In Vivo Performance of Innovative Polyelectrolyte Matrices for Hot Melt Extrusion of Amorphous Drug Systems

Felix Ditzinger, Rebecca Wieland, Marina Statelova, Maria Vertzoni, René Holm, Martin Kuentz*

*Corresponding author

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


Hot melt extrusion of amorphous systems has become a pivotal technology to cope with challenges of poorly water-soluble drugs. Previous research showed that small molecular additives with targeted molecular interactions enabled introduction of a polyelectrolyte matrix into hot melt extrusion that would otherwise not be possible to process due to the unfavorable properties upon heating of the pure polymer. Carboxymethyl cellulose sodium (NaCMC) with lysine or alternatively meglumine led to modified polymeric matrices that showed adequate processability by hot melt extrusion and yielded stable amorphous formulations. The investigated formulations, including fenofibrate as a model drug, were characterized by attenuated total reflectance Fourier transform infrared spectroscopy, differential scanning calorimetry, and viscosity measurements after aqueous dispersion. Further biopharmaceutical assessment started with biorelevant nonsink dissolution testing followed by a pharmacokinetic in vivo study in rats. The in vitro assessment showed superiority of the lysine-containing formulation in the extent of in vitro supersaturation and overall drug release. In accordance with this, the in vivo study also demonstrated increased exposure of the amorphous formulations and in particular for the system containing lysine. In summary, the combination of polyelectrolytes with interacting additives presents a promising opportunity for the formulation of poorly water-soluble drugs.
TidsskriftMolecular Pharmaceutics
Udgave nummer8
Sider (fra-til)3053-3061
Antal sider9
StatusUdgivet - 3 aug. 2020

Bibliografisk note

Funding Information:
This project has received funding from the European Union’s Horizon 2020 Research and Innovation Program under grant agreement No 674909.


  • hot melt extrusion
  • in vivo study
  • NaCMC
  • polyelectrolyte matrices
  • poorly water-soluble drug

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