Ditzinger, Felix

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Ditzinger
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Felix
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Ditzinger, Felix

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2019 - 20202
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Thema: hot melt extrusion × Thema: poorly water-soluble drug ×

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Gerade angezeigt 1 - 2 von 2
  • Vorschaubild
    Publikation
    In Vivo Performance of Innovative Polyelectrolyte Matrices for Hot Melt Extrusion of Amorphous Drug Systems
    (American Chemical Society, 2020) Ditzinger, Felix; Wieland, Rebecca; Statelova, Marina; Vertzoni, Maria; Holm, Rene; Kuentz, Martin [in: Molecular Pharmaceutics]
    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.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Vorschaubild
    Publikation
    Modified Polymer Matrix in Pharmaceutical Hot Melt Extrusion by Molecular Interactions with a Carboxylic Coformer
    (American Chemical Society, 2019) Ditzinger, Felix; Scherer, Uta Maria; Schönenberger, Monica; Holm, Rene; Kuentz, Martin [in: Molecular Pharmaceutics]
    Hot melt extrusion (HME) has become an essential technology to cope with an increasing number of poorly soluble drug candidates. However, there is only a limited choice of pharmaceutical polymers for obtaining suitable amorphous solid dispersions (ASD). Considerations of miscibility, stability, and biopharmaceutical performance narrow the selection of excipients, and further technical constraints arise from needed pharmaceutical processing. The present work introduces the concept of molecularly targeted interactions of a coformer with a polymer to design a new matrix for HME. Model systems of dimethylaminoethyl methacrylate copolymer, Eudragit E (EE), and bicarboxylic acids were studied, and pronounced molecular interactions were demonstrated by 1H, 13C NMR, FTIR spectroscopy, as well as by different techniques of microscopic imaging. A difference was shown between new formulations exploiting specifically the targeted molecular interactions and a common drug−polymer formulation. More specifically, a modified matrix with Malic acid exhibited a technical extrusion advantage over polymer alone, and there was a benefit of improved physical stability revealed for the drug fenofibrate. This model compound displayed greatly enhanced dissolution kinetics from the ASD formulations. It can be concluded that harnessing molecularly designed polymer modifications by coformers has much potential in solid dispersion technology and in particular regarding HME processing.
    01A - Beitrag in wissenschaftlicher Zeitschrift