Performance Evaluation of Montelukast Pediatric Formulations: Part I—Age-Related In Vitro Conditions

Mariana Guimarães, Pascal Somville, Maria Vertzoni, Nikoletta Fotaki

Research output: Contribution to journalArticlepeer-review


This study aimed to explore the potential of biopharmaceutics in vitro tools to predict drug product performance in the pediatric population. Biorelevant dissolution set-ups were used to predict how age and medicine administration practices affect the in vitro dissolution of oral formulations of a poorly water-soluble compound, montelukast. Biorelevant age-appropriate dissolution studies of Singulair® (granules and chewable tablets) were conducted with the µDISS profiler™, USP 4 apparatus, USP 2 apparatus, and mini-paddle apparatus. Biorelevant simulating fluids representative of adult and pediatric conditions were used in the dissolution studies. The biorelevant dissolution conditions were appropriately selected (i.e. volumes, transit times, etc.) to mimic the gastrointestinal conditions of each of the subpopulations tested. Partial least squares regression (PLS-R) was performed to understand the impact of in vitro variables on the dissolution of montelukast. Montelukast dissolution was significantly affected by the in vitro hydrodynamics used to perform the dissolution tests (µDISS profiler™: positive effect); choice of simulation of gastric (negative effect) and/or intestinal conditions (positive effect) of the gastrointestinal tract; and simulation of prandial state (fasted state: negative effect, fed state: positive effect). Age-related biorelevant dissolution of Singulair® granules predicted the in vivo effect of the co-administration of the formulation with applesauce and formula in infants. This study demonstrates that age-appropriate biorelevant dissolution testing can be a valuable tool for the assessment of drug performance in the pediatric population. Graphical Abstract: [Figure not available: see fulltext.].

Original languageEnglish
Article number26
JournalAAPS Journal
Issue number1
Publication statusPublished - 10 Jan 2022

Bibliographical note

Funding Information:
This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 674909 (PEARRL), .


  • adults
  • age-related biorelevant dissolution
  • biopharmaceutics
  • montelukast
  • pediatrics

ASJC Scopus subject areas

  • Pharmaceutical Science


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