphs.2019.09.012

Integrating Drug- and Formulation-Related Properties With Gastrointestinal Tract Variability Using a Product-Specific Particle Size Approach: Case Example Ibuprofen

J Pharm Sci. 2019 Dec;108(12):3842-3847. doi: 10.1016/j.xphs.2019.09.012. Epub 2019 Sep 17.

Authors

Rodrigo Cristofoletti¹, Bart Hens², Nikunjkumar Patel³, Valvanera Vozmediano Esteban⁴, Stephan Schmidt⁴, Jennifer Dressman⁵

Affiliations

¹ Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, Florida 32827. Electronic address: [email protected].
² Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
³ Simcyp Limited (A Certara Company), Blades Enterprise Centre, Sheffield, UK.
⁴ Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, Florida 32827.
⁵ Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.

PMID: 31539541
DOI: 10.1016/j.xphs.2019.09.012

Abstract

In the present study, an in vitro-in vivo extrapolation of dissolution integrated to a physiologically based pharmacokinetics modeling approach, considering a product-specific particle size distribution and a self-buffering effect of the drug, is introduced and appears to be a promising translational modeling strategy to support drug product development, manufacturing changes and setting clinically relevant specifications for immediate release formulations containing ibuprofen and other weak acids with similar properties.

Keywords: absorption; dissolution; in vitro-in vivo (IVIVC) correlation(s); mechanistic modeling; particle size; physiologically based pharmacokinetic (PBPK) modeling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Adult
Chemistry, Pharmaceutical / methods
Drug Development / methods
Drug Liberation / drug effects
Gastrointestinal Tract / drug effects*
Humans
Ibuprofen / administration & dosage*
Ibuprofen / chemistry*
Models, Biological
Particle Size
Solubility / drug effects

Substances

Ibuprofen