Modelling drug diffusion through unstirred water layers allows real-time quantification of free/loaded drug fractions and release kinetics from colloidal-based formulations

Martina M Tzanova, Federica Moretti, Gabriele Grassi, Paul C Stein, Marianne Hiorth, Michela Abrami, Mario Grassi, Massimiliano Pio di Cagno*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

The correlation between in vivo and in vitro data is yet not sufficiently optimized to allow a significant reduction and replacement of animal testing in pharmaceutical development. One of the main reasons for this lies in the poor mechanistic understanding and interpretation of the physical mechanisms enabling formulation rely on for deploying the drug. One mechanism that still lacks a proper interpretation is the kinetics of drug release from nanocarriers. In this work, we investigate two different types of classical enabling formulations - i) cyclodextrin solutions and ii) liposomal dispersions - by a combination of an experimental method (i.e. UV-Vis localized spectroscopy) and mathematical modelling/numerical data fitting. With this approach, we are able to discriminate precisely between the amount of drug bound to nanocarriers or freely dissolved at any time point; in addition, we can precisely estimate the binding and diffusivity constants of all chemical species (free drug/bound drug). The results obtained should serve as the first milestone for the further development of reliable in vitro/in silico models for the prediction of in vivo drug bioavailability when enabling formulations are used.

Original languageEnglish
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume178
Pages (from-to)168-178
ISSN0939-6411
DOIs
Publication statusPublished - Sept 2022

Keywords

  • Cyclodextrins
  • Drug diffusion
  • Liposomes
  • Mathematical modelling
  • Molecularly dissolved drug
  • Numerical data fitting
  • Cyclodextrins/chemistry
  • Animals
  • Liposomes/chemistry
  • Kinetics
  • Water/chemistry
  • Diffusion

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