TY  - JOUR
A1  - Schlauersbach, Jonas
A1  - Hanio, Simon
A1  - Lenz, Bettina
A1  - Vemulapalli, Sahithya P. B.
A1  - Griesinger, Christian
A1  - Pöppler, Ann-Christin
A1  - Harlacher, Cornelius
A1  - Galli, Bruno
A1  - Meinel, Lorenz
T1  - Leveraging bile solubilization of poorly water-soluble drugs by rational polymer selection
JF  - Journal of Controlled Release
N2  - Poorly water-soluble drugs frequently solubilize into bile colloids and this natural mechanism is key for efficient bioavailability. We tested the impact of pharmaceutical polymers on this solubilization interplay using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and by assessing the flux across model membranes. Eudragit E, Soluplus, and a therapeutically used model polymer, Colesevelam, impacted the bile-colloidal geometry and molecular interaction. These polymer-induced changes reduced the flux of poorly water-soluble and bile interacting drugs (Perphenazine, Imatinib) but did not impact the flux of bile non-interacting Metoprolol. Non-bile interacting polymers (Kollidon VA 64, HPMC-AS) neither impacted the flux of colloid-interacting nor colloid-non-interacting drugs. These insights into the drug substance/polymer/bile colloid interplay potentially point towards a practical optimization parameter steering formulations to efficient bile-solubilization by rational polymer selection.
KW  - polymer drug interaction
KW  - flux
KW  - bile salt
KW  - simulated intestinal fluid
KW  - colloid
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-296957
VL  - 330
ET  - Accepted Version
ER  - 
TY  - JOUR
A1  - Schlauersbach, Jonas
A1  - Hanio, Simon
A1  - Raschig, Martina
A1  - Lenz, Bettina
A1  - Scherf-Cavel, Oliver
A1  - Meinel, Lorenz
T1  - Bile and excipient interactions directing drug pharmacokinetics in rats
JF  - European Journal of Pharmaceutics and Biopharmaceutics
N2  - Bile solubilization plays a major role in the absorption of poorly water-soluble drugs. Excipients used in oral drug formulations impact bile-colloidal properties and their molecular interactions. Polymer-induced changes of bile colloids, e.g., by Eudragit E, reduced the flux of the bile interacting drug Perphenazine whereas bile non-interacting Metoprolol was not impacted. This study corroborates these in vitro findings in rats. Eudragit E significantly reduced systemic availability of Perphenazine but not Metoprolol compared to the oral administrations without polymer. This study confirms the necessity to carefully select polymers for bile interacting drugs whereas non-bile interacting drugs are more robust in terms of excipient choice for formulation. The perspective of bile interaction may introduce interesting biopharmaceutical leverage for better performing oral formulations of tomorrow.
KW  - in vitro-in vivo correlation
KW  - pharmacokinetics
KW  - bile
KW  - excipient
KW  - rat study
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-296969
VL  - 178
ET  - accepted version
ER  -