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Leveraging bile solubilization of poorly water-soluble drugs by rational polymer selection.
Schlauersbach, Jonas Hanio, Simon Lenz, Bettina Vemulapalli, Sahithya P B Griesinger, Christian Pöppler, Ann-Christin Harlacher, Cornelius Galli, Bruno Meinel, Lorenz
Schlauersbach, Jonas
Hanio, Simon
Lenz, Bettina
Vemulapalli, Sahithya P B
Griesinger, Christian
Pöppler, Ann-Christin
Harlacher, Cornelius
Galli, Bruno
Meinel, Lorenz
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2020-12-15
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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.
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J Control Release. 2020 Dec 15;330:36-48. doi: 10.1016/j.jconrel.2020.12.016. Epub ahead of print.
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Article
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en
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1873-4995
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Attribution-NonCommercial-NoDerivatives 4.0 International