In vivo performance of innovative polyelectrolyte matrices for hot melt extrusion of amorphous drug systems.

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 to hot melt extrusion that would be otherwise not possible to process due to the unfavorable properties upon heating of the pure polymer. Carboxymethyl cellulose sodium (NaCMC) with lysine or alternatively meglumine was leading 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, as well as viscosity measurements after aqueous dispersion. Further biopharmaceutical assessment started with biorelevant non-sink 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.

• Publication year

  2020

• Venue

  Molecular Pharmaceutics

• Publication date

  2020-06-26

• Fields of study

  Medicine, Materials Science, Chemistry

• Identifiers
  DOI 10.1021/acs.molpharmaceut.0c00485PMID 32589437
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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