Leveraging bile solubilization of poorly water-soluble drugs by rational polymer selection

Please always quote using this URN: urn:nbn:de:bvb:20-opus-296957
  • 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 poorlyPoorly 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.show moreshow less
Metadaten
Author: Jonas SchlauersbachORCiD, Simon Hanio, Bettina Lenz, Sahithya P. B. Vemulapalli, Christian Griesinger, Ann-Christin Pöppler, Cornelius Harlacher, Bruno Galli, Lorenz Meinel
URN:urn:nbn:de:bvb:20-opus-296957
Document Type:Journal article
Faculties:Fakultät für Chemie und Pharmazie / Institut für Organische Chemie
Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie
Language:English
Parent Title (English):Journal of Controlled Release
Year of Completion:2021
Edition:Accepted Version
Volume:330
Pagenumber:36-48
Source:Journal of Controlled Release (2020) 330, 36-48. https://doi.org/10.1016/j.jconrel.2020.12.016
DOI:https://doi.org/10.1016/j.jconrel.2020.12.016
Sonstige beteiligte Institutionen:Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, DE-37077 Goetingen, Germany
Sonstige beteiligte Institutionen:Novartis Pharma AG, Lichtstrasse 35, CH-4056 Basel, Switzerland
Sonstige beteiligte Institutionen:Helmholtz Institute for RNA-based Infection Biology (HIRI), Josef-Schneider-Straße 2/D15, DE-97080 Wuerzburg, Germany
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 547 Organische Chemie
Tag:bile salt; colloid; flux; polymer drug interaction; simulated intestinal fluid
Release Date:2022/12/17
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International