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In Vivo Performance of Innovative Polyelectrolyte Matrices for Hot Melt Extrusion of Amorphous Drug Systems.
Mol Pharm. 2020 Jul 13 [Online ahead of print]MP

Abstract

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.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland. Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, Switzerland.Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland.Department of Pharmacy, National and Kapodistrian University of Athens, 157 84 Athens, Greece.Department of Pharmacy, National and Kapodistrian University of Athens, 157 84 Athens, Greece.Drug Product Development, Janssen Research and Development, Johnson and Johnson, 2340 Beerse, Belgium. Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark.Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, Switzerland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32589437

Citation

Ditzinger, Felix, et al. "In Vivo Performance of Innovative Polyelectrolyte Matrices for Hot Melt Extrusion of Amorphous Drug Systems." Molecular Pharmaceutics, 2020.
Ditzinger F, Wieland R, Statelova M, et al. In Vivo Performance of Innovative Polyelectrolyte Matrices for Hot Melt Extrusion of Amorphous Drug Systems. Mol Pharm. 2020.
Ditzinger, F., Wieland, R., Statelova, M., Vertzoni, M., Holm, R., & Kuentz, M. (2020). In Vivo Performance of Innovative Polyelectrolyte Matrices for Hot Melt Extrusion of Amorphous Drug Systems. Molecular Pharmaceutics. https://doi.org/10.1021/acs.molpharmaceut.0c00485
Ditzinger F, et al. In Vivo Performance of Innovative Polyelectrolyte Matrices for Hot Melt Extrusion of Amorphous Drug Systems. Mol Pharm. 2020 Jul 13; PubMed PMID: 32589437.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In Vivo Performance of Innovative Polyelectrolyte Matrices for Hot Melt Extrusion of Amorphous Drug Systems. AU - Ditzinger,Felix, AU - Wieland,Rebecca, AU - Statelova,Marina, AU - Vertzoni,Maria, AU - Holm,René, AU - Kuentz,Martin, Y1 - 2020/07/13/ PY - 2020/6/27/pubmed PY - 2020/6/27/medline PY - 2020/6/27/entrez KW - NaCMC KW - hot melt extrusion KW - in vivo study KW - polyelectrolyte matrices KW - poorly water-soluble drug JF - Molecular pharmaceutics JO - Mol. Pharm. N2 - 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. SN - 1543-8392 UR - https://www.unboundmedicine.com/medline/citation/32589437/In_vivo_performance_of_innovative_polyelectrolyte_matrices_for_hot_melt_extrusion_of_amorphous_drug_systems L2 - https://doi.org/10.1021/acs.molpharmaceut.0c00485 DB - PRIME DP - Unbound Medicine ER -
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