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

Jonas Schlauersbach; Simon Hanio; Bettina Lenz; Sahithya P B Vemulapalli; Christian Griesinger; Ann-Christin Pöppler; Cornelius Harlacher; Bruno Galli; Lorenz Meinel

doi:10.1016/j.jconrel.2020.12.016

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

J Control Release. 2021 Feb 10:330:36-48. doi: 10.1016/j.jconrel.2020.12.016. Epub 2020 Dec 15.

Authors

Jonas Schlauersbach¹, Simon Hanio¹, Bettina Lenz¹, Sahithya P B Vemulapalli², Christian Griesinger², Ann-Christin Pöppler³, Cornelius Harlacher⁴, Bruno Galli⁴, Lorenz Meinel⁵

Affiliations

¹ Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
² Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, DE-37077 Goetingen, Germany.
³ Institute of Organic Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
⁴ Novartis Pharma AG, Lichtstrasse 35, CH-4056 Basel, Switzerland.
⁵ Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany; Helmholtz Institute for RNA-based Infection Biology (HIRI), DE-97070 Wuerzburg, Germany. Electronic address: lorenz.meinel@uni-wuerzburg.de.

PMID: 33333120
DOI: 10.1016/j.jconrel.2020.12.016

Abstract

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.

Keywords: Bile salt; Colloid; Flux; Polymer drug interaction; Simulated intestinal fluid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bile
Colloids
Polymers*
Solubility
Water*

Substances

Colloids
Polymers
Water