Searching for physiologically relevant in vitro dissolution techniques for orally inhaled drugs

Snezana Radivojev, Sarah Zellnitz, Amrit Paudel, Eleonore Froehlich

Research output: Contribution to journalReview articlepeer-review


Inhalation is the preferred route for the treatment of lung diseases. More recently, also formulations for systemic treatment have been developed. For efficient development of inhalation products it is necessary to identify a link between particle parameters and in vivo performance. Such a relation exists for oral drugs where dissolution and permeation across Caco-2 monolayers are correlated to in vivo absorption. By contrast, the only in vitro parameter with established link to absorption for inhalation is particle size. In vitro dissolution could be another important parameter because low solubility determines bioavailability of inhaled drugs. The review highlights the importance of dissolution for drug availability in general and lists important differences in dissolution testing of oral and inhaled formulations. Dissolution testing protocols are summarized with focus on the composition of the various fluids, which are used to mimic particle dissolution in the deep lung. Finally, a role of in silico modelling in identification of physiologically relevant dissolution fluids and in in vitro in vivo correlation is suggested.
Original languageEnglish
Pages (from-to)45-56
Number of pages12
JournalInternational Journal of Pharmaceutics
Publication statusPublished - 10 Feb 2019


  • In vitro dissolution
  • Oral inhalation
  • Simulated lung fluid
  • Dissolution testing
  • Inhalation treatment
  • PBPK modelling

ASJC Scopus subject areas

  • Pharmaceutical Science

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