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

Loading...
Thumbnail Image
Authors
Wieland, Rebecca
Statelova, Marina
Vertzoni, Maria
Holm, Rene
Author (Corporation)
Publication date
2020
Typ of student thesis
Course of study
Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Molecular Pharmaceutics
Special issue
Link
Series
Series number
Volume
17
Issue / Number
8
Pages / Duration
3053-3061
Patent number
Publisher / Publishing institution
American Chemical Society
Place of publication / Event location
Edition
Version
Programming language
Assignee
Practice partner / Client
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.
Keywords
poorly water-soluble drug, in vivo study, hot melt extrusion, polyelectrolyte matrices, NaCMC, amorphous solid dispersions
Subject (DDC)
Project
Event
Exhibition start date
Exhibition end date
Conference start date
Conference end date
Date of the last check
ISBN
ISSN
1543-8384
1543-8392
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
License
Citation
DITZINGER, Felix, Rebecca WIELAND, Marina STATELOVA, Maria VERTZONI, Rene HOLM und Martin KUENTZ, 2020. In Vivo Performance of Innovative Polyelectrolyte Matrices for Hot Melt Extrusion of Amorphous Drug Systems. Molecular Pharmaceutics. 2020. Bd. 17, Nr. 8, S. 3053–3061. DOI 10.1021/acs.molpharmaceut.0c00485. Verfügbar unter: https://doi.org/10.26041/fhnw-3604